LitCovid-sentences  

PMC:7152911 / 1695-141036 JSONTXT 12 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T16 0-15 Sentence denotes 1 Introduction
T17 16-67 Sentence denotes Pathogens are infectious agents that cause disease.
T18 68-206 Sentence denotes They include microorganisms, such as fungi, protozoans, and bacteria, and molecular-scale infectious agents, including viruses and prions.
T19 207-381 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 382-516 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 517-626 Sentence denotes Pathogens vary in many regards, such as virulence, contagiousness, mode of transmission, and infectious dose.
T22 627-788 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 789-1009 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 1010-1130 Sentence denotes The techniques used to identify and quantify pathogens can be broadly distinguished as immunoassays or DNA-based assays.
T25 1131-1390 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 1391-1475 Sentence denotes Immunoassays are ubiquitous across medical diagnostics and food safety applications.
T27 1476-1669 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 1670-1748 Sentence denotes In such assays, both the biorecognition element and the target are antibodies.
T29 1749-1885 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 1886-2066 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 2067-2312 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 2313-2412 Sentence denotes DNA-based assays require the pathogen to be present in the sample or to have been recently present.
T33 2413-2561 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 2562-2670 Sentence denotes Thus, targets associated with pathogen detection include toxins, nucleic acids, viruses, cells, and oocysts.
T35 2671-2776 Sentence denotes As a result, biorecognition elements widely vary, including antibodies, aptamers, and imprinted polymers.
T36 2777-2956 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 2957-2976 Sentence denotes 2007; Zourob et al.
T38 2977-3045 Sentence denotes 2008), such as enzyme-linked immunosorbent assay (ELISA) (Law et al.
T39 3046-3116 Sentence denotes 2015) and polymerase chain reaction (PCR) (Klein, 2002; Malorny et al.
T40 3117-3179 Sentence denotes 2003), which remain the gold standards for pathogen detection.
T41 3180-3440 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 3441-3671 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 3672-3893 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 3894-4029 Sentence denotes Bioanalytical techniques, such as PCR, may also encounter inhibition effects caused by background species in the sample (Justino et al.
T45 4030-4055 Sentence denotes 2017; Scognamiglio et al.
T46 4056-4072 Sentence denotes 2016; Sin et al.
T47 4073-4163 Sentence denotes 2014), which introduce measurement bias and increase measurement uncertainty (Clark et al.
T48 4164-4186 Sentence denotes 2016; Silverman et al.
T49 4187-4193 Sentence denotes 2019).
T50 4194-4429 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 4430-4538 Sentence denotes Over the past twenty-five years, biosensors have emerged to complement PCR and ELISA for pathogen detection.
T52 4539-4759 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 4760-4956 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 4957-4963 Sentence denotes 2001).
T55 4964-5144 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 5145-5344 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 5345-5491 Sentence denotes Biosensors have achieved sensitive and selective real-time detection of pathogens in various environments without the need for sample preparation.
T58 5492-5660 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 5661-5803 Sentence denotes In addition to sample preparation-free protocols, biosensors are compatible with label-free protocols (Daniels and Pourmand, 2007; Rapp et al.
T60 5804-5821 Sentence denotes 2010; Sang et al.
T61 5822-5846 Sentence denotes 2016; Vestergaard et al.
T62 5847-5853 Sentence denotes 2007).
T63 5854-5974 Sentence denotes Labels, often referred to as reporters, are molecular species, such as organic dyes or quantum dots (Resch-Genger et al.
T64 5975-6198 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 6199-6320 Sentence denotes Thus, label-free biosensors avoid the use of a reporter species to detect the target species (Cooper, 2009; Syahir et al.
T66 6321-6327 Sentence denotes 2015).
T67 6328-6664 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 6665-6671 Sentence denotes 2015).
T69 6672-6768 Sentence denotes While various types of transducers have been investigated for pathogen biosensing (Lazcka et al.
T70 6769-6787 Sentence denotes 2007; Singh et al.
T71 6788-7076 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 7077-7097 Sentence denotes 2018; Saucedo et al.
T73 7098-7104 Sentence denotes 2019).
T74 7105-7268 Sentence denotes Electrochemical biosensors for pathogen detection utilize conducting and semiconducting materials as the transducer, which is commonly referred to as an electrode.
T75 7269-7533 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 7534-7883 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 7884-8087 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 8088-8179 Sentence denotes 2018; Duffy and Moore, 2017; Felix and Angnes, 2018; Furst and Francis, 2019; Mishra et al.
T79 8180-8198 Sentence denotes 2018; Monzó et al.
T80 8199-8230 Sentence denotes 2015; Rastogi and Singh, 2019).
T81 8231-8308 Sentence denotes Here, we critically review electrochemical biosensors for pathogen detection.
T82 8309-8550 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 8551-8557 Sentence denotes 2001).
T84 8558-8784 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 8785-8987 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 8989-9048 Sentence denotes 2 Electrochemical biosensor designs for pathogen detection
T87 9049-9257 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 9258-9264 Sentence denotes 2001).
T89 9265-9360 Sentence denotes The electrochemical method utilized is a distinguishing aspect of an electrochemical biosensor.
T90 9361-9555 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 9556-9721 Sentence denotes Thus, we review electrochemical biosensors for pathogen detection using a framework built upon transducer elements, biorecognition elements, and measurement formats.
T92 9722-9810 Sentence denotes An overview of electrochemical biosensors for pathogen detection is provided in Fig. 1 .
T93 9811-9968 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 9969-10053 Sentence denotes As shown in Fig. 2b, studies have focused on pathogen detection in various matrices.
T95 10054-10212 Sentence denotes We next discuss the transduction elements, biorecognition elements, and measurement formats associated with electrochemical biosensors for pathogen detection.
T96 10213-10321 Sentence denotes Fig. 1 Components and measurement formats associated with electrochemical biosensors for pathogen detection.
T97 10322-10525 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 10527-10553 Sentence denotes 2.1 Transduction elements
T99 10554-10695 Sentence denotes The transduction element of an electrochemical biosensor is an electrochemical cell where the main component is commonly a working electrode.
T100 10696-10940 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 10941-11036 Sentence denotes Electrodes can be fabricated from multiple materials and using various manufacturing processes.
T102 11037-11178 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 11179-11323 Sentence denotes Electrodes are thus fabricated from conducting and semiconducting materials, including metals, such as gold (Au), and nonmetals, such as carbon.
T104 11324-11479 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 11480-11586 Sentence denotes As a result, electrodes can be classified by type and form of material, manufacturing process, and design.
T106 11587-11699 Sentence denotes Electrode designs can be classified by form factor, which includes planar, wire, nanostructured, or array-based.
T107 11700-11932 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 11933-12038 Sentence denotes They also influence the biosensor's cost, manufacturability, disposability, and measurement capabilities.
T109 12040-12063 Sentence denotes 2.1.1 Metal electrodes
T110 12064-12159 Sentence denotes Metal electrodes, such as Au and platinum (Pt), have been commonly used for pathogen detection.
T111 12160-12250 Sentence denotes Thick metal electrodes are commonly fabricated from bulk structures via cutting processes.
T112 12251-12451 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 12452-12492 Sentence denotes 2003) and screen printing (Taleat et al.
T114 12493-12499 Sentence denotes 2014).
T115 12500-12699 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 12700-12839 Sentence denotes While not yet applied to pathogen detection applications, three-dimensional (3D) printing processes, including inkjet printing (Bhat et al.
T117 12840-12867 Sentence denotes 2018; Medina-Sánchez et al.
T118 12868-12890 Sentence denotes 2014; Pavinatto et al.
T119 12891-12937 Sentence denotes 2015), selective laser melting (Ambrosi et al.
T120 12938-12954 Sentence denotes 2016; Loo et al.
T121 12955-13001 Sentence denotes 2017), and microextrusion printing (Foo et al.
T122 13002-13117 Sentence denotes 2018), have also been used for the fabrication of electrochemical sensors and electrodes using a variety of metals.
T123 13118-13206 Sentence denotes As shown in Table 1 , unstructured metal electrodes exhibit a range of detection limits.
