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Web Date: March 12, 2012

New Sensor Listens To Drug Molecules

Pharmaceutical Analysis: Vibrations of a quartz crystal measure properties that could make or break drug candidates
Department: Science & Technology
News Channels: Analytical SCENE, Biological SCENE
Keywords: partition coefficient, pKa, drug discovery, acoustic sensor

Drugmakers rely on many analytical instruments when they screen for potential drug candidates. Now they may want to invest in headphones. Researchers have developed a sensor that uses the sound generated by a vibrating crystal to measure properties of common drugs (Anal. Chem., DOI: 10.1021/ac300087z). This acoustic sensor may offer a new way for drug developers to quickly assess candidate molecules.

For an oral drug to work, the patient’s body must readily absorb it, a process that depends on two of the molecule’s characteristics, says Matthew Cooper of Australia’s University of Queensland: its pKa, or acid dissociation constant, and its partition coefficient, or affinity for fats. Pharmaceutical companies use techniques such as ultraviolet-visible spectroscopy to screen drug candidates for these properties. Cooper wanted to develop a new approach based on the technology behind quartz crystal microbalances. Researchers previously have used these balances to measure other properties of compounds, such as the affinity of odorant molecules for the membranes of olfactory cells.

At the heart of the new acoustic sensor is a quartz crystal that vibrates 17 million times per second when excited by gold electrodes on either end of it. On top of the crystal, the researchers assembled a series of polymer layers crowned by fatty octadecanyl chains. After drug molecules enter the sensor, the fraction of them that nestle into the fat-like chains depends on the drug molecules’ partition coefficient and charge. As molecules join this layer, they add weight to the crystal, which slows its vibrations. The researchers can detect these frequency changes by measuring electrical signals through the flanking gold electrodes.

To test the acoustic biosensor, the researchers placed the quartz assembly inside a microfluidic device. They dissolved a dozen common drugs, including ibuprofen and warfarin, in water and dimethyl sulfoxide, and then used the microfluidics to inject each of them into the sensing cell. As the drug molecules moved from the solution to the fatty layer, the researchers measured changes in vibrational frequency and calculated mass changes. Based on these changes, they estimated how much of the drug had left the solution and could calculate its partition coefficient. By measuring frequency changes at multiple pHs, the researchers created a titration curve to determine the pKa. The values derived from the acoustic sensor matched reference values for all 12 drugs.

Christopher Lipinski, a retired Pfizer scientist and current advisor at Melior Discovery, a company that builds analytical devices for the pharmaceutical industry, calls the paper “a technological tour de force.” But he points out that the pharmaceutical industry has well-established technologies to measure these properties. Unless the researchers can demonstrate that the new sensor has advantages in cost or accuracy, he is unsure of whether it will replace the existing methods.

Still, he imagines novel applications for the device, such as growing a layer of cells on the crystal to measure how much drug a cell takes in. “That’s moving closer to a real-life situation,” Lipinski says.

 
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