We’ve all heard the term “addictive personality,” and many of us know individuals who are consistently more likely to take the extra drink or pill that puts them over the edge. But the specific balance of neurochemicals in the brain that spurs him or her to overdo it is still something of a mystery.
“There’s not really a lot we know about specific molecules that are linked to vulnerability to addiction,” said Tod Kippin, a neuroscientist at UC Santa Barbara who studies cocaine addiction. In a general sense, it is understood that animals — humans included — take substances to derive that pleasurable rush of dopamine, the neurochemical linked with the reward center of the brain. But, according to Kippin, that dopamine rush underlies virtually any type of reward animals seek, including the kinds of urges we need to have in order to survive or propagate, such as food, sex or water. Therefore, therapies that deal with that reward system have not been particularly successful in treating addiction.
However, thanks to a collaboration between UCSB researchers Kippin; Tom Soh, professor of mechanical engineering and of materials; and Kevin Plaxco, professor of chemistry and biochemistry — and funding from a $1 million grant from the W. M. Keck Foundation — the neurochemistry of addiction could become a lot less mysterious and a lot more specific. Their study, “Continuous, Real-Time Measurement of Psychoactive Molecules in the Brain,” could, in time, lead to more effective therapies for those who are particularly inclined toward addictive behaviors.
A biosensor that could continuously measure drugs and biomolecules in the blood of living patients promises to aid early diagnosis of disease and help physicians customize drug doses to individuals, a key goal of personalized medicine.
The technology has been used to monitor drugs in live rats and human blood but not yet in people. However, “in the wide, deep sea of silly biosensors that don’t stand a chance of ever working in practice, this one is the real deal,” comments biosensor expert Richard M. Crooks of the University of Texas, Austin, who wasn’t involved in the study.
Biosensors for specific drugs and biomolecules in body fluids have long been available, but most do single measurements. Continuous monitoring is currently available for only a few analytes, such as glucose, lactose, and oxygen.
Devices for continuous measurement of a wider range of target molecules in blood could help detect the onset of diseases and optimize drug dosing. But creating them is a tall order. They would have to operate without sample preparation, be sensitive and selective enough to analyze targets reliably at low levels in complex matrices, and resist fouling from body fluids.
MEDIC (microfluidic electrochemical detector for in vivo continuous monitoring), devised by Brian Scott Ferguson and professor Hyongsok (Tom) Soh of the University of California, Santa Barbara, and coworkers, meets those requirements (Sci. Transl. Med. 2013, DOI: 10.1126/scitranslmed.3007095). It is based on an electrochemical approach demonstrated earlier by Soh’s UCSB collaborator Kevin W. Plaxco and coworkers.
A sensor that can continuously monitor the concentration of a drug in the bloodstream is set to help personalised medicine take off. This technology will let doctors tailor drug treatment courses for each patient with exceptional precision and according to how fast they excrete or metabolise different medicines.
Continuous, real time monitoring of specific molecules in patients’ bloodstreams is already possible in a few special cases, most notably for glucose, where it has revolutionised the treatment of unstable diabetes. However, these systems are based on enzymes and their highly specific recognition of natural substances such as glucose or lactose. Unfortunately, drug targets are normally membrane proteins, which are notoriously unstable when removed from the cell. This means they can’t be integrated into a sensor to monitor what’s happening to a drug in the body.
Tom Soh and his team at the University of California, Santa Barbara, US, got around this problem by using electronic aptamer sensors developed by the group of co-author Kevin Plaxco, also at Santa Barbara. DNA aptamers are strands of DNA that fold up into specific, protein-like shapes. By systematic selection from large pools of random DNA sequences, researchers can identify aptamers that recognise certain molecules very precisely, including both proteins and small molecule drugs. Once aptamer sequences that bind to the target of interest have been found they can be easily manufactured to order.
It’s every doctor’s dream—a small, wearable sensor that can monitor levels of, say, the heart drug digoxin in a patient’s blood, and make sure that he or she gets just the right amount of medication 24 hours a day.
But the MEDIC biosensor, developed by researchers at the University of California, Santa Barbara (UCSB), can be easily reconfigured to test a person’s blood for just about any substance, including illegal drugs. In fact, the new technology builds on previous research by UCSB mechanical engineer Dr. Hyongsok (Tom) Soh on a microchip that can continuously screen blood for cocaine.
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Soh says that MEDIC could help take the guesswork out of dosing for prescription drugs. Soh and his team published the results of their initial experiments late last month in the journal Science Translational Medicine.
“Such technology would enable truly personalized medicine, wherein therapeutic agents could be tailored with optimal doses for each patient to maximize efficacy and minimize side effects,” Soh’s team wrote in the study.
The National Institutes of Health (NIH) have awarded $3.2 million to a team of preeminent engineering, chemistry, and biology researchers to develop a highly efficient system of generating nucleic acid molecules, called aptamers. The technology provides an entirely new method of discovering and mass producing new high-performance aptamers for a broad range of applications, including next-generation disease diagnosis at the point of care.
Their system, called Quantitative Parallel Aptamer Selection System (QPASS), is a highly efficient process that will pave the way to develop “instant diagnosis” devices, such as those that detect infectious disease or genetically test a person’s response to cancer drugs.
“Our technology is the first step toward devices that could instantly test for HIV or H1N1 in the field or at the bedside, instead of wasting critical time and money waiting for results,” said Tom Soh , professor of mechanical engineering and materials, and Co-Director of the Center for Stem Cell Biology and Engineering at UC Santa Barbara. Earlier this year, Soh and his colleagues at UCSB announced the design of a disposable chip that rapidly detects microbes, called a MIMED device. This new aptamer synthesis technology aims to make devices like MIMED chips ready for widespread clinical use.