After a drug is swallowed or injected, exactly how much of it stays in the blood and for how long becomes a guessing game. Even when the starting dose is well-controlled, each patient’s unique pharmacokinetic profile means that drug concentrations can vary widely. That causes problems for conditions that require drugs at steady levels, or those that don’t work at low levels but cause toxic side effects at high levels. It also makes it difficult for doctors to know whether they need to prescribe a higher dose that could lead to even more side effects — especially for patients undergoing hard-to-tolerate drugs like chemotherapy.
These challenges would quickly disappear if patients had a way to rapidly and safely monitor the concentration of drugs in their blood at home. Last week, scientists at the University of Montreal took steps to make that into a reality with new work published in the Journal of the American Chemical Society. Their team developed a DNA-based electrochemical sensor that monitors drug concentrations from a single drop of blood within five minutes.
“Using this DNA-base assay, we have been able to develop sensors for multiple blood molecules even if their concentration was sometimes less than 100,000 times less concentrated than glucose," said Bal-Ram Adhikari, a biotechnologist at the University of Montreal and co-author on the study, in the press release.
Electric currents reveal concentrations
The device works by imitating nature’s signaling systems. "Cells have developed nanoscale 'signaling cascades' made of biomolecules that are programmed to interact together to activate specific cellular activities in the presence of specific amount of external stimuli or molecules,” said Guichi Zhu, an electrochemist at the University of Montreal and first author on the paper, in the release.
In the case of their new sensor, DNA molecules interact with the molecular drug target and then activate another electro-active DNA molecule that generates an electrochemical current upon hitting an electrode on the device. The researchers demonstrated the concept using an anti-malaria drug in mice and showed that the DNA signaling cascade produced a change in electrical current that was picked up by the sensor and allowed it to quantify the concentration of the drug in the mice.
The team has now secured a patent for their device and licensed it to the Montreal-based company Anasens to move forward with commercialization.
The future of drug monitoring
Point-of-care devices like these could lead to advances in personalized medicine for patients who take drugs to treat cancer, chronic conditions, or even short-term illnesses.
They could also come in less invasive forms with sensors that don’t require blood at all. Earlier this year, researchers at the University of Southern California developed a wearable sensor that uses sweat to track lithium concentrations in patients with bipolar disorder. This population represents a great example of why regular, accessible testing is critical: too little lithium provides no therapeutic benefits to patients, while too much lithium can lead to kidney and thyroid damage or even possibly be fatal.
That device used organic electrochemical transistors that were designed to detect lithium specifically, suggesting that future work could also tailor these transistors to a wide variety of molecules picked up through sweat. In a statement, the researchers noted that they plan to integrate artificial intelligence algorithms into the sensor that would automatically adjust the lithium dosage in patients — showing the possibility for at-home drug sensors to become a crucial part of a patient’s personalized therapy program.
With the market for global therapeutic drug monitoring poised to grow to $2.32 billion by 2030, further research and investment on devices like these could make it routine to measure the concentration of almost any drug from a patient’s home. The end result would be safer drug dosages and better therapeutic outcomes for all patients.
