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Id Subject Object Predicate Lexical cue
T1 0-49 Sentence denotes Electrochemical biosensors for pathogen detection
T2 51-59 Sentence denotes Abstract
T3 60-142 Sentence denotes Recent advances in electrochemical biosensors for pathogen detection are reviewed.
T4 143-328 Sentence denotes Electrochemical biosensors for pathogen detection are broadly reviewed in terms of transduction elements, biorecognition elements, electrochemical techniques, and biosensor performance.
T5 329-412 Sentence denotes Transduction elements are discussed in terms of electrode material and form factor.
T6 413-597 Sentence denotes Biorecognition elements for pathogen detection, including antibodies, aptamers, and imprinted polymers, are discussed in terms of availability, production, and immobilization approach.
T7 598-723 Sentence denotes Emerging areas of electrochemical biosensor design are reviewed, including electrode modification and transducer integration.
T8 724-841 Sentence denotes Measurement formats for pathogen detection are classified in terms of sample preparation and secondary binding steps.
T9 842-1033 Sentence denotes Applications of electrochemical biosensors for the detection of pathogens in food and water safety, medical diagnostics, environmental monitoring, and bio-threat applications are highlighted.
T10 1034-1326 Sentence denotes Future directions and challenges of electrochemical biosensors for pathogen detection are discussed, including wearable and conformal biosensors, detection of plant pathogens, multiplexed detection, reusable biosensors for process monitoring applications, and low-cost, disposable biosensors.
T11 1328-1338 Sentence denotes Highlights
T12 1339-1417 Sentence denotes • Comprehensive review of electrochemical biosensor-based pathogen detection.
T13 1418-1516 Sentence denotes • Review of emerging electrodes for transduction of pathogen binding via electrochemical methods.
T14 1517-1623 Sentence denotes • Discussion of emerging electrochemical biosensor designs, including flexible and wearable form factors.
T15 1624-1693 Sentence denotes • Highlight of electrochemical biosensors for coronavirus detection.
T16 1695-1710 Sentence denotes 1 Introduction
T17 1711-1762 Sentence denotes Pathogens are infectious agents that cause disease.
T18 1763-1901 Sentence denotes They include microorganisms, such as fungi, protozoans, and bacteria, and molecular-scale infectious agents, including viruses and prions.
T19 1902-2076 Sentence denotes Foodborne, waterborne, and airborne pathogens enter the body through various modes of infection and are responsible for over 15 million deaths annually worldwide (Dye, 2014).
T20 2077-2211 Sentence denotes Some of the most common pathogens include viruses, such as norovirus and influenza virus, and bacteria, such as E. coli and S. aureus.
T21 2212-2321 Sentence denotes Pathogens vary in many regards, such as virulence, contagiousness, mode of transmission, and infectious dose.
T22 2322-2483 Sentence denotes For example, the world is currently facing a global pandemic associated with the COVID-19 virus, for which virulence and infectious dose data are still emerging.
T23 2484-2704 Sentence denotes Techniques for sensitive and rapid detection of pathogens in complex matrices, such as body fluids and aerosols, and on surfaces are critical to the treatment of infectious diseases and controlling the spread of disease.
T24 2705-2825 Sentence denotes The techniques used to identify and quantify pathogens can be broadly distinguished as immunoassays or DNA-based assays.
T25 2826-3085 Sentence denotes The use of immunoassays versus DNA-based assays depends on various factors, including the stage of an infection and the availability of antibodies and DNA sequence data, such as viral DNA, toxin-producing genes, as well as species- and strain-selective genes.
T26 3086-3170 Sentence denotes Immunoassays are ubiquitous across medical diagnostics and food safety applications.
T27 3171-3364 Sentence denotes Pathogens can be identified through the presence of generated antibodies in an organism, which may be present both during and after an infection (i.e., after the pathogen is no longer present).
T28 3365-3443 Sentence denotes In such assays, both the biorecognition element and the target are antibodies.
T29 3444-3580 Sentence denotes If antibodies are available for the pathogen (e.g., anti-E. coli O157:H7), one can also directly detect the pathogen using immunoassays.
T30 3581-3761 Sentence denotes The ability to indirectly and directly detect pathogens via generated antibodies and pathogen epitopes, respectively, makes immunoassays flexible techniques for pathogen detection.
T31 3762-4007 Sentence denotes In cases of limited antibody availability, need for highly sensitive results, or infections that do not generate a significant level of antibody production in the organism although the pathogen is present, DNA-based assays are commonly employed.
T32 4008-4107 Sentence denotes DNA-based assays require the pathogen to be present in the sample or to have been recently present.
T33 4108-4256 Sentence denotes In addition to detection of pathogens using antibodies or toxin-producing genes, pathogens can also be detected based on their expression of toxins.
T34 4257-4365 Sentence denotes Thus, targets associated with pathogen detection include toxins, nucleic acids, viruses, cells, and oocysts.
T35 4366-4471 Sentence denotes As a result, biorecognition elements widely vary, including antibodies, aptamers, and imprinted polymers.
T36 4472-4651 Sentence denotes Several comprehensive reviews have been written on pathogen detection using high-throughput, well plate-based bioanalytical techniques (Alahi and Mukhopadhyay, 2017; Lazcka et al.
T37 4652-4671 Sentence denotes 2007; Zourob et al.
T38 4672-4740 Sentence denotes 2008), such as enzyme-linked immunosorbent assay (ELISA) (Law et al.
T39 4741-4811 Sentence denotes 2015) and polymerase chain reaction (PCR) (Klein, 2002; Malorny et al.
T40 4812-4874 Sentence denotes 2003), which remain the gold standards for pathogen detection.
T41 4875-5135 Sentence denotes Few reviews, however, have focused on emerging label-free biosensors for pathogen detection, which provide useful characteristics for applications in process monitoring (e.g., of biomanufacturing processes), environmental monitoring, and precision agriculture.
T42 5136-5366 Sentence denotes Bioanalytical techniques utilize a selective biorecognition element, often called a molecular probe, in combination with an analytical system, such as a plate reader or PCR analyzer, to quantify one or more components of a sample.
T43 5367-5588 Sentence denotes While capable of being highly sensitive and robust, they are destructive testing methods and require the addition of reagents to the sample and extensive sample preparation steps, which increase the time-to-results (TTR).
T44 5589-5724 Sentence denotes Bioanalytical techniques, such as PCR, may also encounter inhibition effects caused by background species in the sample (Justino et al.
T45 5725-5750 Sentence denotes 2017; Scognamiglio et al.
T46 5751-5767 Sentence denotes 2016; Sin et al.
T47 5768-5858 Sentence denotes 2014), which introduce measurement bias and increase measurement uncertainty (Clark et al.
T48 5859-5881 Sentence denotes 2016; Silverman et al.
T49 5882-5888 Sentence denotes 2019).
T50 5889-6124 Sentence denotes Considering such limitations of traditional plate-based bioanalytical techniques and the need for real-time continuous monitoring capabilities among various applications, there is a need to examine alternative bioanalytical techniques.
T51 6125-6233 Sentence denotes Over the past twenty-five years, biosensors have emerged to complement PCR and ELISA for pathogen detection.
T52 6234-6454 Sentence denotes Biosensors are based on the direct integration of a selective biorecognition element and a sensitive transducer element and provide complementary platforms to PCR and ELISA for pathogen identification and quantification.
T53 6455-6651 Sentence denotes According to the International Union of Pure and Applied Chemistry (IUPAC), a biosensor must contain a biorecognition element in direct spatial contact with a transduction element (Thévenot et al.
T54 6652-6658 Sentence denotes 2001).
T55 6659-6839 Sentence denotes In addition, a biosensor should provide quantitative or semi-quantitative analytical information and measurement without the requirement of additional processing steps or reagents.
T56 6840-7039 Sentence denotes While a biosensor should also be a self-contained, integrated device, the measurement approach can vary from droplet formats to continuous flow formats that require associated fluid handling systems.
T57 7040-7186 Sentence denotes Biosensors have achieved sensitive and selective real-time detection of pathogens in various environments without the need for sample preparation.
T58 7187-7355 Sentence denotes For example, biosensors have enabled the detection of an abundance of pathogens in various matrices and environments, including foods, body fluids, and object surfaces.
T59 7356-7498 Sentence denotes In addition to sample preparation-free protocols, biosensors are compatible with label-free protocols (Daniels and Pourmand, 2007; Rapp et al.
T60 7499-7516 Sentence denotes 2010; Sang et al.
T61 7517-7541 Sentence denotes 2016; Vestergaard et al.
T62 7542-7548 Sentence denotes 2007).
T63 7549-7669 Sentence denotes Labels, often referred to as reporters, are molecular species, such as organic dyes or quantum dots (Resch-Genger et al.
T64 7670-7893 Sentence denotes 2008), that are attached to the target, either directly or through a biorecognition element, using a series of sample preparation steps or secondary binding steps to facilitate detection through the properties of the label.
T65 7894-8015 Sentence denotes Thus, label-free biosensors avoid the use of a reporter species to detect the target species (Cooper, 2009; Syahir et al.
T66 8016-8022 Sentence denotes 2015).
T67 8023-8359 Sentence denotes Label-free assays often have fewer sample preparation steps due to the elimination of procedures associated with target labeling and lower cost than label-based assays, which are important considerations for applications in which preparation facilities or trained personnel are either limited or unavailable (Cooper, 2009; Syahir et al.
T68 8360-8366 Sentence denotes 2015).
T69 8367-8463 Sentence denotes While various types of transducers have been investigated for pathogen biosensing (Lazcka et al.
T70 8464-8482 Sentence denotes 2007; Singh et al.
T71 8483-8771 Sentence denotes 2014; Yoo and Lee, 2016), including mechanical and optical transducers, such as cantilever biosensors or surface plasmon resonance (SPR)-based biosensors, electrochemical biosensors have been extensively applied to pathogen detection (Felix and Angnes, 2018; Pereira da Silva Neves et al.
T72 8772-8792 Sentence denotes 2018; Saucedo et al.
T73 8793-8799 Sentence denotes 2019).
T74 8800-8963 Sentence denotes Electrochemical biosensors for pathogen detection utilize conducting and semiconducting materials as the transducer, which is commonly referred to as an electrode.
T75 8964-9228 Sentence denotes The chemical energy associated with binding between target pathogens and electrode-immobilized biorecognition elements is converted into electrical energy through an electrochemical method that involves the electrode and a pathogen-containing electrolyte solution.
T76 9229-9578 Sentence denotes To date, electrochemical biosensors have enabled sample preparation-free detection of pathogens in various matrices, in situ detection of pathogens on surfaces, rapid pathogen detection using low-cost platforms, multiplexed detection of pathogens in practical matrices, and detection of pathogens via wireless actuation and data acquisition formats.
T77 9579-9782 Sentence denotes As a result, electrochemical biosensors for pathogen detection have been widely examined for food and water safety, medical diagnostic, environmental monitoring, and bio-threat applications (Amiri et al.
T78 9783-9874 Sentence denotes 2018; Duffy and Moore, 2017; Felix and Angnes, 2018; Furst and Francis, 2019; Mishra et al.
T79 9875-9893 Sentence denotes 2018; Monzó et al.
T80 9894-9925 Sentence denotes 2015; Rastogi and Singh, 2019).
T81 9926-10003 Sentence denotes Here, we critically review electrochemical biosensors for pathogen detection.
T82 10004-10245 Sentence denotes To gain insight into the trajectory of the field, electrochemical biosensors for pathogen detection reported since 2005 are critically reviewed and classified with respect to IUPAC-recommended definitions and classifications (Thévenot et al.
T83 10246-10252 Sentence denotes 2001).
T84 10253-10479 Sentence denotes Applications of electrochemical biosensors for pathogen detection are critically reviewed with respect to the target pathogen, sample matrix, biosensor design, fabrication method, measurement format, and biosensor performance.
T85 10480-10682 Sentence denotes We also discuss future directions of electrochemical biosensors for pathogen detection, which includes a discussion of present technological and methodological challenges and emerging application areas.
T86 10684-10743 Sentence denotes 2 Electrochemical biosensor designs for pathogen detection
T87 10744-10952 Sentence denotes A chemical sensor is a device that transforms chemical information, such as the concentration of a specific sample component or total compositional analysis into an analytically useful signal (Thévenot et al.
T88 10953-10959 Sentence denotes 2001).
T89 10960-11055 Sentence denotes The electrochemical method utilized is a distinguishing aspect of an electrochemical biosensor.
T90 11056-11250 Sentence denotes In addition to the electrochemical method, the sample handling approach and sensor signal readout format also provide distinguishing aspects of a biosensor-based approach for pathogen detection.
T91 11251-11416 Sentence denotes Thus, we review electrochemical biosensors for pathogen detection using a framework built upon transducer elements, biorecognition elements, and measurement formats.
T92 11417-11505 Sentence denotes An overview of electrochemical biosensors for pathogen detection is provided in Fig. 1 .
T93 11506-11663 Sentence denotes As shown in Fig. 2 a, while the detection of bacterial pathogens remains an area of focus, the detection of viral pathogens and protozoa is an emerging area.
T94 11664-11748 Sentence denotes As shown in Fig. 2b, studies have focused on pathogen detection in various matrices.
T95 11749-11907 Sentence denotes We next discuss the transduction elements, biorecognition elements, and measurement formats associated with electrochemical biosensors for pathogen detection.
T96 11908-12016 Sentence denotes Fig. 1 Components and measurement formats associated with electrochemical biosensors for pathogen detection.
T97 12017-12220 Sentence denotes Fig. 2 a) Trend in pathogens detected by electrochemical biosensors since 2005 based on the data shown in Table 1, Table 2. b) Common matrices associated with the various pathogen detection applications.
T98 12222-12248 Sentence denotes 2.1 Transduction elements
T99 12249-12390 Sentence denotes The transduction element of an electrochemical biosensor is an electrochemical cell where the main component is commonly a working electrode.
T100 12391-12635 Sentence denotes A three electrode format (working, auxiliary, and reference) is commonly employed in a potentiostatic system, while a two electrode format (working and auxiliary) is often used for conductometry and electrochemical impedance spectroscopy (EIS).
T101 12636-12731 Sentence denotes Electrodes can be fabricated from multiple materials and using various manufacturing processes.
T102 12732-12873 Sentence denotes An electrode is an electronic conductor through which charge is transported by the movement of electrons and holes (Bard and Faulkner, 2000).
T103 12874-13018 Sentence denotes Electrodes are thus fabricated from conducting and semiconducting materials, including metals, such as gold (Au), and nonmetals, such as carbon.
T104 13019-13174 Sentence denotes Manufacturing processes can be used to fabricate electrodes of various sizes, including bulk structures (greater than 1 mm) and micro- and nano-structures.
T105 13175-13281 Sentence denotes As a result, electrodes can be classified by type and form of material, manufacturing process, and design.
T106 13282-13394 Sentence denotes Electrode designs can be classified by form factor, which includes planar, wire, nanostructured, or array-based.
T107 13395-13627 Sentence denotes The material, fabrication approach, and design affect the electrode's structure and properties, which ultimately determine the biosensor's performance, including sensitivity, selectivity, limit of detection (LOD), and dynamic range.
T108 13628-13733 Sentence denotes They also influence the biosensor's cost, manufacturability, disposability, and measurement capabilities.
T109 13735-13758 Sentence denotes 2.1.1 Metal electrodes
T110 13759-13854 Sentence denotes Metal electrodes, such as Au and platinum (Pt), have been commonly used for pathogen detection.
T111 13855-13945 Sentence denotes Thick metal electrodes are commonly fabricated from bulk structures via cutting processes.
T112 13946-14146 Sentence denotes Thin-film metal electrodes are often fabricated by deposition of metals on insulating substrates through traditional microfabrication approaches, including physical vapor deposition (Hierlemann et al.
T113 14147-14187 Sentence denotes 2003) and screen printing (Taleat et al.
T114 14188-14194 Sentence denotes 2014).
T115 14195-14394 Sentence denotes Resultant conductive components are often embedded in insulating polymer or ceramic substrates, including Teflon, polyetherkeytone (PEK), and glass, to complete fabrication of the transducer element.
T116 14395-14534 Sentence denotes While not yet applied to pathogen detection applications, three-dimensional (3D) printing processes, including inkjet printing (Bhat et al.
T117 14535-14562 Sentence denotes 2018; Medina-Sánchez et al.
T118 14563-14585 Sentence denotes 2014; Pavinatto et al.
T119 14586-14632 Sentence denotes 2015), selective laser melting (Ambrosi et al.
T120 14633-14649 Sentence denotes 2016; Loo et al.
T121 14650-14696 Sentence denotes 2017), and microextrusion printing (Foo et al.
T122 14697-14812 Sentence denotes 2018), have also been used for the fabrication of electrochemical sensors and electrodes using a variety of metals.
T123 14813-14901 Sentence denotes As shown in Table 1 , unstructured metal electrodes exhibit a range of detection limits.
T124 14902-15062 Sentence denotes For example, the detection limits of electrochemical biosensors for bacteria that employ unstructured metal electrodes range from 1 to 104 CFU/mL (see Table 1).
T125 15063-15288 Sentence denotes Table 1 Classification of label-free electrochemical biosensors for detection of pathogens in terms of: target, working electrode, biorecognition element, electrochemical method, limit of detection, and electrochemical probe.
T126 15289-15736 Sentence denotes Abbreviations: quartz crystal microbalance (QCM), electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), plaque-forming unit (PFU), colony-forming unit (CFU), indium tin oxide (ITO), carbon nanotube (CNT), magnetic bead (MB), nanoparticle (NP), differential pulse voltammetry (DPV), square wave voltammetry (SWV), anodic stripping voltammetry (ASV), hemagglutination units (HAU), and median tissue culture infectious dose (TCID50).
