Skip to main content

Microfluidic Cell Isolation and Recognition for Biomedical Applications

  • Chapter
  • First Online:
Cell Analysis on Microfluidics

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

Abstract

There are hundreds of types of cells in human body, and each type of them regulates specific functions in the activities of daily living. Modern studies have revealed that different types of cells exhibit heterogeneity in gene expression, protein secretion and some crucial information between normal and diseased cells. Thus development of efficient technologies for cell isolation and recognition is valuable to achieve disease diagnosis and other fundamental biological researches. Microfluidic technologies have been increasingly emerged as a powerful tool for the studies of cell isolation and recognition in the field of microfluidic cell analysis, which show great promising in the basic and applied biomedical researches. In this chapter, we present an overview of advanced microfluidics for cell isolation and recognition in the past decade. We also discuss current emergence of the biomedical applications in microfluidics including circulating tumor cells (CTCs) detection , cell-based biological assays and stem cell purification. At the end of this Chapter we make a brief summary on the development and challenge of microfluidic technologies in cell isolation and recognition, followed by a future perspective in this study field.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. El-Ali J, Sorger PK, Jensen KF (2006) Cells on chips. Nature 442:403–411. doi:10.1038/nature05063

    Article  CAS  Google Scholar 

  2. Chen Q, Wu J, Zhang Y, Lin JM (2012) Qualitative and quantitative analysis of tumor cell metabolism via stable isotope labeling assisted microfluidic chip electrospray ionization mass spectrometry. Anal Chem 84:1695–1701. doi:10.1021/ac300003k

    Article  CAS  Google Scholar 

  3. Wang BL, Ghaderi A, Zhou H, Agresti J, Weitz DA, Fink GR, Stephanopoulos G (2014) Microfluidic high-throughput culturing of single cells for selection based on extracellular metabolite production or consumption. Nat Biotechnol 32:473–478. doi:10.1038/nbt.2857

    Article  CAS  Google Scholar 

  4. Sackmann EK, Fulton AL, Beebe DJ (2014) The present and future role of microfluidics in biomedical research. Nature 507:181–189. doi:10.1038/nature13118

    Article  CAS  Google Scholar 

  5. Chen Q, Utech S, Chen D, Prodanovic R, Lin JM, Weitz DA (2016) Controlled assembly of heterotypic cells in a core-shell scaffold: organ in a droplet. Lab Chip 16:1346–1349. doi:10.1039/c6lc00231e

    Article  CAS  Google Scholar 

  6. Dittrich PS, Manz A (2006) Lab-on-a-chip: microfluidics in drug discovery. Nat Rev Drug Discov 5:210–218. doi:10.1038/nrd1985

    Article  CAS  Google Scholar 

  7. Chen Q, He Z, Liu W, Lin X, Wu J, Li H, Lin JM (2015) Engineering cell-compatible paper chips for cell culturing, drug screening, and mass spectrometric sensing. Adv Healthc Mater 4:2291–2296. doi:10.1002/adhm.201500383

    Article  CAS  Google Scholar 

  8. Gobaa S, Hoehnel S, Roccio M, Negro A, Kobel S, Lutolf MP (2011) Artificial niche microarrays for probing single stem cell fate in high throughput. Nat Methods 8:949–955. doi:10.1038/nmeth.1732

    Article  CAS  Google Scholar 

  9. Schasfoort RB, Schlautmann S, Hendrikse J, van den Berg A (1999) Field-effect flow control for microfabricated fluidic networks. Science 286:942–945. doi:10.1126/science.286.5441.942

    Article  CAS  Google Scholar 

  10. Tsang VL, Bhatia SN (2004) Three-dimensional tissue fabrication. Adv Healthc Mater 56(11):1635–1647. doi:10.1016/j.addr.2004.05.001

    Google Scholar 

  11. Wu J, He Z, Chen Q, Lin JM (2016) Biochemical analysis on microfluidic chips. Trends Anal Chem 80:213–231. doi:10.1016/j.trac.2016.03.013

    Article  CAS  Google Scholar 

  12. Thorsen T, Maerkl SJ, Quake SR (2002) Microfluidic large-scale integration. Science 298:580–584. doi:10.1126/science.1076996

