Micro-optical prototyping of a surface acoustic wave-based point-of-care coagulation assay and first application in anticoagulated patients

Clinicians demand for methods to monitor effects of direct anticoagulants in the emergency setting. We recently described a coagulation assay based on surface acoustic waves (SAW) technology, which quantifies anticoagulant effects by image processing. Here we describe the first step in miniaturizing this laboratory method and provide a portable prototype that contains the optical illumination and automatic on-board image processing. A device about the size of a shoebox was realized that contains the SAW-chip, the signal generator, the LED illumination, as well as the necessary lenses, aperture, and CCD sensor. The microspheres in the blood were mixed by SAW, and the movement of the microspheres was quantified by on-board image processing. Upon contact with activation induced coagulation, this movement ceases, and coagulation times were measured and compared to the manual methods obtained by standard fluorescent microscopy. A major advantage of our method is the low amount of blood (~ 6 μL) necessary for testing. Results from the prototype correlated accurately with manual methods (Pearson correlation coefficient r = 0.9644). SAW-induced clotting time under anticoagulant treatment with dabigatran or rivaroxaban was well correlated with physicochemically determined plasma concentrations of these DOACs in anticoagulated patients. Compared to manual alignment of the chip under the fluorescence microscope, the prototype had a lower coefficient of variation. The last evolution step towards a point-of-care (POC)-device would be the development of a cartridge (containing calcium chloride and fluorescent label) such that a drop of blood can be introduced into the reaction vessel by a fluid actuator system.