How Noninvasive Imaging May Finally Eliminate Diabetes Finger Pricks

By John Oncea, Editor

MIT engineers demonstrate Raman spectroscopy can accurately measure blood glucose through skin, offering a needle-free alternative to traditional diabetes monitoring.

The journey to noninvasive glucose monitoring spans centuries, beginning with observations that seem almost medieval by today’s standards. In 1674, English physician Thomas Willis described diabetic urine as being wonderfully sweet, as if imbued with honey or sugar. For the next two centuries, tasting urine remained the primary diagnostic method for detecting diabetes, a practice that persisted until the mid-1800s.

The first genuine scientific breakthrough came in 1841 when German chemist Karl Trommer developed a clinical test for detecting sugar in urine through acid hydrolysis. Hermann von Fehling expanded on this work in 1850, creating quantitative methods that could measure glucose levels rather than simply detecting its presence. These early copper reagent tests formed the foundation for diabetes care throughout the late 19th century.

Benedict’s refinement in 1908 marked the next major milestone, producing a copper reagent that remained in use for over 50 years. The methodology required heating urine samples with chemical reagents and observing color changes, cumbersome but revolutionary for its time. The 1940s brought modified copper reagent tablets that eliminated the need for external heating, making testing somewhat more practical.

The 1950s ushered in a new era with color-changing reagent strips for urine testing. These strips reacted directly with urine, changing color based on glucose concentration. Users could compare the strip against a color chart to estimate their glucose levels – a significant improvement in convenience, though still limited in accuracy and providing only retrospective data from when the bladder was filled.

Blood glucose testing emerged in the 1960s and 1970s, representing a fundamental shift in diabetes management. The Ames Company developed the Dextrostix in 1965, the first blood glucose test strip using glucose oxidase. By 1970, the Ames Reflectance Meter (later marketed as the Glucometer) combined test strips with a digital display, launching the era of home blood glucose monitoring that revolutionized diabetes care and made the landmark Diabetes Control and Complications Trial possible.

The late 1990s and early 2000s brought continuous glucose monitors (CGMs) that measure glucose in interstitial fluid, the liquid surrounding body cells. These devices transformed diabetes management by providing readings every few minutes and showing glucose trends. However, all CGMs required sensor insertion beneath the skin, and many needed frequent calibration with finger stick measurements. The dream of truly noninvasive, optical glucose monitoring remained tantalizingly out of reach for clinical widespread use.

The GlucoWatch: A Pioneering Attempt

The first serious attempt at noninvasive continuous monitoring came with the GlucoWatch Biographer, developed by Cygnus Inc. and later acquired by insulin pump manufacturer Animas Corporation. Approved by the FDA in 2001, the GlucoWatch represented a bold vision: a wristwatch-sized device that could monitor glucose without any needles.

The GlucoWatch employed reverse iontophoresis, using a gentle electrical current to draw glucose molecules from interstitial fluid through the skin to a replaceable sensor pad. Designed to provide readings every ten minutes over twelve hours, the device promised up to 36 measurements per session. However, reality fell short of this promise. Environmental and physiological factors – sweating, movement, cold skin, temperature fluctuations – frequently interfered with readings. Clinical studies showed users received an average of only 26 out of 36 potential readings, with approximately 21% of users getting fewer than 12 usable readings per session.

The device required a three to 3.5-hour warm-up period and couldn’t be exposed to water during operation. More problematically, around 80% of users experienced skin irritation from the electrical current, with 10% finding it intolerable. The GlucoWatch also required manual calibration with traditional glucose meters, introducing additional sources of error. The FDA cautioned that users should never adjust insulin dosage based solely on GlucoWatch readings, as single measurements could be off by more than 30%, particularly during rapid glucose fluctuations.

Despite showing that wearable continuous monitoring was conceptually possible, the GlucoWatch was discontinued in 2007. It faced increasing competition from more accurate sensor-based CGMs that, while still requiring skin insertion, offered superior reliability. Yet the GlucoWatch’s legacy endured – it proved the concept and inspired continued research into truly noninvasive monitoring technologies.

MIT’s Raman Spectroscopy Revolution

Now, researchers at MIT’s Laser Biomedical Research Center have achieved what may finally be the breakthrough the field has awaited. Using Raman spectroscopy – a technique that reveals tissue chemical composition by analyzing how near-infrared light scatters when encountering different molecules – the team has developed a method that can accurately measure blood glucose without any needles.

The MIT approach builds on years of work within the research center. Researchers in 2020 reported a breakthrough that allowed them to directly measure glucose Raman signals from skin tissue, overcoming earlier limitations.

Glucose naturally produces a weak Raman signal that’s typically overwhelmed by signals from other molecules in tissue. The MIT engineers solved this by shining near-infrared light onto the skin at a different angle from which they collected the resulting Raman signal, effectively filtering out much of the unwanted molecular noise. This angular separation technique dramatically improved signal quality.

