Direct detection of analyte binding to single molecularly imprinted polymer particles by confocal Raman spectroscopy

We describe the use of Raman spectroscopy to detect and quantify, for the first time, the presence of the imprinting template in single molecularly imprinted polymer microspheres. The polymers were imprinted with the beta-blocking drugs propranolol and atenolol, and precipitation polymerization was used to obtain spherical particles of diameters of 200 nm and 1.5microm. The size of the Raman laser spot being between 1microm and a few mum, the nanoparticles were used for bulk detection whereas with micrometer-sized particles, quantitative measurements on single particles were possible. The laser power, and consequently the acquisition times, needed to be adapted as a function of the polymer and template used in order to avoid burning. Analyte quantification from Raman spectra is straightforward by determining the peak height of a typical Raman band of the analyte, and by using a typical polymer peak for normalization. Relatively low detection limits down to 1microM have been reached for the detection of S-propranolol through bulk measurements on MIP nanoparticles.