Abstract
Rapid, low-cost, and sensitive nucleic acid detection and quantification assays enabled by microfluidic paper-based analytical devices (μPADs) hold great promise for point-of-care disease diagnostics and field-based molecular tests. Through the capillary action in μPAD, flexible manipulation of nucleic acid samples can be achieved without the need for external pumps or power supplies, making it possible to fabricate highly integrated sample-to-answer devices that streamline the nucleic acid extraction, separation, concentration, amplification, and detection. To detect minute amounts of genetic materials from clinical and biological samples, it is also critical to develop sensitive signal readouts that generate physically detectable signals for in-device nucleic acid detection and/or quantification. In this review, we will focus on μPAD approaches for the facile manipulation of nucleic acids and emerging signal transduction strategies allowing sensitive and specific nucleic acid detection in μPAD.
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References
Yager P, Domingo GJ, Gerdes J. Point-of-care diagnostics for global health. Annu Rev Biomed Eng. 2008;10:107–44.
Martinez AW, Phillips ST, Butte MJ, Whitesides GM. Patterned paper as a platform for inexpensive, low-volume, portable bioassays. Angew Chem Int Ed. 2007;119:1340–2.
Cate DM, Adkins JA, Mettakoonpitak J, Henry CS. Recent developments in paper-based microfluidic devices. Anal Chem. 2015;87:19–41.
Gong MM, Sinton D. Turning the page: advancing paper-based microfluidics for broad diagnostic application. Chem Rev. 2017;117:8447–80.
Magro L, Escadafal C, Garneret P, Jacquelin B, Kwasiborski A, Manuguerra J-C, et al. Paper microfluidics for nucleic acid amplification testing (NAAT) of infectious diseases. Lab Chip. 2017;17:2347–71.
Fronczek CF, Park TS, Harshman DK, Nicolini AM, Yoon J-Y. Paper microfluidic extraction and direct smartphone-based identification of pathogenic nucleic acids from field and clinical samples. RSC Adv. 2014;4:11103.
Govindarajan AV, Ramachandran S, Vigil GD, Yager P, Böhringer KF. A low cost point-of-care viscous sample preparation device for molecular diagnosis in the developing world; an example of microfluidic origami. Lab Chip. 2012;12:174–81.
Li X, Luo L, Crooks RM. Low-voltage paper isotachophoresis device for DNA focusing. Lab Chip. 2015;15:4090–8.
Gong MM, Nosrati R, Gabriel MCS, Zini A, Sinton D. Direct DNA analysis with paper-based ion concentration polarization. J Am Chem Soc. 2015;137:13913–9.
Rohrman BA, Richards-Kortum RR. A paper and plastic device for performing recombinase polymerase amplification of HIV DNA. Lab Chip. 2012;12:3082.
Connelly JT, Rolland JP, Whitesides GM. “Paper Machine” for molecular diagnostics. Anal Chem. 2015;87:7595–601.
Xu G, Nolder D, Reboud J, Oguike MC, Van Schalkwyk DA, Sutherland CJ, et al. Paper-origami-based multiplexed malaria diagnostics from whole blood. Angew Chem Int Ed. 2016;55:15250–3.
Rosenfeld T, Bercovici M. Amplification-free detection of DNA in a paper-based microfluidic device using electroosmotically balanced isotachophoresis. Lab Chip. 2018;18:861–8.
Liu M, Hui CY, Zhang Q, Gu J, Kannan B, Jahanshahi-Anbuhi S, et al. Target-induced and equipment-free DNA amplification with a simple paper device. Angew Chem Int Ed. 2016;55:2709–13.
Seok Y, Joung H-A, Byun J-Y, Jeon H-S, Shin SJ, Kim S, et al. A paper-based device for performing loop-mediated isothermal amplification with real-time simultaneous detection of multiple DNA targets. Theranostics. 2017;7:2220–30.
Yang Z, Xu G, Reboud J, Ali SA, Kaur G, Mcgiven J, et al. Rapid veterinary diagnosis of bovine reproductive infectious diseases from semen using paper-origami DNA microfluidics. ACS Sens. 2018;3:403–9.
Chow WHA, Mccloskey C, Tong Y, Hu L, You Q, Kelly CP, et al. Application of isothermal helicase-dependent amplification with a disposable detection device in a simple sensitive stool test for toxigenic clostridium difficile. J Mol Diagn. 2008;10:452–8.
