Interfacing Pathogen Detection with Smartphones for Point-of-Care Applications

Abstract

Figure 1.

Number of publications as year in the field of smartphone technology for disease-related applications. The data were collected through searching the PubMed database using the keywords of “smartphone” and “disease”.

Figure 2.

Smartphone-based endpoint colorimetric detection of proteins associated with pathogens. (A) Color change (from colorless to blue) developed by using H₂O₂ and 3,3′,5,5′-tetramethylbenzidine (TMB) chromogen to antibody-conjugated horseradish peroxidase (HRP). (B) Direct and indirect dot-blot assays for colorimetric detection of Mycobacterium tuberculosis (Mtb). Reprinted from Sens. Actuators B Chem., Vol. 254, Li, L.; Liu, Z.; Zhang, H.; Yue, W.; Li, C.-W.; Yi, C. A Point-of-need Enzyme Linked Aptamer Assay for Mycobacterium Tuberculosis Detection Using A Smartphone, pp. 337–346 (ref 76). Copyright 2018, with permission from Elsevier. (C) Interfaces of custom-made App displaying the image processing and quantitative testing results for Mtb detection in (B). Reprinted from Sens. Actuators B Chem., Vol. 254, Li, L.; Liu, Z.; Zhang, H.; Yue, W.; Li, C.-W.; Yi, C. A Point-of-need Enzyme Linked Aptamer Assay for Mycobacterium Tuberculosis Detection Using A Smartphone, pp. 337–346 (ref 76). Copyright 2018, with permission from Elsevier. (D) Schematic illustration of ultrasensitive detection of Salmonella Enteritidis using conjugation of magnetic beads-antibody and enzyme-antibody-inorganic nanoflowers. Reprinted from Sens. Actuators B Chem., Vol. 261, Zeinhom, M. M. A.; Wang, Y.; Sheng, L.; Du, D.; Li, L.; Zhu, M.-J.; Lin, Y. Smart Phone Based Immunosensor Coupled with Nanoflower Signal Amplification for Rapid Detection of Salmonella Enteritidis in Milk, Cheese and Water, pp. 75–82 (ref 78). Copyright 2018, with permission from Elsevier. (E) Wide flied-of-view (FOV) achieved by using a microprism array for smartphone imaging of multiple wells. Reproduced from Wang, L.-J.; Sun, R.; Vasile, T.; Chang, Y.-C.; Li, L. Anal. Chem. 2016, 88, 8302–8308 (ref 79). Copyright 2016 American Chemical Society. (F) Schematic illustration of a POC immunoassay in a plastic microchip with micro-pit array (μPAC) for detection of HIV p24 antigen. Reprinted from Sens. Actuators B Chem., Vol. 271, Li, F.; Li, H.; Wang, Z.; Wu, J.; Wang, W.; Zhou, L.; Xiao, Q.; Pu, Q. Mobile Phone Mediated Point-of-care Testing of HIV p24 Antigen Through Plastic Micro-pit Array Chips, pp.189–194 (ref 80). Copyright 2018, with permission from Elsevier.

Figure 3.

Smartphone-based endpoint lateral flow assays (LFAs). (A) Sandwich format in lateral flow immunoassays (LFIAs). (B) Competitive format in LFIAs. (C) Dual LFIAs in a 3D printed cartridge to simultaneously detect Salmonella Enteritidis and Escherichia coli O157:H7 in food samples by a smartphone. Reproduced from Cheng, N.; Song, Y.; Zeinhom, M. M.; Chang, Y.-C.; Sheng, L.; Li, H.; Du, D.; Li, L.; Zhu, M.-J.; Luo, Y. Anal. Chem. 2017, 9, 40671–40680 (ref 94). Copyright 2017 American Chemical Society. (D) Four different strategies in nucleic acid lateral flow assays (NALFAs). Reprinted by permission from Springer Nature: ANALTICAL AND BIOANALYTICAL CHMEISTRY, Posthuma-Trumpie, G. A.; Korf, J.; van Amerongen, A. Anal. Bioanal. Chem. 2009, 393, 569–582 (ref 95). Copyright 2009. (E). A “sample-in and answer-out” NALFA device using smartphone-based signal readout. Reproduced from Choi, J. R.; Hu, J.; Tang, R.; Gong, Y.; Feng, S.; Ren, H.; Wen, T.; Li, X.; Abas, W. A. B. W.; Pingguan-Murphy, B. Lab Chip 2016, 16, 611–621 (ref 96), with permission of The Royal Society of Chemistry.

