Biochemical Analysis Techniques Integrated on Microfluidic Chips and Their Applications

Chapter
Part of the Integrated Analytical Systems book series (ANASYS)

Abstract

Biochemical analysis plays an essential role in understanding mechanism of life activities and giving biological insights into life process. Microfluidic technology explores new paradigms in biochemical analysis field because of its good incorporation with existing analytical techniques. In this chapter, we summarize the typical analytical methods integrated onto microfluidic platforms. Optical, electrical, magnetic and acoustic techniques have been highlighted. Applications of these microfluidic analytical methods into genetic and protein analysis also have been discussed. At last, the challenges and future directions about microfluidics-based biochemical analysis development have been remarked.

Keywords

Biochemical analysis Optical detector Electronic manipulation Magnetic operation Surface acoustic wave Genetic analysis Protein analysis 

References

  1. 1.
    El-Ali J, Sorger PK, Jensen KF (2006) Cells on chips. Nature 442(7101):403–411. doi: 10.1038/nature05063 CrossRefGoogle Scholar
  2. 2.
    Rosenkilde MM, Schwartz TW (2004) The chemokine system—a major regulator of angiogenesis in health and disease. APMIS 112(7–8):481–495. doi: 10.1111/j.1600-0463.2004.apm11207-0808.x CrossRefGoogle Scholar
  3. 3.
    Liu L, Ratner BD, Sage EH, Jiang S (2007) Endothelial cell migration on surface-density gradients of fibronectin, VEGF, or both proteins. Langmuir 23(22):11168–11173. doi: 10.1021/la701435x CrossRefGoogle Scholar
  4. 4.
    Forhead AJ, Fowden AL (2014) Thyroid hormones in fetal growth and prepartum maturation. J Endocrinol 221(3):R87–R103. doi: 10.1530/joe-14-0025 CrossRefGoogle Scholar
  5. 5.
    Belloni AS, Albertin G, Forneris ML, Nussdorfer GG (2001) Proadrenomedullin-derived peptides as autocrine-paracrine regulators of cell growth. Histol Histopathol 16(4):1263–1274Google Scholar
  6. 6.
    Jamora C, Fuchs E (2002) Intercellular adhesion, signalling and the cytoskeleton. Nat Cell Biol 4(4):E101–E108. doi: 10.1038/ncb0402-e101 CrossRefGoogle Scholar
  7. 7.
    Geiger B, Bershadsky A, Pankov R, Yamada KM (2001) Transmembrane extracellular matrix-cytoskeleton crosstalk. Nat Rev Mol Cell Bio 2(11):793–805. doi: 10.1038/35099066 CrossRefGoogle Scholar
  8. 8.
    Fatehullah A, Tan SH, Barker N (2016) Organoids as an in vitro model of human development and disease. Nat Cell Biol 18(3):246–254CrossRefGoogle Scholar
  9. 9.
    Li Y, Zhou Y, Wang H, Perrett S, Zhao Y, Tang Z, Nie G (2011) Chirality of glutathione surface coating affects the cytotoxicity of quantum dots. Angew. Chem Int Edit 50(26):5860–5864. doi: 10.1002/anie.201008206
  10. 10.
    Hoshino A, Fujioka K, Oku T, Suga M, Sasaki YF, Ohta T, Yasuhara M, Suzuki K, Yamamoto K (2004) Physicochemical properties and cellular toxicity of nanocrystal quantum dots depend on their surface modification. Nano Lett 4(11):2163–2169. doi: 10.1021/nl048715d CrossRefGoogle Scholar
  11. 11.
    Culbertson CT, Mickleburgh TG, Stewart-James SA, Sellens KA, Pressnall M (2014) Micro total analysis systems: Fundamental advances and biological applications. Anal Chem 86 (1, SI):95–118. doi: 10.1021/ac403688g
  12. 12.
    Novo P, Dell’Aica M, Janasek D, Zahedi RP (2016) High spatial and temporal resolution cell manipulation techniques in microchannels. Analyst 141(6):1888–1905. doi: 10.1039/c6an00027d CrossRefGoogle Scholar
  13. 13.
    Patabadige DEW, Jia S, Sibbitts J, Sadeghi J, Sellens K, Culbertson CT (2016) Micro total analysis systems: Fundamental advances and applications. Anal Chem 88(1):320–338. doi: 10.1021/acs.analchem.5b04310 CrossRefGoogle Scholar
  14. 14.
    Kovarik ML, Gach PC, Ornoff DM, Wang Y, Balowski J, Farrag L, Allbritton NL (2012) Micro total analysis systems for cell biology and biochemical assays. Anal Chem 84(2):516–540. doi: 10.1021/ac202611x CrossRefGoogle Scholar
  15. 15.
    Kovarik ML, Ornoff DM, Melvin AT, Dobes NC, Wang Y, Dickinson AJ, Gach PC, Shah PK, Allbritton NL (2013) Micro total analysis systems: Fundamental advances and applications in the laboratory, clinic, and field. Anal Chem 85(2, SI):451–472. doi: 10.1021/ac3031543
  16. 16.
