Abstract
Background: Antimicrobial resistance (AMR) occurs when microbes become resistant to antibiotics causing complications and limited treatment options. AMR is more significant where antibiotics use is excessive or abusive and the strains of bacteria become resistant to antibiotic treatments. Current technologies for bacteria and its resistant strains identification and antimicrobial susceptibility testing (AST) are mostly central-lab based in hospitals, which normally take days to weeks to get results. These tools and procedures are expensive, laborious and skills based. There is an ever-increasing demand for developing point-of-care (POC) diagnostics tools for rapid and near patient AMR testing. Microfluidics, an important and fundamental technique to develop POC devices, has been utilized to tackle AMR in healthcare. This review mainly focuses on the current development in the field of microfluidics for rapid AMR testing.
Method: Due to the limitations of conventional AMR techniques, microfluidic-based platforms have been developed for better understandings of bacterial resistance, smart AST and minimum inhibitory concentration (MIC) testing tools and development of new drugs. This review aims to summarize the recent development of AST and MIC testing tools in different formats of microfluidics technology. Results: Various microfluidics devices have been developed to combat AMR. Miniaturization and integration of different tools has been attempted to produce handheld or standalone devices for rapid AMR testing using different formats of microfluidics technology such as active microfluidics, droplet microfluidics, paper microfluidics and capillary-driven microfluidics. Conclusion: Current conventional AMR detection technologies provide time-consuming, costly, labor-intensive and central lab-based solutions, limiting their applications. Microfluidics has been developed for decades and the technology has emerged as a powerful tool for POC diagnostics of antimicrobial resistance in healthcare providing, simple, robust, cost-effective and portable diagnostics. The success has been reported in research articles; however, the potential of microfluidics technology in tackling AMR has not been fully achieved in clinical settings.Keywords: Antibiotic, antimicrobial resistance (AMR), Antimicrobial susceptibility testing (AST), capillary flow, colorimetry, lab-on-a-chip, microfluidics, Minimum inhibitory concentration (MIC), Point-of-care.
Graphical Abstract
[1]
O’Neill, J. Rapid Diagnostics: Stopping Unnecessary Use of Antibiotics. Review on Antimicrobial Resistance; Welcome Trust and HM Government, 2015.
[4]
Lazcka, O.; Del Campo, F.J. Mun˜ oz, F.X. Pathogen detection: a perspective of traditional methods and biosensors. Biosens. Bioelectron., 2007, 22, 1205-1217.
[5]
Aroonnual, A.; Janvilisri, T.; Ounjai, P.; Chankhamhaengdecha, S. Microfluidics: innovative approaches for rapid diagnosis of antibiotic-resistant bacteria. Essays Biochem., 2017, 61, 91-101.
[6]
Pulido, M.R.; García-Quintanilla, M.; Martín-Peña, R.; Cisneros, J.M.; McConnell, M.J. Progress on the development of rapid methods for antimicrobial susceptibility testing. J. Antimicrob. Chemother., 2013, 68, 2710-2717.
[7]
Schofield, C.B. Updating antimicrobial susceptibility testing methods. Clin. Lab. Sci., 2012, 25, 233-239.
[8]
Didelot, X.; Bowden, R.; Wilson, D.J.; Peto, T.E.A.; Crook, D.W. Transforming clinical microbiology with bacterial genome sequencing. Nat. Rev. Genet., 2012, 13, 601-612.
[9]
Hrabak, J.; Chudackova, E.; Walkova, R. Matrix-assisted laser desorption ionization- time of flight (MALDITOF) mass spectrometry for detection of antibiotic resistance mechanisms: from research to routine diagnosis. Clin. Microbiol. Rev., 2013, 26, 103-114.
[10]
Kinnunen, P.; McNaughton, B.H.; Albertson, T.; Sinn, I.; Mofakham, S.; Elbez, R.; Newton, D.W.; Hunt, A.; Kopelman, R. Self-assembled magnetic bead biosensor for measuring bacterial growth and antimicrobial susceptibility testing. Small, 2012, 8, 2477-2482.
[12]
Chiang, Y.L.; Lin, C.H.; Yen, M.Y.; Su, Y.D.; Chen, S.J.; Chen, H.F. Innovative antimicrobial susceptibility testing method using surface plasmon resonance. Biosens. Bioelectron., 2009, 24, 1905-1910.
