Bhavya Sharma

SERS: Materials, applications, and the future

Surface enhanced Raman spectroscopy (SERS) is a powerful vibrational spectroscopy technique that allows for highly sensitive structural detection of low concentration analytes through the amplification of electromagnetic fields generated by the excitation of localized surface plasmons. SERS has progressed from studies of model systems on roughened electrodes to highly sophisticated studies, such as single molecule spectroscopy. We summarize the current state of knowledge concerning the mechanism of SERS and new substrate materials. We highlight recent applications of SERS including sensing, spectroelectrochemistry, single molecule SERS, and real-world applications. We also discuss contributions to the field from the Van Duyne group. This review concludes with a discussion of future directions for this field including biological probing with UV-SERS, tip-enhanced Raman spectroscopy, and ultrafast SERS.

Structure Enhancement Factor Relationships in Single Gold Nanoantennas by Surface-Enhanced Raman Excitation Spectroscopy

Determining the existence of any direct spectral relationship between the far-field scattering properties and the near-field Raman-enhancing properties of surface-enhanced Raman spectroscopy (SERS) substrates has been a challenging task with only a few significant results to date. Here, we prove that hot spot dominated systems show little dependence on the far-field scattering properties because of differences between near- and far-field localized surface plasmon resonance (LSPR) effects as well as excitation of new plasmon modes via a localized emitter. We directly probe the relationship between the near- and far-field light interactions using a correlated LSPR-transmission electron microscopy (TEM) surface-enhanced Raman excitation spectroscopy (SERES) technique. Fourteen individual SERS nanoantennas, Au nanoparticle aggregates ranging from dimers to undecamers, coated in a reporter molecule and encased in a protective silica shell, were excited using eight laser wavelengths. We observed no correlation between the spectral position of the LSPR maxima and the maximum enhancement factor (EF). The single nanoantenna data reveal EFs ranging from (2.5 ± 0.6) × 10(4) to (4.5 ± 0.6) × 10(8) with maximum enhancement for excitation wavelengths of 785 nm and lower energy. The magnitude of maximum EF was not correlated to the number of cores in the nanoantenna or the spectral position of the LSPR, suggesting a separation between near-field SERS enhancement and far-field Rayleigh scattering. Computational electrodynamics confirms the decoupling of maximum SERS enhancement from the peak of the scattering spectrum. It also points to the importance of a localized emitter for radiating Raman photons to the far-field which, in nonsymmetric systems, allows for the excitation of radiative plasmon modes that are difficult to excite with plane waves. Once these effects are considered, we are able to fully explain the hot spot dominated SERS response of the nanoantennas.

Seeing through bone with surface-enhanced spatially offset Raman spectroscopy

Surface-enhanced spatially offset Raman spectroscopy (SESORS) is a label-free vibrational spectroscopy that has the potential for in vivo imaging. Previous SESORS experiments have been limited to acquiring spectra using SERS substrates implanted under the skin or from nanoparticles embedded in tissue. Here we present SESORS measurements of SERS active nanoparticles coated with a Raman reporter molecule (nanotags) acquired, for the first time, through bone. We demonstrate the ability of SESORS to measure spectra through various thicknesses (3-8 mm) of bone. We also show that diluted nanotag samples (~2 × 10(12) particles) can be detected through the bone. We apply a least-squares support vector machine analysis to demonstrate quantitative detection. It is anticipated that these through-bone SESORS measurements will enable real-time, non-invasive spectroscopic measurement of neurochemicals through the skull, as well as other biomedical applications.

Bisboronic Acids for Selective, Physiologically Relevant Direct Glucose Sensing with Surface-Enhanced Raman Spectroscopy.

This paper demonstrates the direct sensing of glucose at physiologically relevant concentrations with surface-enhanced Raman spectroscopy (SERS) on gold film-over-nanosphere (AuFON) substrates functionalized with bisboronic acid receptors. The combination of selectivity in the bisboronic acid receptor and spectral resolution in the SERS data allow the sensors to resolve glucose in high backgrounds of fructose and, in combination with multivariate statistical analysis, detect glucose accurately in the 1-10 mM range. Computational modeling supports assignments of the normal modes and vibrational frequencies for the monoboronic acid base of our bisboronic acids, glucose and fructose. These results are promising for the use of bisboronic acids as receptors in SERS-based in vivo glucose monitoring sensors.

