Optical Detection of Lithium Therapeutic Levels in Porcine Interstitial Fluid Collected Using a Hollow Microneedle

Bipolar disorder (BD), a recurrent chronic disorder characterized by mood fluctuating between episodes of mood elevation and depression, is a leading cause of disability worldwide. Lithium is the most widely used medication for management of BD. However, despite its effectiveness in preventing and reducing mood swings and suicidality, it is a potentially hazardous drug. Lithium has a very narrow therapeutic range (0.4-1.2 mmol/L) with the upper limit being uncomfortably close to toxic levels, hence lithium levels should be monitored regularly. The current techniques of monitoring lithium levels require frequent blood tests and elaborate laboratory methods that cannot be translated into point of care devices for personal monitoring. Dermal interstitial fluid (ISF), an underutilized information-rich biofluid, can be accessed using non-invasive techniques and the lithium concentration in ISF has been found to be proportional to concentration in serum. In the current study a microneedle-based sampling method to extract ISF from porcine skin, as it is similar in anatomy to human skin, was employed. Optical determination of lithium therapeutic concentrations in porcine ISF using a colorimetric method based on the reaction between chromogenic agent Quinizarin and Li⁺ ion was then performed. The resulting spectra show spectral variations which are related to lithium concentrations in spiked samples of porcine ISF, hence suggesting the feasibility of utilizing ISF for real-time and minimally-invasive lithium drug monitoring.