Quantification of Dopamine Using Surface-Enhanced Raman Scattering (SERS) of Constrained Vibrational Mode

Dopamine (DA) is known as a crucial neurotransmitter playing a significant role in the hormonal, nervous, and vascular systems. Abnormal DA levels is related to diverse neurological and psychiatric disorders, including Parkinson’s disease (PD) and Alzheimer’s disease (AD). Therefore, DA quantification in biological samples has drawn attention for the tracking, diagnosis, and therapeutics of DA-related diseases. To date, quantitative detection of DA has been developed using electrochemistry, chromatography, and fluorescence [1,2]. These approaches, however have still confronted great challenges due to low sensitivity and selectivity. Meanwhile, surface-enhanced Raman spectroscopy (SERS) has come into the limelight as an analytical tool over the past few decades due to its extraordinary advantages such as single molecular-level detection and finger-printing signals. Nonetheless, the low affinity of DA to metal surface attenuates DA selectivity and poses a challenge for SERS-based DA sensors [3]. Although aptamer, antibody, and molecular chelation bound noble metals have been employed in several studies to enhance DA selectivity, only few of them are validated with real biological samples [4]. Therefore, it is imperative to devise rapid and simple methods to detect DA with ultra-sensitivity and high-selectivity in complicated biofluids.<br/>Herein, we introduce a SERS-based ultrasensitive DA quantitative sensor adopting Raman-peak shift resulting from the constrained vibration mode of 4-mercaptophenylboronic acid (4-MPBA). Ag nanostructure was fabricated on Si wafer with a simple one-step sputtering process using gas-flow sputtering to augment plasmon resonance. 4-MPBA is a biocompatible Raman reporter, capable of covalently bonding with DA and metal-thiol conjugation to Ag substrate. It is adopted as a linker to enhance the affinity between DA and Ag substrate and the Raman signal of DA. 4-MPBA was coated through vapor-phase deposition to curtail impurity and background noise in Raman spectra. We identified a shift in the position of representative SERS peak of 4-MPBA proportionally to DA concentration. Our experimental result, indicating the peak shift stemming from the combination between 4-MPBA and DA was well supported by numerical simulation based on density functional theory. To the best of our knowledge, although Raman-peak shift has been used in many sensor-based applications previously, it has never been reported for DA sensing with constrained Raman mode. Tracking the peak shift confers more stable and reliable measurement than intensity-based quantification because it focuses more on the analytes themselves rather than the enhancement performances of individual SERS substrates that rely on chip-to-chip variation. We also applied human serum on the DA sensor to validate that it works out similar results in real biological samples. The proposed method based on SERS peak shift depicted the ability to quantitatively detect DA concentrations in biofluids exhibiting selectivity with respect to other biomarkers as well as high sensitivity up to picomolar level.<br/><br/><br/><b>References</b><br/>[1] B. Ferry, E.-P. Gifu, I. Sandu, L. Denoroy, S. Parrot, Analysis of microdialysate monoamines, including noradrenaline, dopamine and serotonin, using capillary ultra-high performance liquid chromatography and electrochemical detection, J. Chromatogr. B 951 (2014) 52-57.<br/>[2] A. Yildirim, M. Bayindir, Turn-on fluorescent dopamine sensing based on in situ formation of visible light emitting polydopamine nanoparticles, Anal. Chem. 86 (2014) 5508-5512.<br/>[3] F. Gao, L. Liu, G. Cui, L. Xu, X. Wu, H. Kuang, et al., Regioselective plasmonic nano-assemblies for bimodal sub-femtomolar dopamine detection, Nanoscale 9 (2017) 223-229.<br/>[4] M. Kaya, M.r. Volkan, New approach for the surface enhanced resonance Raman scattering (SERRS) detection of dopamine at picomolar (pM) levels in the presence of ascorbic acid, Anal. Chem. 84 (2012) 7729-7735.