1932

Abstract

Fast and reliable diagnoses are invaluable in clinical care. Samples (e.g., blood, urine, and saliva) are collected and analyzed for various biomarkers to quickly and sensitively assess disease progression, monitor response to treatment, and determine a patient's prognosis. Processing conventional samples entails many manual time-consuming steps. Consequently, clinical specimens must be processed by skilled technicians before antigens or nucleic acids are detected, and these are often present at dilute concentrations. Recently, several automated microchip technologies have been developed that potentially offer many advantages over traditional bench-top extraction methods. The smaller length scales and more refined transport mechanisms that characterize these microfluidic devices enable faster and more efficient biomarker enrichment and extraction. Additionally, they can be designed to perform multiple tests or experimental steps on one integrated, automated platform. This review explores the current research on microfluidic methods of sample preparation that are designed to aid diagnosis, and covers a broad spectrum of extraction techniques and designs for various types of samples and analytes.

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2015-12-07
2024-06-20
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Literature Cited

  1. Mach AJ, Di Carlo D. 1.  2010. Continuous scalable blood filtration device using inertial microfluidics. Biotechnol. Bioeng. 107:2302–11 [Google Scholar]
  2. Wong I, Ho CM. 2.  2009. Surface molecular property modifications for poly(dimethylsiloxane) (PDMS) based microfluidic devices. Microfluid. Nanofluid. 7:3291–306 [Google Scholar]
  3. Martinez AW, Phillips ST, Whitesides GM, Carrilho E. 3.  2010. Diagnostics for the developing world: microfluidic paper-based analytical devices. Anal. Chem. 82:13–10 [Google Scholar]
  4. Osborn JL, Lutz B, Fu E, Kauffman P, Stevens DY, Yager P. 4.  2010. Microfluidics without pumps: reinventing the T-sensor and H-filter in paper networks. Lab Chip 10:202659–65 [Google Scholar]
  5. Juncker D, Schmid H, Drechsler U, Wolf H, Wolf M. 5.  et al. 2002. Autonomous microfluidic capillary system. Anal. Chem. 74:246139–44 [Google Scholar]
  6. Hosokawa K, Sato K, Ichikawa N, Maeda M. 6.  2004. Power-free poly(dimethylsiloxane) microfluidic devices for gold nanoparticle-based DNA analysis. Lab Chip 4:3181–85 [Google Scholar]
  7. Dimov IK, Basabe-Desmonts L, Garcia-Cordero JL, Ross BM, Park Y. 7.  et al. 2011. Stand-alone self-powered integrated microfluidic blood analysis system (SIMBAS). Lab Chip 11:5845–50 [Google Scholar]
  8. Toner M, Irimia D. 8.  2005. Blood-on-a-chip. Annu. Rev. Biomed. Eng. 7:77–103 [Google Scholar]
  9. Kersaudy-Kerhoas M, Sollier E. 9.  2013. Micro-scale blood plasma separation: from acoustophoresis to egg-beaters. Lab Chip 13:173323–46 [Google Scholar]
  10. Vazquez M, Brabazon D, Shang F, Omamogho JO, Glennon JD, Paull B. 10.  2011. Centrifugally-driven sample extraction, preconcentration and purification in microfluidic compact discs. Trends Anal. Chem. 30:101575–86 [Google Scholar]
  11. Haeberle S, Brenner T, Zengerle R, Ducrée J. 11.  2006. Centrifugal extraction of plasma from whole blood on a rotating disk. Lab Chip 6:6776–81 [Google Scholar]
  12. Gorkin R, Park J, Siegrist J, Amasia M, Lee BS. 12.  et al. 2010. Centrifugal microfluidics for biomedical applications. Lab Chip 10:141758–73 [Google Scholar]
  13. Lee BS, Lee JN, Park JM, Lee JG, Kim S. 13.  et al. 2009. A fully automated immunoassay from whole blood on a disc. Lab Chip 9:111548–55 [Google Scholar]