T124 13207-13367 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 13368-13593 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 13594-14041 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 14042-14158 Sentence denotes Target Pathogen Working Electrode Biorecognition Element Electrochemical Method & Probe Limit of Detection Reference
T128 14159-14269 Sentence denotes E. coli Au interdigitated microelectrode array polyclonal anti-E.coli EIS 104 CFU/mL Radke and Alocilja (2005)
T129 14270-14372 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 14373-14466 Sentence denotes E. coli chromium interdigitated microelectrode array anti-E. coli EIS – Suehiro et al. (2006)
T131 14467-14574 Sentence denotes S. typhimurium ITO interdigitated microelectrode array anti-S. typhimurium EIS 10 CFU/mL Yang and Li (2006)
T132 14575-14673 Sentence denotes V. cholerae carbon electrode polyclonal anti-V. cholerae amperometry 8 CFU/mL Sharma et al. (2006)
T133 14674-14772 Sentence denotes E. coli Pt wire electrode polyclonal anti-E. coli potentiometry 9 × 105 CFU/mL Boehm et al. (2007)
T134 14773-14857 Sentence denotes E. coli Au microelectrode polyclonal anti-E.coli EIS 10 CFU/mL Maalouf et al. (2007)
T135 14858-14972 Sentence denotes L. monocytogenes TiO2 nanowires on Au electrode monoclonal anti-L. monocytogenes EIS 470 CFU/mL Wang et al. (2008)
T136 14973-15068 Sentence denotes E. coli Au electrode polyclonal anti-E. coli CV, EIS; Fe(CN)63-/4- 50 CFU/mL Geng et al. (2008)
T137 15069-15179 Sentence denotes S. typhimurium Au electrode polyclonal anti-S. typhimurium EIS; Fe(CN)63-/4- 10 CFU/mL Pournaras et al. (2008)
T138 15180-15286 Sentence denotes S. typhimurium Au microelectrode anti-S. typhimurium EIS; Fe(CN)63-/4- 500 CFU/mL Nandakumar et al. (2008)
T139 15287-15408 Sentence denotes E. coli graphite interdigitated microelectrode array E. coli-specific bacteriophages EIS 104 CFU/mL Shabani et al. (2008)
T140 15409-15505 Sentence denotes S. typhimurium Au electrode polyclonal anti-S. typhimurium EIS 100 CFU/mL Mantzila et al. (2008)
T141 15506-15603 Sentence denotes S. typhimurium macroporous silicon electrode anti-S. typhimurium EIS 103 CFU/mL Das et al. (2009)
T142 15604-15741 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 15742-15852 Sentence denotes S. typhimurium Au electrode monoclonal anti-S. typhimurium EIS; Fe(CN)63-/4- 100 CFU/mL La Belle et al. (2009)
T144 15853-15978 Sentence denotes S. typhimurium CNTs on carbon rod electrode anti-S. typhimurium aptamer potentiometry 0.2 CFU/mL Zelada-Guillen et al. (2009)
T145 15979-16075 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 16076-16197 Sentence denotes B. anthracis Ag electrode monoclonal and polyclonal anti-B. anthracis conductometry 420 spores/mL Pal and Alocilja (2009)
T147 16198-16317 Sentence denotes E. coli polysilicon interdigitated microelectrode array polyclonal anti-E. coli EIS 300 CFU/mL de la Rica et al. (2009)
T148 16318-16431 Sentence denotes E. coli Au interdigitated microelectrode array E. coli-specific bacteriophages EIS 104 CFU/mL Mejri et al. (2010)
T149 16432-16541 Sentence denotes E. coli CNTs on carbon rod electrode anti-E. coli aptamer potentiometry 6 CFU/mL Zelada-Guillen et al. (2010)
T150 16542-16679 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 16680-16802 Sentence denotes marine pathogenic sulphate-reducing bacteria (SRB) AuNPs on nickel foam electrode anti-SRB EIS 21 CFU/mL Wan et al. (2010)
T152 16803-16920 Sentence denotes E. coli Ag nanofiber array electrode monoclonal and polyclonal anti-E. coli conductometry 61 CFU/mL Luo et al. (2010)
T153 16921-17064 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 17065-17167 Sentence denotes E. coli Au interdigitated microelectrode array magainin I peptide EIS 103 CFU/mL Mannoor et al. (2010)
T155 17168-17256 Sentence denotes E. coli Au rod electrode concanavalin A lectin capacitive 12 CFU/mL Jantra et al. (2011)
T156 17257-17348 Sentence denotes rotavirus graphene microelectrode monoclonal anti-rotavirus CV 103 PFU/mL Liu et al. (2011)
T157 17349-17444 Sentence denotes human influenza A virus H3N2 Au electrode polyclonal anti-H3N2 EIS 8 ng/mL Hassen et al. (2011)
T158 17445-17556 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 17557-17702 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 17703-17831 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 17832-17932 Sentence denotes B. subtilis Au electrode concanavalin A lectin CV, EIS; Fe(CN)63-/4- 1 × 104 CFU/mL Xi et al. (2011)
T162 17933-18004 Sentence denotes E. coli Pt wire electrode anti-E. coli EIS 100 CFU/mL Tan et al. (2011)
T163 18005-18080 Sentence denotes S. aureus Pt wire electrode anti-S. aureus EIS 100 CFU/mL Tan et al. (2011)
T164 18081-18238 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 18239-18366 Sentence denotes swine influenza virus (SIV) H1N1 PDDA/CNT composite on Au microelectrode anti-SIV conductometry 180 TCID50/mL Lee et al. (2011)
T166 18367-18453 Sentence denotes E. coli graphene microelectrode anti-E. coli amperometry 10 CFU/mL Huang et al. (2011)
T167 18454-18534 Sentence denotes E. coli PEDOT:PSS electrode anti-E. coli amperometry 103 CFU/mL He et al. (2012)
T168 18535-18682 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 18683-18814 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 18815-18962 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 18963-19090 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 19091-19216 Sentence denotes E. coli CNT/polyallylamine composite on graphite electrode monoclonal anti-E. coli ASV 800 cells/mL Viswanathan et al. (2012)
T173 19217-19354 Sentence denotes Campylobacter CNT/polyallylamine composite on graphite electrode monoclonal anti-Campylobacter ASV 400 cells/mL Viswanathan et al. (2012)
T174 19355-19494 Sentence denotes S. typhimurium CNT/polyallylamine composite on graphite electrode monoclonal anti-S. typhimurium ASV 400 cells/mL Viswanathan et al. (2012)
T175 19495-19595 Sentence denotes S. aureus CNT electrode anti-S. aureus aptamer potentiometry 800 CFU/mL Zelada-Guillen et al. (2012)
T176 19596-19691 Sentence denotes E. coli Au electrode mannose carbohydrate ligand EIS; Fe(CN)63-/4- 100 CFU/mL Guo et al. (2012)
T177 19692-19819 Sentence denotes S. aureus graphene interdigitated microelectrode array odoranin-HP peptide conductometry 1 × 104 cells/mL Mannoor et al. (2012)
T178 19820-19950 Sentence denotes Helicobacter pylori graphene interdigitated microelectrode array odoranin-HP peptide conductometry 100 cells Mannoor et al. (2012)
T179 19951-20063 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 20064-20163 Sentence denotes E. coli polyaniline on Au electrode monoclonal anti-E. coli EIS 100 CFU/mL Chowdhury et al. (2012).
T181 20164-20265 Sentence denotes E. coli Au interdigitated microelectrode array anti-E. coli EIS 2.5 × 104 CFU/mL Dweik et al. (2012).
T182 20266-20394 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 20395-20534 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 20535-20636 Sentence denotes E. coli Au electrode E. coli-specific bacteriophages EIS; Fe(CN)63-/4- 800 CFU/mL Tlili et al. (2013)
T185 20637-20804 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 20805-20952 Sentence denotes cucumber mosaic virus (CMV) polypyrrole nanoribbons on Au microelectrode array polyclonal anti-CMV amperometry 10 ng/mL Chartuprayoon et al. (2013)
T187 20953-21056 Sentence denotes E. coli Au electrode polyclonal anti-E. coli EIS; Fe(CN)63- 2 CFU/mL Barreiros dos Santos et al. (2013)
T188 21057-21172 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 21173-21250 Sentence denotes E. coli Ag/AgCl wire electrode anti-E. coli EIS 10 CFU/mL Joung et al. (2013)
T190 21251-21408 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 21409-21509 Sentence denotes rotavirus reduced graphene oxide microelectrode anti-rotavirus amperometry 100 PFU Liu et al. (2013)
T192 21510-21677 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 21678-21785 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 21786-21857 Sentence denotes E. coli Pt wire electrode anti-E. coli EIS 10 CFU/mL Chan et al. (2013)
T195 21858-21984 Sentence denotes S. aureus reduced graphene oxide on carbon rod electrode anti-S. aureus aptamer potentiometry 1 CFU/mL Hernandez et al. (2014)
T196 21985-22079 Sentence denotes E. coli PAA/PD/CNT composite on carbon electrode anti-E. coli ASV 13 CFU/mL Chen et al. (2014)
T197 22080-22210 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 22211-22351 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 22352-22446 Sentence denotes E. coli Au electrode mannose carbohydrate ligand CV, mass change 1 CFU/mL Yazgan et al. (2014)
T200 22447-22572 Sentence denotes L. monocytogenes Au interdigitated microelectrode array leucocin A antimicrobial peptide EIS 103 CFU/mL Etayash et al. (2014)
T201 22573-22699 Sentence denotes S. typhimurium Au interdigitated microelectrode array monoclonal anti-S. typhimurium EIS 3 × 103 CFU/mL Dastider et al. (2015)
T202 22700-22801 Sentence denotes S. aureus Au electrode polyclonal anti-S. typhimurium EIS; Fe(CN)63-/4- 10 CFU/mL Bekir et al. (2015)
T203 22802-22900 Sentence denotes E. coli CNTs on Au electrode clavanin A peptide EIS; Fe(CN)63-/4- 100 CFU/mL Andrade et al. (2015)
T204 22901-23013 Sentence denotes Klebsiella pneumoniae CNTs on Au electrode clavanin A peptide EIS; Fe(CN)63-/4- 103 CFU/mL Andrade et al. (2015)
T205 23014-23126 Sentence denotes Enterococcus faecalis CNTs on Au electrode clavanin A peptide EIS; Fe(CN)63-/4- 103 CFU/mL Andrade et al. (2015)
T206 23127-23229 Sentence denotes B. subtilis CNTs on Au electrode clavanin A peptide EIS; Fe(CN)63-/4- 100 CFU/mL Andrade et al. (2015)
T207 23230-23360 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 23361-23493 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 23494-23606 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 23607-23748 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 23749-23857 Sentence denotes C. parvum AuNPs on carbon electrode anti-C. parvum aptamer SWV; Fe(CN)63-/4- 100 oocysts Iqbal et al. (2015)
T212 23858-23977 Sentence denotes E. coli CNT-coated Au-tungsten microwire electrodes polyclonal anti-E. coli amperometry 100 CFU/mL Yamada et al. (2016)
T213 23978-24101 Sentence denotes S. aureus CNT-coated Au-tungsten microwire electrodes polyclonal anti-S. aureus amperometry 100 CFU/mL Yamada et al. (2016)
T214 24102-24218 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 24219-24347 Sentence denotes L. monocytogenes Au interdigitated microelectrode array anti-L. monocytogenes EIS; Fe(CN)63-/4- 5 CFU/mL Primiceri et al. (2016)
T216 24348-24457 Sentence denotes norovirus Au microelectrode anti-norovirus aptamer SWV; Fe(CN)63-/Ru(NH3)63+ 10 PFU/mL Kitajima et al. (2016)
T217 24458-24603 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 24604-24741 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 24742-24851 Sentence denotes E. coli polysilicon interdigitated microelectrodes polyclonal anti-E. coli EIS – Mallén-Alberdi et al. (2016)
T220 24852-24990 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 24991-25108 Sentence denotes E. coli PEI/CNT composite on Au microwire electrode polyclonal anti-E. coli amperometry 100 CFU/mL Lee and Jun (2016)
T222 25109-25223 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 25224-25345 Sentence denotes S. aureus PEI/CNT composite on Au microwire electrode polyclonal anti-S. aureus amperometry 100 CFU/mL Lee and Jun (2016)
T224 25346-25445 Sentence denotes E. coli graphene microelectrode polyclonal anti-E. coli amperometry 5 × 103 CFU/mL Wu et al. (2016)
T225 25446-25538 Sentence denotes E. coli Au electrode concanavalin A lectin EIS; Fe(CN)63-/4- 75 cells/mL Yang et al. (2016b)
T226 25539-25612 Sentence denotes E. coli Pt wire electrodes anti-E. coli EIS 100 CFU/mL Tian et al. (2016)
T227 25613-25690 Sentence denotes S. aureus Pt wire electrodes anti-S. aureus EIS 100 CFU/mL Tian et al. (2016)
T228 25691-25820 Sentence denotes B. subtilis CNTs on Au interdigitated microelectrode array polyclonal anti-B. subtilis conductometry 100 CFU/mL Yoo et al. (2017)
T229 25821-25973 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 25974-26101 Sentence denotes norovirus graphene/AuNP composite on carbon electrode anti-norovirus aptamer DPV; Ferrocene 100 pM Chand and Neethirajan (2017)
T231 26102-26217 Sentence denotes norovirus Au electrode synthetic norovirus-specific peptide CV, EIS; Fe(CN)63-/4- 7.8 copies/mL Hwang et al. (2017)
T232 26218-26348 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 26349-26482 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 26483-26594 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 26595-26762 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 26763-26921 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 26922-27027 Sentence denotes E. coli Au microelectrode E. coli-imprinted MAH/HEMA polymer film capacitive 70 CFU/mL Idil et al. (2017)
T238 27028-27160 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 27161-27276 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 27277-27414 Sentence denotes human influenza A virus H1N1 PEDOT:PSS film electrode hemagglutinin-specific trisaccharide ligand amperometry 0.015 HAU Hai et al. (2018)
T241 27415-27543 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 27544-27658 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 27659-27759 Sentence denotes norovirus Au electrode norovirus-specific peptide EIS; Fe(CN)63-/4- 1.7 copies/mL Baek et al. (2019)
T244 27760-27891 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 27892-28023 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 28024-28159 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 28160-28311 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 28312-28463 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 28465-28490 Sentence denotes 2.1.2 Ceramic electrodes
T250 28491-28653 Sentence denotes Conducting and semiconducting ceramics, including indium tin oxide (ITO), polysilicon, and titanium dioxide (TiO2) have also been examined for pathogen detection.
