Australian researchers have made a world-first breakthrough that has the potential to monitor the changes in pH levels and other responses to therapy in stroke and cancer patients.
Researchers from Monash University and the Baker Heart and Diabetes Institute have developed a biosensor that can be inserted into the human body to measure diagnostic markers in real time. These biosensors emit signals that can be detected by common ultrasound scanners.
The study, published in the journal ACS Sensors, has been granted an international provisional patent.
Currently, ultrasound imaging involves patients injected with gas-filled microbubbles to help clinicians better visualize blood flowing through their vital organs. However, these gas particles last for no longer than 20 minutes because patients exhale the gas over time. This makes long-term diagnostic tracking within a patient nearly impossible.
The new technology, developed through an Australian research team led by Dr Simon Corrie and Dr Kristian Kempe, from the ARC Centre of Excellence in Convergent Bio-Nano Science & Technology and Monash University, can be inserted deep into the tissue and measure biomarkers, such as pH (as a measure of whether a tumor is shrinking following chemotherapy).
More complex markers, such as oxygen (as an indicator of stroke injury) or disease-related proteins, might also be detected using these biomarkers in the near future.
The key to the success of this technology is the use of a solid nanoparticle developed by Julia Walker, a PhD student co-supervised by Dr Corrie and Dr Kempe, which alters its stiffness in response to pH changes in the body and does so over time. The biomarker can transmit these signals, which are then detected by ultrasound scanning.
Dr Corrie says the advantage of the technology is that, eventually, it could be read by something as simple as a mobile phone, making it able to monitor patients in remote areas, without the need for big hospital labs.
Our goal is to give clinicians the power of being able to have a patient sit in a chair and, as they are infusing the drugs, use commonly available ultrasound to monitor drug levels or organ response in real-time, adjusting dosages as a function of the patient’s needs. The technology has been tested in an animal model to detect changes in pH levels. We hope to now continue testing in animal models to determine whether it can accurately monitor rapidly changing pH levels, initially focusing on cancer and stroke.”
Dr Simon Corrie, Department of Chemical Engineering, Monash University
The ability to monitor drug levels and biological molecules inside patients in real time has remained largely elusive.
Most of the implantable monitors invented so far rely on high tech and expensive detectors such as CT scans or MRI. Using ultrasound – which is cheap and portable – as a means to track a disease state in response of a tumor to a new drug, or the risk of a heart attack with the rise of a diagnostic protein called troponin, has been hypothetical at best.
With further trials, Dr Kempe said a viable product may be developed within a decade. However, clinical and commercial partners are essential in order to make this technology a reality.
“Our field is ripe for future development that may include photoacoustic detection or the capacity to use radio frequency signals to ensure real-time monitoring of critically ill patients. This is game-changing technology that can improve people’s lives in all parts of the world,” Dr Kempe, also from the Monash Institute of Pharmaceutical Sciences and the Department of Materials Science and Engineering, said.
The research team comprises Dr Simon Corrie, Dr Kristian Kempe and Julie Ann-Therese Walker (ARC Centre of Excellence in Convergent Bio-Nano Science & Technology); and Xiaowei Wang and Karlheinz Peter (Baker Heart and Diabetes Institute).
Walker, J.A., et al. (2020) Dynamic Solid-State Ultrasound Contrast Agent for Monitoring pH Fluctuations In Vivo. ACS Sensors. doi.org/10.1021/acssensors.0c00245.