Department of Electrical and Computer Engineering, Duke University, Durham, NC, 27708, USA.
Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.
Biosens Bioelectron. 2021 Jan 15;172:112770. doi: 10.1016/j.bios.2020.112770. Epub 2020 Oct 26.
With an increasing number of patients relying on blood thinners to treat medical conditions, there is a rising need for rapid, low-cost, portable testing of blood coagulation time or prothrombin time (PT). Current methods for measuring PT require regular visits to outpatient clinics, which is cumbersome and time-consuming, decreasing patient quality of life. In this work, we developed a handheld point-of-care test (POCT) to measure PT using electrical transduction. Low-cost PT sensors were fully printed using an aerosol jet printer and conductive inks of Ag nanoparticles, Ag nanowires, and carbon nanotubes. Using benchtop control electronics to test this impedance-based biosensor, it was found that the capacitive nature of blood obscures the clotting response at frequencies below 10 kHz, leading to an optimized operating frequency of 15 kHz. When printed on polyimide, the PT sensor exhibited no variation in the measured clotting time, even when flexed to a 35 mm bend radius. In addition, consistent PT measurements for both chicken and human blood illustrate the versatility of these printed biosensors under disparate operating conditions, where chicken blood clots within 30 min and anticoagulated human blood clots within 20-100 s. Finally, a low-cost, handheld POCT was developed to measure PT for human blood, yielding 70% lower noise compared to measurement with a commercial potentiostat. This POCT with printed PT sensors has the potential to dramatically improve the quality of life for patients on blood thinners and, in the long term, could be incorporated into a fully flexible and wearable sensing platform.
随着越来越多的患者依赖血液稀释剂来治疗疾病，对快速、低成本、便携式凝血时间或凝血酶原时间 (PT) 检测的需求也在不断增加。目前测量 PT 的方法需要定期到门诊就诊，这既繁琐又耗时，降低了患者的生活质量。在这项工作中，我们开发了一种使用电转换测量 PT 的手持式即时检测 (POCT)。使用气溶胶喷射打印机和 Ag 纳米粒子、Ag 纳米线和碳纳米管的导电油墨，完全打印出低成本的 PT 传感器。使用台式控制电子设备测试这种基于阻抗的生物传感器，发现血液的电容性质会在低于 10 kHz 的频率下掩盖凝血反应，从而导致优化的工作频率为 15 kHz。当在聚酰亚胺上打印时，即使弯曲到 35 毫米的弯曲半径，测量的凝血时间也没有变化。此外，鸡和人血的一致 PT 测量结果说明了这些打印生物传感器在不同工作条件下的多功能性，其中鸡血液在 30 分钟内凝结，抗凝人血液在 20-100 秒内凝结。最后，开发了一种低成本的手持式 POCT 来测量人血的 PT，与使用商业电位计进行的测量相比，噪声降低了 70%。这种带有打印式 PT 传感器的 POCT 有可能显著改善正在服用血液稀释剂的患者的生活质量，并且从长远来看，它可以集成到一个完全灵活和可穿戴的传感平台中。