    Huh D, Hamilton GA, Ingber DE (2011) From 3D cell culture to organs-on-chips. Trends Cell Biol 21(12):745–754. doi: 10.1016/j.tcb.2011.09.005 CrossRefGoogle Scholar
  17. 17.
    Sung KE, Beebe DJ (2014) Microfluidic 3D models of cancer. Adv Drug Deliver Rev 79–80:68–78. doi: 10.1016/j.addr.2014.07.002 CrossRefGoogle Scholar
  18. 18.
    van Duinen V, Trietsch SJ, Joore J, Vulto P, Hankemeier T (2015) Microfluidic 3D cell culture: From tools to tissue models. Curr Opin Biotech 35:118–126. doi: 10.1016/j.copbio.2015.05.002 CrossRefGoogle Scholar
  19. 19.
    Bersini S, Jeon JS, Dubini G, Arrigoni C, Chung S, Charest JL, Moretti M, Kamm RD (2014) A microfluidic 3D invitro model for specificity of breast cancer metastasis to bone. Biomaterials 35(8):2454–2461. doi: 10.1016/j.biomaterials.2013.11.050 CrossRefGoogle Scholar
  20. 20.
    Unser AM, Mooney B, Corr DT, Tseng Y, Xie Y (2016) 3D brown adipogenesis to create “Brown-Fat-in-Microstrands”. Biomaterials 75:123–134. doi: 10.1016/j.biomaterials.2015.10.017 CrossRefGoogle Scholar
  21. 21.
    Maschmeyer I, Lorenz AK, Schimek K, Hasenberg T, Ramme AP, Hubner J, Lindner M, Drewell C, Bauer S, Thomas A, Sambo NS, Sonntag F, Lauster R, Marx U (2015) A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab Chip 15(12):2688–2699. doi: 10.1039/c5lc00392j CrossRefGoogle Scholar
  22. 22.
    Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE (2010) Reconstituting organ-level lung functions on a chip. Science 328(5986):1662–1668. doi: 10.1126/science.1188302 CrossRefGoogle Scholar
  23. 23.
    Wilmer MJ, Ng CP, Lanz HL, Vulto P, Suter-Dick L, Masereeuw R (2016) Kidney-on-a-chip technology for drug-incuced nephrotoxiciy screening. Trends Biotechnol 34(2):156–170. doi: 10.1016/j.tibtech.2015.11.001 CrossRefGoogle Scholar
  24. 24.
    Wu J, He Z, Chen Q, Lin J-M (2016) Biochemical analysis on microfluidic chips. TrAC. Trends Anal Chem 80:213–231. doi: 10.1016/j.trac.2016.03.013 CrossRefGoogle Scholar
  25. 25.
    Choi J, Song H, Sung JH, Kim D, Kim K (2016) Microfluidic assay-based optical measurement techniques for cell analysis: A review of recent progress. Biosens Bioelectron 77:227–236. doi: 10.1016/j.bios.2015.07.068 CrossRefGoogle Scholar
  26. 26.
    Noh J, Kim HC, Chung TD (2011) Biosensors in microfluidic chips.In Lin BC (ed)Microfluidics: Technologies and applications, Vol. 304, Topics in Current Chemistry, 1st edn. Springer, BerlinGoogle Scholar
  27. 27.
    Schulz CM, Ruzicka J (2002) Real-time determination of glucose consumption by live cells using a lab-on-valve system with an integrated microbioreactor. Analyst 127(10):1293–1298. doi: 10.1039/b206907p CrossRefGoogle Scholar
  28. 28.
    Schulz CM, Scampavia L, Ruzicka J (2002) Real-time monitoring of lactate extrusion and glucose consumption of cultured cells using a lab-on-valve system. Analyst 127(12):1583–1588. doi: 10.1039/b209371p CrossRefGoogle Scholar
  29. 29.
    Srinivasan V, Pamula VK, Fair RB (2004) Droplet-based microfluidic lab-on-a-chip for glucose detection. Anal Chim Acta 507(1):145–150. doi: 10.1016/j.aca.2003.12.030 CrossRefGoogle Scholar
  30. 30.
    Srinivasan V, Pamula VK, Fair RB (2004) An integrated digital microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluids. Lab Chip 4(4):310–315. doi: 10.1039/b403341h CrossRefGoogle Scholar
  31. 31.
    Lee W, Kwon D, Choi W, Jung GY, Au AK, Folch A, Jeon S (2015) 3D-Printed microfluidic device for the detection of pathogenic bacteria using size-based separation in helical channel with trapezoid Cross-Section. Sci Rep 5:7717. doi: 10.1038/srep07717 CrossRefGoogle Scholar
  32. 32.
    Chalfie M, Tu Y, Euskirchen G, Ward WW, Prasher DC (1994) Green fluorescent protein as a marker for gene expression. Science 263(5148):802–805. doi: 10.1126/science.8303295 CrossRefGoogle Scholar
  33. 33.
