A non-invasive method for measuring blood sugar could replace fingerprint tests for diabetes

A non-invasive method for measuring blood sugar could replace fingerprint tests for diabetes

A non-invasive method for measuring blood sugar levels developed at MIT could save diabetes patients from having to prick their fingers multiple times.

The MIT team used Raman spectroscopy—a technique that reveals the chemical composition of tissues by irradiating them with near-infrared or visible light—to develop a shoebox-sized device that can measure blood sugar levels without needles.

When tested on a healthy volunteer, the researchers found that their device's measurements were similar to those obtained with commercial continuous glucose monitoring sensors, which 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 trial.

For a long time, the fingerstick was the standard method for measuring blood sugar, but no one wants to prick their finger every day, multiple times a day. Of course, many diabetics do not measure their blood sugar levels adequately, which can lead to serious complications. If we can produce a noninvasive glucose monitor with high accuracy, then almost every diabetic patient will benefit from this new technology.”

Jeon Woong Kang, MIT researcher and lead author of the study

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

Non-invasive glucose measurement

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

Hoping to develop wearable glucose monitors that would be more comfortable for patients, researchers at MIT's LBRC have pursued 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 when it hits different types of molecules.

In 2010, researchers at the LBRC showed that they could calculate glucose levels indirectly, based on a comparison between Raman signals from the interstitial fluid that coats skin cells and a reference measurement of blood glucose levels. While this approach produced reliable readings, it was not practical for transferring to a glucose meter.

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

The researchers took these measurements using devices about the size of a desktop printer and have since been working to further reduce the device's footprint.

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

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

“By foregoing capturing the entire spectrum, which contains a lot of redundant information, we limit ourselves to three selected bands out of about 1,000,” says Bresci. “This new approach allows us to modify the components commonly used in Raman-based devices, saving space, time and costs.”

Towards a wearable sensor

In a clinical trial conducted at the MIT Center for Clinical Translation Research (CCTR), researchers used the new device to take measurements in a healthy volunteer over a four-hour period. As the subject placed their arm on the device, a near-infrared beam shone through a small glass window onto the skin to take the measurement.

Each measurement lasts just over 30 seconds, and the researchers took a new measurement every five minutes.

During the study, the subject consumed two 75-gram glucose drinks, which allowed researchers to monitor significant changes in blood sugar concentrations. They found that the Raman-based device had similar accuracy to two commercially available invasive glucose monitors that the subject wore.

Since completing this study, researchers have developed a smaller prototype, about the size of an iPhone, which they are currently testing at MIT CCTR as a wearable monitor on healthy and pre-diabetic volunteers. Next year, they plan to conduct a larger study involving people with diabetes in collaboration with a local hospital.

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

The research was funded by the National Institutes of Health, the Korean Technology and Information Promotion Agency for SMEs and Apollon Inc.

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