Microfluidics

Since blood is a moving biological fluid in vivo, it is important to study thrombosis formation in vitro under physiological flow conditions.;To achieve this objective, we seek to develop methods that meet the following criteria in an attempt to mimic in vivo fluid dynamics, molecular transport, and biochemistry: 1) flow channels with physiologically relevant length scales, 2) the ability to introduce soluble molecules with spatial and temporal control, and 3) the ability to pattern surface molecules with spatial control. These criteria can be achieved using standard microfluidic methods. In addition, the small size of microfluidic channels can be utilized to measure hundreds of physical and biochemical interactions on a single device during a single experiment. This feature of microfluidics lends itself to combinatorial studies of pro- and anti-coagulant molecules that are typically done in well-plate assays under static conditions.

The Diamond Lab has developed a novel membrane based microfluidic device for studying the flux of pro-coagulant molecules (thrombin, ADP, thromboxane A2) into flowing blood. This device is being used to characterize fibrin formation as a function of thrombin flux and to investigate the stability of thrombi formed under varying agonist combinations.

Publications

Neeves KB, Diamond SL. A membrane-based microfluidic device for controlling the flux of platelet agonists into flowing blood. Lab Chip. 2008 May;8(5):701-9. Epub 2008 Apr 3.

Okorie UM, Denney WS, Chatterjee MS, Neeves KB, Diamond SL. Determination of surface tissue factor thresholds that trigger coagulation at venous and arterial shear rates: amplification of 100 fM circulating tissue factor requires flow. Blood. 2008 Apr 1;111(7):3507-13. Epub 2008 Jan 18.

Neeves KB, Maloney SF, Fong KP, Schmaier AA, Kahn ML, Brass LF, Diamond SL. Microfluidic focal thrombosis model for measuring murine platelet deposition and stability: PAR4 signaling enhances shear-resistance of platelet aggregates. J Thromb Haemost. 2008 Oct 7.

Wong EY, Diamond SL. Enzyme microarrays assembled by acoustic dispensing technology. Anal Biochem. 2008 Oct 1;381(1):101-6.

Diamond SL, Lawrence MB, Neelamegham S. Harry L. Goldsmith, Ph.d. Ann Biomed Eng. 2008 Apr;36(4):523-6.

Wong EY, Diamond SL.Advancing Microarray Assembly with Acoustic Dispensing Technology. Anal Chem. 2008 Nov 26.