    Kijanka GS, Dimov IK, Burger R, Ducrée J (2015) Real-time monitoring of cell migration, phagocytosis and cell surface receptor dynamics using a novel, live-cell opto-microfluidic technique. Anal Chim Acta 872:95–99. doi: 10.1016/j.aca.2014.12.035 CrossRefGoogle Scholar
  34. 34.
    Valero A, Merino F, Wolbers F, Luttge R, Vermes I, Andersson H, van den Berg A (2005) Apoptotic cell death dynamics of HL60 cells studied using a microfluidic cell trap device. Lab Chip 5(1):49–55. doi: 10.1039/b415813j CrossRefGoogle Scholar
  35. 35.
    Lockwood SY, Meisel JE, Monsma JFJ, Spence DM (2016) A Diffusion-Based and dynamic 3D-Printed device that enables parallel in vitro pharmacokinetic profiling of molecules. Anal Chem 88(3):1864–1870. doi: 10.1021/acs.analchem.5b04270 CrossRefGoogle Scholar
  36. 36.
    Mazutis L, Gilbert J, Ung WL, Weitz DA, Griffiths AD, Heyman JA (2013) Single-cell analysis and sorting using droplet-based microfluidics. Nat Protoc 8(5):870–891. doi: 10.1038/nprot.2013.046 CrossRefGoogle Scholar
  37. 37.
    Wu J, Chen Q, Liu W, Zhang Y, Lin J-M (2012) Cytotoxicity of quantum dots assay on a microfluidic 3D-culture device based on modeling diffusion process between blood vessels and tissues. Lab Chip 12(18):3474–3480. doi: 10.1039/c2lc40502d CrossRefGoogle Scholar
  38. 38.
    Wu J, Chen Q, Liu W, Lin J-M (2013) A simple and versatile microfluidic cell density gradient generator for quantum dot cytotoxicity assay. Lab Chip 13(10):1948–1954. doi: 10.1039/c3lc00041a CrossRefGoogle Scholar
  39. 39.
    Gashti MP, Asselin J, Barbeau J, Boudreau D, Greener J (2016) A microfluidic platform with pH imaging for chemical and hydrodynamic stimulation of intact oral biofilms. Lab Chip 16(8):1412–1419. doi: 10.1039/c5lc01540e CrossRefGoogle Scholar
  40. 40.
    Zhu X, Xu L, Wu T, Xu A, Zhao M, Liu S (2014) Continuous monitoring of bisulfide variation in microdialysis effluents by on-line droplet-based microfluidic fluorescent sensor. Biosens Bioelectron 55:438–445. doi: 10.1016/j.bios.2013.12.056 CrossRefGoogle Scholar
  41. 41.
    Kim S, Streets AM, Lin RR, Quake SR, Weiss S, Majumdar DS (2011) High-throughput single-molecule optofluidic analysis. Nat Methods 8(3):242–245. doi: 10.1038/nmeth.1569 CrossRefGoogle Scholar
  42. 42.
    Chen C, Ahmed M, Häfner T, Klämpfl F, Stelzle F, Schmidt M (2016) Fabrication of a turbid optofluidic phantom device with tunable μ a and μ s to simulate cutaneous vascular perfusion. Sci Rep 6:30567. doi: 10.1038/srep30567 CrossRefGoogle Scholar
  43. 43.
    Valero A, Braschler T, Renaud P (2010) A unified approach to dielectric single cell analysis: impedance and dielectrophoretic force spectroscopy. Lab Chip 10(17):2216–2225. doi: 10.1039/c003982a CrossRefGoogle Scholar
  44. 44.
    Simon P, Frankowski M, Bock N, Neukammer J (2016) Label-free whole blood cell differentiation based on multiple frequency AC impedance and light scattering analysis in a micro flow cytometer. Lab Chip 16(12):2326–2338. doi: 10.1039/c6lc00128a CrossRefGoogle Scholar
  45. 45.
    Zhou Y, Basu S, Laue E, Seshia AA (2016) Single cell studies of mouse embryonic stem cell (mESC) differentiation by electrical impedance measurements in a microfluidic device. Biosens Bioelectron 81:249–258. doi: 10.1016/j.bios.2016.02.069 CrossRefGoogle Scholar
  46. 46.
    Cheng I, Huang W, Chen T, Liu C, Lin Y, Su W (2015) Antibody-free isolation of rare cancer cells from blood based on 3D lateral dielectrophoresis. Lab Chip 15(14):2950–2959. doi: 10.1039/c5lc00120j CrossRefGoogle Scholar
  47. 47.
    Kim SH, Fujii T (2016) Efficient analysis of a small number of cancer cells at the single-cell level using an electroactive double-well array. Lab Chip 16(13):2440–2449. doi: 10.1039/c6lc00241b CrossRefGoogle Scholar
  48. 48.
    Adekanmbi EO, Srivastava SK (2016) Dielectrophoretic applications for disease diagnostics using lab-on-a-chip platforms. Lab Chip 16(12):2148–2167. doi: 10.1039/c6lc00355a CrossRefGoogle Scholar
  49. 49.
