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A Review on Recent Trends in the Segregation of Red Blood Cells Using Microfluidic Devices

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MEMS and Microfluidics in Healthcare

Abstract

The isolation of Red Blood Cells (RBCs) has become a broad area of research in recent times. The early segregation of RBCs from the blood prevents them from lysis. The segregation of RBCs using traditional techniques like centrifugation has become outdated due to the usage of bulky equipment. This paper reviews the functions of RBCs, the age-old techniques that were practically used to distinguish RBCs, and their drawbacks. The assessment of microfluidic devices which are prevalently used in present-day diagnostics that are promised to replace the bottlenecks posed by the traditional methods is also presented. This review aims to project the recent advancements in microfluidics, their applications, and the segregation of microfluidic particles using them. The modern approaches that can separate RBCs virtually using electroosmotic phenomena like di-electrophoresis are also reviewed. The present scenarios for the separation of RBCs with a FEM tool computer-aided design for virtual analysis are also discussed.

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References

  1. Waugh A, Grant A (2014) Ross & Wilson anatomy and physiology in health and illness E-book. Elsevier Health Sciences

    Google Scholar 

  2. Pal GK, Pal P, Nanda N (2016) Comprehensive textbook of medical physiology-two volume set. JP Medical Ltd

    Google Scholar 

  3. Pearson HA (1967) Life-span of the fetal red blood cell. J Pediatr 70(2):166–171

    Article  Google Scholar 

  4. Turrigiano G (2007) Homeostatic signaling: the positive side of negative feedback. Curr Opin Neurobiol 17(3):318–324

    Article  Google Scholar 

  5. Bunn HF (2013) Erythropoietin. Cold Spring Harb Perspect Med 3(3):a011619

    Article  Google Scholar 

  6. Saba TM (2018) Fibronectin: role in phagocytic host defense and lung vascular integrity. In: Fibronectin in Health and Disease. pp 49–68

    Google Scholar 

  7. Weaver L, Hamoud AR, Stec DE, Hinds TD Jr (2018) Biliverdin reductase and bilirubin in hepatic disease. Am J Physiol Gastrointest Liver Physiol 314(6):G668–G676

    Google Scholar 

  8. Mitra S, Rahman MH, Prince HA, Rozin EH (2020) Numerical investigation on dielectrophoresis blood cell separation for different applied voltage and red blood cell size. In: 2020 IEEE Region 10 Symposium (TENSYMP). IEEE, pp 730–733

    Google Scholar 

  9. Danon D, Marikovsky Y (1964) Determination of density distribution of red cell population. J Lab Clin Med 64(4):668–674

    Google Scholar 

  10. Piomelli S, Lurinsky G, Wasserman LR (1967) The mechanism of red cell aging. I. Relationship between cell age and specific gravity evaluated by ultracentrifugation in a discontinuous density gradient. J Lab Clin Med 69(4):659–674

    Google Scholar 

  11. Corash LM, Piomelli S, Chen HC, Seaman C, Gross E (1974) Separation of erythrocytes according to age on a simplified density gradient. J Lab Clin Med 84(1):147–151

    Google Scholar 

  12. Vettore L, De Matteis MC, Zampini P (1980) A new density gradient system for the separation of human red blood cells. Am J Hematol 8(3):291–297

    Article  Google Scholar 

  13. Marikovsky Y, Danon D (1971) Agglutination of young and old human red cells by blood group antibodies. Vox Sang 20(2):174–177

    Article  Google Scholar 

  14. Bartos HR, Desforges JF (1967) Enzymes as erythrocyte age reference standards. Am J Med Sci 254(6):862–865

    Article  Google Scholar 

  15. Walter H, Krob EJ, Garza R (1968) Factors in the partition of red blood cells in aqueous dextran-polyethylene glycol two-phase systems. Biochim Biophys Acta (BBA)-Gen Subj 165(3):507–514

    Google Scholar 

  16. Costa JAV, de Morais MG (2014) An open pond system for microalgal cultivation. In: Biofuels from algae. Elsevier, pp 1–22

    Google Scholar 

  17. Rigas DA, Koler RD (1961) Ultracentrifugal fractionation of human erythrocytes on the basis of cell age. J Lab Clin Med 58:242–246

    Google Scholar 

  18. Boyd EM, Thomas DR, Horton BF, Huisman THJ (1967) The quantities of various minor hemoglobin components in old and young human red blood cells. Clin Chim Acta 16(3):333–341

    Article  Google Scholar 

  19. Pertoft H, Bäck O, Lindahl-Kiessling K (1968) Separation of various blood cells in colloidal silica-polyvinylpyrrolidone gradients. Exp Cell Res 50(2):355–368

    Article  Google Scholar 

  20. Desimone J, Kleve L, Shaeffer J (1974) Isolation of a reticulocyte-rich fraction from normal human blood on renografin gradients. J Lab Clin Med 84(4):517–524

