Test Strip for Point-Of-Care Monitoring of Serum/Whole Blood Lithium Levels

描述(由申请人提供)：这项建议的长期目标是开发一种廉价、易用的护理点检测方法，用于从手指棒样本中定量测定全血锂浓度。锂被用来治疗双相情感障碍，也被称为躁郁症。双相情感障碍是一种慢性大脑疾病，会导致一个人的情绪、精力和功能发生不寻常的变化。大约有570万美国人患有这种疾病。锂是治疗双相情感障碍最常用的药物。由于血清锂的治疗范围很窄(0.5至1.5 mM)，以及并发疾病、肾功能下降或联合处方药物的潜在毒性，锂监测是必不可少的。目前的检测大多需要静脉穿刺血样本，然后送到实验室进行检测。拟议中的项目旨在设计一种测试试纸，类似于用于血糖测试的试纸，可以由医生使用从患者那里获得的手指棒状血液样本进行操作。在仍与患者在一起的情况下获得结果，将允许医生在必要时修改治疗计划。拟议的最终产品将包括一条含有干燥试剂的试纸(固相格式)和一台手持数字仪表。使用者将试纸插入计量器，用手指棒状样本涂抹全血，等待固定时间，然后从计量器读取锂浓度。第一阶段提案的目标是确定将实验室测试中使用的现有液态锂测试化学转换为固态测试条格式的可行性。最初的开发工作将使用添加锂的血清样本。加锂的全血或临床样本的使用将被添加到 第二阶段设计。第一阶段有五个目标。目标1是鉴定一种血清锂灵敏度为0.3至3.0 mm的单或二元染料底物体系，该体系可用于固相格式。除了最终的灵敏度外，还将考虑染料底物体系的其他特性，如摩尔吸光系数和稳定性。目标2将专注于确定膜材料、添加剂和稳定剂。一些需要评估的成分包括：用于膜支持材料的纤维素和尼龙；作为添加剂的表面活性剂，以帮助样品应用后的试剂重建；作为稳定剂的聚合物/共聚合物，以保护干燥的试剂(酶、染料底物)。目标3将评估相关性和精确度。测试试纸将用添加锂的血清进行检测。同样的血清将被送往实验室进行检测。这两个系统的结果将用于计算相关性。精确度将在三种锂浓度下确定。Aim 4将开始评估试纸在冷藏条件下的稳定性。目标5是改进第二阶段提交的设计。第二阶段将继续该项目，已经确定了以下目标：(1)在试纸上增加一个血液分离系统，以允许手指棒样本；(2)将试纸与手持数字仪表耦合，以获得定量结果；以及(3)研究允许室温储存与公共卫生相关的方法。有了结果，而不需要送到实验室，意味着医生可以更容易地管理患者的治疗范围。这有助于提高患者的生活质量，并有助于预防锂中毒。

DESCRIPTION (provided by applicant): The long-term objective of this proposal is the development of an inexpensive, simple-to-use, point-of-care test for the quantitative determination of whole blood lithium concentration from a finger-stick sample. Lithium is used to treat bipolar disorder, also known as manic-depressive illness. Bipolar disorder is a chronic brain disorder that causes unusual shifts in a person's mood, energy, and ability to function. Approximately 5.7 million Americans suffer from the condition. Lithium is the most commonly used agent for treating bipolar disorder. Lithium monitoring is essential due to the narrow therapeutic range of serum lithium (0.5 to 1.5 mM); and to the potential toxicity from intercurrent illness, declining renal function, or co-prescription of drugs. Current tests most often require a venipuncture blood sample that is sent to a laboratory for testing. The proposed project aims to design a test strip, similar to those used for glucose testing, that can be run by the physician using a finger-stick blood sample obtained from their patient. Obtaining a result, while still with the patient, will allow the physician to modify the treatment plan if necessary. The proposed final product will consist of a test strip containing dried reagents (solid phase format) and a hand-held digital meter. The user will insert the test strip into the meter, apply whole blood using a finger-stick sample, wait a fixed time, and then read the lithium concentration from the meter. The goal of the Phase I proposal is to determine the feasibility of transferring existing liquid format lithium test chemistry - used in laboratory testing -to a solid state, test strip format. Initial development work will use lithium spiked serum samples. Use of lithium spiked whole blood or clinical samples will be added in the Phase II design. Phase I has five aims. Aim 1 is to identify a single or binary dye substrate system with serum lithium sensitivity of 0.3 to 3.0 mM that can be used in a solid phase format. In addition to final sensitivity, other characteristics of the dye substrate system will be considered, such as molar absorptivity and stability. Aim 2 will focus on identifying membrane materials, additives, and stabilizers. Some examples of components to be evaluated are: cellulose and nylon for membrane support materials; surfactants as additives to aid in reagent reconstitution once sample is applied; and polymers/co-polymers as stabilizers to protect the dried reagents (enzymes, dye substrate). Aim 3 will evaluate for correlation and precision. Test strips will be run with lithium spiked serum. The same serum will be sent to a lab for testing. The results of the two systems will be used to compute correlation. Precision will be determined at three lithium concentrations. Aim 4 will start evaluating the stability of the test strips when stored with refrigeration. Aim 5 is to refine design for Phase II submission. Phase II will continue the project with the following aims already having been defined: (1) add a blood separation system to the test strip to allow for finger-stick samples; (2) couple the test strip with a hand-held digital meter to obtain quantitative results; and (3) investigate methods to allow for room temperature storage PUBLIC HEALTH RELEVANCE The proposed test strip for lithium will allow a physician to determine serum lithium concentration while still with a patient. Having a result, without sending out to a lab, means the physician can more easily manage a patient's therapeutic range. This can help improve the patient's quality of life and help prevent lithium toxicity.