    Liu Q, Lin X, Lin L, Yi L, Li H, Lin J-M (2015) A comparative study of three different nucleic acid amplification techniques combined with microchip electrophoresis for HPV16 E6/E7 mRNA detection. Analyst 140(19):6736–6741. doi: 10.1039/c5an00944h CrossRefGoogle Scholar
  50. 50.
    Deng Y, Yi L, Lin X, Lin L, Li H, Lin J-M (2015) A non-invasive genomic diagnostic method for bladder cancer using size-based filtration and microchip electrophoresis. Talanta 144:136–144. doi: 10.1016/j.talanta.2015.05.065 CrossRefGoogle Scholar
  51. 51.
    Sheng P, Wen W (2012) Electrorheological fluids: Mechanisms, dynamics, and microfluidics applications. Annu Rev Fluid Mech 44:143–174. doi: 10.1146/annurev-fluid-120710-101024 CrossRefGoogle Scholar
  52. 52.
    Wang L, Zhang M, Li J, Gong X, Wen W (2010) Logic control of microfluidics with smart colloid. Lab Chip 10(21):2869–2874. doi: 10.1039/c0lc00003e CrossRefGoogle Scholar
  53. 53.
    Zhang M, Wang L, Wang X, Wu J, Li J, Gong X, Qin J, Li W, Wen W (2011) Microdroplet-based universal logic gates by electrorheological fluid. Soft Matter 7(16):7493–7497. doi: 10.1039/c1sm05687e CrossRefGoogle Scholar
  54. 54.
    van Reenen A, de Jong AM, den Toonder JMJ, Prins MWJ (2014) Integrated lab-on-chip biosensing systems based on magnetic particle actuation—a comprehensive review. Lab Chip 14(12):1966–1986. doi: 10.1039/c3lc51454d CrossRefGoogle Scholar
  55. 55.
    Jamshaid T, Neto ETT, Eissa MM, Zine N, Kunita MH, El-Salhi AE, Elaissari A (2016) Magnetic particles: From preparation to lab-on-a-chip, biosensors, microsystems and microfluidics applications. TrAC. Trends Anal Chem 79:344–362. doi: 10.1016/j.trac.2015.10.022 CrossRefGoogle Scholar
  56. 56.
    Zhou B, Xu W, Syed AA, Chau Y, Chen L, Chew B, Yassine O, Wu X, Gao Y, Zhang J, Xiao X, Kosel J, Zhang X, Yao Z, Wen W (2015) Design and fabrication of magnetically functionalized flexible micropillar arrays for rapid and controllable microfluidic mixing. Lab Chip 15(9):2125–2132. doi: 10.1039/c5lc00173k CrossRefGoogle Scholar
  57. 57.
    Kahkeshani S, Di Carlo D (2016) Drop formation using ferrofluids driven magnetically in a step emulsification device. Lab Chip 16(13):2474–2480. doi: 10.1039/c6lc00645k CrossRefGoogle Scholar
  58. 58.
    Shi X, Chen C, Gao W, Chao S, Meldrum DR (2015) Parallel RNA extraction using magnetic beads and a droplet array. Lab Chip 15(4):1059–1065. doi: 10.1039/c4lc01111b CrossRefGoogle Scholar
  59. 59.
    Chao C, Wang C, Che Y, Kao C, Wu J, Lee G (2016) An integrated microfluidic system for diagnosis of the resistance of Helicobacter pylori to quinolone-based antibiotics. Biosens Bioelectron 78:281–289. doi: 10.1016/j.bios.2015.11.046 CrossRefGoogle Scholar
  60. 60.
    Hejazian M, Li W, Nguyen N (2015) Lab on a chip for continuous-flow magnetic cell separation. Lab Chip 15(4):959–970. doi: 10.1039/c4lc01422g CrossRefGoogle Scholar
  61. 61.
    Figueredo F, Garcia PT, Corton E, Coltro WKT (2016) Enhanced analytical performance of paper microfluidic devices by using Fe3O4 nanoparticles, MWCNT, and graphene oxide. ACS Appl Mater Inter 8(1):11–15. doi: 10.1021/acsami.5b10027 CrossRefGoogle Scholar
  62. 62.
    Liu F, Pawan KC, Zhang G, Zhe J (2016) Microfluidic magnetic bead assay for cell detection. Anal Chem 88(1):711–717. doi: 10.1021/acs.analchem.5b02716 CrossRefGoogle Scholar
  63. 63.
    Chen J, Kang Z, Wang G, Loo JFC, Kong SK, Ho H (2015) Optofluidic guiding, valving, switching and mixing based on plasmonic heating in a random gold nanoisland substrate. Lab Chip 15(11):2504–2512. doi: 10.1039/c5lc00406c CrossRefGoogle Scholar
  64. 64.
