Preventing Memory Effects in Surface-Enhanced Raman Scattering Substrates by Polymer Coating and Laser-Activated Deprotection

Abstract

The development of continuous monitoring systems requires in situ sensors that are capable of screening multiple chemical species and providing real-time information. Such in situ measurements, in which the sample is analyzed at the point of interest, are hindered by underlying problems derived from the recording of successive measurements within complex environments. In this context, surface-enhanced Raman scattering (SERS) spectroscopy appears as a noninvasive technology with the ability of identifying low concentrations of chemical species as well as resolving dynamic processes under different conditions. To this aim, the technique requires the use of a plasmonic substrate, typically made of nanostructured metals such as gold or silver, to enhance the Raman signal of adsorbed molecules (the analyte). However, a common source of uncertainty in real-time SERS measurements originates from the irreversible adsorption of (analyte) molecules onto the plasmonic substrate, which may interfere in subsequent measurements. This so-called "SERS memory effect" leads to measurements that do not accurately reflect varying conditions of the sample over time. We introduce herein the design of plasmonic substrates involving a nonpermeable poly(lactic-co-glycolic acid) (PLGA) thin layer on top of the plasmonic nanostructure, toward controlling the adsorption of molecules at different times. The polymeric layer can be locally degraded by irradiation with the same laser used for SERS measurements (albeit at a higher fluence), thereby creating a micrometer-sized window on the plasmonic substrate available to molecules present in solution at a selected measurement time. Using SERS substrates coated with such thermolabile polymer layers, we demonstrate the possibility of performing over 10,000 consecutive measurements per substrate as well as accurate continuous monitoring of analytes in microfluidic channels and biological systems. KEYWORDS: surface-enhanced Raman spectroscopy, real-time monitoring, plasmonic heating, in situ sensing S urface-enhanced Raman scattering (SERS) spectroscopy is a highly sensitive vibrational spectroscopy technique that facilitates the identification of trace analytes and allows the multiplexed detection of their characteristic vibrational fingerprints. 1 On this account, SERS has emerged as a promising chemical monitoring method, with applications in various fields including biosensing, 2 food control, 3 and detection of hazardous materials, 4 among others. SERS relies on the plasmonic properties of noble metal nanostructures to enhance the Raman signal of adsorbed molecules. The confinement of light at nanoscale volumes by plasmonic nanomaterials is responsible for a dramatic increase in sensitivity, which can go as far as single-molecule detection. 5 Key features of SERS are its noninvasive character and labelfree detection, which promise the potential of implementing in situ measurements, for example, in the clinic or in the field. However, to achieve in situ monitoring, not only further development ...

A Dual‐Modal Single‐Antibody Plasmonic Spectro‐Immunoassay for Detection of Small Molecules

“…However, the irreversible capturing processes through either antibody‐antigen interaction, streptavidin‐biotin binding, enzymatic reaction, or DNA hybridization, [ 45–46 ] imposed a considerable interfering effect on subsequent measurements owing to the so‐called SERS memory effect. [ 47 ] This could compromise SERS measurements over time due to the changing surface conditions of the substrate. The repeated incubations are also time‐consuming, hindering the deployment of biosensor devices for rapid analytes screening.…”

Prospects of Surface-Enhanced Raman Spectroscopy for Biomarker Monitoring toward Precision Medicine

“…The SERS spectra confirm that the vibrational fingerprint of molecules in solution (4-mercaptobenzoic acid in this case) is only registered after opening a measurement window by sufficient laser irradiation. Adapted with permission from ref ( 186 ). Copyright ACS 2021.…”

“…Finally, it has been recently reported that the irreversible adsorption of (analyte) molecules onto plasmonic substrates may interfere in subsequent measurements, which is known as the SERS-memory effect and represents a source of uncertainty in real-time measurements. 186 To resolve this issue, micron-thick, thermolabile polymer layers were deposited on top of plasmonic substrates, providing a physical barrier against molecular diffusion and adsorption. Laser irradiation at high fluence induces plasmonic heating of the underlying nanoparticles, so the sheathing layer degrades under high local temperature and opens a measurement window at the selected measurement time and location.…”

“…Laser irradiation at high fluence induces plasmonic heating of the underlying nanoparticles, so the sheathing layer degrades under high local temperature and opens a measurement window at the selected measurement time and location. Depending on the nature of the polymer layer, this process can be applied in a reversible (poly- N -isopropylacrylamide, pNIPAm) 187 or an irreversible (poly(lactic-glycolyc acid), PLGA) 186 manner. As soon as a micrometer-sized window is created in the polymer layer, the molecules in solution can reach the plasmonic surface and can be registered by SERS ( Figure 5 d).…”

Microfluidics and surface-enhanced Raman spectroscopy, a win–win combination?

“…Along this direction, recently, Plou et al demonstrated a novel method to prevent the memory effect in microfluidic SERS measurements. 259 A non-permeable polymer layer was coated on a plasmonic SERS substrate to control the adsorption of analyte molecules. This polymeric layer was degraded by the same laser to create a micrometer sized window for consecutive SERS measurements.…”