[13]
Karasinski, J.; White, L.; Zhang, Y.; Wang, E.; Andreescu, S.; Sadik, O.A.; Lavine, B.K.; Vora, M. Detection and identification of bacteria using antibiotic susceptibility and a multi-array electrochemical sensor with pattern recognition. Biosens. Bioelectron., 2007, 22, 2643-2649.
[14]
Tang, Y.; Zhen, L.; Liu, J.; Wu, J. Rapid antibiotic susceptibility testing in a microfluidic pH sensor. Anal. Chem., 2013, 85, 2787-2794.
[15]
Lu, X.; Samuelson, D.R.; Xu, Y.; Zhang, H.; Wang, S.; Rasco, B.A.; Xu, J.; Konke, M.E. Detecting and tracking nosocomial methicillin-resistant Staphylococcus aureus using a microfluidic SERS biosensor. Anal. Chem., 2013, 85, 2320-2327.
[16]
Bauer, K.A.; Perez, K.K.; Forrest, G.N.; Goff, D.A. Review of rapid diagnostic tests used by antimicrobial stewardship programs. Clin. Infect. Dis., 2014, 59, S134-S145.
[17]
Kerremans, J.J.; Verboom, P.; Stijnen, T.; Hakkaart-van, R.L.; Goessens, W.; Verbrugh, H.A.; Vos, M.C. Rapid identification and antimicrobial susceptibility testing reduce antibiotic use and accelerate pathogen-directed antibiotic use. J. Antimicrob. Chemother., 2008, 61, 428-435.
[18]
Choi, J.; Yoo, J.; Lee, M.; Kim, E.G.; Lee, J.S.; Lee, S.; Joo, S.; Song, S.H.; Kim, E.C.; Lee, J.C.; Kim, H.C.; Jung, Y.G.; Kwon, S. A rapid antimicrobial susceptibility test based on single-cell morphological analysis. Sci. Transl. Med., 2014, 6267ra174
[19]
Choi, J.; Yoo, J.; Kim, K.J.; Kim, E.G.; Park, K.O.; Kim, H.; Kim, H.; Jung, H.; Kim, T.; Choi, M.; Kim, H.C.; Ryoo, S.; Jung, Y.G.; Kwon, S. Rapid drug susceptibility test of Mycobacterium tuberculosis using microscopic time-lapse imaging in an agarose matrix. Appl. Microbiol. Biotechnol., 2016, 100, 2355.
[20]
Mohan, R.; Mukherjee, A.; Sevgen, S.E.; Sanpitakseree, C.; Lee, J. Schroeder, Paul, C. M.; Kenis, J. A. A multiplexed microfluidic platform for rapid antibiotic susceptibility testing. Biosens. Bioelectron., 2013, 49, 118-125.
[21]
Mohan, R.; Sanpitakseree, C.; Desai, A.V.; Sevgen, S.E.; Schroedera, C.M.; Paul, J.A. Kenis. A microfluidic approach to study the effect of bacterial interactions on antimicrobial susceptibility in polymicrobial cultures. RSC Advances, 2015, 5, 35211-35223.
[22]
Sun, H.; Liu, Z.; Hua, C.; Ren, K. Cell-on-hydrogel platform made of agar and alginate for rapid, low-cost, multidimensional test of antimicrobial susceptibility. Lab Chip, 2016, 16, 3130-3138.
[23]
Liu, Z. Sun, Han.; Ren, Dr. K. A Multiplexed, Gradient‐Based, Full‐Hydrogel Microfluidic Platform for Rapid, High‐Throughput Antimicrobial Susceptibility Testing. ChemPlusChem, 2017, 82, 792.
[24]
Lee, W.B.; Fu, C.Y.; Chang, W.H.; You, H.L.; Wang, C.H.; Lee, M.S.; Lee, G.B. A microfluidic device for antimicrobial susceptibility testing based on a broth dilution method. Biosens. Bioelectron., 2017, 87, 669-678.
[25]
Kim, S.C.; Cestellos-Blanco, S.; Inoue, K.; Zare, R.N. Miniaturized Antimicrobial Susceptibility Test by Combining Concentration Gradient Generation and Rapid Cell Culturing. Antibiotics (Basel), 2015, 4, 455-466.
