Continuous Glucose Monitoring Enabled by Fluorescent Nanodiamond Boronic Hydrogel

Abstract

Continuous monitoring of glucose allows diabetic patients to better maintain blood glucose level by altering insulin dosage or diet according to prevailing glucose values and thus to prevent potential hyperglycemia and hypoglycemia. However, current continuous glucose monitoring (CGM) relies mostly on enzyme electrodes or micro‐dialysis probes, which suffer from insufficient stability, susceptibility to corrosion of electrodes, weak or inconsistent correlation, and inevitable interference. A fluorescence‐based glucose sensor in the skin will likely be more stable, have improved sensitivity, and can resolve the issues of electrochemical interference from the tissue. This study develops a fluorescent nanodiamond boronic hydrogel system in porous microneedles for CGM. Fluorescent nanodiamond is one of the most photostable fluorophores with superior biocompatibility. When surface functionalized, the fluorescent nanodiamond can integrate with boronic polymer and form a hydrogel, which can produce fluorescent signals in response to environmental glucose concentration. In this proof‐of‐concept study, the strategy for building a miniatured device with fluorescent nanodiamond hydrogel is developed. The device demonstrates remarkable long‐term photo and signal stability in vivo with both small and large animal models. This study presents a new strategy of fluorescence based CGM toward treatment and control of diabetes.

Zero-Dimensional Carbon Nanomaterials for Fluorescent Sensing and Imaging

“…This study proposes a strategy for fluorescencebased continuous glucose monitoring for treating and controlling diabetes (Figure 16b). 641 The combination of nanostructured gold and nanodiamonds offers new options for optical labeling, imaging, sensing, drug delivery, and targeted therapeutics. ND@Au core−shell nanoparticles comprising nanodiamond (ND) cores doped with Si vacancies and Au shell layers were synthesized and characterized for biomedical applications by Cheng et al 353 Several bioimaging modalities based on a combination of the optical and spectroscopic properties of hybrid nanosystems were demonstrated in cellular and developing zebrafish larva models (Figure 16c).…”

“…The devices showed considerable long-term light and signal stability in both small and large animal models. This study proposes a strategy for fluorescence-based continuous glucose monitoring for treating and controlling diabetes (Figure b) …”

“…(b) Schematic illustration of the glucose-responsive hydrogel that can change fluorescence output according to glucose concentration. Reproduced from ref . Copyright 2023 Wiley-VCH.…”

Microneedle-based glucose monitoring: a review from sampling methods to wearable biosensors

“…108 Furthermore, they designed and successfully loaded the hydrogel system into MNs with a porous hollow structure by porogen leaching technology. 108 The porous structure can effectively enhance the extraction of ISF by capillary action, reducing the lag time and facilitating glucose monitoring in vivo . The device demonstrated remarkable long-term photo- and signal stability in vivo with both small and large animal models.…”

Wearable Sensor Patch with Hydrogel Microneedles for In Situ Analysis of Interstitial Fluid

“…Microneedles (MNs), which come in a variety of materials and structures, offer a way to extract ISF in a minimally invasive manner by piercing the skin. − However, hollow MNs face challenges, such as fracturing, complex manufacturing, empirical/iterative design, limited flexibility and durability, or brittleness. − Hydrogel-based MNs constructed from materials such as poly­(vinyl alcohol) (PVA), chitosan, osmolytes, and methacrylated hyaluronic acid (MeHA) have demonstrated their efficacy in ISF extraction, attributed to their rapid fluid extraction rates, biosafety, and streamlined synthesis procedure. − Yet, integrating these hydrogel MNs with sensing modules remains challenging because of mechanical mismatches or complications arising from hydrogel swelling upon absorbing ISF . As a result, ISF is often collected using MNs and subsequently extracted and then analyzed using specialized lab equipment, facing issues such as sampling variability, time lags, sample degradation, and contamination, ultimately diminishing measurement accuracy and convenience. − This highlights the need for in situ ISF analysis to provide real-time data on multiple target biomarkers, thus improving both accuracy and user acceptance.…”