Rapid Electronic Detection of Drug Analytes in Blood

血液中药物分析物的快速电子检测

• 批准号: 7804563
• 负责人: Ryan J. White
• 金额: $ 5.05万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7804563
• 关键词: Accounting; Affect; Affinity; Beds; Binding; Biocompatible; Biomedical Engineering; Biophysics; Blood; Blood drug level result; Blood flow; Buffers; Chemistry; Complex; Conflict (Psychology); Detection; Development; Devices; Drug Controls; Drug Delivery Systems; Drug Monitoring; Electrochemistry; Electrodes; Electronics; Elements; Employee Strikes; Engineering; Exhibits; Exposure to; Feedback; Free Energy; Generations; Goals; Healthcare; Ionic Strengths; Kinetics; Laboratories; Lead; Left; Measurement; Measures; Methods; Methylene blue; Modification; Oxidation-Reduction; Patients; Performance; Pharmaceutical Preparations; Plasma; Play; Population; Property; Reaction Time; Reporter; Research; Research Training; Role; Sampling; Serum; Signal Transduction; Surface; Surveys; Technology; Temperature; Testing; Therapeutic; Thermodynamics; Time; Training; Urine; Variant; Whole Blood; aptamer; base; career; clinically relevant; density; design; dosage; drug efficacy; drug testing; electric field; environmental change; improved; meetings; method development; novel diagnostics; operation; point of care; programs; response; sensor; small molecule

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.

描述（由申请人提供）：开发用于测量血液药物水平的实时方法将彻底改变当代医疗保健的许多方面。例如，它可以提供一种在fly中调节药物输送（例如化学治疗剂）的方法，而这反过来又可以大大提高药物疗效，同时减少过量剂量的潜在有毒后果。拟议的研究的目的是调整现有的电化学适体（E-AB）传感技术来满足这种苛刻的应用。对于这种方法至关重要，E -AB平台已经证明了敏感的（微摩尔）可重复使用，快速（秒 - 分钟），无用的，并且有足够的选择性，可以直接使用血清和其他复杂的，临床上相关的样品矩阵。但是，尽管在理想的实验室条件下用尿液，血清和其他复杂材料进行挑战时，E-AB传感器的表现良好，但该技术需要进一步发展，然后才能实现流动，全血的临床相关检测。因此，我在此提出了提高E-AB平台的敏感性，稳定性和检测信心的方法的发展，以改善这项技术，从而满足这一雄心勃勃的目标的需求。为此，我将重点关注三个特定目标：1）通过系统地研究适体生物物理学和传感器制造对E-AB信号的影响，优化传感器检测限制和响应时间，2）通过通过综合和应用替代性redox的应用来提高全血的传感器性能，以衡量和纠正e-ab背景的能力，并纠正e-ab背景的准确性和置于置信度。这些特定目标中的每个特定目标都包含多种，以表征，修改和优化DMA Aptamer传感器的生物物理特性的多种免费策略，这些策略应该显着提高我们对这一潜在重要的新诊断技术的理解。在流血的血液中，开发监测药物水平的实时方法，例如治疗药物，将在护理点上彻底改变现代医疗保健。例如，护理点检测可以实现对患者个性化的前所未有的精度的反馈控制药物剂量。在这里，我提出了传感器的发展，即使雄心勃勃的最终目标是能够直接支持全血中的药物实时量化的目标。