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.

总结 体液中电解质的测量对于诊断和管理许多慢性心脏病， 肾脏、甲状旁腺和神经疾病。离子选择性电极已常规用于电解质 自20世纪80年代以来，医院的临床化学分析仪和血液分析仪一直在进行测量。然而，在这方面， 患有甲状旁腺功能减退、心力衰竭、双相情感障碍和终末期肾病等疾病的患者 通常需要比医院允许的更频繁地监测他们的电解质。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。 在过去的十年中，人们对基于电解质监测的可获得和可负担的电解质监测的兴趣激增。 家用传感器、可穿戴传感器、透皮传感器和植入式传感器。离子选择性 电极只有在使用时用标准溶液校准时才是准确的。全部集中， 带有离子选择性电极的台式和手持式仪器使用泵或致动器来处理校准 溶液和样品通过复杂的流体系统。因为这个技术要求很高的校准程序 不能在身体上或家里的低成本和紧凑的传感器中实现，这些新兴的传感器 无法为医疗决策提供可靠的数据。因此，校准一直是一个根本的瓶颈 用于将新的电解质监测模式转化为医疗实践。 该项目旨在开发一种全新的离子选择性电极校准策略， 移动部件或射流。工作电极和参比电极之间内置了一个狭窄的校准阶段， 提供用作单点校准的基线电位。令人惊讶的是，校准桥不 因为样品主导界面电荷转移， 电位信号。这种高度独特的内置校准方法不会增加复杂性， 因此，能够将它们用于低容量的环境中。 在分散设置的样本。这项R21赠款将重点放在家用Ca2+和K+选择性传感器上，因为 在家里监测毛细血管血液中电解质的迫切和被忽视的需要。在目标1中， 我们将使用3D打印和微制造技术来制备全固态自校准传感器， 便携、可运输、稳定和可批量生产。在目标2中，我们将确定分析性能 这些传感器的特性，并验证其在人体血液样本中的准确度和精密度， 商用血液分析仪这一探索性的赠款将使我们能够确认自我校准的可行性 概念在家用传感器中使用Ca2+和K+作为示例分析物。在今后的工作中，我们将采用 传感器的概念，在各种分散的设置更多和多种电解质。最终目标是 使患者能够以频繁和微创的方式监测电解质浓度， 慢性病的自我管理。