T251 28654-28768 Sentence denotes For example, Das et al. used a silicon electrode for Salmonella typhimurium (S. typhimurium) detection (Das et al.
T252 28769-28775 Sentence denotes 2009).
T253 28776-28949 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 28950-28956 Sentence denotes 2015).
T255 28957-29202 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 29203-29410 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 29411-29417 Sentence denotes 2018).
T258 29418-29614 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 29616-29641 Sentence denotes 2.1.3 Polymer electrodes
T260 29642-29716 Sentence denotes Polymers have also been investigated as electrodes for pathogen detection.
T261 29717-29841 Sentence denotes Polymers have various advantages, including tunable electrical conductivity, biocompatiblity, and environmentally stability.
T262 29842-29960 Sentence denotes Polymer electrodes are also compatible with a range of biorecognition element immobilization techniques (Arshak et al.
T263 29961-29981 Sentence denotes 2009; Guimard et al.
T264 29982-29988 Sentence denotes 2007).
T265 29989-30163 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 30164-30260 Sentence denotes Polymer electrodes can be broadly classified as (1) conjugated polymer or (2) polymer composite.
T267 30261-30427 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 30428-30434 Sentence denotes 2015).
T269 30435-30556 Sentence denotes Moreover, polypyrrole has been shown to be biocompatible and exhibit affinity for methylated nucleic acids (Arshak et al.
T270 30557-30563 Sentence denotes 2009).
T271 30564-30746 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 30747-30952 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 30953-30959 Sentence denotes 2010).
T274 30960-31103 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 31104-31110 Sentence denotes 2012).
T276 31111-31340 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 31341-31356 Sentence denotes 2018; He et al.
T278 31357-31363 Sentence denotes 2012).
T279 31364-31498 Sentence denotes Polymer composite electrodes are often composed of a non-conducting polymer mixed with a conducting or semiconducting dispersed phase.
T280 31499-31676 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 31677-31693 Sentence denotes 2013; Lee et al.
T282 31694-31727 Sentence denotes 2011; Lee and Jun 2016; Li et al.
T283 31728-31752 Sentence denotes 2012; Viswanathan et al.
T284 31753-31829 Sentence denotes 2012) in combination with various polymers, including chitosan (Güner et al.
T285 31830-31917 Sentence denotes 2017), polyethylenimine (PEI) (Lee and Jun 2016), and polyallyamine (Viswanathan et al.
T286 31918-31924 Sentence denotes 2012).
T287 31925-32178 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 32179-32185 Sentence denotes 2012).
T289 32186-32342 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 32343-32349 Sentence denotes 2013).
T291 32350-32511 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 32512-32772 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 32773-32865 Sentence denotes Polymer electrode development has been, in part, driven by the need for flexible biosensors.
T294 32866-33032 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 33033-33039 Sentence denotes 2019).
T296 33040-33143 Sentence denotes Given conjugated polymers and polymer composites are compatible with 3D printing processes (Kong et al.
T297 33144-33268 Sentence denotes 2014), polymer electrodes are also emerging as attractive candidates for wearable conformal (i.e., form-fitting) biosensors.
T298 33269-33449 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 33450-33573 Sentence denotes A comprehensive discussion of biosensor LOD and dynamic range for all electrode materials is provided in Table 1, Table 2 .
T300 33574-33837 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 33838-34285 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 34286-34425 Sentence denotes Target Pathogen Working Electrode Biorecognition Element Electrochemical Method & Probe Limit of Detection Secondary Binding Step Reference
T303 34426-34561 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 34562-34726 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 34727-34879 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 34880-35051 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 35052-35219 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 35220-35426 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 35427-35604 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 35605-35851 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 35852-36078 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 36079-36243 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 36244-36513 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 36514-36697 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 36698-36916 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 36917-37169 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 37170-37406 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 37407-37620 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 37621-37799 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 37800-38022 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 38023-38278 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 38279-38471 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 38472-38644 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 38645-38789 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 38790-38995 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 38996-39188 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 39189-39436 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 39437-39622 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 39623-39864 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 39865-40063 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 40064-40246 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 40247-40459 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 40460-40672 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 40673-40893 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 40894-41003 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 41004-41208 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 41209-41390 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 41391-41580 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 41581-41749 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 41750-41977 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 41978-42159 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 42160-42320 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 42321-42484 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 42485-42644 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 42645-42839 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 42841-42884 Sentence denotes 2.1.4 Electrode form factor and patterning
T347 42885-42990 Sentence denotes As shown in Table 1, Au electrodes of various size and form factor have been used for pathogen detection.
T348 42991-43179 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 43180-43195 Sentence denotes 2018; Xu et al.
T350 43196-43202 Sentence denotes 2017).
T351 43203-43403 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 43404-43410 Sentence denotes 1994).
T353 43411-43605 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 43606-43741 Sentence denotes Interdigitated array microelectrodes (IDAMs) consist of alternating, parallel-electrode fingers organized in an interdigitated pattern.
T355 43742-43845 Sentence denotes IDAMs have been shown to exhibit rapid response and high signal-to-noise ratio (Varshney and Li, 2009).
T356 43846-43982 Sentence denotes As shown in Table 1, Au interdigitated microelectrode arrays are one of the most common electrode configurations for pathogen detection.
T357 43983-44126 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 44127-44133 Sentence denotes 2015).
T359 44134-44281 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 44282-44388 Sentence denotes Mannoor et al. also examined interdigitated carbon-based electrodes for pathogen detection (Mannoor et al.
T361 44389-44395 Sentence denotes 2012).
T362 44396-44591 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 44592-44716 Sentence denotes For example, Yang et al. used aerosol jet additive manufacturing to fabricate silver (Ag) microelectrode arrays (Yang et al.
T364 44717-44724 Sentence denotes 2016a).
T365 44726-44758 Sentence denotes 2.1.5 Electrode nanostructuring
T366 44759-44916 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 44917-44936 Sentence denotes 2004; Pumera et al.
T368 44937-44955 Sentence denotes 2007; Singh et al.
T369 44956-44972 Sentence denotes 2010; Wei et al.
T370 44973-44979 Sentence denotes 2009).
T371 44980-45082 Sentence denotes Thus, electrodes ranging from micrometers to nanometers have been investigated for pathogen detection.
T372 45083-45189 Sentence denotes While nanoscale planar electrodes are among the most commonly examined for pathogen detection (Hong et al.
T373 45190-45500 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 45501-45671 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 45672-45832 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 45833-45866 Sentence denotes 1999; Yogeswaran and Chen, 2008).
T377 45867-45974 Sentence denotes A detailed review of nanomanufacturing processes for nanowire fabrication can be found elsewhere (Hu et al.
T378 45975-45981 Sentence denotes 1999).
T379 45982-46060 Sentence denotes Nanowires can exhibit circular, hexagonal, and even triangular cross-sections.
T380 46061-46182 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 46183-46243 Sentence denotes 1999; Vaseashta and Dimova-Malinovska, 2005; Wanekaya et al.
T382 46244-46250 Sentence denotes 2006).
T383 46251-46376 Sentence denotes As shown in Table 1, metallic and ceramic microwire- and nanowire-based electrodes have been examined for pathogen detection.
T384 46377-46567 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 46568-46574 Sentence denotes 2008).
T386 46575-46762 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 46763-46769 Sentence denotes 2012).