    Article  CAS  Google Scholar 

  13. Gomez-Sjoberg R, Leyrat AA, Pirone DM, Chen CS, Quake SR (2007) Versatile, fully automated, microfluidic cell culture system. Anal Chem 79:8557–8563. doi:10.1021/ac071311w

    Article  Google Scholar 

  14. Young EW, Beebe DJ (2010) Fundamentals of microfluidic cell culture in controlled microenvironments. Chem Soc Rev 39:1036–1048. doi:10.1039/b909900j

    Article  CAS  Google Scholar 

  15. Yu L, Ng SR, Xu Y, Dong H, Wang YJ, Li CM (2013) Advances of lab-on-a-chip in isolation, detection and post-processing of circulating tumour cells. Lab Chip 13:3163–3182. doi:10.1039/c3lc00052d

    Article  CAS  Google Scholar 

  16. Esmaeilsabzali H, Beischlag TV, Cox ME, Parameswaran AM, Park EJ (2013) Detection and isolation of circulating tumor cells: principles and methods. Biotechnol Adv 31:1063–1084. doi:10.1016/j.biotechadv.2013.08.016

    Article  CAS  Google Scholar 

  17. Shields CW, Reyes CD, Lopez GP (2015) Microfluidic cell sorting: a review of the advances in the separation of cells from debulking to rare cell isolation. Lab Chip 15:1230–1249. doi:10.1039/c4lc01246a

    Article  Google Scholar 

  18. Chen Y, Li P, Huang PH, Xie Y, Mai JD, Wang L, Nguyen NT, Huang TJ (2014) Rare cell isolation and analysis in microfluidics. Lab Chip 14:626–645. doi:10.1039/c3lc90136j

    Article  CAS  Google Scholar 

  19. Wheeler AR, Throndset WR, Whelan RJ, Leach AM, Zare RN, Liao YH, Farrell K, Manger ID, Daridon A (2003) Microfluidic device for single-cell analysis. Anal Chem 75:3581–3586

    Article  CAS  Google Scholar 

  20. Skelley AM, Kirak O, Suh H, Jaenisch R, Voldman J (2009) Microfluidic control of cell pairing and fusion. Nat Methods 6:147–152. doi:10.1038/nmeth.1290

    Article  CAS  Google Scholar 

  21. Gao Y, Li W, Pappas D (2013) Recent advances in microfluidic cell separations. Analyst 138:4714–4721. doi:10.1039/c3an00315a

    Article  CAS  Google Scholar 

  22. Hou S, Zhao H, Zhao L, Shen Q, Wei KS, Suh DY, Nakao A, Garcia MA, Song M, Lee T, Xiong B, Luo SC, Tseng HR, Yu HH (2013) Capture and stimulated release of circulating tumor cells on polymer-grafted silicon nanostructures. Adv Mater 25:1547–1551. doi:10.1002/adma.201203185

    Article  CAS  Google Scholar 

  23. Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, Ryan P, Balis UJ, Tompkins RG, Haber DA, Toner M (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450:1235–1239. doi:10.1038/nature06385

    Article  CAS  Google Scholar 

  24. Torres-Garcia W, Ashili S, Kelbauskas L, Johnson RH, Zhang W, Runger GC, Meldrum DR (2012) A statistical framework for multiparameter analysis at the single-cell level. Mol BioSyst 8:804–817. doi:10.1039/c2mb05429a

    Article  CAS  Google Scholar 

  25. Lin M, Chen JF, Lu YT, Zhang Y, Song J, Hou S, Ke Z, Tseng HR (2014) Nanostructure embedded microchips for detection, isolation, and characterization of circulating tumor cells. Acc Chem Res 47:2941–2950. doi:10.1021/ar5001617

    Article  CAS  Google Scholar 

  26. Vona G, Sabile A, Louha M, Sitruk V, Romana S, Schutze K, Capron F, Franco D, Pazzagli M, Vekemans M, Lacour B, Brechot C, Paterlini-Brechot P (2000) Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulatingtumor cells. Am J Pathol 156:57–63. doi:10.1016/S0002-9440(10)64706-2

    Article  CAS  Google Scholar 

  27. Yu M, Stott S, Toner M, Maheswaran S, Haber DA (2011) Circulating tumor cells: approaches to isolation and characterization. J Cell Biol 192:373–382. doi:10.1083/jcb.201010021

