Collaborative Research: Sense-and-Act Systems for Substance Release Modeling Drug Delivery Triggered by Immune-Sensing Based on Nanostructured Electrodes

合作研究：基于纳米结构电极的免疫传感触发的物质释放建模药物输送的感知与行动系统

• 批准号: 1403208
• 负责人: Evgeny Katz
• 金额: $ 33万
• 依托单位: Clarkson University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1403208&HistoricalAwards=false
• 关键词: Collaborative; Research; Sense; Act; Systems

Proposal: 1403208/1403228PI: Katz, Evgeny/Martinez-Lemus, LuisInstitution: Clarkson University/University of Missouri, ColumbiaTitle: Collaborative Research: Sense-and-Act Systems for Substance Release Modeling Drug Delivery Triggered by Immune-Sensing Based on Nanostructured ElectrodesThis research program combines a nanostructured biosensing system with a drug-release system. The transformative nature of this work is in the novel concept of integrating the electrochemical sensing and electrochemical release processes, promising revolutionary changes in personalized drug administration, particularly in emergency situations and in point-of-care and end-user applications. Specifically, the program aims at designing new systems for detecting critical conditions associated with diabetes, with the detection followed by automated drug release to compensate for the medical problem. The research is initially carried out with model systems, but will culminate in animal study. Technical description of the projectThis research program addresses key challenges to developing bioelectronic systems for sensing non-electrochemically active biomolecules, e.g., proteins, as well as redox non-active low-molecular-weight substances. The sensing process is integrated with the actuation resulting in the signal-triggered release of biomolecular substances mimicking drug-release, for example, Insulin release triggered by ketone bodies that are biomarkers of ketoacidosis. The developed bioelectronic systems integrate parts characteristic of biosensing/immunesensing systems, biofuel cells and signal-triggered substance-releasing systems, thus representing a unique combination of components for autonomous self-powered operation. Specifically, model systems of increasing complexity are developed that can yield negative potential at a nanostructured electrode by utilizing attached enzymes and immunesensing assemblies, in response to antigens. The resulting potential suffices for activation, on another part of the connected electrode system, of the process of dissolution of an alginate layer in which the molecules mimicking drug are entrapped, triggering drug release. Such self-powered and self-activated drug-release systems operating in response to biomarker sensing represent novel approach to the "Sense-and-Act" systems.

提案：1403208/1403228 PI：Katz，Evgeny/Martinez-Lemus，Luis机构：克拉克森大学/密苏里州大学，哥伦比亚标题：合作研究：基于纳米结构电极的免疫传感触发的物质释放建模药物递送的感知和行为系统这项研究计划将纳米结构生物传感系统与药物释放系统相结合。这项工作的变革性在于整合电化学传感和电化学释放过程的新概念，有望在个性化药物管理方面实现革命性的变化，特别是在紧急情况下以及在护理点和最终用户应用中。具体来说，该计划旨在设计新的系统，用于检测与糖尿病相关的关键状况，检测后自动释放药物，以弥补医疗问题。这项研究最初是用模型系统进行的，但最终将在动物研究中达到高潮。该项目的技术描述该研究计划解决了开发用于感测非电化学活性生物分子的生物电子系统的关键挑战，例如，蛋白质以及氧化还原非活性低分子量物质。感测过程与致动集成，导致模拟药物释放的生物分子物质的信号触发释放，例如，由酮体触发的胰岛素释放，酮体是酮症酸中毒的生物标志物。所开发的生物电子系统集成了生物传感/免疫传感系统、生物燃料电池和信号触发物质释放系统的部件特征，从而代表了用于自主自供电操作的部件的独特组合。具体而言，开发了越来越复杂的模型系统，其可以通过利用附着的酶和免疫传感组件响应于抗原而在纳米结构电极处产生负电位。所产生的电势足以在连接的电极系统的另一部分上激活藻酸盐层的溶解过程，其中捕获模拟药物的分子，从而触发药物释放。这种自供电和自激活的药物释放系统响应于生物标志物感测而操作，代表了“感测和行动”系统的新方法。