    Google Scholar 

  21. Goebel KM, Goebel FD, Schubotz R, Schneider J (1977) Red cell metabolic and membrane features in haemolytic anaemia of alcoholic liver disease (Zieve’s syndrome). Br J Haematol 35(4):573–585

    Article  Google Scholar 

  22. Danon D, Marikovsky Y (1961) Difference de charge electrique de surface entre erythrocytes jeunes et ages. Comptes Rendus Hebd Seances L Acad Sci 253(12):1271

    Google Scholar 

  23. Mantegazza A, Clavica F, Obrist D (2020) In vitro investigations of red blood cell phase separation in a complex microchannel network. Biomicrofluidics 14(1):014101

    Article  Google Scholar 

  24. Dennison C, Lovrien R (1997) Three phase partitioning: concentration and purification of proteins. Protein Expr Purif 11(2):149–161

    Article  Google Scholar 

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

    Google Scholar 

  26. Weibel DB, Whitesides GM (2006) Applications of microfluidics in chemical biology. Curr Opin Chem Biol 10(6):584–591

    Article  Google Scholar 

  27. Beebe DJ, Mensing GA, Walker GM (2002) Physics and applications of microfluidics in biology. Annu Rev Biomed Eng 4(1):261–286

    Article  Google Scholar 

  28. Groisman A, Lobo C, Cho H, Campbell JK, Dufour YS, Stevens AM, Levchenko A (2005) A microfluidic chemostat for experiments with bacterial and yeast cells. Nat Methods 2(9):685–689

    Article  Google Scholar 

  29. Balagaddé FK, You L, Hansen CL, Arnold FH, Quake SR (2005) Long-term monitoring of bacteria undergoing programmed population control in a microchemostat. Science 309(5731):137–140

    Article  Google Scholar 

  30. Lee H, Purdon AM, Chu V, Westervelt RM (2004) Controlled assembly of magnetic nanoparticles from magnetotactic bacteria using microelectromagnets arrays. Nano Lett 4(5):995–998

    Article  Google Scholar 

  31. Weston AD, Hood L (2004) Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine. J Proteome Res 3(2):179–196

    Article  Google Scholar 

  32. Reyes DR, Iossifidis D, Auroux PA, Manz A (2002) Micro total analysis systems. 1. Introduction, theory, and technology. Anal Chem 74(12):2623–2636

    Google Scholar 

  33. Gravesen P, Branebjerg J, Jensen OS (1993) Microfluidics-a review. J Micromech Microeng 3(4):168

    Article  Google Scholar 

  34. Whitesides G, Stroock A (2001) Flexible methods for microfluidics. Phys Today 54:42–48

    Article  Google Scholar 

  35. Jakeway SC, de Mello AJ, Russell EL (2000) Miniaturized total analysis systems for biological analysis. Fresenius J Anal Chem 366(6):525–539

    Article  Google Scholar 

  36. Ho CM, Tai YC (1998) Micro-electro-mechanical-systems (MEMS) and fluid flows. Annu Rev Fluid Mech 30:579–612

    Article  Google Scholar 

  37. Becker H, Gärtner C (2000) Polymer microfabrication methods for microfluidic analytical applications. ELECTROPHORESIS Int J 21(1):12–26

    Google Scholar 

  38. Brody JP, Yager P, Goldstein RE, Austin RH (1996) Biotechnology at low Reynolds numbers. Biophys J 71(6):3430–3441

    Article  Google Scholar 

  39. Purcell EM (1977) Life at low Reynolds number. Am J Phys 45(1):3–11

    Article  Google Scholar 

  40. Flow VF (1991) Frank M. White

    Google Scholar 

  41. Brody JP, Yager P (1997) Diffusion-based extraction in a microfabricated device. Sens Actuat A 58(1):13–18

    Article  Google Scholar 

  42. Hatch A, Kamholz AE, Hawkins KR, Munson MS, Schilling EA, Weigl BH, Yager P (2001) A rapid diffusion immunoassay in a T-sensor. Nat Biotechnol 19(5):461–465

    Article  Google Scholar 

  43. Yeo LY, Chang HC, Chan PP, Friend JR (2011) Microfluidic devices for bioapplications. Small 7(1):12–48

    Google Scholar 

  44. Ren K, Zhou J, Wu H (2013) Materials for microfluidic chip fabrication. Acc Chem Res 46(11):2396–2406

    Article  Google Scholar 

  45. Friend J, Yeo L (2010) Fabrication of microfluidic devices using polydimethylsiloxane. Biomicrofluidics 4(2):026502

    Article  Google Scholar 

  46. Catarino SO, Rodrigues RO, Pinho D, Miranda JM, Minas G, Lima R (2019) Blood cells separation and sorting techniques of passive microfluidic devices: from fabrication to applications. Micromachines 10(9):593