    Article  CAS  Google Scholar 

  28. Mohamed H, Murray M, Turner JN, Caggana M (2009) Isolation of tumor cells using size and deformation. J Chromatogr A 1216:8289–8295. doi:10.1016/j.chroma.2009.05.036

    Article  CAS  Google Scholar 

  29. Sarioglu AF, Aceto N, Kojic N, Donaldson MC, Zeinali M, Hamza B, Engstrom A, Zhu H, Sundaresan TK, Miyamoto DT, Luo X, Bardia A, Wittner BS, Ramaswamy S, Shioda T, Ting DT, Stott SL, Kapur R, Maheswaran S, Haber DA, Toner M (2015) A microfluidic device for label-free, physical capture of circulating tumor cell clusters. Nat Methods 12:685–691. doi:10.1038/nmeth.3404

    Article  CAS  Google Scholar 

  30. Hosokawa M, Hayata T, Fukuda Y, Arakaki A, Yoshino T, Tanaka T, Matsunaga T (2010) Size-selective microcavity array for rapid and efficient detection of circulating tumor cells. Anal Chem 82:6629–6635. doi:10.1021/ac101222x

    Article  CAS  Google Scholar 

  31. Zheng S, Lin HK, Lu B, Williams A, Datar R, Cote RJ, Tai YC (2011) 3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood. Biomed Microdevices 13:203–213. doi:10.1007/s10544-010-9485-3

    Article  Google Scholar 

  32. Chen W, Huang NT, Oh B, Lam RH, Fan R, Cornell TT, Shanley TP, Kurabayashi K, Fu J (2013) Surface-micromachined microfiltration membranes for efficient isolation and functional immunophenotyping of subpopulations of immune cells. Adv Healthc Mater 2:965–975. doi:10.1002/adhm.201200378

    Article  CAS  Google Scholar 

  33. Lim LS, Hu M, Huang MC, Cheong WC, Gan AT, Looi XL, Leong SM, Koay ES, Li MH (2012) Microsieve lab-chip device for rapid enumeration and fluorescence in situ hybridization of circulating tumor cells. Lab Chip 12:4388–4396. doi:10.1039/c2lc20750h

    Article  CAS  Google Scholar 

  34. Wei H, Chueh BH, Wu H, Hall EW, Li CW, Schirhagl R, Lin JM, Zare RN (2011) Particle sorting using a porous membrane in a microfluidic device. Lab Chip 11:238–245. doi:10.1039/c0lc00121

    Article  CAS  Google Scholar 

  35. Schirhagl R, Fuereder I, Hall EW, Medeiros BC, Zare RN (2011) Microfluidic purification and analysis of hematopoietic stem cells from bone marrow. Lab Chip 11:3130–3135. doi:10.1039/c1lc20353c

    Article  CAS  Google Scholar 

  36. Gossett DR, Weaver WM, Mach AJ, Hur SC, Tse HT, Lee W, Amini H, Di Carlo D (2010) Label-free cell separation and sorting in microfluidic systems. Anal Bioanal Chem 397:3249–3267. doi:10.1007/s00216-010-3721-9

    Article  CAS  Google Scholar 

  37. Hur SC, Mach AJ, Di Carlo D (2011) High-throughput size-based rare cell enrichment using microscale vortices. Biomicrofluidics 5:22206. doi:10.1063/1.3576780

    Article  Google Scholar 

  38. Moon HS, Kwon K, Hyun KA, Seok Sim T, Chan Park J, Lee JG, Jung HI (2013) Continual collection and re-separation of circulating tumor cells from blood using multi-stage multi-orifice flow fractionation. Biomicrofluidics 7:14105. doi:10.1063/1.4788914

    Article  Google Scholar 

  39. Warkiani ME, Khoo BL, Wu L, Tay AK, Bhagat AA, Han J, Lim CT (2016) Ultra-fast, label-free isolation of circulating tumor cells from blood using spiral microfluidics. Nat Protocols 11:134–148. doi:10.1038/nprot.2016.003

    Article  CAS  Google Scholar 

  40. Hou HW, Warkiani ME, Khoo BL, Li ZR, Soo RA, Tan DS, Lim WT, Han J, Bhagat AA, Lim CT (2013) Isolation and retrieval of circulating tumor cells using centrifugal forces. Sci Rep 3:1259. doi:10.1038/srep01259

