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Microfluidic Techniques for Platelet Separation and Enrichment

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Journal of the Indian Institute of Science Aims and scope

Abstract

One of the major areas of active research in microfluidics is in biological applications. These applications often require complex analysis of biological fluids for clinical diagnostics. One such complex multicomponent suspension is blood, a mixture of cells suspended in plasma. The cellular components constitute RBCs, WBCs, and platelets. Platelets play a fundamental role in blood clotting mechanism and their efficient functioning is of utmost importance. Platelet separation is necessary for disease diagnostics, transfusion, and research purposes. Centrifugation is commonly employed for platelet separation. However, researchers are developing techniques to enable platelet separation using microfluidics as a tool, primarily due to the various advantages offered while working at microscale. In this review, we investigate and highlight various microscale platelet separation techniques currently available, focusing on their design, working principle, and performance aspects. The issues, challenges, and further possibilities of research and development are also underscored. Our review indicates that not many microdevices for platelet separation are currently available, pointing to an important void that needs to be urgently filled. A brief discussion on the conventional method of platelet separation and platelet dynamics is also included.

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Adapted from Ref.45 by permission from The Royal Society of Chemistry.

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Adapted from Ref.21 by permission from The Royal Society of Chemistry.

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Adapted from Ref.58 by permission from American Chemical Society.

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References

  1. Janasek D, Franzke J, Manz A (2006) Scaling and the design of miniaturized chemical-analysis systems. Nature 442(7101):374–380

    Article  Google Scholar 

  2. Sackmann EK, Fulton AL, Beebe DJ (2014) The present and future role of microfluidics in biomedical research. Nature 507(7491):181–189

    Article  Google Scholar 

  3. Whitesides GM (2006) The origins and the future of microfluidics. Nature 442(7101):368–373

    Article  Google Scholar 

  4. Chakraborty S (ed) (2012) Microfluidics and microscale transport processes. CRC Press, Boca Raton

    Google Scholar 

  5. Panigrahi PK (2016) Transport phenomena in microfluidic systems. John Wiley, Hoboken

    Book  Google Scholar 

  6. Stone HA, Stroock AD, Ajdari A (2004) Engineering flows in small devices: microfluidics toward a lab-on-a-chip. Annu Rev Fluid Mech 36:381–411

    Article  Google Scholar 

  7. Fung YC (1981) Biomechanics: mechanical properties of living tissues. Springer, New York

    Book  Google Scholar 

  8. Caro CG (2011) The mechanics of the circulation. Cambridge University Press, Cambridge

    Book  Google Scholar 

  9. Toner M, Irimia D (2005) Blood-on-a-chip. Annu Rev Biomed Eng 7:77–103

    Article  Google Scholar 

  10. Hou HW, Bhagat AAS, Lee WC, Huang S, Han J, Lim CT (2011) Microfluidic devices for blood fractionation. Micromachines 2(3):319–343

    Article  Google Scholar 

  11. Yu ZTF, Aw Yong KM, Fu J (2014) Microfluidic blood cell sorting: now and beyond. Small 10(9):1687–1703

    Article  Google Scholar 

  12. Shields CW IV, 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(5):1230–1249

    Article  Google Scholar 

  13. Gossett DR, Weaver WM, Mach AJ, Hur SC, Tse HTK, Lee W, Di Carlo D (2010) Label-free cell separation and sorting in microfluidic systems. Anal Bioanal Chem 397(8):3249–3267

    Article  Google Scholar 

  14. Kersaudy-Kerhoas M, Sollier E (2013) Micro-scale blood plasma separation: from acoustophoresis to egg-beaters. Lab Chip 13(17):3323–3346

    Article  Google Scholar 

  15. Lima R, Ishikawa T, Imai Y, Yamaguchi T (2012) Blood flow behavior in microchannels: past, current and future trends. In: Dias R, Lima R, Martins AA, Mata TM (eds) Single and two phase flows on chemical and biomedical engineering. Bentham Science, United States of America, pp 513–547

