Ultrasonic quantification using smart hydrogel sensors

Analyte quantification in samples with extensive matrix effects can be challenging using conventional analytical techniques. Ultrasound has been shown to easily penetrate samples that can be difficult to measure optically or electrochemically, though it provides little chemical information. Recent ultrasound contrast agents provide highly localized contrast within a sample based on concentration. We have developed a general approach for creating smart biosensors based on molecularly imprinted hydrogel polymers that recognize and bind a target analyte, changing ultrasonic properties with analyte concentration. Multilinear analyte calibration in hydrogel solutions provided quantification of the chosen analyte, theophylline, from 8.4 μM to 6.1 mM with a high degree of linearity (correlation coefficient exceeding 0.99). Simultaneous quantification of both theophylline and of an interfering species, caffeine, was also carried out, providing an avenue for simultaneous analyte analysis with one smart biosensor that can be dispersed and remotely detected.