Dual-monitoring of β-hydroxybutyrate and glucose via a microneedles-based biosensor for personalized nutrition

Personalized nutrition has rapidly emerged as a highly interdisciplinary field dedicated to preventing and managing diseases by tailoring nutrition based on the specific requirements and unique metabolic profiles of each individual. This approach addresses the profound heterogeneity in how individuals respond to diet, considering factors such as genetics, lifestyle, and microbiome composition. The successful realization of effective personalized nutrition requires the development and synergy of diverse sensor modalities. Microneedles-based biosensors are excellent candidates as they are capable of continuously tracking temporal bioanalytes variations in the interstitial fluid (ISF), following the intake of food and supplements. In this work, we present a wearable minimally-invasive electrochemical biosensor for dual-monitoring of β-hydroxybutyrate (β-HB) and glucose in ISF, based on a gold microneedles array with two working electrodes. Functionalization with electropolymerized poly-methylene blue (poly-MB), β-hydroxybutyrate dehydrogenase (3-HBDH) with nicotinamide adenine dinucleotide oxidized form (NAD + ) and chitosan nanoparticles (ChitNPs) (working electrode 1), and FAD-glucose-dehydrogenase (FADGDH) (working electrode 2), enabled the dual-monitoring of β-HB and glucose, with linear range in the clinically relevant range of both analytes, high sensitivity, stability, and selectivity, avoiding cross-talk between the two closely modified working electrodes. An outer poly(vinyl) chloride (PVC) diffusion-limiting membrane was used to protect the modified microneedles array. The developed biosensor was tested in artificial ISF, in a phantom gel skin-mimicking model as well as in human ISF. This pilot study involved three human healthy subjects before and after taking supplements, and the results, compared to those obtained with a commercial ketone/glucose meter, showed excellent agreement. • The first on-body microneedles-array based biosensor for dual β-hydroxybutyrate (β-HB) and glucose monitoring was successfully developed. • The biosensor prototype was tested in artificial interstitial fluid (ISF), in a phantom gel skin-mimicking model and in human ISF showing excellent performances. • The microneedles-array biosensor offers a dual sensing capability for the simultaneous monitoring of two key biomarkers towards a personalized nutrition. • The microneedles-array biosensing technology has been assessed in this very first application for in vivo β-HB and glucose detection, allowing for minimally-invasive, pain-free, continuous monitoring, with reduced tissue inflammation and rapid skin recovery.