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Enabling Continuous in vivo Metabolic Monitoring with Microencapsulated SERS Assays

通过微胶囊 SERS 检测实现连续体内代谢监测

基本信息

批准号：
10224620
负责人：
Mike McShane
金额：
$ 18.48万
依托单位：
TEXAS ENGINEERING EXPERIMENT STATION
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10224620
关键词：
Address Affinity Animal Experiments Biological Assay Biological Markers Blood Caregivers Chronic Chronic Disease Chronic Kidney Failure Clinic Clinical Complex Data Devices Diabetes Mellitus Diagnosis Diffusion Disease Disease Progression Effectiveness Elements Encapsulated Equilibrium Evaluation Frequencies Goals Health Status Hot Spot Hydrogels Immune response Implant Individual Injectable Intercellular Fluid Kidney Malignant Neoplasms Measurement Measures Metabolic Metals Microencapsulations Monitor Optical Methods Optics Patient-Focused Outcomes Patients Performance Permeability Phase Prognostic Marker Proteins Quality of life Raman Spectrum Analysis Reporter Signal Transduction Surface Suspensions System Testing Tissues Transducers Treatment Cost base biomaterial compatibility capsule density disorder control health assessment implant material implanted sensor improved improved outcome in vivo individualized medicine innovation instrumentation interstitial metabolomics nanoGold nanomaterials nanoparticle non-invasive monitor novel novel strategies personalized medicine plasmonics prognostic tool prototype response sensor small molecule solid state specific biomarkers subcutaneous success targeted biomarker technology development temporal measurement tool

项目摘要

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.

项目总结/摘要最近的研究表明，使用特定的生物标志物调整的个体化治疗可以显着提高患者的生活质量。改善慢性肾病（CKD）等慢性病患者的预后，降低患病率的进步。然而，这些策略的广泛应用需要改善预后标志物，提高监测能力、准确性和频率的工具。随着代谢组学的进步揭示了新的生物标志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测，使患者能够采取行动，更集中地管理他们的病情。该项目旨在通过开发一种新型传感器来解决这个问题，代谢物生物标志物的测量。所提出的解决方案利用了一个微小的，可注射的，被动的“化学光学”，传感器”和光学系统来非侵入性地测量表面增强拉曼散射（Sers）谱这一概念是基于PI先前成功地开发了使用生物相容性传感器的植入式传感器。水凝胶，但采用广泛应用于各种目标的新方法。这种感知的可行性平台需要证明选择性，敏感性和可逆的传感材料，以及证据表明，目标生物标记物存在于植入物周围的间隙空间中。为了实现这一目标，已经确定了两个独立的具体目标来测试Sers的总体假设- 激活的植入物可用于追踪与慢性疾病状态相关的代谢物。目标1将涉及对三种类型的纳米材料传感封装提供的保护值的评估测定（直接、间接、亲和力）。将对存在复合介质时的功能进行量化，以评价封装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）植入的SERS使能的水凝胶的光学询问以识别材料要求、深度限制和宿主响应对测量信号的影响，以及（B）阐明血液和间质室之间的代谢物平衡。如果成功，该项目将为开发广谱代谢物传感器奠定基础，包括使得多分析物系统能够同时监测几个目标。这种能力将提高通过动物实验研究慢性疾病，并为临床代谢组学提供基础增强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，为慢性病患者和护理人员提供更完整的信息，对疾病进行适当的分期和追踪。除了研究的生物标志物，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，更精细的个性化治疗，这将提高生活质量。