A wearable electrochemical sensing system for non-invasive monitoring of lithium drug in bipolar disorder

Lithium represents the main drug for the treatment of Bipolar Disorder (BD) as it acts as a mood stabilizer. However, because of its narrow therapeutic window, psychiatric patients are obliged to frequent tests in hospital to control their lithium blood concentration during therapy. In this paper, we fabricate for the first time a complete non-invasive system for the Therapeutic Drug Monitoring (TDM) of lithium in sweat in people suffering from BD. The wearable electrochemical sensing platform includes a paper fluidics and a stable Reference Electrode (RE). Lithium detection is based on the use of a potentiometric Ion-Selective Electrode (ISE) with a nanostructured solid contact in order to increase the potential stability of the sensor. A chemical chlorination combined with the use of a PVC membrane doped with an Ionic Liquid (IL) is used to minimize possible potential drifts of the RE. The Nernstian response (56.8±3.9 mV /decade) of the system in the range of clinical interest is then proved in aqueous solution and in sweat. The integration of the sensing platform with a paper fluidics transporting fresh sweat sample to the sensing area is also considered. The already tested sweat is collected in a reservoir made of slow adsorbing paper. The complete wearable system is then successfully tested in a simulated setup by using a mannequin. The measured potential is well compared to the predicted ones in the therapeutic window of lithium drug, proving the good sensing capability in artificial sweat.