T127 15737-15853 Sentence denotes Target Pathogen Working Electrode Biorecognition Element Electrochemical Method & Probe Limit of Detection Reference
T128 15854-15964 Sentence denotes E. coli Au interdigitated microelectrode array polyclonal anti-E.coli EIS 104 CFU/mL Radke and Alocilja (2005)
T129 15965-16067 Sentence denotes E. coli ITO electrode monoclonal anti-E. coli CV, EIS; Fe(CN)63-/4- 4 × 103 CFU/mL Zhang et al. (2005)
T130 16068-16161 Sentence denotes E. coli chromium interdigitated microelectrode array anti-E. coli EIS – Suehiro et al. (2006)
T131 16162-16269 Sentence denotes S. typhimurium ITO interdigitated microelectrode array anti-S. typhimurium EIS 10 CFU/mL Yang and Li (2006)
T132 16270-16368 Sentence denotes V. cholerae carbon electrode polyclonal anti-V. cholerae amperometry 8 CFU/mL Sharma et al. (2006)
T133 16369-16467 Sentence denotes E. coli Pt wire electrode polyclonal anti-E. coli potentiometry 9 × 105 CFU/mL Boehm et al. (2007)
T134 16468-16552 Sentence denotes E. coli Au microelectrode polyclonal anti-E.coli EIS 10 CFU/mL Maalouf et al. (2007)
T135 16553-16667 Sentence denotes L. monocytogenes TiO2 nanowires on Au electrode monoclonal anti-L. monocytogenes EIS 470 CFU/mL Wang et al. (2008)
T136 16668-16763 Sentence denotes E. coli Au electrode polyclonal anti-E. coli CV, EIS; Fe(CN)63-/4- 50 CFU/mL Geng et al. (2008)
T137 16764-16874 Sentence denotes S. typhimurium Au electrode polyclonal anti-S. typhimurium EIS; Fe(CN)63-/4- 10 CFU/mL Pournaras et al. (2008)
T138 16875-16981 Sentence denotes S. typhimurium Au microelectrode anti-S. typhimurium EIS; Fe(CN)63-/4- 500 CFU/mL Nandakumar et al. (2008)
T139 16982-17103 Sentence denotes E. coli graphite interdigitated microelectrode array E. coli-specific bacteriophages EIS 104 CFU/mL Shabani et al. (2008)
T140 17104-17200 Sentence denotes S. typhimurium Au electrode polyclonal anti-S. typhimurium EIS 100 CFU/mL Mantzila et al. (2008)
T141 17201-17298 Sentence denotes S. typhimurium macroporous silicon electrode anti-S. typhimurium EIS 103 CFU/mL Das et al. (2009)
T142 17299-17436 Sentence denotes West Nile virus (WNV) nanostructured alumina on Pt wire electrode monoclonal anti-WNV AC voltammetry 0.02 viruses/mL Nguyen et al. (2009)
T143 17437-17547 Sentence denotes S. typhimurium Au electrode monoclonal anti-S. typhimurium EIS; Fe(CN)63-/4- 100 CFU/mL La Belle et al. (2009)
T144 17548-17673 Sentence denotes S. typhimurium CNTs on carbon rod electrode anti-S. typhimurium aptamer potentiometry 0.2 CFU/mL Zelada-Guillen et al. (2009)
T145 17674-17770 Sentence denotes E. coli Au electrode anti-E. coli CV, EIS; Fe(CN)63-/4- 3.3 CFU/mL Escamilla-Gomez et al. (2009)
T146 17771-17892 Sentence denotes B. anthracis Ag electrode monoclonal and polyclonal anti-B. anthracis conductometry 420 spores/mL Pal and Alocilja (2009)
T147 17893-18012 Sentence denotes E. coli polysilicon interdigitated microelectrode array polyclonal anti-E. coli EIS 300 CFU/mL de la Rica et al. (2009)
T148 18013-18126 Sentence denotes E. coli Au interdigitated microelectrode array E. coli-specific bacteriophages EIS 104 CFU/mL Mejri et al. (2010)
T149 18127-18236 Sentence denotes E. coli CNTs on carbon rod electrode anti-E. coli aptamer potentiometry 6 CFU/mL Zelada-Guillen et al. (2010)
T150 18237-18374 Sentence denotes Campylobacter jejuni Fe3O4 nanoparticles on carbon electrode monoclonal anti-Flagellin A EIS; Fe(CN)63-/4- 103 CFU/mL Huang et al. (2010)
T151 18375-18497 Sentence denotes marine pathogenic sulphate-reducing bacteria (SRB) AuNPs on nickel foam electrode anti-SRB EIS 21 CFU/mL Wan et al. (2010)
T152 18498-18615 Sentence denotes E. coli Ag nanofiber array electrode monoclonal and polyclonal anti-E. coli conductometry 61 CFU/mL Luo et al. (2010)
T153 18616-18759 Sentence denotes bovine viral diarrhea virus (BVDV) Ag nanofiber array electrode monoclonal and polyclonal anti-BVDV conductometry 103 CCID/mL Luo et al. (2010)
T154 18760-18862 Sentence denotes E. coli Au interdigitated microelectrode array magainin I peptide EIS 103 CFU/mL Mannoor et al. (2010)
T155 18863-18951 Sentence denotes E. coli Au rod electrode concanavalin A lectin capacitive 12 CFU/mL Jantra et al. (2011)
T156 18952-19043 Sentence denotes rotavirus graphene microelectrode monoclonal anti-rotavirus CV 103 PFU/mL Liu et al. (2011)
T157 19044-19139 Sentence denotes human influenza A virus H3N2 Au electrode polyclonal anti-H3N2 EIS 8 ng/mL Hassen et al. (2011)
T158 19140-19251 Sentence denotes E. coli Au microelectrode polyclonal anti-E. coli capacitive, EIS, CV; Fe(CN)63-/4- 220 CFU/mL Li et al. (2011)
T159 19252-19397 Sentence denotes Enterobacter cloacae Au electrode concanavalin A lectin, ricinus communis agglutinin lectin CV, EIS; Fe(CN)63-/4- 1 × 103 CFU/mL Xi et al. (2011)
T160 19398-19526 Sentence denotes E. coli Au electrode concanavalin A lectin, ricinus communis agglutinin lectin CV, EIS; Fe(CN)63-/4- 100 CFU/mL Xi et al. (2011)
T161 19527-19627 Sentence denotes B. subtilis Au electrode concanavalin A lectin CV, EIS; Fe(CN)63-/4- 1 × 104 CFU/mL Xi et al. (2011)
T162 19628-19699 Sentence denotes E. coli Pt wire electrode anti-E. coli EIS 100 CFU/mL Tan et al. (2011)
T163 19700-19775 Sentence denotes S. aureus Pt wire electrode anti-S. aureus EIS 100 CFU/mL Tan et al. (2011)
T164 19776-19933 Sentence denotes marine pathogenic sulphate-reducing bacteria (SRB) graphene/chitosan composite on carbon electrode anti-SRB CV, EIS; Fe(CN)63-/4- 18 CFU/mL Wan et al. (2011)
T165 19934-20061 Sentence denotes swine influenza virus (SIV) H1N1 PDDA/CNT composite on Au microelectrode anti-SIV conductometry 180 TCID50/mL Lee et al. (2011)
T166 20062-20148 Sentence denotes E. coli graphene microelectrode anti-E. coli amperometry 10 CFU/mL Huang et al. (2011)
T167 20149-20229 Sentence denotes E. coli PEDOT:PSS electrode anti-E. coli amperometry 103 CFU/mL He et al. (2012)
T168 20230-20377 Sentence denotes dengue type 2 virus (DENV-2) nanostructured alumina on Pt wire electrode monoclonal anti-DENV-2 DPV;Ferrocene methanol 1 PFU/mL Cheng et al. (2012)
T169 20378-20509 Sentence denotes DENV-2 nanostructured alumina on Pt wire electrode monoclonal anti-DENV-2 CV, EIS; Ferrocene methanol 1 PFU/mL Nguyen et al. (2012)
T170 20510-20657 Sentence denotes human influenza A viruses H1N1 and H3N2 silicon nanowire electrode array anti-H1N1, anti-H3N2 conductometry 2.9 × 104 viruses/mL Shen et al. (2012)
T171 20658-20785 Sentence denotes E. coli AuNP/Chitosan/CNT and SiO2/thionine NP composite on Au electrode monoclonal anti-E. coli CV 250 CFU/mL Li et al. (2012)
T172 20786-20911 Sentence denotes E. coli CNT/polyallylamine composite on graphite electrode monoclonal anti-E. coli ASV 800 cells/mL Viswanathan et al. (2012)
T173 20912-21049 Sentence denotes Campylobacter CNT/polyallylamine composite on graphite electrode monoclonal anti-Campylobacter ASV 400 cells/mL Viswanathan et al. (2012)
T174 21050-21189 Sentence denotes S. typhimurium CNT/polyallylamine composite on graphite electrode monoclonal anti-S. typhimurium ASV 400 cells/mL Viswanathan et al. (2012)
T175 21190-21290 Sentence denotes S. aureus CNT electrode anti-S. aureus aptamer potentiometry 800 CFU/mL Zelada-Guillen et al. (2012)
T176 21291-21386 Sentence denotes E. coli Au electrode mannose carbohydrate ligand EIS; Fe(CN)63-/4- 100 CFU/mL Guo et al. (2012)
T177 21387-21514 Sentence denotes S. aureus graphene interdigitated microelectrode array odoranin-HP peptide conductometry 1 × 104 cells/mL Mannoor et al. (2012)
T178 21515-21645 Sentence denotes Helicobacter pylori graphene interdigitated microelectrode array odoranin-HP peptide conductometry 100 cells Mannoor et al. (2012)
T179 21646-21758 Sentence denotes L. innocua Au electrode L. innocua-specific bacteriophage EIS; Fe(CN)63-/4- 1.1 × 104 CFU/mL Tolba et al. (2012)
T180 21759-21858 Sentence denotes E. coli polyaniline on Au electrode monoclonal anti-E. coli EIS 100 CFU/mL Chowdhury et al. (2012).
T181 21859-21960 Sentence denotes E. coli Au interdigitated microelectrode array anti-E. coli EIS 2.5 × 104 CFU/mL Dweik et al. (2012).
T182 21961-22089 Sentence denotes E. coli ultra-nanocrystalline diamond microelectrode array anti-E. coli EIS; Fe(CN)63-/4- 1 × 103 CFU/mL Siddiqui et al. (2012).
T183 22090-22229 Sentence denotes human influenza A virus H1N1 Au microelectrode phenotype-specific sialic acid-galactose moieties EIS; Fe(CN)63-/4- – Wicklein et al. (2013)
T184 22230-22331 Sentence denotes E. coli Au electrode E. coli-specific bacteriophages EIS; Fe(CN)63-/4- 800 CFU/mL Tlili et al. (2013)
T185 22332-22499 Sentence denotes DENV-2, dengue virus 3 (DENV-3) Pt-coated nanostructured alumina membrane electrode monoclonal anti-dengue EIS; Fe(CN)63-/4- 0.23 PFU/mL, 0.71 PFU/mL Peh and Li (2013)
T186 22500-22647 Sentence denotes cucumber mosaic virus (CMV) polypyrrole nanoribbons on Au microelectrode array polyclonal anti-CMV amperometry 10 ng/mL Chartuprayoon et al. (2013)
T187 22648-22751 Sentence denotes E. coli Au electrode polyclonal anti-E. coli EIS; Fe(CN)63- 2 CFU/mL Barreiros dos Santos et al. (2013)
T188 22752-22867 Sentence denotes E. coli AuNPs on reduced graphene oxide microelectrode anti-E. coli EIS; Fe(CN)63-/4- 150 CFU/mL Wang et al. (2013)
T189 22868-22945 Sentence denotes E. coli Ag/AgCl wire electrode anti-E. coli EIS 10 CFU/mL Joung et al. (2013)
T190 22946-23103 Sentence denotes murine norovirus (MNV) AuNPs on carbon electrode anti-norovirus (MNV) aptamer SWV, fluorescence; Fe(CN)63-/Ru(NH3)63+ 180 viruses Giamberardino et al. (2013)
T191 23104-23204 Sentence denotes rotavirus reduced graphene oxide microelectrode anti-rotavirus amperometry 100 PFU Liu et al. (2013)
T192 23205-23372 Sentence denotes S. typhimurium AuNP-functionalized poly(amidoamine)-CNT-chitosan composite on carbon electrode anti- S. typhimurium CV, EIS; Fe(CN)63-/4- 500 CFU/mL Dong et al. (2013)
T193 23373-23480 Sentence denotes E. coli Au-tungsten microwire electrode monoclonal anti-E. coli EIS; Fe(CN)63-/4- 5 CFU/mL Lu et al. (2013)
T194 23481-23552 Sentence denotes E. coli Pt wire electrode anti-E. coli EIS 10 CFU/mL Chan et al. (2013)
T195 23553-23679 Sentence denotes S. aureus reduced graphene oxide on carbon rod electrode anti-S. aureus aptamer potentiometry 1 CFU/mL Hernandez et al. (2014)
T196 23680-23774 Sentence denotes E. coli PAA/PD/CNT composite on carbon electrode anti-E. coli ASV 13 CFU/mL Chen et al. (2014)
T197 23775-23905 Sentence denotes S. typhimurium AuNPs on graphene oxide on carbon electrode anti-S. typhimurium aptamer EIS; Fe(CN)63-/4- 3 CFU/mL Ma et al. (2014)
T198 23906-24046 Sentence denotes S. aureus AuNPs on reduced graphene oxide on carbon electrode anti-S. aureus synthetic aptamer EIS; Fe(CN)63-/4- 10 CFU/mL Jia et al. (2014)
T199 24047-24141 Sentence denotes E. coli Au electrode mannose carbohydrate ligand CV, mass change 1 CFU/mL Yazgan et al. (2014)
T200 24142-24267 Sentence denotes L. monocytogenes Au interdigitated microelectrode array leucocin A antimicrobial peptide EIS 103 CFU/mL Etayash et al. (2014)
T201 24268-24394 Sentence denotes S. typhimurium Au interdigitated microelectrode array monoclonal anti-S. typhimurium EIS 3 × 103 CFU/mL Dastider et al. (2015)
T202 24395-24496 Sentence denotes S. aureus Au electrode polyclonal anti-S. typhimurium EIS; Fe(CN)63-/4- 10 CFU/mL Bekir et al. (2015)
T203 24497-24595 Sentence denotes E. coli CNTs on Au electrode clavanin A peptide EIS; Fe(CN)63-/4- 100 CFU/mL Andrade et al. (2015)
T204 24596-24708 Sentence denotes Klebsiella pneumoniae CNTs on Au electrode clavanin A peptide EIS; Fe(CN)63-/4- 103 CFU/mL Andrade et al. (2015)
T205 24709-24821 Sentence denotes Enterococcus faecalis CNTs on Au electrode clavanin A peptide EIS; Fe(CN)63-/4- 103 CFU/mL Andrade et al. (2015)
T206 24822-24924 Sentence denotes B. subtilis CNTs on Au electrode clavanin A peptide EIS; Fe(CN)63-/4- 100 CFU/mL Andrade et al. (2015)
T207 24925-25055 Sentence denotes E. coli PEI/CNT composite on carbon electrode E. coli-specific bacteriophages EIS; Fe(CN)63-/4- 50 CFU/mL Zhou and Ramasamy (2015)
T208 25056-25188 Sentence denotes dengue virus 1–4 AuNPs on Au electrode anti-DENV-1, anti-DENV-2, anti-DENV-3, anti-DENV-4 CV, EIS; Fe(CN)63-/4- – Luna et al. (2015)
T209 25189-25301 Sentence denotes E. coli ITO microelectrode monoclonal anti-E. coli EIS; Fe(CN)63-/4- 1 CFU/mL Barreiros dos Santos et al. (2015)
T210 25302-25443 Sentence denotes avian influenza virus (AIV) H5N1 Au interdigitated microelectrode array monoclonal anti-AIV-H5N1 EIS; Fe(CN)63-/4- 4 HAU/mL Lin et al. (2015)
T211 25444-25552 Sentence denotes C. parvum AuNPs on carbon electrode anti-C. parvum aptamer SWV; Fe(CN)63-/4- 100 oocysts Iqbal et al. (2015)
T212 25553-25672 Sentence denotes E. coli CNT-coated Au-tungsten microwire electrodes polyclonal anti-E. coli amperometry 100 CFU/mL Yamada et al. (2016)
T213 25673-25796 Sentence denotes S. aureus CNT-coated Au-tungsten microwire electrodes polyclonal anti-S. aureus amperometry 100 CFU/mL Yamada et al. (2016)
T214 25797-25913 Sentence denotes S. aureus Au interdigitated microelectrode array anti-S. aureus EIS; Fe(CN)63-/4- 1.3 CFU/mL Primiceri et al. (2016)
T215 25914-26042 Sentence denotes L. monocytogenes Au interdigitated microelectrode array anti-L. monocytogenes EIS; Fe(CN)63-/4- 5 CFU/mL Primiceri et al. (2016)
T216 26043-26152 Sentence denotes norovirus Au microelectrode anti-norovirus aptamer SWV; Fe(CN)63-/Ru(NH3)63+ 10 PFU/mL Kitajima et al. (2016)
T217 26153-26298 Sentence denotes avian influenza virus (AIV) H5N1 Au interdigitated microelectrode array anti-AIV-H5N1 aptamer EIS; Fe(CN)63-/4- 4.2 HAU/mL Callaway et al. (2016)
T218 26299-26436 Sentence denotes S. typhimurium poly[pyrrole-co-3-carboxyl-pyrrole] copolymer electrode anti-S. typhimurium aptamer EIS 3 CFU/mL Sheikhzadeh et al. (2016)
T219 26437-26546 Sentence denotes E. coli polysilicon interdigitated microelectrodes polyclonal anti-E. coli EIS – Mallén-Alberdi et al. (2016)
T220 26547-26685 Sentence denotes human influenza A virus H3N2 Au electrode phenotype-specific oligoethylene glycol moieties EIS 1.3 × 104 viruses/mL Hushegyi et al. (2016)
T221 26686-26803 Sentence denotes E. coli PEI/CNT composite on Au microwire electrode polyclonal anti-E. coli amperometry 100 CFU/mL Lee and Jun (2016)
T222 26804-26918 Sentence denotes V. cholerae CeO2 nanowires on Pt microelectrode anti-V. cholerae EIS; Fe(CN)63-/4- 100 CFU/mL Tam and Thang (2016)
T223 26919-27040 Sentence denotes S. aureus PEI/CNT composite on Au microwire electrode polyclonal anti-S. aureus amperometry 100 CFU/mL Lee and Jun (2016)
T224 27041-27140 Sentence denotes E. coli graphene microelectrode polyclonal anti-E. coli amperometry 5 × 103 CFU/mL Wu et al. (2016)
T225 27141-27233 Sentence denotes E. coli Au electrode concanavalin A lectin EIS; Fe(CN)63-/4- 75 cells/mL Yang et al. (2016b)
T226 27234-27307 Sentence denotes E. coli Pt wire electrodes anti-E. coli EIS 100 CFU/mL Tian et al. (2016)
T227 27308-27385 Sentence denotes S. aureus Pt wire electrodes anti-S. aureus EIS 100 CFU/mL Tian et al. (2016)
T228 27386-27515 Sentence denotes B. subtilis CNTs on Au interdigitated microelectrode array polyclonal anti-B. subtilis conductometry 100 CFU/mL Yoo et al. (2017)
T229 27516-27668 Sentence denotes S. epidermidis Au microelectrode S. epidermidis-imprinted poly(3-aminophenylboronic acid) polymer film EIS; Fe(CN)63-/4- 103 CFU/mL Golabi et al. (2017)
T230 27669-27796 Sentence denotes norovirus graphene/AuNP composite on carbon electrode anti-norovirus aptamer DPV; Ferrocene 100 pM Chand and Neethirajan (2017)
T231 27797-27912 Sentence denotes norovirus Au electrode synthetic norovirus-specific peptide CV, EIS; Fe(CN)63-/4- 7.8 copies/mL Hwang et al. (2017)
T232 27913-28043 Sentence denotes E. coli CuO/cysteine/reduced graphene/Au oxide electrode monoclonal anti-E. coli EIS; Fe(CN)63-/4- 3.8 CFU/mL Pandey et al. (2017)
T233 28044-28177 Sentence denotes Japanese encephalitis virus (JEV) carbon NPs on carbon electrode monoclonal anti-JEV CV, EIS; Fe(CN)63-/4- 2 ng/mL Chin et al. (2017)
T234 28178-28289 Sentence denotes S. aureus CNTs on carbon electrode polyclonal anti-S. aureus DPV; Fe(CN)63-/4- 13 CFU/mL Bhardwaj et al. (2017)
T235 28290-28457 Sentence denotes human influenza A virus H1N1 PEDOT film electrode hemagglutinin-specific trisaccharide ligand EIS, potentiometry, mass change; Fe(CN)63-/4- 0.013 HAU Hai et al. (2017)
T236 28458-28616 Sentence denotes human influenza A virus H1N1 reduced graphene oxide on Au microelectrode monoclonal anti-H1N1 chrono-amperometry; Fe(CN)63-/4- 0.5 PFU/mL Singh et al. (2017b)
T237 28617-28722 Sentence denotes E. coli Au microelectrode E. coli-imprinted MAH/HEMA polymer film capacitive 70 CFU/mL Idil et al. (2017)
T238 28723-28855 Sentence denotes E. coli chitosan/polypyrrole/CNT/AuNP composite on graphite electrode monoclonal coli CV; Fe(CN)63-/4- 30 CFU/mL Güner et al. (2017)
T239 28856-28971 Sentence denotes S. dysenteriae AuNPs on carbon electrode anti-S. dysenteriae aptamer EIS; Fe(CN)63-/4- 1 CFU/mL Zarei et al. (2018)
T240 28972-29109 Sentence denotes human influenza A virus H1N1 PEDOT:PSS film electrode hemagglutinin-specific trisaccharide ligand amperometry 0.015 HAU Hai et al. (2018)
T241 29110-29238 Sentence denotes S. aureus fluoride-doped tin oxide electrode S. aureus-imprinted Ag–MnO2 film DPV; Fe(CN)63-/4- 103 CFU/mL Divagar et al. (2019)
T242 29239-29353 Sentence denotes E. coli Au microelectrode E. coli-imprinted TEOS/MTMS sol-gel film EIS; Fe(CN)63-/4- 1 CFU/mL Jafari et al. (2019)
T243 29354-29454 Sentence denotes norovirus Au electrode norovirus-specific peptide EIS; Fe(CN)63-/4- 1.7 copies/mL Baek et al. (2019)
T244 29455-29586 Sentence denotes C. parvum Au interdigitated microelectrode array monoclonal anti-C. parvum Capacitive; Fe(CN)63-/4- 40 cells/mm2 Luka et al. (2019)
T245 29587-29718 Sentence denotes E. coli 4-(3-pyrrol) butryic acid electrode concanavalin A lectin, Arachis hypogaea lectin EIS 6 × 103 CFU/mL Saucedo et al. (2019)
T246 29719-29854 Sentence denotes B. subtilis 4-(3-pyrrol) butryic acid electrode concanavalin A lectin, Arachis hypogaea lectin EIS 6 × 103 CFU/mL Saucedo et al. (2019)
T247 29855-30006 Sentence denotes E. coli silica NPs on polyelectrolyte multilayer on Au electrode polyclonal anti-E. coli CV; Fe(CN)63-/4- 2 × 103 CFU/mL Mathelie-Guinlet et al. (2019)
T248 30007-30158 Sentence denotes E. coli silica NPs on polyelectrolyte multilayer on Au electrode polyclonal anti-E. coli CV; Fe(CN)63-/4- 2 × 103 CFU/mL Mathelie-Guinlet et al. (2019)
T249 30160-30185 Sentence denotes 2.1.2 Ceramic electrodes
T250 30186-30348 Sentence denotes Conducting and semiconducting ceramics, including indium tin oxide (ITO), polysilicon, and titanium dioxide (TiO2) have also been examined for pathogen detection.
T251 30349-30463 Sentence denotes For example, Das et al. used a silicon electrode for Salmonella typhimurium (S. typhimurium) detection (Das et al.
T252 30464-30470 Sentence denotes 2009).
T253 30471-30644 Sentence denotes Barreiros dos Santos et al. developed an antibody-functionalized ITO electrode for the detection of E. coliwith a dynamic range of 10–106 CFU/mL (Barreiros dos Santos et al.
T254 30645-30651 Sentence denotes 2015).
T255 30652-30897 Sentence denotes In addition to high conductivity, ITO is transparent, which presents various measurement advantages, including the ability to accurately correlate biosensor response with pathogen surface coverage (Aydın and Sezgintürk, 2017; Yang and Li, 2005).
T256 30898-31105 Sentence denotes Transparent electrodes also enable in situ verification of target binding via microscopic techniques and offer compatibility with optical approaches, such as those based on optical stimulation (Wenzel et al.
T257 31106-31112 Sentence denotes 2018).
T258 31113-31309 Sentence denotes Carbon electrodes based on various allotropes of carbon, such as graphite and glass-like carbon, can also be classified as ceramic materials due to their mechanical properties (e.g., brittleness).
T259 31311-31336 Sentence denotes 2.1.3 Polymer electrodes
T260 31337-31411 Sentence denotes Polymers have also been investigated as electrodes for pathogen detection.
T261 31412-31536 Sentence denotes Polymers have various advantages, including tunable electrical conductivity, biocompatiblity, and environmentally stability.
