Continuous metabolite and protein profiling for immune monitoring

用于免疫监测的连续代谢物和蛋白质分析

• 批准号: 10501149
• 负责人: Limei Tian
• 金额: $ 36.54万
• 依托单位: TEXAS ENGINEERING EXPERIMENT STATION
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10501149
• 关键词: Address; Biochemical; Biological; Biological Assay; Biosensing Techniques; Biosensor; Body Fluids; Chemicals; Clinical; Complex; Consumption; Detection; Devices; Diagnosis; Disease; Enzyme-Linked Immunosorbent Assay; Equipment; Fluorescence; Goals; Health; Human Resources; Human body; Immune; Immunologic Monitoring; Immunological Diagnosis; Immunosorbents; Intervention; Link; Measurement; Medical; Methods; Molecular; Monitor; Outcome; Process; Prognosis; Proteins; Public Health; Reagent; Research; Sensitivity and Specificity; Technology; Time; Training; Transistors; Western Blotting; accurate diagnosis; bioelectronics; cytokine; design; flexibility; in vivo monitoring; insight; molecular marker; molecular phenotype; novel; personalized medicine; programs; protein biomarkers; protein profiling; systemic inflammatory response; temporal measurement; therapeutically effective; tool; wearable device

Project Summary The PI's research program aims to introduce novel wearable and implantable technologies that enable continuous measurements of biochemical parameters for immune monitoring by addressing fundamental scientific challenges associated with current biosensing methods. Accurate diagnosis of immune-related diseases and realization of personalized medicine require real-time information of physical and chemical parameters of the human body, which need to be continuously monitored at many different time scales from minutes to days. Recent advances in bioelectronics enable many health and disease-related physical parameters to be continuously monitored over long durations. However, continuous monitoring of biochemical parameters in the human body remains extremely challenging. At present, very few biosensors are proven to be clinically viable for continuous biochemical monitoring. Quantifying the temporal changes in the concentrations of cytokines in body fluids is essential for characterizing time-resolved systemic inflammation across many diseases. Current “end-point” methods such as enzyme-linked immunosorbent assay, Western blot, and fluorescence-linked immunosorbent assay are not suitable for continuous monitoring of protein biomarkers, such as cytokines. This is because of several limitations, including the reliance on external reagents and multiple washing steps, time-consuming processes, and the need for highly trained personnel and bulky equipment. Existing biosensors for real-time measurements of proteins do not have device built-in refreshing capabilities and provide only a limited monitoring duration. In addition, most biosensors are limited to the quantification of single analytes. Therefore, the PI aims to address these limitations over the next five years by developing a novel biosensing platform that offers high sensitivity, specificity, and stability for real-time, quantitative, simultaneous, and continuous monitoring of a panel of molecular biomarkers, including metabolites and proteins, over long durations. Goal 1: Molecular encapsulation of biomolecules for thermal, chemical, and biological stability in continuous monitoring. Goal 2: Multiplexed transistors for continuous detection and quantification of molecular biomarkers. Goal 3: Soft and flexible wearable devices for automated multiparametric monitoring in vivo. The outcomes of this proposal will enable real-time, quantitative, and continuous measurements of a panel of molecular biomarkers for immune monitoring over long durations. The continuous molecular monitoring technologies will serve as a platform to (i) enable timely diagnosis and prognosis of immune-related diseases and medical conditions for prompt clinical intervention; (ii) function as molecular phenotyping tools to guide effective therapeutic strategies; and (iii) provide valuable insight into the molecular mechanisms of those complex and heterogeneous diseases and medical conditions.

项目摘要 PI的研究计划旨在引入新颖的可穿戴和可植入技术来实现 通过解决基本的基本监测的生化参数的连续测量 与当前的生物传感方法相关的科学挑战。与免疫相关的准确诊断 疾病和个性化医学的实现需要实时的物理和化学信息 人体的参数，需要在许多不同的时间范围内连续监测 几分钟到几天。生物电子学的最新进展使许多健康和疾病有关的身体 在长时间内将连续监控参数。但是，持续监测生化 人体中的参数仍然极为挑战。目前，很少有生物传感器被证明是 对于连续生化监测，临床上可行。量化浓度的临时变化 体液中的细胞因子的表征对于在许多人的时间分辨全身注射表征至关重要 疾病。当前的“终点”方法，例如酶相关的免疫吸附测定法，蛋白质印迹和 荧光连接的免疫吸附测定不适合连续监测蛋白质生物标志物，例如 作为细胞因子。这是由于几个限制，包括依赖外部试剂和多个 洗涤步骤，耗时的过程以及训练有素的人员和笨重的设备的需求。 实时测量蛋白质的现有生物传感器没有设备内置的刷新功能 并仅提供有限的监视时间。另外，大多数生物传感器仅限于 单个分析物。因此，PI旨在通过开发小说来解决未来五年的这些局限性 具有高灵敏度，特异性和稳定性的生物传感平台，可用于实时，定量，简单， 并连续监测一组分子生物标志物，包括代谢物和蛋白质，长期 持续时间。目标1：用于热，化学和生物学稳定性生物分子的分子封装 连续监视。目标2：多路复用晶体管，用于连续检测和定量分子 生物标志物。目标3：用于体内自动化多组合监测的柔软柔软可穿戴设备。这 该提案的结果将实时，定量和连续测量 长时间长时间进行免疫监测的分子生物标志物。连续的分子监测 技术将作为（i）启用与免疫相关疾病的及时诊断和预后的平台 以及迅速临床干预的医疗条件； （ii）作为指导分子表型工具的功能 有效的治疗策略； （iii）对那些复杂的分子机制提供了宝贵的见解 以及异质性疾病和医疗状况。