Revolutionizing diabetes management with reliable blood glucose monitoring without finger pricking

By Dr. Liji Thomas, MDReviewed by Benedette Cuffari, M.Sc.Mar 28 2024

A new technology recently reported in Nature Metabolism utilizes signal localization to improve the accuracy of non-invasive glucose measurement (NIGM).

Study: Non-invasive measurements of blood glucose levels by time-gating mid-infrared optoacoustic signals. Image Credit: Andrey_Popov / Shutterstock.com

About NIGM

Abbott, Dexcom, and other pharmaceutical companies have released wearable patches that bear microneedles designed for intracutaneous implants. These devices offer a more convenient and less painful way to monitor blood glucose levels; however, they can only measure glucose levels in interstitial fluid (ISF) rather than within the blood.

ISF glucose leaks from the blood capillaries, thus making ISF levels lower than those present within the blood. Additionally, ISF glucose levels change with pH, hydration levels, and temperature, the latter of which can alter ISF volume.

Another limitation of NIGM is the use of microneedles that could irritate the skin and cause microbial infections. This has led researchers to investigate needleless technologies, such as terahertz (THz) spectroscopy.

THz spectroscopy can detect glucose based on light absorption; however, this method is subject to relatively high noise, has broad absorption bands, and can mistake glucose for other biomolecules. Raman scattering spectroscopy is another NIGM that uses vibrational spectral profiles to detect glucose. The weak signals of Raman scattering spectroscopy can be improved through coherent anti-stokes Raman spectroscopy (CARS) or stimulated Raman scattering (SRS).

The current study discussed the use of mid-infrared (mid-IR) absorption spectroscopy, which uses optical, optoacoustic, or thermal detection methods and produces strong signals. Importantly, one challenge associated with this approach is the absorption of light by the superficial skin layers rather than by glucose, which can lead to false results.

The researchers aimed to utilize the strong signals while improving the sensitivity and accuracy of glucose detection using a depth-gated mid-infrared optoacoustic sensor (DIROS). DIROS exploits time-gated mid-IR optoacoustic signals to determine the exact depth at which glucose absorption is measured in the skin.

DIROS detects glucose in blood-rich skin areas and, as a result, can measure real-time blood glucose levels rather than ISF glucose. Importantly, DIROS can avoid glucose sensing from the stratum corneum and epidermis, thus minimizing potential errors due to variations in skin humidity or the presence of fats and other molecules in the skin.

Study findings

Mid-IR measurements of blood glucose levels on a mouse ear were obtained using depth-selective optoacoustic detection. These measurements were in agreement with those obtained by optoacoustic measurements directed at the capillaries at 532 nm illumination, thus validating the mid-IR-based findings.

Optoacoustic sensing was used to ensure deeper penetration of the skin at 100 micrometers (µm) or more. The maximum depth was sufficient to reach the junction of the dermis and epidermis, which is rich in capillaries, thus making real-time blood glucose assessment possible.

Using nearly 5,000 optoacoustic measurement points in a 70x70 point grid, slight variation was observed in the depth at which measurements were collected at various points between 4-6%. Accurate blood glucose values with sufficient signal-to-noise ratios (SNR) were also obtained, thereby allowing in vivo glucose detection at normal concentrations, even when other potentially contaminating molecules like lactate are present.

The measurements were obtained at two locations, one rich in blood capillaries (P1) and one relatively avascular (P2). P1 values were closer to the glucometer-recorded blood glucose concentrations as compared to the P2 values; however, both values changed after glucose was administered. P2 values changed more slowly, thus reflecting the delayed changes in ISF glucose.

The most sensitive performance was achieved for measurements obtained from the P1 position after applying a time gate.”

After demonstrating that vascular areas provided more accurate and repeatable values, the investigators explored the utility of depth selection to enhance DIROS performance beyond that of currently available sensors.

Time-gated measurements eliminated non-specific and bulk measurements from the skin surface and other skin molecules using only those from capillary-rich layers of the skin. Compared to Raman spectroscopy, which detects glucose levels within the 260-460 mg/dL range, DIROS detected changes in glucose levels below 100 mg/dL.

What is the future?

The current study presents DIROS, a new glucose-sensing tool that could help increase the precision of blood glucose measurement within the physiological range in an effort to advance diabetes management.

DIROS could be extended beyond glucose measurements, or instance, the development of a continuous metabolic sensing system to alert a user to deviations from healthy metabolic parameter.”