T388 46770-46895 Sentence denotes Although polymer nanowires have been relatively more applied to the detection of non-pathogenic species (Travas-Sejdic et al.
T389 46896-46977 Sentence denotes 2014), there appears to be potential for their application to pathogen detection.
T390 46978-47221 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 47222-47228 Sentence denotes 2010).
T392 47229-47345 Sentence denotes A comprehensive summary of studies using micro- and nano-wire electrodes for pathogen detection is shown in Table 1.
T393 47346-47501 Sentence denotes For example, Chartuprayoon et al. used Au microelectrode arrays modified with polypyrrole nanoribbons to detect cucumber mosaic virus (Chartuprayoon et al.
T394 47502-47508 Sentence denotes 2013).
T395 47509-47681 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 47682-47897 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 47898-47904 Sentence denotes 2009).
T398 47905-48005 Sentence denotes Topographical modification of electrodes can also affect their mechanical and electrical properties.
T399 48006-48250 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 48251-48257 Sentence denotes 2006).
T401 48258-48460 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 48461-48543 Sentence denotes Among the wet chemistry approaches for electrode nanostructuring (Eftekhari et al.
T403 48544-48666 Sentence denotes 2008), nanostructured electrodes are often fabricated by the deposition or coupling of nanoparticles to planar electrodes.
T404 48667-48808 Sentence denotes For example, AuNPs are commonly deposited on planar electrodes to provide a nanostructured surface for biorecognition element immobilization.
T405 48809-48921 Sentence denotes In such studies, the particles are bound to the planar electrode via physical adsorption processes (Attar et al.
T406 48922-48960 Sentence denotes 2016) or chemical methods (Wang et al.
T407 48961-48967 Sentence denotes 2013).
T408 48968-49115 Sentence denotes In addition to AuNPs, CNTs have also been extensively investigated as potentially useful nanomaterials for electrode nanostructuring (see Table 1).
T409 49116-49432 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 49433-49453 Sentence denotes 2017; Mahshid et al.
T411 49454-49460 Sentence denotes 2016).
T412 49461-49705 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 49706-49712 Sentence denotes 2017).
T414 49713-49899 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 49900-50104 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 50105-50111 Sentence denotes 2019).
T417 50112-50351 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 50352-50513 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 50514-50658 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 50659-50665 Sentence denotes 2016).
T421 50666-50968 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 50969-51161 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 51162-51168 Sentence denotes 2015).
T424 51169-51389 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 51390-51517 Sentence denotes For example, Nguyen et al. utilized nanoporous alumina-coated Pt microwires for the detection of West Nile virus (Nguyen et al.
T426 51518-51524 Sentence denotes 2009).
T427 51525-51771 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 51772-52039 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 52040-52056 Sentence denotes 2015; Lam et al.
T430 52057-52077 Sentence denotes 2012; Mahshid et al.
T431 52078-52084 Sentence denotes 2017).
T432 52085-52208 Sentence denotes There also remains a need to understand device-to-device and batch-to-batch variation in electrode nanostructuring quality.
T433 52209-52419 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 52420-52535 Sentence denotes It is also unclear how such variance in nanostructuring quality affects the repeatability of biosensor performance.
T435 52537-52594 Sentence denotes 2.1.6 Integration of complementary transduction elements
T436 52595-52783 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 52784-52939 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 52940-52946 Sentence denotes 2011).
T439 52947-53173 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 53174-53317 Sentence denotes Hybrid electrochemical biosensors for pathogen detection have been developed by integrating electrodes with optical and mechanical transducers.
T441 53318-53474 Sentence denotes Electrochemical-optical waveguide light mode spectroscopy (EC-OWLS) combines evanescent-field optical sensing with electrochemical sensing (Bearinger et al.
T442 53475-53481 Sentence denotes 2003).
T443 53482-53611 Sentence denotes EC-OWLS optically monitors changes and growth at the electrode surface to provide complementary information on surface reactions.
T444 53612-53682 Sentence denotes EC-OWLS has been used to monitor the growth of bacteria (Nemeth et al.
T445 53683-53758 Sentence denotes 2007) and could potentially be applied to selective detection of pathogens.
T446 53759-54003 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 54004-54010 Sentence denotes 2008).
T448 54011-54097 Sentence denotes This approach has been used for monitoring molecular binding events (Juan-Colas et al.
T449 54098-54173 Sentence denotes 2017) and could potentially be applied to selective detection of pathogens.
T450 54174-54319 Sentence denotes In addition to their combination with optical transducers, hybrid electrochemical biosensors have also been combined with mechanical transducers.
T451 54320-54452 Sentence denotes Mechanical transducers have included shear-mode resonators, such as the quartz crystal microbalance (QCM) and cantilever biosensors.
T452 54453-54569 Sentence denotes Electrochemical-QCMs (E-QCMs) integrate mass-change and electrochemical sensing capabilities into a single platform.
T453 54570-54800 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 54801-54807 Sentence denotes 2011).
T455 54808-54924 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 54925-54931 Sentence denotes 2008).
T457 54932-55291 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 55292-55298 Sentence denotes 2018).
T459 55299-55440 Sentence denotes Thus, secondary transducers can apply force to bound species, such as nonspecifically adsorbed background species or captured target species.
T460 55441-55652 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 55653-55659 Sentence denotes 2007).
T462 55660-56086 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 56087-56093 Sentence denotes 2015).
T464 56094-56184 Sentence denotes Hybrid designs may also be useful for electrodes that exhibit a high extent of biofouling.
T465 56185-56465 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 56466-56626 Sentence denotes For example, electrochemical-colorimetric (EC-C) biosensing combines an electrochemical method and a colorimetric, fluorescent, or luminescent detection method.
T467 56627-56847 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 56848-56854 Sentence denotes 2018).
T469 56855-57060 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 57061-57067 Sentence denotes 2018).
T471 57068-57267 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 57268-57536 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 57537-57659 Sentence denotes Various techniques often rely on the use of optically-active labels for colorimetric, fluorescent, or luminescent sensing.
T474 57660-57993 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 57994-58000 Sentence denotes 2014).
T476 58001-58113 Sentence denotes The use of such additional reagents to detect the target species is discussed further in the following sections.
T477 58115-58143 Sentence denotes 2.2 Biorecognition elements
T478 58144-58269 Sentence denotes The previous section discussed the transduction elements associated with pathogen detection using electrochemical biosensors.
T479 58270-58526 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 58527-58638 Sentence denotes Biorecognition elements for electrochemical biosensors can be defined as (1) biocatalytic or (2) biocomplexing.
T481 58639-58766 Sentence denotes In the case of biocatalytic biorecognition elements, the biosensor response is based on a reaction catalyzed by macromolecules.
T482 58767-58864 Sentence denotes Enzymes, whole cells, and tissues are the most commonly used biocatalytic biorecognition element.
T483 58865-59077 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 59078-59249 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 59250-59401 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 59402-59576 Sentence denotes In addition to biomacromolecules, imprinted polymers have also been examined as biocomplexing biorecognition elements for pathogen detection using electrochemical biosensors.
T487 59578-59618 Sentence denotes 2.2.1 Antibodies and antibody fragments
T488 59619-59770 Sentence denotes Antibodies and antibody fragments are among the most commonly utilized biorecognition elements for pathogen detection using electrochemical biosensors.
T489 59771-59873 Sentence denotes Biosensors employing antibody-based biorecognition elements are commonly referred to as immunosensors.
T490 59874-60095 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 60096-60249 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 60250-60256 Sentence denotes 2016).
T493 60257-60381 Sentence denotes Antibodies can be labeled with fluorescent or enzymatic tags, which leads to the designation of the approach as label-based.
T494 60382-60537 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 60538-60662 Sentence denotes 2016), antibody labeling may also alter the binding affinity to the antigen, which could affect the biosensor's selectivity.
T496 60663-60786 Sentence denotes A detailed discussion of label-based biosensing approaches for pathogen detection has been reported elsewhere (Ahmed et al.
T497 60787-60845 Sentence denotes 2014; Alahi and Mukhopadhyay, 2017; Bozal-Palabiyik et al.
T498 60846-60866 Sentence denotes 2018; Leonard et al.
T499 60867-60873 Sentence denotes 2003).
T500 60874-61003 Sentence denotes A list of recent label-based approaches for pathogen detection using electrochemical biosensors, however, is provided in Table 2.
T501 61004-61110 Sentence denotes While both monoclonal and polyclonal antibodies enable the selective detection of pathogens (Patris et al.
T502 61111-61193 Sentence denotes 2016), they vary in terms of production method, selectivity, and binding affinity.
T503 61194-61300 Sentence denotes Monoclonal antibodies are produced by hybridoma technology (Birch and Racher, 2006; James and Bell, 1987).
T504 61301-61428 Sentence denotes Thus, monoclonal antibodies are highly selective and bind to a single epitope, making them less vulnerable to cross-reactivity.
T505 61429-61580 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 61581-61717 Sentence denotes Polyclonal antibodies are produced by separation of immunoglobulin proteins from the blood of an infected host (Birch and Racher, 2006).
T507 61718-61786 Sentence denotes Polyclonal antibodies target different epitopes on a single antigen.
T508 61787-62003 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 62004-62010 Sentence denotes 2009).
T510 62011-62126 Sentence denotes Drawbacks to antibody use include high cost and stability challenges, such as the need for low-temperature storage.
T511 62127-62258 Sentence denotes As shown in Table 1, Table 2, both monoclonal and polyclonal antibodies are used as biorecognition elements for pathogen detection.
T512 62259-62530 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 62531-62694 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 62695-62903 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 62904-62910 Sentence denotes 2017).
T516 62911-63040 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 63041-63047 Sentence denotes 2016).
T518 63048-63309 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 63310-63316 Sentence denotes 2015).
T520 63317-63455 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 63456-63462 Sentence denotes 2019).
T522 63463-63709 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 63710-63981 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 63982-64133 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 64134-64140 Sentence denotes 2009).
T526 64142-64178 Sentence denotes 2.2.2 Carbohydrate-binding proteins
T527 64179-64366 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 64367-64536 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 64537-64745 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 64746-64752 Sentence denotes 2008).