  14. Kazmierczak SC, Ostoich V, Aron K, Hickey A, Kazmierczak DE, Bleile DM. 14.  2004. Clinical evaluation of an algorithm for short sample detection on a multi-analyte panel using a point-of-care analyzer. Clin. Chem. 50:1947–49 [Google Scholar]
  15. Schaff UY, Sommer GJ. 15.  2011. Whole blood immunoassay based on centrifugal bead sedimentation. Clin. Chem. 57:5753–61 [Google Scholar]
  16. Son JH, Lee SH, Hong S, Park SM, Lee J. 16.  et al. 2014. Hemolysis-free blood plasma separation. Lab Chip 14:132287–92 [Google Scholar]
  17. Liu C, Mauk M, Gross R, Bushman FD, Edelstein PH. 17.  et al. 2013. Membrane-based, sedimentation-assisted plasma separator for point-of-care applications. Anal. Chem. 85:2110463–70 [Google Scholar]
  18. Tachi T, Kaji N, Tokeshi M, Baba Y. 18.  2009. Simultaneous separation, metering, and dilution of plasma from human whole blood in a microfluidic system. Anal. Chem. 81:83194–98 [Google Scholar]
  19. Yoon JS, Germaine JT, Culligan PJ. 19.  2006. Visualization of particle behavior within a porous medium: Mechanisms for particle filtration and retardation during downward transport. Water Resour. Res. 42:6W0641 [Google Scholar]
  20. Zhang XB, Wu ZQ, Wang K, Zhu J, Xu JJ. 20.  et al. 2012. Gravitational sedimentation induced blood delamination for continuous plasma separation on a microfluidics chip. Anal. Chem. 84:83780–86 [Google Scholar]
  21. Sun M, Khan ZS, Vanapalli SA. 21.  2012. Blood plasma separation in a long two-phase plug flowing through disposable tubing. Lab Chip 12:245225–30 [Google Scholar]
  22. Choi S, Park JK. 22.  2007. Continuous hydrophoretic separation and sizing of microparticles using slanted obstacles in a microchannel. Lab Chip 7:7890–97 [Google Scholar]
  23. Yang S, Undar A, Zahn JD. 23.  2006. A microfluidic device for continuous, real time blood plasma separation. Lab Chip 6:7871–80 [Google Scholar]
  24. Qin LD, Vermesh O, Shi Q, Heath JR. 24.  2009. Self-powered microfluidic chips for multiplexed protein assays from whole blood. Lab Chip 9:142016–20 [Google Scholar]
  25. Fan R, Vermesh O, Srivastava A, Yen BKH, Qin L. 25.  et al. 2008. Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood. Nat. Biotechnol. 26:121373–78 [Google Scholar]
  26. Geng ZX, Ju Y, Wang W, Li Z. 26.  2013. Continuous blood separation utilizing spiral filtration microchannel with gradually varied width and micro-pillar array. Sens. Actuators B Chem. 180:122–29 [Google Scholar]
  27. Sollier E, Rostaing H, Pouteau P, Fouillet Y, Achard J-L. 27.  2009. Passive microfluidic devices for plasma extraction from whole human blood. Sens. Actuators B Chem. 141:2617–24 [Google Scholar]
  28. Sollier E, Cubizolles M, Fouillet Y, Achard JL. 28.  2010. Fast and continuous plasma extraction from whole human blood based on expanding cell-free layer devices. Biomed. Microdevices 12:3485–97 [Google Scholar]
  29. Marchalot J, Fouillet Y, Achard JL. 29.  2014. Multi-step microfluidic system for blood plasma separation: architecture and separation efficiency. Microfluid. Nanofluid. 17:1167–80 [Google Scholar]
  30. Doyeux V, Podgorski T, Peponas S, Ismail M, Coupier G. 30.  2011. Spheres in the vicinity of a bifurcation: elucidating the Zweifach–Fung effect. J. Fluid Mech. 674:359–88 [Google Scholar]
  31. Maltezos G, Lee J, Rajagopal A, Scholten K, Kartalov E, Scherer A. 31.  2011. Microfluidic blood filtration device. Biomed. Microdevices 13:1143–46 [Google Scholar]
  32. Li CY, Liu C, Xu Z, Li J. 32.  2012. A power-free deposited microbead plug-based microfluidic chip for whole-blood immunoassay. Microfluid. Nanofluid. 12:5829–34 [Google Scholar]
  33. Homsy A, van der Wal PD, Doll W, Schaller R, Korsatko S. 33.  et al. 2012. Development and validation of a low cost blood filtration element separating plasma from undiluted whole blood. Biomicrofluidics 6:112804–49 [Google Scholar]