Initially, this work produced a desktop printer-sized device. The recent advance published in Analytical Chemistry has shrunk the system to shoebox size by focusing on just three spectral bands rather than analyzing the entire 1,000-band Raman spectrum. One band corresponds to glucose, while the other two provide background measurements. This targeted approach reduced equipment requirements, cost, and size while maintaining accuracy.

In a clinical study conducted at the MIT Center for Clinical Translation Research, the team tested the device on a healthy volunteer over four hours. The subject rested their arm on the device while a near-infrared beam shone through a small glass window onto the skin. Each measurement took slightly more than 30 seconds, with new readings taken every five minutes. After the volunteer consumed two 75-gram glucose drinks to induce significant blood sugar changes, the Raman-based device demonstrated accuracy levels comparable to two commercially available invasive glucose monitors worn simultaneously by the subject.

The technical implications are significant. Unlike CGMs that measure interstitial fluid glucose – which lags behind blood glucose by several minutes – Raman spectroscopy potentially offers real-time blood glucose measurements. The method requires no consumable sensors, no skin penetration, and no calibration with finger stick measurements. For engineering applications, the system’s reliance on well-established optical components and signal processing techniques means it could potentially be manufactured at scale using existing photonics industry infrastructure.

Senior author Jeon Woong Kang, an MIT research scientist, emphasizes the clinical motivation: “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. If we can make a noninvasive glucose monitor with high accuracy, then almost everyone with diabetes will benefit from this new technology.”

The research team, led by postdoc Arianna Bresci and including Peter So, director of the Laser Biomedical Research Center, has already developed a cellphone-sized prototype currently undergoing testing as a wearable monitor with healthy and prediabetic volunteers at MIT’s clinical center. Next year, they plan a larger study with a local hospital, including people with diabetes. The ultimate goal is a watch-sized device.

One critical challenge remains: ensuring accurate readings across different skin tones. The team is actively exploring methods to account for melanin content and other skin characteristics that could affect light penetration and signal quality. This diversity consideration is essential for any device intended for widespread clinical use.

The Future Of Noninvasive Glucose Monitoring

The potential impact of successful noninvasive glucose monitoring extends far beyond patient convenience. Studies consistently show that more frequent glucose monitoring improves diabetes management and reduces complications. Yet the pain and inconvenience of finger sticks lead many patients to test less frequently than recommended. A truly painless, continuous monitoring system could dramatically improve adherence and health outcomes.

The technical pathway forward appears increasingly clear. MIT’s work demonstrates that Raman spectroscopy can achieve clinically relevant accuracy levels. The remaining challenges are primarily engineering ones: further miniaturization, ensuring consistency across diverse patient populations, reducing power consumption for extended battery life, and developing robust algorithms that maintain accuracy across various real-world conditions.

Industry interest is substantial. Multiple companies are pursuing the commercialization of various noninvasive technologies. DiaMonTech in Berlin has developed infrared laser technology targeting glucose in interstitial fluid, with clinical trials initiated in December 2024. Other research groups worldwide are exploring alternative optical approaches, each with distinct technical advantages and challenges.

A realistic timeline for widespread clinical availability likely spans five to ten years. The MIT team’s cellphone-sized prototype represents a crucial step toward practical devices. Clinical trials must demonstrate not just accuracy in controlled settings, but reliability during daily activities, exercise, temperature changes, and other real-world conditions. Regulatory approval will require extensive validation across diverse patient populations.

The watch-sized form factor the MIT team envisions would be transformative. Integrated with smartphone connectivity and cloud-based data analysis, such devices could provide not just glucose readings but predictive alerts, personalized insights, and seamless data sharing with healthcare providers. The device could potentially measure multiple blood analytes simultaneously, as Raman spectroscopy can detect various molecular species beyond glucose.

Cost considerations will prove crucial for adoption. While current CGMs have become more affordable, they still require regular sensor replacements that can cost thousands of dollars annually. A durable optical device with no consumables could dramatically reduce long-term costs, making continuous monitoring accessible to far more patients globally.

The convergence of multiple factors – proven optical techniques, miniaturized photonics components, advanced signal processing algorithms, and growing clinical evidence – suggests noninvasive glucose monitoring is transitioning from research curiosity to clinical reality. MIT’s Raman spectroscopy work, along with parallel efforts by other research groups, indicates we may finally be approaching the endpoint of a journey that began with tasting urine over three centuries ago.

For the millions living with diabetes worldwide, the promise is simple but profound: accurate glucose monitoring without pain, without skin punctures, and without barriers to the frequent testing that optimizes health outcomes. The technology to realize this vision appears closer than ever before.