Figure 4.

Smartphone-based endpoint fluorescent detection. (A) SYBR Green I (SG) (above) and EvaGreen™ (below) as ds-DNA intercalating fluorescent dyes. (B) A smartphone-based fluorescence detection platform for LAMP amplification detection with EvaGreen™ fluorescence dye. Reproduced from Chen, W.; Yu, H.; Sun, F.; Ornob, A.; Brisbin, R.; Ganguli, A.; Vemuri, V.; Strzebonski, P.; Cui, G.; Allen, K. J. Anal. Chem. 2017, 89, 11219–11226 (ref 98). Copyright 2017 American Chemical Society. (C) Schematic diagram of calcein-based fluorescent detection in LAMP assay. Reprinted by permission from Springer Nature: NATURE PROTOCOLS, Tomita, N.; Mori, Y.; Kanda, H.; Notomi, T. Nat. Protoc. 2008, 3, 877 (ref 66). Copyright 2008. (D) A smartphone-based imaging system for multiple DNA detection by LAMP assay with calcein fluorescent dye. Reproduced Hui, J.; Gu, Y.; Zhu, Y.; Chen, Y.; Guo, S.-J.; Tao, S.-C.; Zhang, Y.; Liu, P. Lab Chip 2018, 18, 2854–2864 (ref 100) with permission of The Royal Society of Chemistry. (E) TwistAmp exo probes used for smartphone-based RPA detection. Reprinted from Anal. Biochem., Vol. 545, Chan, K.; Wong, P.-Y.; Parikh, C.; Wong, S. Moving Toward Rapid and Low-cost Point-of-care Molecular Diagnostics with a Repurposed 3D Printer and RPA, pp.4–12 (ref 106). Copyright 2018, with permission from Elsevier. (F) Fluorescence-based LFIAs using NIR-to-NIR up-conversion nanoparticle and a smartphone as a fluorescence reader for the detection of avian influenza virus in opaque stool samples. Reprinted from Biosens. Bioelectron., Vol. 112, Kim, J.; Kwon, J. H.; Jang, J.; Lee, H.; Kim, S.; Hahn, Y. K.; Kim, S. K.; Lee, K. H.; Lee, S.; Pyo, H. Rapid and Background-free Detection of Avian Influenza Virus in Opaque Sample using NIR-to-NIR Up-conversion Nanoparticle-based Lateral Flow Immunoassay Platform, pp.209–215 (ref 108). Copyright 2018, with permission from Elsevier.

Figure 5.

Smartphone-based real-time fluorescence detection. (A) A typical workflow of real-time fluorescence detection of nucleic acid amplification by a smartphone. Reprinted by permission from Springer Nature: BIOSENSORS AND BIODETECTION, Priye, A.; Ugaz, V. M. In Biosensors and Biodetection; Springer, 2017, pp 251–266. (ref 109) Copyright 2017. (B) Smart Cup for herpes virus detection at the point of care. Reprinted from Sens. Actuators B Chem., Vol. 229, Liao, S.-C.; Peng, J.; Mauk, M. G.; Awasthi, S.; Song, J.; Friedman, H.; Bau, H. H.; Liu, C. Smart Cup: A Minimally-instrumented, Smartphone-based Point-of-care Molecular Diagnostic Device, pp.232–238 (ref 110). Copyright 2016, with permission from Elsevier. (C) Workflow illustration of an “all-in-one” diagnostic platform for multiplex detection of Zika, Chikungunya, and Dengue. Reprinted by permission from Springer Nature: BIOMEDICAL MICRODEVICES, Ganguli, A.; Ornob, A.; Yu, H.; Damhorst, G.; Chen, W.; Sun, F.; Bhuiya, A.; Cunningham, B.; Bashir, R. Biomed. Microdevices 2017, 19, 73 (ref 111). Copyright 2017. (D) Real-time convection PCR detection by a smartphone using TaqMan probes. Reprinted by permission from Springer Nature: MICROSYSTEM TECHNOLOGIES, Qiu, X.; Ge, S.; Gao, P.; Li, K.; Yang, S.; Zhang, S.; Ye, X.; Xia, N.; Qian, S. Microsyst. Technol. 2017, 23, 2951–2956 (ref 112). Copyright 2017.

