Biosensor Prototype Monitors and Controls Personalized Drug Delivery in Real Time

A Stanford research team was able to continuously control drug levels in live animals using a tool that has big implications for advanced medical treatment.

When it comes to therapeutic drugs, one size does not fit all. This is particularly true for medicine that has a slim margin for error in being effective and safe. Too little of a chemotherapy drug, immunosuppressant, anticoagulant, or anesthetic may not be effective. Too much can be life-threatening.

A novel biosensor that continuously monitors and controls the drug levels in a person’s bloodstream in real time would bring a precision to drug dosing that hasn’t been seen before — and a team of researchers at Stanford says that it has developed technology with this potential.

“It’s hard to predict how a dose of drugs that you give to an individual will translate to the concentration of the drug in the body,” Peter Mage, a postdoctoral research fellow in electrical engineering at Stanford University, told Seeker.

Mage and Stanford electrical engineer H. Tom Soh published a paper this week in Nature Biomedical Engineering in which they describe a drug delivery tool they created for this purpose. The sensor has the potential to work for a range of drugs at once and eventually could be designed to test whether a drug is having the desired effect.

Before administering a dose of medicine, clinicians take many different variables into consideration, such as a person’s age, weight, and sex, whether they’re taking other medications, and the health of the patient’s liver and kidneys. Once the drug enters the body, muscle, fat, and other tissues absorb it. Enzymes begin to break it down and the kidneys and liver begin to filter it out of the bloodstream.

But everyone is different, and the ways in which individual bodies absorb and break down the drug are as numerous as there are patients. Clinicians monitor how the level of a drug is changing over time by drawing blood samples and running lab tests, but that can take hours.

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In lab experiments, the researchers used their biosensor to administer a common chemotherapy drug, doxorubicin, in live rabbits and rats. Although this drug has a narrow window of effectiveness, the biosensor was able to maintain consistent drug levels, compensating for differences in the size and physiology of the animals.

The biosensor was also able to maintain the appropriate drug concentrations of doxorubicin even when another chemotherapy drug, cisplatin, was injected into the bloodstream. 

“This is the first time anyone has been able to continuously control the drug levels in the body in real time,” Soh said in a statement. “This is a novel concept with big implications because we believe we can adapt our technology to control the levels of a wide range of drugs.”

The new biosensor, which is about the size of microscope slide, directly monitors the drugs levels in the blood stream and also adjusts the concentrations in real time.

It has two innovations. The first is a glass chip with tiny fluid channels that transport drug-laced blood, and the second is a short strand of synthetic DNA called an aptamer that’s designed to bind and then unbind from specific drug molecules.

Aptamers are put inside the microchannels, with each end of a strand anchored to a bit of gold on the bottom of the chip. The top end floats up and at its tips has an electroactive molecule that produces a current. Blood moving through the channels flows past these aptamers like river water flowing through reeds.

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When drug molecules in the blood bind with an aptamer, it folds down, bringing the electroactive tip closer the chip’s gold bottom, where it induces a current. Then the aptamer releases the drug molecule and straightens up again.

Billions of aptamers in the channels binding and unbinding to drug molecules, bending and straightening, create an overall electrical signal that relates to the amount of drug in the bloodstream. An algorithm computes that signal and uses it to adjust an infusion pump that delivers the appropriate amount of medicine into the bloodstream in a closed-loop system.

“This whole process is repeated once every 10 seconds, so you’re getting very, very fast corrections,” said Mage. “By measuring it so quickly and in real time, you’re able to very quickly achieve the desired concentrations of the drug automatically.”

Although the biosensor is a lab prototype, in a hospital setting it could monitor a patient through a catheter and control the drug dosage through an infusion pump connected to the patient’s intravenous drip port.

And although the current design contains aptamers that bind to one drug molecule at a time, Mage said that the device could theoretically monitor a range of molecules. These could include molecules from other drugs but could also include molecular indicators, such as proteins, that show whether the drug is working.

“In the case of chemotherapy drugs, you can look for proteins that indicate that tumor cells have died,” he said.

Mage and his team are preparing to determine whether the device could work in humans, a step that will take several years to ensure that the method is safe.

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