CRII: SCH: A Smart Biosensor for Monitoring Cell Sickling in Patients with Sickle Cell Disease

本研究项目的目的是开发一种便携式智能生物传感器，用于监测镰状细胞病（SCD）患者的异常血液活动。尽管美国拥有先进的医疗保健系统，但SCD患者的预期寿命仅限于约50年，患者遭受不可预测的疼痛危机。血管闭塞是各种临床并发症和缩短寿命的主要原因。开发的方法将以微创方式提供快速血液检测。具体而言，将对作为血管闭塞的主要促成因素的细胞镰状化进行定量测量。该项目将为收集大量与临床结果相关的纵向细胞镰状化数据开辟新的机会，并帮助建立预测个体SCD患者疼痛危机的标准。当测得的细胞镰状化水平高于患者的“正常”范围时，将发出警报，从而可以更快地进行干预，以防止进一步的并发症和疼痛危机。这一努力可能会彻底改变SCD的诊断和个性化管理。智能生物传感器的基本思想是将微流体阻抗传感模块和传感接口模块集成在单个便携式设备上。一次性传感模块消耗一滴血，允许原位测量由脱氧异常镰状血红蛋白诱导的细胞镰状化。智能手机与生物传感器的集成将为SCD患者提供灵活的机会，以便在医院和实验室之外长期监测异常血液活动。为了实现这一目标，PI将集中于以下研究目标：（a）将微电极阻抗传感器集成到模拟体内缺氧诱导细胞镰状化条件的微流体缺氧通道中;确定电阻抗作为细胞镰状化传感信号的准确性和灵敏度;（B）用氧化还原酶试剂使微流体通道官能化以使缺氧控制单元官能化以及加速细胞镰状化速率;（c）通过蓝牙技术在微流体阻抗感测模块和智能手机之间建立通信，以分析和显示结果。这项研究将是第一次尝试在便携式设备中电测量由片上缺氧引发的细胞镰状化事件。该项目为生物传感、血液病理学和医疗监测领域做出了贡献。

The objective of this research project is to develop a portable, smart biosensor for monitoring of abnormal blood activities in patients with sickle cell disease (SCD). Despite the advanced healthcare system in the US, life expectancy of SCD patients is limited to about 50 years and patients suffer from unpredictable pain crises. Vascular occlusion is the primary cause of various clinical complications and shortened lifespan. The developed method will provide rapid blood testing in a minimally-invasive manner. Specifically, a quantitative measurement of cell sickling that is a primary contributing factor of vascular occlusion will be made. This project will open up new opportunities to gather large quantities of longitudinal cell sickling data to be associated with clinical outcomes and to help establish criteria for prediction of pain crises in individual SCD patients. Alerts will be raised when the measured cell sickling level is higher than the patient's "normal" range, allowing quicker interventions to prevent further complications and pain crises. This effort can potentially revolutionize the diagnostics and personalized-management of SCD. The essential idea of the smart biosensor is to integrate a microfluidic impedance sensing module and a sensing interface module on a single portable device. The disposable sensing module consumes a single drop of blood, allowing in situ measurement of cell sickling induced by deoxygenated abnormal sickle hemoglobin. The integration of smart phone with the biosensor will provide flexible opportunities to SCD patients for long-term monitoring of abnormal blood activities outside hospital and laboratory. To accomplish this goal, the PI will focus on the following research objectives: (a) Integrate a microelectrode impedance transducer into a microfluidic hypoxia channel that mimics in vivo hypoxia-induced cell sickling conditions; determine the accuracy and sensitivity of electrical impedance as a sensing signal of cell sickling; (b) Functionalize the microfluidic channel with oxidoreductase agent to miniaturize the hypoxia control unit as well as to accelerate the cell sickling rate; (c) Establish communication between the microfluidic impedance sensing module and a smartphone through Bluetooth technology for analysis and display of results. This research will be the first attempt to electrically measure cell sickling events triggered by on-chip hypoxia in a portable device. This project makes contributions to the fields of biosensing, hematopathology, and healthcare monitoring.