T531 64753-64866 Sentence denotes Concanavalin A (ConA) lectin has been extensively investigated for E. coli detection (see Table 1) (Jantra et al.
T532 64867-64887 Sentence denotes 2011; Saucedo et al.
T533 64888-64903 Sentence denotes 2019; Xi et al.
T534 64904-64921 Sentence denotes 2011; Yang et al.
T535 64922-64929 Sentence denotes 2016b).
T536 64930-65197 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 65198-65204 Sentence denotes 2015).
T538 65206-65229 Sentence denotes 2.2.3 Oligosaccharides
T539 65230-65334 Sentence denotes Trisaccharides are carbohydrates that can selectively bind carbohydrate-specific receptors on pathogens.
T540 65335-65461 Sentence denotes Thus, trisaccharide ligands have been used as biorecognition elements for pathogen detection using electrochemical biosensors.
T541 65462-65636 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 65637-65643 Sentence denotes 2017).
T543 65644-65871 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 65872-65878 Sentence denotes 2012).
T545 65880-65903 Sentence denotes 2.2.4 Oligonucleotides
T546 65904-65998 Sentence denotes Single-stranded DNA (ssDNA) is a useful biorecognition element for the detection of pathogens.
T547 65999-66167 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 66168-66300 Sentence denotes Aptamers are single-stranded oligonucleotides capable of binding various molecules with high affinity and selectivity (Lakhin et al.
T549 66301-66324 Sentence denotes 2013; Reverdatto et al.
T550 66325-66331 Sentence denotes 2015).
T551 66332-66528 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 66529-66535 Sentence denotes 2007).
T553 66536-66664 Sentence denotes Suitable binding sequences can be isolated from a large random oligonucleotide sequence pool and subsequently amplified for use.
T554 66665-66746 Sentence denotes Thus, aptamers can exhibit high selectivity to target species (Stoltenburg et al.
T555 66747-66753 Sentence denotes 2007).
T556 66754-66861 Sentence denotes Aptamers can also be produced at a lower cost than alternative biorecognition elements, such as antibodies.
T557 66862-67089 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 67090-67096 Sentence denotes 2013).
T559 67097-67248 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 67249-67255 Sentence denotes 2015).
T561 67256-67553 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 67554-67560 Sentence denotes 2013).
T563 67562-67575 Sentence denotes 2.2.5 Phages
T564 67576-67731 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 67732-67738 Sentence denotes 2012).
T566 67739-67884 Sentence denotes Thus, they have been examined as biorecognition elements for pathogen detection using electrochemical biosensors (Kutter and Sulakvelidze, 2004).
T567 67885-67982 Sentence denotes Bacteriophages exhibit varying morphologies and are thus classified by selectivity and structure.
T568 67983-68090 Sentence denotes A variety of bacteriophage-based electrochemical biosensors for pathogen detection can be found in Table 1.
T569 68091-68219 Sentence denotes For example, Shabani et al. used E. coli-specific T4 bacteriophages for selective impedimetric detection studies (Shabani et al.
T570 68220-68226 Sentence denotes 2008).
T571 68227-68351 Sentence denotes Mejri et al. compared the use of bacteriophages to antibodies as biorecognition elements for E. coli detection (Mejri et al.
T572 68352-68358 Sentence denotes 2010).
T573 68359-68604 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 68605-68611 Sentence denotes 2010).
T575 68612-68822 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 68823-68829 Sentence denotes 2012).
T577 68830-69025 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 69027-69074 Sentence denotes 2.2.6 Cell- and molecularly-imprinted polymers
T579 69075-69467 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 69468-69485 Sentence denotes 2018; Zhou et al.
T581 69486-69492 Sentence denotes 2019).
T582 69493-69646 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 69647-69653 Sentence denotes 2018).
T584 69654-69809 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 69810-69827 Sentence denotes 2016a; Pan et al.
T586 69828-69834 Sentence denotes 2018).
T587 69835-70057 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 70058-70064 Sentence denotes 2019).
T589 70065-70218 Sentence denotes Similarly, Golabi et al. used imprinted poly(3-aminophenylboronic acid) films for detection of Staphylococcus epidermidis (S. epidermidis) (Golabi et al.
T590 70219-70225 Sentence denotes 2017).
T591 70226-70432 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 70433-70452 Sentence denotes 2017; Jafari et al.
T593 70453-70468 Sentence denotes 2019; Qi et al.
T594 70469-70475 Sentence denotes 2013).
T595 70476-70566 Sentence denotes MIPs and CIPs are also of interest with regard to opportunities in biosensor regeneration.
T596 70567-70750 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 70751-70950 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 70951-71002 Sentence denotes 2013; Kryscio and Peppas, 2012; Yáñez-Sedeño et al.
T599 71003-71009 Sentence denotes 2017).
T600 71011-71054 Sentence denotes 2.3 Immobilization and surface passivation
T601 71055-71326 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 71327-71568 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 71569-71706 Sentence denotes Electrochemical biosensors for pathogen detection have typically used established techniques for preparation of the biorecognition layer.
T604 71707-71820 Sentence denotes A detailed discussion of immobilization and surface passivation techniques is provided in Supporting Information.
T605 71822-71894 Sentence denotes 2.4 Thermodynamics of pathogen-biorecognition element binding reactions
T606 71895-72156 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 72157-72346 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 72347-72557 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 72558-72704 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 72705-72848 Sentence denotes One important consideration when immobilizing biorecognition elements is potential effects of immobilization on binding affinity to the target.
T611 72849-72921 Sentence denotes Traditionally, K D is obtained from a kinetic or thermodynamic analysis.
T612 72922-73060 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 73061-73355 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 73356-73545 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 73547-73592 Sentence denotes 3 Measurement formats for pathogen detection
T616 73593-73915 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 73916-74032 Sentence denotes The associated protocols for sample preparation and sample handling are often referred to as the measurement format.
T618 74033-74348 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 74349-74508 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 74509-74631 Sentence denotes Similarly, the use of a label-based biosensing approach requires sample preparation steps associated with target labeling.
T621 74632-74767 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 74768-74897 Sentence denotes Applications to process monitoring, such in bioreactor or tissue-chip monitoring, may require flow-based sample handling formats.
T623 74898-75024 Sentence denotes We next discuss the measurement formats associated with pathogen detection in terms of sample preparation and sample handling.
T624 75026-75050 Sentence denotes 3.1 Sample preparation:
T625 75051-75083 Sentence denotes Filtration and pre-concentration
T626 75084-75379 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 75380-75386 Sentence denotes 2008).
T628 75387-75454 Sentence denotes We next discuss sample filtration and pre-concentration techniques.
T629 75456-75480 Sentence denotes 3.1.1 Sample filtration
T630 75481-75605 Sentence denotes Generally, sample filtration relies on the principle of size discrepancy between the target pathogen and background species.
T631 75606-75727 Sentence denotes Membranes, fibers, and channels have been used in size-selective sample filtration processes for biosensing applications.
T632 75728-75891 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 75892-76078 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 76079-76085 Sentence denotes 2008).
T635 76086-76328 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 76329-76335 Sentence denotes 2010).
T637 76336-76483 Sentence denotes This physical property of cell-based pathogens is leveraged in biofiltration processes, for example, using electropositive filters (Altintas et al.
T638 76484-76490 Sentence denotes 2015).
T639 76491-76694 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 76695-76701 Sentence denotes 2013).
T641 76702-76900 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 76902-76931 Sentence denotes 3.1.2 Centrifugal separation
T643 76932-77059 Sentence denotes Centrifugation can be used as a density gradient-based separation principle for concentrating target pathogens within a sample.
T644 77060-77211 Sentence denotes In cases where the target species exhibits similar density to background species, the approach is often implemented with antibody-functionalized beads.
T645 77212-77333 Sentence denotes This technique is commonly employed in applications requiring pathogen detection in complex matrices (e.g., body fluids).
T646 77334-77452 Sentence denotes Centrifugation-based separation techniques can also potentially be applied to microfluidic-based biosensing platforms.
T647 77453-77591 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 77592-77712 Sentence denotes 2009), suggesting that this approach could be extended to electrochemical biosensor-based assays for pathogen detection.
T649 77714-77737 Sentence denotes 3.1.3 Broth enrichment
T650 77738-77959 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 77960-78019 Sentence denotes The technique is commonly used in food safety applications.
T652 78020-78229 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 78230-78236 Sentence denotes 2009).
T654 78237-78424 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 78425-78600 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 78601-78759 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 78760-78894 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 78896-78922 Sentence denotes 3.1.4 Magnetic separation
T659 78923-79085 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 79086-79251 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 79252-79361 Sentence denotes The bead-target complexes are subsequently separated from the solution by externally-applied magnetic fields.
T662 79362-79596 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 79597-79603 Sentence denotes 2017).
T664 79604-79763 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 79764-79935 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 79936-80045 Sentence denotes Such assays have been used to detect a variety of pathogens, including bacteria, such as E. coli (Chan et al.
T667 80046-80177 Sentence denotes 2013 ) and Bacillus anthracis (B. anthracis) (Pal and Alocilja, 2009), and viruses, such as bovine viral diarrhea virus (Luo et al.
T668 80178-80224 Sentence denotes 2010) and human influenza A virus (Shen et al.
T669 80225-80231 Sentence denotes 2012).
T670 80232-80314 Sentence denotes In addition to serving as a separation agent, magnetic beads also serve as labels.
T671 80316-80344 Sentence denotes 3.2 Sample handling formats
T672 80345-80422 Sentence denotes The sample handling format is highly influenced by the biosensor application.
T673 80423-80578 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 80579-80737 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 80738-80827 Sentence denotes Sample handling formats can be generally classified as droplet-, flow-, or surface-based.
T676 80828-80935 Sentence denotes Droplet formats involve sampling from a larger volume of potentially pathogen-containing material or fluid.
T677 80936-81069 Sentence denotes The sample droplet is subsequently analyzed by deposition on a functionalized transducer or transferred to a fluidic delivery system.
