spacer Institute of Medicine & Engineering (IME) spacer|spacer Biotech spacer|spacer BE spacer|spacer CBE spacer|spacer Penn Center for Molecular Discovery spacer|spacer Blood Systems Biology spacer
   
   
arrow Home
spacer spacer
arrow Director
spacer spacer
arrow Laboratory/Directions
spacer spacer
arrow Members
spacer spacer
arrow Alumni
spacer spacer
arrow News
spacer spacer
arrow Calendar
spacer spacer
arrow Publications
spacer spacer
arrow Research
 

Mechanobiology
Thrombolysis
Coagulation
Bioadhesion
Gene Therapy
Drug/Device
Proteomics
Drug Discovery
Systems Biology
Microfluidics

spacer spacer
arrow Pubmed
spacer spacer
arrow Cell Lines
spacer spacer
arrow Software
spacer spacer
arrow Pubchem
 
   

 

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

1. 2008

Diamond SL, Lawrence MB, Neelamegham S. Harry L. Goldsmith, Ph.d. Ann Biomed Eng 2008; 36 (4): 523-526

2.

Neeves KB, Diamond SL. A membrane-based microfluidic device for controlling the flux of platelet agonists into flowing blood. Lab Chip 2008; 8 (5): 701-709

3.

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; 6 (12): 2193-2201

4.

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; 111 (7): 3507-3513

5.

Wong EY, Diamond SL. Enzyme microarrays assembled by acoustic dispensing technology. Anal Biochem 2008; 381 (1): 101-106

6. 2009

Wong EY, Diamond SL. Advancing microarray assembly with acoustic dispensing technology. Anal Chem 2009; 81 (1): 509-514

7. 2010

Maloney SF, Brass LF, Diamond SL. P2Y12 or P2Y1 inhibitors reduce platelet deposition in a microfluidic model of thrombosis while apyrase lacks efficacy under flow conditions. Integr Biol (Camb) 2010; 2 (4): 183-192

8. 2012

Muthard RW, Diamond SL. Blood clots are rapidly assembled hemodynamic sensors: flow arrest triggers intraluminal thrombus contraction. Arterioscler Thromb Vasc Biol 2012; 32 (12): 2938-2945

9.

Welsh JD, Colace TV, Muthard RW, Stalker TJ, Brass LF, Diamond SL. Platelet-targeting sensor reveals thrombin gradients within blood clots forming in microfluidic assays and in mouse. J Thromb Haemost 2012; :

10. 2013

Colace TV, Diamond SL. Direct observation of von Willebrand factor elongation and fiber formation on collagen during acute whole blood exposure to pathological flow. Arterioscler Thromb Vasc Biol 2013; 33 (1): 105-113

11.

Colace TV, Tormoen GW, McCarty OJ, Diamond SL. Microfluidics and coagulation biology. Annu Rev Biomed Eng 2013; 15 : 283-303

12.

Li R, Fries S, Li X, Grosser T, Diamond SL. Microfluidic assay of platelet deposition on collagen by perfusion of whole blood from healthy individuals taking aspirin. Clin Chem 2013; 59 (8): 1195-1204

13.

Muthard RW, Diamond SL. Side view thrombosis microfluidic device with controllable wall shear rate and transthrombus pressure gradient. Lab Chip 2013; 13 (10): 1883-1891

 

 

 

spacer Institute of Medicine & Engineering (IME) spacer|spacer Biotech spacer|spacer BE spacer|spacer CBE spacer|spacer EMTM spacer|spacer Penn Center for Molecular Discovery spacer|spacer Blood Systems Biology spacer


    Institute for Medicine & Engineering (IME)
    3340 Smith Walk
    1020 Vagelos Research Laboratories
    University of Pennsylvania
    Philadelphia, PA 19104-6383
    Lab No.: (215) 573-5704
    Fax: (215) 573-7227