This paper reports on the methodology and creation of a nanoparticle-decorated microneedle substrate that is both a SERS substrate and a substrate-supported electrospray ionization mass spectrometry sample ionization platform; the creation of the substrate contributes to the detection of any analyte type without performing any complicated sample preparation.
Microneedles are widely used substrates for various chemical and biological sensing applications utilizing surface-enhanced Raman spectroscopy (SERS), which is indeed a highly sensitive and specific analytical approach. This article reports the fabrication of a nanoparticle (NP)-decorated microneedle substrate that is both a SERS substrate and a substrate-supported electrospray ionization (ssESI) mass spectrometry (MS) sample ionization platform. Polymeric ligand-functionalized gold nanorods (Au NRs) are adsorbed onto superhydrophobic surface-modified polydimethylsiloxane (PDMS) microneedles through the control of various interfacial interactions. The authors show that the chain length of the polymer ligands dictates the NR adsorption process. Importantly, assembling Au NRs onto the micrometer-diameter needle tips allows the formation of highly concentrated electromagnetic hot spots, which provide the SERS enhancement factor as high as 1.0 × 106. The micrometer-sized area of the microneedle top and high electromagnetic field enhancement of their system can be loosely compared with tip-enhanced Raman spectroscopy, where the apex of a plasmonic NP-functionalized sharp probe produces high-intensity plasmonic hot spots. Utilizing the authors’ NR-decorated microneedle substrates, the synthetic drugs fentanyl and alprazolam are analyzed with a subpicomolar limit of detection. Further analysis of drug-molecule interactions on the NR surface utilizing the Langmuir adsorption model suggests that the higher polarizability of fentanyl allows for a stronger interaction with hydrophilic polymer layers on the NR surface. The authors further demonstrate the translational aspect of the microneedle substrate for both SERS- and ssESI-MS-based detection of these two potent drugs in 10 drug-of-abuse (DOA) patient plasma samples with minimal preanalysis sample preparation steps. Chemometric analysis for the SERS-based detection shows a very good classification between fentanyl, alprazolam, or a mixture thereof in their selected 10 samples. Most importantly, ssESI-MS analysis also successfully identifies fentanyl or alprazolam in these same 10 DOA plasma samples. The authors believe that their multimodal detection approach presented herein is a highly versatile detection technology that can be applicable to the detection of any analyte type without performing any complicated sample preparation. (Published Abstract Provided)