The real-time monitoring of specific medicine in situ in the body would provide high-precision, patient-specific pharmacokinetic information in support of the paradigm of personalized medicine. Therefore, it is of significance to develop such a platform that supports precision, real-time measurement of medicine in undiluted whole blood and even in vivo. In response, we propose here the use of electrochemical aptamer-based (E-AB) sensors for such application. Due to the fact that E-AB sensor suffers from low sensor-to-sensor reproducibility and often-severe baseline drift issues when deployed directly in whole blood, we propose here to use a dual redox-reporter system and use their ratio as sensor read-out to improve the reproducibility of E-AB sensors. In addition, we propose a biomimetic surface to improve the baseline stability, investigating the stability dependence on difference in charge effect and monolayer thickness. Finally, we believe the synergistic effect of these two would achieve the precise, real-time measurement of medicine directly in situ in the undiluted whole blood for a period of several days or even longer. This platform proposed here will achieve real-time continuous monitoring of pharmacokinetics to provide patients with personalized medicine.
临床上对病人体内的药物浓度进行精准、实时监测可以准确地提供个体差异化的药物代谢动力学信息,对实现个性化医疗具有非常重要的意义。因此,如何开发出一种对全血液样本中的药物浓度进行可持续地、高灵敏度、高选择性的实时监控平台,成为亟待解决的问题。本项目拟采用基于DNA适配体的电化学生物传感器为检测平台,针对其在全血样本持续测试中存在的器件差异性大和基线漂移两大难题,开展研究工作。本研究拟通过在同一适配体上引入两个氧化还原探针分子,利用内标比率法,降低电极的差异性,提高测试的可重现性。另一方面,通过引入仿生膜,降低传感器件表面的非特异性吸附,解决基线漂移问题,避免假性结果,重点考察膜电荷、膜厚对基线稳定性能的影响。最后利用比率法和仿生膜这两者的协同效应,实现对全血样本中药物浓度的精准、实时检测。这一平台将为实时监控药物代谢提供良好方案,推动电化学传感器在精准医疗领域中的应用。
临床对病人体内的药物代谢动力学信息进行精准、实时的监测对实现个性化医疗的实现具有重要意义。因此,目前亟需开发一种无需频繁校准、具有良好稳定性、可持续高灵敏度、高选择性的实时监控平台。本项目从核酸探针分子结构设计、电活性信使分子以及自组装膜等多方面出发,开发能够适应于复杂样本体系(如全血)中分析检测的核酸适配体型电化学生物传感器。具体地,将基于电化学适配体的传感器(E-AB 传感器)和双信号分子相结合,使用化学键合以及非共价键结合(插层法)两种方法引入双信号,大大解决器件批间差异性、需要频繁校准的问题。同时,通过在E-AB 传感器中引入不同亲水性自组装单分子膜,改善了基线稳定性以及选择性。为了适应体内不同体液环境的pH值变化, 本项目开发了能够适应不同pH值体液中测试的新型电活性分子,表现出优异的稳定性。此外,本项目的研究成果已应用于智能可穿戴医疗装备的研发之中,期望实现从基础研发到产业化应用的转化。
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数据更新时间:2023-05-31
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