    Article  Google Scholar 

  41. Ozkumur E, Shah AM, Ciciliano JC, Emmink BL, Miyamoto DT, Brachtel E, Yu M, Chen PI, Morgan B, Trautwein J, Kimura A, Sengupta S, Stott SL, Karabacak NM, Barber TA, Walsh JR, Smith K, Spuhler PS, Sullivan JP, Lee RJ, Ting DT, Luo X, Shaw AT, Bardia A, Sequist LV, Louis DN, Maheswaran S, Kapur R, Haber DA, Toner M (2013) Inertial focusing for tumor antigen-dependent and -independent sorting of rare circulating tumor cells. Sci Transl Med 5(179):179ra47. doi:10.1126/scitranslmed.3005616

  42. Karabacak NM, Spuhler PS, Fachin F, Lim EJ, Pai V, Ozkumur E, Martel JM, Kojic N, Smith K, Chen PI, Yang J, Hwang H, Morgan B, Trautwein J, Barber TA, Stott SL, Maheswaran S, Kapur R, Haber DA, Toner M (2014) Microfluidic, marker-free isolation of circulating tumor cells from blood samples. Nat Protocols 9:694–710. doi:10.1038/nprot.2014.044

    Article  CAS  Google Scholar 

  43. Hyun KA, Kwon K, Han H, Kim SI, Jung HI (2013) Microfluidic flow fractionation device for label-free isolation of circulating tumor cells (CTCs) from breast cancer patients. Biosens Bioelectron 40:206–212. doi:10.1016/j.bios.2012.07.021

    Article  CAS  Google Scholar 

  44. Ding X, Li P, Lin SC, Stratton ZS, Nama N, Guo F, Slotcavage D, Mao X, Shi J, Costanzo F, Huang TJ (2013) Surface acoustic wave microfluidics. Lab Chip 13:3626–3649. doi:10.1039/c3lc50361e

    Article  CAS  Google Scholar 

  45. Petersson F, Aberg L, Sward-Nilsson AM, Laurell T (2007) Free flow acoustophoresis: microfluidic-based mode of particle and cell separation. Anal Chem 79:5117–5123. doi:10.1021/ac070444e

    Article  CAS  Google Scholar 

  46. Chen Y, Nawaz AA, Zhao Y, Huang PH, McCoy JP, Levine SJ, Wang L, Huang TJ (2014) Standing surface acoustic wave (SSAW)-based microfluidic cytometer. Lab Chip 14:916–923. doi:10.1039/c3lc51139a

    Article  Google Scholar 

  47. Ding X, Peng Z, Lin SC, Geri M, Li S, Li P, Chen Y, Dao M, Suresh S, Huang TJ (2014) Cell separation using tilted-angle standing surface acoustic waves. PNAS 111:12992–12997. doi:10.1073/pnas.1413325111

    Article  CAS  Google Scholar 

  48. Li P, Mao Z, Peng Z, Zhou L, Chen Y, Huang PH, Truica CI, Drabick JJ, El-Deiry WS, Dao M, Suresh S, Huang TJ (2015) Acoustic separation of circulating tumor cells. PNAS 112:4970–4975. doi:10.1073/pnas.1504484112

    Article  CAS  Google Scholar 

  49. Senveli SU, Ao Z, Rawal S, Datar RH, Cote RJ, Tigli O (2016) A surface acoustic wave biosensor for interrogation of single tumour cells in microcavities. Lab Chip 16:163–171. doi:10.1039/c5lc01212k

    Article  CAS  Google Scholar 

  50. Shafiee H, Caldwell JL, Sano MB, Davalos RV (2009) Contactless dielectrophoresis: a new technique for cell manipulation. Biomed Microdevices 11:997–1006. doi:10.1007/s10544-009-9317-5

    Article  CAS  Google Scholar 

  51. Gupta V, Jafferji I, Garza M, Melnikova VO, Hasegawa DK, Pethig R, Davis DW (2012) ApoStream(), a new dielectrophoretic device for antibody independent isolation and recovery of viable cancer cells from blood. Biomicrofluidics 6:24133. doi:10.1063/1.4731647