    Monat C, Domachuk P, Eggleton BJ (2007) Integrated optofluidics: A new river of light. Nat Photonics 1(2):106–114. doi: 10.1038/nphoton.2006.96 CrossRefGoogle Scholar
  65. 65.
    Schmidt H, Hawkins AR (2011) The photonic integration of non-solid media using optofluidics. Nat Photonics 5(10):598–604. doi: 10.1038/nphoton.2011.163 CrossRefGoogle Scholar
  66. 66.
    Zhu H, Lin X, Su Y, Dong H, Wu J (2015) Screen-printed microfluidic dielectrophoresis chip for cell separation. Biosens Bioelectron 63:371–378. doi: 10.1016/j.bios.2014.07.072 CrossRefGoogle Scholar
  67. 67.
    Anand RK, Johnson ES, Chiu DT (2015) Negative dielectrophoretic capture and repulsion of single cells at a bipolar electrode: The impact of faradaic ion enrichment and depletion. J Am Chem Soc 137(2):776–783. doi: 10.1021/ja5102689 CrossRefGoogle Scholar
  68. 68.
    Hai A, Shappir J, Spira ME (2010) In-cell recordings by extracellular microelectrodes. Nat Methods 7(3):200–202. doi: 10.1038/nmeth.1420 CrossRefGoogle Scholar
  69. 69.
    Cornaglia M, Trouillon R, Tekin HC, Lehnert T, Gijs MAM (2014) Magnetic particle-scanning for ultrasensitive immunodetection On-Chip. Anal Chem 86(16):8213–8223. doi: 10.1021/ac501568g CrossRefGoogle Scholar
  70. 70.
    Zhu G, Nguyen N (2012) Rapid magnetofluidic mixing in a uniform magnetic field. Lab Chip 12(22):4772–4780. doi: 10.1039/c2lc40818j CrossRefGoogle Scholar
  71. 71.
    Li S, Guo F, Chen Y, Ding X, Li P, Wang L, Cameron CE, Huang TJ (2014) Standing surface acoustic wave based cell coculture. Anal Chem 86(19):9853–9859. doi: 10.1021/ac502453z CrossRefGoogle Scholar
  72. 72.
    Yeo LY, Friend JR (2014) Surface acoustic wave microfluidics. Annu Rev Fluid Mech 46(1):379–406. doi: 10.1146/annurev-fluid-010313-141418 CrossRefGoogle Scholar
  73. 73.
    Ding X, Li P, Lin SS, Stratton ZS, Nama N, Guo F, Slotcavage D, Mao X, Shi J, Costanzo F, Huang TJ (2013) Surface acoustic wave microfluidics. Lab Chip 13(18):3626–3649. doi: 10.1039/c3lc50361e CrossRefGoogle Scholar
  74. 74.
    Gedge M, Hill M (2012) Acoustofluidics 17: Theory and applications of surface acoustic wave devices for particle manipulation. Lab Chip 12(17):2998–3007. doi: 10.1039/c2lc40565b CrossRefGoogle Scholar
  75. 75.
    Wiklund M, Green R, Ohlin M (2012) Acoustofluidics 14: applications of acoustic streaming in microfluidic devices. Lab Chip 12(14):2438–2451. doi: 10.1039/c2lc40203c CrossRefGoogle Scholar
  76. 76.
    Destgeer G, Sung HJ (2015) Recent advances in microfluidic actuation and micro-object manipulation via surface acoustic waves. Lab Chip 15(13):2722–2738. doi: 10.1039/c5lc00265f CrossRefGoogle Scholar
  77. 77.
    Collins DJ, Neild A, Ai Y (2016) Highly focused high-frequency travelling surface acoustic waves (SAW) for rapid single-particle sorting. Lab Chip 16(3):471–479. doi: 10.1039/c5lc01335f CrossRefGoogle Scholar
  78. 78.
    Ma Z, Collins DJ, Ai Y (2016) Detachable acoustofluidic system for particle separation via a traveling surface acoustic wave. Anal Chem 88(10):5316–5323. doi: 10.1021/acs.analchem.6b00605 CrossRefGoogle Scholar
  79. 79.
    Destgeer G, Cho H, Ha BH, Jung JH, Park J, Sung HJ (2016) Acoustofluidic particle manipulation inside a sessile droplet: four distinct regimes of particle concentration. Lab Chip 16(4):660–667. doi: 10.1039/c5lc01104c CrossRefGoogle Scholar
  80. 80.
    Shilton RJ, Travagliati M, Beltram F, Cecchini M (2014) Nanoliter-droplet acoustic streaming via ultra high frequency surface acoustic waves. Adv Mater 26(29):4941–4946. doi: 10.1002/adma.201400091 CrossRefGoogle Scholar
  81. 81.
    Gracioso Martins AM, Glass NR, Harrison S, Rezk AR, Porter NA, Carpenter PD, Du Plessis J, Friend JR, Yeo LY (2014) Toward complete miniaturisation of flow injection analysis systems: microfluidic enhancement of chemiluminescent detection. Anal Chem 86(21):10812–10819. doi: 10.1021/ac502878p CrossRefGoogle Scholar
  82. 82.
