A microfluidic device for continuous, real time blood plasma separation.

A microfluidic device for continuous, real time blood plasma separation is introduced. The principle of the blood plasma separation from blood cells is supported by the Zweifach-Fung effect and was experimentally demonstrated using simple microchannels. The blood plasma separation device is composed of a blood inlet, a bifurcating region which leads to a purified plasma outlet, and a concentrated blood cell outlet. It was designed to separate blood plasma from an initial blood sample of up to 45% inlet hematocrit (volume percentage of cells). The microfluidic network was designed using an analogous electrical circuit, as well as analytical and numerical studies. The functionality of this device was demonstrated using defibrinated sheep blood. During 30 minutes of continuous blood infusion through the device, all the erythrocytes (red blood cells) traveled through the device toward the concentrated blood outlet while only the plasma was separated at the bifurcating regions and flowed towards the plasma outlet. The device has been operated continuously without any clogging or hemolysis of cells. The experimentally determined plasma selectivity with respect to blood hematocrit level was almost 100% regardless of the inlet hematocrit. The total plasma separation volume percent varied from 15% to 25% with increasing inlet hematocrit. Due to the device's simple structure and control mechanism, this microdevice is expected to be used for highly efficient continuous, real time cell-free blood plasma separation from blood samples for use in lab on a chip applications.

[1]  S Chien,et al.  Comparative hemorheology--hematological implications of species differences in blood viscosity. , 1971, Biorheology.

[2]  G. Cokelet,et al.  The Fahraeus effect. , 1971, Microvascular research.

[3]  Y. Fung.  Stochastic flow in capillary blood vessels. , 1973, Microvascular research.

[4]  R. Skalak,et al.  Cell distribution in capillary networks. , 1980, Microvascular research.

[5]  S Westaby,et al.  Complement and the damaging effects of cardiopulmonary bypass. , 1983, The Journal of thoracic and cardiovascular surgery.

[6]  E. Blackstone,et al.  Effects of protamine administration after cardiopulmonary bypass on complement, blood elements, and the hemodynamic state. , 1986, The Annals of thoracic surgery.

[7]  E. Fosse,et al.  Complement activation during major operations with or without cardiopulmonary bypass. , 1987, The Journal of thoracic and cardiovascular surgery.

[8]  S. Khuri,et al.  The Effects of Complement Activation During Cardiopulmonary Bypass: Attenuation by Hypothermia, Heparin, and Hemodilution , 1988, Annals of surgery.

[9]  J. Utley.  Pathophysiology of Cardiopulmonary Bypass: Current Issues , 1990, Journal of cardiac surgery.

[10]  H. Redl,et al.  The cell in shock: the origin of multiple organ failure. , 1991, Resuscitation.

[11]  L. Sarkozi,et al.  Analytical evaluation of i-STAT Portable Clinical Analyzer and use by nonlaboratory health-care professionals. , 1993, Clinical chemistry.

[12]  J. Weiler,et al.  Cytokine and complement levels in patients undergoing cardiopulmonary bypass. , 1993, The Journal of thoracic and cardiovascular surgery.

[13]  G. von Bernuth,et al.  Complement activation during cardiopulmonary bypass in infants and children. Relation to postoperative multiple system organ failure. , 1993, The Journal of thoracic and cardiovascular surgery.

[14]  W. Olbricht,et al.  Effects of particle concentration on the partitioning of suspensions at small divergent bifurcations. , 1996, Journal of biomechanical engineering.

[15]  R. Astumian.  Thermodynamics and kinetics of a Brownian motor. , 1997, Science.

[16]  G. Whitesides,et al.  Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane). , 1998, Analytical chemistry.

[17]  Y. Zhao,et al.  Finite element analysis of the lift on a slightly deformable and freely rotating and translating cylinder in two-dimensional channel flow. , 1999, Journal of biomechanical engineering.

[18]  I. Birdi,et al.  The effects of cardiopulmonary bypass temperature on inflammatory response following cardiopulmonary bypass. , 1999, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[19]  G. Asimakopoulos.  Mechanisms of the systemic inflammatory response , 1999, Perfusion.

[20]  F F Becker,et al.  Differential analysis of human leukocytes by dielectrophoretic field-flow-fractionation. , 2000, Biophysical journal.

[21]  Frederick F Becker,et al.  Microsample preparation by dielectrophoresis: isolation of malaria. , 2002, Lab on a chip.

[22]  B. W. Roberts,et al.  Flow‐induced particulate separations , 2003 .

[23]  M. Yamada,et al.  Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel. , 2004, Analytical chemistry.

[24]  S. Westaby.  Organ dysfunction after cardiopulmonary bypass. A systemic inflammatory reaction initiated by the extracorporeal circuit , 2004, Intensive Care Medicine.

[25]  J. Sturm,et al.  Continuous Particle Separation Through Deterministic Lateral Displacement , 2004, Science.

[26]  T. Laurell,et al.  Continuous separation of lipid particles from erythrocytes by means of laminar flow and acoustic standing wave forces. , 2005, Lab on a chip.

[27]  T. Crowley,et al.  Isolation of plasma from whole blood using planar microfilters for lab-on-a-chip applications. , 2005, Lab on a chip.

[28]  Sung-Dong Yang,et al.  Blood Plasma Separation in Microfluidic Channels Using Flow Rate Control , 2005, ASAIO journal.

[29]  M. Yamada,et al.  Hydrodynamic filtration for on-chip particle concentration and classification utilizing microfluidics. , 2005, Lab on a chip.

[30]  B. W. Roberts,et al.  The distribution of freely suspended particles at microfluidic bifurcations , 2006 .