Piezoresistive Sensing Platform for High-Throughput Single Platelet Nanomechanics

Georgia Tech Research Corporation, Atlanta GA

Investigators

Abstract

Abnormal clotting and bleeding are the cause, or a lethal complication, of many diseases including heart disease, stroke, and cancer. During the formation of blood clots, biochemically activated platelets interact with growing networks of fibrin polymers and contract against this fibrin scaffold. Today, few tools exist to predict when a person may experience abnormal clotting or bleeding, and nearly all of these tools rely on sensing biochemicals associated with clot formation or breakup. However, new research has shown that changes to the physical forces nominally applied by platelets are associated with bleeding. Rather than attempting to sense trace amounts of biochemicals associated with clotting, the ultimate goal of this project is, thus, to examine platelet forces to predict abnormal bleeding and clotting. The physical strength of a cell may be directly linked to bleeding and clotting, thus representing a potentially "disruptive" paradigm of biophysical testing that could be applied to many other diseases. While promising, this novel approach requires assaying a large population of platelets to gain clinically relevant data and predict bleeding and clotting disorders. Using today's technologies, which are mostly utilizing microscopy-based optical techniques, this still requires too much time to be useful in the clinic. To overcome the limitations of optical techniques to measure platelet forces, this proposal seeks to explore non-optical transduction mechanisms to create a rapid, high-throughput platform capable of assaying large numbers of individual platelets. More specifically, the goal of this project is to develop piezoresistive sensing platforms for high-throughput mechanical testing of single blood platelets. Using piezoresistive transducers for force sensing, the proposed platforms will overcome the key bottleneck to high-throughput single-cell force analysis with all existing techniques, namely their reliance on optical imaging. The two proposed sensing platforms are based on arrays of microdots and nanopillars and mimic the two most common optical platforms for cell force measurements, traction force microscopy and microfabricated post array detectors, respectively. Thereby, the contraction force exerted by a blood platelet on a pair of microdots is measured with underlying sub-micrometer strain gauges, while the platelet-contraction-induced deflection of nanopillars is sensed by stress-sensitive metal-oxide-semiconductor field effect transistors (MOSFET) embedded into the underlying substrate. On the sensing system side, the intellectual merit lies in the design and fabrication of large arrays of piezoresistive force sensors with nano-Newton force resolution in an ultra-small form factor, targeting a pitch for the microdot/pillar pairs of less than 15µm.