Id |
Subject |
Object |
Predicate |
Lexical cue |
T914 |
0-37 |
Sentence |
denotes |
4 Applications to pathogen detection |
T915 |
38-234 |
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 |
235-434 |
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 |
436-475 |
Sentence |
denotes |
4.1 Food and water safety applications |
T918 |
476-568 |
Sentence |
denotes |
Detection of foodborne and waterborne pathogens is an essential aspect of public healthcare. |
T919 |
569-736 |
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 |
737-836 |
Sentence |
denotes |
Waterborne pathogens are responsible for about 2.2 million deaths annually worldwide (Pandey et al. |
T921 |
837-927 |
Sentence |
denotes |
2014), and contaminated food-related deaths amount to around 420,000 annually (WHO, 2015). |
T922 |
928-1153 |
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 |
1154-1450 |
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 |
1451-1666 |
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 |
1667-1673 |
Sentence |
denotes |
2017). |
T926 |
1674-1767 |
Sentence |
denotes |
The selective detection of pathogens in food and water remains a global healthcare challenge. |
T927 |
1768-1895 |
Sentence |
denotes |
Several comprehensive reviews have been written on biosensors for food and water safety (Baeumner, 2003; Bozal-Palabiyik et al. |
T928 |
1896-1916 |
Sentence |
denotes |
2018; Leonard et al. |
T929 |
1917-1940 |
Sentence |
denotes |
2003; Ye et al., 2019). |
T930 |
1941-2010 |
Sentence |
denotes |
Here, we describe the most common foodborne and waterborne pathogens. |
T931 |
2011-2256 |
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 |
2257-2277 |
Sentence |
denotes |
2013; Cabral, 2010). |
T933 |
2278-2436 |
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 |
2437-2594 |
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 |
2595-2818 |
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 |
2819-3046 |
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 |
3047-3248 |
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 |
3249-3401 |
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 |
3402-3441 |
Sentence |
denotes |
2013; Mehrotra, 2016; Ye et al., 2019). |
T940 |
3442-3588 |
Sentence |
denotes |
As a result, biosensors for food and water safety applications should facilitate pathogen detection at various stages of the processing operation. |
T941 |
3589-3831 |
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 |
3833-3897 |
Sentence |
denotes |
4.2 Environmental monitoring and infection control applications |
T943 |
3898-4032 |
Sentence |
denotes |
In addition to foodborne and waterborne pathogens, the detection of environmental pathogens is also an important aspect of healthcare. |
T944 |
4033-4171 |
Sentence |
denotes |
For example, diseases associated with environmental pathogens are one of the leading causes of death in low-income economies (WHO, 2018a). |
T945 |
4172-4264 |
Sentence |
denotes |
For example, malaria was reported to cause an estimated 435,000 deaths in 2017 (WHO, 2018b). |
T946 |
4265-4488 |
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 |
4489-4573 |
Sentence |
denotes |
Thus, environmental pathogens are often targets in medical diagnostics applications. |
T948 |
4574-4814 |
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 |
4815-4893 |
Sentence |
denotes |
Thus, the distinction is based on the matrix in which the pathogen is present. |
T950 |
4894-5123 |
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 |
5124-5432 |
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 |
5433-5680 |
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 |
5681-5687 |
Sentence |
denotes |
2009). |
T954 |
5688-5812 |
Sentence |
denotes |
Several comprehensive reviews have been provided on the detection of environmental pathogens (Baeumner, 2003; Justino et al. |
T955 |
5813-5819 |
Sentence |
denotes |
2017). |
T956 |
5820-5925 |
Sentence |
denotes |
Here, we describe the most common environmental pathogens found both in and outside of clinical settings. |
T957 |
5926-6146 |
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 |
6147-6248 |
Sentence |
denotes |
In addition to bacteria and protozoa, fungi, nematodes, and insects are also environmental pathogens. |
T959 |
6249-6701 |
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 |
6702-6854 |
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 |
6855-7003 |
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 |
7004-7199 |
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 |
7200-7321 |
Sentence |
denotes |