    Article  Google Scholar 

  52. Shim S, Stemke-Hale K, Tsimberidou AM, Noshari J, Anderson TE, Gascoyne PR (2013) Antibody-independent isolation of circulating tumor cells by continuous-flow dielectrophoresis. Biomicrofluidics 7:11807. doi:10.1063/1.4774304

    Article  Google Scholar 

  53. Cheng IF, Huang WL, Chen TY, Liu CW, Lin YD, Su WC (2015) Antibody-free isolation of rare cancer cells from blood based on 3D lateral dielectrophoresis. Lab Chip 15:2950–2959. doi:10.1039/c5lc00120j

    Article  CAS  Google Scholar 

  54. Sano MB, Caldwell JL, Davalos RV (2011) Modeling and development of a low frequency contactless dielectrophoresis (cDEP) platform to sort cancer cells from dilute whole blood samples. Biosens Bioelectron 30:13–20. doi:10.1016/j.bios.2011.07.048

    Article  CAS  Google Scholar 

  55. Mazutis L, Gilbert J, Ung WL, Weitz DA, Griffiths AD, Heyman JA (2013) Single-cell analysis and sorting using droplet-based microfluidics. Nat Protocols 8:870–891. doi:10.1038/nprot.2013.046

    Article  CAS  Google Scholar 

  56. Klein AM, Mazutis L, Akartuna I, Tallapragada N, Veres A, Li V, Peshkin L, Weitz DA, Kirschner MW (2015) Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161:1187–1201. doi:10.1016/j.cell.2015.04.044

    Article  CAS  Google Scholar 

  57. Huang SB, Wu MH, Lin YH, Hsieh CH, Yang CL, Lin HC, Tseng CP, Lee GB (2013) High-purity and label-free isolation of circulating tumor cells (CTCs) in a microfluidic platform by using optically-induced-dielectrophoretic (ODEP) force. Lab Chip 13:1371–1383. doi:10.1039/c3lc41256c

    Article  CAS  Google Scholar 

  58. Galletti G, Sung MS, Vahdat LT, Shah MA, Santana SM, Altavilla G, Kirby BJ, Giannakakou P (2014) Isolation of breast cancer and gastric cancer circulating tumor cells by use of an anti HER2-based microfluidic device. Lab Chip 14:147–156. doi:10.1039/c3lc51039e

    Article  CAS  Google Scholar 

  59. Stott SL, Hsu CH, Tsukrov DI, Yu M, Miyamoto DT, Waltman BA, Rothenberg SM, Shah AM, Smas ME, Korir GK, Floyd FP Jr, Gilman AJ, Lord JB, Winokur D, Springer S, Irimia D, Nagrath S, Sequist LV, Lee RJ, Isselbacher KJ, Maheswaran S, Haber DA, Toner M (2010) Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. PNAS 107:18392–18397. doi:10.1073/pnas.1012539107

    Article  CAS  Google Scholar 

  60. Adams AA, Okagbare PI, Feng J, Hupert ML, Patterson D, Gottert J, McCarley RL, Nikitopoulos D, Murphy MC, Soper SA (2008) Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor. JACS 130:8633–8641. doi:10.1021/ja8015022

    Article  CAS  Google Scholar 

  61. Yoon HJ, Kim TH, Zhang Z, Azizi E, Pham TM, Paoletti C, Lin J, Ramnath N, Wicha MS, Hayes DF, Simeone DM, Nagrath S (2013) Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets. Nat Nanotechnol 8:735–741. doi:10.1038/nnano.2013.194

    Article  CAS  Google Scholar 

  62. Dharmasiri U, Njoroge SK, Witek MA, Adebiyi MG, Kamande JW, Hupert ML, Barany F, Soper SA (2011) High-throughput selection, enumeration, electrokinetic manipulation, and molecular profiling of low-abundance circulating tumor cells using a microfluidic system. Anal Chem 83:2301–2309. doi:10.1021/ac103172y

    Article  CAS  Google Scholar 

  63. Fang X, Tan W (2010) Aptamers generated from cell-SELEX for molecular medicine: a chemical biology approach. Acc Chem Res 43:48–57. doi:10.1021/ar900101s

    Article  CAS  Google Scholar 

  64. Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249:505–510

    Article  CAS  Google Scholar 

  65. Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822. doi:10.1038/346818a0