    Lin SS, Mao X, Huang TJ (2012) Surface acoustic wave (SAW) acoustophoresis: now and beyond. Lab Chip 12(16):2766–2770. doi: 10.1039/c2lc90076a CrossRefGoogle Scholar
  83. 83.
    Petersson F, Nilsson A, Holm C, Jonsson H, Laurell T (2004) Separation of lipids from blood utilizing ultrasonic standing waves in microfluidic channels. Analyst 129(10):938–943. doi: 10.1039/b409139f CrossRefGoogle Scholar
  84. 84.
    Laurell T, Petersson F, Nilsson A (2007) Chip integrated strategies for acoustic separation and manipulation of cells and particles. Chem Soc Rev 36(3):492–506. doi: 10.1039/B601326K CrossRefGoogle Scholar
  85. 85.
    Lenshof A, Laurell T (2010) Continuous separation of cells and particles in microfluidic systems. Chem Soc Rev 39(3):1203–1217. doi: 10.1039/b915999c CrossRefGoogle Scholar
  86. 86.
    Nawaz AA, Chen Y, Narna N, Nissly RH, Ren L, Ozcelik A, Wang L, McCoy JP, Levine SJ, Huang TJ (2015) Acoustofluidic fluorescence activated cell sorter. Anal Chem 87(24):12051–12058. doi: 10.1021/acs.analchem.5b02398 CrossRefGoogle Scholar
  87. 87.
    Ren L, Chen Y, Li P, Mao Z, Huang P, Rufo J, Guo F, Wang L, McCoy JP, Levine SJ, Huang TJ (2015) A high-throughput acoustic cell sorter. Lab Chip 15(19):3870–3879. doi: 10.1039/c5lc00706b CrossRefGoogle Scholar
  88. 88.
    Li S, Ding X, Mao Z, Chen Y, Nama N, Guo F, Li P, Wang L, Cameron CE, Huang TJ (2015) Standing surface acoustic wave (SSAW)-based cell washing. Lab Chip 15(1):331–338. doi: 10.1039/c4lc00903g CrossRefGoogle Scholar
  89. 89.
    Li P, Mao Z, Peng Z, Zhou L, Chen Y, Huang P, Truica CI, Drabick JJ, El-Deiry WS, Dao M, Suresh S, Huang TJ (2015) Acoustic separation of circulating tumor cells. Proc Natl Acad Sci U S A 112(16):4970–4975. doi: 10.1073/pnas.1504484112 CrossRefGoogle Scholar
  90. 90.
    Chen Y, Wu M, Ren L, Liu J, Whitley PH, Wang L, Huang TJ (2016) High-throughput acoustic separation of platelets from whole blood. Lab Chip 16:3466–3472. doi: 10.1039/c6lc00682e CrossRefGoogle Scholar
  91. 91.
    Lin X, Sun X, Luo S, Liu B, Yang C (2016) Development of DNA-based signal amplification and microfluidic technology for protein assay: A review. TrAC. Trends Anal Chem 80:132–148. doi: 10.1016/j.trac.2016.02.020 CrossRefGoogle Scholar
  92. 92.
    Zhang Y, Jiang H (2016) A review on continuous-flow microfluidic PCR in droplets: Advances, challenges and future. Anal Chim Acta 914:7–16. doi: 10.1016/j.aca.2016.02.006 CrossRefGoogle Scholar
  93. 93.
    Dalerba P, Kalisky T, Sahoo D, Rajendran PS, Rothenberg ME, Leyrat AA, Sim S, Okamoto J, Johnston DM, Qian D, Zabala M, Bueno J, Neff NF, Wang J, Shelton AA, Visser B, Hisamori S, Shimono Y, van de Wetering M, Clevers H, Clarke MF, Quake SR (2011) Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nat Biotechnol 29(12):1120–1127. doi: 10.1038/nbt.2038 CrossRefGoogle Scholar
  94. 94.
    White AK, VanInsberghe M, Petriv OI, Hamidi M, Sikorski D, Marra MA, Piret J, Aparicio S, Hansen CL (2011) High-throughput microfluidic single-cell RT-qPCR. Proc Natl Acad Sci U S A 108(34):13999–14004. doi: 10.1073/pnas.1019446108 CrossRefGoogle Scholar
  95. 95.
    Lin X, Wu J, Li H, Wang Z, Lin J-M (2013) Determination of mini-short tandem repeat (miniSTR) loci by using the combination of polymerase chain reaction (PCR) and microchip electrophoresis. Talanta 114:131–137. doi: 10.1016/j.talanta.2013.04.012 CrossRefGoogle Scholar
  96. 96.
    Lin X, Wu J, Liu W, Li H, Wang Z, Lin J-M (2013) Detection of BCR-ABL using one step reverse transcriptase-polymerase chain reaction and microchip electrophoresis. Methods 64(3):250–254. doi: 10.1016/j.ymeth.2013.05.010 CrossRefGoogle Scholar
  97. 97.
