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

摘要 测量体液中的电解质对于诊断和处理许多慢性心脏是必不可少的， 肾脏、甲状旁腺和神经疾病。离子选择电极通常用作电解液。 自20世纪80年代以来，医院临床化学分析仪和血液分析仪的测量。然而， 患有甲状旁腺功能减退症、心力衰竭、双相情感障碍和终末期肾病的患者 经常需要比医院允许的更频繁地监测他们的电解质。它是一个更大的 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面临的问题。 在过去的十年里，人们对可获得和负担得起的电解液监测的兴趣激增， 家用传感器、可穿戴传感器、经皮传感器和植入式传感器。然而，离子选择性 电极只有在使用时用标准溶液校准时才准确。都是集中式的， 具有离子选择电极的台式和手持式仪器使用泵或致动器来处理校准 通过复杂的流体系统提供解决方案和样品。因为这个对技术要求很高的校准程序 无法在低成本和紧凑的人体上或家中实施传感器，这些新兴的传感器 无法为医疗决策生成可靠的数据。因此，校准一直是一个根本性的瓶颈 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电极校准策略，而不使用任何 活动部件或流体。在工作电极和参考电极之间建立窄的校准阶段，以 提供作为一点校准的基准电势。令人惊讶的是，校准电桥没有 样品测试时需要去除，因为样品主导界面电荷转移， 电位法信号。这种高度独特的内置校准方法不会增加复杂性， 电解液传感器的占地面积、成本和样本量，因此使其能够用于低容量 分散设置中的样本。这项R21拨款将集中在家用钙离子和钾离子选择性传感器上，因为 在家中监测毛细血管血液中的这些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，这些传感器 可携带、可运输、性能稳定、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，并在人体血液样本中验证它们的准确性和精密度 商用血液分析仪。这笔探索性赠款将使我们能够确认自我校准的可行性。 以Ca~(2+)和K~+为例分析的家用传感器的概念。在今后的工作中，我们将采用这一点 传感器中的概念在各种分散的环境中朝向更多和多种电解液。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 慢性病自我管理。

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.