[26]
Matsumoto, Y.; Sakakihara, S.; Grushnikov, A.; Kikuchi, K.; Noji, H.; Yamaguchi, A.; Iino, R.; Yagi, Y.; Nishino, K. A microfluidic channel method for rapid drug susceptibility testing of pseudomonas aeruginosa. PLoS One, 2016, 11e0148797
[27]
Syal, K.; Shen, S.; Yang, Y.; Wang, S.; Haydel, S.E.; Tao, N. Rapid antibiotic susceptibility testing of uropathogenic E. coli by tracking submicron scale motion of single bacterial cells. ACS Sens., 2017, 2, 1231-1239.
[28]
Baltekin, O.; Boucharin, A.; Tano, E.; Andersson, D.I.; Elf, J. Antibiotic susceptibility testing in less than 30 min using direct single-cell imaging. Proc. Natl. Acad. Sci. USA, 2017, 34, 9170-9175.
[29]
Hassan, S.; Nightingale, A.M.; Niu, X. Continuous measurement of enzymatic kinetics in droplet flow for point-of-care monitoring. Analyst (Lond.), 2016, 141, 3266-3273.
[30]
Theberge, A.B.; Courtois, F.; Schaerli, Y.; Fischlechner, M.; Abell, C.; Hollfelder, F.; Huck, W.T.S. Microdroplets in microfluidics: An evolving platform for discoveries in chemistry and biology. Angew. Chem. Int. Ed., 2010, 49, 5846-5868.
[31]
Schaerli, Y.; Hollfelder, F. The potential of microfluidic water-in-oil droplets in experimental biology. Mol. Biosyst., 2009, 5, 1392-1404.
[32]
Avesar, J.; Rosenfeld, D.; Truman-Rosentsvit, M.; Ben-Arye, T.; Geffen, Y.; Bercovici, M.; Levenberg, S. Rapid phenotypic antimicrobial susceptibility testing using nanoliter arrays. Proc. Natl. Acad. Sci. USA, 2017, 114(29), E5787-E5795.
[http://dx.doi.org/10.1073/pnas.1703736114]
[http://dx.doi.org/10.1073/pnas.1703736114]
[33]
Kaushika, A.M. Hsieha, k.; Chena, L.; Shina, D. J.; Liaob, j. C.; Wang, T. Accelerating bacterial growth detection and antimicrobial susceptibility assessment in integrated picoliter droplet platform. Biosens. Bioelectron., 2017, 97, 260-266.
[34]
Keays, M.C.; O’Brien, M.; Hussain, A.; Kiely, P.A.; Dalton, T. Rapid identification of antibiotic resistance using droplet microfluidics. Bioengineered, 2016, 7, 79-87.
[35]
Churski, K.; Kaminski, T.S.; Jakiela, S.; Kamysz, W.; Baranska-Rybak, W.; Weibeld, D.B.; Garstecki, P. Rapid screening of antibiotic toxicity in an automated microdroplet system. Lab Chip, 2012, 12, 1629.
[36]
Boedicker, J.Q.; Li, L.; Kline, T.R.; Ismagilov, R.F. Detecting bacteria and determining their susceptibility to antibiotics by stochastic confinement in nanoliter droplets using plug-based microfluidics. Lab Chip, 2008, 8, 1265-1272.
[37]
Mettakoonpitak, J.; Boehle, K.; Nantaphol, S.; Teengam, P.; Adkins, J.A.; Srisa-Art, M.; Henry, C.S. Electrochemistry on paper‐based analytical devices: A review. Electroanalysis, 2016, 28, 1420-1436.
[38]
Yang, Y.Y.; Noviana, E.; Nguyen, M.P.; Geiss, B.J.; Dandy, D.S.; Henry, C.S. Paper-Based Microfluidic Devices: Emerging Themes and Applications. Anal. Chem., 2017, 89, 71-91.
[39]
Choi, J.R.; Tang, R.; Wang, S.; Wan Abas, W.A. PingguanMurphy, B.; Xu, F. Paper-based sample-to-answer molecular diagnostic platform for point-of-care diagnostics. Biosens. Bioelectron., 2015, 74, 427-439.