T262 31537-31655 Sentence denotes Polymer electrodes are also compatible with a range of biorecognition element immobilization techniques (Arshak et al.
T263 31656-31676 Sentence denotes 2009; Guimard et al.
T264 31677-31683 Sentence denotes 2007).
T265 31684-31858 Sentence denotes Polymers also exhibit mechanical properties that enable electrode-tissue mechanical matching, an important consideration in the design of implantable and wearable biosensors.
T266 31859-31955 Sentence denotes Polymer electrodes can be broadly classified as (1) conjugated polymer or (2) polymer composite.
T267 31956-32122 Sentence denotes Polyaniline and polypyrrole have been the most commonly used conjugated polymers for pathogen detection due to their high conductivity in the doped state (Kaur et al.
T268 32123-32129 Sentence denotes 2015).
T269 32130-32251 Sentence denotes Moreover, polypyrrole has been shown to be biocompatible and exhibit affinity for methylated nucleic acids (Arshak et al.
T270 32252-32258 Sentence denotes 2009).
T271 32259-32441 Sentence denotes However, polyaniline films lose electrochemical activity in solutions of pH greater than 4, which presents a measurement challenge when considering samples of varying pH (Wan, 2008).
T272 32442-32647 Sentence denotes Conjugated polymer electrodes commonly exhibit thin-film form factors and are deposited onto insulating substrates via layer-by-layer approaches, spin coating, or electrochemical polymerization (Xia et al.
T273 32648-32654 Sentence denotes 2010).
T274 32655-32798 Sentence denotes For example, Chowdhury et al. used a polyaniline electrode for detection of E. coli over a dynamic range of 102 to 107 CFU/mL (Chowdhury et al.
T275 32799-32805 Sentence denotes 2012).
T276 32806-33035 Sentence denotes Hai et al. and He et al. used organic transistors based on spin-coated poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) films for detection of human influenza A virus (H1N1) and E. coli, respectively (Hai et al.
T277 33036-33051 Sentence denotes 2018; He et al.
T278 33052-33058 Sentence denotes 2012).
T279 33059-33193 Sentence denotes Polymer composite electrodes are often composed of a non-conducting polymer mixed with a conducting or semiconducting dispersed phase.
T280 33194-33371 Sentence denotes Micro-particles and nanomaterials, such as graphite, Au nanoparticles (AuNPs), graphene, and carbon nanotubes (CNTs), have been commonly used as the dispersed phase (Dong et al.
T281 33372-33388 Sentence denotes 2013; Lee et al.
T282 33389-33422 Sentence denotes 2011; Lee and Jun 2016; Li et al.
T283 33423-33447 Sentence denotes 2012; Viswanathan et al.
T284 33448-33524 Sentence denotes 2012) in combination with various polymers, including chitosan (Güner et al.
T285 33525-33612 Sentence denotes 2017), polyethylenimine (PEI) (Lee and Jun 2016), and polyallyamine (Viswanathan et al.
T286 33613-33619 Sentence denotes 2012).
T287 33620-33873 Sentence denotes For example, Viswanathan et al. developed a polyallylamine/CNT polymer composite electrode for the detection of E. coli, S. typhimurium, and Campylobacter via anodic stripping voltammetry over the dynamic range of 103 to 105 cells/mL (Viswanathan et al.
T288 33874-33880 Sentence denotes 2012).
T289 33881-34037 Sentence denotes A multicomponent polymer composite electrode of poly(amidoamine), CNTs, and chitosan layered with AuNPs enabled the detection of S. typhimurium (Dong et al.
T290 34038-34044 Sentence denotes 2013).
T291 34045-34206 Sentence denotes The detection limits associated with polymer composite electrodes are comparable to metallic and polymer electrodes and range from 1 to 103 CFU/mL (see Table 1).
T292 34207-34467 Sentence denotes While polymer composite electrodes often contain nanomaterials, they are dispersed throughout the bulk of polymer, which is in contrast to the electrode nanostructuring techniques that occur at the electrode surface and are discussed in the following sections.
T293 34468-34560 Sentence denotes Polymer electrode development has been, in part, driven by the need for flexible biosensors.
T294 34561-34727 Sentence denotes For example, free-standing film electrodes and polymer electrodes on flexible substrates, such as paper, are now being examined for biosensing applications (Xu et al.
T295 34728-34734 Sentence denotes 2019).
T296 34735-34838 Sentence denotes Given conjugated polymers and polymer composites are compatible with 3D printing processes (Kong et al.
T297 34839-34963 Sentence denotes 2014), polymer electrodes are also emerging as attractive candidates for wearable conformal (i.e., form-fitting) biosensors.
T298 34964-35144 Sentence denotes While polymer electrodes typically exhibit planar form factors, such as thin films, they can also be constructed as nanowires and nanofibers, as discussed in the following section.
T299 35145-35268 Sentence denotes A comprehensive discussion of biosensor LOD and dynamic range for all electrode materials is provided in Table 1, Table 2 .
T300 35269-35532 Sentence denotes Table 2 Classification of electrochemical biosensors employing labels for pathogen detection in terms of: target, working electrode, biorecognition element, electrochemical method, limit of detection, electrochemical probe, and label or secondary processing step.
T301 35533-35980 Sentence denotes Abbreviations: quartz crystal microbalance (QCM), electrochemical impedance spectroscopy (EIS), cyclic voltommetry (CV), plaque-forming unit (PFU), colony-forming unit (CFU), indium tin oxide (ITO), carbon nanotube (CNT), magnetic bead (MB), nanoparticle (NP), differential pulse voltammetry (DPV), square wave voltammetry (SWV), anodic stripping voltammetry (ASV), hemagglutination units (HAU), and median tissue culture infectious dose (TCID50).
T302 35981-36120 Sentence denotes Target Pathogen Working Electrode Biorecognition Element Electrochemical Method & Probe Limit of Detection Secondary Binding Step Reference
T303 36121-36256 Sentence denotes E. coli ITO electrode anti-E. coli EIS; Fe(CN)63-/4- 6 × 105 cells/mL antibody/ALP conjugate label for amplification Yang and Li (2005)
T304 36257-36421 Sentence denotes V. cholerae carbon/polystyrene electrode polyclonal anti-V.cholerae chrono-amperometry 105 cells/mL antibody-ALP conjugate label for amplification Rao et al. (2006)
T305 36422-36574 Sentence denotes E. coli Au interdigitated microelectrode array polyclonal anti-E. coli EIS 2.67 × 106 cells/mL antibody-coated MBs for separation Varshney et al. (2007)
T306 36575-36746 Sentence denotes V. parahaemolytic carbon electrode anti-V. parahaemolytic CV; thionine/hydrogen peroxide 7.37 × 104 CFU/mL antibody/HRP conjugate label for transduction Zhao et al. (2007)
T307 36747-36914 Sentence denotes E. coli Au interdigitated microelectrode array polyclonal anti-E. coli EIS 7.4 × 104 CFU/mL antibody-coated MBs for separation and amplification Varshney and Li (2007)
T308 36915-37121 Sentence denotes E. coli AuNPs on carbon electrode monoclonal and polyclonal anti-E. coli CV; ferrocenedicarboxylic acid/hydrogen peroxide 6 CFU/mL polyclonal antibody/HRP conjugate label for amplification Lin et al. (2008)
T309 37122-37299 Sentence denotes S. aureus Au electrode anti-S. aureus amperometry; tetrathiafulvalene/hydrogen peroxide 370 cells/mL antibody/HRP conjugate label for amplification Escamilla-Gomez et al. (2008)
T310 37300-37546 Sentence denotes S. typhimurium Au electrode monoclonal anti-S. typhimurium chrono-amperometry; tetramethylbenzidine dihydrochloride/hydrogen peroxide 21 CFU/mL anti-S. typhimurium polyclonal antibody/HRP conjugate label for amplification Salam and Tothill (2009)
T311 37547-37773 Sentence denotes S. typhimurium graphite-epoxy composite electrode polyclonal anti-S. typhimurium amperometry 0.1 CFU/mL primary antibody-coated MBs for separation, secondary antibody/HRP conjugate label for amplification Liebana et al. (2009)
T312 37774-37938 Sentence denotes avian influenza virus (AIV) H5N1 Au interdigitated microelectrode array monoclonal anti-AIV-H5 EIS 0.26 HAU/mL antibody-coated MBs for separation Wang et al. (2010)
T313 37939-38208 Sentence denotes Streptococcus pneumoniae Au electrode polyclonal anti-S. pneumoniae amperometry; tetrathiafulvalene/hydrogen peroxide 1.5 × 104 CFU/mL antibody-coated MBs for separation and bacteria immobilization, antibody/HRP conjugate label for amplification Campuzano et al. (2010)
T314 38209-38392 Sentence denotes E. coli carbon-graphite electrode monoclonal anti-E. coli CV 7 CFU/mL antibody-coated MBs for separation, antibody/polyaniline label for amplification Setterington and Alocilja (2011)
T315 38393-38611 Sentence denotes S. aureus MBs on Au electrode polyclonal anti-Protein A (S. aureus) amperometry; tetrathiafulvalene/hydrogen peroxide 1 CFU/mL antibody/Protein A/HRP conjugate for amplification Esteban-Fernandez de Avila et al. (2012)
T316 38612-38864 Sentence denotes avian influenza virus (AIV) H5N1 Au interdigitated microelectrode array monoclonal anti-AIV-H5, polyclonal anti-AIV-N1 EIS 103 EDI50/mL anti-AIV-H5 monoclonal antibody- coated MBs for separation, red blood cell label for amplification Lum et al. (2012)
T317 38865-39101 Sentence denotes E. coli AuNPs/SiO2 nanocomposite on sulfhydryl chitosan/Fe(C2H5)2/C60 composite on carbon electrode monoclonal anti-E. coli CV; ferrocene 15 CFU/mL antibody/glucose oxidase/Pt nanochain conjugate label for amplification Li et al. (2013)
T318 39102-39315 Sentence denotes C. parvum polypyrrole-coated carbon electrode polyclonal anti-C. parvum chrono-potentiometry; o-phenylenediamine/hydrogen peroxide 500 oocysts/mL antibody/HRP conjugate label for amplification Laczka et al. (2013)
T319 39316-39494 Sentence denotes L. monocytogenes polymeric ion-selective membrane electrode anti-L. monocytogenes InlA aptamer potentiometry 10 CFU/mL aptamer/protamine label for transduction Ding et al. (2014)
T320 39495-39717 Sentence denotes avian influenza virus (AIV) H5N1 Au interdigitated electrode array anti-AIVH5N1 aptamer EIS 0.04 HAU/mL aptamer-coated MBs for separation, Concanavalin A/glucose oxide-coated AuNP labels for amplification Fu et al. (2014).
T321 39718-39973 Sentence denotes L. monocytogenes interdigitated microelectrode array monoclonal and polyclonal anti-L. monocytogenes EIS 300 CFU/mL monoclonal antibody-coated MBs for separation, polyclonal antibody-coated AuNP label for secondary binding amplification Chen et al. (2015)
T322 39974-40166 Sentence denotes E. coli carbon electrode polyclonal anti-E.coli chrono-amperometry 148 CFU/mL primary antibody-coated MBs for separation, secondary antibody-coated AuNPs for amplification Hassan et al. (2015)
T323 40167-40339 Sentence denotes avian influenza virus (AIV) H5N1 AuNPs on ITO microelectrode polyclonal anti-AIVH5N1 ASV 10 pg/mL antibody-coated MBs for separation and anodic stripping Zhou et al. (2015)
T324 40340-40484 Sentence denotes E. coli Au interdigitated microelectrode array anti-E.coli EIS; Fe(CN)63-/4- 100 CFU/mL wheat germ agglutinin for amplification Li et al. (2015)
T325 40485-40690 Sentence denotes E. coli carbon electrode monoclonal and polyclonal anti-E. coli DPV 10 CFU/mL monoclonal antibody-coated MBs for separation, polyclonal antibody-coated AuNP label for amplification Wang and Alocilja (2015)
T326 40691-40883 Sentence denotes norovirus nanostructured Au microelectrode concanavalin A lectin, polyclonal anti-norovirus CV, EIS; Fe(CN)63-/4- 35 copies/mL antibody-ALP conjugate label for amplification Hong et al. (2015)
T327 40884-41131 Sentence denotes Legionella pneumophila carbon electrode polyclonal anti-L. pneumophila amperometry; hydroquinone/hydrogen peroxide 10 CFU/mL primary antibody- coated MBs for separation, secondary antibody/HRP conjugate label for amplification Martin et al. (2015)
T328 41132-41317 Sentence denotes S. aureus carbon electrode anti-S.aureus aptamer ASV 1 CFU/mL primary aptamer-coated MBs for separation, secondary aptamer-coated AgNP label for anodic stripping Abbaspour et al. (2015)
T329 41318-41559 Sentence denotes L. monocytogenes Au interdigitated microelectrode array monoclonal and polyclonal anti-L. monocytogenes EIS 160 CFU/mL monoclonal antibody-coated MBs for separation, polyclonal antibody-coated AuNP label for amplification Chen et al. (2016b)
T330 41560-41758 Sentence denotes E. coli Au interdigitated microelectrode array polyclonal anti-E. coli CV, amperometry 52 CFU/mL antibody-coated, AuNP/glucose oxidase-modified MBs for separation and amplification Xu et al. (2016a)
T331 41759-41941 Sentence denotes E. coli Au interdigitated microelectrode array anti- E. coli EIS 100 CFU/mL antibody-coated MBs for separation, antibody/glucose oxidase conjugate for amplification Xu et al. (2016b)
T332 41942-42154 Sentence denotes S. typhimurium Au interdigitated microelectrode array monoclonal anti-S. typhimurium EIS 100 CFU/mL antibody-coated MBs for separation, antibody/glucose oxidase conjugate label for amplification Xu et al. (2016b)
T333 42155-42367 Sentence denotes E. coli chitosan/CNT composite on carbon electrode polyclonal anti-E. coli CV; thionine/hydrogen peroxide 50 CFU/mL secondary antibody/HRP conjugate label enzyme-assisted reduction reaction Gayathri et al. (2016)
T334 42368-42588 Sentence denotes S. typhimurium carbon electrode polyclonal and monoclonal anti-S. typhimurium DPV 100 cells/mL polyclonal antibody- coated MBs for separation, monoclonal antibody- coated AuNP label for amplification Afonso et al. (2016)
T335 42589-42698 Sentence denotes E. coli Au electrode anti-E. coli EIS; Fe(CN)63-/4- 100 CFU/mL AuNP label for amplification Wan et al. (2016)
T336 42699-42903 Sentence denotes L. monocytogenes Au interdigitated electrode array polyclonal anti-L. monocytogenes EIS 1.6 × 103 CFU/mL antibody-coated MBs for separation, antibody-coated AuNP label for amplification Wang et al. (2017)
T337 42904-43085 Sentence denotes E. coli Au microelectrode monoclonal anti-E. coli LSV 39 CFU/mL antibody-coated MBs for separation, antibody/AuNP/nucleotide/CdSNP conjugate label for amplification Li et al. (2017)
T338 43086-43275 Sentence denotes V. cholerae Au microelectrode polyclonal anti-V. cholerae LSV 32 CFU/mL antibody-coated MBs for separation, antibody/AuNP/nucleotide/PbSNP conjugate label for amplification Li et al. (2017)
T339 43276-43444 Sentence denotes avian influenza virus (AIV) H5N1 Au electrode anti-AIVH5N1, concanavalin A lectin CV 0.367 HAU/mL Concanavalin A- coated MB labels for amplification Zhang et al. (2017)
T340 43445-43672 Sentence denotes human influenza A virus H9N2 carbon electrode polyclonal anti-influenza A virus M2 protein, fetuin A chrono-amperometry 16 HAU antibody-coated MBs for separation, fetuin A-coated AuNP label for amplification Sayhi et al. (2018)
T341 43673-43854 Sentence denotes human enterovirus 71 (EV71) AuNPs on ITO electrode monoclonal anti-EV71 CV, EIS, colorimetry; Fe(CN)63-/4- 10 pg/mL antibody/HRP-coated MB labels for amplification Hou et al. (2018)
T342 43855-44015 Sentence denotes E. coli Ag interdigitated microelectrode array melittin peptide EIS 1 CFU/mL MLT-coated MBs used for separation and bacteria immobilization Wilson et al. (2019)
T343 44016-44179 Sentence denotes S. typhimurium Ag interdigitated electrode array melittin peptide EIS 10 CFU/mL MLT-coated MBs used for separation and bacteria immobilization Wilson et al. (2019)
T344 44180-44339 Sentence denotes S. aureus Ag interdigitated electrode array melittin peptide EIS 110 CFU/mL MLT-coated MBs used for separation and bacteria immobilization Wilson et al. (2019)
T345 44340-44534 Sentence denotes Middle East respiratory syndrome corona virus (MERS-CoV) AuNPs on carbon electrode MERS-CoV antigen-antibody complex SWV; Fe(CN)63-/4- 400 fg/mL MERS CoV-antibody complex Layqah and Eissa (2019)
T346 44536-44579 Sentence denotes 2.1.4 Electrode form factor and patterning
T347 44580-44685 Sentence denotes As shown in Table 1, Au electrodes of various size and form factor have been used for pathogen detection.
T348 44686-44874 Sentence denotes The use of complex masks and programmable tool paths with lithographic and 3D printing processes, respectively, also enable the fabrication of complex electrode geometries (Cesewski et al.
T349 44875-44890 Sentence denotes 2018; Xu et al.
T350 44891-44897 Sentence denotes 2017).
T351 44898-45098 Sentence denotes In addition to complex form factor, lithographic processes, 3D printing processes, and assembly operations also enable the fabrication of electrode arrays through electrode patterning (Hintsche et al.
T352 45099-45105 Sentence denotes 1994).
T353 45106-45300 Sentence denotes Electrode arrays, including interdigitated microelectrodes and other patterned electrodes, have been developed in an attempt to enhance the sensitivity and multiplexing capability of biosensors.
T354 45301-45436 Sentence denotes Interdigitated array microelectrodes (IDAMs) consist of alternating, parallel-electrode fingers organized in an interdigitated pattern.
T355 45437-45540 Sentence denotes IDAMs have been shown to exhibit rapid response and high signal-to-noise ratio (Varshney and Li, 2009).
T356 45541-45677 Sentence denotes As shown in Table 1, Au interdigitated microelectrode arrays are one of the most common electrode configurations for pathogen detection.
T357 45678-45821 Sentence denotes For example, Dastider et al. usedinterdigitated Au microelectrode arrays for detection of S. typhimurium via EIS (see Fig. 4a) (Dastider et al.
T358 45822-45828 Sentence denotes 2015).
T359 45829-45976 Sentence denotes Ceramic electrodes, such as ITO, with interdigitated array designs have also been examined for the detection of S. typhimurium (Yang and Li, 2006).
T360 45977-46083 Sentence denotes Mannoor et al. also examined interdigitated carbon-based electrodes for pathogen detection (Mannoor et al.
T361 46084-46090 Sentence denotes 2012).
T362 46091-46286 Sentence denotes The aforementioned emerging manufacturing processes are also used to construct electrode arrays that exhibit geometries other than interdigitated designs for electrochemical sensing applications.
T363 46287-46411 Sentence denotes For example, Yang et al. used aerosol jet additive manufacturing to fabricate silver (Ag) microelectrode arrays (Yang et al.
T364 46412-46419 Sentence denotes 2016a).
T365 46421-46453 Sentence denotes 2.1.5 Electrode nanostructuring
T366 46454-46611 Sentence denotes Transducers with physical dimensions comparable to the target species have been widely investigated as a means of creating sensitive biosensors (Gupta et al.
T367 46612-46631 Sentence denotes 2004; Pumera et al.
T368 46632-46650 Sentence denotes 2007; Singh et al.
T369 46651-46667 Sentence denotes 2010; Wei et al.
T370 46668-46674 Sentence denotes 2009).
T371 46675-46777 Sentence denotes Thus, electrodes ranging from micrometers to nanometers have been investigated for pathogen detection.
T372 46778-46884 Sentence denotes While nanoscale planar electrodes are among the most commonly examined for pathogen detection (Hong et al.
T373 46885-47195 Sentence denotes 2015; Peh and Li, 2013), the fabrication of nanoscale structures of conducting and semiconducting materials using a wide range of bottom-up and top-down nanomanufacturing processes, such as nanowires, has led to the investigation of nanostructured electrodes for pathogen detection (Patolsky and Lieber, 2005).
T374 47196-47366 Sentence denotes Nanostructuring can be performed simultaneously with bottom-up electrode fabrication processes or as a post-processing step with top-down electrode fabrication processes.
T375 47367-47527 Sentence denotes Nanowire-based electrodes have been fabricated using a variety of engineering materials using both bottom-up and top-down nanomanufacturing processes (Hu et al.
T376 47528-47561 Sentence denotes 1999; Yogeswaran and Chen, 2008).
T377 47562-47669 Sentence denotes A detailed review of nanomanufacturing processes for nanowire fabrication can be found elsewhere (Hu et al.
T378 47670-47676 Sentence denotes 1999).
T379 47677-47755 Sentence denotes Nanowires can exhibit circular, hexagonal, and even triangular cross-sections.
T380 47756-47877 Sentence denotes The nanowire aspect ratio, defined as the ratio of the length to width, often ranges from 1 to greater than 10 (Hu et al.
T381 47878-47938 Sentence denotes 1999; Vaseashta and Dimova-Malinovska, 2005; Wanekaya et al.
T382 47939-47945 Sentence denotes 2006).
T383 47946-48071 Sentence denotes As shown in Table 1, metallic and ceramic microwire- and nanowire-based electrodes have been examined for pathogen detection.
