PROJECT SUMMARY Circulating nutrients, metabolites and hormones are both useful biomarkers for risk assessment and causal agents of chronic diseases including obesity, diabetes, hypertension, chronic kidney disease (CKD) and cancer. The current methods for monitoring nutrients and hormones involve measurement of concentrations in blood samples and/or body fluids using benchtop instruments, such as automated Bioanalyzers and liquid chromatography–mass spectrometry (LC-MS) stationed in Clinical Diagnostic Labs, leading to discomfort and high costs associated with repeated measures. Recent advances in continuous glucose monitoring in skin interstitial fluid (ISF) have revolutionized the study of Precision Nutrition/Medicine and Circadian metabolism, due to the wearable nature and continuity of monitoring. Because of the costs associated with CKD progression (7% of Medicare expenditures) and the associated morbidity and mortality, the development of tools to continuously monitor nutrients, metabolites and hormones beyond the continuous glucose monitor is highly desirable in order to alter the course of CKD progression. It is therefore proposed to develop an innovative wearable multimodal sensing system for continuous monitoring of nutrients (sodium, potassium and calcium) and hormones, including 25OH Vitamin D (VitD), intact parathyroid hormone (iPTH), and fibroblast growth factor 23 (FGF23). This high-risk/high-reward approach is fundamentally different from traditional method of periodic blood sampling for the trending of lab values and correlation with other clinical parameters. In the R21 phase (exploratory), wearable multimodal sensors will be developed for continuous monitoring of nutrients and hormones. The wearable sensors will be developed modeled on aptamer-based biosensors for continuous monitoring of individual small molecules and a minimally-invasive, microneedle-based potentiometric sensor for multiplexed and continuous monitoring of nutrients (sodium and potassium). In Aim 1, we will adapt and build on these biosensors for continuous monitoring of three nutrients (sodium, potassium and calcium) and three hormones (iPTH, FGF23 and VitD), simultaneously. A miniaturized print circuit board and associated electronics for wireless data communication with a smartphone App will be developed. In Aim 2, a deep recurrent neural network approach for joint multi-modal sensor data calibration will be utilized and the utility and reliability of wearable sensors validated in rat models. The R33 phase (Clinical Trial) will be undertaken based on achieving well-defined milestones in the R21 phase. In Aim 3, the device will be further refined and the ranges of skin ISF hormones in human subjects established. In Aim 4, the contribution of diet on nutrients/ hormones concentrations will be assessed and machine learning algorithms developed to predict CKD progression. The overall goal of these studies is to develop an innovative wearable multimodal sensing...