Painful departure for diabetes testing

An urgent, early morning call from her family doctor sounded a terrifying alarm for Teresa Brauer. The results of routine blood tests for her little girl were in, revealing a soaring blood glucose count of 27 (mmol/L), well above the safe range of 4-8 (mmol/L).

Her doctor’s advice was solemn enough to chill the blood of any parent “This is life threatening, take her immediately to emergency”. With shaking hands Teresa put down her phone and stammered into action.

Two years on, the memory of that call still convinces Teresa’s voice to crack.

“That call was the beginning of the worst day of my life. I had no idea what was going to happen. I couldn’t stop crying,” recalled Teresa.

Four-year-old Gabrielle’s body was running out of insulin, a consequence of undiagnosed Type 1 diabetes. Without insulin, her body could not process sugar, a scenario that carries the risk of coma, organ failure, and catastrophically for some families, results in loved ones never making it home.

Tucked up in the safety of the John Hunter Hospital, a new reality was taking shape.

With all the bravery a four-year-old could muster, Gabrielle surrendered her fingers to a punishing regime of hourly finger prick tests for the first few days of her week-long hospital stay. At such regular intervals, it wasn’t long before Gabrielle’s fingers were swollen and sore and her brave face had wilted.

“She’d see the nurse appear and burst into tears, saying ‘no I don’t want my finger pricks’. It was an incredibly difficult time for her. I could only watch on in sad disbelief, thinking to myself ‘this is your life now’,” shares Teresa.

It was difficult to watch her daughter being poked, prodded and upset and unthinkable to have to wield the needle herself. At the Hospital’s world-class endocrine unit, Teresa received a crash course in diabetes management, including the daunting combination of carbohydrate counting, insulin administration, and blood testing that would now keep Gabrielle alive.

“There’s always a reluctance to test and give insulin injections, knowing you have to cause your child pain and upset them. As a parent you’re hardwired to do the opposite. For anyone with diabetes, it’s a painful reality you face multiple times a day for the rest of your life. There are no days off. It’s always there,” said Teresa.

Sadly, for parents in the Hunter, finding themselves in this distressing scenario is more likely, with the region registering the highest incidence of Type 1 diabetes in the country.

It’s little wonder that other significant caregivers, such as teachers, have stepped up to the plate to learn how to look after kids with diabetes. Although for one such teacher, and her scientist husband, stepping up to the plate was just the beginning. The ball is now well and truly out of the park.

It was through the prism of his schoolteacher wife, Diana, that University of Newcastle physicist, Professor Paul Dastoor first confronted the challenges of living with diabetes.

“My wife helped children with diabetes administer their insulin and prick their fingers for testing at school. It’s a painful task, and really magnified when observed in children. I was taken aback that such frequent discomfort was a necessary part of their day. As a scientist, I couldn’t help but wonder if there was a better way to test,” offered Professor Dastoor.

At that time, in the early 2000s, Professor Dastoor’s team at the University’s Centre for Organic Electronics (COE) was already working on another technology – ultra thin, flexible printed solar cells for renewable energy generation - and were seeing great results. Professor Dastoor wondered if they could convert their solar cells to make transistors, which when combined with biological material such as enzymes, could function as a biological sensor for saliva. Put simply, a ‘lickable’ glucose sensor as opposed to one that draws blood.

With funding secured through the Australian Research Council (ARC) the team embarked on their mission to nix the human pin cushion approach to diabetes management.

“Often the way science is portrayed is that you have a genius moment and then everything falls into place. That was absolutely not the case here. On our first attempt we got nothing, we just learnt how not to do things,” said Professor Dastoor.

At 100 times less concentrated than blood glucose, salivary glucose exists in minute concentrations. If sheer scarcity of material wasn’t enough to thwart the team’s campaign, saliva’s plethora of other substances, or ‘noise’ that requires tuning out, was poised for interference.

“In this instance I’m just glad I wasn’t a biologist. If I look back now at how naïve I was, and all the ways it shouldn’t work, I never would have tried it,” said Professor Dastoor.

Undeterred, the team forged on - a course of action Professor Dastoor attributes to him being “bloody minded at times”.