T384 48072-48262 Sentence denotes For example, Wang et al. used nanowire-bundled TiO2 electrodes synthesized using a bottom-up wet chemistry process for the detection of Listeria monocytogenes (L. monocytogenes) (Wang et al.
T385 48263-48269 Sentence denotes 2008).
T386 48270-48457 Sentence denotes Shen et al. fabricated silicon nanowire-based electrodes using a chemical vapor deposition process for the rapid detection of human influenza A virus in an array-based format (Shen et al.
T387 48458-48464 Sentence denotes 2012).
T388 48465-48590 Sentence denotes Although polymer nanowires have been relatively more applied to the detection of non-pathogenic species (Travas-Sejdic et al.
T389 48591-48672 Sentence denotes 2014), there appears to be potential for their application to pathogen detection.
T390 48673-48916 Sentence denotes Polymer nanowires are also synthesized via bottom-up and top-down nanomanufacturing processes, including hard template methods, soft template methods, or physical approaches, but efficient, large-scale synthesis remains a challenge (Xia et al.
T391 48917-48923 Sentence denotes 2010).
T392 48924-49040 Sentence denotes A comprehensive summary of studies using micro- and nano-wire electrodes for pathogen detection is shown in Table 1.
T393 49041-49196 Sentence denotes For example, Chartuprayoon et al. used Au microelectrode arrays modified with polypyrrole nanoribbons to detect cucumber mosaic virus (Chartuprayoon et al.
T394 49197-49203 Sentence denotes 2013).
T395 49204-49376 Sentence denotes The topographical modification of electrode surfaces with micro- and nano-structured features beyond wire-like structures has also been investigated for pathogen detection.
T396 49377-49592 Sentence denotes Electrode nanostructuring increases the electrode surface area without significantly increasing the electrode volume, thereby increasing the ratio of electrode surface area to fluid volume analyzed (Soleymani et al.
T397 49593-49599 Sentence denotes 2009).
T398 49600-49700 Sentence denotes Topographical modification of electrodes can also affect their mechanical and electrical properties.
T399 49701-49945 Sentence denotes For example, electrochemical deposition of PEDOT on silicon electrodes reduces the electrode electrical impedance across a wide frequency range, which offers measurement advantages for neural monitoring and recording applications (Ludwig et al.
T400 49946-49952 Sentence denotes 2006).
T401 49953-50155 Sentence denotes Electrode nanostructuring for pathogen detection beyond the fabrication of nanowire-based electrodes has been accomplished primarily using bottom-up wet chemistry approaches and electrochemical methods.
T402 50156-50238 Sentence denotes Among the wet chemistry approaches for electrode nanostructuring (Eftekhari et al.
T403 50239-50361 Sentence denotes 2008), nanostructured electrodes are often fabricated by the deposition or coupling of nanoparticles to planar electrodes.
T404 50362-50503 Sentence denotes For example, AuNPs are commonly deposited on planar electrodes to provide a nanostructured surface for biorecognition element immobilization.
T405 50504-50616 Sentence denotes In such studies, the particles are bound to the planar electrode via physical adsorption processes (Attar et al.
T406 50617-50655 Sentence denotes 2016) or chemical methods (Wang et al.
T407 50656-50662 Sentence denotes 2013).
T408 50663-50810 Sentence denotes In addition to AuNPs, CNTs have also been extensively investigated as potentially useful nanomaterials for electrode nanostructuring (see Table 1).
T409 50811-51127 Sentence denotes De Luna et al. found that high-curvature nanostructured Au microelectrodes exhibited a reduced extent of biorecognition element aggregation relative to that found on planar electrodes in DNA sensing studies using a combination of experimental studies and molecular dynamics simulations (see Fig. 3 a) (De Luna et al.
T410 51128-51148 Sentence denotes 2017; Mahshid et al.
T411 51149-51155 Sentence denotes 2016).
T412 51156-51400 Sentence denotes A study by Chin et al. found that nanostructuring of carbon electrodes with carbon nanoparticles enhanced the electron transfer kinetics and current intensity of the electrode by 63% for the detection of Japanese encephalitis virus (Chin et al.
T413 51401-51407 Sentence denotes 2017).
T414 51408-51594 Sentence denotes Fig. 3 Emerging transduction approaches associated with electrochemical biosensors for pathogen detection. a) A nanostructured Au microelectrode array with high curvature (De Luna et al.
T415 51595-51799 Sentence denotes 2017). b) Cell-imprinted polymer (CIP) with ‘artificial’ biorecognition elements for detection of E. coli using electrochemical impedance spectroscopy (EIS) and the Fe(CN)63-/4- redox probe (Jafari et al.
T416 51800-51806 Sentence denotes 2019).
T417 51807-52046 Sentence denotes Fig. 4 Measurement settings associated with electrochemical biosensor-based multiplexed pathogen detection. a) Microfluidic device with an interdigitated Au microelectrode array for continuous measurement of S. typhimurium (Dastider et al.
T418 52047-52208 Sentence denotes 2015). b) Conjugated nanoparticles with two different biorecognition elements for E. coli and V. cholerae detection via voltammetry using Fe(CN)63-/4- (Li et al.
T419 52209-52353 Sentence denotes 2017). c) Schematic of a microfluidic device with two separate spatial regions of biorecognition elements for E. coli and S. aureus (Tian et al.
T420 52354-52360 Sentence denotes 2016).
T421 52361-52663 Sentence denotes In addition to fabricating nanostructured electrodes by coupling already processed nanomaterials to planar electrodes, electrochemical methods are also commonly used for bottom-up electrode nanostructuring processes and have been leveraged to fabricate nanostructured electrodes for pathogen detection.
T422 52664-52856 Sentence denotes For example, Hong et al. fabricated a nanostructured Au electrode via electrochemical deposition of gold (III) chloride hydrates for the detection of norovirus in lettuce extracts (Hong et al.
T423 52857-52863 Sentence denotes 2015).
T424 52864-53084 Sentence denotes While the physical or chemical deposition of materials on planar electrodes provides a useful nanostructuring approach, introducing porosity to the electrode, such as nanoporosity, also enables electrode nanostructuring.
T425 53085-53212 Sentence denotes For example, Nguyen et al. utilized nanoporous alumina-coated Pt microwires for the detection of West Nile virus (Nguyen et al.
T426 53213-53219 Sentence denotes 2009).
T427 53220-53466 Sentence denotes While studies have reported improved biosensor performance using electrode nanostructuring, such as improved sensitivity and LOD, it is prudent to consider the effect of nanostructuring on biorecognition element immobilization and target binding.
T428 53467-53734 Sentence denotes For example, nanostructured electrodes that exhibit high-aspect-ratio structures and other three-dimensional structures have also been shown to enhance biomolecular steric hindrance effects, which may have implications for pathogen detection applications (Hong et al.
T429 53735-53751 Sentence denotes 2015; Lam et al.
T430 53752-53772 Sentence denotes 2012; Mahshid et al.
T431 53773-53779 Sentence denotes 2017).
T432 53780-53903 Sentence denotes There also remains a need to understand device-to-device and batch-to-batch variation in electrode nanostructuring quality.
T433 53904-54114 Sentence denotes For example, it is presently unclear how the structure (e.g., topography, crystal structure) and material properties (e.g., electrical properties) of nanostructured surfaces vary among mass-produced electrodes.
T434 54115-54230 Sentence denotes It is also unclear how such variance in nanostructuring quality affects the repeatability of biosensor performance.
T435 54232-54289 Sentence denotes 2.1.6 Integration of complementary transduction elements
T436 54290-54478 Sentence denotes Given the need for rapid and reliable measurements, biosensors that contain integrated electrodes and complementary transducers have also been examined for pathogen detection applications.
T437 54479-54634 Sentence denotes For example, electrodes have been integrated with transducers that enable simultaneous fluid mixing and monitoring of molecular binding events (Choi et al.
T438 54635-54641 Sentence denotes 2011).
T439 54642-54868 Sentence denotes Biosensors composed of multiple transducers, referred to as hybrid biosensors, also offer unique opportunities for in situ verification of target binding as well as complementary analytical measurements (i.e., dual detection).
T440 54869-55012 Sentence denotes Hybrid electrochemical biosensors for pathogen detection have been developed by integrating electrodes with optical and mechanical transducers.
T441 55013-55169 Sentence denotes Electrochemical-optical waveguide light mode spectroscopy (EC-OWLS) combines evanescent-field optical sensing with electrochemical sensing (Bearinger et al.
T442 55170-55176 Sentence denotes 2003).
T443 55177-55306 Sentence denotes EC-OWLS optically monitors changes and growth at the electrode surface to provide complementary information on surface reactions.
T444 55307-55377 Sentence denotes EC-OWLS has been used to monitor the growth of bacteria (Nemeth et al.
T445 55378-55453 Sentence denotes 2007) and could potentially be applied to selective detection of pathogens.
T446 55454-55698 Sentence denotes Electrochemical-surface plasmon resonance (EC-SPR) combines SPR sensing capability based on binding-induced refractive index changes at the electrode-electrolyte interface with electrochemical sensing capability on the same electrode (Hu et al.
T447 55699-55705 Sentence denotes 2008).
T448 55706-55792 Sentence denotes This approach has been used for monitoring molecular binding events (Juan-Colas et al.
T449 55793-55868 Sentence denotes 2017) and could potentially be applied to selective detection of pathogens.
T450 55869-56014 Sentence denotes In addition to their combination with optical transducers, hybrid electrochemical biosensors have also been combined with mechanical transducers.
T451 56015-56147 Sentence denotes Mechanical transducers have included shear-mode resonators, such as the quartz crystal microbalance (QCM) and cantilever biosensors.
T452 56148-56264 Sentence denotes Electrochemical-QCMs (E-QCMs) integrate mass-change and electrochemical sensing capabilities into a single platform.
T453 56265-56495 Sentence denotes For example, Li et al. used an antibody-functionalized E-QCM for the detection of E. coli, which provided complementary cyclic voltammetry, EIS, and capacitive sensing measurements associated with the detection response (Li et al.
T454 56496-56502 Sentence denotes 2011).
T455 56503-56619 Sentence denotes Serra et al. used a lectin-modified E-QCM to detect E. coli using the biosensor's mass-change response (Serra et al.
T456 56620-56626 Sentence denotes 2008).
T457 56627-56986 Sentence denotes Besides providing complementary responses for verification of binding events (Johnson and Mutharasan, 2012, 2013a), hybrid biosensors for pathogen detection can also generate fluid and particle mixing at the electrode-electrolyte interface and in the bulk solution via acoustic streaming or primary radiation effects of mechanical transducers (Cesewski et al.
T458 56987-56993 Sentence denotes 2018).
T459 56994-57135 Sentence denotes Thus, secondary transducers can apply force to bound species, such as nonspecifically adsorbed background species or captured target species.
T460 57136-57347 Sentence denotes For example, various studies have reported the removal of surface-bound biomolecules using mechanical transducers, such as shear-mode resonators or cantilever biosensors (Johnson and Mutharasan, 2014; Yeh et al.
T461 57348-57354 Sentence denotes 2007).
T462 57355-57781 Sentence denotes While the impediment or removal of nonspecifically adsorbed background species is a vital biosensor characteristic in pathogen detection applications that involve complex matrices, the regeneration of biosensor surfaces that contain specifically bound target species is essential for applications involving high-throughput characterization or process monitoring (e.g., bioprocesses or biomanufacturing processes) (Goode et al.
T463 57782-57788 Sentence denotes 2015).
T464 57789-57879 Sentence denotes Hybrid designs may also be useful for electrodes that exhibit a high extent of biofouling.
T465 57880-58160 Sentence denotes In addition to hybrid biosensor designs composed of combinations of electrodes with other transducers, hybrid biosensor-based assays for pathogen detection based on the combination of an electrochemical biosensor with a traditional bioanalytical technique have also been utilized.
T466 58161-58321 Sentence denotes For example, electrochemical-colorimetric (EC-C) biosensing combines an electrochemical method and a colorimetric, fluorescent, or luminescent detection method.
T467 58322-58542 Sentence denotes The electrode detects the presence of a target species, while the colorimetric transduction pathway enables quantification of the products associated with the reaction between the target and an active species (Hou et al.
T468 58543-58549 Sentence denotes 2018).
T469 58550-58755 Sentence denotes For example, Hou et al. used an EC-C approach based on a monoclonal antibody-functionalized AuNP-modified ITO electrode and dual-labeled magnetic beads for the detection of human enterovirus 71 (Hou et al.
T470 58756-58762 Sentence denotes 2018).
T471 58763-58962 Sentence denotes In that study, antibody- and horseradish peroxidase (HRP)-labeled magnetic nanobeads were introduced as a secondary binding step following exposure of the electrode to enterovirus-containing samples.
T472 58963-59231 Sentence denotes Following the secondary binding step, the HRP-nanobead conjugates enabled colorimetric detection via monitoring of oxidative products produced by HRP-catalyzed redox reactions, while the functionalized electrode enabled electrochemical detection via chronoamperometry.
T473 59232-59354 Sentence denotes Various techniques often rely on the use of optically-active labels for colorimetric, fluorescent, or luminescent sensing.
T474 59355-59688 Sentence denotes The optical labels used in pathogen detection applications commonly include biological fluorophores, such as green fluorescent protein, non-protein organic fluorophores, such as fluorescein and rhodamine, and nanoparticles, such as quantum dots, including CdS, CdSe, and GaAs, among others (Mungroo and Neethirajan 2016; Pires et al.
T475 59689-59695 Sentence denotes 2014).
T476 59696-59808 Sentence denotes The use of such additional reagents to detect the target species is discussed further in the following sections.
T477 59810-59838 Sentence denotes 2.2 Biorecognition elements
T478 59839-59964 Sentence denotes The previous section discussed the transduction elements associated with pathogen detection using electrochemical biosensors.
T479 59965-60221 Sentence denotes Given a biosensor is a device composed of integrated transducer and biorecognition elements, we next discuss the biorecognition elements used for selective detection of pathogens and corresponding immobilization techniques for their coupling to electrodes.
T480 60222-60333 Sentence denotes Biorecognition elements for electrochemical biosensors can be defined as (1) biocatalytic or (2) biocomplexing.
T481 60334-60461 Sentence denotes In the case of biocatalytic biorecognition elements, the biosensor response is based on a reaction catalyzed by macromolecules.
T482 60462-60559 Sentence denotes Enzymes, whole cells, and tissues are the most commonly used biocatalytic biorecognition element.
T483 60560-60772 Sentence denotes While enzyzmes provide biorecognition elements in various chemical sensing applications, they are often used as labels for pathogen detection applications and most commonly introduced via secondary binding steps.
T484 60773-60944 Sentence denotes In the case of biocomplexing biorecognition elements, the biosensor response is based on the interaction of analytes with macromolecules or organized molecular assemblies.
T485 60945-61096 Sentence denotes As shown in Table 1, Table 2, antibodies, peptides, and phages are the most commonly used biocomplexing biorecognition elements for pathogen detection.
T486 61097-61271 Sentence denotes In addition to biomacromolecules, imprinted polymers have also been examined as biocomplexing biorecognition elements for pathogen detection using electrochemical biosensors.
T487 61273-61313 Sentence denotes 2.2.1 Antibodies and antibody fragments
T488 61314-61465 Sentence denotes Antibodies and antibody fragments are among the most commonly utilized biorecognition elements for pathogen detection using electrochemical biosensors.
T489 61466-61568 Sentence denotes Biosensors employing antibody-based biorecognition elements are commonly referred to as immunosensors.
T490 61569-61790 Sentence denotes Given antibodies exhibit high selectivity and binding affinity for target species and can be generated for a wide range of infectious agents, antibodies are the gold-standard biorecognition element for pathogen detection.
T491 61791-61944 Sentence denotes Antibodies contain recognition sites that selectively bind to antigens through a specific region of the antigen, referred to as an epitope (Patris et al.
T492 61945-61951 Sentence denotes 2016).
T493 61952-62076 Sentence denotes Antibodies can be labeled with fluorescent or enzymatic tags, which leads to the designation of the approach as label-based.
T494 62077-62232 Sentence denotes While label-based approaches present measurement constraints associated with the use of additional reagents and processing steps (Cooper, 2009; Sang et al.
T495 62233-62357 Sentence denotes 2016), antibody labeling may also alter the binding affinity to the antigen, which could affect the biosensor's selectivity.
T496 62358-62481 Sentence denotes A detailed discussion of label-based biosensing approaches for pathogen detection has been reported elsewhere (Ahmed et al.
T497 62482-62540 Sentence denotes 2014; Alahi and Mukhopadhyay, 2017; Bozal-Palabiyik et al.
T498 62541-62561 Sentence denotes 2018; Leonard et al.
T499 62562-62568 Sentence denotes 2003).
T500 62569-62698 Sentence denotes A list of recent label-based approaches for pathogen detection using electrochemical biosensors, however, is provided in Table 2.
T501 62699-62805 Sentence denotes While both monoclonal and polyclonal antibodies enable the selective detection of pathogens (Patris et al.
T502 62806-62888 Sentence denotes 2016), they vary in terms of production method, selectivity, and binding affinity.
T503 62889-62995 Sentence denotes Monoclonal antibodies are produced by hybridoma technology (Birch and Racher, 2006; James and Bell, 1987).
T504 62996-63123 Sentence denotes Thus, monoclonal antibodies are highly selective and bind to a single epitope, making them less vulnerable to cross-reactivity.
T505 63124-63275 Sentence denotes While monoclonal antibodies tend to have a higher degree of selectivity, they are more expensive and take longer to develop than polyclonal antibodies.
T506 63276-63412 Sentence denotes Polyclonal antibodies are produced by separation of immunoglobulin proteins from the blood of an infected host (Birch and Racher, 2006).
T507 63413-63481 Sentence denotes Polyclonal antibodies target different epitopes on a single antigen.
T508 63482-63698 Sentence denotes While polyclonal antibodies exhibit increased variability between batches, they are relatively less expensive to produce than monoclonal antibodies and facilitate robust measurements in various settings (Byrne et al.
T509 63699-63705 Sentence denotes 2009).
T510 63706-63821 Sentence denotes Drawbacks to antibody use include high cost and stability challenges, such as the need for low-temperature storage.
T511 63822-63953 Sentence denotes As shown in Table 1, Table 2, both monoclonal and polyclonal antibodies are used as biorecognition elements for pathogen detection.
T512 63954-64225 Sentence denotes For assays involving secondary binding steps, monoclonal antibodies typically serve as the primary biorecognition element and are immobilized on the electrode, while polyclonal antibodies serve as the secondary biorecognition element and often facilitate target labeling.
T513 64226-64389 Sentence denotes For assays that do not require secondary binding steps, polyclonal antibodies are also commonly used as immobilized biorecognition elements for pathogen detection.
T514 64390-64598 Sentence denotes For example, Pandey et al. immobilized monoclonal anti-E. coli on a composite nanostructured electrode to detect E. coli across a wide dynamic range of 10 to 108 CFU/mL with a LOD of 3.8 CFU/mL (Pandey et al.
T515 64599-64605 Sentence denotes 2017).
T516 64606-64735 Sentence denotes Wu et al. used polyclonal anti-E. coli for detection of E. coli via amperometry that exhibited a LOD of 5 × 103 CFU/mL (Wu et al.
T517 64736-64742 Sentence denotes 2016).
T518 64743-65004 Sentence denotes Lin et al. used monoclonal antibodies for detection of avian influenza virus H5N1 in chicken swabs across a dynamic range of 2- 1 to 24 hemagglutination units (HAU)/50 μL using EIS and the ferri/ferrocyanide (Fe(CN)6 3 - /4-) couple as a redox probe (Lin et al.
T519 65005-65011 Sentence denotes 2015).
T520 65012-65150 Sentence denotes Luka et al. detected Cryptosporidium parvum (C. parvum) with a LOD of 40 cells/mm2 via capacitive sensing and Fe(CN)6 3 - /4- (Luka et al.
T521 65151-65157 Sentence denotes 2019).
T522 65158-65404 Sentence denotes Antibody fragments, such as single-chain variable fragments (scFvs), offer selectivity similar to antibodies, but they have the advantage of achieving relatively higher packing densities on electrode surfaces due to their relatively smaller size.
T523 65405-65676 Sentence denotes For example, half-antibody fragments have been shown to improve biosensor sensitivity without the loss of selectivity, which warrants further investigation of reduced antibodies as biorecognition elements for pathogen detection applications (Sharma and Mutharasan, 2013).
T524 65677-65828 Sentence denotes In addition to scFvs, Fabs, re-engineered IgGs, and dimers can also potentially be used as biorecognition elements for pathogen detection (Byrne et al.
T525 65829-65835 Sentence denotes 2009).
T526 65837-65873 Sentence denotes 2.2.2 Carbohydrate-binding proteins
T527 65874-66061 Sentence denotes Carbohydrate-binding proteins, such as lectins, also provide selective biorecognition elements for pathogen detection based on their ability to selectively bind ligands on target species.
T528 66062-66231 Sentence denotes Peptide-based biorecognition elements are relatively low-cost, can be produced with high yield automated synthesis processes, and are modifiable (Pavan and Berti, 2012).
T529 66232-66440 Sentence denotes For example, lectins have been investigated as biorecognition elements for pathogen detection through their ability to selectively bind glycosylated proteins on the surfaces of viruses and cells (Reina et al.
T530 66441-66447 Sentence denotes 2008).
T531 66448-66561 Sentence denotes Concanavalin A (ConA) lectin has been extensively investigated for E. coli detection (see Table 1) (Jantra et al.
T532 66562-66582 Sentence denotes 2011; Saucedo et al.
T533 66583-66598 Sentence denotes 2019; Xi et al.
T534 66599-66616 Sentence denotes 2011; Yang et al.