[40]
Funes-Huacca, M.; Wu, A.; Szepesvari, E.; Rajendran, P. KwanWong, N.; Razgulin, A.; Shen, Y.; Kagira, J.; Campbell, R.; Derda, R., Portable self-contained cultures for phage and bacteria made of paper and tape. Lab Chip, 2012, 12, 4269-4278.
[41]
Li, C-z.; Vandenberg, K.; Prabhulkar, S.; Zhu, X.; Schneper, L.; Methee, K.; Rosser, C.J.; Almeide, E. Paper based point-of-care testing disc for multiplex whole cell bacteria analysis. Biosens. Bioelectron., 2011, 26, 4342-4348.
[42]
Adkins, J.A.; Boehle, K.; Friend, C.; Chamberlain, B.; Bisha, B.; Henry, C.S. Colorimetric and electrochemical bacteria detection using printed paper- and transparency-based analytic devices. Anal. Chem., 2017, 89, 3613-3621.
[43]
Park, T.S.; Li, W.; McCracken, K.E.; Yoon, J-Y. Smartphone quantifies Salmonella from paper microfluidics. Lab Chip, 2013, 13, 4832-4840.
[44]
Jokerst, J.C.; Adkins, J.A.; Bisha, B.; Mentele, M.M.; Goodridge, L.D.; Henry, C.S. Development of a Paper-Based Analytical Device for Colorimetric Detection of Select Foodborne Pathogens. Anal. Chem., 2012, 84, 2900-2907.
[45]
Srisa-Art, M.; Boehle, K.E.; Geiss, B.J.; Henry, C.S. Highly sensitive detection of salmonella typhimurium using a colorimetric paper-based analytical device coupled with immunomagnetic separation. Anal. Chem., 2018, 90, 1035-1043.
[46]
Boehle, K.E.; Gilliand, J.; Wheeldon, C.R.; Holder, A.; Adkins, J.A.; Geiss, B.J.; Ryan, E.P.; Henry, C.S. Utilizing Paper-Based Devices for Antimicrobial-Resistant Bacteria Detection. Angew. Chem. Int. Ed., 2017, 56, 6886-6890.
[47]
Xu, B.; Du, Y.; Lin, J.; Qi, M.; Shu, B.; Wen, X.; Liang, G.; Chen, B.; Liu, D. Simultaneous identification and antimicrobial susceptibility testing of multiple uropathogens on a microfluidic chip with paper-supported cell culture arrays. Anal. Chem., 2016, 88, 11593-11600.
[48]
Reis, N.M.; Pivetal, J.; Loo-Zazueta, A.L.; Barrosb, J.M.S.; Edwards, A.D. Lab on a stick: Multi-analyte cellular assays in a microfluidic dipstick. Lab Chip, 2016, 16, 2891.
[49]
Gervais, L.; Delamarche, E. Toward one-step point-of-care immunodiagnostics using capillary-driven microfluidics and PDMS substrates. Lab Chip, 2009, 9, 3330-3337.
[50]
Walker, G.M.; Beebe, D.J. A passive pumping method for microfluidic devices. Lab Chip, 2002, 2, 131-134.
[51]
Desai, D.; Wu, G.; Zaman, M.H. Tackling HIV through robust diagnostics in the developing world: current status and future opportunities. Lab Chip, 2011, 11, 194-211.
[52]
Tseng, D.; Mudanyali, O.; Oztoprak, C.; Isikman, S.O.; Sencan, I.; Yaglidere, O.; Ozcan, A. Lensfree microscopy on a cellphone. Lab Chip, 2010, 10, 1787-1792.
[53]
Barbosa, A.I.; Gehlot, P.; Sidapra, K.; Edwards, A.D.; Reis, N.M. Portable smartphone quantitation of prostate specific antigen (PSA) in a fluoropolymer microfluidic device. Biosens. Bioelectron., 2015, 70, 5-14.
[54]
Feng, S.; Tseng, D.; Carlo, D.D.; Garner, O.B.; Ozcan, A. High-throughput and automated diagnosis of antimicrobial resistance using a cost-effective cellphone-based micro-plate reader. Sci. Rep., 2016, 6, 39203.
[55]
Kadlec, M.W.; You, D.; Liao, J.C.; Wong, P.K. A cell phone-based microphotometric system for rapid antimicrobial susceptibility testing. J. Lab. Autom., 2014, 19, 258-266.
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