Pioneering flexible gold sensors for next-gen medical implants

In the realm of healthcare innovation, the marriage of engineering and nanotechnology continues to push the boundaries of what is possible.

At the forefront of this cutting-edge field are Dr Mostafa Kamal Masud and PhD candidate Aditya Ashok. The pair are researchers at the esteemed Australian Institute for Bioengineering and Nanotechnology (AIBN) at the University of Queensland, they have spearheaded the development of a flexible gold sensor that represents a paradigm shift in the world of medical implants.

By combining the remarkable properties of gold with the precision of nanotechnology, this sensor offers unparalleled adaptability, thereby enabling seamless integration with a variety of implant designs, from cardiac pacemakers to neurostimulation devices and beyond, as Dr Masud details.

“Currently, wearable and flexible devices are gaining traction in medical sciences. If you want to monitor any responses from the human body such as glucose or cardiovascular biomarkers – we need smart sensors,” Dr Masud explained.

“Although modern implanted electronics have developed rapidly over the past 60 years, most commercially available devices are still built on similar – and limiting – design concepts such as thick ceramic or titanium packaging.”

A fundamental requirement for these sensors is that they should be flexible, as the human body continually undergoes movement.

By utilising nanotechnology, Dr Masud and Mr Ashok have successfully engineered an ultra-thin, flexible, and electrically conductive gold sensor. Unlike conventional rigid sensors, their flexible gold sensor conforms effortlessly to complex anatomical structures, reducing discomfort, irritation, and the risk of device failure.

The research was pioneered by Professor Yusuke Yamauchi in 2007, senior group leader at AIBN and a professor at the School of Chemical Engineering at the University of Queensland. Professor Yamauchi specialises in the design of novel nanocrystals and nanoporous materials for practical applications.

Dr Masud joined the project in 2016 and Mr Ashok began working on the materials when he began his PhD program in 2019 – 2020. Under Professor Yamauchi’s guidance, they were able to synthesise a mesoporous gold film that acts as an electrode for biosensing and bioimplant applications.

The process behind developing the flexible sensor

Aditya Ashok says they were attempting to make different types of mesoporous materials. Mesoporous materials are nanoporous materials containing pores with diameters between two and fifty nanometres. The AIBN research group is a pioneer in mesoporous structures, not only just with metals, but also with semiconductors, and other mesoporous structures of different pore sizes.

Key advantages of mesoporous materials include:

• Ultrahigh surface areas, large pore volumes, tunable pore sizes and shapes.
• High surface areas provide large number of reaction or interaction sites for surface or interface-related processes.
• They exhibit nanoscale effects in their meso-channels and on their pore walls.
• Fascinating nanoconfinement effects in the voids of uniform mesochannels, which are advantageous in catalysis and energy storage.
• 3D nano-meter-sized frameworks can produce extraordinary nanoscale effects (surface and quantum effects) that result in unusual mechanical, electrical, and optical properties.

“Our group was focussed on making this mesoporous material, establishing its structural stability, and finding different fields where we could analyse the sample,” said Mr Ashok.

“While the structure gave us a better surface area with high sensitivity and scalability based on the deposition method that we used, it had not been tried on a flexible substrate,” he said.

A flexible substrate is important because it makes it easier to use the material in different non-invasive and minimally invasive, wearable, and implantable applications. Rigid substrates are difficult to use in applications involving direct-touch- based sampling from curved objects.

“Flexible substrates can take on any surface, including curved surfaces, and can be used for diverse applications – not only for biological sensing but also physical sensing. We used a two-step method to translate the mesoporous material onto a flexible substrate. We formulated and made the flexible substrate, and we then translated it for electrochemical deposition,” Mr Ashok added.

“The result we were hoping for was for the material to be flexible, stretchable, and lightweight so it could be mounted onto the human body. It also had to be less expensive, while not compromising on its sensitivity. On the engineering and commercial side of things, the material could not lose its ability to perform and had to be scalable.”

Many researchers in Australia and abroad have attempted to make a similar type of structure on a flexible substrate, but this was a challenging task. Dr Masud and Mr Ashok noted the problems in doing so and worked towards addressing them.

The first step was to translate the mesoporous material onto a flexible substrate electrochemically analyse it biologically and chemically. The researchers then took up a microfabrication method and the mesoporous electric chemical structure formation and combined them together to form these flexible mesoporous structures.

The inherent biocompatibility and resistance to corrosion found in gold make it an ideal foundation for implantable sensors.

“We made the gold design or patterns in micron skin, and then we used those substrates, removing them individually and depositing the mesoporous gold film. After an electrochemical deposition, we used the porous film and we confirmed the structure, and the growth on the 16 micrometre-wide gold electrode and successfully formulated the mesoporous structure,” said Mr Ashok.