Figure 6.

Smartphone-based real-time bioluminescence detection. (A) Biochemical reactions for bioluminescent assay in real-time LAMP amplification. Reproduced with permission from Public Library of Science, Gandelman, O. A.; Church, V. L.; Moore, C. A.; Kiddle, G.; Carne, C. A.; Parmar, S.; Jalal, H.; Tisi, L. C.; Murray, J. A. PLoS ONE 2010, 5, e14155 (ref 114). Copyright 2010. (B) A typical bioluminescence intensity curve for real-time bioluminescence detection using LAMP. Reproduced with permission from Public Library of Science, Gandelman, O. A.; Church, V. L.; Moore, C. A.; Kiddle, G.; Carne, C. A.; Parmar, S.; Jalal, H.; Tisi, L. C.; Murray, J. A. PLoS ONE 2010, 5, e14155 (ref 114). Copyright 2010. (C) Smart connected cup platform and its microfluidic chip for real-time bioluminescence detection of LAMP amplification. Reprinted from Song, J.; Pandian, V.; Mauk, M. G.; Bau, H. H.; Cherry, S.; Tisi, L. C.; Liu, C. Anal. Chem. 2018, 90, 4823–4831 (ref 115). Copyright 2018 American Chemical Society. (D) Real-time bioluminescence curves of RT-LAMP for ZIKV detection on smart connected cup shown in (C). Reprinted from Song, J.; Pandian, V.; Mauk, M. G.; Bau, H. H.; Cherry, S.; Tisi, L. C.; Liu, C. Anal. Chem. 2018, 90, 4823–4831 (ref 115). Copyright 2018 American Chemical Society. (E) Spatiotemporal mapping of disease detection on a Google Map using smart connected cup shown in (C). Reprinted from Song, J.; Pandian, V.; Mauk, M. G.; Bau, H. H.; Cherry, S.; Tisi, L. C.; Liu, C. Anal. Chem. 2018, 90, 4823–4831 (ref 115). Copyright 2018 American Chemical Society.

Figure 7.

Smartphone-based real-time electrochemical detection platforms. (A) Smartphone-based potentiostat platform for detection of the core antibody of hepatitis C virus (HCV). Reprinted from Biosens. Bioelectron. Vol. 86, Aronoff-Spencer, E.; Venkatesh, A.; Sun, A.; Brickner, H.; Looney, D.; Hall, D. A. Detection of Hepatitis C Core Antibody by Dual-affinity Yeast Chimera and Smartphone-based Electrochemical Sensing, pp. 690–696 (ref 117). Copyright 2016, with permission from Elsevier. (B) Smartphone-based handheld electrochemical detection system to measure the malarial antigen. Reproduced with permission from Proceedings of the National Academy of Sciences USA Nemiroski, A.; Christodouleas, D. C.; Hennek, J. W.; Kumar, A. A.; Maxwell, E. J.; Fernández-Abedul, M. T.; Whitesides, G. M. Proc. Natl. Acad. Sci. U.S.A. 2014, 111, 11984–11989 (ref 118). (C) Universal wireless electrochemical detector (UWED) coupled with a smartphone. Reprinted from Ainla, A.; Mousavi, M. P.; Tsaloglou, M.-N.; Redston, J.; Bell, J. G.; Fernández-Abedul, M. T.; Whitesides, G. M. Anal. Chem. 2018, 90, 6240–6246 (ref 119). Copyright 2018 American Chemical Society. (D) Schematic illustration of different strategies to immobilize the analyte-specific aptamers and various sandwich-type strategies to construct electrochemical aptasensor. Reproduced with permission from Molecular Diversity Preservation International and Multidisciplinary Digital Publishing Institute. Mishra, G. K.; Sharma, V.; Mishra, R. K. Biosensors 2018, 8, 28 (ref 120). Copyright 2018. (E) General design for electrochemical DNA detection. Reprinted by permission from Springer Nature: NATURE BIOTECHNOLOGY, Drummond, T. G.; Hill, M. G.; Barton, J. K. Nat. Biotechnol. 2003, 21, 1192 (ref 121). Copyright 2003. (F) DNA-mediated electrochemical detection using methylene blue (MB+) molecules. Reprinted by permission from Springer Nature: NATURE BIOTECHNOLOGY, Drummond, T. G.; Hill, M. G.; Barton, J. K. Nat. Biotechnol. 2003, 21, 1192 (ref 121). Copyright 2003. (G) Smartphone-based microfluidic pre-concentrator and EIS sensor for E. coli detection. Reprinted from Sens. Actuators B Chem. Vol. 193, Jiang, J.; Wang, X.; Chao, R.; Ren, Y.; Hu, C.; Xu, Z.; Liu, G. L. Smartphone Based Portable Bacteria Pre-concentrating Microfluidic Sensor and Impedance Sensing System, pp. 653–659 (ref 122). Copyright 2014, with permission from Elsevier. (H) Smartphone-based EIS electrochemical sensor for the detection of Zika-virus protein. Reprinted by Reprinted by permission from Springer Nature: SCIENTIFIC REPORTS, Kaushik, A.; Yndart, A.; Kumar, S.; Jayant, R. D.; Vashist, A.; Brown, A. N.; Li, C.-Z.; Nair, M. Sci. Rep. 2018, 8, 9700 (ref 123). Copyright 2018.

