Enabling Continuous in vivo Metabolic Monitoring with Microencapsulated SERS Assays

项目摘要/摘要 最近的研究表明，使用特定生物标记物调整的个体化治疗可以显著 改善慢性疾病患者的预后，如慢性肾脏疾病(CKD)，降低 进步的力量。然而，广泛应用这类策略需要改善预后标志物和 提高监测能力、准确性和频率的工具。代谢组学的进展揭示了新的 生物标记物有望跟踪进展并提供可操作的数据，因此需要开发工具 用于自我监控，使患者能够采取行动并更深入地管理自己的病情。 该项目旨在通过开发一种新型传感器来解决这一问题，该传感器能够频繁、非侵入性地 代谢物生物标志物的测定。所提出的解决方案利用了一种微小的、可注射的、被动的“化学光学” “换能器”和无损测量表面增强拉曼散射(SERS)的光学系统 光谱。这一概念是基于PI在开发可植入传感器方面的先前成功，该传感器使用生物兼容性 水凝胶，但采用了一种新的方法广泛应用于各种目标。这种感知的可行性 平台需要具有选择性、敏感性和可逆性的传感材料的证明，以及 靶向生物标记物存在于种植体周围的间隙中。 为了实现这一目标，已经确定了两个独立的具体目标，以检验SERS- 启用的植入物可用于跟踪与慢性病状态相关的代谢物。目标1将涉及 封装对三种纳米材料传感保护作用的评价 分析(直接、间接、亲和)。在复杂介质中存在的功能将被量化以评估 包埋和水凝胶包埋的性能和有效性，以防止干扰。 在目标2中，皮下植入物可用于代谢监测的条件将是 确定，包括(A)对植入的表面增强拉曼散射水凝胶进行光学询问以识别材料 寄主反应对测量信号的要求、深度限制和影响以及(B)阐明 血液和间质之间的代谢物平衡。 如果成功，该项目将为开发广泛的代谢物传感器奠定基础，包括 使多分析系统能够同时监测多个目标。这一能力将增加 通过动物实验研究慢性病，并为临床代谢组学提供基础 具有增强的信息密度和时间分辨率的研究。如果成功，该项目将进一步支持 发展技术，为慢性病患者和照顾者提供更完整的信息 适当地分期和跟踪疾病的进展。除了所研究的生物标记物，这种方法可能是 适应其他目标。最终，这些工具将允许更频繁地评估健康状况，从而 更精致的个性化治疗，将提高生活质量。

Project Summary/Abstract Recent studies have shown that individualized therapies adjusted using specific biomarkers can significantly improve outcomes for patients with chronic diseases, such as chronic kidney disease (CKD), reducing the rate of progression. However, broad application such strategies requires improvement in prognostic markers and tools to enhance monitoring capacity, accuracy, and frequency. With advances in metabolomics revealing new biomarkers with promise for tracking progression and providing actionable data, there is a need to develop tools for self-monitoring that enable patients to take action and more intensively manage their condition. This project aims to address this problem by developing a novel sensor that enables frequent, noninvasive measurement of metabolite biomarkers. The proposed solution utilizes a tiny, injectable, passive “chemo-optical transducer” and an optical system to noninvasively measure Surface-Enhanced Raman Scattering (SERS) spectra. This concept is based on the PI’s prior success in developing implantable sensors using biocompatible hydrogels, but employs a new approach for broad application to a variety of targets. Feasibility of this sensing platform requires proof of selective, sensitive, and reversible sensing materials, as well as evidence that the target biomarkers are present in the interstitial space around implants. Towards this goal, two independent Specific Aims have been identified to test the overall hypothesis that SERS- enabled implants may be used to track metabolites of relevance to state of chronic disease. Aim 1 will involve evaluation of the protective value provided by encapsulation for three types of nanomaterial-based sensing assays (direct, indirect, affinity). Functionality in the presence of complex medium will be quantified to evaluate performance and effectiveness of encapsulation and hydrogel embedding for protection against interferences. In Aim 2, the conditions of under which subcutaneous implants may be used for metabolic monitoring will be determined, including (a) optical interrogation of implanted SERS-enabled hydrogels to identify material requirements, depth limitations, and effects of host response on measured signals and (b) elucidation of metabolite balance between blood and interstitial compartments. If successful, this project will lay the groundwork for developing a broad spectrum of metabolite sensors, including enabling multianalyte systems to simultaneously monitor several targets. This capability will increase the throughput of animal experiments to study chronic diseases as well as provide a basis for clinical metabolomics studies with enhanced information density and temporal resolution. If successful, this project will support further development of technology to provide chronic disease patients and caregivers more complete information to properly stage and track progression of the disease. Beyond the biomarkers studied, this approach may be adapted to other targets. Ultimately, these tools will allow more frequent assessment of health status, allowing more refined personalized therapy that will improve quality of life.