Companion Diagnostics for Management of Mental Health Medications

Introduction: Mental disorders are recognized as the leading causes of worldwide disabilities, impacting millions globally and causing a significant increase in DALYs (disability-adjusted life-years), where individuals diagnosed with mental disorders have a decreased life expectancy of 10–15 years in comparison with the general population. However, early interventions at the first onset of mental disorders can improve the outcomes. Over the past decades, despite several advances in the management of mental disorders, treatment outcomes for mental disorders have been unsound due to treatment adherence, high interpersonal variability of efficacy, and the narrow therapeutic window of mood stabilizers and antipsychotic medications. Traditional monitoring methods for mental health medications often require sophisticated equipment and expert personnel. Thus, there is an emergent need to develop affordable, rapid monitoring tools for therapeutic drug monitoring, including lithium, valproic acid, and olanzapine. Therefore, we created a miniaturized electrochemical sensing platform for the real-time screening of mood stabilizers in saliva.

Materials and

Methods: We prepared electrodes by carbonizing the thin polyimide films via laser ablation. LIG (Laser-Induced Graphene) electrodes were functionalized by polymeric membranes selective toward lithium and valproic acid. Next, we modified the surface of LIGs with nanoparticles to enhance the selectivity of the platform for electroactive compounds, including olanzapine. We performed all potential measurements using a 16-channel potentiometer relative to a commercial reference electrode. Voltammetry measurements were performed in an electrode setup. All measurements were performed at room temperature with freshly prepared solutions from 0.1 M stock solutions using the standard addition of deionized water (18.2 MΩ/cm). We prepared the artificial biofluids based on their physiologically relevant composition.

Results, Conclusions, and Discussions: We validated the platforms' practicability by comparing the obtained slope, 60.8±0.45 mV/dec for Li and -51.26±0.19 mV/dec for VA, to the theoretical Nerstian value of 59.2/z (mV/dec), with a detection limit of 17 µM and 27 µM, respectively. We assessed the reproducibility of the platform by finding the repeatability of the standard potential (SD=±2.10 mV), indicating excellent electrode-to-electrode reproducibility. Selectivity against interfering molecules is a critical parcel of any sensing electrode. Therefore, we quantified the selectivity of the SAVE against physiologically relevant interfering electrolytes by utilizing a well-established fixed-interference method (FIM). Results indicated that the platform is more selective toward the target medication in the presence of physiologically relevant interfering compounds. Finally, we assessed the feasibility of the platform by measuring medication concentrations in a panel of biofluids where the errors were within the FDA's acceptable range (Less than 20%).

The fabricated miniaturized platform illustrated a promising potential to be incorporated into point-of-care wearable applications or as a point-of-care companion diagnostic tool. The value of such a technology for mental health patients can be compared to the value of glucometers for managing diabetes.

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