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

描述（由申请人提供）：本提案的长期目标是开发一种廉价、简单易用的即时检测方法，用于定量测定手指棒样品的全血锂浓度。锂被用于治疗双相情感障碍，也被称为躁狂抑郁症。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 ~ 1.5 mM），因此监测锂至关重要；并注意到合并疾病、肾功能下降或合用药物的潜在毒性。目前的测试通常需要静脉穿刺血液样本送到实验室进行测试。该项目旨在设计一种测试条，类似于用于葡萄糖测试的测试条，可以由医生使用从患者身上获得的手指棒血液样本进行测试。在和病人在一起的时候获得一个结果，将允许医生在必要时修改治疗计划。建议的最终产品将包括含有干燥试剂（固相格式）的测试条和手持式数字仪表。用户将测试条插入仪表，用手指棒取样涂上全血，等待固定时间，然后从仪表上读取锂浓度。第一阶段提案的目标是确定将现有的液态锂测试化学（用于实验室测试）转变为固态测试条形式的可行性。最初的开发工作将使用加锂的血清样本。使用加锂的全血或临床样品将添加

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.