Precision medicine aims to optimize drug dosages for each individual in a manner that maximizes efficacy while minimizing side effects. In practice, however, the cumbersome and invasive nature of blood draws, and the labor-intensive nature of their subsequent laboratory analysis has precluded the personalization of dosing. In the face of this, clinicians base dosing decisions on indirect, and thus often highly inaccurate estimators of drug concentrations in the body, leading to undesired side effects and >$500 billion in additional annual cost to the health-care system. Given this, there exists a major need for technologies supporting convenient and accurate measurement of drug concentrations at the point of care, with even greater value if such technology could be used by patients at home or work. Performing rapid measurement of drug concentrations can be complex, however, because a significant fraction of most drugs is bound to blood proteins. The project proposes an aptamer based biochemical sensor capable of performing rapid, point-of-care measurements of both protein-bound and unbound drug concentrations for personalized medicine. The work includes an integrated education plan that involves the participation of undergraduate research co-ops with a focus on underrepresented groups.
The technical objective of this proposal is design and fabrication of biochemical sensor device that can rapidly measure both the active (unbound) and the total (unbound+protein bound) concentrations of drugs in blood circulation. The proposed research is based on the hypothesis that microfluidic devices can quickly sample biofluids such as blood and interstitial fluid, and efficiently denature the binding-protein for the drug such that both the unbound and total (unbound+protein-bound) drug concentrations can be measured by quantitative electrochemical aptamer sensors. This will be accomplished by implementing a novel membrane that protects the drug-detecting sensor from the harsh conditions necessary to liberate protein-bound drugs. Specifically, the membrane will be permeable to drugs but will be impermeable to acids and bases needed to release drug from proteins and which would otherwise harm the sensor. The proposal aims to advance knowledge spanning the physics of membranes, the influence of acid, base, and salt conditions on sensors, and shed new light on the percentage of drugs that are bound to proteins in the body. The understanding of how much drug is bound to proteins will lead to fundamental knowledge of the unbound portion of drug in blood that provides a therapeutic effect, as well as causes toxicity or unwanted side-effects. The technique will provide information on drug bioavailability, toxicity, interference, metabolism, clearance, and absorption rates. In general, the proposed devices will result in improved patient health and will reduce the complexity of workflow in healthcare delivery.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
