SaMD Diabetes Software Experts

Advancements & Opportunities in Continuous Glucose Monitoring

Current research into improving the accuracy and usability of continuous glucose monitors has left few stones unturned. From sweat-based sensors to contact lenses, boundless opportunities are waiting to be explored in this arena. Find out which of those opportunities holds the most promise and how your company can capitalize on advancements in this technology.

Continuous glucose monitors (CGMs) are a wonderful example of a sophisticated software-based medical device that has improved rapidly over the last decade but still has miles to go before reaching perfection. These high-tech wearables provide users with invaluable data to help them make informed treatment decisions. They require far less user input than previous iterations, are less invasive, and are more accurate than ever. 

Still, the limited number of CGMs available on the market today leave a lot to be desired. They come with short lifespans, see frequent disruptions in usage due to warm-up times and charging periods, and are still not as accurate as age-old blood glucose meters.

To overcome the persistent disadvantages of current CGM devices, many researchers are turning to new means of measuring body glucose levels. Within these uncharted waters, there is a ton of potential and boundless opportunities for new companies to break through. Today, we’ll look at current CGM technology on the market and the potential avenues for innovation being explored.

Types of CGMs Currently Available

There are currently four CGM systems available on the American market FDA approved for use in people living with diabetes: Medtronic’s Guardian Sensor 3, Dexcom’s G6, Abbot’s Freestyle Libre, and Sensonic’s Eversense. The first three utilize electrochemical sensors to interpret glucose concentrations within interstitial fluid. Eversense also measures interstitial glucose concentrations, but through the use of optical sensors.

Electrochemical sensing relies on the flow of current that results from an oxidation reaction at one electrode and a reduction reaction at another. For glucose sensors, it is the H2O2 reduction product of the Glucose/GOx system that is measured. 

This mode of measurement comes with some notable drawbacks. The lifespan of the sensors is limited, with most lasting between 7 and 14 days. Most require an external transmitter and power source, which requires disruptive charging periods or disposable transmitters that must be replaced. And all require warm-up periods to allow electrochemical input to stabilize. All of these result in use downtime that can be disruptive to users who require constant input from their CGMs to make informed treatment decisions.

The optical detection of glucose in interstitial fluid utilized by the Eversense CGM relies on fluorescence spectroscopy. In this implanted sensor, a fluorophore molecule is introduced to interact with glucose molecules. This interaction results in fluorescence that is then measured and interpreted by an external transmitter. 

The major benefit of this technology is a longer use life. The current Eversense device is approved for 90 days of use. The newest generation to receive FDA approval has a runtime of 180 days. But this technology still requires a lengthy 24-hour warm-up period for reading stabilization, frequent charging of the external transmitter, and the inconvenience of implantation that must occur at the doctor’s office.

CGM Technology In the Works

While the technology of continuous glucose monitors today has come a long way since the first device hit the market, these CGMs still leave a lot to be desired. To overcome the drawbacks of interstitial electrochemical and optical sensing, many researchers have turned to more novel approaches to gathering real-time glucose data.

Urine-Based Sensors

Body glucose readings can be determined through urine levels using the changing refractive index and shifting resonance frequency. Due to the natural availability of this fluid, both show promise for innovative CGM devices. One such experimental device takes the form of a tiny crystal ring capable of instantaneously predicting the levels of urea, albumin, bilirubin, and glucose concentration in sampled urine. A device such as this would be immensely useful to people living with both diabetes and kidney disease.

Another device in the works relies on a screen-printed biofuel cell array to detect glucose levels in urine. This self-powered glucose sensor has limitations as a continuous reading device but could be implemented as a wearable diaper for young and geriatric patients in the diabetic community.

Saliva-Based Sensors

Saliva is another readily available fluid in the body that can theoretically be used to predict blood glucose values. Experimental technology in this arena detects minute glucose concentrations at extremely precise margins, making for a valuable tool for hypoglycemia detection. Devices using this technology have the potential to be non-invasive, low-cost, and highly accurate. However, the glucose reading range is restricted in saliva sampling, making it less useful for hyperglycemic readings.

