STTR Phase I: Microfluidic quartz resonator based blood plasma coagulation monitors

该STTR第一阶段项目旨在开发一种新型微流体传感器技术，可以在护理点（POC）测量血液凝固时间（特别是凝血酶原时间-PT，以国际标准化比率-INR测量）。对于数百万口服华法林（一种防止凝血的抗凝剂）的患者，必须经常监测PT/INR，以使其保持在安全的治疗范围内。本项目开发的POC传感器有望提供独立于影响患者血细胞计数因素的PT/INR测量，使其更安全、更准确。该研究的技术基础是将声传感与微流体技术联合收割机相结合。初步数据表明，该传感器可以测量粘度和密度的非常小的液体体积（~ 10 nL）准确。这项创新的成功实施和商业化将在快速增长的POC凝血测试市场中占据很大的市场份额，并创造数百个就业机会。本次STTR期间的研发过程也将有助于对该技术的充分理解？的潜力，这可能会导致其他自我/家庭测试仪器的病人。所提出的新型凝血监测器是基于微流控石英谐振器传感器。石英谐振器传感器可用于通过监测谐振频率的相关变化来测量耦合到其表面的流体粘度或质量的变化（这两者都发生在血液凝固期间）。石英谐振器的基础技术是成熟的、简单的和鲁棒的，并且适合于提供便携式和紧凑的仪器。这里的创新是集成的微流体技术，它将带来极低的液体体积要求，控制传感器如何观察液体（可用于增强由于凝固引起的传感器输出）以及芯片上血浆分离的好处。拟议的研究的主要目标是确定微流体设计和表面功能化，将优化微流体石英谐振器传感器？的凝血测量灵敏度，并实现片上血浆分离PT/INR测量。

This STTR Phase I project aims to develop a novel microfluidic sensor technology that can measure blood coagulation times (specifically prothrombin time-PT, measured in international normalized ratio-INR) at point-of-care (POC). PT/INR has to be monitored frequently for millions of patients on oral Warfarin (an anticoagulant that prevents clotting) to keep them in a safe therapeutic range. The POC sensor developed in this project is expected to provide PT/INR measurements independent of factors influencing the blood counts of the patients, making it safer and more accurate. The technological foundation of the proposed research is to combine acoustic sensing with microfluidics. The preliminary data demonstrates that the proposed sensor can measure viscosity and density of extremely small liquid volumes (~ 10 nL) accurately. The successful implementation and commercialization of this innovation will result in a big market share in the rapidly growing POC coagulation test market and create hundreds of jobs. The research and development process during this STTR will also contribute to the full understanding of this technology?s potential, which can result in other self/home testing instruments for patients. The proposed novel coagulation monitor is based on microfluidic quartz resonator sensors. Quartz resonator sensors can be used to measure changes in fluid viscosity or mass coupled to their surfaces (both of which occur during coagulation of blood) by monitoring the associated changes in the resonance frequency. The technology underlying quartz resonators is well established, simple and robust, and amenable to provide portable and compact instrumentation. The innovation here is the integrated microfluidics, which will bring the benefits of extremely low liquid volume requirements, control over how liquid is observed by the sensor (which can be used to enhance sensor output due to the coagulation), and on-chip blood plasma separation. The key objectives of the proposed research are to determine the microfluidics design and the surface functionalization that will optimize a microfluidic quartz resonator sensor?s coagulation measurement sensitivity, and to implement on-chip blood plasma separation for PT/INR measurements.