Scott Laboratory - Immios Biologics

Assessing Blood Cell Deformability:  From Ektacytometry to Microfluidics

Scott Laboratory Website

Canadian Blood Service • University of British Columbia • Centre for Blood Research • Vancouver, BC  Canada

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The physiology and morphology of the vascular bed and blood cells imparts unique rheological stress on circulating blood cells. Panel A: The vascular bed is composed of blood vessels of various sizes which create significant disparity in blood (fluid and cellular) velocity consequent to vessel diameter. The fluid flow induces rheological sheer stress while the vessel size can create biomechanical deformation of cellular elements.  Panel B:  Shown are the general physical parameters of human RBC and WBC.  Note that the biconcave RBC is a anuclear while within the WBC, the nucleus:cytoplasm (N:C) ratio of monocytes and lymphocytes are quite divergent.  RBC cytoplasmic viscosity is primarily defined by hemoglobin while in WBC, in addition to the nucleus, the presence of granules and vacuoles also impact intracellular viscosity and the aggregate cellular deformability. Panel C:  Blood cell deformability is crucial during vascular flow due to the size disparity between red blood cells and various leukocytes (e.g., monocytes and lymphocytes) and the capillary (4-5 µm) and splenic interendothelial clefts (0.5 µm).  Panels B-C are drawn approximately to scale.

Among the most crucial rheological characteristics of blood cells within the vasculature is their ability to undergo the shape change (i.e., deform).  The significance of cellular deformability is readily apparent based solely on the disparate mean size of human erythrocytes (~8 µm) and leukocytes (10-25 µm) compared to the minimum luminal size of capillaries (4-5 µm) and splenic interendothelial clefts (0.5-1.0 µm) they must transit. Over the past several years our laboratory has investigated the deformability of normal and abnormal blood cell using a variety of techniques (ektacytometry, micropore cell transit times and microfluidics).  Most recently, we have been investigating how a new generation of small, inexpensive, microfluidic devices can be used to examine the vascular deformability of erythrocytes and leukocytes.  These new microfluidic devices may prove useful in evaluating donor blood prior to transfusion and even in evaluating donors prior to blood collection.

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Measuring Deformability

RBC Deformability

WBC Deformability

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Jump To Lab Publications

Bütikofer, P., Lin, Z.W., Kuypers, F.A., Scott, M.D., Xu, C., Wagner, G.M., Chiu, D.T.-Y., and Lubin, B. Chlorpromazine inhibits vesiculation, alters phosphoinositide turnover and improves deformability of ATP-depleted red blood cells. Blood 73:1699-1704(1989). PMID: 2540856

Scott, M.D., Meshnick, S.R., Williams, R.A., Chiu, D.T.-Y., Pan, H.C., Lubin, B.H., and Kuypers, F.A. Qinghaosu-mediated oxidation in normal and abnormal erythrocytes. J. Lab. Clin. Med. 114:401-406(1989). PMID: 2794752

Scott, M.D., Eaton, J.W., Chiu, D. T.-Y., Kuypers, F.A., and Lubin, B.H. Enhancement of erythrocyte superoxide dismutase activity: Effect on cellular oxidant defense. Blood 74:2542-2549(1989). PMID: 2553167

Scott, M.D., Kuypers, F.A., Bütikofer, P., Bookchin, R.M., Ortiz, O., and Lubin, B.H. Effect of osmotic lysis and resealing on red cell structure and function. J. Lab. Clin. Med. 115:470-480(1990). PMID: 1691257

Rouyer-Fessard, P., Scott, M.D., Garel, M.C., Bachir, D., Galacteros, F., and Beuzard, Y. Fate of α-hemoglobin chains and erythrocyte defects in β Thalassemia. in Sixth Cooley’s Anemia Symposium (Bank, A. ed.) Annals of the New York Academy of Sciences, 612:106-117(1990). DOI: https://doi.org/10.1111/j.1749-6632.1990.tb24296.x

Scott, M.D., Rouyer-Fessard, P., Lubin, B.H., and Beuzard, Y. Entrapment of purified α-hemoglobin chains in normal erythrocytes: A model for β thalassemia. J. Biol. Chem. 265:17953-17959(1990). PMID: 2211672

Kuypers, F.A., Scott, M.D., Schott, M.A., Chiu, D.T.-Y., and Lubin, B.H. Use of ektacytometry to assess red cell susceptibility to oxidative stress. J. Lab. Clin. Med. 116:535-545(1990). PMID: 2212862

Scott, M.D., Rouyer-Fessard, P., Ba, M.S., Lubin, B.H., and Beuzard, Y. α- and β-hemoglobin chain induced changes in normal erythrocyte deformability: Comparison to β thalassemia intermedia and Hb H disease. Br. J. Haem., 80:519-526(1992). DOI: https://doi.org/10.1111/j.1365-2141.1992.tb04567.x

Leroy-Viard, K., Royer-Fessard, P., Sauvage, C., Scott, M.D., and Beuzard, Y. Modéles expérimentaux de la ß-thalassémie (Experimental models for ß-Thalassemia). Medicinè/Science, 8:784-789(1992). DOI: https://doi.org/10.4267/10608/3228

Scott, M.D. Entrapment of purified α-hemoglobin chains in normal erythrocytes as a model of human β thalassemia. in: The Use of Resealed Erythrocytes as Carriers and Bioreactors. (Magnani, M. and DeLoach, J.R., eds.) Plenum, New York, pgs. 139-148(1992). ISBN: 0-306-44345-7

