Supporting glucose sensor technology to build a universal drug monitoring system

Supporting glucose sensor technology to build a universal drug monitoring system

Synthetic biologists at Rice University have found a way to take the glucose monitoring technology used in automated insulin dosing systems and make it universally applicable for monitoring and dosing virtually any drug.

In a recently published study in Nature Communicationsresearchers in Caroline Ajo-Franklin’s lab demonstrated the technique by modifying a blood glucose sensor to detect the cancer drug afimoxifen, an estrogen inhibitor that patients’ bodies also produce after they take the chemotherapy drug tamoxifen.

By building on mature biosensing technology that is commercially available at most pharmacies for under $20, the Ajo-Franklin team hopes to accelerate the development of automated dosing systems for chemotherapies and other drugs, as well as other real-time monitoring technologies of biomarkers in the blood.

The dream is to have technology similar to what is available today to monitor and treat variations in blood glucose, and that would be true for any drug. Millions of people use blood glucose monitors every day. If we could use the same basic technology to monitor other drugs and biomarkers, we could move away from the one-size-fits-all dosing regimens we’re stuck with today.

Caroline Ajo-Franklin, bioscientist, cancer researcher and director of the Rice Synthetic Biology Institute

The heart of blood glucose monitoring technology is a biochemical reaction in which specific proteins bind to glucose molecules and release electrons. Millions of these reactions occur in seconds, creating a small electrical current that is proportional to the amount of glucose in the blood sample.

Rong Cai, a postdoctoral researcher and lead author of the study, tested more than 400 slightly modified versions of the electron-releasing protein and found a version that reacted with afimoxifene, reducing the current from the blood glucose response. This allowed the team to detect the presence of afimoxifene by comparing the current produced by the regular glucose test with the reduced current from the modified test.

To demonstrate the technology in an electronic device, the Ajo-Franklin team worked with Rice engineer and materials scientist Rafael Verduzco’s research group to create a sensor for afimoxifene that emits a current when the drug is detected.

Ajo-Franklin said her lab is already working on both ways to improve the sensitivity of glucose-based drug tests and methods to rapidly identify glucose-oxidizing proteins that can detect drugs other than afimoxifene.

“The meter is the part that’s so well developed,” Kai said. “Although our target is different, it’s just a matter of engineering and changing the protein from the inside. Outside, everything will be the same. You can still do the test with a strip or on your arm.”

She said another key feature of the technology is that it produces an electrical output.

“If your signal is electrical, you can read it on your phone, store its data on your phone, send it to the cloud, whatever,” Kai said. “That’s the part, this marriage of electricity and biology, that’s very appealing.”

Ajo-Franklin is a professor of biosciences in the Weiss School of Life Sciences and a CPRIT Cancer Research Fellow at the Cancer Prevention and Research Institute of Texas (CPRIT). Verduzco is a professor of chemical and biomolecular engineering and of materials science and nanoengineering at the George R. Brown School of Engineering.

The research was supported by CPRIT (RR190063), the National Science Foundation (1828869, 2223678), and the Army Research Service (W911NF-22-1-0239).

source:

Journal reference:

Kai, R., et al. (2024). Creating a therapeutic sensor in situ using protein engineering, electrochemical sensing, and electronic integration. Nature Communications. doi.org/10.1038/s41467-024-45789-9.

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