Tailoring Polymer Micro-extraction Phases to Enhance the Sensitivity and Selectivity of Raman Spectroscopy

Raman Spectroscopy (RS) systems are evolving toward portable, affordable, and highly versatile analytical chemistry platforms, though sensitivity, selectivity, and fluorescence in many complex multi-component real-world samples remains challenging. We investigated the combination of solid phase micro-extraction (SPME) with Raman spectroscopy as a strategy to address some of these limitations. SPME is best known as a technique in chromatography that uses hydrophobic polymer phases like polydimethylsiloxane (PDMS) to extract and preconcentrate non-polar target analyte in headspace analysis. SPME not only enhances detection by pre-concentration of analytes, but when combined with Raman spectroscopy, offers an opportunity to reduce interference from the background by tailoring the polymer phase to specific classes of analytes in complex mixtures. Here we establish SPME/Raman as a quantitative technique that is capable of enhancing the measurement of organic contaminates in water, anesthetic compounds in serum, and inhibitory molecules in the multi-phase and multi-component broths produced by pretreatment of biomass. Flory-Huggins theory is used to describe the predicted trends in the thermodynamic partitioning of dilute analytes into polymer phases. We show experimentally and theoretically that the equilibrium partitioning, denoted by the partition coefficient K, can enhance the Raman signal by 2 orders of magnitude or more when the analyte is detected in the polymer phase rather than the solvent phase. Specifically, we find that SPME/Raman measurements of aqueous benzene and toluene partitioning into PDMS phases have log (K) values of 2.35 and 1.90, respectively, matching literature values determined with other methods. We also examine the use of SPME/Raman for enhanced detection of general anesthetics (halothane, isofluorane, propofol), quinoline, and fermentation inhibitors (furfural, HMF) into either PDMS or epoxy polymer phases. We then demonstrate the utility of Flory-Huggins theory in understanding and optimizing the selection of polymer-analyte pairs to enhance the sensitivity and selectivity of SPME/RS.