    Chapter  Google Scholar 

  16. Tripathi S, Kumar YBV, Prabhakar A, Joshi SS, Agrawal A (2015) Passive blood plasma separation at the microscale: a review of design principles and microdevices. J Micromech Microeng 25(8):083001

    Article  Google Scholar 

  17. Liesner RJ, Machin SJ (1997) ABC of clinical haematology: platelet disorders. BMJ 314(7083):809

    Article  Google Scholar 

  18. Harmening DM (1997) Clinical hematology and fundamentals of hemostasis. F. A. Davis Company, Philadelphia

    Google Scholar 

  19. Rodak BF, Carr JH (2015) Clinical hematology, Atlas-E-Book. Elsevier, New York City

    Google Scholar 

  20. Hou Y, Carrim N, Wang Y, Gallant RC, Marshall A, Ni H (2015) Platelets in hemostasis and thrombosis: novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis. Biomed Res 29(6):437

    Google Scholar 

  21. Choi S, Ku T, Song S, Choi C, Park JK (2011) Hydrophoretic high-throughput selection of platelets in physiological shear-stress range. Lab Chip 11(3):413–418

    Article  Google Scholar 

  22. Yazdani A, Karniadakis GE (2016) Sub-cellular modeling of platelet transport in blood flow through microchannels with constriction. Soft Matter 12(19):4339–4351

    Article  Google Scholar 

  23. Gale AJ (2011) Continuing education course# 2: current understanding of hemostasis. Toxicol Pathol 39(1):273–280

    Article  Google Scholar 

  24. Boon GD (1993) An overview of hemostasis. Toxicol Pathol 21(2):170–179

    Article  Google Scholar 

  25. Santos-Martínez MJ, Prina-Mello A, Medina C, Radomski MW (2011) Analysis of platelet function: role of microfluidics and nanodevices. Analyst 136(24):5120–5126

    Article  Google Scholar 

  26. Leslie M (2010) Beyond clotting: the powers of platelets. Science 328:562–564

    Article  Google Scholar 

  27. von Hundelshausen P, Weber C (2007) Platelets as immune cells: bridging inflammation and cardiovascular disease. Circ Res 100(1):27–40

    Article  Google Scholar 

  28. Huebsch LB, Harker LA (1981) Disorders of platelet function: mechanisms, diagnosis and management. West J Med 134(2):109

    Google Scholar 

  29. Dhurat R, Sukesh MS (2016) Principles and methods of preparation of platelet-rich plasma: a review and author’s perspective. J Cutan Aesthet Surg 7:189–197

    Article  Google Scholar 

  30. Marx RE (2001) Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent 10(4):225–228

    Article  Google Scholar 

  31. Lana JFSD, Santana MHA, Belangero WD, Luzo ACM (eds) (2013) Platelet-rich plasma: regenerative medicine: sports medicine, orthopedic, and recovery of musculoskeletal injuries. Springer, Berlin

    Google Scholar 

  32. Smith RG, Gassmann CJ, Campbell MS (2007) Platelet-rich plasma: properties and clinical applications. J Lanc Gen Hosp 2(2):73–77

    Google Scholar 

  33. Maffulli N (ed) (2016) Platelet rich plasma in musculoskeletal practice. Springer, London

    Google Scholar 

  34. Tripathi S, Kumar YBV, Agrawal A, Prabhakar A, Joshi SS (2016) Microdevice for plasma separation from whole human blood using bio-physical and geometrical effects. Sci Rep 6:26749

    Article  Google Scholar 

  35. Savage B, Ruggeri ZM (2007) Platelet thrombus formation in flowing blood. In: Michelson AD (ed) Platelets, 2nd edn. Elsevier/Academic Press, San Diego, pp 359–367

    Chapter  Google Scholar 

  36. Pamme N (2007) Continuous flow separations in microfluidic devices. Lab Chip 7(12):1644–1659

    Article  Google Scholar 

  37. Gulliksson H (2012) Platelets from platelet-rich-plasma versus buffy-coat-derived platelets: what is the difference? Rev Bras Hematol Hemoter 34(2):76