Scott, M.D., van den Berg, J.J.M., Repka, T., Rouyer-Fessard, P., Hebbel, R.P., Beuzard, Y., and Lubin, B.H. Effect of excess α-hemoglobin chains on cellular and membrane oxidation in model ß thalassemic erythrocytes. J. Clin. Invest., 91:1706-1712(1993). DOI: https://doi.org/10.1172/jci116380

Lubin, B.H., van den Berg, J.J.M., Lewis, R.A., Scott, M.D., and Kuypers, F.A. Unique properties of the neonatal red cell. In: Neonatal Immunology and Haematology II (Xanthou, X., Bracci, R., and Prindull, G., eds.) Elsevier Science Publishers, Amsterdam., pgs. 79-89(1993). ISBN: 9780444816566

Lopez-Shirley, K., Zhang, F., Gosser, D., Scott, M.D., and Meshnick, S.R. Antimalarial quinones: Redox potential dependence of methemoglobin formation and heme release in erythrocytes. J. Lab. Clin. Med. 123:126-130(1994). PMID: 8288952

Scott, M.D. and Eaton, J.W. Thalassemic Erythrocytes: Cellular suicide arising from iron and glutathione-dependent oxidation reactions? Br. J. Haem., 91:811-819(1995). DOI: https://doi.org/10.1111/j.1365-2141.1995.tb05394.x

Kuypers, F.A., Schott, M.A. and Scott, M.D. Phospholipid composition in model ß thalassemic erythrocytes. Am. J. Hematol., 51:45-54(1996). DOI: https://doi.org/10.1002/(sici)1096-8652(199601)51:1%3C45::aid-ajh8%3E3.0.co;2-7

Murad, K.L., Mahany, K.L. Kuypers, F.A., Brugnara, C., Eaton, J.W, and Scott, M.D. Structural and functional consequences of antigenic modulation of red cells with methoxypoly(ethylene glycol). Blood, 93:2121-2127(1999). PMID: 10068687

Scott, M.D. H2O2 injury in ß thalassemic erythrocytes: Protective role of catalase and the prooxidant effects of GSH. Free Radicals in Biology & Medicine, 40:1264-1272(2006). DOI: https://doi.org/10.1016/j.freeradbiomed.2005.11.017

Kwan, J.M., Guo, Q., Kyluik-Price D.L., Ma, H. and Scott, M.D. Microfluidic Analysis of Cellular Deformability of Normal and Oxidatively-Damaged Red Blood Cells. American Journal of Hematology, 88:682–689 (2013). DOI: https://doi.org/10.1002/ajh.23476

Guo, Q., Duffy, S.P., Matthews, K., Santoso, A.T., Scott, M.D. and Ma, H. Microfluidic Analysis of Red Blood Cell Deformability. Journal of Biomechanics, 47:1767–1776 (2014). DOI: https://doi.org/10.1016/j.jbiomech.2014.03.038

Matthews, K., Myrand-Lapierre, M.-E., Ang, R.R., Duffy, S.P., Scott, M.D., and Ma, H. Microfluidic Deformability Analysis of the Red Cell Storage Lesion. Journal of Biomechanics, 48(15):4065-4072 (2015). DOI: https://doi.org/10.1016/j.jbiomech.2015.10.002

Matthews, K., Duffy, S.P., Myrand-Lapierre, M.-E., Ang, R.R., Li, L., Scott, M.D., and Ma, H. Microfluidic analysis of red blood cell deformability as a means to assess hemin-induced oxidative stress resulting from Plasmodium falciparum intraerythrocytic parasitism. Integrative Biology, 9(6):519-528 (2017). DOI: https://doi.org/10.1039/c7ib00039a

Kang, N., Guo, Q., Islamzada, E., Ma, H., and Scott, M.D., Microfluidic Determination of Lymphocyte Vascular Deformability: Effects of Intracellular Complexity and Early Immune Activation. Integrative Biology, 10:207-217 (2018). DOI: https://doi.org/10.1039/c7ib00191f

Scott, M.D., Matthews, K., and Ma, H. Assessing the Vascular Deformability of Erythrocytes and Leukocytes: From Micropipettes to Microfluidics. In: Current and Future Aspects of Nanomedicine (Editor: Khalil, I.), INTECH Croatia. ISBN 978-1-78985-870-9 (2019).  DOI: 10.5772/intechopen.90131

Islamzada, E., Matthews, K., Guo, Q, Santoso, A.T., Duffy, S.P., Scott, M.D., and Ma, H. Deformability based sorting of stored red blood cells reveals donor-dependent aging curves. Lab on a Chip, 2020, in press.  DOI: 10.1039/C9LC01058K

Scott, M.D. Model Human ß Thalassemic Erythrocytes: Effect of unpaired purified α-hemoglobin chains on normal erythrocytes. In: Beta Thalassemia (Editor: Zakaria, M.), INTECH.  ISBN: 978-1-83880-587-6 (2019). DOI: 10.5772/intechopen.90288


Relevant Laboratory Publications

Scott, M.D., Matthews, K., and Ma, H. Assessing the Vascular Deformability of Erythrocytes and Leukocytes: From Micropipettes to Microfluidics. In: Current and Future Aspects of Nanomedicine (Editor: Khalil, I.), INTECH Croatia. ISBN 978-1-78985-870-9 (2019). in press.  DOI: 10.5772/intechopen.90131

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