Development and utility of a wearable sensor for continuous monitoring of nutrients and hormones in subjects with chronic kidney disease

项目摘要 循环营养素、代谢物和激素都是用于风险评估和因果关系评估的有用生物标志物。 慢性疾病包括肥胖症、糖尿病、高血压、慢性肾病（CKD）和癌症。 目前监测营养素和激素的方法包括测量血液中的浓度 样品和/或体液，使用台式仪器，如自动生物分析仪和液体 色谱-质谱（LC-MS）驻扎在临床诊断实验室，导致不适， 与重复措施相关的高成本。皮肤动态血糖监测的研究进展 间质液（ISF）已经彻底改变了精确营养/医学和昼夜代谢的研究， 由于监测的可穿戴性质和连续性。由于与CKD进展相关的费用 （医疗保险支出的7%）和相关的发病率和死亡率，开发工具， 连续监测营养物质，代谢物和激素，超出连续葡萄糖监测仪的高度 以改变CKD进展的过程。因此，建议开发一种创新的 用于连续监测营养素（钠、钾和钙）的可穿戴多模式传感系统 和激素，包括25 OH维生素D（VitD）、全段甲状旁腺激素（iPTH）和成纤维细胞生长因子 23（FGF 23）。这种高风险/高回报的方法与传统的定期 用于实验室值趋势分析以及与其他临床参数相关性的血样采集。在R21阶段 （探索性），可穿戴的多模态传感器将被开发用于持续监测营养物质， 荷尔蒙可穿戴传感器将以基于适体的生物传感器为模型进行开发，用于连续测量。 单个小分子的监测和微创、基于微针的电位传感器， 多路复用和连续监测营养素（钠和钾）。在目标1中，我们将适应并建立在 这些生物传感器用于连续监测三种营养素（钠，钾和钙）和三种 激素（iPTH，FGF 23和VitD）。一种小型化印刷电路板及相关电子设备 将开发用于与智能手机进行无线数据通信的App。在目标2中，一个深层递归神经元 将利用网络方法进行联合多模态传感器数据校准，并评估 在大鼠模型中验证的可穿戴传感器。R33阶段（临床试验）将在达到 R21阶段的明确里程碑。在目标3中，该设备将进一步完善，皮肤ISF的范围 激素在人体实验中的作用在目标4中，饮食对营养素/激素浓度的贡献 将进行评估，并开发机器学习算法来预测CKD进展。的总目标 这些研究旨在开发一种创新的可穿戴多模态传感系统，用于连续监测 营养素和激素。这将为未来的工作奠定基础，其中这些和其他营养素/激素 对慢性病至关重要的营养成分可以被改变，从而实现精准营养的承诺。

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 system for continuous monitoring of nutrients and hormones. This will set the stage for future work wherein these and other nutrients/hormones critical to chronic diseases can be modified, thereby fulfilling the promise of Precision Nutrition.