On-Chip Titration of an Anticoagulant Argatroban and Determination of the Clotting Time within Whole Blood or Plasma Using a Plug-Based Microfluidic System
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- 作者：Helen Song ; Hung-Wing Li ; Matthew S. Munson ; Thuong G. Van Ha ; and Rustem F. Ismagilov
- 刊名：Analytical Chemistry
- 出版年：2006
- 出版时间：July 15, 2006
- 年：2006
- 卷：78
- 期：14
- 页码：4839 - 4849
- 全文大小：665K
- 年卷期：v.78,no.14(July 15, 2006)
- ISSN：1520-6882
文摘
This paper describes extending plug-based microfluidicsto handling complex biological fluids such as blood,solving the problem of injecting additional reagents intoplugs, and applying this system to measuring of clottingtime in small volumes of whole blood and plasma. Plugsare droplets transported through microchannels by fluorocarbon fluids. A plug-based microfluidic system wasdeveloped to titrate an anticoagulant (argatroban) intoblood samples and to measure the clotting time using theactivated partial thromboplastin time (APTT) test. To carryout these experiments, the following techniques weredeveloped for a plug-based system: (i) using Teflon AFcoating on the microchannel wall to enable formation ofplugs containing blood and transport of the solid fibrinclots within plugs, (ii) using a hydrophilic glass capillaryto enable reliable merging of a reagent from an aqueousstream into plugs, (iii) using bright-field microscopy todetect the formation of a fibrin clot within plugs and usingfluorescent microscopy to detect the production of thrombin using a fluorogenic substrate, and (iv) titration ofargatroban (0-1.5 
g/mL) into plugs and measurementof the resulting APTTs at room temperature (23 
C) andphysiological temperature (37 C). APTT measurementswere conducted with normal pooled plasma (platelet-poorplasma) and with donor's blood samples (both wholeblood and platelet-rich plasma). APTT values and APTTratios measured by the plug-based microfluidic devicewere compared to the results from a clinical laboratoryat 37 C. APTT obtained from the on-chip assay wereabout double those from the clinical laboratory but theAPTT ratios from these two methods agreed well with eachother.
g/mL) into plugs and measurementof the resulting APTTs at room temperature (23 C) andphysiological temperature (37 C). APTT measurementswere conducted with normal pooled plasma (platelet-poorplasma) and with donor's blood samples (both wholeblood and platelet-rich plasma). APTT values and APTTratios measured by the plug-based microfluidic devicewere compared to the results from a clinical laboratoryat 37 C. APTT obtained from the on-chip assay wereabout double those from the clinical laboratory but theAPTT ratios from these two methods agreed well with eachother.