T535 66617-66624 Sentence denotes 2016b).
T536 66625-66892 Sentence denotes While not yet widely investigated for pathogen detection using electrochemical biosensors, Etayash et al. recently showed that oligopeptides also provide attractive biorecognition elements for real-time biosensor-based detection of breast cancer cells (Etayash et al.
T537 66893-66899 Sentence denotes 2015).
T538 66901-66924 Sentence denotes 2.2.3 Oligosaccharides
T539 66925-67029 Sentence denotes Trisaccharides are carbohydrates that can selectively bind carbohydrate-specific receptors on pathogens.
T540 67030-67156 Sentence denotes Thus, trisaccharide ligands have been used as biorecognition elements for pathogen detection using electrochemical biosensors.
T541 67157-67331 Sentence denotes For example, Hai et al. used a hybrid E-QCM biosensor coated with hemagglutinin-specific trisaccharide ligands for the detection of human influenza A virus (H1N1) (Hai et al.
T542 67332-67338 Sentence denotes 2017).
T543 67339-67566 Sentence denotes The use of carbohydrates as biorecognition elements is limited in part due to the weak affinity of carbohydrate-protein interactions and low selectivity, which are currently mitigated through secondary interactions (Zeng et al.
T544 67567-67573 Sentence denotes 2012).
T545 67575-67598 Sentence denotes 2.2.4 Oligonucleotides
T546 67599-67693 Sentence denotes Single-stranded DNA (ssDNA) is a useful biorecognition element for the detection of pathogens.
T547 67694-67862 Sentence denotes While ssDNA is commonly used as a biorecognition element for DNA-based assays, ssDNA aptamers are commonly used for pathogen detection using electrochemical biosensors.
T548 67863-67995 Sentence denotes Aptamers are single-stranded oligonucleotides capable of binding various molecules with high affinity and selectivity (Lakhin et al.
T549 67996-68019 Sentence denotes 2013; Reverdatto et al.
T550 68020-68026 Sentence denotes 2015).
T551 68027-68223 Sentence denotes Aptamers are isolated from a large random sequence pool through a selection process that utilizes systematic evolution of ligands by exponential enrichment, also known as SELEX (Stoltenburg et al.
T552 68224-68230 Sentence denotes 2007).
T553 68231-68359 Sentence denotes Suitable binding sequences can be isolated from a large random oligonucleotide sequence pool and subsequently amplified for use.
T554 68360-68441 Sentence denotes Thus, aptamers can exhibit high selectivity to target species (Stoltenburg et al.
T555 68442-68448 Sentence denotes 2007).
T556 68449-68556 Sentence denotes Aptamers can also be produced at a lower cost than alternative biorecognition elements, such as antibodies.
T557 68557-68784 Sentence denotes Giamberardino et al. used SELEX to discover an aptamer for norovirus detection, which showed a million-fold higher binding affinity for the target than a random DNA strand that served as a negative control (Giamberardino et al.
T558 68785-68791 Sentence denotes 2013).
T559 68792-68943 Sentence denotes Iqbal et al. performed 10 rounds of SELEX to discover 14 aptamer clones with high affinities for C. parvum for detection in fruit samples (Iqbal et al.
T560 68944-68950 Sentence denotes 2015).
T561 68951-69248 Sentence denotes However, the use of aptamers as biorecognition elements has not yet replaced traditional biorecognition elements, such as antibodies, because of several challenges, such as aptamer stability, degradation, cross-reactivity, and reproducibility using alternative processing approaches (Lakhin et al.
T562 69249-69255 Sentence denotes 2013).
T563 69257-69270 Sentence denotes 2.2.5 Phages
T564 69271-69426 Sentence denotes Phages, also referred to as bacteriophages, are viruses that infect and replicate in bacteria through selective binding via tail-spike proteins (Haq et al.
T565 69427-69433 Sentence denotes 2012).
T566 69434-69579 Sentence denotes Thus, they have been examined as biorecognition elements for pathogen detection using electrochemical biosensors (Kutter and Sulakvelidze, 2004).
T567 69580-69677 Sentence denotes Bacteriophages exhibit varying morphologies and are thus classified by selectivity and structure.
T568 69678-69785 Sentence denotes A variety of bacteriophage-based electrochemical biosensors for pathogen detection can be found in Table 1.
T569 69786-69914 Sentence denotes For example, Shabani et al. used E. coli-specific T4 bacteriophages for selective impedimetric detection studies (Shabani et al.
T570 69915-69921 Sentence denotes 2008).
T571 69922-70046 Sentence denotes Mejri et al. compared the use of bacteriophages to antibodies as biorecognition elements for E. coli detection (Mejri et al.
T572 70047-70053 Sentence denotes 2010).
T573 70054-70299 Sentence denotes In that study, they found that bacteriophages improved the water stability of the biosensor and increased the sensitivity by approximately a factor of four relative to the response obtained with antibodies based on EIS measurements (Mejri et al.
T574 70300-70306 Sentence denotes 2010).
T575 70307-70517 Sentence denotes In another study, Tolba et al. utilized immobilized bacteriophage-encoded peptidoglycan hydrolases on Au screen-printed electrodes for detection of L. innocua in pure milk with a LOD of 105 CFU/mL (Tolba et al.
T576 70518-70524 Sentence denotes 2012).
T577 70525-70720 Sentence denotes These results suggest that bacteriophages are potentially attractive biorecognition elements for water safety and environmental monitoring applications that require chronic monitoring of liquids.
T578 70722-70769 Sentence denotes 2.2.6 Cell- and molecularly-imprinted polymers
T579 70770-71162 Sentence denotes Given traditional biorecognition elements used in biosensing exhibit stability concerns, such as antibodies or aptamers, as discussed in Sections 2.2.1–2.2.4, there have been efforts to create engineered molecular biorecognition elements, such as scFvs. In contrast, materials-based biorecognition elements exploit the principle of target-specific morphology for selective capture (Pan et al.
T580 71163-71180 Sentence denotes 2018; Zhou et al.
T581 71181-71187 Sentence denotes 2019).
T582 71188-71341 Sentence denotes The most common approach in materials-based biorecognition is based on cell- and molecularly-imprinted polymers (CIPs and MIPs, respectively) (Gui et al.
T583 71342-71348 Sentence denotes 2018).
T584 71349-71504 Sentence denotes CIPs and MIPs have been created using various processes, including bacteria-mediated lithography, micro-contact stamping, and colloid imprints (Chen et al.
T585 71505-71522 Sentence denotes 2016a; Pan et al.
T586 71523-71529 Sentence denotes 2018).
T587 71530-71752 Sentence denotes As shown in Fig. 3b, Jafari et al. used imprinted organosilica sol-gel films of tetraethoxysilane and (3-mercaptopropyl)trimethoxysilane (MPTS) for selective detection of E. coli using an impedimetric method (Jafari et al.
T588 71753-71759 Sentence denotes 2019).
T589 71760-71913 Sentence denotes Similarly, Golabi et al. used imprinted poly(3-aminophenylboronic acid) films for detection of Staphylococcus epidermidis (S. epidermidis) (Golabi et al.
T590 71914-71920 Sentence denotes 2017).
T591 71921-72127 Sentence denotes Despite the absence of a highly selective molecular biorecognition element, CIPs and MIPs exhibit selectivity when exposed to samples that contain multiple analytes (i.e., non-target species) (Golabi et al.
T592 72128-72147 Sentence denotes 2017; Jafari et al.
T593 72148-72163 Sentence denotes 2019; Qi et al.
T594 72164-72170 Sentence denotes 2013).
T595 72171-72261 Sentence denotes MIPs and CIPs are also of interest with regard to opportunities in biosensor regeneration.
T596 72262-72445 Sentence denotes Common adverse effects of regeneration on biosensors that employ molecular biorecognition elements, such as irreversible changes in structure, are less likely to affect MIPs and CIPs.
T597 72446-72645 Sentence denotes However, it is generally accepted that current CIPs and MIPs exhibit lower selectivity to target species than antibodies and aptamers due to reduction of available chemical selectivity (Cheong et al.
T598 72646-72697 Sentence denotes 2013; Kryscio and Peppas, 2012; Yáñez-Sedeño et al.
T599 72698-72704 Sentence denotes 2017).
T600 72706-72749 Sentence denotes 2.3 Immobilization and surface passivation
T601 72750-73021 Sentence denotes Given biosensors are self-contained devices composed of integrated transducer-biorecognition elements, the immobilization of biorecognition elements on electrodes is central to the design, fabrication, and performance of electrochemical biosensors for pathogen detection.
T602 73022-73263 Sentence denotes The goal of immobilization is to achieve a stable, irreversible bond between the biorecognition element and the electrode with suitable packing density and orientation that maintains high accessibility and binding affinity to target species.
T603 73264-73401 Sentence denotes Electrochemical biosensors for pathogen detection have typically used established techniques for preparation of the biorecognition layer.
T604 73402-73515 Sentence denotes A detailed discussion of immobilization and surface passivation techniques is provided in Supporting Information.
T605 73517-73589 Sentence denotes 2.4 Thermodynamics of pathogen-biorecognition element binding reactions
T606 73590-73851 Sentence denotes While the rate of biosensor response is typically governed by a mass transfer-limited heterogeneous reaction between the immobilized biorecognition element and target species, the net change in the biosensor response is dependent on the reaction thermodynamics.
T607 73852-74041 Sentence denotes The binding affinity between a biorecognition element and target species, such as an antibody and antigen, is often reported in terms of a dissociation constant (K D), which has units of M.
T608 74042-74252 Sentence denotes While the value of K D, solution = 1 nM provides a reasonable estimate for biosensor design considerations, such as understanding the mass transfer limitations associated with biosensor response (Squires et al.
T609 74253-74399 Sentence denotes 2008), the binding affinity of antibodies can vary by orders of magnitude depending on the pathogen of interest and the clonality of the antibody.
T610 74400-74543 Sentence denotes One important consideration when immobilizing biorecognition elements is potential effects of immobilization on binding affinity to the target.
T611 74544-74616 Sentence denotes Traditionally, K D is obtained from a kinetic or thermodynamic analysis.
T612 74617-74755 Sentence denotes Kinetic analyses measure association and dissociation rate constants (k a and k d, respectively) and enable calculation of K D as k d/k a.
T613 74756-75050 Sentence denotes Thermodynamic analyses, such as calorimetric techniques, measure the binding enthalpy and entropy, which in turn provides the standard Gibbs free energy of the reaction (ΔG°), and thus, K A = K D −1 though the expression K A = exp(-ΔG°/RT), where R is the gas constant and T is the temperature.
T614 75051-75240 Sentence denotes A detailed discussion of the kinetics and thermodynamics of biorecognition element-target binding reactions for solution- and surface-based biosensors is provided in Supporting Information.
T615 75242-75287 Sentence denotes 3 Measurement formats for pathogen detection
T616 75288-75610 Sentence denotes In addition to a physical device composed of an integrated transduction element and biorecognition element, an electrochemical biosensor-based assay for pathogen detection potentially involves processing steps associated with sample preparation and complementary physical systems for biosensor housing and sample handling.
T617 75611-75727 Sentence denotes The associated protocols for sample preparation and sample handling are often referred to as the measurement format.
T618 75728-76043 Sentence denotes Several important considerations regarding the measurement format for pathogen detection applications can be considered and vary based on the assay design, the biosensor performance (e.g., sensitivity and LOD), the volume, material properties, and composition of the pathogen-containing sample, and the application.
T619 76044-76203 Sentence denotes For example, the use of DNA-based assays for pathogen detection typically requires sample preparation steps associated with the extraction of genetic material.
T620 76204-76326 Sentence denotes Similarly, the use of a label-based biosensing approach requires sample preparation steps associated with target labeling.
T621 76327-76462 Sentence denotes In cases where the concentration of target species in the sample is below the biosensor's LOD, pre-concentration steps may be required.
T622 76463-76592 Sentence denotes Applications to process monitoring, such in bioreactor or tissue-chip monitoring, may require flow-based sample handling formats.
T623 76593-76719 Sentence denotes We next discuss the measurement formats associated with pathogen detection in terms of sample preparation and sample handling.
T624 76721-76745 Sentence denotes 3.1 Sample preparation:
T625 76746-76778 Sentence denotes Filtration and pre-concentration
T626 76779-77074 Sentence denotes Sample preparation steps have various purposes, including concentrating or amplifying the target species through separation and growth processes, reducing the concentration of background inhibitory species, and reducing the heterogeneity of the sample's composition and properties (Zourob et al.
T627 77075-77081 Sentence denotes 2008).
T628 77082-77149 Sentence denotes We next discuss sample filtration and pre-concentration techniques.
T629 77151-77175 Sentence denotes 3.1.1 Sample filtration
T630 77176-77300 Sentence denotes Generally, sample filtration relies on the principle of size discrepancy between the target pathogen and background species.
T631 77301-77422 Sentence denotes Membranes, fibers, and channels have been used in size-selective sample filtration processes for biosensing applications.
T632 77423-77586 Sentence denotes Biorecognition elements are commonly used to assist the separation process when the target species exhibits similar properties to background species or the matrix.
T633 77587-77773 Sentence denotes For example, biorecognition elements that exhibit affinity to a broad group of pathogens, such as lectins, have been used in pre-concentration steps for pathogen detection (Zourob et al.
T634 77774-77780 Sentence denotes 2008).
T635 77781-78023 Sentence denotes Bacteria typically exhibit a net negative charge at physiological pH (7.4) because of an abundance of lipopolysaccharides or teichoic acids on the cell membrane (Gram-negative bacteria and Gram-positive bacteria, respectively) (Silhavy et al.
T636 78024-78030 Sentence denotes 2010).
T637 78031-78178 Sentence denotes This physical property of cell-based pathogens is leveraged in biofiltration processes, for example, using electropositive filters (Altintas et al.
T638 78179-78185 Sentence denotes 2015).
T639 78186-78389 Sentence denotes While the majority of the aforementioned separation processes involve manual handling steps, sample filtration processes are now being integrated with microfluidic-based biosensing platforms (Song et al.
T640 78390-78396 Sentence denotes 2013).
T641 78397-78595 Sentence denotes For example, Chand and Neethirajan incorporated an integrated sample filtration technique using silica microbeads for the detection of norovirus in spiked blood samples (Chand and Neethirajan 2017).
T642 78597-78626 Sentence denotes 3.1.2 Centrifugal separation
T643 78627-78754 Sentence denotes Centrifugation can be used as a density gradient-based separation principle for concentrating target pathogens within a sample.
T644 78755-78906 Sentence denotes In cases where the target species exhibits similar density to background species, the approach is often implemented with antibody-functionalized beads.
T645 78907-79028 Sentence denotes This technique is commonly employed in applications requiring pathogen detection in complex matrices (e.g., body fluids).
T646 79029-79147 Sentence denotes Centrifugation-based separation techniques can also potentially be applied to microfluidic-based biosensing platforms.
T647 79148-79286 Sentence denotes For example, Lee et al. utilized centrifugal microfluidics to process a whole blood sample for subsequent analysis using ELISA (Lee et al.
T648 79287-79407 Sentence denotes 2009), suggesting that this approach could be extended to electrochemical biosensor-based assays for pathogen detection.
T649 79409-79432 Sentence denotes 3.1.3 Broth enrichment
T650 79433-79654 Sentence denotes Broth enrichment is a technique used to increase the concentration of target species in the sample through growth or replication of target species prior to measurement, thereby increasing the number present for detection.
T651 79655-79714 Sentence denotes The technique is commonly used in food safety applications.
T652 79715-79924 Sentence denotes For example, Liebana et al. enriched S. typhimurium-spiked milk samples in Luria broth (LB) for 8 h to improve the assay LOD from 7.5 × 103 CFU/mL for the 50-min enriched sample to 0.108 CFU/mL (Liebana et al.
T653 79925-79931 Sentence denotes 2009).
T654 79932-80119 Sentence denotes Salam et al. enriched fresh chicken samples in enrichment buffer peptone for 18–24 h to recover injured S. typhimurium cells for detection via chronoamperometry (Salam and Tothill, 2009).
T655 80120-80295 Sentence denotes While enrichment can be a useful sample preparation step when the target concentration is below the biosensor's LOD, it is inherently limited to viable and cultural organisms.
T656 80296-80454 Sentence denotes Further, analysis of the results obtained from multiple samples should consider potential differences in the growth rate of bacteria across different samples.
T657 80455-80589 Sentence denotes It is important to note that the need for sample enrichment significantly increases the TTR and impedes rapid and real-time detection.
T658 80591-80617 Sentence denotes 3.1.4 Magnetic separation
T659 80618-80780 Sentence denotes The separation of the target species from a sample using magnetic beads has become a commonly used sample preparation approach in pathogen detection applications.
T660 80781-80946 Sentence denotes Target pre-concentration via magnetic bead-based separation processes typically involves the binding of antibody-functionalized magnetic beads to the target species.
T661 80947-81056 Sentence denotes The bead-target complexes are subsequently separated from the solution by externally-applied magnetic fields.
T662 81057-81291 Sentence denotes Magnetic-assisted separation processes are useful when the target species exhibits similar properties to other analytes or background species in the sample, such as those with similar size, density, or chemical properties (Chen et al.
T663 81292-81298 Sentence denotes 2017).
T664 81299-81458 Sentence denotes The bead-target complexes are then introduced directly to the biosensor to enable quantification of the target pathogen that was present in the initial sample.
T665 81459-81630 Sentence denotes As shown in Table 2, magnetic bead-based separation processes have been extensively used for pathogen detection as well as general substrates for traditional immunoassays.
T666 81631-81740 Sentence denotes Such assays have been used to detect a variety of pathogens, including bacteria, such as E. coli (Chan et al.
T667 81741-81872 Sentence denotes 2013 ) and Bacillus anthracis (B. anthracis) (Pal and Alocilja, 2009), and viruses, such as bovine viral diarrhea virus (Luo et al.
T668 81873-81919 Sentence denotes 2010) and human influenza A virus (Shen et al.
T669 81920-81926 Sentence denotes 2012).
T670 81927-82009 Sentence denotes In addition to serving as a separation agent, magnetic beads also serve as labels.
T671 82011-82039 Sentence denotes 3.2 Sample handling formats
T672 82040-82117 Sentence denotes The sample handling format is highly influenced by the biosensor application.
T673 82118-82273 Sentence denotes As discussed in further detail in the following sections, pathogens are present in liquid and solid matrices and on surfaces (e.g., of biomedical devices).
T674 82274-82432 Sentence denotes In addition, pathogens can be aerosolized, which is a significant mode of disease transmission associated with viral pathogens (e.g., influenza and COVID-19).
T675 82433-82522 Sentence denotes Sample handling formats can be generally classified as droplet-, flow-, or surface-based.
T676 82523-82630 Sentence denotes Droplet formats involve sampling from a larger volume of potentially pathogen-containing material or fluid.
T677 82631-82764 Sentence denotes The sample droplet is subsequently analyzed by deposition on a functionalized transducer or transferred to a fluidic delivery system.
T678 82765-82948 Sentence denotes For example, Cheng et al. created an electrochemical biosensor based on a nanoporous alumina electrode tip capable of analyzing 5 μL of dengue virus-containing solutions (Cheng et al.
T679 82949-82955 Sentence denotes 2012).
T680 82956-83072 Sentence denotes Droplet formats are simplistic sample handling formats and have the advantage of being performed by unskilled users.
T681 83073-83210 Sentence denotes While dropletformats have been extensively used with colorimetric biosensors, they have also been adapted for electrochemical biosensors.
T682 83211-83304 Sentence denotes For example, commercially-available blood glucose meters use a droplet format (Vashist et al.
T683 83305-83311 Sentence denotes 2011).
T684 83312-83464 Sentence denotes Examples of low-cost, paper-based, or disposable electrochemical biosensors for pathogen detection that utilize droplet formats are provided in Table 1.
T685 83465-83653 Sentence denotes For example, Zhao et al. created a screen-printed graphite-based electrode for electrochemical detection of Vibrio parahaemolyticus (V. parahaemolyticus) based on 5 μL samples (Zhao et al.
T686 83654-83660 Sentence denotes 2007).
T687 83661-83967 Sentence denotes However, while droplet formats minimize the technical and methodological barriers to measurement, such as eliminating the need for physical systems associated with biosensor housing and sample handling, they can exhibit measurement challenges associated with mass transport and target sampling limitations.
T688 83968-84266 Sentence denotes One of the most critical considerations associated with application of droplet formats to pathogen detection is sampling, specifically if sufficient sampling has been performed on the system for which bioanalytical information is desired (e.g., a human, a food source, or source of drinking water).
T689 84267-84527 Sentence denotes For example, the rationale that the bioanalytical characteristics of a droplet represent that of the bulk system is sound only in a well-mixed system, specifically, a system that exhibits a uniform spatial distribution of species (i.e., concentration profile).
T690 84528-84765 Sentence denotes We note that while this is typically the case for samples acquired from closed, convective systems, such as body fluids, it should be challenged when considering open systems that exhibit complex flow profiles or regions of static fluid.
T691 84766-84907 Sentence denotes For example, groundwater systems (e.g., aquifers), rivers, and lakes have been reported to have complex flow profiles (Ji, 2017; Zhang et al.
T692 84908-84914 Sentence denotes 1996).
T693 84915-85034 Sentence denotes Thus, the sampling approach should be considered when examining droplet formats for food and water safety applications.
T694 85035-85275 Sentence denotes In addition to a consideration of system mixing, one should also consider the potential measurement pitfalls when analyzing samples that contain dilute levels of highly infectious pathogens, such as the potential for false-negative results.
T695 85276-85360 Sentence denotes Flow formats involve the detection of target species in the presence of flow fields.