High-Throughput, High-Resolution Echelle Deep-UV Raman Spectrometer

We constructed an ultrahigh-throughput, high-resolution ultraviolet (UV) Raman spectrograph that utilizes a high-efficiency filter-stage monochromator and a high-dispersion Echelle spectrograph. The spectrograph utilizes a total of six mirrors and two gratings, with an overall efficiency at 229 nm of ∼18%. The limiting resolution of our spectrometer is 0.6 cm−1 full width half-maximum (FWHM), as measured for 229 nm Rayleigh scattering. Use of a 1 mm–wide entrance slit gives rise to an approximately 10 cm−1 FWHM resolution at 229 nm. The ultrahigh spectrograph throughput enables ultrahigh signal-to-noise ratio, deep UV Raman spectra that allow us to monitor <1% changes in peptide bond composition. The throughput is measured to be 35-fold greater than conventional deep UV Raman spectrometers.

UV Resonance Raman Investigation of the Conformations and Lowest Energy Allowed Electronic Excited States of Tri- and Tetraalanine: Charge Transfer Transitions

UV resonance Raman excitation profiles and Raman depolarization ratios were measured for trialanine and tetraalanine between 198 and 210 nm. Excitation within the pi --> pi* electronic transitions of the peptide bond results in UVRR spectra dominated by amide peptide bond vibrations. In addition to the resonance enhancement of the normal amide vibrations, we find enhancement of the symmetric terminal COO(-) vibration. The Ala(3) UVRR AmIII(3) band frequencies indicate that poly-proline II and 2.5(1) helix conformations and type II turns are present in solution. We also find that the conformation of the interior peptide bond of Ala(4) is predominantly poly-proline-II-like. The Raman excitation profiles of both Ala(3) and Ala(4) reveal a charge transfer electronic transition at 202 nm, where electron transfer occurs from the terminal nonbonding carboxylate orbital to the adjacent peptide bond pi* orbital. Raman depolarization ratio measurements support this assignment. An additional electronic transition is found in Ala(4) at 206 nm.

Surface Enhanced Spatially Offset Raman Spectroscopy Detection of Neurochemicals Through the Skull

The ability to noninvasively detect neurotransmitters through the skull would aid in understanding brain function and the development of neurological diseases. Surface enhanced spatially offset Raman spectroscopy (SESORS) is a powerful technique that combines the sensitivity of surface-enhanced Raman spectroscopy (SERS) with the ability of spatially offset Raman spectroscopy (SORS) to probe subsurface layers. Here we present SERS measurements of neurotransmitters (melatonin, serotonin, and epinephrine) at various concentrations followed by the SESORS measurements of the neurotransmitters to a concentration as low as 100 μM in a brain tissue mimic through a cat skull. Principal components analysis was performed to distinguish between the surface bone layer and the subsurface layer, comprised of a brain tissue mimic modified with neurotransmitters, and to determine if each individual neurotransmitter could be accurately identified.

UV Resonance Raman Finds Peptide Bond – Arg Side Chain Electronic Interactions

We measured the UV resonance Raman excitation profiles and Raman depolarization ratios of the arginine (Arg) vibrations of the amino acid monomer as well as Arg in the 21-residue predominantly alanine peptide AAAAA(AAARA)(3)A (AP) between 194 and 218 nm. Excitation within the π → π* peptide bond electronic transitions result in UVRR spectra dominated by amide peptide bond vibrations. The Raman cross sections and excitation profiles indicate that the Arg side chain electronic transitions mix with the AP peptide bond electronic transitions. The Arg Raman bands in AP exhibit Raman excitation profiles similar to those of the amide bands in AP which are conformation specific. These Arg excitation profiles distinctly differ from the Arg monomer. The Raman depolarization ratios of Arg in monomeric solution are quite simple with ρ = 0.33 indicating enhancement by a single electronic transition. In contrast, we see very complex depolarization ratios of Arg in AP that indicate that the Arg residues are resonance enhanced by multiple electronic transitions.

In Vitro and In Vivo SERS Biosensing for Disease Diagnosis

For many disease states, positive outcomes are directly linked to early diagnosis, where therapeutic intervention would be most effective. Recently, trends in disease diagnosis have focused on the development of label-free sensing techniques that are sensitive to low analyte concentrations found in the physiological environment. Surface-enhanced Raman spectroscopy (SERS) is a powerful vibrational spectroscopy that allows for label-free, highly sensitive, and selective detection of analytes through the amplification of localized electric fields on the surface of a plasmonic material when excited with monochromatic light. This results in enhancement of the Raman scattering signal, which allows for the detection of low concentration analytes, giving rise to the use of SERS as a diagnostic tool for disease. Here, we present a review of recent developments in the field of in vivo and in vitro SERS biosensing for a range of disease states including neurological disease, diabetes, cardiovascular disease, cancer, and viral disease.