Integrated microcantilever fluid sensor as a blood coagulometer

Abstract

The work presented concerns the improvement in mechanical to thermal signal of a microcantilever fluid probe for monitoring patient prothrombin time (PT) and international normalized ratio (INR) based on the physical measurement of the clotting cascade. The current device overcomes hydrodynamic damping limitations by providing an internal thermal actuation force and is realised as a disposable sensor using an integrated piezoresistive deflection measurement. Unfortunately, the piezoresistor is sensitive to thermal changes and in the current design the signal is saturated by the thermal actuation. Overcoming this problem is critical for demonstrating a blood coagulometer and in the wider field as a microsensor capable of simultaneously monitoring rheological and thermal measurements of micro-litre samples. Thermal, electrical, and mechanical testing of a new design indicates a significant reduction in the thermal crosstalk and has led to a breakthrough in distinguishing the mechanical signal when operated in moderately viscous fluids (2-3 cP). A clinical evaluation has been conducted at The Royal London Hospital to measure the accuracy and precision of the improved microcantilever fluid probe. The correlation against the standard laboratory analyser INR, from a wide range of patient clotting times(INR 0.9-6.08) is equal to 0.987 (n=87) and precision of the device measured as the percentage coefficient of variation, excluding patient samples tested < 3 times, is equal to 4.00% (n=64). The accuracy and precision is comparable to that of currently available point-of-care PT/INR devices. The response of the fluid probe in glycerol solutions indicates the potential for simultaneous measurement of rheological and thermal properties though further work is required to establish the accuracy and range of the device as a MEMS based viscometer.