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

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. Lithiu m 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 co ndition. 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 f unction, 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 containi ng 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 lit hium 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 f ormat. 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 compon ents 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 thre e 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 HEALT H 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 ra nge. This can help improve the patient's quality of life and help prevent lithium toxicity.