Microrheological Coagulation Assay Exploiting Micromechanical Resonators

Rheological measurements in biological liquids yield insights into homeostasis and provide information on important molecular processes that affect fluidity. We present a fully automated.cantilever-based method for :highly precise and sensitive measurements of microliter sample volumes of human blood plasma coagulation (0.009-cP for viscosity range 0.5-3 cP and 0.0012 g/crn(3) for density range 0.91.1 g/cm(3)). Microcantilever at-rays are- driven by a piezoelectric element, and resonance frequencies and quality-factors of sensors that change over time are evaluated. A-highly accurate 'approximation of the hydrodynamic function is introduced that correlates resonance frequency and quality factor of cantilever beams immersed in a fluid to the viscosity and density of that fluid. The theoretical model was validated using glycerol reference solutions. We present a surface functionalization protocol- that allows minimization of unspecific protein adsorption onto cantilevers. Adsorption leads to measurement distortions and incorrect estimation- of-the fluid parameters (viscosity and density). Two hydrophilic terminated self-assembled. monolayers (SAMs) sensor surfaces are compared to a hydrophobic terminated SAM coating. As expected, the hydrophobic modified surfaces induced the highest mass adsorption and could promote Conformational changes of the proteins and subsequent abnormal: biological activity. Finally, the activated partial thromboplastan time (aPTT) coagulation assay was performed, and the viscosity, density, and cOagulation rate of human blood plasma were measured along with the standard-coagulation time.. The method could extend and improve current coagulation testing.