    Article  CAS  Google Scholar 

  66. Shen Q, Xu L, Zhao L, Wu D, Fan Y, Zhou Y, Ouyang WH, Xu X, Zhang Z, Song M, Lee T, Garcia MA, Xiong B, Hou S, Tseng HR, Fang X (2013) Specific capture and release of circulating tumor cells using aptamer-modified nanosubstrates. Adv Mater 25:2368–2373. doi:10.1002/adma.201300082

    Article  CAS  Google Scholar 

  67. Wan Y, Tan J, Asghar W, Kim YT, Liu Y, Iqbal SM (2011) Velocity effect on aptamer-based circulating tumor cell isolation in microfluidic devices. J Phy Chem B 115:13891–13896. doi:10.1021/jp205511m

    Article  CAS  Google Scholar 

  68. Phillips JA, Xu Y, Xia Z, Fan ZH, Tan W (2009) Enrichment of cancer cells using aptamers immobilized on a microfluidic channel. Anal Chem 81:1033–1039. doi:10.1021/ac802092j

    Article  CAS  Google Scholar 

  69. Xu Y, Phillips JA, Yan J, Li Q, Fan ZH, Tan W (2009) Aptamer-based microfluidic device for enrichment, sorting, and detection of multiple cancer cells. Anal Chem 81:7436–7442. doi:10.1021/ac9012072

    Article  CAS  Google Scholar 

  70. Zhao W, Cui CH, Bose S, Guo D, Shen C, Wong WP, Halvorsen K, Farokhzad OC, Teo GS, Phillips JA, Dorfman DM, Karnik R, Karp JM (2012) Bioinspired multivalent DNA network for capture and release of cells. PNAS 109:19626–19631. doi:10.1073/pnas.1211234109

    Article  CAS  Google Scholar 

  71. Liu W, Wei H, Lin Z, Mao S, Lin JM (2011) Rare cell chemiluminescence detection based on aptamer-specific capture in microfluidic channels. Biosens Bioelectron 28:438–442. doi:10.1016/j.bios.2011.07.067

    Article  CAS  Google Scholar 

  72. Wang S, Wang H, Jiao J, Chen KJ, Owens GE, Kamei K, Sun J, Sherman DJ, Behrenbruch CP, Wu H, Tseng HR (2009) Three-dimensional nanostructured substrates toward efficient capture of circulating tumor cells. Angew Chem Int Ed 48:8970–8973. doi:10.1002/anie.200901668

    Article  CAS  Google Scholar 

  73. Wang S, Liu K, Liu J, Yu ZT, Xu X, Zhao L, Lee T, Lee EK, Reiss J, Lee YK, Chung LW, Huang J, Rettig M, Seligson D, Duraiswamy KN, Shen CK, Tseng HR (2011) Highly efficient capture of circulating tumor cells by using nanostructured silicon substrates with integrated chaotic micromixers. Angew Chem Int Ed 50:3084–3088. doi:10.1002/anie.201005853

    Article  CAS  Google Scholar 

  74. Sheng W, Chen T, Tan W, Fan ZH (2013) Multivalent DNA nanospheres for enhanced capture of cancer cells in microfluidic devices. ACS Nano 7:7067–7076. doi:10.1021/nn4023747

    Article  CAS  Google Scholar 

  75. Zhu J, Nguyen T, Pei R, Stojanovic M, Lin Q (2012) Specific capture and temperature-mediated release of cells in an aptamer-based microfluidic device. Lab Chip 12:3504–3513. doi:10.1039/c2lc40411g

    Article  CAS  Google Scholar 

  76. Hou S, Zhao L, Shen Q, Yu J, Ng C, Kong X, Wu D, Song M, Shi X, Xu X, OuYang WH, He R, Zhao XZ, Lee T, Brunicardi FC, Garcia MA, Ribas A, Lo RS, Tseng HR (2013) Polymer nanofiber-embedded microchips for detection, isolation, and molecular analysis of single circulating melanoma cells. Angew Chem Int Ed 52:3379–3383. doi:10.1002/anie.201208452

    Article  CAS  Google Scholar 

  77. Zhao L, Lu YT, Li F, Wu K, Hou S, Yu J, Shen Q, Wu D, Song M, OuYang WH, Luo Z, Lee T, Fang X, Shao C, Xu X, Garcia MA, Chung LW, Rettig M, Tseng HR, Posadas EM (2013) High-purity prostate circulating tumor cell isolation by a polymer nanofiber-embedded microchip for whole exome sequencing. Adv Mater 25:2897–2902. doi:10.1002/adma.201205237

