Nanoparticle Decorated Porous Micropillars as SERS and ESI-MS Substrates for Ultrasensitive Synthetic Drug Analysis in Blood Plasma

Strikingly, in 2022 DEA has seized enough fentanyl that can kill the entire US population. Furthermore, CDC data from January 2022 to September 2022 reveal the second largest number of drug related death (80,000) for a 9-month period ever recorded, including 1150 adolescents. Currently, there is no routine way to perform high-throughput toxicology drug assays without resorting to complex and expensive sample handling. Therefore, reliable and fast analyses will assist more rapid turn-around times and lower the cost of toxicology analyses. Herein, we present the first of its kind, the fabrication of metal nanoparticle (MNP)-decorated micropillar arrays, which are both a surface-enhanced Raman spectroscopy (SERS) substrate and a substrate-supported electrospray ionization (ssESI) mass spectrometry (MS) sample prep/ionization platform. We designed and fabricated porous, hydrophilic polydimethylsiloxane (PDMS) micropillars with extremely sharp tips. The porosity (10 – 200 micrometer) allows drug preconcentration within the micropillar as a form of solid-state microextraction, which enhances the sensitivity in the MS analysis. The decoration of porous PDMS micropillars with plasmonic MNPs allows ultrasensitive SERS analysis. Utilizing our porous PDMS micropillars, several synthetic drugs including designer benzodiazepines, fentanyl analogs, and non-fentanyl synthetic opioids are analyzed simultaneously by SERS and ESI-MS at a concentration of parts-per-trillion (ppt) in blood plasma. Most importantly, this fabrication strategy serves as a high throughput analytical detection tool as different drug types and/or analogue of a particular drug are detected on each individual micropillars by SERS and ESI-MS analyses. Together, we believe that our research has the unique potential to detect, quantify, and identify most potent drugs from human biofluids with a minimum sample preparation, thus the methodology can be adopted by forensic toxicology labs around the country.