    Article  Google Scholar 

  38. Hoareau GL, Jandrey KE, Burges J, Bremer D, Tablin F (2014) Comparison of the platelet-rich plasma and buffy coat protocols for preparation of canine platelet concentrates. Vet Clin Pathol 43(4):513–518

    Article  Google Scholar 

  39. Sabarish R, Lavu V, Rao SR (2015) A comparison of platelet count and enrichment percentages in the platelet rich plasma (prp) obtained following preparation by three different methods. J Clin Diagn Res 9(2):ZC10–ZC12

    Google Scholar 

  40. Fitzpatrick J, Bulsara MK, McCrory PR, Richardson D, Zheng MH (2017) Analysis of platelet-rich plasma extraction-variations in platelet and blood components between 4 common commercial kits. Orthop J Sports Med 5:1–8

    Article  Google Scholar 

  41. Marques FP, Ingham SJM, Forgas A, Franciozi CEDS, Sasaki PH, Abdalla RJ (2014) A manual method to obtain platelet rich plasma. Acta Ortop Bras 22(2):75–77

    Article  Google Scholar 

  42. Pommer MS, Zhang Y, Keerthi N, Chen D, Thomson JA, Meinhart CD, Soh HT (2008) Dielectrophoretic separation of platelets from diluted whole blood in microfluidic channels. Electrophoresis 29(6):1213–1218

    Article  Google Scholar 

  43. Piacentini N, Mernier G, Tornay R, Renaud P (2011) Separation of platelets from other blood cells in continuous-flow by dielectrophoresis field-flow-fractionation. Biomicrofluidics 5(3):034122

    Article  Google Scholar 

  44. Nam J, Lim H, Kim D, Shin S (2011) Separation of platelets from whole blood using standing surface acoustic waves in a microchannel. Lab Chip 11(19):3361–3364

    Article  Google Scholar 

  45. 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(18):3466–3472

    Article  Google Scholar 

  46. Dykes J, Lenshof A, Astrand-Grundstrom B, Laurell T, Scheding S (2011) Efficient removal of platelets from peripheral blood progenitor cell products using a novel micro-chip based acoustophoretic platform. PLoS One 6(8):e23074

    Article  Google Scholar 

  47. Yousuff CM, Ho ETW, Hussain KI, Hamid NHB (2017) Microfluidic platform for cell isolation and manipulation based on cell properties. Micromachines 8(1):15

    Article  Google Scholar 

  48. Moen ST, Hatcher CL, Singh AK (2016) A centrifugal microfluidic platform that separates whole blood samples into multiple removable fractions due to several discrete but continuous density gradient sections. PLoS One 11(4):e0153137

    Article  Google Scholar 

  49. Prabhakar A, Kumar YBV, Tripathi S, Agrawal A (2015) A novel, compact and efficient microchannel arrangement with multiple hydrodynamic effects for blood plasma separation. Microfluid Nanofluidics 18(5–6):995–1006

    Article  Google Scholar 

  50. Di Carlo D, Edd JF, Irimia D, Tompkins RG, Toner M (2008) Equilibrium separation and filtration of particles using differential inertial focusing. Anal Chem 80(6):2204–2211

    Article  Google Scholar 

  51. Choi S, Song S, Choi C, Park JK (2007) Continuous blood cell separation by hydrophoretic filtration. Lab Chip 7(11):1532–1538

    Article  Google Scholar 

  52. Huang LR, Cox EC, Austin RH, Sturm JC (2004) Continuous particle separation through deterministic lateral displacement. Science 304(5673):987–990

    Article  Google Scholar 

  53. McGrath J, Jimenez M, Bridle H (2014) Deterministic lateral displacement for particle separation: a review. Lab Chip 14(21):4139–4158

    Article  Google Scholar 

  54. Li N, Kamei DT, Ho CM (2007) On-chip continuous blood cell subtype separation by deterministic lateral displacement. In: Nano/micro engineered and molecular systems, 2007. NEMS’07. 2nd IEEE International Conference, pp 932–936

  55. Inglis DW, Morton KJ, Davis JA, Zieziulewicz TJ, Lawrence DA, Austin RH, Sturm JC (2008) Microfluidic device for label-free measurement of platelet activation. Lab Chip 8(6):925–931