Shetty P, Ghosh D, Singh M, Tripathi A, Paul D. Rapid amplification of Mycobacterium tuberculosis DNA on a paper substrate. RSC Adv. 2016;6:56205–12.
Lafleur LK, Bishop JD, Heiniger EK, Gallagher RP, Wheeler MD, Kauffman P, et al. A rapid, instrument-free, sample-to-result nucleic acid amplification test. Lab Chip. 2016;16:3777–87.
Toley BJ, Covelli I, Belousov Y, Ramachandran S, Kline E, Scarr N, et al. Isothermal strand displacement amplification (iSDA): a rapid and sensitive method of nucleic acid amplification for point-of-care diagnosis. Analyst. 2015;140:7540–9.
Choi JR, Hu J, Tang R, Gong Y, Feng S, Ren H, et al. An integrated paper-based sample-to-answer biosensor for nucleic acid testing at the point of care. Lab Chip. 2016;16:611–21.
Bender AT, Borysiak MD, Levenson AM, Lillis L, Boyle DS, Posner JD. Semiquantitative nucleic acid test with simultaneous isotachophoretic extraction and amplification. Anal Chem. 2018;90:7221–9.
Tang R, Yang H, Gong Y, You M, Liu Z, Choi JR, et al. A fully disposable and integrated paper-based device for nucleic acid extraction, amplification and detection. Lab Chip. 2017;17:1270–9.
Phillips EA, Moehling TJ, Bhadra S, Ellington AD, Linnes JC. Strand displacement probes combined with isothermal nucleic acid amplification for instrument-free detection from complex samples. Anal Chem. 2018;90:6580–6.
Choi JR, Liu Z, Hu J, Tang R, Gong Y, Feng S, et al. Polydimethylsiloxane-paper hybrid lateral flow assay for highly sensitive point-of-care nucleic acid testing. Anal Chem. 2016;88:6254–64.
He Y, Zeng K, Zhang S, Gurung AS, Baloda M, Zhang X, et al. Visual detection of gene mutations based on isothermal strand-displacement polymerase reaction and lateral flow strip. Biosens Bioelectron. 2012;31:310–5.
Xu Y, Liu Y, Wu Y, Xia X, Liao Y, Li Q. Fluorescent probe-based lateral flow assay for multiplex nucleic acid detection. Anal Chem. 2014;86:5611–4.
Dragan AI, Pavlovic R, Mcgivney JB, Casas-Finet JR, Bishop ES, Strouse RJ, et al. SYBR Green I: fluorescence properties and interaction with DNA. J Fluoresc. 2012;22:1189–99.
Cosa G, Focsaneanu K-S, Mclean JRN, Mcnamee JP, Scaiano JC. Photophysical properties of fluorescent DNA-dyes bound to single- and double-stranded DNA in aqueous buffered solution. Photochem Photobiol. 2007;73:585–99.
Roy S, Mohd-Naim NF, Safavieh M, Ahmed MU. Colorimetric nucleic acid detection on paper microchip using loop mediated isothermal amplification and crystal violet dye. ACS Sens. 2017;2:1713–20.
Wang AG, Dong T, Mansour H, Matamoros G, Sanchez AL, Li F. Paper-based DNA reader for visualized quantification of soil-transmitted helminth infections. ACS Sens. 2018;3:205–10.
Gootenberg JS, Abudayyeh OO, Lee JW, Essletzbichler P, Dy AJ, Joung J, et al. Nucleic acid detection with CRISPR-Cas13a/C2c2. Science. 2017;356:438–42.
Gootenberg JS, Abudayyeh OO, Kellner MJ, Joung J, Collins JJ, Zhang F. Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6. Science. 2018;360:439–44.
Myhrvold C, Freije CA, Gootenberg JS, Abudayyeh OO, Metsky HC, Durbin AF, et al. Field-deployable viral diagnostics using CRISPR-Cas13. Science. 2018;360:444–8.
Mao X, Ma Y, Zhang A, Zhang L, Zeng L, Liu G. Disposable nucleic acid biosensors based on gold nanoparticle probes and lateral flow strip. Anal Chem. 2009;81:1660–8.
Ali MM, Aguirre SD, Xu Y, Filipe CDM, Pelton R, Li Y. Detection of DNA using bioactive paper strips. Chem. Commun. 2009;0:6640–2.
Hu J, Wang L, Li F, Han YL, Lin M, Lu TJ, et al. Oligonucleotide-linked gold nanoparticle aggregates for enhanced sensitivity in lateral flow assays. Lab Chip. 2013;13:4352.
