A Comparison of Optical, Electrochemical, Magnetic, and Colorimetric Point-of-Care Biosensors for Infectious Disease Diagnosis

Abstract

Each year, infectious diseases are responsible for millions of deaths, most of which occur in the rural areas of developing countries. Many of the infectious disease diagnostic tools used today require a great deal of time, a laboratory setting, and trained personnel. Due to this, the need for effective point-of-care (POC) diagnostic tools is greatly increasing with an emphasis on affordability, portability, sensitivity, specificity, timeliness, and ease of use. In this Review, we discuss the various diagnostic modalities that have been utilized toward this end and are being further developed to create POC diagnostic technologies, and we focus on potential effectiveness in resource-limited settings. The main modalities discussed herein are optical-, electrochemical-, magnetic-, and colorimetric-based modalities utilized in diagnostic technologies for infectious diseases. Each of these modalities feature pros and cons when considering application in POC settings but, overall, reveal a promising outlook for the future of this field of technological development.

Keywords: biosensors; detection; diagnosis; infectious diseases; point-of-care.

Figure 1:

A) representation of MEQ-LAMP chip used by Hsieh et al. for the detection of Salmonella for infectious disease detection. B) The Methylene Blue molecule in this electrochemical setup allow for real-time detection of the LAMP reaction. Reprinted with permission from reference (79) Hsieh, K.; Patterson, A. S.; Ferguson, B. S.; Plaxco, K. W.; Soh, H. T. Rapid, sensitive, and quantitative detection of pathogenic DNA at the point of care through microfluidic electrochemical quantitative loop-mediated isothermal amplification. Angew. Chemie - Int. Ed. 2012, 51 (20), 4896–4900. Copyright 2012, John Wiley and Sons.

Figure 2:

Sandwich type immunoassay based magnetoresistive sensors which can be utilized to detect various infectious diseases. (A) Antibody is fixed to a surface. (B) Analyte is washed over and allowed to bind to antibody. (C) Biotinylated antibody is washed over to create a sandwich of the analyte. (D) Magnetic nanotags bind to the biotinylated antibody to allow for quantitative detection. Reprinted with permission from reference (101) Osterfeld, S. J.; Yu, H.; Gaster, R. S.; Caramuta, S.; Xu, L.; Han, S.-J.; Hall, D. A.; Wilson, R. J.; Sun, S.; White, R. L.; Davis, R. W.; Pourmand, N.; Wang, S. X. Multiplex protein assays based on real-time magnetic nanotag sensing. Proc. Natl. Acad. Sci. 2008, 105 (52), 20637–20640. Copyright 2008, National Academy of Sciences, U.S.A

Figure 3:

Iron oxide nanoparticles functionalized into MFnS with conjugated antibody and DiI dye when incubated with bacteria allows for the quantitative detection of the bacteria through magnetic resonance and optical detection. Reprinted with permission from reference (55) Banerjee, T.; Sulthana, S.; Shelby, T.; Heckert, B.; Jewell, J.; Woody, K.; Karimnia, V.; McAfee, J.; Santra, S. Multiparametric Magneto-fluorescent Nanosensors for the Ultrasensitive Detection of Escherichia coli O157:H7. ACS Infect. Dis. 2016, 2 (10), 667–673. Copyright 2016, American Chemical Society.

Figure 4:

(A) H3N2/Panama was detected using DRELFA but did not cross react with the subtypes H3N2/Udorn and H3N2/Aichi, unlike (B) the antibody-LFA which cross reacted with the other subtypes. Reprinted from reference (123) Le, T. T.; Chang, P.; Benton, D.; John, W.; Iqbal, M.; Edward, A.; Cass, G. Dual Recognition Element Lateral Flow Assay (DRELFA) - Towards Multiplex Strain Specific Influenza Virus Detection. Anal. Chem. 2017, 89 (12), 6781–6786, under open access liscense CC-BY.

Figure 5:

Visual representation of a lateral flow type assay utilized to detect H1N1. The specimen is allowed to flow down the strip and the bioconjugate binds to the viral particles while the viral particles bind to the test line, creating a sandwich type interaction. Reprinted from reference (124) Yeo, S.; Choi, K.; Cuc, B. T.; Hong, N. N.; Bao, D. T.; Minh, N. Smartphone-Based Fluorescent Diagnostic System for Highly Pathogenic H5N1 Viruses. Theranostics 2016, 6 (2), under open access liscence CC BY-NC.