    Zhu Z, Jenkins G, Zhang W, Zhang M, Guan Z, Yang CJ (2012) Single-molecule emulsion PCR in microfluidic droplets. Anal Bioanal Chem 403(8):2127–2143. doi: 10.1007/s00216-012-5914-x CrossRefGoogle Scholar
  98. 98.
    Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, Berka J, Braverman MS, Chen Y, Chen Z, Dewell SB, Du L, Fierro JM, Gomes XV, Godwin BC, He W, Helgesen S, Ho CH, Irzyk GP, Jando SC, Alenquer MLI, Jarvie TP, Jirage KB, Kim J, Knight JR, Lanza JR, Leamon JH, Lefkowitz SM, Lei M, Li J, Lohman KL, Lu H, Makhijani VB, McDade KE, McKenna MP, Myers EW, Nickerson E, Nobile JR, Plant R, Puc BP, Ronan MT, Roth GT, Sarkis GJ, Simons JF, Simpson JW, Srinivasan M, Tartaro KR, Tomasz A, Vogt KA, Volkmer GA, Wang SH, Wang Y, Weiner MP, Yu P, Begley RF, Rothberg JM (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature 437(7057):376–380. doi: 10.1038/nature03959 Google Scholar
  99. 99.
    Tanaka H, Yamamoto S, Nakamura A, Nakashoji Y, Okura N, Nakamoto N, Tsukagoshi K, Hashimoto M (2015) Hands-off preparation of monodisperse emulsion droplets using a poly(dimethylsiloxane) microfluidic chip for droplet digital PCR. Anal Chem 87(8):4134–4143. doi: 10.1021/ac503169h CrossRefGoogle Scholar
  100. 100.
    Wang P, Jing F, Li G, Wu Z, Cheng Z, Zhang J, Zhang H, Jia C, Jin Q, Mao H, Zhao J (2015) Absolute quantification of lung cancer related microRNA by droplet digital PCR. Biosens Bioelectron 74:836–842. doi: 10.1016/j.bios.2015.07.048 CrossRefGoogle Scholar
  101. 101.
    Zhu H, Wang G, Xie D, Cai B, Liu Y, Zhao X (2014) Au nanoparticles enhanced fluorescence detection of DNA hybridization in picoliter microfluidic droplets. Biomed Microdevices 16(3):479–485. doi: 10.1007/s10544-014-9850-8 CrossRefGoogle Scholar
  102. 102.
    Wang J, Aki M, Onoshima D, Arinaga K, Kaji N, Tokeshi M, Fujita S, Yokoyama N, Baba Y (2014) Microfluidic biosensor for the detection of DNA by fluorescence enhancement and the following streptavidin detection by fluorescence quenching. Biosens Bioelectron 51:280–285. doi: 10.1016/j.bios.2013.07.058 CrossRefGoogle Scholar
  103. 103.
    Li H, Fang X, Cao H, Kong J (2016) Paper-based fluorescence resonance energy transfer assay for directly detecting nucleic acids and proteins. Biosens Bioelectron 80:79–83. doi: 10.1016/j.bios.2015.12.065 CrossRefGoogle Scholar
  104. 104.
    Lubin AA, Plaxco KW (2010) Folding-based electrochemical biosensors: the case for responsive nucleic acid architectures. Accounts Chem Res 43(4):496–505. doi: 10.1021/ar900165x CrossRefGoogle Scholar
  105. 105.
    Fan CH, Plaxco KW, Heeger AJ (2003) Electrochemical interrogation of conformational changes as a reagentless method for the sequence-specific detection of DNA. Proc Natl Acad Sci U S A 100(16):9134–9137. doi: 10.1073/pnas.1633515100 CrossRefGoogle Scholar
  106. 106.
    Xiao Y, Lubin AA, Baker BR, Plaxco KW, Heeger AJ (2006) Single-step electronic detection of femtomolar DNA by target-induced strand displacement in an electrode-bound duplex. Proc Natl Acad Sci U S A 103(45):16677–16680. doi: 10.1073/pnas.0607693103 CrossRefGoogle Scholar
  107. 107.
    Ben-Yoav H, Dykstra PH, Bentley WE, Ghodssi R (2015) A controlled microfluidic electrochemical lab-on-a-chip for label-free diffusion-restricted DNA hybridization analysis. Biosens Bioelectron 64:579–585. doi: 10.1016/j.bios.2014.09.069 CrossRefGoogle Scholar
  108. 108.
    Maerkl SJ (2011) Next generation microfluidic platforms for high-throughput protein biochemistry. Curr Opin Biotech 22(1):59–65. doi: 10.1016/j.copbio.2010.08.010 CrossRefGoogle Scholar
  109. 109.
    Wang C, Ouyang J, Wang Y, Ye D, Xia X (2014) Sensitive assay of protease activity on a micro/nanofluidics preconcentrator fused with the fluorescence resonance energy transfer detection technique. Anal Chem 86(6):3216–3221. doi: 10.1021/ac500196s CrossRefGoogle Scholar
  110. 110.