    Article  CAS  Google Scholar 

  78. Qian W, Zhang Y, Chen W (2015) Capturing cancer: emerging microfluidic technologies for the capture and characterization of circulating tumor cells. Small 11:3850–3872. doi:10.1002/smll.201403658

    Article  CAS  Google Scholar 

  79. Gleghorn JP, Pratt ED, Denning D, Liu H, Bander NH, Tagawa ST, Nanus DM, Giannakakou PA, Kirby BJ (2010) Capture of circulating tumor cells from whole blood of prostate cancer patients using geometrically enhanced differential immunocapture (GEDI) and a prostate-specific antibody. Lab Chip 10:27–29. doi:10.1039/b917959c

    Article  CAS  Google Scholar 

  80. Sheng W, Chen T, Kamath R, Xiong X, Tan W, Fan ZH (2012) Aptamer-enabled efficient isolation of cancer cells from whole blood using a microfluidic device. Anal Chem 84:4199–4206. doi:10.1021/ac3005633

    Article  CAS  Google Scholar 

  81. Oh SS, Qian J, Lou X, Zhang Y, Xiao Y, Soh HT (2009) Generation of highly specific aptamers via micromagnetic selection. Anal Chem 81:5490–5495. doi:10.1021/ac900759k

    Article  CAS  Google Scholar 

  82. McFaul SM, Lin BK, Ma H (2012) Cell separation based on size and deformability using microfluidic funnel ratchets. Lab Chip 12:2369–2376. doi:10.1039/c2lc21045b

    Article  CAS  Google Scholar 

  83. Adams DL, Zhu P, Makarova OV, Martin SS, Charpentier M, Chumsri S, Li S, Amstutz P, Tang CM (2014) The systematic study of circulating tumor cell isolation using lithographic microfilters. RSC Adv 9:4334–4342. doi:10.1039/C3RA46839A

    Article  Google Scholar 

  84. Tang Y, Shi J, Li S, Wang L, Cayre YE, Chen Y (2014) Microfluidic device with integrated microfilter of conical-shaped holes for high efficiency and high purity capture of circulating tumor cells. Sci Rep 4:6052. doi:10.1038/srep06052

    Article  CAS  Google Scholar 

  85. Gorkin R, Park J, Siegrist J, Amasia M, Lee BS, Park JM, Kim J, Kim H, Madou M, Cho YK (2010) Centrifugal microfluidics for biomedical applications. Lab Chip 10(14):1758–1773. doi:10.1039/b924109d

    Article  CAS  Google Scholar 

  86. Burger R, Kirby D, Glynn M, Nwankire C, O’Sullivan M, Siegrist J, Kinahan D, Aguirre G, Kijanka G, Gorkin RA 3rd, Ducree J (2012) Centrifugal microfluidics for cell analysis. Curr Opin Chem Biol 16:409–414. doi:10.1016/j.cbpa.2012.06.002

    Article  CAS  Google Scholar 

  87. Liu C, Liu J, Gao D, Ding M, Lin JM (2010) Fabrication of microwell arrays based on two-dimensional ordered polystyrene microspheres for high-throughput single-cell analysis. Anal Chem 82:9418–9424. doi:10.1021/ac102094r

    Article  CAS  Google Scholar 

  88. Chen Q, Wu J, Zhang Y, Lin Z, Lin JM (2012) Targeted isolation and analysis of single tumor cells with aptamer-encoded microwell array on microfluidic device. Lab Chip 12:5180–5185. doi:10.1039/c2lc40858a

    Article  CAS  Google Scholar 

  89. Ma C, Fan R, Ahmad H, Shi Q, Comin-Anduix B, Chodon T, Koya RC, Liu CC, Kwong GA, Radu CG, Ribas A, Heath JR (2011) A clinical microchip for evaluation of single immune cells reveals high functional heterogeneity in phenotypically similar T cells. Nat Med 17:738–743. doi:10.1038/nm.2375

