Noninvasive imaging could replace finger pricks for people with diabetes

In tests in a healthy volunteer, the researchers found that the measurements from their device were similar to those obtained by commercial continuous glucose monitoring sensors that require a wire to be implanted under the skin. While the device presented in this study is too large to be used as a wearable sensor, the researchers have since developed a wearable version that they are now testing in a small clinical study.

“For a long time, the finger stick has been the standard method for measuring blood sugar, but nobody wants to prick their finger every day, multiple times a day. Naturally, many diabetic patients are under-testing their blood glucose levels, which can cause serious complications,” says Jeon Woong Kang, an MIT research scientist and the senior author of the study. “If we can make a noninvasive glucose monitor with high accuracy, then almost everyone with diabetes will benefit from this new technology.”

MIT postdoc Arianna Bresci is the lead author of the new study, which appears today in the journal Analytical Chemistry. Other authors include Peter So, director of the MIT Laser Biomedical Research Center (LBRC) and an MIT professor of biological engineering and mechanical engineering, and Youngkyu Kim and Miyeon Jue of Apollon Inc., a biotechnology company based in South Korea.

Noninvasive glucose measurement

While most diabetes patients measure their blood glucose levels by drawing blood and testing it with a glucometer, some use wearable monitors, which have a sensor that is inserted just under the skin. These sensors provide continuous glucose measurements from the interstitial fluid, but they can cause skin irritation and they need to be replaced every 10 to 15 days.

In hopes of creating wearable glucose monitors that would be more comfortable for patients, researchers in MIT’s LBRC have been pursuing noninvasive sensors based on Raman spectroscopy. This type of spectroscopy reveals the chemical composition of tissue or cells by analyzing how near-infrared light is scattered, or deflected, as it encounters different kinds of molecules.

In 2010, researchers at the LBRC showed that they could indirectly calculate glucose levels based on a comparison between Raman signals from the interstitial fluid that bathes skin cells and a reference measurement of blood glucose levels. While this approach produced reliable measurements, it wasn’t practical for translating to a glucose monitor.

More recently, the researchers reported a breakthrough that allowed them to directly measure glucose Raman signals from the skin. Normally, this glucose signal is too small to pick out from all of the other signals generated by molecules in tissue. The MIT team found a way to filter out much of the unwanted signal by shining near-infrared light onto the skin at a different angle from which they collected the resulting Raman signal.

The researchers obtained those measurements using equipment that was around the size of a desktop printer, and since then, they have been working on further shrinking the footprint of the device.

In their new study, they were able to create a smaller device by analyzing just three bands — spectral regions that correspond to specific molecular features — in the Raman spectrum.

Typically, a Raman spectrum may contain about 1,000 bands. However, the MIT team found that they could determine blood glucose levels by measuring just three bands — one from the glucose plus two background measurements. This approach allowed the researchers to reduce the amount and cost of equipment needed, allowing them to perform the measurement with a cost-effective device about the size of a shoebox.

“By refraining from acquiring the whole spectrum, which has a lot of redundant information, we go down to three bands selected from about 1,000,” Bresci says. “With this new approach, we can change the components commonly used in Raman-based devices, and save space, time and cost.”

Toward a wearable sensor

In a clinical study performed at the MIT Center for Clinical Translation Research (CCTR), the researchers used the new device to take readings from a healthy volunteer over a four-hour period. As the subject rested their arm on top of the device, a near-infrared beam shone through a small glass window onto the skin to perform the measurement.

Each measurement takes a little more than 30 seconds, and the researchers took a new reading every five minutes.

During the study, the subject consumed two 75-gram glucose drinks, allowing the researchers to monitor significant changes in blood glucose concentration. They found that the Raman-based device showed accuracy levels similar to those of two commercially available, invasive glucose monitors worn by the subject.

Since finishing that study, the researchers have developed a smaller prototype, about the size of an iPhone, that they are currently testing at the MIT CCTR as a wearable monitor in healthy and prediabetic volunteers. Next year, they plan to run a larger study working with a local hospital, which will include people with diabetes.

The researchers are also working on making the device even smaller, about the size of a watch. Additionally, they are exploring ways to ensure that the device can obtain accurate readings from people with different skin tones.

Reference:

Jeon Woong Kang, “Band-pass Raman spectroscopy unlocks compact non-invasive continuous glucose monitoring”, Analytical Chemistry, DOI: 10.1021/acs.analchem.5c01146