Continuous metabolite and protein profiling for immune monitoring

项目摘要 PI的研究计划旨在引入新颖的可穿戴和植入式技术， 通过解决基本的生物化学参数的连续测量， 与当前生物传感方法相关的科学挑战。免疫相关的准确诊断 疾病和个性化医疗的实现需要实时的物理和化学信息 人体参数，需要在许多不同的时间尺度上连续监测， 几分钟到几天生物电子学的最新进展使许多健康和疾病相关的物理 需要长时间持续监测的参数。然而，持续监测生化 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 临床上可行的连续生化监测。量化浓度的时间变化 体液中的细胞因子对于表征许多疾病中时间分辨的全身性炎症是必不可少的。 疾病目前的“终点”方法，如酶联免疫吸附测定，蛋白质印迹， 荧光连接的免疫吸附测定不适合于连续监测蛋白质生物标志物，例如 作为细胞因子。这是因为有几个局限性，包括依赖外部试剂和多个 洗涤步骤、耗时的过程以及需要训练有素的人员和庞大的设备。 用于实时测量蛋白质的现有生物传感器不具有设备内置刷新能力 并且仅提供有限的监视持续时间。此外，大多数生物传感器仅限于定量 单个分析物。因此，PI的目标是在未来五年内通过开发一种新的 生物传感平台，提供高灵敏度，特异性和稳定性的实时，定量，同时， 以及长期持续监测一组分子生物标志物，包括代谢物和蛋白质， 持续时间。目标1：对生物分子进行分子封装，以实现热稳定性、化学稳定性和生物稳定性， 持续监测。目标2：用于连续检测和定量分子的多路复用晶体管 生物标志物。目标3：柔软灵活的可穿戴设备，用于体内自动多参数监测。的 该提案的结果将使实时，定量和连续测量的面板， 用于长期免疫监测的分子生物标志物。连续分子监测 技术将作为一个平台，（i）能够及时诊断和预测免疫相关疾病 和医疗条件，以及时进行临床干预;（ii）作为分子表型分析工具， 有效的治疗策略;和（iii）提供有价值的洞察这些复杂的分子机制 以及异质性疾病和医疗状况。

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.