    Article  CAS  Google Scholar 

  90. Autebert J, Coudert B, Champ J, Saias L, Guneri ET, Lebofsky R, Bidard FC, Pierga JY, Farace F, Descroix S, Malaquin L, Viovy JL (2015) High purity microfluidic sorting and analysis of circulating tumor cells: towards routine mutation detection. Lab Chip 15:2090–2101. doi:10.1039/c5lc00104h

    Article  CAS  Google Scholar 

  91. Guo MT, Rotem A, Heyman JA, Weitz DA (2012) Droplet microfluidics for high-throughput biological assays. Lab Chip 12:2146–2155. doi:10.1039/c2lc21147e

    Article  CAS  Google Scholar 

  92. Spencer SJ, Tamminen MV, Preheim SP, Guo MT, Briggs AW, Brito IL, David AW, Pitkanen LK, Vigneault F, Juhani Virta MP, Alm EJ (2016) Massively parallel sequencing of single cells by epicPCR links functional genes with phylogenetic markers. ISME J 10:427–436. doi:10.1038/ismej.2015.124

    Article  CAS  Google Scholar 

  93. Hattori F, Chen H, Yamashita H, Tohyama S, Satoh YS, Yuasa S, Li W, Yamakawa H, Tanaka T, Onitsuka T, Shimoji K, Ohno Y, Egashira T, Kaneda R, Murata M, Hidaka K, Morisaki T, Sasaki E, Suzuki T, Sano M, Makino S, Oikawa S, Fukuda K (2010) Nongenetic method for purifying stem cell-derived cardiomyocytes. Nat Methods 7:61–66. doi:10.1038/nmeth.1403

    Article  CAS  Google Scholar 

  94. Lecault V, Vaninsberghe M, Sekulovic S, Knapp DJ, Wohrer S, Bowden W, Viel F, McLaughlin T, Jarandehei A, Miller M, Falconnet D, White AK, Kent DG, Copley MR, Taghipour F, Eaves CJ, Humphries RK, Piret JM, Hansen CL (2011) High-throughput analysis of single hematopoietic stem cell proliferation in microfluidic cell culture arrays. Nat Methods 8:581–586. doi:10.1038/nmeth.1614

    Article  CAS  Google Scholar 

  95. Singh A, Suri S, Lee T, Chilton JM, Cooke MT, Chen W, Fu J, Stice SL, Lu H, McDevitt TC, Garcia AJ (2013) Adhesion strength-based, label-free isolation of human pluripotent stem cells. Nat Methods 10:438–444. doi:10.1038/nmeth.2437

    Article  CAS  Google Scholar 

  96. Chen Q, Wu J, Zhuang Q, Lin X, Zhang J, Lin JM (2013) Microfluidic isolation of highly pure embryonic stem cells using feeder-separated co-culture system. Sci Rep 3:2433. doi:10.1038/srep02433

    Article  Google Scholar 

  97. Wang X, Chen S, Kong M, Wang Z, Costa KD, Li RA, Sun D (2011) Enhanced cell sorting and manipulation with combined optical tweezer and microfluidic chip technologies. Lab Chip 11:3656–3662. doi:10.1039/c1lc20653b

    Article  CAS  Google Scholar 

  98. Wang MM, Tu E, Raymond DE, Yang JM, Zhang H, Hagen N, Dees B, Mercer EM, Forster AH, Kariv I, Marchand PJ, Butler WF (2005) Microfluidic sorting of mammalian cells by optical force switching. Nat Biotechnol 23:83–87. doi:10.1038/nbt1050

    Article  CAS  Google Scholar 

  99. Au AK, Huynh W, Horowitz LF, Folch A (2016) 3D-Printed Microfluidics. Angew Chem Int Ed 55:3862–3881. doi:10.1002/anie.201504382

    Article  CAS  Google Scholar 

  100. Wu J, Chen Q, Lin JM (2017) Microfluidic technologies in cell isolation and analysis for biomedical applications. Analyst 142:421–441. doi:10.1039/C6AN01939K

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jin-Ming Lin .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Cite this chapter

Chen, Q., Lin, JM. (2018). Microfluidic Cell Isolation and Recognition for Biomedical Applications. In: Lin, JM. (eds) Cell Analysis on Microfluidics. Integrated Analytical Systems. Springer, Singapore. https://doi.org/10.1007/978-981-10-5394-8_3

Download citation

Publish with us

Policies and ethics