    Article  Google Scholar 

  56. Geislinger TM, Eggart B, Braunmüller S, Schmid L, Franke T (2012) Separation of blood cells using hydrodynamic lift. Appl Phys Lett 100(18):183701

    Article  Google Scholar 

  57. Dickson MN, Amar L, Hill M, Schwartz J, Leonard EF (2012) A scalable, micropore, platelet rich plasma separation device. Biomed Microdevices 14(6):1095–1102

    Article  Google Scholar 

  58. Basabe-Desmonts L, Ramstrom S, Meade G, O’neill S, Riaz A, Lee LP, Kenny D (2010) Single-step separation of platelets from whole blood coupled with digital quantification by interfacial platelet cytometry (iPC). Langmuir 26(18):14700–14706

    Article  Google Scholar 

  59. Cokelet GR, Goldsmith HL (1991) Decreased hydrodynamic resistance in the two-phase flow of blood through small vertical tubes at low flow rates. Circ Res 68:1–17

    Article  Google Scholar 

  60. Goldsmith HL, Cokelet GR, Gaehtgens P (1989) Robin Fahraeus: evolution of his concepts in cardiovascular physiology. Am J Physiol Heart Circ Physiol 257:H1005–H10015

    Article  Google Scholar 

  61. Thurston GB (1988) Plasma release-cell layering theory for blood flow. Biorheology 26:199–214

    Article  Google Scholar 

  62. Fedosov DA, Caswell BB, Popel AS, Karniadakis GE (2010) Blood flow and cell-free layer in microvessels. Microcirculation 17:615–628

    Article  Google Scholar 

  63. Zhang J, Johnson PC, Popel AS (2009) Effects of erythrocyte deformability and aggregation on the cell free layer and apparent viscosity of microscopic blood flows. Microvasc Res 77:265–272

    Article  Google Scholar 

  64. Fahraeus R (1929) The suspension stability of the blood. Physiol Rev 9:241–274

    Article  Google Scholar 

  65. Barbee JH, Cokelet GH (1971) The Fahraeus effect. Microvasc Res 3:6–16

    Article  Google Scholar 

  66. Fahraeus R, Lindqvist T (1931) The viscosity of the blood in narrow capillary tubes. Am J Physiol 96:562–568

    Google Scholar 

  67. Nicholson JW (2007) The chemistry of medical and dental materials. Royal Society of Chemistry, London

    Google Scholar 

  68. Wang W, Diacovo TG, Chen J, Freund JB, King MR (2013) Simulation of platelet, thrombus and erythrocyte hydrodynamic interactions in a 3D arteriole with in vivo comparison. PLoS One 8(10):e76949

    Article  Google Scholar 

  69. Fogelson AL, Neeves KB (2015) Fluid mechanics of blood clot formation. Annu Rev Fluid Mech 47:377–403

    Article  Google Scholar 

  70. Tangelder GJ, Slaaf DW, Muijtjens AM, Arts T, Oude Egbrink MG, Reneman RS (1986) Velocity profiles of blood platelets and red blood cells flowing in arterioles of the rabbit mesentery. Circ Res 59(5):505–514

    Article  Google Scholar 

  71. Woldhuis B, Tangelder GJ, Slaaf DW, Reneman RS (1992) Concentration profile of blood platelets differs in arterioles and venules. Am J Physiol 262:H1217–H1223

    Google Scholar 

  72. Aarts PA, Van den Broek SA, Prins GW, Kuiken GD, Sixma JJ, Heethaar RM (1988) Blood platelets are concentrated near the wall and red blood cells, in the center in flowing blood. Arterioscler Thromb Vasc Biol 8(6):819–824

    Article  Google Scholar 

  73. Tilles AW, Eckstein EC (1987) The near-wall excess of platelet-sized particles in blood flow: its dependence on hematocrit and wall shear rate. Microvasc Res 33(2):211–223

    Article  Google Scholar 

  74. Eckstein EC, Tilles AW, Millero FJ III (1988) Conditions for the occurrence of large near-wall excesses of small particles during blood flow. Microvasc Res 36(1):31–39

