Researchers are a step closer to transforming a US$70 billion global diagnostic industry with new designer biosensors that ‘switch on’ color or electrical responses to drugs used in cancer, arthritis, and organ transplant treatment.

Researchers have proven their modular approach to constructing small molecule biosensors – artificial proteins designed to capture biomarkers of choice and produce measurable responses.

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 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,” the senior author said.

“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.

“With further development, the biosensor technology could lead to a fingerstick test that potentially provides doctors with patient results in 3-5 minutes during a standard consultation,” the author said.

The senior author said 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 therapeutic drugs.

The author said 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,” the author said.

When activated, the different protein biosensors produce either a change of colour for hue-based readings, or electrochemical current.

The author said 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,” the author said.

“The Clarkson team also demonstrated the feasibility of multiplexing this technology to detect two different biomarkers at the same time.”

Despite experiment success, the author said glucometer technology was use-specific, and researchers would need to re-engineer devices and manufacturing processes for new clinical uses.

“There are a huge number of parameters to reconcile when building a medical device. It’s incredibly hard and that’s why new diagnostic technologies come to the market very slowly,” the author said.

https://www.nature.com/articles/s41467-021-27184-w

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fdesign-of-a-methotrexate&filter=22