T696 85361-85488 Sentence denotes Flow formats include continuously-stirred systems (e.g., continuously-stirred tank bioreactors), flow cells, and microfluidics.
T697 85489-85741 Sentence denotes Flow formats have the advantage of exposing the biosensor to target-containing samples in a controlled and repeatable fashion and the benefit of driving exposure of the functionalized biosensor to target species via convective mass transfer mechanisms.
T698 85742-85819 Sentence denotes Flow formatsare also typically compatible with large sample volumes (liters).
T699 85820-85936 Sentence denotes Flow cells are typically fabricated via milling and extrusion processes using materials such as Teflon or Plexiglas.
T700 85937-86058 Sentence denotes They have the advantage of accommodating a variety of biosensor form factors, such as rigid three-dimensional biosensors.
T701 86059-86148 Sentence denotes In addition to flow cells, flow formats are commonly achieved using microfluidic devices.
T702 86149-86328 Sentence denotes While microfluidic devices are typically used with biosensors that exhibit thin two-dimensional form factors, such as planar electrodes, they offer various measurement advantages.
T703 86329-86585 Sentence denotes Unlike flow cells, which are typically fabricated from machinable polymers, microfluidics are typically fabricated using polydimethylsiloxane (PDMS) and polymethyl methacrylate (PMMA) given their low cost and compatibility with microfabrication approaches.
T704 86586-86779 Sentence denotes One advantage of microfluidic devices is their ability to perform integrated sample preparation steps, which eliminates the need for additional steps in the sample-to-result process (Sin et al.
T705 86780-86786 Sentence denotes 2014).
T706 86787-86967 Sentence denotes For example, microfluidic formats for pathogen detection using electrochemical biosensors have demonstrated fluid pumping, valving, and mixing of small sample volumes (Rivet et al.
T707 86968-86974 Sentence denotes 2011).
T708 86975-87106 Sentence denotes An example of a microfluidic format created by Dastider et al. for detection of S. typhimurium is shown in Fig. 4a (Dastider et al.
T709 87107-87113 Sentence denotes 2015).
T710 87114-87244 Sentence denotes Detection in the presence of flow fields requires high stability of immobilized biorecognition elements (Bard and Faulkner, 2000).
T711 87245-87444 Sentence denotes The effect of flow characteristics on biosensor collection rates is an important consideration, especially when considering micro- and nano-scale transducers with microfluidic formats (Squires et al.
T712 87445-87451 Sentence denotes 2008).
T713 87452-87625 Sentence denotes For example, emerging nanostructured electrodes, such as functionalized nanoporous membranes, have been shown to achieve high stability in microfluidic devices (Joung et al.
T714 87626-87642 Sentence denotes 2013; Tan et al.
T715 87643-87649 Sentence denotes 2011).
T716 87650-87854 Sentence denotes A detailed discussion on the relationship between device dimensions, flow characteristics, achievable target collection rates, and equilibrium measurement times has been provided elsewhere (Squires et al.
T717 87855-87861 Sentence denotes 2008).
T718 87862-88147 Sentence denotes It is paramount for interpreting biosensor response that users understand the interplay between mass transport of target molecules (both diffusive and convective mechanisms) and reaction at the biosensor surface (i.e., binding of target species to immobilized biorecognition elements).
T719 88148-88327 Sentence denotes Such fundamental understanding can also be employed in biosensor and experiment design to create improved assay outcomes, such as reducing TTR or improving measurement confidence.
T720 88328-88666 Sentence denotes While the presence of pathogens on the surfaces of objects can be analyzed using droplet- and flow-based sample handling formats using material transfer processes, such as swabbing, in situ pathogen detection on the object surfaces is a vital measurement capability for medical diagnostic, infection control, and food safety applications.
T721 88667-88792 Sentence denotes Surface-based measurement formats typically require biosensors with flexible or conforming (i.e., form-fitting) form factors.
T722 88793-88940 Sentence denotes For example, Mannoor et al. detected the presence of pathogenic species directly on teeth using a flexible graphene-based biosensor (Mannoor et al.
T723 88941-88947 Sentence denotes 2012).
T724 88948-89055 Sentence denotes Further discussion of surface-based pathogen detection applications are provided in the following sections.
T725 89056-89139 Sentence denotes The sample handling format often provides insight into the biosensor's reusability.
T726 89140-89258 Sentence denotes Biosensors within the aforementioned measurement formats can be broadly classified as single- or multi-use biosensors.
T727 89259-89441 Sentence denotes Single-use biosensors are unable to monitor the analyte concentration continuously or upon regeneration, while multiple-use biosensors can be repeatedly recalibrated (Thévenot et al.
T728 89442-89448 Sentence denotes 2001).
T729 89449-89694 Sentence denotes For example, droplet-based low-cost, disposable biosensors for water safety are typically single-use, while biosensors for process monitoring applications can be recalibrated to characterize multiple samples and facilitate continuous monitoring.
T730 89695-89981 Sentence denotes The ability to regenerate biosensor surfaces following pathogen detection (i.e., remove selectively-bound pathogens) is a significant technical barrier limiting progress in multiple-use biosensors, and industrial applications thereof, and is discussed further in the following sections.
T731 89983-90067 Sentence denotes 3.3 Electrochemical methods for pathogen detection using electrochemical biosensors
T732 90068-90204 Sentence denotes Various electrochemical methods can be performed using functionalized electrodes to enable pathogen detection (Bard and Faulkner, 2000).
T733 90205-90358 Sentence denotes These methods differ in electrode configuration, applied signals, measured signals, mass transport regimes, binding information provided (Thévenot et al.
T734 90359-90407 Sentence denotes 2001), and target size-selectivity (Amiri et al.
T735 90408-90414 Sentence denotes 2018).
T736 90415-90632 Sentence denotes Electrochemical methods used for pathogen detection can be classified as potentiometric, amperometric, conductometric, impedimetric, or ion-charge/field-effect, which often signify the measured signal (Thévenot et al.
T737 90633-90639 Sentence denotes 2001).
T738 90640-90692 Sentence denotes The applied signals may be constant or time-varying.
T739 90693-90847 Sentence denotes The result of the electrochemical method may require analysis of the output signal's transient response, steady-steady response, or a combination of both.
T740 90848-90970 Sentence denotes A detailed discussion of the aforementioned electrochemical methods has been provided elsewhere (Bard and Faulkner, 2000).
T741 90971-91084 Sentence denotes Here, we briefly review the most recent methods employed for pathogen detection using electrochemical biosensors.
T742 91086-91106 Sentence denotes 3.3.1 Potentiometry
T743 91107-91294 Sentence denotes Potentiometric methods, also referred to as controlled-current methods, are those in which an electrical potential is measured in response to an applied current (Bard and Faulkner, 2000).
T744 91295-91342 Sentence denotes The applied current is typically low amplitude.
T745 91343-91504 Sentence denotes An advantage of controlled-current methods is the ability to use low-cost measurement instrumentation relative to that required for controlled-potential methods.
T746 91505-91651 Sentence denotes Hai et al. used potentiometry with a conductive polymer-based biosensor to detect human influenza A virus (H1N1) at a LOD of 0.013 HAU (Hai et al.
T747 91652-91658 Sentence denotes 2017).
T748 91659-91826 Sentence denotes Hernandez et al. used potentiometry with a carbon-rod modified electrode that contained reduced graphene oxide to detect S. aureus at a single CFU/mL (Hernandez et al.
T749 91827-91833 Sentence denotes 2014).
T750 91834-91925 Sentence denotes Boehm et al. detected E. coli via potentiometry utilizing a Pt wire electrode (Boehm et al.
T751 91926-91932 Sentence denotes 2007).
T752 91933-92024 Sentence denotes Further studies utilizing potentiometric sensing approaches are listed in Table 1, Table 2.
T753 92026-92044 Sentence denotes 3.3.2 Voltammetry
T754 92045-92259 Sentence denotes Voltammetric methods, also referred to as controlled-potential methods, are those in which a current is measured in response to an applied electrical potential that drives redox reactions (Bard and Faulkner, 2000).
T755 92260-92407 Sentence denotes The measured current is indicative of electron transfer within the sample and at the electrode surface, and thus, the concentration of the analyte.
T756 92408-92561 Sentence denotes In chronoamperometry, the electrical potential at the working electrode is applied in steps, and the resulting current is measured as a function of time.
T757 92562-92668 Sentence denotes The applied electrical potential can also be held constant or varied with time as the current is measured.
T758 92669-92882 Sentence denotes Although various types of biosensors are compatible with voltammetry-based measurements, field-effect transistor (FET)-based biosensors often utilize amperometric-based methods for pathogen detection (Huang et al.
T759 92883-92899 Sentence denotes 2011; Liu et al.
T760 92900-92906 Sentence denotes 2013).
T761 92907-93058 Sentence denotes FET biosensors detect pathogens via measured changes in source-drain channel conductivity that arise from the electric field of the sample environment.
T762 93059-93169 Sentence denotes This is achieved by immobilizing biorecognition elements on the metal or polymer gate electrode of the device.
T763 93170-93359 Sentence denotes He et al. showed that FETs based on PEDOT:PSS organic electrochemical transistor electrodes enabled the detection of E. coli in KCl solutions using Pt and Ag/AgCl gate electrodes (He et al.
T764 93360-93366 Sentence denotes 2012).
T765 93367-93545 Sentence denotes Wu et al. used a graphene-based FET to detect E. coli in nutrient broth diluted with phosphate buffered saline solution with amperometry using a Ag/AgCl gate electrode (Wu et al.
T766 93546-93552 Sentence denotes 2016).
T767 93553-93809 Sentence denotes Further examples of amperometric sensing include the detection of human influenza A virus by Singh et al. using a reduced graphene oxide-based electrode and chronoamperometry using Fe(CN)6 3 - /4- at a LOD of 0.5 plaque-forming units (PFU)/mL (Singh et al.
T768 93810-93817 Sentence denotes 2017b).
T769 93818-93932 Sentence denotes Lee and Jun utilized wire-based electrodes for amperometric detection of E. coli and S. aureus (Lee and Jun 2016).
T770 93933-94048 Sentence denotes A detailed list of studies that utilize amperometric methods for pathogen detection is provided in Table 1, Table 2
T771 94050-94094 Sentence denotes 3.3.2.1 Linear sweep and cyclic voltammetry
T772 94095-94321 Sentence denotes Linear sweep voltammetry (LSV) methods are those in which a current is measured in response to an applied electrical potential that is swept at a constant rate across a range of electrical potentials (Bard and Faulkner, 2000).
T773 94322-94525 Sentence denotes Cyclic voltammetry (CV) is a commonly used linear-sweep method in which the electrical potential is swept in both the forward and reverse directions in partial cycles, full cycles, or a series of cycles.
T774 94526-94604 Sentence denotes CV is one of the most widely used voltammetric methods for pathogen detection.
T775 94605-94737 Sentence denotes Hong et al. used sweep voltammetry to detect norovirus in a sample solution with Fe(CN)6 3 - /4- extracted from lettuce (Hong et al.
T776 94738-94744 Sentence denotes 2015).
T777 94745-94937 Sentence denotes A typical CV response using Fe(CN)6 3 - /4- associated with pathogen detection is shown in Fig. 5 a for various concentrations of E. coli binding to a polymer composite electrode (Güner et al.
T778 94938-94944 Sentence denotes 2017).
T779 94945-95039 Sentence denotes A detailed overview of pathogen detection studies based on CV is provided in Table 1, Table 2.
T780 95040-95247 Sentence denotes Fig. 5 Typical responses associated with the common electrochemical methods used for pathogen detection. a) Cyclic voltammetry (CV) data using Fe(CN)63-/4- for varying concentrations of E. coli (Güner et al.
T781 95248-95375 Sentence denotes 2017). b) Differential pulse voltammetry (DPV) data using Fe(CN)63-/4- for varying concentrations of S. aureus (Bhardwaj et al.
T782 95376-95635 Sentence denotes 2017). c) Electrochemical impedance spectroscopy (EIS) in 100 mM LiClO4 solution in the form of a Nyquist plot and corresponding equivalent circuit model associated with biorecognition element immobilization and detection of S. typhimurium (Sheikhzadeh et al.
T783 95636-95718 Sentence denotes 2016). d) Conductometry data for varying concentrations of B. subtilis (Yoo et al.
T784 95719-95725 Sentence denotes 2017).
T785 95727-95753 Sentence denotes 3.3.2.2 Pulse voltammetry
T786 95754-95852 Sentence denotes Pulse voltammetry is a type of voltammetry in which the electrical potential is applied in pulses.
T787 95853-96020 Sentence denotes The technique has the advantage of improved speed and sensitivity relative to traditional voltammetric techniques (Bard and Faulkner, 2000; Molina and González, 2016).
T788 96021-96235 Sentence denotes In staircase voltammetry, the electrical potential is pulsed in a series of stair steps and the current is measured following each step change, which reduces the effect of capacitive charging on the current signal.
T789 96236-96391 Sentence denotes Square wave voltammetry (SWV) is a type of staircase voltammetry that applies a symmetric square-wave pulse superimposed on a staircase potential waveform.
T790 96392-96460 Sentence denotes The forward pulse of the waveform coincides with the staircase step.
T791 96461-96624 Sentence denotes In differential pulse voltammetry (DPV), the electrical potential is scanned with a series of fixed amplitude pulses and superimposed on a changing base potential.
T792 96625-96781 Sentence denotes The current is measured before the pulse application and again at the end of the pulse, which allows for the decay of the nonfaradaic current (Scott, 2016).
T793 96782-96922 Sentence denotes For example, Iqbal et al. used SWV with AuNP-modified carbon electrodes for detection of C. parvum in samples taken from fruit (Iqbal et al.
T794 96923-96929 Sentence denotes 2015).
T795 96930-97042 Sentence denotes Kitajima et al. also used SWV with Au microelectrodes to detect norovirus at a LOD of 10 PFU/mL (Kitajima et al.
T796 97043-97049 Sentence denotes 2016).
T797 97050-97184 Sentence denotes Cheng et al. used DPV and a nanostructured alumina electrode for detection of dengue type 2 virus with a LOD of 1 PFU/mL (Cheng et al.
T798 97185-97191 Sentence denotes 2012).
T799 97192-97304 Sentence denotes As shown in Fig. 5b, Bhardwaj et al. used DPV with a carbon-based electrode to detect S. aureus (Bhardwaj et al.
T800 97305-97311 Sentence denotes 2017).
T801 97312-97423 Sentence denotes Additional studies that utilize pulse voltammetry methods forpathogen detection are listed in Table 1, Table 2.
T802 97425-97455 Sentence denotes 3.3.2.3 Stripping voltammetry
T803 97456-97602 Sentence denotes Many of the previously described voltammetric methods can be modified to include a step that pre-concentrates the target on the electrode surface.
T804 97603-97716 Sentence denotes Subsequently, the pre-concentrated target is stripped from the surface by application of an electrical potential.
T805 97717-97842 Sentence denotes In anodic stripping voltammetry (ASV), a negative potential is used to pre-concentrate metal ions onto the electrode surface.
T806 97843-97920 Sentence denotes These ions are then stripped from the surface by applied positive potentials.
T807 97921-98190 Sentence denotes Although most commonly used to detect trace amounts of metals, this method has been adapted for pathogen detection by electrocatalytically coating metallic labels on bound targets for oxidative stripping and subsequently measuring the current response (Abbaspour et al.
T808 98191-98197 Sentence denotes 2015).
T809 98198-98334 Sentence denotes Chen et al. used stripping voltammetry with a polymer-CNT composite-based electrode to detect E. coli at a LOD of 13 CFU/mL (Chen et al.
T810 98335-98341 Sentence denotes 2014).
T811 98342-98404 Sentence denotes In that study, the biosensor was first incubated with E. coli.
T812 98405-98579 Sentence denotes Silica-coated Ag nanoparticles conjugated with anti-E.coli were subsequently introduced to the system, inducing a binding reaction between the bacteria and the nanoparticles.
T813 98580-98731 Sentence denotes After rinsing non-specifically bound particles, acid was introduced to dissolve Ag(s), and the resulting Ag+-rich solution was characterized using DPV.
T814 98732-98965 Sentence denotes Viswanathan et al. used ASV with screen-printed composite electrodes for multiplexed detection of Campylobacter, S. typhimurium, and E. coli with a LOD of 400 cells/mL, 400 cells/mL, and 800 cells/mL, respectively (Viswanathan et al.
T815 98966-98972 Sentence denotes 2012).
T816 98973-99226 Sentence denotes In that study, antibody-functionalized nanocrystalline bioconjugates were first introduced to biosensor-bound bacteria, the specifically bound particles were dissolved with acid, and the ions were then stripped using a square-wave voltammetric waveform.
T817 99227-99350 Sentence denotes Additional studies using stripping voltammetry for electrochemical detection of pathogens can be found in Table 1, Table 2.
T818 99352-99397 Sentence denotes 3.3.3 Electrochemical impedance spectroscopy
T819 99398-99598 Sentence denotes The aforementioned electrochemical methods involved responses based on step changes or continuous sweeps in the applied current or voltage that drove the electrode to a condition far from equilibrium.
T820 99599-99916 Sentence denotes Alternatively, frequency response methods, often referred to as impedance-based or impedimetric methods, are based on frequency response analysis (i.e., the response of the system to periodic applied current or potential waveforms at either a fixed frequency or over a range of frequencies) (Bard and Faulkner, 2000).
T821 99917-100062 Sentence denotes This provides several advantages, including measurement over a wide range of times and frequencies and high precision in time-averaged responses.
T822 100063-100179 Sentence denotes We next discuss impedance-based electrochemical methods for detection of pathogens using electrochemical biosensors.
T823 100180-100311 Sentence denotes In EIS the impedance and phase angle of the system are measured as a function of the frequency of the applied electrical potential.
T824 100312-100547 Sentence denotes EIS is a diverse electrochemical method, which can be done as a faradaic or non-faradaic process, and enables the study of intrinsic material properties, experiment-specific processes, or biorecognition events at the electrode surface.
T825 100548-100670 Sentence denotes EIS is often performed using an applied low-amplitude sinusoidal electrical potential and a three-electrode configuration.
T826 100671-100873 Sentence denotes Equivalent circuit models are commonly fit to experimental impedance and phase angle data to interpret the electrochemical process in terms of passive circuit elements, such as resistors and capacitors.
T827 100874-101129 Sentence denotes For example, the electric double layer is typically modeled as a capacitive element, while the resistance to faradaic charge transfer at the electrode-electrolyte interface is represented as a resistor, often referred to as the charge transfer resistance.
T828 101130-101378 Sentence denotes Additional circuit elements, such as constant-phase or Warburg elements, can also be included to represent other features of the electrochemical cell and process, such transport characteristics of the species at the electrode-electrolyte interface.
T829 101379-101476 Sentence denotes The Randles model is a commonly used equivalent circuit for interpretation of biosensor EIS data.
T830 101477-101683 Sentence denotes The circuit consists of an electrolyte resistance in series with a parallel combination of the double-layer capacitance with the charge transfer resistance and the Warburg impedance element (Randles, 1947).
T831 101684-101766 Sentence denotes Variations of this model have been formulated for a variety of biosensing studies.
T832 101767-102009 Sentence denotes For example, the equivalent circuit model and associated Nyquist plot for electrochemical detection of S. typhimurium using EIS with a poly(pyrrole-co-3-carboxyl-pyrrole) copolymer supported aptamer can be found in Fig. 5c (Sheikhzadeh et al.
T833 102010-102016 Sentence denotes 2016).
T834 102017-102278 Sentence denotes The equivalent circuit model consists of the solution resistance, charge transfer resistance at the copolymer-aptamer/electrolyte interface, and constant phase element for the charge capacitance at the copolymer-aptamer/electrolyte interface (Sheikhzadeh et al.
T835 102279-102285 Sentence denotes 2016).
T836 102286-102535 Sentence denotes While the impedance can be measured across a range of frequencies and interpreted using equivalent circuit models that describe impedance response over a wide frequency range, fixed-frequency measurements are also useful for biosensing applications.
T837 102536-102732 Sentence denotes Fixed-frequency measurements are typically based on the identification of single frequencies or small frequency ranges in the impedance spectra that are most sensitive to molecular binding events.
T838 102733-102833 Sentence denotes Fixed-frequency approaches have the advantage of increasing the sampling frequency of the biosensor.
T839 102834-103106 Sentence denotes As a result, impedance-based electrochemical methods generate biosensor responses in terms of changes in the measured physical quantities (e.g., changes in impedance) or calculated equivalent circuit elements (e.g., double-layer capacitance or charge-transfer resistance).
T840 103107-103225 Sentence denotes As shown in Table 1, Table 2, EIS is one of the most commonly used methods for electrochemical detection of pathogens.
T841 103226-103406 Sentence denotes For example, Zarei et al. used EIS with an Au nanoparticle-modified carbon-based electrode for detection of Shigella dysenteriae (S. dysenteriae) at a LOD of 1 CFU/mL (Zarei et al.
T842 103407-103413 Sentence denotes 2018).
T843 103414-103570 Sentence denotes Primiceri et al. used EIS with Au interdigitated microelectrode arrays and Fe(CN)6 3 - /4- to detect L. monocytogenes at a LOD of 5 CFU/mL (Primiceri et al.
T844 103571-103577 Sentence denotes 2016).
T845 103578-103721 Sentence denotes Andrade et al. used EIS with a CNT-based electrode for multiplexed detection of E. coli, B. subtilis, and Enterococcus faecalis (Andrade et al.
T846 103722-103728 Sentence denotes 2015).
T847 103729-103830 Sentence denotes Redox reactions at the electrode-electrolyte interface are typically established using a redox probe.
