Context                

The next generation of continuous glucose monitors – an implantable continuous blood glucose monitor – promise “set and forget” convenience for people with diabetes. This makes the lifetime of the glucose sensor within the body a key performance metric.

Solution                

To inform Glucotrack’s technical and commercial strategy, TTP created an in silico model of the company’s glucose sensor, predicting a 3+ year lifespan. This was backed up by physical measurements without the need for lengthy in vivo trials.          

Result                

The ability to understand what happens within the implanted sensor dramatically accelerated the design and allowed Glucotrack to confidently predict a sensor lifetime of over 3 years to differentiate its technology.

Improving on Wearable Blood Glucose Monitors

Wearable continuous glucose monitors, also known as CGMs, have transformed the way we manage diabetes. By using an enzyme-containing sensor to continuously monitor glucose levels just under the skin, they avoid the need for painful and cumbersome finger-stick tests. This makes it easier for people with diabetes to manage their condition effectively, leading to better long-term outcomes and reduced impact on healthcare systems.

But revolutionary though they are, wearable CGMs aren’t the most beneficial option for every person with diabetes. US-based start-up Glucotrack have come up with a design for an implantable glucose-monitoring sensor that offers several innovative improvements, offering a valuable alternative for certain patient populations. Most importantly, it measures glucose in the blood, not in the interstitial fluid just below the skin, meaning that it eliminates the 10–15-minute time lag during rapid changes that are common with wearables. It’s also more discreet and avoids the plastic waste of replacing a wearable device every couple of weeks.

Glucotrack’s sensor will need to be implanted by a medical professional, and although this would be done in a routine outpatient procedure, a long lifetime is key to avoid these visits to “fit” the device being too frequent. But rather than go down the route of lengthy and expensive in vivo tests to assess sensor lifetime, the team realised that an in-depth modelling study could provide answers, and so in May 2023 they got in touch with TTP.

Dr Sophie Meredith, who specialises in implantable medical devices and biosensors at TTP, explains why estimating the lifetime of Glucotrack’s sensor wasn’t simple: “The challenge is that their sensor – like nearly all CGMs – doesn’t measure glucose directly. Instead, it contains an enzyme that oxidises glucose, after which the reduced enzyme is regenerated by oxygen to yield hydrogen peroxide. An electrode within the sensor measures this hydrogen peroxide, and uses that value to infer the level of glucose”.

This means, says Dr Meredith, that there are a large number of interacting factors that might influence the lifetime of the sensor. For example, the glucose concentration within the sensor must be high enough to provide a detectable current, but not so high that it saturates the enzyme or consumes it too rapidly; whereas the oxygen from the surrounding solution must be able to diffuse into the sensor to maintain the reaction.

Developing an in silico Model

TTP worked closely with Glucotrack to assess whether in silico modelling would be an effective approach to achieve their goals. Together, we evaluated various strategies to ensure that the model would serve as a practical, commercial asset for design acceleration.

Then, to deal with the complexities of interacting factors, the team designed experiments to test each factor individually and determine its effect. “We were looking at things like the structure and thickness of the various membranes within the sensor, rates of transport of glucose and oxygen, rates of enzyme consumption and natural decay, efficiency of hydrogen peroxide capture by the electrode, and long-term signal drift”, she says.

Once these experiments were completed, the team were able to construct a robust in silico model that not only provided accurate lifetime predictions but also became an invaluable tool for guiding strategic design choices.

Shorter Design Cycle, Longer Sensor Lifetime

With the model in place, TTP and Glucotrack used the insights provided by the model to make faster, data-driven design decisions to balance technical performance with commercial viability. Visualising what happens within the sensor, both spatially and temporally, made it possible to assess multiple designs and dramatically accelerated the overall design cycle.

To ensure that the model’s predictions were accurate, we also carried out rigorous in vitro tests to compare the in silico results with real-world data. This validation process reinforced the commercial value of the model as a decision-making tool that could be relied upon to guide the development process.

The final design selected – just 9 months after the start of the collaboration – had a predicted sensor longevity of at least 3 years, a considerable improvement upon an earlier estimate of 2+ years. As well as relating to a previous sensor design, this earlier prediction was also based on methodology that wasn’t as precisely tailored to Glucotrack’s sensor setup. “The new results gave them a lot more confidence in how well their sensor should perform in the real world”, says Dr Meredith.

Dr Paul Goode, CEO of Glucotrack, says that it also shows to investors and potential collaborators that the product is on-track for commercialisation: “The projected increase in sensor longevity to beyond three years demonstrates that our technology is truly differentiated in the glucose monitoring space”.

Going the Extra Mile to Deliver an Improved Design

Dr Goode also has positive words to say about what Glucotrack gained from the project: “TTP’s scientific team was very collaborative while providing solid technical guidance and direction. They also ‘went the extra mile’ time and again by asking questions, identifying and pursuing pathways, and presenting complete solutions to unforeseen findings that were impactful to our goal of improving sensor longevity”.

“This project not only displayed TTP’s capabilities in tackling such highly complex systems, but also demonstrated the incredible utility of developing and using a validated in silico model to both understand and improve a biosensor design”.

‍

TTP’s scientific team ‘went the extra mile’ time and again by asking questions, identifying and pursuing pathways, and presenting complete solutions to unforeseen findings.

Dr Paul Goode, Glucotrack, USA

‍

Glucotrack’s new sensor design should ultimately have major benefits for specific patients with diabetes – those for whom an implantable option is the most suitable or desired choice. “An implantable sensor with a longer lifetime will mean that people can ‘set and forget’ the technology”, says Dr Meredith. “Along with the expected reduction in measurement time lag, that should make it easier for them to correctly dose their insulin. That in turn may mean fewer hospitalisations, and better outcomes”.

And finally the collaboration with Glucotrack has been a fascinating test case of the expertise TTP has developed around automated test systems for glucose sensors, combining biochemical sensing, physical processes, medical devices, and modelling software. The result has been a better understanding of the processes at play, leading in this case to an improved design, delivered to a tight schedule, with a promise of further advances to come.

This project exemplifies TTP’s collaborative approach, supporting clients in making the right decisions at every stage of development to ensure both technical excellence and commercially successful outcomes.

About TTP’s Biosensing Team

Specialising in the development of wearable and implantable biosensors, TTP’s Biosensing consulting team deploys multidisciplinary teams, combining expert capabilities from electrochemistry and optics to human factors, mechanical design, software, electronics, wireless power and communications to deliver tailored solutions that meet the most demanding project requirements.

Partnering with us means working with experts who understand the CGM industry inside out. Whether navigating uncharted territories, supporting your next innovation or accelerating time to market, we solve complex challenges with engineering and scientific rigour, finding and retiring risks early to deliver high-impact, human-centred results. When your internal bandwidth is constrained, TTP is ready to deliver. With deep expertise and a 25-year track record, we provide the agility and expertise needed to ensure your commercial success.