集成微流控多电极聚集法用于即时血小板功能分析。
Integrated microfluidic multiple electrode aggregometry for point-of-care platelet function analysis.
机构信息
State Key Laboratory of Radio Frequency Heterogeneous Integration, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, Shanghai 200240, China.
Atantares Corp, One Broadway, Cambridge, MA, USA.
出版信息
Lab Chip. 2024 Oct 9;24(20):4859-4868. doi: 10.1039/d4lc00469h.
Point-of-care (POC) platelet function analysis can enable timely and precise management of bleeding and clotting in emergency rooms, operation rooms and intensive care units. However, POC platelet testing is currently not commonly performed, due to the complexity of sample preparation and limitations of existing technologies. Here, we report the development of an integrated microfluidic multiple electrode aggregometry (μMEA) sensor which uses multi-frequency impedance measurement of an embedded microelectrode array to perform platelet aggregometry directly from whole blood, sensing and measuring platelet activation in a label-free manner and without requiring any additional sample preparation. Additionally, the sensor incorporates blood flow during the assay to account for physiological flow and shear conditions. We show that the impedance signal from the sensor can be used to accurately detect and quantify platelet aggregation in a label-free manner, which was further validated by simultaneous fluorometric measurement and visualization of platelet aggregation. Further, we optimized the sensitivity and repeatability of the sensor using its frequency response and demonstrated that the sensor could be used to characterize drug dose-response in antiplatelet therapy with a frequency-tunable dynamic range. We also demonstrate that the sensor provides high sensitivity to perform platelet aggregometry under thrombocytopenic or low platelet count conditions. The μMEA sensor could thus enable POC platelet function analysis across several clinical applications.
即时检测(POC)血小板功能分析可以实现对急诊室、手术室和重症监护病房出血和凝血的及时和精确管理。然而,由于样本制备的复杂性和现有技术的局限性,POC 血小板检测目前并未广泛开展。在此,我们报告了一种集成的微流控多电极聚集仪(μMEA)传感器的开发,该传感器使用嵌入式微电极阵列的多频阻抗测量直接从全血中进行血小板聚集检测,以无标记的方式感应和测量血小板激活,而无需任何额外的样本制备。此外,该传感器在检测过程中整合了血液流动,以考虑生理流动和剪切条件。我们表明,传感器的阻抗信号可用于准确地以无标记方式检测和定量血小板聚集,这通过同时进行荧光测量和血小板聚集的可视化得到了进一步验证。此外,我们使用传感器的频率响应优化了其灵敏度和重复性,并展示了传感器可以用于在抗血小板治疗中以可调谐频率的动态范围来表征药物剂量反应。我们还表明,该传感器在血小板减少或血小板计数较低的情况下也能提供高灵敏度以进行血小板聚集检测。因此,μMEA 传感器可以实现多个临床应用场景下的即时检测血小板功能分析。