Advances in Plasmonic Substrates for the Detection of Trace Fentanyl using Surface Enhanced Raman Spectroscopy

McGarry, Paige

Advances in Plasmonic Substrates for the Detection of Trace Fentanyl using Surface Enhanced Raman Spectroscopy

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McGarry_Paige_MSc_2025_Thesis.pdf (7.71 MB)

Date

2025-12-12

Authors

McGarry, Paige

Abstract

Fentanyl is a potent synthetic opioid which can be lethal in doses of less than 2 mg. This drug is highly effective in medical applications; however, it is also commonly used as a cutting agent in street drugs. Fentanyl provides increased potency without altering the taste or appearance of select street drugs. Fentanyl is approximately 100x stronger than morphine, and 50x more potent than heroin; Two opioids which are also used for medicinal and recreational purposes. Unfortunately, fentanyl’s rapid onset and fleeting highs make it highly addictive. This often leads to overdose and death when abused. Most victims are unaware that their substance has been tainted with fentanyl until it’s too late. Detecting the presence of trace amounts of fentanyl in street drugs at the earliest point of exposure is therefore invaluable. Established methods require sensitive and specific instrumentation. This thesis presents spectroscopy-based approaches that detect low concentrations of fentanyl in fabricated mixtures through surface modification. Surface enhanced Raman spectroscopy (SERS) is used to enhance the inelastic scattering of light, where a change in energy is detected as a molecule’s vibrational mode. However, SERS lacks specificity towards target molecules. Using fentanyl specific DNA aptamers conjugated to gold nanoparticles (AuNPs), we achieve enhanced fentanyl-specific detection at low concentrations to improve specificity. Spectroscopy-based approaches can help identify fentanyl before it is consumed and increase public safety.

Summary for Lay Audience

The composition of street drugs is constantly changing. Drug dealers are finding new ways to “cut” street drugs with potent fillers to create stronger and more addictive substances to distribute to vulnerable and oblivious users. This trend is leading to a greater number of dangerous substances in the drug market and increasing the frequency of fatal overdoses. The ability to easily and reliably determine the composition of a drug sample is therefore essential; however, this requires complicated techniques with sensitive equipment. Currently, multiple scientific methods are used for drug detection, including mass spectrometry, immunoassays, electrochemical techniques, and spectroscopy-based techniques. Throughout this thesis, surface enhanced Raman spectroscopy (SERS) is investigated for its potential in detecting trace amounts of fentanyl, a potent synthetic opioid, within fabricated drug mixtures. Traditional Raman spectroscopy is a non-destructive analytical technique that measures the inelastic (Raman) scattering of light. Inelastic scattering is rare: only one in a million photons undergoes this process, in which the scattered light has a different energy than the initial light, providing unique vibrational information about a molecule. SERS utilizes a rough metallic surface (e.g., gold nanoparticles) to enhance the signal intensity and therefore detectability of Raman-scattered light, and to improve spectral resolution and sensitivity through chemical and electromagnetic enhancement factors. The main drawback of SERS is its poor replicability due to the random distribution of SERS “hotspots” and the lack of specificity towards a target molecule. To improve the specificity of fentanyl in a drug mixture using SERS, DNA aptamers that are specific only to fentanyl in a mixture have been introduced to the SERS strategy. This aptamer is capable of structure-switching functionality, and when a target (i.e., fentanyl) is introduced with the aptamer, the aptamer-target binding triggers a conformational change that brings fentanyl closer to the nanoparticle surface, thus increasing the likelihood of SERS specificity at designated hotspots, both in fabricated drug mixtures and in the presence of other drugs. This approach enables the specific detection of fentanyl, improving detection at low concentrations. Lastly, alternative spectroscopy approaches to detecting fentanyl are explored. Surface enhanced infrared absorption spectroscopy (SEIRAS) was used to compare and validate the results with those obtained using SERS. As infrared spectroscopy is complementary to Raman spectroscopy, the two methods yielded similar yet distinct results for the detection of fentanyl.