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，可以测量护理点(POC)的凝血时间(特别是凝血酶原时间-PT，以国际标准化比率-INR测量)。数百万服用华法林(一种防止凝血的抗凝剂)的患者必须经常监测PT/INR，以保持他们在安全的治疗范围内。在该项目中开发的POC传感器有望提供独立于影响患者血细胞计数的因素的PT/INR测量，使其更安全和更准确。本研究的技术基础是将声传感技术与微流控技术相结合。初步数据表明，该传感器能够准确测量极小体积液体(~10nL)的粘度和密度。这项创新的成功实施和商业化将导致在快速增长的POC凝聚测试市场占据很大的市场份额，并创造数百个就业机会。在此期间的研发过程也将有助于充分理解这项技术-S的潜力，这可能会导致其他自我/家庭测试仪器的患者。提出的新型凝血监测仪是基于微流控石英谐振器传感器。石英谐振器传感器可以通过监测共振频率的相关变化来测量流体粘度或耦合到其表面的质量的变化(这两者都发生在血液凝固过程中)。石英谐振器的基础技术成熟、简单而坚固，并可提供便携和紧凑的仪器。这里的创新是集成的微流体，它将带来极低的液体体积要求的好处，控制传感器观察液体的方式(由于凝血可以用来增强传感器输出)，以及芯片上的血浆分离。这项研究的主要目标是确定微流控设计和表面功能化，以优化微流控石英谐振器传感器-S凝血测量灵敏度，并实现用于PT/INR测量的芯片上血浆分离。

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.