Rapid Electronic Detection of Drug Analytes in Blood

描述（由申请人提供）：用于测量血液药物水平的实时方法的开发将彻底改变当代医疗保健的许多方面。例如，它可以提供一种调节药物输送的手段（例如......化学治疗剂），这反过来可以大大提高药物功效，同时减少过量的潜在毒性后果。拟议研究的目标是调整现有的基于电化学适体（E-AB）的传感技术，以满足这一苛刻的应用。对于这种方法至关重要的是，E-AB平台已被证明具有灵敏（微摩尔）、可重复使用、快速（秒-分钟）、无试剂和选择性，足以直接用于血清和其他复杂的临床相关样品基质。然而，虽然E-AB传感器在理想的实验室条件下，在尿液、血清和其他复杂材料的挑战下表现良好，但该技术需要进一步发展，才能在流动的全血中实现临床相关检测。因此，我在此提出开发方法来提高E-AB平台的灵敏度、稳定性和检测置信度，以改进这项技术，使其满足这一雄心勃勃的目标的要求。为此，我将重点关注三个具体目标：1）通过系统研究适体生物物理学和传感器制造对E-AB信号传导的影响来优化传感器检测极限和响应时间，2）通过合成和应用替代的氧化还原标签来改善传感器在全血中的操作性能，以及3）开发测量和校正E-AB背景电流的方法，从而提高检测精度和置信度。包含在每个这些特定的目标是多个，互补的策略，表征，修改和优化的生物物理特性的DMA适配体传感器，应显着提高我们的理解，这一潜在的重要的新的诊断技术。用于监测流动血液中药物水平（如治疗药物）的实时方法的开发将彻底改变护理点的现代医疗保健。例如，床旁检测可以使反馈控制的药物剂量具有前所未有的精确度，该精确度针对患者进行个性化。在这里，我建议开发传感器，最终的目标是能够支持直接在全血中实时定量药物。

DESCRIPTION (provided by applicant): The development of real-time methods for the measurement of blood drug levels would revolutionize many aspects of contemporary healthcare. It could, for example, provide a means of regulating drug delivery (e.g....chemotherapeutics) on-the-fly which, in turn, could greatly improve drug efficacy while reducing the potentially toxic consequences of over-dosage. The goal of the proposed research is to adapt an existing, electrochemical aptamer-based (E-AB) sensing technology to meet this demanding application. Critical to this approach, the E-AB platform has already proven sensitive (micromolar) reusable, rapid (seconds - minutes), reagentless, and selective enough to employ directly in blood serum and other complex, clinically relevant sample matrices. However, while E-AB sensors perform well when challenged with urine, blood serum and other complex materials under ideal laboratory conditions, the technology requires further development before it will achieve clinically-relevant detection in flowing, whole blood. Thus motivated, I hereby propose the development of methods to improve the sensitivity, stability and detection confidence of the E-AB platform in order to improve this technology such that it meets the demands of this ambitious goal. To do so I will focus on three specific aims: 1) optimize sensor detection limits and response times via a systematic study of the effect of aptamer biophysics and sensor fabrication on E-AB signaling, 2) improve sensor performance for operation in whole blood via the synthesis and application of alternative redox tags, and 3) develop methods to measure and correct E-AB background current thus improving detection accuracy and confidence. Contained within each of these specific aims are multiple, complimentary strategies for characterization, modification and optimization of the biophysical properties of DMA aptamer sensors that should significantly improve our understanding of this potentially important new diagnostic technology. The development of real-time methods for monitoring drug levels, such as therapeutics, in flowing blood would revolutionize modern healthcare at the point-of-care. Point-of-care detection could, for example, enable feedback controlled drug dosage of unprecedented precision that is individualized to the patient. Here I propose the development of sensors, with the ultimate, if ambitious, goal of being capable of supporting the real-time quantification of drugs directly in whole blood.