Real-Time Measurement of Drug Concentration Levels in the Bloodstream

Scientists have invented an aptamer-based sensor that allows for real-time detection of small molecule drugs in a patient’s bloodstream. in order to help physicians better understand how a patient’s body responds to administered drugs,

Current techniques that allow the measurement of the concentration of circulating molecules in the bloodstream are mostly based on enzymes and their highly-selective binding mechanisms, and hence are only tailored for enzyme substrates such as glucose. In comparison, synthetic drugs are usually designed to selectively bind to cell membrane receptors, and these receptors cannot be incorporated into sensors because they denature readily outside of their cells.

To overcome this limitation, Soh et al. designed MEDIC (Microfluidic Electrochemical Detector for In vivo Continuous monitoring), a novel sensor system that incorporates DNA aptamer-probes. Aptamers are DNA strands that can selectively bind to molecules. Specific binding of a drug molecule to an aptamer strand causes the aptamer to undergo a reversible conformational change. This change produces increased current flow through the aptamer-linked probe, and MEDIC quantifies the drug concentration through the change in current. A filter that only allows small-molecule drugs to diffuse through to reach the aptamer-probe is fitted to prevent the probe from being clogged by larger bodies such as blood cells. This design allows MEDIC to achieve sensitive and continuous measurement of the target drug’s concentration in a flowing stream of human whole blood for over 4 hours of operation, even in the presence of co-administered drugs that are in 1000 times higher concentrations.

Quantitatively tracking how individual patients respond to drugs in real time would allow physicians to optimize dosages at point of care, making MEDIC an invaluable complement to drugs with narrow therapeutic ranges, such as those used in chemotherapy that are highly deleterious when overdosed.

Source: B S Ferguson et al, Sci. Transl. Med., 2013, 5, 213ra165 (DOI: 10.1126/scitranslmed.3007095)