T678 81070-81253 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 81254-81260 Sentence denotes 2012).
T680 81261-81377 Sentence denotes Droplet formats are simplistic sample handling formats and have the advantage of being performed by unskilled users.
T681 81378-81515 Sentence denotes While dropletformats have been extensively used with colorimetric biosensors, they have also been adapted for electrochemical biosensors.
T682 81516-81609 Sentence denotes For example, commercially-available blood glucose meters use a droplet format (Vashist et al.
T683 81610-81616 Sentence denotes 2011).
T684 81617-81769 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 81770-81958 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 81959-81965 Sentence denotes 2007).
T687 81966-82272 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 82273-82571 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 82572-82832 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 82833-83070 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 83071-83212 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 83213-83219 Sentence denotes 1996).
T693 83220-83339 Sentence denotes Thus, the sampling approach should be considered when examining droplet formats for food and water safety applications.
T694 83340-83580 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 83581-83665 Sentence denotes Flow formats involve the detection of target species in the presence of flow fields.
T696 83666-83793 Sentence denotes Flow formats include continuously-stirred systems (e.g., continuously-stirred tank bioreactors), flow cells, and microfluidics.
T697 83794-84046 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 84047-84124 Sentence denotes Flow formatsare also typically compatible with large sample volumes (liters).
T699 84125-84241 Sentence denotes Flow cells are typically fabricated via milling and extrusion processes using materials such as Teflon or Plexiglas.
T700 84242-84363 Sentence denotes They have the advantage of accommodating a variety of biosensor form factors, such as rigid three-dimensional biosensors.
T701 84364-84453 Sentence denotes In addition to flow cells, flow formats are commonly achieved using microfluidic devices.
T702 84454-84633 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 84634-84890 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 84891-85084 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 85085-85091 Sentence denotes 2014).
T706 85092-85272 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 85273-85279 Sentence denotes 2011).
T708 85280-85411 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 85412-85418 Sentence denotes 2015).
T710 85419-85549 Sentence denotes Detection in the presence of flow fields requires high stability of immobilized biorecognition elements (Bard and Faulkner, 2000).
T711 85550-85749 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 85750-85756 Sentence denotes 2008).
T713 85757-85930 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 85931-85947 Sentence denotes 2013; Tan et al.
T715 85948-85954 Sentence denotes 2011).
T716 85955-86159 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 86160-86166 Sentence denotes 2008).
T718 86167-86452 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 86453-86632 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 86633-86971 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 86972-87097 Sentence denotes Surface-based measurement formats typically require biosensors with flexible or conforming (i.e., form-fitting) form factors.
T722 87098-87245 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 87246-87252 Sentence denotes 2012).
T724 87253-87360 Sentence denotes Further discussion of surface-based pathogen detection applications are provided in the following sections.
T725 87361-87444 Sentence denotes The sample handling format often provides insight into the biosensor's reusability.
T726 87445-87563 Sentence denotes Biosensors within the aforementioned measurement formats can be broadly classified as single- or multi-use biosensors.
T727 87564-87746 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 87747-87753 Sentence denotes 2001).
T729 87754-87999 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 88000-88286 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 88288-88372 Sentence denotes 3.3 Electrochemical methods for pathogen detection using electrochemical biosensors
T732 88373-88509 Sentence denotes Various electrochemical methods can be performed using functionalized electrodes to enable pathogen detection (Bard and Faulkner, 2000).
T733 88510-88663 Sentence denotes These methods differ in electrode configuration, applied signals, measured signals, mass transport regimes, binding information provided (Thévenot et al.
T734 88664-88712 Sentence denotes 2001), and target size-selectivity (Amiri et al.
T735 88713-88719 Sentence denotes 2018).
T736 88720-88937 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 88938-88944 Sentence denotes 2001).
T738 88945-88997 Sentence denotes The applied signals may be constant or time-varying.
T739 88998-89152 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 89153-89275 Sentence denotes A detailed discussion of the aforementioned electrochemical methods has been provided elsewhere (Bard and Faulkner, 2000).
T741 89276-89389 Sentence denotes Here, we briefly review the most recent methods employed for pathogen detection using electrochemical biosensors.
T742 89391-89411 Sentence denotes 3.3.1 Potentiometry
T743 89412-89599 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 89600-89647 Sentence denotes The applied current is typically low amplitude.
T745 89648-89809 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 89810-89956 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 89957-89963 Sentence denotes 2017).
T748 89964-90131 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 90132-90138 Sentence denotes 2014).
T750 90139-90230 Sentence denotes Boehm et al. detected E. coli via potentiometry utilizing a Pt wire electrode (Boehm et al.
T751 90231-90237 Sentence denotes 2007).
T752 90238-90329 Sentence denotes Further studies utilizing potentiometric sensing approaches are listed in Table 1, Table 2.
T753 90331-90349 Sentence denotes 3.3.2 Voltammetry
T754 90350-90564 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 90565-90712 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 90713-90866 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 90867-90973 Sentence denotes The applied electrical potential can also be held constant or varied with time as the current is measured.
T758 90974-91187 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 91188-91204 Sentence denotes 2011; Liu et al.
T760 91205-91211 Sentence denotes 2013).
T761 91212-91363 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 91364-91474 Sentence denotes This is achieved by immobilizing biorecognition elements on the metal or polymer gate electrode of the device.
T763 91475-91664 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 91665-91671 Sentence denotes 2012).
T765 91672-91850 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 91851-91857 Sentence denotes 2016).
T767 91858-92114 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 92115-92122 Sentence denotes 2017b).
T769 92123-92237 Sentence denotes Lee and Jun utilized wire-based electrodes for amperometric detection of E. coli and S. aureus (Lee and Jun 2016).
T770 92238-92353 Sentence denotes A detailed list of studies that utilize amperometric methods for pathogen detection is provided in Table 1, Table 2
T771 92355-92399 Sentence denotes 3.3.2.1 Linear sweep and cyclic voltammetry
T772 92400-92626 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 92627-92830 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 92831-92909 Sentence denotes CV is one of the most widely used voltammetric methods for pathogen detection.
T775 92910-93042 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 93043-93049 Sentence denotes 2015).
T777 93050-93242 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 93243-93249 Sentence denotes 2017).
T779 93250-93344 Sentence denotes A detailed overview of pathogen detection studies based on CV is provided in Table 1, Table 2.
T780 93345-93552 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 93553-93680 Sentence denotes 2017). b) Differential pulse voltammetry (DPV) data using Fe(CN)63-/4- for varying concentrations of S. aureus (Bhardwaj et al.
T782 93681-93940 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 93941-94023 Sentence denotes 2016). d) Conductometry data for varying concentrations of B. subtilis (Yoo et al.
T784 94024-94030 Sentence denotes 2017).
T785 94032-94058 Sentence denotes 3.3.2.2 Pulse voltammetry
T786 94059-94157 Sentence denotes Pulse voltammetry is a type of voltammetry in which the electrical potential is applied in pulses.
T787 94158-94325 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 94326-94540 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 94541-94696 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 94697-94765 Sentence denotes The forward pulse of the waveform coincides with the staircase step.
T791 94766-94929 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 94930-95086 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 95087-95227 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 95228-95234 Sentence denotes 2015).
T795 95235-95347 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 95348-95354 Sentence denotes 2016).
T797 95355-95489 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 95490-95496 Sentence denotes 2012).
T799 95497-95609 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 95610-95616 Sentence denotes 2017).
T801 95617-95728 Sentence denotes Additional studies that utilize pulse voltammetry methods forpathogen detection are listed in Table 1, Table 2.
T802 95730-95760 Sentence denotes 3.3.2.3 Stripping voltammetry
T803 95761-95907 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 95908-96021 Sentence denotes Subsequently, the pre-concentrated target is stripped from the surface by application of an electrical potential.
T805 96022-96147 Sentence denotes In anodic stripping voltammetry (ASV), a negative potential is used to pre-concentrate metal ions onto the electrode surface.
T806 96148-96225 Sentence denotes These ions are then stripped from the surface by applied positive potentials.
T807 96226-96495 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 96496-96502 Sentence denotes 2015).
T809 96503-96639 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 96640-96646 Sentence denotes 2014).
T811 96647-96709 Sentence denotes In that study, the biosensor was first incubated with E. coli.
T812 96710-96884 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 96885-97036 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 97037-97270 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 97271-97277 Sentence denotes 2012).
T816 97278-97531 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 97532-97655 Sentence denotes Additional studies using stripping voltammetry for electrochemical detection of pathogens can be found in Table 1, Table 2.
T818 97657-97702 Sentence denotes 3.3.3 Electrochemical impedance spectroscopy
T819 97703-97903 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 97904-98221 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 98222-98367 Sentence denotes This provides several advantages, including measurement over a wide range of times and frequencies and high precision in time-averaged responses.
T822 98368-98484 Sentence denotes We next discuss impedance-based electrochemical methods for detection of pathogens using electrochemical biosensors.
T823 98485-98616 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 98617-98852 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 98853-98975 Sentence denotes EIS is often performed using an applied low-amplitude sinusoidal electrical potential and a three-electrode configuration.
T826 98976-99178 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 99179-99434 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 99435-99683 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 99684-99781 Sentence denotes The Randles model is a commonly used equivalent circuit for interpretation of biosensor EIS data.
T830 99782-99988 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 99989-100071 Sentence denotes Variations of this model have been formulated for a variety of biosensing studies.
T832 100072-100314 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 100315-100321 Sentence denotes 2016).
T834 100322-100583 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 100584-100590 Sentence denotes 2016).
T836 100591-100840 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 100841-101037 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 101038-101138 Sentence denotes Fixed-frequency approaches have the advantage of increasing the sampling frequency of the biosensor.
T839 101139-101411 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 101412-101530 Sentence denotes As shown in Table 1, Table 2, EIS is one of the most commonly used methods for electrochemical detection of pathogens.
T841 101531-101711 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 101712-101718 Sentence denotes 2018).
T843 101719-101875 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 101876-101882 Sentence denotes 2016).
