Biosensor Strip for Rapid On-site Assessment of Levodopa Pharmacokinetics along with Motor Performance in Parkinson's Disease.

While levodopa (L-Dopa) is the primary treatment for alleviating Parkinson's disease (PD), its efficacy is hindered by challenges such as a short half-life and inconsistent plasma levels. As PD progresses, the rising need for increased and more frequent L-Dopa doses coupled with symptom fluctuations and dyskinesias underscores the urgency for improved comprehension of the interplay between L-Dopa levels and PD motor symptoms. Addressing this critical need, we present a decentralized testing method using a disposable biosensor strip and a universal slope (U-slope) calibration-free approach. This enables reliable, rapid, simple, and cost-effective decentralized L-Dopa measurements from capillary blood. A pilot study with PD persons demonstrates the ability to monitor real-time L-Dopa pharmacokinetics from fingerstick blood after oral L-Dopa-Carbidopa (C-Dopa) tablet administration. Correlating capillary blood L-Dopa levels with PD motor scores revealed a well-defined inverse correlation with temporal motor fluctuations. We compared the resulting dynamic capillary blood L-Dopa levels with plasma L-Dopa levels using the traditional but clinically impractical high-performance liquid chromatography technique. By providing timely feedback on a proper L-Dopa dosing regimen in a decentralized and rapid fashion, this new biosensing platform will facilitate tailored optimal L-Dopa dosing, towards improving symptom management and enhancing health-related quality of life.

Continuous Ketone Monitoring via Wearable Microneedle Patch Platform.

Ketone bodies (KBs), especially ß-hydroxybutyrate (BHB), have gained tremendous attention as potential biomarkers as their presence in bodily fluids is closely associated with health and wellness. While a variety of blood fingerstick test strips are available for self-testing of BHB, there are major needs for wearable devices capable of continuously tracking changing BHB concentrations. To address these needs, we present here the first demonstration of a wearable microneedle-based continuous ketone monitoring (CKM) in human interstitial fluid (ISF) and illustrate its ability to closely follow the intake of ketone drinks. To ensure highly stable and selective continuous detection of ISF BHB, the new enzymatic microneedle BHB sensor relies on a gold-coated platinum working electrode modified with a reagent layer containing toluidine blue O (TBO) redox mediator, ß-hydroxybutyrate dehydrogenase (HBD) enzyme, a nicotinamide adenine dinucleotide (NAD+) cofactor, along with carbon nanotubes (CNTs), chitosan (Chit), and a poly(vinyl chloride) (PVC) outer protective layer. The skin-worn microneedle sensing device operates with a miniaturized electrochemical analyzer connected wirelessly to a mobile electronic device for capturing, processing, and displaying the data. Cytotoxicity and skin penetration studies indicate the absence of potential harmful effects. A pilot study involving multiple human subjects evaluated continuous BHB monitoring in human ISF, against gold standard BHB meter measurements, revealing the close correlation between the two methods. Such microneedle-based CKM offers considerable promise for dynamic BHB tracking toward the management of diabetic ketoacidosis and personal nutrition and wellness.