Wearable sensors in the works include mouthguard-type apparatuses with a proven ability to predict blood glucose highly accurately with near-instantaneous readings. 

Serum Implants

Multiple devices have been theorized and tested that measure serum glucose levels as a predictor of blood glucose concentration. These devices work primarily on functionalized reduced graphene oxide combined with nanotechnology to measure glucose with limited interference from other biomarkers. Fluorescent optical detection and traditional electrochemical readings of serum have also been proposed.   

Current research suggests CGMs using serum detection would be low cost and offer highly accurate readings, especially within the hypoglycemic range. They also show quick steady state response for reduced warm-up periods. However, current models show reduced run-life with glucose sensitivity dropping rapidly over time.

But the real challenge of developing a glucose sensor using serum detection is creating a noninvasive wearable device. While the latter part of that technology has been accomplished, the “noninvasive” piece has, to this point, eluded developers. 

Tear-Based Sensors

Tear-based biosensors are becoming more popular due to the fluid’s simple accessibility and a clear correlation with blood glucose levels. Devices in the experimental phase have shown high precision in low glucose readings but often fall below current options in terms of precision as glucose levels rise.

Another challenge within this realm is the need for self-powered sensors. Researchers have explored many options, including solar battery, biofuel cell, inductive power, and radiofrequency. These wearable sensors could take many forms. Those currently being researched include a flexible coil implanted under the lower eyelid, contact lenses, and eyeglasses with special miniaturized flow detectors. 

While there is some concern that users may see wearable tear-detecting devices as invasive, these still show a high potential for accuracy and would offer a longer run life.

Sweat-Based Sensors

Perspiration-based glucose sensing holds a lot of promise, especially in terms of non-invasive, low-cost wearables. Predicting blood glucose levels from sweat requires only a tiny fluid sample that can be collected without any needles or implanted parts. Current experimentation predicts a flexible, disposable patch-type apparatus that utilizes optic or electrochemical sensors.

Experiments into these types of sensors have proved to be highly accurate with a high sensitivity rating, especially at hypoglycemic levels. They also show relatively fast response times and quick stabilizing periods for shorter warm-ups. Like other methods investigated here, perspiration-measured glucose is less accurate at higher levels and the overall run life of the devices was not much longer than current options. 

But if these drawbacks can be overcome, this painless method of glucose monitoring could quickly become the preferred CGM option for many users.

Advanced Interstitial Sensing

Despite the promise held by many other bodily fluids, interstitial fluid still remains one of the most heavily researched options for glucose sensing. Advancements in this field look to reduce the drawbacks of current technology, focusing on less intrusive and painful means of collecting data.

Microneedles represent one of the most attainable leaps forward for CGM devices. By using an array of tiny needles to collect interstitial fluid or measure glucose levels in fluid just below the skin’s surface, these devices completely remove the pain aspect of CGM use. They also reduce scarring allowing for repeat application on the same site. These two factors have led to the development of a smartwatch CGM (by PKVitality) that allows the measurement and display of glucose information in a single, compact smartwatch component.

Other companies pursuing microneedle technology, including Biolinq and Sano, are working to develop patches with similar usability as current CGMs but with less pain during application.

The Future of Continuous Glucose Monitoring

Already, continuous glucose monitors represent a wealth of untapped potential within the medical device world. The current uses for CGMs beyond diabetes monitoring have only scratched the surface of the possibilities out there. And wearable devices, in general, are only growing in complexity and reach. 

Looking beyond interstitial glucose detection as a means to track blood glucose readings is just the first step to tapping into the potential of this market. New methods of measuring glucose open up a realm of possibilities for non-invasive CGMs with improved accuracy, longer wear time, and fewer reading disruptions. With these new methods also comes the potential for multi-use biosensors that can track not just blood sugar, but other biomarkers that could provide valuable feedback to users and doctors to better inform short and long-term treatment decisions. 

Further Reading

Share:

More Posts

Get in Touch

SaMD Diabetes Software Experts

Copyright © 2022 Sequenex