T845 101883-102026 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 102027-102033 Sentence denotes 2015).
T847 102034-102135 Sentence denotes Redox reactions at the electrode-electrolyte interface are typically established using a redox probe.
T848 102136-102393 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 102394-102517 Sentence denotes While useful electrochemical probes, redox reactions may also affect the electrode and immobilized biorecognition elements.
T850 102518-102717 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 102718-102724 Sentence denotes 2016).
T852 102725-102873 Sentence denotes This observation warrants further investigation, particularly in the context of establishing the effects on biosensor repeatability and reusability.
T853 102874-102959 Sentence denotes The use of alternative redox probes or electrode materials may mitigate such effects.
T854 102960-103064 Sentence denotes For example, ferrocene and ferrocenemethanol have also been used as redox probes for pathogen detection.
T855 103065-103116 Sentence denotes Ruthenium(III)/ruthenium(II) (Schrattenecker et al.
T856 103117-103165 Sentence denotes 2019) and immobilized quinone pairs (Piro et al.
T857 103166-103213 Sentence denotes 2013) are also potentially useful alternatives.
T858 103214-103404 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 103405-103668 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 103669-103798 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 103799-103895 Sentence denotes Importantly, both characteristics could be affected by molecular binding events on an electrode.
T862 103896-104091 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 104092-104098 Sentence denotes 2001).
T864 104099-104255 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 104256-104357 Sentence denotes Idil et al. used the capacitive response of a MIP electrode for the detection of E. coli (Idil et al.
T866 104358-104364 Sentence denotes 2017).
T867 104365-104484 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 104485-104491 Sentence denotes 2011).
T869 104492-104658 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 104659-104665 Sentence denotes 2019).
T871 104666-104812 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 104814-104834 Sentence denotes 3.3.4 Conductometry
T873 104835-105025 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 105026-105137 Sentence denotes The principle relies on conductivity change in the sample via the production or consumption of charged species.
T875 105138-105341 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 105342-105466 Sentence denotes Given the method can be performed using a two-electrode configuration, conductometric biosensors can be easily miniaturized.
T877 105467-105619 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 105620-105754 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 105755-105761 Sentence denotes 2017).
T880 105762-105905 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 105906-105912 Sentence denotes 2012).
T882 105913-106077 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 106078-106084 Sentence denotes 2012).
T884 106085-106216 Sentence denotes Additional studies that have examined the use of conductometric biosensors for pathogen detection can be found in Table 1, Table 2.
T885 106218-106251 Sentence denotes 3.4 Secondary binding approaches
T886 106252-106360 Sentence denotes Electrochemical biosensors would ideally produce sensitive and selective results using label-free protocols.
T887 106361-106561 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 106562-106685 Sentence denotes Secondary binding steps can facilitate target labeling, biosensor signal amplification, and verification of target binding.
T889 106686-106858 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 106859-106986 Sentence denotes Secondary binding steps also provide opportunities for acquiring additional bioanalytical information about the target species.
T891 106987-107149 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 107150-107306 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 107307-107387 Sentence denotes Labels often include a biorecognition element-enzyme or -nanoparticle conjugate.
T894 107388-107606 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 107607-107768 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 107769-107871 Sentence denotes Enzymes are among the most commonly used secondary binding species for label-based pathogen detection.
T897 107872-108013 Sentence denotes As shown in Table 2, electrochemical biosensors for pathogen detection that employ enzymes are commonly performed as a sandwich assay format.
T898 108014-108166 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 108167-108173 Sentence denotes 2016).
T900 108174-108355 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 108356-108362 Sentence denotes 2015).
T902 108363-108612 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 108613-108619 Sentence denotes 2016).
T904 108620-108901 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 108902-108909 Sentence denotes 2016b).
T906 108910-109487 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 109488-109601 Sentence denotes 2016). b) Signal amplification via non-selective binding of AuNPs to bound bacterial target (E. coli) (Wan et al.
T908 109602-109608 Sentence denotes 2016).
T909 109609-109710 Sentence denotes In addition to enzymes, secondary binding of nanoparticles has also been used for pathogen detection.
T910 109711-109884 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 109885-109891 Sentence denotes 2016).
T912 109892-109984 Sentence denotes A detailed overview of studies that employ enzymes and nanoparticles is provided in Table 2.
T913 109985-110263 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 110265-110302 Sentence denotes 4 Applications to pathogen detection
T915 110303-110499 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 110500-110699 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 110701-110740 Sentence denotes 4.1 Food and water safety applications
T918 110741-110833 Sentence denotes Detection of foodborne and waterborne pathogens is an essential aspect of public healthcare.
T919 110834-111001 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 111002-111101 Sentence denotes Waterborne pathogens are responsible for about 2.2 million deaths annually worldwide (Pandey et al.
T921 111102-111192 Sentence denotes 2014), and contaminated food-related deaths amount to around 420,000 annually (WHO, 2015).
T922 111193-111418 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 111419-111715 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 111716-111931 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 111932-111938 Sentence denotes 2017).
T926 111939-112032 Sentence denotes The selective detection of pathogens in food and water remains a global healthcare challenge.
T927 112033-112160 Sentence denotes Several comprehensive reviews have been written on biosensors for food and water safety (Baeumner, 2003; Bozal-Palabiyik et al.
T928 112161-112181 Sentence denotes 2018; Leonard et al.
T929 112182-112205 Sentence denotes 2003; Ye et al., 2019).
T930 112206-112275 Sentence denotes Here, we describe the most common foodborne and waterborne pathogens.
T931 112276-112521 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 112522-112542 Sentence denotes 2013; Cabral, 2010).
T933 112543-112701 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 112702-112859 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 112860-113083 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 113084-113311 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 113312-113513 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 113514-113666 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 113667-113706 Sentence denotes 2013; Mehrotra, 2016; Ye et al., 2019).
T940 113707-113853 Sentence denotes As a result, biosensors for food and water safety applications should facilitate pathogen detection at various stages of the processing operation.
T941 113854-114096 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 114098-114162 Sentence denotes 4.2 Environmental monitoring and infection control applications
T943 114163-114297 Sentence denotes In addition to foodborne and waterborne pathogens, the detection of environmental pathogens is also an important aspect of healthcare.
T944 114298-114436 Sentence denotes For example, diseases associated with environmental pathogens are one of the leading causes of death in low-income economies (WHO, 2018a).
T945 114437-114529 Sentence denotes For example, malaria was reported to cause an estimated 435,000 deaths in 2017 (WHO, 2018b).
T946 114530-114753 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 114754-114838 Sentence denotes Thus, environmental pathogens are often targets in medical diagnostics applications.
T948 114839-115079 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 115080-115158 Sentence denotes Thus, the distinction is based on the matrix in which the pathogen is present.
T950 115159-115388 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 115389-115697 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 115698-115945 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 115946-115952 Sentence denotes 2009).
T954 115953-116077 Sentence denotes Several comprehensive reviews have been provided on the detection of environmental pathogens (Baeumner, 2003; Justino et al.
T955 116078-116084 Sentence denotes 2017).
T956 116085-116190 Sentence denotes Here, we describe the most common environmental pathogens found both in and outside of clinical settings.
T957 116191-116411 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 116412-116513 Sentence denotes In addition to bacteria and protozoa, fungi, nematodes, and insects are also environmental pathogens.
T959 116514-116966 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 116967-117119 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 117120-117268 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 117269-117464 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 117465-117586 Sentence denotes Thus, traditional bioanalytical techniques, such as PCR, are often utilized for the detection of environmental pathogens.
T964 117587-117780 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 117781-117871 Sentence denotes However, they also require measurement formats for the detection of aerosolized pathogens.
T966 117872-118124 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 118125-118387 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 118388-118394 Sentence denotes 2008).
T969 118395-118555 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 118556-118574 Sentence denotes 2006; Weber et al.
T971 118575-118581 Sentence denotes 2010).
T972 118582-118816 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 118817-118823 Sentence denotes 2015).
T974 118824-118911 Sentence denotes Hospital-acquired infections are prevalent causes of morbidity in patients (Orsi et al.
T975 118912-118918 Sentence denotes 2002).
T976 118919-119105 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 119106-119238 Sentence denotes In addition to clinical pathogens, it is also of interest to detect pathogens in non-clinical settings (Faucher and Charette, 2015).
T978 119239-119429 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 119431-119467 Sentence denotes 4.3 Medical diagnostic applications
T980 119468-119654 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 119655-119885 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 119886-120126 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 120127-120317 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 120318-120339 Sentence denotes 2000; Beekmann et al.
T985 120340-120360 Sentence denotes 2003; Dierkes et al.
T986 120361-120379 Sentence denotes 2009; Rappo et al.
T987 120380-120386 Sentence denotes 2016).
T988 120387-120610 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 120611-120617 Sentence denotes 2006).
T990 120618-120757 Sentence denotes Additionally, the need for rapid antibody screening has been identified as an important aspect of mitigating the ongoing COVID-19 pandemic.
T991 120758-120994 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 120995-121189 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 121190-121345 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 121346-121641 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 121642-121831 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 121832-122019 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 122020-122263 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 122264-122411 Sentence denotes The diagnostically-relevant concentration of pathogens in each type of matrix must be considered when designing a biosensor for pathogen detection.
T999 122412-122528 Sentence denotes For example, the detection of bacteria in blood versus urine exhibit different diagnostic thresholds (Kelley, 2017).
T1000 122529-122593 Sentence denotes Such knowledge can inform the need for sample preparation steps.
T1001 122595-122646 Sentence denotes 4.4 Biological defense and bio-threat applications
T1002 122647-122783 Sentence denotes The potential for the weaponization of pathogens drives the need for rapid and sensitive biosensors for biological defense applications.
T1003 122784-123001 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 123002-123267 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 123268-123496 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 123497-123516 Sentence denotes 2004; Mirski et al.
T1007 123517-123547 Sentence denotes 2014; Shah and Wilkins, 2003).
T1008 123548-123688 Sentence denotes The reader is directed to various comprehensive reviews on biosensor-based assays for the detection of biowarfare agents (Christopher et al.