    Wang C, Shi Y, Wang J, Pang J, Xia X (2015) Ultrasensitive protein concentration detection on a micro/nanofluidic enrichment chip using fluorescence quenching. ACS Appl Mater Inter 7(12):6835–6841. doi: 10.1021/acsami.5b00383 CrossRefGoogle Scholar
  111. 111.
    Jiang L, Zeng Y, Sun Q, Sun Y, Guo Z, Qu JY, Yao S (2015) Microsecond protein folding events revealed by time-resolved fluorescence resonance energy transfer in a microfluidic mixer. Anal Chem 87(11):5589–5595. doi: 10.1021/acs.analchem.5b00366 CrossRefGoogle Scholar
  112. 112.
    Benz C, Retzbach H, Nagl S, Belder D (2013) Protein-protein interaction analysis in single microfluidic droplets using FRET and fluorescence lifetime detection. Lab Chip 13(14):2808–2814. doi: 10.1039/c3lc00057e CrossRefGoogle Scholar
  113. 113.
    Homola J (2008) Surface plasmon resonance sensors for detection of chemical and biological species. Chem Rev 108(2):462–493. doi: 10.1021/cr068107d CrossRefGoogle Scholar
  114. 114.
    Im H, Sutherland JN, Maynard JA, Oh S (2012) Nanohole-based surface plasmon resonance instruments with improved spectral resolution quantify a broad range of antibody-ligand binding kinetics. Anal Chem 84(4):1941–1947. doi: 10.1021/ac300070t CrossRefGoogle Scholar
  115. 115.
    Guo T, Liu F, Liang X, Qiu X, Huang Y, Xie C, Xu P, Mao W, Guan B, Albert J (2016) Highly sensitive detection of urinary protein variations using tilted fiber grating sensors with plasmonic nanocoatings. Biosens Bioelectron 78:221–228. doi: 10.1016/j.bios.2015.11.047 CrossRefGoogle Scholar
  116. 116.
    Xiao B, Pradhan SK, Santiago KC, Rutherford GN, Pradhan AK (2016) Topographically engineered large scale nanostructures for plasmonic biosensing. Sci Rep 6:24385. doi: 10.1038/srep24385 CrossRefGoogle Scholar
  117. 117.
    Tassa C, Liong M, Hilderbrand S, Sandler JE, Reiner T, Keliher EJ, Weissleder R, Shaw SY (2012) On-chip bioorthogonal chemistry enables immobilization of in situ modified nanoparticles and small molecules for label-free monitoring of protein binding and reaction kinetics. Lab Chip 12(17):3103–3110. doi: 10.1039/c2lc40337d CrossRefGoogle Scholar
  118. 118.
    Krivitsky V, Hsiung L, Lichtenstein A, Brudnik B, Kantaev R, Elnathan R, Pevzner A, Khatchtourints A, Patolsky F (2012) Si nanowires forest-based on-chip biomolecular filtering, separation and preconcentration devices: nanowires do it all. Nano Lett 12(9):4748–4756. doi: 10.1021/nl3021889 CrossRefGoogle Scholar
  119. 119.
    Lin X, Leung K, Lin L, Lin L, Lin S, Leung C, Ma D, Lin J (2016) Determination of cell metabolite VEGF165 and dynamic analysis of protein-DNA interactions by combination of microfluidic technique and luminescent switch-on probe. Biosens Bioelectron 79:41–47. doi: 10.1016/j.bios.2015.11.089 CrossRefGoogle Scholar
  120. 120.
    Lin X, Chen Q, Liu W, Zhang J, Wang S, Lin Z, Lin J-M (2015) Oxygen-induced cell migration and on-line monitoring biomarkers modulation of cervical cancers on a microfluidic system. Sci Rep 5:9643. doi: 10.1038/srep09643 CrossRefGoogle Scholar
  121. 121.
    Lin X, Chen Q, Liu W, Yi L, Li H, Wang Z, Lin J-M (2015) Assay of multiplex proteins from cell metabolism based on tunable aptamer and microchip electrophoresis. Biosens Bioelectron 63:105–111. doi: 10.1016/j.bios.2014.07.013 CrossRefGoogle Scholar
  122. 122.
    Lin X, Chen Q, Liu W, Li H, Lin J-M (2014) A portable microchip for ultrasensitive and high-throughput assay of thrombin by rolling circle amplification and hemin/G-quadruplex system. Biosens Bioelectron 56:71–76. doi: 10.1016/j.bios.2013.12.061 CrossRefGoogle Scholar
  123. 123.
    Liu W, Chen Q, Lin X, Lin J-M (2015) Online multi-channel microfluidic chip-mass spectrometry and its application for quantifying noncovalent protein-protein interactions. Analyst 140(5):1551–1554. doi: 10.1039/c4an02370f CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.School of ScienceChina University of Geosciences (Beijing)BeijingPeople’s Republic of China
  2. 2.Department of ChemistryTsinghua UniversityBeijingChina

Personalised recommendations