“Next, we used the porous structure/ electrode for electrochemical measurements, which meant we needed to detect molecules on the surface of human skin as well as inside mice for bio- action potential. We recorded the signals that were produced by the sciatic nerve muscle of the mice at different intervals and different voltages, comparing its sensitivity to the traditional materials that we use now.”

Additionally, to achieve this, the material would need to have low impedance as the mesoporous material had a large surface area and would need to be flexible as well. To prove this, the researchers subjected was subjected to 1,000 bend cycles and physical strain, in addition to physiological monitoring applications. The result was a breakthrough moment for them – the materials performed twice as better as conventional flat gold samples.

“With these types of metal structures, there are significant problems with cracking. But our technology, in substrates where we deposited our mesoporous gold, despite undergoing several bend cycles, the connectivity and structural integrity was attained for a longer time,” said lead researcher Dr Mostafa Kamal Masud.

It is important to note that fat in the human body is absorbed by any metals implanted in the body. Dr Masud said that until now, no one had attempted to implant these types of substrates in the human body.

“While this is a single material, it has several layers, and each layer is connected to one another. Once implanted in the body, fat begins to deposit on the surface as it always does. But due to the nature of our system, the fat blocks the top surface, and the inner surface remains active. And the material will work for longer than conventional systems as long as it takes the fat to block the innermost ground layer.”

Applications in advancing healthcare

The exceptional sensitivity of the gold sensor is a game-changer. By enabling precise monitoring of vital signs, biomarkers, and other physiological parameters within the body, healthcare providers can gather comprehensive and accurate data in real-time.

This paves the way for personalised and proactive healthcare, where treatment plans can be tailored to individual needs and interventions can be made promptly, ultimately leading to improved patient outcomes.

There can be two potential applications for sensors such as this one, says Dr Masud, one is a wearable device outside the body and the second is an implantable device inside the body.

“In chronic or infectious diseases today such as COVID-19, the most advanced technique is real-time qRT-PCR (Quantitative Reverse Transcription PCR). As our substrate is highly porous and highly active, there is immense potential to revolutionise this technology.

Another example is breast cancer, where if we consider a biomarker such as heart to protein, or heart to microRNA – with the progression of the disease over multiple stages, the change in those protein expressions or microRNA is extremely minor,” said Dr Masud.

“Traditional or flat gold sensors may not detect such low levels of changes. And the sensitivity of our materials can detect at the microRNA level as well as the protein level. Therefore, through flexible wearable devices on the outside of the body, we can determine cardiovascular disease biomarkers, as well as glucose and cholesterol.”

For implanted devices inside the body, initial studies have demonstrated promising results for cardiac implants.

By seamlessly integrating the sensor into pacemakers and defibrillators, clinicians gain unprecedented access to vital cardiac data. The sensor’s ability to detect even subtle changes in electrical signals and biomarkers allows for early identification of irregularities, enabling healthcare providers to proactively address potential cardiac events before they occur.

Additionally, the research team is  actively exploring the integration of the gold sensor with neurostimulation devices, to advance treatment options for patients with neurological disorders. By closely monitoring brain activity and the response to stimulation, this innovative sensor has the potential to significantly improve therapeutic outcomes for conditions such as epilepsy, Parkinson’s disease, and chronic pain.

“Finally, we have drug monitoring,” said Dr Masud. “In drug delivery, it is important to see how drugs are being released and how they affect metabolic processes in the human body. Since our material has a large surface and several pores, it can be used to load drugs on the surface. These are a few of many potential medical applications.”

Dr Mostafa Kamal Masud says the potential of the flexible gold sensors extends beyond biomedical sensing, including applications in energy, hydrogen generation and electrocatalysis.

“The aim of our research is to have practical applications and to do something for society. Therefore, we always encourage collaboration with people who are aligned with similar research areas as us. Dr Hoang-Phuong Phan from the School of Mechanical and Manufacturing Engineering at the University of New South Wales, and previously at Griffith University, was an important collaborator in the broader work we did.

“Me and Aditya – we are physical scientists, focussing on physical and chemical aspects of nanomaterials. And we’ve used our collaboration for biological study. By integrating our expertise with highly specialised bio-scientists, we can always achieve a better outcome.”

As Dr Masud and Mr Ashok continue to refine the flexible gold sensor and explore its potential in other medical fields, they envision a future where the sensor can transform the landscape of healthcare and beyond.

“The potential and possibilities in this field are vast and we will continue to explore them,” concluded Dr Masud.