Developing an Affordable and Pocketable POC Device for Monitoring Lithium and Sodium in Patients with Bipolar Disorder

Glucosentient, Inc., Champaign IL

Investigators

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Abstract

Project Summary/Abstract The objective of this Phase I STTR project is to demonstrate feasibility of developing a selective, affordable, and pocket-sized device to enable regular and quantitative monitoring of both Li+ and Na+ levels in the blood of patients with bipolar disorder (BD), which is one of the most common mental illnesses affecting over 6 million Americans, costing the healthcare system over $45 billion dollars annually. Even though lithium (Li+) therapy is one of the most effective and affordable long-term treatments for BD, < 25% of BD patients are prescribed with Li+, in large part because of its very narrow therapeutic window (0.5 ? 1.2 mM) between ineffectiveness or very severe side effects. Managing the inherent risk and maximizing the benefit of Li+ therapy requires convenient and regular monitoring of Li+ and Na+ (whose level can fluctuate during Li+ therapy), a technological niche that remains unfilled, because of current POC devices are either too expensive, bulky or vulnerable to interferences from other metal ions or species in blood. To achieve the objective, we will employ a combinatorial method called in vitro selection to obtain DNA molecules with enzymatic activity (DNAzymes) that are highly specific for either Li+ or Na+ from a large library of up to 1015 differences and will include ?negative selection? to remove the populations that interact with known or anticipated interfering ions or species. In addition, we will repurpose the low-cost and pocket-sized blood glucose meter (BGM) into a more general meter for monitoring Li+ and Na+ levels. The innovation lies in converting the selective Li+- or Na+-dependent cleavage by DNAzymes to effective release of an enzyme called invertase that can catalyze conversion of sucrose into glucose, which can then be quantified using the BGM. By combining DNAzymes with the BGM platform, we can mitigate the risk associated with developing and manufacturing medical devices, while ensuring the end product will be low-cost, convenient, user friendly and amenable for scale-up production. Specifically, we propose to employ in vitro selection to obtain and optimize Li+- or Na+-specific DNAzymes with high activity for cleavage. We will develop solution assays for Li+ and Na+, relaying the selective recognition/catalysis of DNAzymes to a BGM-detectable glucose signal, using invertase, a protein that hydrolyses sucrose into glucose, for both signal transduction and amplification. The assay will be validated in clinical samples. Finally, we will develop disposable cartridges for BGM-based POC monitoring of Li+ and Na+. The expected outcomes for this Phase I project are BGM-based Li+ and Na+ assays with analytical performance validated in clinical samples and demonstrating the feasibility of performing the developed assays in a prototype cartridge system. The product can be readily adapted to other biomarkers that will be relevant in assessing the states and needs of the patient.