Real-time continuous measurement of lactate through a minimally invasive microneedle patch: a phase I clinical study

Abstract

IntroductionDetermination of blood lactate levels supports decision-making in a range of medical conditions. Invasive blood-sampling and laboratory access are often required, and measurements provide a static profile at each instance. We conducted a phase I clinical study validating performance of a microneedle patch for minimally invasive, continuous lactate measurement in healthy volunteers.MethodsFive healthy adult participants wore a solid microneedle biosensor patch on their forearms and undertook aerobic exercise for 30 min. The microneedle biosensor quantifies lactate concentrations in interstitial fluid within the dermis continuously and in real-time. Outputs were captured as sensor current and compared with lactate concentrations from venous blood and microdialysis.ResultsThe biosensor was well-tolerated. Participants generated a median peak venous lactate of 9.25 mmol/L (IQR 6.73–10.71). Microdialysate concentrations of lactate closely correlated with blood. Microneedle biosensor current followed venous lactate concentrations and dynamics, with good agreement seen in all participants. There was an estimated lag-time of 5 min (IQR −4 to 11 min) between microneedle and blood lactate measurements.ConclusionThis study provides first-in-human data on use of a minimally invasive microneedle patch for continuous lactate measurement, providing dynamic monitoring. This low-cost platform offers distinct advantages to frequent blood sampling in a wide range of clinical settings, especially where access to laboratory services is limited or blood sampling is infeasible. Implementation of this technology in healthcare settings could support personalised decision-making in a variety of hospital and community settings.Trial registration numberNCT04238611.

Continuous Measurement of Lactate Concentration in Human Subjects through Direct Electron Transfer from Enzymes to Microneedle Electrodes

“…An easy-to-apply, inherently safe, and comfortably wearable lactate sensor would allow decision makers at all levels of pre- to post-hospital care to make better-informed choices surrounding treatment. 11 Lactate concentrations would also be opened up as a dataset for decision makers outside critical care settings in hospitals, such as in healthcare facilities in low- to middle-income countries, carers for lower-risk patients at home, the patients themselves, and paramedics.…”

Microneedle-based transdermal detection and sensing devices

“…They found good tolerance and good agreement among volunteers in the phase I clinical study. 76 Lactate oxidase (LOX), the endogenous specialized enzyme for lactate oxidization, is the most frequently used lactate recognition element. Based on LOX catalysis, Bollella et al fabricated gold microneedles with nanocarbons to realize real-time lactate monitoring in artificial interstitial fluid and human serum.…”

“…Recently, Ming et al has published the first in-human data of the dynamic determination of lactate levels using microneedles. They found good tolerance and good agreement among volunteers in the phase I clinical study 76. Lactate oxidase (LOX), the endogenous specialized enzyme for lactate oxidization, is the most frequently used lactate recognition element.…”

Molecular Imprinted Polymers on Microneedle Arrays for Point of Care Transdermal Sampling and Sensing of Inflammatory Biomarkers

“…Typically ranging from 0.5 to 1 mm in height and with tip dimensions ranging from 10–40 μm, they offer a platform for wearable molecular sensing of analytes present in the skin ISF. Biomarkers such as metabolites including glucose, lactate, and alcohol have been monitored continuously in real time using microneedle-based wearable molecular biosensors. Similarly, therapeutic drug levels have been monitored over several hours, sufficient to follow their pharmacodynamics and pharmacokinetics in this compartment .…”

“…So far, the microneedle-based continuous and point of care diagnostic devices have mainly employed enzymes − or aptamers as bioreceptor elements for the construction of biosensing devices. Molecular imprinting is a technique used to synthesize highly cross-linked polymers capable of selective molecular recognition.…”