T848 103831-104088 Sentence denotes Owing to its high reversibility, the Fe(CN)6 3 - /4- redox couple has been widely investigated as an electrochemical probe for biosensing applications and is regarded as a standard model for highly reversible electrochemical reactions (Daum and Enke, 1969).
T849 104089-104212 Sentence denotes While useful electrochemical probes, redox reactions may also affect the electrode and immobilized biorecognition elements.
T850 104213-104412 Sentence denotes For example, redox reactions associated with the Fe(CN)6 3 - /4- probe can cause etching of Au electrodes due to the presence of CN− ions when using the redox couple for EIS measurements (Vogt et al.
T851 104413-104419 Sentence denotes 2016).
T852 104420-104568 Sentence denotes This observation warrants further investigation, particularly in the context of establishing the effects on biosensor repeatability and reusability.
T853 104569-104654 Sentence denotes The use of alternative redox probes or electrode materials may mitigate such effects.
T854 104655-104759 Sentence denotes For example, ferrocene and ferrocenemethanol have also been used as redox probes for pathogen detection.
T855 104760-104811 Sentence denotes Ruthenium(III)/ruthenium(II) (Schrattenecker et al.
T856 104812-104860 Sentence denotes 2019) and immobilized quinone pairs (Piro et al.
T857 104861-104908 Sentence denotes 2013) are also potentially useful alternatives.
T858 104909-105099 Sentence denotes Biosensors that use impedance-based methods and whose impedance response can be modeled using equivalent circuit models can be used to calculate the capacitance of the electric double layer.
T859 105100-105363 Sentence denotes The double-layer capacitance is recognized to be sensitive to the structure of the electrode, the characteristics and concentration of analytes at the electrode surface and in the electrolyte, and the characteristics of the electrolyte (Lisdat and Schäfer, 2008).
T860 105364-105493 Sentence denotes As a capacitor, the double-layer is not only dependent on the dielectric material but also the thickness of the dielectric layer.
T861 105494-105590 Sentence denotes Importantly, both characteristics could be affected by molecular binding events on an electrode.
T862 105591-105786 Sentence denotes For example, when a target analyte binds to an immobilized biorecognition element, counter ions around the electrode surface are displaced, leading to a change in the capacitance (Berggren et al.
T863 105787-105793 Sentence denotes 2001).
T864 105794-105950 Sentence denotes The capacitance can be determined from the reactive component of the impedance or by fitting of an equivalent circuit model (Barsoukov and Macdonald, 2018).
T865 105951-106052 Sentence denotes Idil et al. used the capacitive response of a MIP electrode for the detection of E. coli (Idil et al.
T866 106053-106059 Sentence denotes 2017).
T867 106060-106179 Sentence denotes Jantra et al. similarly used the capacitive response of an Au rod electrode for the detection of E. coli (Jantra et al.
T868 106180-106186 Sentence denotes 2011).
T869 106187-106353 Sentence denotes Luka et al. used the capacitive response of an Au interdigitated microelectrode array based on equivalent circuit analysis for the detection of C. parvum (Luka et al.
T870 106354-106360 Sentence denotes 2019).
T871 106361-106507 Sentence denotes See Table 1, Table 2 for a detailed list of studies that have used the capacitive response of an electrochemical biosensor for pathogen detection.
T872 106509-106529 Sentence denotes 3.3.4 Conductometry
T873 106530-106720 Sentence denotes Conductometry methods are those in which the conductivity of the sample solution is monitored using a low-amplitude alternating electrical potential (Dzyadevych and Jaffrezic-Renault, 2014).
T874 106721-106832 Sentence denotes The principle relies on conductivity change in the sample via the production or consumption of charged species.
T875 106833-107036 Sentence denotes The measurement has the advantage of not requiring a reference electrode and can be used to detect both electroactive and electroinactive analytes (Jaffrezic-Renault and Dzyadevych, 2008; Narayan, 2016).
T876 107037-107161 Sentence denotes Given the method can be performed using a two-electrode configuration, conductometric biosensors can be easily miniaturized.
T877 107162-107314 Sentence denotes In addition, they are less vulnerable to many types of interference due to their differential measurement mode (Jaffrezic-Renault and Dzyadevych, 2008).
T878 107315-107449 Sentence denotes As shown in Fig. 5d, Yoo et al. used a conductometric biosensor with CNT-based electrodes for the detection of B. subtilis (Yoo et al.
T879 107450-107456 Sentence denotes 2017).
T880 107457-107600 Sentence denotes Mannoor et al. used a previously described conductometric biosensor to detect S. aureus and Helicobacter pylori on tooth enamel (Mannoor et al.
T881 107601-107607 Sentence denotes 2012).
T882 107608-107772 Sentence denotes Shen et al. detected two strains of human influenza A virus (H1N1 and H3N2) using conductometry with a silicon nanowire array at a LOD of 29 viruses/μL (Shen et al.
T883 107773-107779 Sentence denotes 2012).
T884 107780-107911 Sentence denotes Additional studies that have examined the use of conductometric biosensors for pathogen detection can be found in Table 1, Table 2.
T885 107913-107946 Sentence denotes 3.4 Secondary binding approaches
T886 107947-108055 Sentence denotes Electrochemical biosensors would ideally produce sensitive and selective results using label-free protocols.
T887 108056-108256 Sentence denotes However, secondary binding reactions are sometimes required to facilitate the robust detection of pathogens that lack initial labels depending on the biosensor characteristics and measurement demands.
T888 108257-108380 Sentence denotes Secondary binding steps can facilitate target labeling, biosensor signal amplification, and verification of target binding.
T889 108381-108553 Sentence denotes Secondary binding steps provide useful in situ controls and can increase sensitivity, LOD, dynamic range, and measurement confidence (e.g., verification of target binding).
T890 108554-108681 Sentence denotes Secondary binding steps also provide opportunities for acquiring additional bioanalytical information about the target species.
T891 108682-108844 Sentence denotes Here, we classify assays that use secondary binding steps as labeled approaches in Table 1, Table 2 regardless of if the primary binding step produced a response.
T892 108845-109001 Sentence denotes There is, however, a more subtle distinction if binding of the secondary species is used for amplification or verification purposes as previously discussed.
T893 109002-109082 Sentence denotes Labels often include a biorecognition element-enzyme or -nanoparticle conjugate.
T894 109083-109301 Sentence denotes In electrochemical biosensing applications, such labels often serve the purpose of altering the material properties or transport processes of the electrode-electrolyte interface, often by inducing a secondary reaction.
T895 109302-109463 Sentence denotes Secondary binding of optically-active nanomaterials to captured targets can also enable the use of optical transducers for simultaneous detection or bioanalysis.
T896 109464-109566 Sentence denotes Enzymes are among the most commonly used secondary binding species for label-based pathogen detection.
T897 109567-109708 Sentence denotes As shown in Table 2, electrochemical biosensors for pathogen detection that employ enzymes are commonly performed as a sandwich assay format.
T898 109709-109861 Sentence denotes A schematic of secondary binding steps for biosensor amplification based on the binding of HRP-antibody conjugates is shown in Fig. 6 a (Kokkinos et al.
T899 109862-109868 Sentence denotes 2016).
T900 109869-110050 Sentence denotes Hong et al. used HRP-labeled secondary antibodies to amplify the CV and EIS responses of a concanavalin A-functionalized nanostructured Au electrode to detect norovirus (Hong et al.
T901 110051-110057 Sentence denotes 2015).
T902 110058-110307 Sentence denotes Gayathri et al. used an HRP-antibody conjugate to induce an enzyme-assisted reduction reaction with an immobilized thionine-antibody receptor in an H2O2 system for detection of E. coli down to 50 CFU/mL using a sandwich assay format (Gayathri et al.
T903 110308-110314 Sentence denotes 2016).
T904 110315-110596 Sentence denotes Xu et al. used glucose oxidase and monoclonal anti-S. typhimurium to functionalize magnetic bead labels for separation and detection of S. typhimurium on an Au IDAM using EIS and glucose to catalyze the reaction that exhibited a linear working range of 102 to 106 CFU/mL (Xu et al.
T905 110597-110604 Sentence denotes 2016b).
T906 110605-111182 Sentence denotes Fig. 6 Highlight of secondary binding and signal amplification approaches utilized in electrochemical biosensor-based pathogen detection. a) Four amplification approaches associated with the secondary binding of enzyme-labeled secondary antibodies: (A) electron transfer mediation; (B) nanostructuring of surface for increased rate of charge transfer kinetics; (C) conversion of electrochemically inactive substrate into a detectable electroactive product; (D) catalysis of oxidation of glucose for production of hydrogen peroxide for electrochemical detection (Kokkinos et al.
T907 111183-111296 Sentence denotes 2016). b) Signal amplification via non-selective binding of AuNPs to bound bacterial target (E. coli) (Wan et al.
T908 111297-111303 Sentence denotes 2016).
T909 111304-111405 Sentence denotes In addition to enzymes, secondary binding of nanoparticles has also been used for pathogen detection.
T910 111406-111579 Sentence denotes As shown in Fig. 6b, Wan et al. utilized non-functionalized AuNPs to amplify the EIS response of an antibody-immobilized planar Au electrode to E. coli detection (Wan et al.
T911 111580-111586 Sentence denotes 2016).
T912 111587-111679 Sentence denotes A detailed overview of studies that employ enzymes and nanoparticles is provided in Table 2.
T913 111680-111958 Sentence denotes We remind the reader that while secondary binding steps are useful techniques, assays that avoid secondary binding steps have advantages for bioprocess monitoring and control applications, as they avoid the addition of reagents to a process that may compromise product quality).
T914 111960-111997 Sentence denotes 4 Applications to pathogen detection
T915 111998-112194 Sentence denotes As identified in the previous sections, the application influences the biosensor design and measurement format associated with a given electrochemical biosensor-based assay for pathogen detection.
T916 112195-112394 Sentence denotes We next review applications of electrochemical biosensors for pathogen detection in food and water safety, environmental monitoring and infection control, medical diagnostics, and bio-threat defense.
T917 112396-112435 Sentence denotes 4.1 Food and water safety applications
T918 112436-112528 Sentence denotes Detection of foodborne and waterborne pathogens is an essential aspect of public healthcare.
T919 112529-112696 Sentence denotes Foodborne and waterborne pathogens originate from a variety of sources and matrices and typically infect humans through the consumption of contaminated food and water.
T920 112697-112796 Sentence denotes Waterborne pathogens are responsible for about 2.2 million deaths annually worldwide (Pandey et al.
T921 112797-112887 Sentence denotes 2014), and contaminated food-related deaths amount to around 420,000 annually (WHO, 2015).
T922 112888-113113 Sentence denotes In 2019, the United States suffered an outbreak of multidrug-resistant S. typhimurium in turkey products caused 358 infections across 42 states, demonstrating the importance of detecting pathogens in food sources (CDC, 2019).
T923 113114-113410 Sentence denotes While biosensors for pathogen detection are critical to water and food safety in developed regions, biosensors are particularly important aspects of public healthcare in remote and under-developed regions due to relatively reduced infrastructure and resources for food and water quality analysis.
T924 113411-113626 Sentence denotes For example, in 2014, a cholera outbreak linked to V. cholerae in Ghana, which has been associated with poor environmental water management and sanitation issues, infected over 20,000 individuals (Ohene-Adjei et al.
T925 113627-113633 Sentence denotes 2017).
T926 113634-113727 Sentence denotes The selective detection of pathogens in food and water remains a global healthcare challenge.
T927 113728-113855 Sentence denotes Several comprehensive reviews have been written on biosensors for food and water safety (Baeumner, 2003; Bozal-Palabiyik et al.
T928 113856-113876 Sentence denotes 2018; Leonard et al.
T929 113877-113900 Sentence denotes 2003; Ye et al., 2019).
T930 113901-113970 Sentence denotes Here, we describe the most common foodborne and waterborne pathogens.
T931 113971-114216 Sentence denotes Common foodborne and waterborne pathogens include protozoa, such as C. parvum and G. lamblia, bacteria, such as E. coli, L. monocytogenes, S. typhimurium, S. aureus, and Campylobacter, and viruses, such as norovirus and rotavirus (Beuchat et al.
T932 114217-114237 Sentence denotes 2013; Cabral, 2010).
T933 114238-114396 Sentence denotes The infectious dose of foodborne and waterborne pathogens can vary by 4–6 orders of magnitude, from a single cell or oocyst to greater than one million cells.
T934 114397-114554 Sentence denotes For example, the infectious dose of S. dysenteriae is 200 CFU (Greig and Todd, 2010), while that of S. aureus is 100,000 CFU (Schmid-Hempel and Frank, 2007).
T935 114555-114778 Sentence denotes Given the extensive use of immunoassays in food and water safety, such as ELISA, it is possible to obtain commercially-available monoclonal and polyclonal antibodies for a large number of foodborne and waterborne pathogens.
T936 114779-115006 Sentence denotes Biosensor applications associated with process monitoring applications may require biosensor designs and measurement formats that facilitate high-throughput analysis, continuous monitoring capability, and biosensor reusability.
T937 115007-115208 Sentence denotes Alternatively, those for water safety applications in under-developed regions may require biosensor designs and measurement formats that facilitate field use, such as sample preparation-free protocols.
T938 115209-115361 Sentence denotes Pathogens can also enter food and water through processing, packaging, distribution, and storage processes (e.g., via workers and pests) (Beuchat et al.
T939 115362-115401 Sentence denotes 2013; Mehrotra, 2016; Ye et al., 2019).
T940 115402-115548 Sentence denotes As a result, biosensors for food and water safety applications should facilitate pathogen detection at various stages of the processing operation.
T941 115549-115791 Sentence denotes Recent advances in electrochemical biosensors for food and water safety applications have established new low-cost biosensor designs, portable measurement formats, and flexible form-factors and are discussed further in the following sections.
T942 115793-115857 Sentence denotes 4.2 Environmental monitoring and infection control applications
T943 115858-115992 Sentence denotes In addition to foodborne and waterborne pathogens, the detection of environmental pathogens is also an important aspect of healthcare.
T944 115993-116131 Sentence denotes For example, diseases associated with environmental pathogens are one of the leading causes of death in low-income economies (WHO, 2018a).
T945 116132-116224 Sentence denotes For example, malaria was reported to cause an estimated 435,000 deaths in 2017 (WHO, 2018b).
T946 116225-116448 Sentence denotes Environmental pathogens are microorganisms that typically spend a substantial part of their lifecycle outside human hosts, but when introduced to humans through contact or inhalation cause disease with measurable frequency.
T947 116449-116533 Sentence denotes Thus, environmental pathogens are often targets in medical diagnostics applications.
T948 116534-116774 Sentence denotes However, here, we choose to distinguish environmental monitoring applications, which require pathogen detection in the environment (e.g., in air or on surfaces), from medical diagnostics applications, which require detection in body fluids.
T949 116775-116853 Sentence denotes Thus, the distinction is based on the matrix in which the pathogen is present.
T950 116854-117083 Sentence denotes Similar to food and water safety applications, which require biosensors capable of analyzing pathogen-containing complex matrices, such as a water or food matrix, environmental pathogens are present in multiple types of matrices.
T951 117084-117392 Sentence denotes While environmental pathogens can enter the body through direct physical contact, they can also be transmitted through aerosols or interaction with organisms that serve as vectors for the infectious agent, such as mosquitos in the case of Plasmodium falciparum (the infectious agent associated with malaria).
T952 117393-117640 Sentence denotes Thus, the detection of environmental pathogens often requires analysis of matrices, such as air, and objects, such as the surfaces of biomedical devices or objects within healthcare facilities, that are present in the human environment (Lai et al.
T953 117641-117647 Sentence denotes 2009).
T954 117648-117772 Sentence denotes Several comprehensive reviews have been provided on the detection of environmental pathogens (Baeumner, 2003; Justino et al.
T955 117773-117779 Sentence denotes 2017).
T956 117780-117885 Sentence denotes Here, we describe the most common environmental pathogens found both in and outside of clinical settings.
T957 117886-118106 Sentence denotes Common environmental pathogens in a non-clinical setting include Legionella spp., which cause Legionnellosis, Mycobacterium tuberculosis, which causes tuberculosis, and Naegleria fowleri, which causes amoebic meningitis.
T958 118107-118208 Sentence denotes In addition to bacteria and protozoa, fungi, nematodes, and insects are also environmental pathogens.
T959 118209-118661 Sentence denotes Common environmental pathogens in clinical settings associated with healthcare-acquired infections include drug-resistant and multi-drug resistant (MDR) pathogens, such as Clostridium difficile (CD) (Hookman and Barkin, 2009), which causes CD-associated diarrhea and antibiotic-induced colitis, and methicillin-resistant S. aureus (MRSA), which causes severe infections in various parts of the body, including the urinary tract (Gordon and Lowy, 2008).
T960 118662-118814 Sentence denotes The infectious dose of environmental pathogens also varies by orders of magnitude depending on the pathogen as well as age and health of the individual.
T961 118815-118963 Sentence denotes For example, the infectious dose of CD is less than 10 spores, while that of MRSA is greater than 100,000 organisms (Schmid-Hempel and Frank, 2007).
T962 118964-119159 Sentence denotes While it is possible to obtain antibodies for foodborne and waterborne pathogens, it can be challenging to obtain antibodies for various environmental pathogens, including protozoa and nematodes.
T963 119160-119281 Sentence denotes Thus, traditional bioanalytical techniques, such as PCR, are often utilized for the detection of environmental pathogens.
T964 119282-119475 Sentence denotes Similar to food and water safety applications, biosensor-based assays for environmental pathogen detection applications also utilize measurement formats that facilitate the analysis of liquids.
T965 119476-119566 Sentence denotes However, they also require measurement formats for the detection of aerosolized pathogens.
T966 119567-119819 Sentence denotes In addition to airborne transmission, environmental pathogens are transmitted by direct surface contact (similar to many foodborne pathogens), which is a significant mode of transmission in healthcare settings (e.g., of healthcare-acquired infections).
T967 119820-120082 Sentence denotes Standardized guidelines for disinfecting and sterilizing the surfaces of medical equipment, assistive technologies, counters, and doors, among other surfaces, have emerged as an important aspect of infection control in modern healthcare facilities (Fraise et al.
T968 120083-120089 Sentence denotes 2008).
T969 120090-120250 Sentence denotes Thus, the detection of pathogens on the surfaces of biomedical devices and objects present in healthcare facilities is an important research area (Kramer et al.
T970 120251-120269 Sentence denotes 2006; Weber et al.
T971 120270-120276 Sentence denotes 2010).
T972 120277-120511 Sentence denotes For example, bacterial contamination of inanimate surfaces and equipment has been examined as a source of intensive care unit-acquired infections, a global healthcare challenge, especially when caused by MDR pathogens (Russotto et al.
T973 120512-120518 Sentence denotes 2015).
T974 120519-120606 Sentence denotes Hospital-acquired infections are prevalent causes of morbidity in patients (Orsi et al.
T975 120607-120613 Sentence denotes 2002).
T976 120614-120800 Sentence denotes This problem has only been exasperated by the rise of MDR CD, as well as drug-resistant strains of Campylobacter, Enterococcus, Salmonella, S. aureus, and S. dysenteriae (Ventola, 2015).
T977 120801-120933 Sentence denotes In addition to clinical pathogens, it is also of interest to detect pathogens in non-clinical settings (Faucher and Charette, 2015).
T978 120934-121124 Sentence denotes Toxin-producing algae, such as cyanobacteria and sulphate-reducing bacteria, are also important targets for electrochemical biosensors associated with the prevention of water-based diseases.
T979 121126-121162 Sentence denotes 4.3 Medical diagnostic applications
T980 121163-121349 Sentence denotes The field of medical diagnostics heavily relies on the identification and quantification of pathogens found in body fluids, including whole blood, stool, urine, mucus, saliva, or sputum.
T981 121350-121580 Sentence denotes Diagnostic assays based on traditional bioanalytical techniques for detection of pathogens in body fluids are the gold standard and serve an essential role in healthcare by enabling the diagnosis and treatment of various diseases.
T982 121581-121821 Sentence denotes Biosensors offer a complementary diagnostic platform that enable rapid and cost-effective measurements, high sensitivity, and the ability to make measurements in complex matrices that pose challenges to traditional bioanalytical techniques.
T983 121822-122012 Sentence denotes Studies suggest that rapid diagnostic testing can potentially reduce the chance of hospitalization, duration of hospitalization and antimicrobial use, and mortality rates (Barenfanger et al.
T984 122013-122034 Sentence denotes 2000; Beekmann et al.
T985 122035-122055 Sentence denotes 2003; Dierkes et al.
T986 122056-122074 Sentence denotes 2009; Rappo et al.
T987 122075-122081 Sentence denotes 2016).
T988 122082-122305 Sentence denotes For example, repeated rapid screening programs for human immunodeficiency virus (HIV) detection is recommended as a means of increasing quality-adjusted life years of health for citizens in the United States (Paltiel et al.
T989 122306-122312 Sentence denotes 2006).
T990 122313-122452 Sentence denotes Additionally, the need for rapid antibody screening has been identified as an important aspect of mitigating the ongoing COVID-19 pandemic.
T991 122453-122689 Sentence denotes Several comprehensive reviews have been published on traditional bioanalytical assays and biosensor-based assays for pathogen detection in medical diagnostics applications (Ahmed et al., 2014; da Silva et al., 2017; Singh et al., 2014).
T992 122690-122884 Sentence denotes Common pathogens include the aforementioned foodborne, waterborne, and environmental pathogens (e.g., Mycobacterium and Plasmodium spp.), as well as additional airborne and bloodborne pathogens.
