Synthetic biologists at Rice University have found a way to take advantage of the glucose monitoring technology used in automated insulin dosing systems and make it universally applicable for the monitoring and dosing of virtually any medication.
In a study recently published in Nature CommunicationsResearchers in Caroline Ajo-Franklin’s lab demonstrated the technique by modifying a blood glucose sensor to detect the anti-cancer drug afimoxifen, an estrogen inhibitor that patients’ bodies also produce after taking the chemotherapy tamoxifen.
By taking advantage of a mature biosensing technology that is commercially available in most pharmacies for less than $20, the Ajo-Franklin team hopes to accelerate the development of automated dosing systems for chemotherapies and other drugs, as well as other technologies for the real-time monitoring 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 for that to be true for basically any drug,” said Ajo-Franklin, a bioscientist, cancer researcher and director of the Rice Synthetic Biology Institute. . “Millions of people use blood glucose monitors every day. If we can use that same basic technology to monitor other medications and biomarkers, we could move away from the one-size-fits-all dosing regimens we have today.”
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 take place in seconds, creating a small electrical current that is proportional to the amount of glucose in the blood sample.
Rong Cai, a postdoctoral research associate and lead author of the study, tested more than 400 slightly modified versions of the electron-releasing protein and found one version that reacted with afimoxifen, reducing the current output of the blood glucose reaction. This allowed the team to detect the presence of afimoxifen by comparing the current produced by the regular glucose test with the reduced current of the modified test.
To demonstrate the technology in an electronic device, the Ajo-Franklin team worked with the research group of Rice engineer and materials scientist Rafael Verduzco to create an afimoxifene sensor that emitted a current when the drug was detected.
Ajo-Franklin said his lab is already working on both ways to improve the sensitivity of glucose-based drug tests and on methods to quickly identify glucose-oxidizing proteins that can detect other drugs besides afimoxifene.
“The glucometer is the part that is so well developed,” Cai said. “While our goal is different, it’s just a matter of engineering and changing the protein on the inside. On the outside, everything will be the same. You can still test with a strip or on your arm.”
He 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,” Cai said. “That’s the part, that marriage between electricity and biology, that’s very attractive.”
Ajo-Franklin is a professor of biosciences in the Weiss College of Natural Sciences and a CPRIT Fellow in Cancer Research 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 Office (W911NF-22-1-0239).