Self-calibrated ionophore-based ion-selective electrodes for at-home measurements of blood electrolytes

用于家庭测量血液电解质的自校准离子载体离子选择电极

• 批准号: 10592523
• 负责人: Xuewei Wang
• 金额: $ 42.69万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592523
• 关键词: 3D Print; Adopted; Area; Bipolar Depression; Bipolar Disorder; Blood; Blood capillaries; Blood specimen; Body Fluids; Calibration; Characteristics; Charge; Chronic; Chronic Disease; Clinical Chemistry; Clinical Trials; Data; Decentralization; Dependence; Devices; Diagnosis; Disabled Persons; Disease; Disease of parathyroid glands; Dose; Drops; Early identification; Elderly; Electrodes; Electrolyte Disorder; Electrolytes; Electron Beam; Electrons; End stage renal failure; Ensure; Fingers; Foundations; Future; Goals; Grant; Healthcare; Heart; Heart Diseases; Heart failure; Home; Hospitals; Human; Hydrogels; Hypoparathyroidism; In Situ; Ion-Selective Electrodes; Ionophores; Ions; Kidney; Kidney Diseases; Kidney Failure; Liquid substance; Low income; Measurement; Measures; Medical; Membrane; Methods; Microfabrication; Modality; Monitor; Nerve; Oils; Parathyroid gland; Patients; Performance; Pharmaceutical Preparations; Phase; Plasticizers; Polymers; Procedures; Process; Pump; Reaction Time; Resistance; Salts; Sampling; Self Management; Side; Signal Transduction; Sodium Chloride; System; Techniques; Technology; Testing; Thinness; Transducers; Translating; Visit; Water; Work; commercialization; cost; design; diabetes management; electrical potential; empowerment; evaporation; experimental study; glucose monitor; implantable device; implanted sensor; innovation; instrument; interest; interfacial; manufacture; minimally invasive; mobile sensor; photocuring; point of care; polyacrylate; prevent; response; rural area; sensor; solid state; underserved area; wearable device; wearable sensor technology

SUMMARY Measurements of electrolytes in body fluids are essential for diagnosing and managing many chronic heart, kidney, parathyroid, and nerve disorders. Ion-selective electrodes have been routinely used for electrolyte measurements in clinical chemistry analyzers and blood analyzers in hospitals since the 1980s. However, patients with conditions such as hypoparathyroidism, heart failure, bipolar disorder, and end-stage renal disease often need to monitor their electrolytes much more frequently than allowed by hospital visits. It is an even bigger problem for disabled, elderly, and low-income patients as well as patients living in rural and underserved areas. The past decade has witnessed a surge of interest in accessible and affordable electrolyte monitoring based on home-use sensors, wearable sensors, transdermal sensors, and implantable sensors. However, ion-selective electrodes are only accurate when calibrated with a standard solution at the point of use. All centralized, benchtop, and handheld instruments with ion-selective electrodes use pumps or actuators to handle calibration solutions and samples via complicated fluidic systems. Because this technically demanding calibration procedure cannot be implemented in the low-cost and compact sensors on the body or at home, these emerging sensors cannot generate reliable data for medical decisions. Therefore, calibration has been a fundamental bottleneck for translating new electrolyte monitoring modalities into healthcare practice. This project aims to develop a completely new calibration strategy for ion-selective electrodes without using any moving parts or fluidics. A narrow calibration phase is built in between the working and reference electrodes to provide a baseline potential that serves as a one-point calibration. Surprisingly, the calibration bridge does not need to be removed for the sample testing because the sample dominates the interfacial charge transfer and the potentiometric signal. This highly unique built-in calibration method does not increase the complexity, footprint, cost, and sample volume of the electrolyte sensors and, therefore, enables their use for low-volume samples in decentralized settings. This R21 grant will focus on home-use Ca2+ and K+ selective sensors because of the urgent and overlooked need for at-home monitoring of these electrolytes from capillary blood. In Aim 1, we will use 3D printing and microfabrication techniques to prepare all-solid-state self-calibrating sensors that are portable, transportable, stable, and mass-producible. In Aim 2, we will determine the analytical performance characteristics of these sensors and validate their accuracy and precision in human blood samples against a commercial blood analyzer. This exploratory grant will allow us to confirm the feasibility of the self-calibration concept in home-use sensors using Ca2+ and K+ as the example analytes. In future work, we will adopt this concept in sensors toward more and multiple electrolytes in various decentralized settings. The ultimate goal is to empower patients to monitor electrolyte concentrations in a frequent and minimally invasive manner for their self-management of chronic diseases.

概括 体液中电解质的测量对于诊断和管理许多慢性心脏至关重要， 肾脏，甲状旁腺和神经疾病。离子选择性电极通常用于电解质 自1980年代以来，医院的临床化学分析仪和血液分析仪的测量。然而， 患有甲状腺功能减退症，心力衰竭，躁郁症和终末期肾脏疾病等疾病的患者 通常需要比医院访问允许的频率更频繁地监测电解质。这是一个更大的 残疾人，老年人和低收入患者以及生活在农村和服务不足地区的患者的问题。 过去的十年见证了基于可访问且负担得起的电解质监控的兴趣激增 家庭使用传感器，可穿戴传感器，透皮传感器和可植入的传感器。但是，离子选择性 仅在使用点用标准溶液校准时，电极才能准确。所有集中 台式和带有离子选择电极的手持仪器使用泵或执行器来处理校准 通过复杂的流体系统解决方案和样品。因为这个技术要求的校准程序 这些新兴传感器无法在体内或家里的低成本和紧凑传感器中实现 无法为医疗决策生成可靠的数据。因此，校准一直是一种基本的瓶颈 将新的电解质监测方式转化为医疗保健实践。 该项目旨在为离子选择电极制定全新的校准策略，而无需使用任何 运动部件或流体。在工作和参考电极之间建立一个狭窄的校准阶段 提供可作为单点校准的基线电位。令人惊讶的是，校准桥没有 需要删除样品测试，因为样品主导了界面电荷转移和 电位测量信号。这种高度独特的内置校准方法不会增加复杂性， 电解质传感器的足迹，成本和样品体积，因此可以用于低量 在分散设置中的样本。此R21赠款将重点放在家庭使用CA2+和K+选择性传感器上，因为 紧急和忽视的需要从毛细血管血液中监测这些电解质的需求。在AIM 1中， 我们将使用3D打印和微加工技术来准备全稳态的自校准传感器 便携式，可运输，稳定且可实现的。在AIM 2中，我们将确定分析性能 这些传感器的特征，并验证其在人类血液样本中的准确性和精度 商业血液分析仪。这种探索性赠款将使我们能够确认自我校准的可行性 使用Ca2+和K+作为示例分析物中的家庭使用传感器中的概念。在以后的工作中，我们将采用这个 在各种分散设置中，传感器朝向更多和多个电解质的概念。最终目标是 使患者能够以频繁且微创的方式监测电解质浓度 慢性疾病的自我管理。