Blood coagulation screening using a paper-based microfluidic lateral flow device.

A simple approach to the evaluation of blood coagulation using a microfluidic paper-based lateral flow assay (LFA) device for point-of-care (POC) and self-monitoring screening is reported. The device utilizes whole blood, without the need for prior separation of plasma from red blood cells (RBC). Experiments were performed using animal (rabbit) blood treated with trisodium citrate to prevent coagulation. CaCl2 solutions of varying concentrations are added to citrated blood, producing Ca(2+) ions to re-establish the coagulation cascade and mimic different blood coagulation abilities in vitro. Blood samples are dispensed into a paper-based LFA device consisting of sample pad, analytical membrane and wicking pad. The porous nature of the cellulose membrane separates the aqueous plasma component from the large blood cells. Since the viscosity of blood changes with its coagulation ability, the distance RBCs travel in the membrane in a given time can be related to the blood clotting time. The distance of the RBC front is found to decrease linearly with increasing CaCl2 concentration, with a travel rate decreasing from 3.25 mm min(-1) for no added CaCl2 to 2.2 mm min(-1) for 500 mM solution. Compared to conventional plasma clotting analyzers, the LFA device is much simpler and it provides a significantly larger linear range of measurement. Using the red colour of RBCs as a visible marker, this approach can be utilized to produce a simple and clear indicator of whether the blood condition is within the appropriate range for the patient's condition.

[1]  Audrey K. Ellerbee,et al.  Quantifying colorimetric assays in paper-based microfluidic devices by measuring the transmission of light through paper. , 2009, Analytical chemistry.

[2]  A. B. Frazier,et al.  Paramagnetic capture mode magnetophoretic microseparator for high efficiency blood cell separations. , 2006, Lab on a chip.

[3]  G. Whitesides,et al.  Paper-based piezoresistive MEMS sensors. , 2011, Lab on a chip.

[4]  D. Ingber,et al.  Micromagnetic-microfluidic blood cleansing device. , 2009, Lab on a chip.

[5]  Anthony J. Killard,et al.  Development of a fluorescent method for detecting the onset of coagulation in human plasma on microstructured lateral flow platforms. , 2011, The Analyst.

[6]  Han Wei Hou,et al.  Microfluidic Devices for Blood Fractionation , 2011, Micromachines.

[7]  S. Shevkoplyas,et al.  Integrated separation of blood plasma from whole blood for microfluidic paper-based analytical devices. , 2012, Lab on a chip.

[8]  R. Crooks,et al.  Three-dimensional paper microfluidic devices assembled using the principles of origami. , 2011, Journal of the American Chemical Society.

[9]  A. J. Steckl,et al.  Circuits on cellulose , 2013, IEEE Spectrum.

[10]  P. Yager,et al.  Controlled reagent transport in disposable 2D paper networks. , 2010, Lab on a chip.

[11]  George M Whitesides,et al.  Electrochemical sensing in paper-based microfluidic devices. , 2010, Lab on a chip.

[12]  M. A. Mansfield,et al.  The Use of Nitrocellulose Membranes in Lateral-Flow Assays , 2005 .

[13]  Bridget B. Kelly,et al.  Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health , 2010 .

[14]  Chong H Ahn,et al.  An on-chip whole blood/plasma separator with bead-packed microchannel on COC polymer , 2010, Biomedical microdevices.

[15]  Raphael C. Wong,et al.  Lateral flow immunoassay , 2009 .

[16]  G. Whitesides,et al.  Patterned paper as a platform for inexpensive, low-volume, portable bioassays. , 2007, Angewandte Chemie.

[17]  D. Bjoraker,et al.  3.8% sodium citrate (1:9) is an inadequate anticoagulant for rabbit blood with high calcium. , 1981, Thrombosis research.

[18]  Mehmet Toner,et al.  Blood-on-a-chip. , 2005, Annual review of biomedical engineering.

[19]  J. L. Delaney,et al.  Electrogenerated chemiluminescence detection in paper-based microfluidic sensors. , 2011, Analytical chemistry.

[20]  E. W. Washburn The Dynamics of Capillary Flow , 1921 .

[21]  P. Sperryn,et al.  Blood. , 1989, British journal of sports medicine.

[22]  T. Lindahl,et al.  Development of a point of care lateral flow device for measuring human plasma fibrinogen. , 2010, Analytical chemistry.

[23]  Luke P. Lee,et al.  Stand-alone self-powered integrated microfluidic blood analysis system (SIMBAS). , 2011, Lab on a chip.

[24]  Claudio Parolo,et al.  Paper-based nanobiosensors for diagnostics. , 2013, Chemical Society reviews.

[25]  F. Ataullakhanov,et al.  Calcium threshold in human plasma clotting kinetics. , 1994, Thrombosis research.

[26]  M. Dembo,et al.  Reversible sodium pump defect and swelling in the diabetic rat erythrocyte: effects on filterability and implications for microangiopathy. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[27]  David E. Williams,et al.  Point of care diagnostics: status and future. , 2012, Analytical chemistry.

[28]  J. Koepke Point-of-Care Coagulation Testing , 2000 .

[29]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[30]  Ali Kemal Yetisen,et al.  Paper-based microfluidic point-of-care diagnostic devices. , 2013, Lab on a chip.

[31]  Wei Shen,et al.  Progress in patterned paper sizing for fabrication of paper-based microfluidic sensors , 2010 .

[32]  G. Whitesides,et al.  Understanding wax printing: a simple micropatterning process for paper-based microfluidics. , 2009, Analytical chemistry.

[33]  D. Beebe,et al.  Physics and applications of microfluidics in biology. , 2002, Annual review of biomedical engineering.