Aptamer-Hydrogel Hybrid Sensors for Continuous Therapeutic Drug Monitoring

用于连续治疗药物监测的适体-水凝胶混合传感器

• 批准号: 9187878
• 负责人: Ryan J. White
• 金额: $ 12.96万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE COUNTY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2017-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9187878
• 关键词: Antibiotics; Architecture; Beds; Biocompatible Materials; Biological; Biosensor; Blood; Chemicals; Chemistry; Clinic; Collaborations; Complex; Couples; Coupling; Data; Detection; Development; Diagnostic; Dose; Drug Monitoring; Electrodes; Engineering; Failure; Feedback; Formulation; Foundations; Goals; Guidelines; Healthcare; Hour; Hybrids; Hydrogels; Individual; Intravenous; Knowledge; Masks; Membrane; Methodology; Modeling; Monitor; Nature; Neurons; Patient-Focused Outcomes; Patients; Performance; Pharmaceutical Preparations; Pulmonary Cystic Fibrosis; Renal function; Research; Resolution; Sampling; Science; Signal Transduction; Silicon; Specificity; Surface; System; Testing; Therapeutic; Time; Tissues; Tobramycin; Toxic effect; Translations; Treatment Efficacy; Whole Blood; Work; aptamer; base; biochip; biological systems; biomaterial compatibility; clinically actionable; combat; design; dosage; improved; in vivo; individual patient; ototoxicity; personalized medicine; point of care; polyacrylamide hydrogels; response; sensor; small molecule; temporal measurement

 DESCRIPTION: The objective of this proposal is to develop electrochemical biosensors capable of providing continuous real-time therapeutic drug monitoring with unprecedented chemical specificity and temporal resolution. The ability to provide real-time information about an individual's response to therapeutics has the potential to revolutionize healthcare by offering personalized treatment. Drugs with narrow therapeutic windows become toxic or ineffective if over- or under-dosed. Maintaining the most efficient dosage, personalized to the patient, can reduce toxicity, maximize efficacy of treatment, and ultimately improve patient outcome. Unfortunately, current methodologies for monitoring therapeutics are cumbersome (requiring tens of minutes to hours) and are performed removed from the point of care precluding real-time feedback. Biosensors represent a promising alternative but often fail to respond to specific targets when challenged in biological sample matrices. This failure is a result of biofouling, which masks the true sensor response. Here, we aim to leverage state-of-the-art bioanalytical science with biocompatible material (hydrogel) engineering to develop hybrid sensors capable of real-time continuous therapeutic drug monitoring in vivo. The specific goal is to couple the biocompatibility of hydrogel membranes with the rapid, selective, and specific recognition capabilities of electrochemical, aptamer-based (E-AB) sensors. The aims of the proposal are to first establish fundamental and universal sensor design and biomaterial engineering guidelines followed by the translation of the sensor to commercially engineered in vivo probes for multi- analyte detection. The short-term goal is to develop sensors for the real-time monitoring of the antibiotic tobramycin used for treatment of cystic fibrosis pulmonary exacerbations. In the long-term, combining the sensor development expertise of the PI and the biomaterial engineering expertise of the Co-PI, the general sensors developed here will be adapted to interface with a variety of biological interfaces including tissue and neuronal systems.

 描述：该提案的目的是开发能够以前所未有的化学特异性和临时分辨率提供连续实时治疗药物监测的电化学生物传感器。提供有关个人对治疗反应的实时信息的能力，有可能通过提供个性化治疗来彻底改变医疗保健。如果过度或剂量不足，则具有狭窄治疗窗口的药物会变得有毒或无效。维持对患者个性化的最有效剂量可以降低毒性，治疗的最大有效性，并最终改善患者预后。不幸的是，目前的监测治疗方法很麻烦（需要数十分钟到小时），并且从护理点进行删除，从而排除了实时反馈。生物传感器代表了一种有希望的替代方案，但在生物样品材料中挑战时通常无法对特定目标做出反应。该故障是生物污染的结果，它掩盖了真实的传感器响应。在这里，我们旨在利用生物相容性材料（水凝胶）工程来利用最先进的生物分析科学，以开发能够在体内实时连续治疗药物监测的混合传感器。具体的目标是将水凝胶膜的生物相容性与电化学基于基于合化的（E-AB）传感器的快速，选择性和特定的识别能力相结合。该提案的目的是首先建立基本和通用的传感器设计和生物材料工程指南，然后将传感器转换为在体内进行商业设计以进行多种分析的检测。短期目标是开发传感器，以实时监测用于治疗囊性纤维化肺部恶化的抗生素毒素。从长远来看，将PI的传感器开发专业知识与Co-Pi的生物材料工程专业知识相结合，此处开发的一般传感器将适应与包括组织和神经元系统在内的各种生物接口的接口。