  34. Gong MM, Macdonald BD, Vu Nguyen T, Van Nguyen K, Sinton D. 34.  2013. Field tested milliliter-scale blood filtration device for point-of-care applications. Biomicrofluidics 7:444111 [Google Scholar]
  35. Wang SQ, Sarenac D, Chen MH, Huang SH, Giguel FF. 35.  et al. 2012. Simple filter microchip for rapid separation of plasma and viruses from whole blood. Int. J. Nanomed. 7:5019–28 [Google Scholar]
  36. Li CY, Liu C, Xu Z, Li J. 36.  2012. The dual role of deposited microbead plug (DMBP): A blood filter and a conjugate reagent carrier toward point-of-care microfluidic immunoassay. Talanta 97:376–81 [Google Scholar]
  37. Shim JS, Ahn CH. 37.  2012. An on-chip whole blood/plasma separator using hetero-packed beads at the inlet of a microchannel. Lab Chip 12:5863–66 [Google Scholar]
  38. Li CY, Liu C, Xu Z, Li J. 38.  2012. Extraction of plasma from whole blood using a deposited microbead plug (DMBP) in a capillary-driven microfluidic device. Biomed. Microdevices 14:3565–72 [Google Scholar]
  39. Chung KH, Choi YH, Yang JH, Park CW, Kim WJ. 39.  et al. 2012. Magnetically-actuated blood filter unit attachable to pre-made biochips. Lab Chip 12:183272–76 [Google Scholar]
  40. Yang XX, Forouzan O, Brown TP, Shevkoplyas SS. 40.  2012. Integrated separation of blood plasma from whole blood for microfluidic paper-based analytical devices. Lab Chip 12:2274–80 [Google Scholar]
  41. Songjaroen T, Dungchai W, Chailapakul O, Henry CS, Laiwattanapaisal W. 41.  2012. Blood separation on microfluidic paper-based analytical devices. Lab Chip 12:183392–98 [Google Scholar]
  42. Lenshof A, Ahmad-Tajudin A, Järås K, Swärd-Nilsson AM, Aberg L. 42.  et al. 2009. Acoustic whole blood plasmapheresis chip for prostate specific antigen microarray diagnostics. Anal. Chem. 81:156030–37 [Google Scholar]
  43. Nam J, Lim H, Kim D, Shin S. 43.  2011. Separation of platelets from whole blood using standing surface acoustic waves in a microchannel. Lab Chip 11:193361–64 [Google Scholar]
  44. Lin SCS, Mao XL, Huang TJ. 44.  2012. Surface acoustic wave (SAW) acoustophoresis: now and beyond. Lab Chip 12:162766–70 [Google Scholar]
  45. Burguillos MA, Magnusson C, Nordin M, Lenshof A, Augustsson P. 45.  et al. 2013. Microchannel acoustophoresis does not impact survival or function of microglia, leukocytes or tumor cells. PLOS ONE 8:5e64233 [Google Scholar]
  46. Kim J, Johnson M, Hill P, Gale BK. 46.  2009. Microfluidic sample preparation: cell lysis and nucleic acid purification. Integr. Biol. 1:10574–86 [Google Scholar]
  47. Mahalanabis M, Al-Muayad H, Kulinski MD, Altman D, Klapperich CM. 47.  2009. Cell lysis and DNA extraction of gram-positive and gram-negative bacteria from whole blood in a disposable microfluidic chip. Lab Chip 9:192811–17 [Google Scholar]
  48. Nan L, Jiang Z, Wei X. 48.  2014. Emerging microfluidic devices for cell lysis: a review. Lab Chip 14:61060–73 [Google Scholar]
  49. Wen J, Legendre LA, Bienvenue JM, Landers JP. 49.  2008. Purification of nucleic acids in microfluidic devices. Anal. Chem. 80:176472–79 [Google Scholar]
  50. Breadmore MC, Wolfe KA, Arcibal IG, Leung WK, Dickson D. 50.  et al. 2003. Microchip-based purification of DNA from biological samples. Anal. Chem. 75:81880–86 [Google Scholar]
  51. Cady NC, Stelick S, Batt CA. 51.  2003. Nucleic acid purification using microfabricated silicon structures. Biosens. Bioelectron. 19:159–66 [Google Scholar]
  52. Wu Q, Bienvenue JM, Hassan BJ, Kwok YC, Giordano BC. 52.  et al. 2006. Microchip-based macroporous silica sol−gel monolith for efficient isolation of DNA from clinical samples. Anal. Chem. 78:165704–10 [Google Scholar]
  53. Hagan KA, Meier WL, Ferrance JP, Landers JP. 53.  2009. Chitosan-coated silica as a solid phase for RNA purification in a microfluidic device. Anal. Chem. 81:135249–56 [Google Scholar]
