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: 10425111
• 负责人: Ravi Nistala
• 金额: $ 21.29万
• 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/10425111
• 关键词: Address; 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; Data; Development; Devices; Diabetes Mellitus; Diabetic Nephropathy; Dialysis procedure; Diet; Disease Progression; 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; Knowledge; Lead; Machine Learning; Malnutrition; Measurement; Measures; Medicare; Medicine; Metabolism; Methods; Missouri; Modeling; Monitor; Morbidity - disease rate; Nature; Nutrient; Obesity; Onset of illness; Outcome; Outpatients; PTH gene; Patients; Performance; Periodicity; Phase; Potassium; 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; base; cancer cachexia; cardiovascular health; circadian; clinical diagnostics; cost; cytotoxicity; data communication; design; dietary; fibroblast growth factor 23; glucose monitor; 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; trend; wearable device; wearable sensor technology; wireless; 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.

项目摘要 循环营养素，代谢产物和赛马既是风险评估和因果的有用的生物标志物 慢性疾病药物，包括肥胖，糖尿病，高血压，慢性肾脏疾病（CKD）和癌症。 当前监测养分和激素的方法涉及测量血液的浓度 使用台式仪器（例如自动生物分析仪和液体）的样品和/或体液 驻扎在临床诊断实验室中的色谱 - 质谱法（LC-MS），导致不适和 与重复措施相关的高成本。皮肤连续葡萄糖监测的最新进展 间质性液体（ISF）彻底改变了精确营养/医学和昼夜代谢的研究， 由于可穿戴的性质和监测的连续性。由于与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 不断监测连续葡萄糖监测器以外的营养，代谢产物和激素 为了改变CKD进展的过程。因此，建议开发创新的 可穿戴的多模式感应系统，用于连续监测营养（钠，钾和钙） 和激素，包括25OH维生素D（VITD），完整的甲状旁腺马酮（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根本不同 血液采样用于实验室值的趋势以及与其他临床参数相关的血液采样。在R21阶段 （探索性），将开发可穿戴的多模式传感器，以连续监测营养和 骑马。可穿戴传感器将开发在基于APATMER的生物传感器上建模的连续生物传感器 监测单个小分子和最小侵入性的基于微针的电位测量传感器 养分（钠和钾）的多路复用和连续监测。在AIM 1中，我们将适应并建立 这些生物传感器用于连续监测三种营养素（钠，钾和钙）和三个生物传感器 激素（IPTH，FGF23和VITD），简单。微型印刷电路板和相关的电子设备 对于无线数据通信，将开发智能手机应用程序。在AIM 2中，一个深度反复的神经 联合多模式传感器数据校准的网络方法将被利用，并将其实用性和可靠性 可穿戴传感器在大鼠型号中验证。 R33阶段（临床试验）将根据成就进行 R21阶段定义明确的里程碑。在AIM 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AIM 4中，饮食对营养/激素浓度的贡献 将进行评估，并开发了用于预测CKD进程的机器学习算法。总体目标 这些研究是为了开发创新的可穿戴多模式传感系统，以连续监测 营养和激素。这将为未来的工作奠定舞台，这些工作和其他营养/激素 可以修改对慢性疾病至关重要的慢性疾病，从而实现精确营养的承诺。