T993 122885-123040 Sentence denotes Pathogens such as Mycobacterium, HIV, and Plasmodium falciparum, represent some of the top causes of death from infectious diseases worldwide (WHO, 2018a).
T994 123041-123336 Sentence denotes Other common pathogens associated with medical diagnostics applications include those that cause respiratory infections, urinary tract infections, and diarrheal diseases, such as CD and MRSA, which can be life-threatening to the children, elderly and individuals with compromised immune systems.
T995 123337-123526 Sentence denotes Other airborne and bloodborne pathogens of interest include the influenza virus, COVID-19, hepatitis virus, rabies virus, and bacteria such as Mycoplasma pneumonia and Bordetella pertussis.
T996 123527-123714 Sentence denotes The infectious dose of airborne and bloodborne pathogens also varies by orders of magnitude depending on the pathogen, the method of contraction, and the age and health of the individual.
T997 123715-123958 Sentence denotes For example, the infectious dose of influenza is between 100–1000 particles (Gürtler, 2006), while the median infectious dose of HIV can vary, for example, from two RNA copies to 65,000 depending on the strain and source (Reid and Juma, 2009).
T998 123959-124106 Sentence denotes The diagnostically-relevant concentration of pathogens in each type of matrix must be considered when designing a biosensor for pathogen detection.
T999 124107-124223 Sentence denotes For example, the detection of bacteria in blood versus urine exhibit different diagnostic thresholds (Kelley, 2017).
T1000 124224-124288 Sentence denotes Such knowledge can inform the need for sample preparation steps.
T1001 124290-124341 Sentence denotes 4.4 Biological defense and bio-threat applications
T1002 124342-124478 Sentence denotes The potential for the weaponization of pathogens drives the need for rapid and sensitive biosensors for biological defense applications.
T1003 124479-124696 Sentence denotes Biosensor applications to biological defense and bio-threat are related to the aforementioned applications in food and water safety, environmental monitoring, and medical diagnostics but consider weaponized pathogens.
T1004 124697-124962 Sentence denotes However, while pathogens found in environmental monitoring applications are often native and endogenous agents, pathogens found in biological defense and bio-threat applications are often exogenous agents, which may have been weaponized and intentionally dispersed.
T1005 124963-125191 Sentence denotes For example, pathogen-based bio-threat situations typically involve the overt or covert introduction of an exogenous pathogen into either the food or water supply or environments which with humans closely interact (Cirino et al.
T1006 125192-125211 Sentence denotes 2004; Mirski et al.
T1007 125212-125242 Sentence denotes 2014; Shah and Wilkins, 2003).
T1008 125243-125383 Sentence denotes The reader is directed to various comprehensive reviews on biosensor-based assays for the detection of biowarfare agents (Christopher et al.
T1009 125384-125414 Sentence denotes 1997; Shah and Wilkins, 2003).
T1010 125415-125476 Sentence denotes Common targets include the aforementioned airborne pathogens.
T1011 125477-125684 Sentence denotes In addition to the aforementioned naturally-occurring pathogens, pathogens for bio-threat may include engineered pathogens, such as genetically-modified viruses that can be transmitted via airborne pathways.
T1012 125685-125859 Sentence denotes B. anthracis (Anthrax), yersinia pestis (plague), and vaccinia virus are among several pathogens that have been utilized or suggested as biowarfare agents (Christopher et al.
T1013 125860-125890 Sentence denotes 1997; Shah and Wilkins, 2003).
T1014 125891-126142 Sentence denotes While pathogen-based bio-threats may be introduced to the water and food supply, the detection of pathogen-based bio-threats in air is particularly critical to biowarfare defense, as they may be introduced into the battlefield in the form of aerosols.
T1015 126143-126305 Sentence denotes Further, the dispersal of pathogen-based bio-threats by air in facilities (e.g., via air-handling systems) represents a significant domestic bioterrorism concern.
T1016 126306-126529 Sentence denotes Thus, biosensor-based assays for bio-threat applications should be low-cost and portable to enable integration with existing physical systems (e.g., facilities) and movement with the warfighter or drones on the battlefield.
T1017 126530-126806 Sentence denotes Having discussed transduction elements, biorecognition elements, electrochemical methods, measurement formats, and pathogen detection applications, we next discuss the present challenges and future directions in the field of electrochemical biosensor-based pathogen detection.
T1018 126808-126907 Sentence denotes 5 Present challenges and future directions for pathogen detection using electrochemical biosensors
T1019 126908-127112 Sentence denotes Here, we discuss the present challenges and future directions associated with pathogen detection using electrochemical biosensors to identify future research opportunities and emerging areas in the field.
T1020 127114-127188 Sentence denotes 5.1 Emerging electrode materials, fabrication processes, and form factors
T1021 127189-127302 Sentence denotes The ability to create robust, low-cost biosensors for pathogen detection is a significant challenge in the field.
T1022 127303-127390 Sentence denotes One of the primary methods of reducing cost is decreasing the material cost per device.
T1023 127391-127495 Sentence denotes Carbon-based electrodes (e.g., graphite, graphene, CNTs), such as those shown in Fig. 7 a (Afonso et al.
T1024 127496-127521 Sentence denotes 2016) and 7b (Wang et al.
T1025 127522-127638 Sentence denotes 2013), are now being examined as potential alternatives to relatively more expensive metallic or ceramic electrodes.
T1026 127639-127761 Sentence denotes Many of these carbon-based materials are also nanoscale in structure, and thus offer advantages regarding nanostructuring.
T1027 127762-127897 Sentence denotes Similarly, polymer-based electrodes have also been examined as low-cost alternatives to metal electrodes as described in Section 2.1.3.
T1028 127898-128067 Sentence denotes For example, Afonso et al. used a home craft cutter printer as a highly accessible means of fabricating high quantities of disposable carbon-based sensors (Afonso et al.
T1029 128068-128074 Sentence denotes 2016).
T1030 128075-128238 Sentence denotes Fig. 7 State-of-the-art developments in electrochemical biosensors for pathogens. a) Low-cost, flexible, disposable screen-printed carbon electrodes (Afonso et al.
T1031 128239-128295 Sentence denotes 2016). b) Free-standing graphene electrodes (Wang et al.
T1032 128296-128398 Sentence denotes 2013). c) Paper-based substrates for pathogen detection using electrochemical methods (Bhardwaj et al.
T1033 128399-128479 Sentence denotes 2017). d) Wearable wireless bacterial biosensor for tooth enamel (Mannoor et al.
T1034 128480-128581 Sentence denotes 2012). e) Smartphone-enabled signal processing for field-based environmental monitoring (Jiang et al.
T1035 128582-128588 Sentence denotes 2014).
T1036 128589-128722 Sentence denotes In addition to reducing the material cost per device, efforts to reduce the manufacturing cost of biosensors have also been examined.
T1037 128723-128803 Sentence denotes 3D printing processes have emerged as popular methods for biosensor fabrication.
T1038 128804-128879 Sentence denotes For example, 3D printing is compatible with flexible and curved substrates.
T1039 128880-129063 Sentence denotes 3D printing has also been used for the fabrication of various components of electrochemical biosensors, such as electrodes, substrates, fluid handling components, or device packaging.
T1040 129064-129194 Sentence denotes In particular, 3D printing has emerged as a useful fabrication platform for microfluidic-based analytical platforms (Waheed et al.
T1041 129195-129201 Sentence denotes 2016).
T1042 129202-129315 Sentence denotes For example, to date, 3D printing has enabled the fabrication of electrode-integrated microfluidics (Erkal et al.
T1043 129316-129385 Sentence denotes 2014), 3D microfluidics, organ-conforming microfluidics (Singh et al.
T1044 129386-129450 Sentence denotes 2017a), and transducer-integrated microfluidics (Cesewski et al.
T1045 129451-129457 Sentence denotes 2018).
T1046 129458-129621 Sentence denotes Thus, 3D printing may serve as an important fabrication platform for the creation of wearable microfluidic-based electrochemical biosensors for pathogen detection.
T1047 129622-129790 Sentence denotes The ability to quantify the level of pathogens on the surfaces of objects (e.g., skin, food, and medical equipment) remains a present challenge in the biosensing field.
T1048 129791-129909 Sentence denotes Wearable biomedical devices have emerged as promising tools for point-of-care (POC) diagnostics and health monitoring.
T1049 129910-130011 Sentence denotes The application constraints of wearable devices require them to be lightweight and simple to operate.
T1050 130012-130222 Sentence denotes Wearable devices can provide continuous monitoring of body fluids, such as blood and sweat, allowing patients to obtain real-time bioanalytical information without the inconvenience of facility-based screening.
T1051 130223-130394 Sentence denotes To date, biosensors have been incorporated into a variety of wearable devices, including contact lenses, clothing, bandages, rings, and tattoos (Bandodkar and Wang, 2014).
T1052 130395-130498 Sentence denotes This is a rapidly emerging area linked to smartphone technology for biosensor actuation and monitoring.
T1053 130499-130684 Sentence denotes The rise of flexible electronics has also contributed to the success of incorporating electrochemical biosensors into flexible textiles, which has enhanced their wearability (Rim et al.
T1054 130685-130691 Sentence denotes 2016).
T1055 130692-130893 Sentence denotes Although most wearable electrochemical biosensors are used to detect small molecules, such as lactate, glucose, or electrolytes, there is increasing interest in their application to pathogen detection.
T1056 130894-131049 Sentence denotes Challenges include biocompatibility (e.g., reduction of skin irritation), device power consumption, and biosensor-tissue mechanical and geometric matching.
T1057 131050-131257 Sentence denotes Because of the small sample size of body fluid secretions and the need to transport the sample to the electrode surface, microfluidic formats are now emerging for wearable bioanalytical systems (Singh et al.
T1058 131258-131265 Sentence denotes 2017a).
T1059 131267-131293 Sentence denotes 5.2 Detection of protozoa
T1060 131294-131462 Sentence denotes Importantly, the size of the pathogen may have a significant impact on a given electrochemical biosensor's performance based on the type of electrochemical method used.
T1061 131463-131543 Sentence denotes For example, pathogens can range greater than three orders of magnitude in size.
T1062 131544-131623 Sentence denotes For example, the diameter of norovirus was estimated at 27 nm (Robilotti et al.
T1063 131624-131695 Sentence denotes 2015), while the diameter of G. lamblia oocysts is ~14 μm (Adam, 2001).
T1064 131696-131808 Sentence denotes Electrochemical biosensors for the detection of protozoa-based pathogens is an area requiring further attention.
T1065 131809-132012 Sentence denotes Protozoa, as large pathogens, achieve relatively less coverage of the electrode than small pathogens, thereby having a relatively smaller effect on charge transfer at the electrode-electrolyte interface.
T1066 132013-132133 Sentence denotes C. parvum is at present the most commonly detected protozoa using electrochemical biosensors (see Table 1) (Iqbal et al.
T1067 132134-132152 Sentence denotes 2015) (Luka et al.
T1068 132153-132159 Sentence denotes 2019).
T1069 132161-132194 Sentence denotes 5.3 Detection of plant pathogens
T1070 132195-132485 Sentence denotes While the majority of infectious agents detected using electrochemical biosensors are human pathogens, emerging agricultural applications of electrochemical biosensors, such as in smart agriculture, suggest the need for biosensors capable of detecting plant pathogens (Khater et al., 2017).
T1071 132486-132665 Sentence denotes For example, crop yield losses associated with plant pathogens range from 8.1 to 41.1% based on global production of wheat, rice, maize, potato, and soybean (Savary et al., 2019).
T1072 132666-132746 Sentence denotes Common plant pathogens include viruses, viroids, bacteria, fungi, and oomycetes.
T1073 132747-132916 Sentence denotes Chartuprayoon et al. recently established a polypyrrole nanoribbon-based chemiresistive immunosensor for detection of viral plant pathogens (Chartuprayoon et al., 2013).
T1074 132918-132944 Sentence denotes 5.4 Multiplexed detection
T1075 132945-133086 Sentence denotes Multiplexed detection of pathogens has emerged as a technique for phenotype identification and identification of multiple pathogenic threats.
T1076 133087-133242 Sentence denotes Multiplexing can be achieved via various approaches, but typically involves the use of multiple transducers that exhibit different biorecognition elements.
T1077 133243-133411 Sentence denotes For example, a strategy for multiplexed bacterial detection by Li et al. via immobilization of anti-E. coli and anti-V. cholerae on AuNPs is shown in Fig. 4b (Li et al.
T1078 133412-133418 Sentence denotes 2017).
T1079 133419-133551 Sentence denotes Spatially-distributed biorecognition elements on a single electrode or multiple electrodes can also provide multiplexing capability.
T1080 133552-133724 Sentence denotes For example, a strategy based on the immobilization of anti-E. coli and anti-S. aureus within a microfluidic chamber created by Tian et al. is shown in Fig. 4c (Tian et al.
T1081 133725-133731 Sentence denotes 2016).
T1082 133733-133783 Sentence denotes 5.5 Saturation-free continuous monitoring formats
T1083 133784-133907 Sentence denotes The inability to regenerate biosensors is a major hindrance to biosensor-based process monitoring and control applications.
T1084 133908-134109 Sentence denotes While various biosensors must be disposed of after a single use, the regeneration of biosensor surfaces using chemical approaches has been leveraged as an approach for creating multiple-use biosensors.
T1085 134110-134305 Sentence denotes Biosensor regeneration approaches typically involve chemically-mediated dissociation of the target from the immobilized biorecognition element or removal of the biorecognition element altogether.
T1086 134306-134519 Sentence denotes This can be accomplished through acid-base mediated regeneration, detergents, glycine, and urea as well as achieved by thermal regeneration, plasma cleaning, or even direct electrochemical desorption (Goode et al.
T1087 134520-134538 Sentence denotes 2015; Huang et al.
T1088 134539-134566 Sentence denotes 2010; Zelada-Guillen et al.
T1089 134567-134573 Sentence denotes 2010).
T1090 134574-134797 Sentence denotes For example, Dweik et al. used a combination of organic (acetone) and plasma cleaning protocols to regenerate an Au interdigitated microelectrode array after detection of E. coli to use devices five times each (Dweik et al.
T1091 134798-134804 Sentence denotes 2012).
T1092 134805-135085 Sentence denotes Johnson and Mutharasan used a liquid-phase hydrogen peroxide-mediated UV-photooxidation process for regeneration of biosensor surfaces as an alternative to aggressive chemical treatments, such as those based on the use of high- or low-pH solutions (Johnson and Mutharasan, 2013b).
T1093 135086-135331 Sentence denotes We note that an ideal biosensor regeneration (i.e., cleaning) approach for process monitoring applications would remove the captured target in situ using a chemical-free approach and preserve the biorecognition layer for subsequent measurements.
T1094 135333-135378 Sentence denotes 5.6 Low-cost, single-use portable biosensors
T1095 135379-135500 Sentence denotes The creation of environmentally-friendly disposable substrates is a present challenge for low-cost single-use biosensors.
T1096 135501-135620 Sentence denotes Paper-based substrates have recently emerged as attractive alternatives to costlier ceramic substrates (Martinez et al.
T1097 135621-135627 Sentence denotes 2009).
T1098 135628-135746 Sentence denotes Paper-based substrates can also eliminate the need for supporting fluid handling components through capillary effects.
T1099 135747-135872 Sentence denotes For example, paper substrates can be patterned with hydrophobic and hydrophilic regions to direct fluid flow (Carrilho et al.
T1100 135873-135879 Sentence denotes 2009).
T1101 135880-136002 Sentence denotes Paper-based devices are also relatively environmentally friendly in terms of material sourcing, disposal, and degradation.
T1102 136003-136235 Sentence denotes However, the potential toxicity of materials that may have been deposited on paper substrates, such as nanomaterials, should still be considered when assessing the environmental impact of a disposable single-use biosensing platform.
T1103 136236-136373 Sentence denotes For example, the long-term environmental and health impacts of nanomaterials remain active areas of research (Colvin, 2003; Klaine et al.
T1104 136374-136391 Sentence denotes 2008; Lead et al.
T1105 136392-136398 Sentence denotes 2018).
T1106 136399-136593 Sentence denotes Although paper-based devices have historically been most commonly used with colorimetric sensing techniques, they have been increasingly investigated for electrochemical biosensing (Ahmed et al.
T1107 136594-136615 Sentence denotes 2016; Meredith et al.
T1108 136616-136622 Sentence denotes 2016).
T1109 136623-136684 Sentence denotes A highlight of paper-based substrates is provided in Fig. 7c.
T1110 136685-136838 Sentence denotes The need for water safety and medical diagnostics in remote and under-developed regions has led to the demand for low-cost portable biosensing platforms.
T1111 136839-137075 Sentence denotes One of the major challenges in creating portable biosensors for field use is the need to establish sample preparation-free protocols (Johnson and Mutharasan, 2012) and miniaturize components for actuation, data acquisition, and readout.
T1112 137076-137212 Sentence denotes However, device miniaturization also presents measurement challenges, such as increasing the biosensor signal-to-noise ratio (Wei et al.
T1113 137213-137219 Sentence denotes 2009).
T1114 137220-137391 Sentence denotes Further, portable biosensing platforms should exhibit biorecognition elements that remain stable for extended periods and at a variety of temperatures and humidity levels.
T1115 137392-137611 Sentence denotes The measurement robustness associated with the analysis of small sample volumes also requires further attention with the use of emerging low-cost materials, fabrication approaches, and transduction methods (Kumar et al.
T1116 137612-137630 Sentence denotes 2013; Luppa et al.
T1117 137631-137662 Sentence denotes 2016; Narayan, 2016; Wan et al.
T1118 137663-137669 Sentence denotes 2013).
T1119 137670-138003 Sentence denotes The elimination of sample preparation steps from biosensor-based assays represents a significant advantage relative to traditional bioanalytical techniques (Johnson and Mutharasan, 2012) and is an important advantage and consideration for single-use biosensors and remote biosensing applications based on portable low-cost platforms.
T1120 138004-138163 Sentence denotes Sample preparation-free protocols can improve measurement confidence, repeatability, and reduce TTR, which are important aspects of healthcare decision-making.
T1121 138164-138330 Sentence denotes For example, it has been shown that a reduction in turnaround time for diagnostic assays could have a positive effect on clinical treatment outcomes (Davenport et al.
T1122 138331-138347 Sentence denotes 2017; Sin et al.
T1123 138348-138354 Sentence denotes 2014).
T1124 138355-138546 Sentence denotes When sample preparation is required, integrated alternatives to manual techniques, such as microfluidic processes, may provide a new path toward achieving rapid and robust pathogen detection.
T1125 138547-138817 Sentence denotes For example, separation and pre-concentration steps have been increasingly examined for integration with microfluidic-based biosensor platforms to reduce the number of steps, materials needed, and required technical personnel, and thus TTR (Bunyakul and Baeumner, 2014).
T1126 138819-138856 Sentence denotes 5.7 Wireless transduction approaches
T1127 138857-139122 Sentence denotes The examination of wireless transduction and monitoring approaches has an important role in creating portable and wearable biosensing platforms for pathogen detection and distributed sensing systems for infection control and process monitoring (Ghafar-Zadeh, 2015).
T1128 139123-139293 Sentence denotes Wireless biosensing platforms are also essential to the creation of implantable and integrated biosensors for pathogen detection, including those for medical diagnostics.
T1129 139294-139480 Sentence denotes For example, as previously referenced, Mannoor et al. fabricated a conformal biosensor for bacteria detection on tooth enamel based on a radiofrequency (RF) link approach (Mannoor et al.
T1130 139481-139501 Sentence denotes 2012) (see Fig. 7d).
T1131 139502-139583 Sentence denotes Wireless transduction approaches remains an emerging area for pathogen detection.
T1132 139584-139706 Sentence denotes An example of smartphone-enabled wireless signal processing for detection of E. coli can be found in Fig. 7e (Jiang et al.
T1133 139707-139713 Sentence denotes 2014).
T1134 139715-139729 Sentence denotes 6 Conclusions
T1135 139730-139819 Sentence denotes Here, we provided a critical review of electrochemical biosensors for pathogen detection.
T1136 139820-139933 Sentence denotes Biosensor transduction elements and biorecognition elements for electrochemical pathogen detection were reviewed.
T1137 139934-140123 Sentence denotes Bacteria remain the most commonly detected pathogens using electrochemical biosensors, though the detection of viruses and protozoa have been increasingly examined over the past five years.
T1138 140124-140307 Sentence denotes Electrochemical biosensors now exhibit LODs as low as a single plaque-forming unit (PFU)/mL and colony-forming unit (CFU)/mL and dynamic ranges that span multiple orders of magnitude.
T1139 140308-140530 Sentence denotes While planar Au electrodes remain the most commonly utilized working electrode, nanostructured electrodes derived from a variety of engineering materials, including polymers and composites, have been increasingly examined.
T1140 140531-140674 Sentence denotes Present challenges and future directions in the field were discussed, including a need for further low-cost, reusable, and wearable biosensors.
T1141 140675-140830 Sentence denotes Electrochemical biosensors offer great potential as resources for improving global healthcare, such as preventing the spread of highly contagious diseases.
T1142 140832-140865 Sentence denotes Declaration of competing interest
T1143 140866-141036 Sentence denotes The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
T1144 141038-141068 Sentence denotes Appendix A Supplementary data
T1145 141069-141147 Sentence denotes The following is the Supplementary data to this article:Multimedia component 1
T1146 141149-141165 Sentence denotes Acknowledgments:
T1147 141166-141361 Sentence denotes The authors are grateful for the generous support of the United States 10.13039/100000001National Science Foundation (CBET-1650601 and CMMI-1739318), which provided funding for the reported work.
T1148 141362-141475 Sentence denotes Appendix A Supplementary data to this article can be found online at https://doi.org/10.1016/j.bios.2020.112214.