  54. Lounsbury JA, Karlsson A, Miranian DC, Cronk SM, Nelson DA. 54.  et al. 2013. From sample to PCR product in under 45 minutes: a polymeric integrated microdevice for clinical and forensic DNA analysis. Lab Chip 13:71384–93 [Google Scholar]
  55. Qu Y, Marshall LA, Santiago JG. 55.  2014. Simultaneous purification and fractionation of nucleic acids and proteins from complex samples using bidirectional isotachophoresis. Anal. Chem. 86:157264–68 [Google Scholar]
  56. Chen L, Prest JE, Fielden PR, Goddard NJ, Manz A, Day PJ. 56.  2006. Miniaturised isotachophoresis analysis. Lab Chip 6:4474–87 [Google Scholar]
  57. Persat A, Marshall LA, Santiago JG. 57.  2009. Purification of nucleic acids from whole blood using isotachophoresis. Anal. Chem. 81:229507–11 [Google Scholar]
  58. Schoch RB, Ronaghi M, Santiago JG. 58.  2009. Rapid and selective extraction, isolation, preconcentration, and quantitation of small RNAs from cell lysate using on-chip isotachophoresis. Lab Chip 9:152145–52 [Google Scholar]
  59. Marshall LA, Han CM, Santiago JG. 59.  2011. Extraction of DNA from malaria-infected erythrocytes using isotachophoresis. Anal. Chem. 83:249715–18 [Google Scholar]
  60. Rogacs A, Qu Y, Santiago JG. 60.  2012. Bacterial RNA extraction and purification from whole human blood using isotachophoresis. Anal. Chem. 84:145858–63 [Google Scholar]
  61. Borysiak MD, Kimura KW, Posner JD. 61.  2015. NAIL: nucleic acid detection using isotachophoresis and loop-mediated isothermal amplification. Lab Chip 15:1697–707 [Google Scholar]
  62. Bordelon H, Adams NM, Klemm AS, Russ PK, Williams JV. 62.  et al. 2011. Development of a low-resource RNA extraction cassette based on surface tension valves. ACS Appl. Mater. Interfaces 3:62161–68 [Google Scholar]
  63. Berry SM, LaVanway AJ, Pezzi HM, Guckenberger DJ, Anderson MA. 63.  et al. 2014. HIV viral RNA extraction in wax immiscible filtration assisted by surface tension (IFAST) devices. J. Mol. Diagn. 16:3297–304 [Google Scholar]
  64. Sur K, McFall SM, Yeh ET, Jangam SR, Hayden MA, Stroupe SD, Kelso DM. 64.  2010. Immiscible phase nucleic acid purification eliminates PCR inhibitors with a single pass of paramagnetic particles through a hydrophobic liquid. J. Mol. Diagn. 12:5620–28 [Google Scholar]
  65. Berry SM, Alarid ET, Beebe DJ. 65.  2011. One-step purification of nucleic acid for gene expression analysis via Immiscible Filtration Assisted by Surface Tension (IFAST). Lab Chip 11:101747–53 [Google Scholar]
  66. Berry SM, Maccoux LJ, Beebe DJ. 66.  2012. Streamlining immunoassays with immiscible filtrations assisted by surface tension. Anal. Chem. 84:135518–23 [Google Scholar]
  67. den Dulk RC, Schmidt KA, Sabatté G, Liébana S, Prins MW. 67.  2013. Magneto-capillary valve for integrated purification and enrichment of nucleic acids and proteins. Lab Chip 13:1106–18 [Google Scholar]
  68. Srinivasan V, Pamula VK, Fair RB. 68.  2004. An integrated digital microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluids. Lab Chip 4:4310–15 [Google Scholar]
  69. Srinivasan V, Pamula VK, Fair RB. 69.  2004. Droplet-based microfluidic lab-on-a-chip for glucose detection. Anal. Chim. Acta 507:1145–50 [Google Scholar]
  70. Jebrail MJ, Bartsch MS, Patel KD. 70.  2012. Digital microfluidics: a versatile tool for applications in chemistry, biology and medicine. Lab Chip 12:142452–63 [Google Scholar]
  71. Sista R, Hua Z, Thwar P, Sudarsan A, Srinivasan V. 71.  et al. 2008. Development of a digital microfluidic platform for point of care testing. Lab Chip 8:122091–104 [Google Scholar]