Thus, traditional bioanalytical techniques, such as PCR, are often utilized for the detection of environmental pathogens. |
T964 |
7322-7515 |
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 |
7516-7606 |
Sentence |
denotes |
However, they also require measurement formats for the detection of aerosolized pathogens. |
T966 |
7607-7859 |
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 |
7860-8122 |
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 |
8123-8129 |
Sentence |
denotes |
2008). |
T969 |
8130-8290 |
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 |
8291-8309 |
Sentence |
denotes |
2006; Weber et al. |
T971 |
8310-8316 |
Sentence |
denotes |
2010). |
T972 |
8317-8551 |
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 |
8552-8558 |
Sentence |
denotes |
2015). |
T974 |
8559-8646 |
Sentence |
denotes |
Hospital-acquired infections are prevalent causes of morbidity in patients (Orsi et al. |
T975 |
8647-8653 |
Sentence |
denotes |
2002). |
T976 |
8654-8840 |
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 |
8841-8973 |
Sentence |
denotes |
In addition to clinical pathogens, it is also of interest to detect pathogens in non-clinical settings (Faucher and Charette, 2015). |
T978 |
8974-9164 |
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 |
9166-9202 |
Sentence |
denotes |
4.3 Medical diagnostic applications |
T980 |
9203-9389 |
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 |
9390-9620 |
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 |
9621-9861 |
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 |
9862-10052 |
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 |
10053-10074 |
Sentence |
denotes |
2000; Beekmann et al. |
T985 |
10075-10095 |
Sentence |
denotes |
2003; Dierkes et al. |
T986 |
10096-10114 |
Sentence |
denotes |
2009; Rappo et al. |
T987 |
10115-10121 |
Sentence |
denotes |
2016). |
T988 |
10122-10345 |
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 |
10346-10352 |
Sentence |
denotes |
2006). |
T990 |
10353-10492 |
Sentence |
denotes |
Additionally, the need for rapid antibody screening has been identified as an important aspect of mitigating the ongoing COVID-19 pandemic. |
T991 |
10493-10729 |
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 |
10730-10924 |
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 |
10925-11080 |
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 |
11081-11376 |
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 |
11377-11566 |
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 |
11567-11754 |
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 |
11755-11998 |
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 |
11999-12146 |
Sentence |
denotes |
The diagnostically-relevant concentration of pathogens in each type of matrix must be considered when designing a biosensor for pathogen detection. |
T999 |
12147-12263 |
Sentence |
denotes |
For example, the detection of bacteria in blood versus urine exhibit different diagnostic thresholds (Kelley, 2017). |
T1000 |
12264-12328 |
Sentence |
denotes |
Such knowledge can inform the need for sample preparation steps. |
T1001 |
12330-12381 |
Sentence |
denotes |
4.4 Biological defense and bio-threat applications |
T1002 |
12382-12518 |
Sentence |
denotes |
The potential for the weaponization of pathogens drives the need for rapid and sensitive biosensors for biological defense applications. |
T1003 |
12519-12736 |
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 |
12737-13002 |
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 |
13003-13231 |
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 |
13232-13251 |
Sentence |
denotes |
2004; Mirski et al. |
T1007 |
13252-13282 |
Sentence |
denotes |
2014; Shah and Wilkins, 2003). |
T1008 |
13283-13423 |
Sentence |
denotes |
The reader is directed to various comprehensive reviews on biosensor-based assays for the detection of biowarfare agents (Christopher et al. |
T1009 |
13424-13454 |
Sentence |
denotes |
1997; Shah and Wilkins, 2003). |
T1010 |
13455-13516 |
Sentence |
denotes |
Common targets include the aforementioned airborne pathogens. |
T1011 |
13517-13724 |
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 |
13725-13899 |
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 |
13900-13930 |
Sentence |
denotes |
1997; Shah and Wilkins, 2003). |
T1014 |
13931-14182 |
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 |
14183-14345 |
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 |
14346-14569 |
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 |
14570-14846 |
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. |