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

项目总结 循环营养素、代谢物和激素都是风险评估和病因分析的有用生物标志物。 慢性疾病的病原体，包括肥胖、糖尿病、高血压、慢性肾脏疾病(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。 使用自动生物分析仪和液体等台式仪器采集样本和/或体液 色质联用(LC-MS)进驻临床诊断实验室，导致不适和 与重复措施相关的高成本。皮肤血糖连续监测的研究进展 间质液(ISF)使精确营养/医学和昼夜代谢的研究发生了革命性的变化， 由于可穿戴的性质和监测的连续性。因为与CKD进展相关的成本 (占医疗保险支出的7%)以及相关的发病率和死亡率，开发工具以 持续监测营养素、代谢物和激素超越连续血糖监测是非常重要的 以改变CKD进展的进程是可取的。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25OH维生素D(维生素D)、完整甲状旁腺激素(IPTH)和成纤维细胞生长因子 23(FGF23)。这种高风险/高回报的方法与传统的定期方法有根本的不同。 采集血样以了解实验室数值的变化趋势以及与其他临床参数的相关性。在R21阶段 (探索性)，将开发可穿戴的多模式传感器，用于持续监测营养和 荷尔蒙。可穿戴传感器将在基于适体的生物传感器的基础上开发，用于连续 监测单个小分子和一种基于微针的微创电位传感器 对营养素(钠和钾)进行多路连续监测。在目标1中，我们将适应并在此基础上发展 这些生物传感器用于连续监测三种营养素(钠、钾和钙)和三种营养素 激素(iPTH、FGF23和VitD)同时进行。一种小型化印刷电路板及相关电子设备 对于与智能手机的无线数据通信，将开发应用程序。在《目标2》中，一种深层递归神经 利用网络方法进行联合多模传感器数据定标，提高了系统的实用性和可靠性。 可穿戴传感器在大鼠模型中得到验证。R33阶段(临床试验)将根据实现 R21阶段中定义明确的里程碑。在目标3中，该装置将进一步改进，皮肤的范围将被扩大 受试者体内的荷尔蒙已经确定。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。的总目标是 这些研究旨在开发一种创新的可穿戴式多模式传感系统，用于持续监测 营养素和荷尔蒙。这将为未来的工作奠定基础，在这些和其他营养素/激素中 对慢性病至关重要的疾病可以被修改，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.