Figure 8.

Smartphone-based digital detection platforms. (A) Handheld smartphone-based digital PCR system using a self-priming fractal branching microchannel net chip for digital PCR. Reproduced from Biosens. Bioelectron., Vol. 120, Gou, T.; Hu, J.; Wu, W.; Ding, X.; Zhou, S.; Fang, W.; Mu, Y. Biosens. Bioelectron. 2018, 120, pp. 144–152 (ref 124). Copyright 2018, with permission from Elsevier. (B) Smartphone-based microdroplet megascale detector (μMD). Reproduced from Yelleswarapu, V. R.; Jeong, H.-H.; Yadavali, S.; Issadore, D. Lab Chip 2017, 17, 1083–1094 (ref 128) with permission of The Royal Society of Chemistry.

Figure 9.

Smartphone-based microscopy imaging platforms. (A) Smartphone-based clinical microscopy with eyepieces and objectives of standard microscope. Reproduced with permission from Public Library of Science, Breslauer, D. N.; Maamari, R. N.; Switz, N. A.; Lam, W. A.; Fletcher, D. A. PLoS ONE 2009, 4, e6320 (ref 129). Copyright 2009. (B) Smartphone-based microscopy for cell counting. Reprinted from Sens. Actuators A Phys. Vol. 274, Zeng, Y.; Jin, K.; Li, J.; Liu, J.; Li, J.; Li, T.; Li, S. Sens. A Low Cost and Portable Smartphone Microscopic Device for Cell Counting, pp. 57–63 (ref 130). Copyright 2018, with permission from Elsevier. (C) Lens-free cellphone-based microscopy. Reproduced from Tseng, D.; Mudanyali, O.; Oztoprak, C.; Isikman, S. O.; Sencan, I.; Yaglidere, O.; Ozcan, A. Lab Chip 2010, 10, 1787–1792 (ref 131) with permission of The Royal Society of Chemistry. (D) Smartphone-based microscopy using ambient illumination as a light source. Reproduced from Lee, S. A.; Yang, C. Lab Chip 2014, 14, 3056–3063 (ref 132) with permission of The Royal Society of Chemistry. (E) Smartphone-based quantitative fluorescence microscopy for detecting S. aureus cells. Reprinted from Biosens. Bioelectron. Vol. 109, Shrivastava, S.; Lee, W.-I.; Lee, N.-E. Culture-free, Highly Sensitive, Quantitative Detection of Bacteria from Minimally Processed Samples Using Fluorescence Imaging by Smartphone, pp. 90–97 (ref 133), with permission from Elsevier. (F) Portable smartphone-based microscope with exchangeable 3D printed accessories for detection of E. coli O157:H7 in foods. Reprinted from Biosens. Bioelectron. Vol. 99, Zeinhom, M. M. A.; Wang, Y.; Song, Y.; Zhu, M.-J.; Lin, Y.; Du, D. A Portable Smart-phone Device for Rapid and Sensitive Detection of E. coli O157:H7 in Yoghurt and Egg, pp. 479–485 (ref 134), with permission from Elsevier.