Continuous metabolite and protein profiling for immune monitoring

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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.