“What the research did show, was there was no reason that the concept shouldn’t work, so we kept at it. Serendipity intervened to provide momentum at several points, and through perseverance and incremental gains we managed to hit those milestones we set for ourselves. It took us longer than we expected, but we did it,” said Professor Dastoor.

The first major win for the team arrived when they managed to successfully print a transistor, the next when they succeeded in incorporating glucose oxidase – a natural enzyme that reacts with glucose - into that transistor. The result was an ultra-thin, chewing gum-stick-sized device that, when licked, would react with saliva glucose via the glucose oxidase coating, producing a tiny electrical current then amplified by the transistor.

“It’s huge. Diabetes is a relentless disease. Anything that can reduce pain and make life feel more ‘normal’ will have an enormous impact on people living with the condition,” said Teresa.

Most assume the sensors must be 3D printed, the way of many modern high-tech consumer devices. The reality is ground-breaking in its simplicity. Professor Dastoor’s team employ ubiquitous printing machines, not unlike the humble home printers adorning remote work stations the world over. At a commercial scale, printing feedstock is loaded in a continuous roll, known as ‘reel-to-reel’ or ‘roll-to-roll’ printing - a technique that brings us mass produced newspapers, books, magazines and packaging. In place of standard ink, Professor Dastoor’s team use their high performance, proprietary electronic inks that they have synthesized in their labs and perfected over many years. The sensor is achieved by printing several nano-scale layers of different inks on top of each other with incredible precision.

Crucially, this reel-to-reel technique allows for kilometres of material to be printed per day on a single print line, translating to low-cost production and an affordable product shelf price. It’s an exciting new wave of manufacturing known as ‘functional printing’, where instead of producing text and images, factory printers are producing futuristic printed electronic or ‘functional’ devices.

Via a commercial partnership with IQ Group Global, a listing of the technology on the NASDAQ stock exchange, and assistance from a $6.3 million Australian Government Modern Manufacturing Initiative grant, preparations are now underway for construction of the first commercial-scale manufacturing facility for this product. Such a feat could have profound benefits, enabling the manufacture of the first needle free diabetes tests for use in human trials, and establishing desirable new on-shore med-tech manufacturing capabilities. The facility will be located on the University of Newcastle’s STEM-strong Callaghan campus, offering the prospect of student exposure to and immersion in the industry via work integrated learning (WIL) and PhD placements.

The team is now adapting the saliva glucose biosensor for use in a wide range of other diseases.

“This is a platform technology, which means it will be widely applicable to detect a variety of substances that identify a range of diseases. We’re already looking for the substances that identify cancer, heart disease and allergies,” said Professor Dastoor.

Amid frustrating global shortages of rapid COVID-19 tests, the team has been working in partnership with The Wyss Institute for Biologically Inspired Engineering at Harvard University, to help develop the sensor platform for COVID-19.

“While we’re fortunate to have PCR and RA tests for COVID-19, they still present significant challenges at an individual and population health level. The Wyss Institute has developed a clever antifouling coating that we can incorporate into the biosensor platform, offering a new diagnostic tool for COVID-19,” said Professor Dastoor.

The sensors represent a fundamental shift in disease management, removing typical barriers to health testing such as pain, cost or availability, and empowering people to monitor their own health.

For mums like Teresa, this is a life-changing prospect.

“It’s huge. Diabetes is a relentless disease. Anything that can reduce pain and make life feel more ‘normal’ will have an enormous impact on people living with the condition,” said Teresa.

“In her first few weeks of kindergarten, Gabrielle was attracting a lot of questions from her classmates because they could see she was different in some ways. She said ‘Mum, I want to take Rufus (an educational diabetes teddy bear she received in hospital) for show and tell and talk about my diabetes’. The teacher sent me a picture of her up in front of the class with Rufus. It brings a tear to me eye even now. She’s so brave,” shared Teresa.

For Professor Dastoor, this is what it’s always been about.

“Fundamentally, scientists are interested in solving problems and fixing things. There’s nothing more satisfying than seeing something you’ve worked on go out into the world to improve lives and help people. It’s why we do the work we do,” said Professor Dastoor.

Professor Dastoor is based at the University’s Newcastle Institute of Energy and Resources (NIER) facility and is supported by the Australian National Fabrication Facility.

Aligned with the United Nations Sustainable Development Goals