CoESB researchers have proven their modular approach to constructing small molecule biosensors – artificial proteins designed to capture biomarkers of choice and produce measurable responses – in collaboration with Clarkson University in the US and Pathology Queensland.
In two separate studies, biosensors were adapted to accurately measure immunosuppressant drugs cyclosporine A, tacrolimus and rapamycin and anticancer drug methotrexate, which requires close monitoring to reduce toxicity and organ damage.
Lead researcher, Chief Investigator Professor Kirill Alexandrov from the QUT Centre for Genomics and Personalised Health said the protein biosensors had potential to expand patient care by enabling sophisticated tests on cheaper lab equipment and new point-of-care devices.
‘Proteins are at the core of a US$70-billion-dollar global diagnostic market that relies heavily on central lab processing,’ says Professor Alexandrov. ‘Our biosensor technology will enable tests like therapeutic drug monitoring on less sophisticated equipment that you are more likely to find in small, regional or remote labs and hospitals.’
Future tests may also require smaller biological samples with researchers proving a biosensor could accurately measure cyclosporine A levels in one microlitre blood samples—100 times smaller than samples needed for central lab analysis.
‘With further development, the biosensor technology could lead to a fingerstick test that potentially provides doctors with patient results in three to five minutes during a standard consultation, says Professor Alexandrov.
Professor Alexandrov says protein complexity and fragility made construction and use of protein biosensors difficult but the modular design helped alleviate the problem and could be adapted to potentially target any small molecule – not just to therapeutic drugs.
He says the new proteins were produced by engineered bacteria, altered using recombinant DNA technology to produce artificial switch molecules that were tailored to recognise a particular drug.
‘The protein biosensors are ‘”switched off’– like an electrical circuit with a missing piece. Only the targeted biochemical in human fluids like blood or saliva can complete the circuit and ’switch on’ a signal proportional to the amount of biomarker detected,’ he says.
When activated, the different protein biosensors produce either a change of colour for visual readings or electrochemical current.
Professor Alexandrov says the team experimented with applications using common glucometer technology to develop a cheap, portable and accurate device.
‘Activated electrochemical biosensors broke down glucose and generated electrons as by-products to produce electrical current proportional to the amount of captured target molecule,’ he says.