Continuous metabolite and protein profiling for immune monitoring

项目摘要 PI的研究计划旨在引入新的可穿戴和可植入技术，使 免疫监测中生化参数的连续测量 与当前生物传感方法相关的科学挑战。免疫相关疾病的准确诊断 疾病和个性化医疗的实现需要实时的物理化学信息 人体参数，需要在许多不同的时间尺度上连续监测，从 几分钟到几天。生物电子学的最新进展使许多与健康和疾病相关的物理 在较长时间内持续监测参数。然而，生化指标的连续监测 人体内的参数仍然极具挑战性。目前，很少有生物传感器被证明是 临床上可以进行连续的生化监测。对浓度的时间变化进行量化 体液中细胞因子的变化对于描述时间分辨的系统性炎症是至关重要的 疾病。目前的“终点”方法，如酶联免疫吸附试验、Western印迹和 荧光免疫吸附试验不适合连续监测蛋白质生物标志物，如 作为细胞因子。这是由于几个限制，包括对外部试剂的依赖和多种 洗涤步骤、耗时的过程，以及对训练有素的人员和笨重设备的需求。 现有的用于蛋白质实时测量的生物传感器不具有设备内置的刷新功能 并且只提供有限的监测持续时间。此外，大多数生物传感器仅限于对 单一分析物。因此，PI的目标是在未来五年内通过开发一部小说来解决这些限制 生物传感平台，为实时、定量、同时、 以及对一组分子生物标志物的持续监测，包括代谢物和蛋白质 持续时间。目标1：生物分子在热稳定性、化学稳定性和生物稳定性方面的分子封装 持续监测。目标2：用于连续检测和量化分子的多路复用晶体管 生物标志物。目标3：用于体内自动多参数监测的软而灵活的可穿戴设备。这个 这项提议的结果将使实时、定量和连续的小组测量成为可能 用于长期免疫监测的分子生物标记物。连续的分子监测 技术将作为一个平台，以(I)实现免疫相关疾病的及时诊断和预后 和医疗条件，以便及时进行临床干预；(Ii)作为分子表型工具来指导 有效的治疗策略；以及(Iii)为这些复合体的分子机制提供有价值的见解 以及异质疾病和医疗条件。

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.