    Article  Google Scholar 

  47. Haeberle S, Zengerle R (2007) Microfluidic platforms for lab-on-a-chip applications. Lab Chip 7(9):1094–1110

    Article  Google Scholar 

  48. Rife JC, Bell MI, Horwitz JS, Kabler MN, Auyeung RCY, Kim WJ (2000) Miniature valveless ultrasonic pumps and mixers. Sens Actuat A 86(1–2):135–140

    Article  Google Scholar 

  49. Yc F (1997) Biomechanics: circulation

    Google Scholar 

  50. Roselli RJ, Diller KR (2011) Biotransport: principles and applications. Springer, New York, p 139

    Book  Google Scholar 

  51. Mohamed H (2012) Use of microfluidic technology for cell separation. In: Blood cell-an overview of studies in hematology, pp 195–226

    Google Scholar 

  52. Shields CW IV, Reyes CD, López 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 

  53. 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 

  54. Bharat et al (2020) Modelling of dielectrophoretic separation platelets from red blood cells. ISSN 2394–5125

    Google Scholar 

  55. Pethig R (2010) Dielectrophoresis: Status of the theory, technology, and applications. Biomicrofluidics 4(2):022811

    Article  Google Scholar 

  56. Khoshmanesh K, Nahavandi S, Baratchi S, Mitchell A, Kalantar-zadeh K (2011) Dielectrophoretic platforms for bio-microfluidic systems. Biosens Bioelectron 26(5):1800–1814

    Article  Google Scholar 

  57. Demircan Y, Özgür E, Külah H (2013) Dielectrophoresis: applications and future outlook in point of care. Electrophoresis 34(7):1008–1027

    Article  Google Scholar 

  58. Li M, Li WH, Zhang J, Alici G, Wen W (2014) A review of microfabrication techniques and dielectrophoretic microdevices for particle manipulation and separation. J Phys D Appl Phys 47(6):063001

    Article  Google Scholar 

  59. Jubery TZ, Srivastava SK, Dutta P (2014) Dielectrophoretic separation of bioparticles in microdevices: a review. Electrophoresis 35(5):691–713

    Article  Google Scholar 

  60. Sahin O, Kosar A, Yapici MK (2021) Modeling the dielectrophoretic separation of red blood cells (RBCs) from B-Lymphocytes (B-Cells). In: 2021 43rd annual international conference of the IEEE engineering in medicine & biology society (EMBC). IEEE, pp 1238–1241

    Google Scholar 

  61. Salahi A, Honrado C, Rane A, Caselli F, Swami NS (2022) Modified red blood cells as multimodal standards for benchmarking single-cell cytometry and separation based on electrical physiology. Anal Chem 94(6):2865–2872

    Article  Google Scholar 

  62. Praveenkumar S, Srigitha SN, Dinesh RG, Ramesh R (2020) Computational modeling of dielectrophoretic microfluidic channel for simultaneous separation of red blood cells and platelets. Curr Signal Transduct Ther 15(3):243–251

    Article  Google Scholar 

  63. Shirmohammadli V, Manavizadeh N (2019) Application of differential electrodes in a dielectrophoresis-based device for cell separation. IEEE Trans Electron Devices 66(9):4075–4080

    Article  Google Scholar 

  64. Shamloo A, Parast FY (2019) Simulation of blood particle separation in a trapezoidal microfluidic device by acoustic force. IEEE Trans Electron Devices 66(3):1495–1503

    Article  Google Scholar 

  65. Zhao S, Wu M, Yang S, Wu Y, Gu Y, Chen C, Huang TJ (2020) A disposable acoustofluidic chip for nano/microparticle separation using unidirectional acoustic transducers. Lab Chip 20(7):1298–1308

    Article  Google Scholar 

  66. Zhang Y, Chen X (2020) Dielectrophoretic microfluidic device for separation of red blood cells and platelets: a model-based study. J Braz Soc Mech Sci Eng 42(2):1–11

    Article  Google Scholar 

  67. Chiriac E, Avram M, Bălan C (2020) Dielectrophoretic separation of circulating tumor cells and red blood cells in a microfluidic device. In: 2020 International semiconductor conference (CAS). IEEE, pp 211–214

    Google Scholar 

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Acknowledgements

The authors would like to thank the Department of Electronics and Communication Engineering, Velagapudi Ramakrishna Siddhartha Engineering College for providing the necessary infrastructure.

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Correspondence to Jasti Sateesh .

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Turaka, S. et al. (2023). A Review on Recent Trends in the Segregation of Red Blood Cells Using Microfluidic Devices. In: Guha, K., Dutta, G., Biswas, A., Srinivasa Rao, K. (eds) MEMS and Microfluidics in Healthcare. Lecture Notes in Electrical Engineering, vol 989. Springer, Singapore. https://doi.org/10.1007/978-981-19-8714-4_3

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