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

开发和使用可穿戴传感器，用于连续监测慢性肾病患者的营养和激素

• 批准号: 10641823
• 负责人: Ravi Nistala
• 金额: $ 23.33万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-10 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10641823
• 关键词: Affect; Algorithms; Back; Biological Markers; Biosensor; Blood; Blood Vessels; Blood specimen; Body Fluids; Calcium; Calibration; Cause of Death; Cellular Phone; Cessation of life; Chronic; Chronic Disease; Chronic Kidney Failure; Clinic; Clinic Visits; Clinical; Clinical Trials; Concentration measurement; Consumption; Continuous Glucose Monitor; Data; Development; Devices; Diabetes Mellitus; Diabetic Nephropathy; Dialysis procedure; Diet; Disease Progression; Drops; Electronics; End stage renal failure; Excess Dietary Salt; Expenditure; Food Interactions; Future; Glomerular Filtration Rate; Goals; Health; Healthcare; Heart failure; Hormones; Human; Hyperglycemia; Hypertension; Hypocalcemia; Hypoglycemia; Hypokalemia; Incidence; Individual; Inflammation; Insulin Resistance; Intercellular Fluid; Joints; Kidney; Kidney Diseases; Knowledge; Machine Learning; Malnutrition; Measurement; Measures; Medicare; Medicine; Metabolism; Methods; Missouri; Modeling; Monitor; Morbidity - disease rate; Nature; Needles; Nutrient; Obesity; Onset of illness; Outcome; Outpatients; PTH gene; Patients; Performance; Periodicals; Phase; Potassium; Potassium Deficiency; Rattus; Recurrence; Regimen; Renal carcinoma; Renal dialysis; Risk Assessment; Role; Serum; Skin; Sodium; Sodium Chloride; System; Time; Transistors; Universities; Variant; Veins; Vitamin D; Vitamins; Work; aptamer; bariatric surgery; cancer cachexia; cardiovascular health; circadian; clinical diagnostics; cost; cytotoxicity; data communication; design; dietary; fibroblast growth factor 23; graphene; high reward; high risk; human subject; hyperkalemia; innovation; inorganic phosphate; instrument; liquid chromatography mass spectrometry; machine learning algorithm; machine learning method; miniaturize; minimally invasive; mortality; multimodality; precision nutrition; prevent; printed circuit board; recruit; recurrent neural network; saturated fat; sensor; slow potential; small molecule; smartphone application; standard of care; sugar; tool development; transmission process; trend; wearable device; wearable sensor technology; wireless; wireless electronic; wireless sensor

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.

项目概要 循环营养物、代谢物和激素都是用于风险评估和因果关系的有用生物标志物 慢性疾病的诱因包括肥胖、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 使用台式仪器（例如自动生物分析仪和液体）分析样品和/或体液 临床诊断实验室中的色谱-质谱联用仪 (LC-MS) 会导致不适和 重复措施带来的高成本。皮肤连续血糖监测的最新进展 间质液（ISF）彻底改变了精准营养/医学和昼夜节律代谢的研究， 由于可穿戴性质和监测的连续性。由于 CKD 进展相关的成本 （医疗保险支出的 7%）以及相关的发病率和死亡率，开发工具 除了连续血糖监测仪之外，还可以连续监测营养物质、代谢物和激素 是为了改变 CKD 进展过程所需要的。因此，建议开发一种创新的 用于连续监测营养物质（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 (VitD)、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周期性方法有根本的不同。 血液采样以了解实验室值的趋势以及与其他临床参数的相关性。 R21阶段 （探索性），将开发可穿戴多模式传感器，用于连续监测营养物质和 荷尔蒙。可穿戴传感器将以基于适配体的生物传感器为模型进行开发，以实现连续 监测单个小分子和微创、基于微针的电位传感器 营养物质（钠和钾）的多重连续监测。在目标 1 中，我们将进行调整并在此基础上继续发展 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 同时使用激素（iPTH、FGF23 和 VitD）。小型化印刷电路板和相关电子设备 将开发用于与智能手机进行无线数据通信的应用程序。在目标 2 中，深度循环神经网络 将利用网络方法进行联合多模态传感器数据校准，并评估其实用性和可靠性 可穿戴传感器在大鼠模型中得到验证。 R33阶段（临床试验）将在实现的基础上进行 R21 阶段明确的里程碑。在目标3中，该设备将进一步完善，皮肤ISF的范围 建立了人类受试者的激素。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。总体目标为 这些研究旨在开发一种创新的可穿戴多模式传感系统，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 慢性病的关键因素可以得到改变，从而实现精准营养的承诺。