  72. Jebrail MJ, Sinha A, Vellucci S, Renzi RF, Ambriz C. 72.  et al. 2014. World-to-digital-microfluidic interface enabling extraction and purification of RNA from human whole blood. Anal. Chem. 86:83856–62 [Google Scholar]
  73. Mousa NA, Jebrail MJ, Yang H, Abdelgawad M, Metalnikov P. 73.  et al. 2009. Droplet-scale estrogen assays in breast tissue, blood, and serum. Sci. Transl. Med. 1:11ra2 [Google Scholar]
  74. Jebrail MJ, Yang H, Mudrik JM, Lafrenière NM, McRoberts C. 74.  et al. 2011. A digital microfluidic method for dried blood spot analysis. Lab Chip 11:193218–24 [Google Scholar]
  75. Moon H, Wheeler AR, Garrell RL, Loo JA, Kim CJ. 75.  2006. An integrated digital microfluidic chip for multiplexed proteomic sample preparation and analysis by MALDI-MS. Lab Chip 6:91213–19 [Google Scholar]
  76. Shih SC, Yang H, Jebrail MJ, Fobel R, McIntosh N. 76.  et al. 2012. Dried blood spot analysis by digital microfluidics coupled to nanoelectrospray ionization mass spectrometry. Anal. Chem. 84:83731–38 [Google Scholar]
  77. Lin CC, Tseng CC, Chuang TK, Lee DS, Lee GB. 77.  2011. Urine analysis in microfluidic devices. Analyst 136:132669–88 [Google Scholar]
  78. Mach AJ, Adeyiga OB, Di Carlo D. 78.  2013. Microfluidic sample preparation for diagnostic cytopathology. Lab Chip 13:61011–26 [Google Scholar]
  79. Miyaguchi H, Tokeshi M, Kikutani Y, Hibara A, Inoue H, Kitamori T. 79.  2006. Microchip-based liquid-liquid extraction for gas-chromatography analysis of amphetamine-type stimulants in urine. J. Chromatogr. A 1129:1105–10 [Google Scholar]
  80. Wang XC, Yang XH, Zrang XM. 80.  2006. Preparation of the capillary-based microchips for solid phase extraction by using the monolithic frits prepared by UV-initiated polymerization. Anal. Sci. 22:81099–104 [Google Scholar]
  81. Yang YN, Li C, Lee KH, Craighead HG. 81.  2005. Coupling on-chip solid-phase extraction to electrospray mass spectrometry through an integrated electrospray tip. Electrophoresis 26:193622–30 [Google Scholar]
  82. Ellerbee AK, Phillips ST, Siegel AC, Mirica KA, Martinez AW. 82.  et al. 2009. Quantifying colorimetric assays in paper-based microfluidic devices by measuring the transmission of light through paper. Anal. Chem. 81:208447–52 [Google Scholar]
  83. Martinez AW, Phillips ST, Carrilho E, Thomas SW 3rd, Sindi H, Whitesides GM. 83.  2008. Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis. Anal. Chem. 80:103699–707 [Google Scholar]
  84. Sechi D, Greer B, Johnson J, Hashemi N. 84.  2013. Three-dimensional paper-based microfluidic device for assays of protein and glucose in urine. Anal. Chem. 85:2210733–37 [Google Scholar]
  85. von Lode P. 85.  2005. Point-of-care immunotesting: approaching the analytical performance of central laboratory methods. Clin. Biochem. 38:7591–606 [Google Scholar]
  86. Helton KL, Nelson KE, Fu E, Yager P. 86.  2008. Conditioning saliva for use in a microfluidic biosensor. Lab Chip 8:111847–51 [Google Scholar]
  87. Herr AE, Hatch AV, Throckmorton DJ, Tran HM, Brennan JS. 87.  et al. 2007. Microfluidic immunoassays as rapid saliva-based clinical diagnostics. PNAS 104:135268–73 [Google Scholar]
  88. Sorsa T, Tjaderhane L, Salo T. 88.  2004. Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis. 10:6311–18 [Google Scholar]
  89. Jokerst JV, Raamanathan A, Christodoulides N, Floriano PN, Pollard AA. 89.  et al. 2009. Nano-bio-chips for high performance multiplexed protein detection: Determinations of cancer biomarkers in serum and saliva using quantum dot bioconjugate labels. Biosens. Bioelectron. 24:123622–29 [Google Scholar]
  90. Andreou C, Hoonejani MR, Barmi MR, Moskovits M, Meinhart CD. 90.  2013. Rapid detection of drugs of abuse in saliva using surface enhanced Raman spectroscopy and microfluidics. ACS Nano 7:87157–64 [Google Scholar]
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