    Article  Google Scholar 

  75. Zhao R, Kameneva MV, Antaki JF (2007) Investigation of platelet margination phenomena at elevated shear stress. Biorheology 44(3):161–177

    Google Scholar 

  76. Tangelder GJ, Slaaf DW, Teirlinck HC, Alewijnse R, Reneman RS (1982) Localization within a thin optical section of fluorescent blood platelets flowing in a microvessel. Microvasc Res 23(2):214–230

    Article  Google Scholar 

  77. Kruger T (2016) Effect of tube diameter and capillary number on platelet margination and near-wall dynamics. Rheol Acta 55(6):511–526

    Article  Google Scholar 

  78. AlMomani T, Udaykumar HS, Marshall JS, Chandran KB (2008) Micro-scale dynamic simulation of erythrocyte–platelet interaction in blood flow. Ann Biomed Eng 36(6):905–920

    Article  Google Scholar 

  79. Eckstein EC, Belgacem F (1991) Model of platelet transport in flowing blood with drift and diffusion terms. Biophys J 60(1):53–69

    Article  Google Scholar 

  80. Turitto VT, Benis AM, Leonard EF (1972) Platelet diffusion in flowing blood. Ind Eng Chem Fundam 11(2):216–223

    Article  Google Scholar 

  81. Crowl LM, Fogelson AL (2010) Computational model of whole blood exhibiting lateral platelet motion induced by red blood cells. Int J Numer Method Biomed Eng 26(3–4):471–487

    Article  Google Scholar 

  82. Jordan A, David T, Homer-Vanniasinkam S, Graham A, Walker P (2004) The effects of margination and red cell augmented platelet diffusivity on platelet adhesion in complex flow. Biorheology 41(5):641–653

    Google Scholar 

  83. Goldsmith HL (1971) Red cell motions and wall interactions in tube flow. Fed Proc 30:1578–1588

    Google Scholar 

  84. Zhao H, Shaqfeh ES (2011) Shear-induced platelet margination in a microchannel. Phys Rev E 83(6):061924

    Article  Google Scholar 

  85. Zhao H, Shaqfeh ES, Narsimhan V (2012) Shear-induced particle migration and margination in a cellular suspension. Phys Fluids 24(1):011902

    Article  Google Scholar 

  86. Reasor DA, Mehrabadi M, Ku DN, Aidun CK (2013) Determination of critical parameters in platelet margination. Ann Biomed Eng 41(2):238–249

    Article  Google Scholar 

  87. Segre G, Silberber A (1961) Radial particle displacements in Poiseuille flow of suspensions. Nature 189:209–210

    Article  Google Scholar 

  88. Kumar A, Graham MD (2012) Margination and segregation in confined flows of blood and other multicomponent suspensions. Soft Matter 8(41):10536–10548

    Article  Google Scholar 

  89. Zhao R, Marhefka JN, Shu F, Hund SJ, Kameneva MV, Antaki JF (2008) Micro-flow visualization of red blood cell-enhanced platelet concentration at sudden expansion. Ann Biomed Eng 36(7):1130

    Article  Google Scholar 

  90. Rasche H (2001) Haemostasis and thrombosis: an overview. Eur Heart J 3(suppl_Q):Q3–Q7

    Article  Google Scholar 

  91. Aarts PA, Heethaar RM, Sixma JJ (1984) Red blood cell deformability influences platelets-vessel wall interaction in flowing blood. Blood 64(6):1228–1233

    Google Scholar 

  92. Wu WT, Aubry N, Massoudi M, Antaki JF (2017) Transport of platelets induced by red blood cells based on mixture theory. Int J Eng Sci 118:16–27

    Article  Google Scholar 

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Acknowledgements

This work is supported by the IMPRINT scheme of MHRD (Ministry of Human resource Development), Government of India.

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Correspondence to Amit Agrawal.

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Laxmi, V., Tripathi, S., Joshi, S.S. et al. Microfluidic Techniques for Platelet Separation and Enrichment. J Indian Inst Sci 98, 185–200 (2018). https://doi.org/10.1007/s41745-018-0072-6

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