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On-chip titration of an anticoagulant argatroban and determination of the clotting time within whole blood or plasma using a plug-based microfluidic system

Song, Helen and Li, Hung-Wing and Munson, Matthew S. and Van Ha, Thuong G. and Ismagilov, Rustem F. (2006) On-chip titration of an anticoagulant argatroban and determination of the clotting time within whole blood or plasma using a plug-based microfluidic system. Analytical Chemistry, 78 (14). pp. 4839-4849. ISSN 0003-2700. doi:10.1021/ac0601718.

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This paper describes extending plug-based microfluidics to handling complex biological fluids such as blood, solving the problem of injecting additional reagents into plugs, and applying this system to measuring of clotting time in small volumes of whole blood and plasma. Plugs are droplets transported through microchannels by fluorocarbon fluids. A plug-based microfluidic system was developed to titrate an anticoagulant (argatroban) into blood samples and to measure the clotting time using the activated partial thromboplastin time (APTT) test. To carry out these experiments, the following techniques were developed for a plug-based system: (i) using Teflon AF coating on the microchannel wall to enable formation of plugs containing blood and transport of the solid fibrin clots within plugs, (ii) using a hydrophilic glass capillary to enable reliable merging of a reagent from an aqueous stream into plugs, (iii) using bright-field microscopy to detect the formation of a fibrin clot within plugs and using fluorescent microscopy to detect the production of thrombin using a fluorogenic substrate, and (iv) titration of argatroban (0-1.5 mu g/mL) into plugs and measurement of the resulting APTTs at room temperature (23 degrees C) and physiological temperature (37 degrees C). APTT measurements were conducted with normal pooled plasma (platelet-poor plasma) and with donor's blood samples ( both whole blood and platelet-rich plasma). APTT values and APTT ratios measured by the plug-based microfluidic device were compared to the results from a clinical laboratory at 37 degrees C. APTT obtained from the on-chip assay were about double those from the clinical laboratory but the APTT ratios from these two methods agreed well with each other.

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URLURL TypeDescription CentralArticle Information
Ismagilov, Rustem F.0000-0002-3680-4399
Additional Information:Copyright © 2006 American Chemical Society. Published In Issue: July 15, 2006. Received for review January 25, 2006. Accepted April 21, 2006. This work was supported by NIH (R01 EB001903) and performed in part in the MRSEC microfluidic facility funded by NSF. We thank Jeffrey Gist, Krzysztof Mikrut, and Charlot Webb from the Coagulation Lab at the University of Chicago Hospital for measurement of the APTT with the commercial STA Coagulation instrument. We thank Matthew Runyon and Christian Kastrup for invaluable suggestions and assistance. We thank Bethany Johnson-Kerner for preliminary results. We thank Dr. Jonathan Miller and Dr. Rocky Shiu-ki Hui for helpful discussions. We thank Liang Li for surface tension and viscosity measurements for the carrier fluid. Supporting Information Available: Additional information as noted in the text:  a movie of the merging junction with the hydrophilic glass capillary, where CaCl2 solution is injected into a plug containing whole blood; a movie of a single plug being followed through a microchannel as a fibrin clot formed within the plug; and characterization of the size of the aqueous plug and the carrier fluid spacing between plugs for various water fractions. This material is available free of charge via the Internet at
Funding AgencyGrant Number
NIBIBR01 EB001903
Subject Keywords:flow-injection analysis; electrowetting-based actuation; protein crystallization conditions; heparin-induced thrombocytopenia; polymerase-chain-reaction; gas-liquid flow; of-care poc; a-chip; platelet-function; clinical diagnostics
Issue or Number:14
Record Number:CaltechAUTHORS:20130821-160732540
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:40873
Deposited By: Whitney Barlow
Deposited On:28 Aug 2013 16:14
Last Modified:10 Nov 2021 04:23

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