The United States faces soaring challenges in public health due to the significant increase in the manufacture, smuggling, and abuse of controlled substances. Since 2019, the number of illicit drug (e.g., opioids, cannabinoids, and benzodiazepines) related death has increased significantly due to the COVID-19 pandemic.
SERS & Toxicology *
Nationally, the CDC reports that in 2022 nearly 108,000 people died from drug overdoses, including 1150 adolescents. The CDC reports between 38-50% increases in opioid overdoses in 28 states. Strikingly, in 2022 the DEA seized enough fentanyl to kill the entire US population. There is an unmet need for the development of widely applicable, quantitative, and high-throughput techniques able to analyze drugs in plasma and/or whole blood without lengthy purification steps to overcome existing bottlenecks in drug testing.
Raman spectroscopy detects all the vibrational frequency stretches from a molecule, and therefore displays a characteristic spectrum or “molecular fingerprint”. The Raman effect alone, however, is fairly weak and only works for bulk samples. This has partially hindered its widespread application, particularly in forensic toxicology where ng/mL or even lower concentrations of drugs are present in biofluids.
Molecular Raman signal can be amplified up to 106 by bringing the molecule in close contact with metallic NCs. The NPs act as a SERS substrate, where the SERS signal amplification comes from the localized surface plasmon resonance (LSPR) properties of NCs. The LSPR properties create strong electromagnetic (EM)-field enhancements (“hot spots”) around the NCs, leading to enhancement of the normal Raman signature by up to 105 or 106. NC self-assemblies with large numbers of hot spots make excellent SERS substrates. Despite the tremendous promise of SERS for forensic toxicology applications, its utilization in the toxicology laboratories has been hindered by: (i) low sensitivity of current SERS substrates, (ii) inefficient identification of target analytes from complex toxicology samples, (iii) lack of standardization of the measurements, and (iv) the poor stability of existing Ag-based SERS substrates. We have designed and fabricated flexible SERS substrates for ultrasensitive potent drug detection from drug-of-abuse patient plasma samples. Leap forward, we have fabricated NC-decorated microneedle substrate which is both a SERS substrate and a substrate-supported electrospray ionization (ssESI) mass spectrometry (MS) sample ionization platform. We collaborate with Professor Nick Manicke (IUI, C&CB) for the ESI-MS-based characterization. Chemometric analysis (Collaboration with Professor John Goodpaster, IUI C&CB) for the SERS-based detection shows very good classification between fentanyl, or alprazolam, or mixture thereof. Our multimodal detection approach presented herein is a highly versatile detection technology that can be applicable for the detection of any analyte type without performing any complicated sample preparation. We aim to develop unique, NC-decorated microneedle substrates for preconcentration of drugs through reverse phase extraction, reducing or eliminating the need for sample dilution or off-line sample preparation. Our target drugs are: fentanyl analogs, non-fentanyl synthetic opioids, synthetic cannabinoids, designer benzodiazepines, amphetamine-type stimulants, cocaine, heroin, prescription opioids, prescription benzodiazepines, and cannabinoids. We also collaborate with Indiana State Department of Toxicology to analyze real-world toxicology samples (de-identified) to validate our technology and demonstrate the potential transformative potential of our unique SERS-ssESI-MS construct.
* Collaborators
- Professor John Goodpaster, Indiana University Indianapolis
- Professor Nicolas Manicke, Indiana University Indianapolis
- Dr. Christina Beymer, Director, Indiana State Department of Toxicology
Representative Publications
- Simas, M. V.; Olaniyan, P. O.; Hati, S.; Davis, G. A.; Anspach, G.; Goodpaster, J. V.; Manicke, N. E.; Sardar, R. Superhydrophobic Surface Modification of Polymer Microneedles Enables Fabrication of Multimodal SERS and MS Substrates for Synthetic Drug Detection in Blood Plasma. ACS Appl. Mater. Interfaces 2023, 15, 46681-46696.
- Masterson, A. N.; Hati, S.; Ren, G. J.; Liyanage, T.; Manicke, N.; Goodpaster, J. V.; Sardar, R. Enhancing non-fouling and sensitivity of surface-enhanced Raman scattering substrates for potent drug analysis in blood plasma via fabrication of flexible plasmonic patch. Anal. Chem. 2021. 93, 2578-2588.
- Liyanage, T.; Masterson, A. N.; Hati, S.; Ren, G. J.; Manicke, N.; Rusyniak, D.; Sardar, R. Optimization of electromagnetic hot spots in surface-enhanced Raman scattering substrates for an ultrasensitive drug assay of emergency department patients’ plasma. Analyst, 2020, 145, 7662-7672.
- Liyanage, T.; Rael, A.; #Shaffer, S.; #Zaidi, S.; Goodpaster, J. V.; Sardar, R. Fabrication of a self-assembled and flexible SERS nanosensor for explosive detection at parts-per-quadrillion levels from fingerprints. Analyst, 2018, 143, 2012-2022.
- Joshi, G. K.; White, S, L.; Johnson, M. A.; Sardar, R.; Jain, P. K. Ultrashort, angstrom-scale decay of surface enhanced Raman scattering hot spots. J. Phys. Chem. C 2016, 120, 24973-24981.