Takalkar S, Baryeh K, Liu G. Fluorescent carbon nanoparticle-based lateral flow biosensor for ultrasensitive detection of DNA. Biosens Bioelectron. 2017;98:147–54.
Noor MO, Krull UJ. Camera-based ratiometric fluorescence transduction of nucleic acid hybridization with reagentless signal amplification on a paper-based platform using immobilized quantum dots as donors. Anal Chem. 2014;86:10331–9.
Noor MO, Hrovat D, Moazami-Goudarzi M, Espie GS, Krull UJ. Ratiometric fluorescence transduction by hybridization after isothermal amplification for determination of zeptomole quantities of oligonucleotide biomarkers with a paper-based platform and camera-based detection. Anal Chim Acta. 2015;885:156–65.
Doughan S, Uddayasankar U, Krull UJ. A paper-based resonance energy transfer nucleic acid hybridization assay using upconversion nanoparticles as donors and quantum dots as acceptors. Anal Chim Acta. 2015;878:1–8.
Doughan S, Uddayasankar U, Peri A, Krull UJ. A paper-based multiplexed resonance energy transfer nucleic acid hybridization assay using a single form of upconversion nanoparticle as donor and three quantum dots as acceptors. Anal Chim Acta. 2017;962:88–96.
Lu J, Ge S, Ge L, Yan M, Yu J. Electrochemical DNA sensor based on three-dimensional folding paper device for specific and sensitive point-of-care testing. Electrochim Acta. 2012;80:334–41.
Teengam P, Siangproh W, Tuantranont A, Vilaivan T, Chailapakul O, Henry CS. Electrochemical impedance-based DNA sensor using pyrrolidinyl peptide nucleic acids for tuberculosis detection. Anal Chim Acta. 2018;1044:102–9.
Li X, Scida K, Crooks RM. Detection of hepatitis B virus DNA with a paper electrochemical sensor. Anal Chem. 2015;87:9009–15.
Du Y, Pothukuchy A, Gollihar JD, Nourani A, Li B, Ellington AD. Coupling sensitive nucleic acid amplification with commercial pregnancy test strips. Angew Chem In Ed. 2017;129:1012–6.
Scida K, Li B, Ellington AD, Crooks RM. DNA detection using origami paper analytical devices. Anal Chem. 2013;85:9713–20.
Allen PB, Arshad SA, Li B, Chen X, Ellington AD. DNA circuits as amplifiers for the detection of nucleic acids on a paperfluidic platform. Lab Chip. 2012;12:2951–8.
Ying N, Ju C, Sun X, Li L, Chang H, Song G, et al. Lateral flow nucleic acid biosensor for sensitive detection of microRNAs based on the dual amplification strategy of duplex specific nuclease and hybridization chain reaction. PLoS One. 2017;12:e0185091.
Green AA, Silver PA, Collins JJ, Yin P. Toehold switches: de-novo-designed regulators of gene expression. Cell. 2014;159:925–39.
Pardee K, Green AA, Ferrante T, Cameron DE, Daleykeyser A, Yin P, et al. Paper-based synthetic gene networks. Cell. 2014;159:940–54.
Pardee K, Green AA, Takahashi MK, Braff D, Lambert G, Lee JW, et al. Rapid, low-cost detection of Zika virus using programmable biomolecular components. Cell. 2016;165:1255–66.
Noh H, Phillips ST. Fluidic timers for time-dependent, point-of-care assays on paper. Anal Chem. 2010;82:8071–8.
Yamada K, Suzuki K, Citterio D. Text-displaying colorimetric paper-based analytical device. ACS Sens. 2017;2:1247–54.
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This study received a financial support from the National Sciences and Engineering Research Council of Canada, the Ontario Centres of Excellence, the Ontario Ministry of Research, Innovation and Science, and the Brock University Start-Up Fund.
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Published in the topical collection Young Investigators in (Bio-)Analytical Chemistry with guest editors Erin Baker, Kerstin Leopold, Francesco Ricci, and Wei Wang.
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Dong, T., Wang, G.A. & Li, F. Shaping up field-deployable nucleic acid testing using microfluidic paper-based analytical devices. Anal Bioanal Chem 411, 4401–4414 (2019). https://doi.org/10.1007/s00216-019-01595-7
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DOI: https://doi.org/10.1007/s00216-019-01595-7