T1009 123689-123719 Sentence denotes 1997; Shah and Wilkins, 2003).
T1010 123720-123781 Sentence denotes Common targets include the aforementioned airborne pathogens.
T1011 123782-123989 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 123990-124164 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 124165-124195 Sentence denotes 1997; Shah and Wilkins, 2003).
T1014 124196-124447 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 124448-124610 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 124611-124834 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 124835-125111 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 125113-125212 Sentence denotes 5 Present challenges and future directions for pathogen detection using electrochemical biosensors
T1019 125213-125417 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 125419-125493 Sentence denotes 5.1 Emerging electrode materials, fabrication processes, and form factors
T1021 125494-125607 Sentence denotes The ability to create robust, low-cost biosensors for pathogen detection is a significant challenge in the field.
T1022 125608-125695 Sentence denotes One of the primary methods of reducing cost is decreasing the material cost per device.
T1023 125696-125800 Sentence denotes Carbon-based electrodes (e.g., graphite, graphene, CNTs), such as those shown in Fig. 7 a (Afonso et al.
T1024 125801-125826 Sentence denotes 2016) and 7b (Wang et al.
T1025 125827-125943 Sentence denotes 2013), are now being examined as potential alternatives to relatively more expensive metallic or ceramic electrodes.
T1026 125944-126066 Sentence denotes Many of these carbon-based materials are also nanoscale in structure, and thus offer advantages regarding nanostructuring.
T1027 126067-126202 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 126203-126372 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 126373-126379 Sentence denotes 2016).
T1030 126380-126543 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 126544-126600 Sentence denotes 2016). b) Free-standing graphene electrodes (Wang et al.
T1032 126601-126703 Sentence denotes 2013). c) Paper-based substrates for pathogen detection using electrochemical methods (Bhardwaj et al.
T1033 126704-126784 Sentence denotes 2017). d) Wearable wireless bacterial biosensor for tooth enamel (Mannoor et al.
T1034 126785-126886 Sentence denotes 2012). e) Smartphone-enabled signal processing for field-based environmental monitoring (Jiang et al.
T1035 126887-126893 Sentence denotes 2014).
T1036 126894-127027 Sentence denotes In addition to reducing the material cost per device, efforts to reduce the manufacturing cost of biosensors have also been examined.
T1037 127028-127108 Sentence denotes 3D printing processes have emerged as popular methods for biosensor fabrication.
T1038 127109-127184 Sentence denotes For example, 3D printing is compatible with flexible and curved substrates.
T1039 127185-127368 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 127369-127499 Sentence denotes In particular, 3D printing has emerged as a useful fabrication platform for microfluidic-based analytical platforms (Waheed et al.
T1041 127500-127506 Sentence denotes 2016).
T1042 127507-127620 Sentence denotes For example, to date, 3D printing has enabled the fabrication of electrode-integrated microfluidics (Erkal et al.
T1043 127621-127690 Sentence denotes 2014), 3D microfluidics, organ-conforming microfluidics (Singh et al.
T1044 127691-127755 Sentence denotes 2017a), and transducer-integrated microfluidics (Cesewski et al.
T1045 127756-127762 Sentence denotes 2018).
T1046 127763-127926 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 127927-128095 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 128096-128214 Sentence denotes Wearable biomedical devices have emerged as promising tools for point-of-care (POC) diagnostics and health monitoring.
T1049 128215-128316 Sentence denotes The application constraints of wearable devices require them to be lightweight and simple to operate.
T1050 128317-128527 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 128528-128699 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 128700-128803 Sentence denotes This is a rapidly emerging area linked to smartphone technology for biosensor actuation and monitoring.
T1053 128804-128989 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 128990-128996 Sentence denotes 2016).
T1055 128997-129198 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 129199-129354 Sentence denotes Challenges include biocompatibility (e.g., reduction of skin irritation), device power consumption, and biosensor-tissue mechanical and geometric matching.
T1057 129355-129562 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 129563-129570 Sentence denotes 2017a).
T1059 129572-129598 Sentence denotes 5.2 Detection of protozoa
T1060 129599-129767 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 129768-129848 Sentence denotes For example, pathogens can range greater than three orders of magnitude in size.
T1062 129849-129928 Sentence denotes For example, the diameter of norovirus was estimated at 27 nm (Robilotti et al.
T1063 129929-130000 Sentence denotes 2015), while the diameter of G. lamblia oocysts is ~14 μm (Adam, 2001).
T1064 130001-130113 Sentence denotes Electrochemical biosensors for the detection of protozoa-based pathogens is an area requiring further attention.
T1065 130114-130317 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 130318-130438 Sentence denotes C. parvum is at present the most commonly detected protozoa using electrochemical biosensors (see Table 1) (Iqbal et al.
T1067 130439-130457 Sentence denotes 2015) (Luka et al.
T1068 130458-130464 Sentence denotes 2019).
T1069 130466-130499 Sentence denotes 5.3 Detection of plant pathogens
T1070 130500-130790 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 130791-130970 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 130971-131051 Sentence denotes Common plant pathogens include viruses, viroids, bacteria, fungi, and oomycetes.
T1073 131052-131221 Sentence denotes Chartuprayoon et al. recently established a polypyrrole nanoribbon-based chemiresistive immunosensor for detection of viral plant pathogens (Chartuprayoon et al., 2013).
T1074 131223-131249 Sentence denotes 5.4 Multiplexed detection
T1075 131250-131391 Sentence denotes Multiplexed detection of pathogens has emerged as a technique for phenotype identification and identification of multiple pathogenic threats.
T1076 131392-131547 Sentence denotes Multiplexing can be achieved via various approaches, but typically involves the use of multiple transducers that exhibit different biorecognition elements.
T1077 131548-131716 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 131717-131723 Sentence denotes 2017).
T1079 131724-131856 Sentence denotes Spatially-distributed biorecognition elements on a single electrode or multiple electrodes can also provide multiplexing capability.
T1080 131857-132029 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 132030-132036 Sentence denotes 2016).
T1082 132038-132088 Sentence denotes 5.5 Saturation-free continuous monitoring formats
T1083 132089-132212 Sentence denotes The inability to regenerate biosensors is a major hindrance to biosensor-based process monitoring and control applications.
T1084 132213-132414 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 132415-132610 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 132611-132824 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 132825-132843 Sentence denotes 2015; Huang et al.
T1088 132844-132871 Sentence denotes 2010; Zelada-Guillen et al.
T1089 132872-132878 Sentence denotes 2010).
T1090 132879-133102 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 133103-133109 Sentence denotes 2012).
T1092 133110-133390 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 133391-133636 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 133638-133683 Sentence denotes 5.6 Low-cost, single-use portable biosensors
T1095 133684-133805 Sentence denotes The creation of environmentally-friendly disposable substrates is a present challenge for low-cost single-use biosensors.
T1096 133806-133925 Sentence denotes Paper-based substrates have recently emerged as attractive alternatives to costlier ceramic substrates (Martinez et al.
T1097 133926-133932 Sentence denotes 2009).
T1098 133933-134051 Sentence denotes Paper-based substrates can also eliminate the need for supporting fluid handling components through capillary effects.
T1099 134052-134177 Sentence denotes For example, paper substrates can be patterned with hydrophobic and hydrophilic regions to direct fluid flow (Carrilho et al.
T1100 134178-134184 Sentence denotes 2009).
T1101 134185-134307 Sentence denotes Paper-based devices are also relatively environmentally friendly in terms of material sourcing, disposal, and degradation.
T1102 134308-134540 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 134541-134678 Sentence denotes For example, the long-term environmental and health impacts of nanomaterials remain active areas of research (Colvin, 2003; Klaine et al.
T1104 134679-134696 Sentence denotes 2008; Lead et al.
T1105 134697-134703 Sentence denotes 2018).
T1106 134704-134898 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 134899-134920 Sentence denotes 2016; Meredith et al.
T1108 134921-134927 Sentence denotes 2016).
T1109 134928-134989 Sentence denotes A highlight of paper-based substrates is provided in Fig. 7c.
T1110 134990-135143 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 135144-135380 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 135381-135517 Sentence denotes However, device miniaturization also presents measurement challenges, such as increasing the biosensor signal-to-noise ratio (Wei et al.
T1113 135518-135524 Sentence denotes 2009).
T1114 135525-135696 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 135697-135916 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 135917-135935 Sentence denotes 2013; Luppa et al.
T1117 135936-135967 Sentence denotes 2016; Narayan, 2016; Wan et al.
T1118 135968-135974 Sentence denotes 2013).
T1119 135975-136308 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 136309-136468 Sentence denotes Sample preparation-free protocols can improve measurement confidence, repeatability, and reduce TTR, which are important aspects of healthcare decision-making.
T1121 136469-136635 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 136636-136652 Sentence denotes 2017; Sin et al.
T1123 136653-136659 Sentence denotes 2014).
T1124 136660-136851 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 136852-137122 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 137124-137161 Sentence denotes 5.7 Wireless transduction approaches
T1127 137162-137427 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 137428-137598 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 137599-137785 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 137786-137806 Sentence denotes 2012) (see Fig. 7d).
T1131 137807-137888 Sentence denotes Wireless transduction approaches remains an emerging area for pathogen detection.
T1132 137889-138011 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 138012-138018 Sentence denotes 2014).
T1134 138020-138034 Sentence denotes 6 Conclusions
T1135 138035-138124 Sentence denotes Here, we provided a critical review of electrochemical biosensors for pathogen detection.
T1136 138125-138238 Sentence denotes Biosensor transduction elements and biorecognition elements for electrochemical pathogen detection were reviewed.
T1137 138239-138428 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 138429-138612 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 138613-138835 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 138836-138979 Sentence denotes Present challenges and future directions in the field were discussed, including a need for further low-cost, reusable, and wearable biosensors.
T1141 138980-139135 Sentence denotes Electrochemical biosensors offer great potential as resources for improving global healthcare, such as preventing the spread of highly contagious diseases.
T1142 139137-139170 Sentence denotes Declaration of competing interest
T1143 139171-139341 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.