Waveguide-based surface-enhanced Raman spectroscopy detection of protease activity using non-natural aromatic amino acids

Abstract

Surface enhanced Raman spectroscopy (SERS) is a selective and sensitive technique, which allows for the detection of protease activity by monitoring the cleavage of peptide substrates. Commonly used free-space based SERS substrates, however, require the use of bulky and expensive instrumentation, limiting their use to laboratory environments. An integrated photonics approach aims to implement various free-space optical components to a reliable, mass-reproducible and cheap photonic chip. We here demonstrate integrated SERS detection of trypsin activity using a nanoplasmonic slot waveguide as a waveguide-based SERS substrate. Despite the continuously improving SERS performance of the waveguide-based SERS substrates, they currently still do not reach the SERS enhancements of free-space substrates. To mitigate this, we developed an improved peptide substrate in which we incorporated the non-natural aromatic amino acid 4-cyano-phenylalanine, which provides a high intrinsic SERS signal. The use of non-natural aromatics is expected to extend the possibilities for multiplexing measurements, where the activity of several proteases can be detected simultaneously.

Waveguide-Enhanced Raman Spectroscopy (WERS): An Emerging Chip-Based Tool for Chemical and Biological Sensing

“…Lastly, using a composite core material, an intriguing combination of WERS and SERS was described by the Baets group [ 60 , 61 ]. They covered Si 3 N 4 slot waveguides first with Al 2 O 3 to narrow the slot, and then with Au to serve as an extended enhancing hotspot ( Figure 7 ).…”

“… (Reprinted with permission from [ 61 ] © Optica) Waveguide-based nanoplasmonic slot waveguide top view and cross-section. …”

Roadmap on Universal Photonic Biosensors for Real-Time Detection of Emerging Pathogens

“…The cleavage multiplication factor M has an even stronger effect on the LOD reduction than the large polarizability of the probes since a single CRISPR complex, activated by the hybridization of viral RNA/DNA to CRISPR RNA/DNA, can produce thousands of non-specific collateral cleavages. Furthermore, the probes can be chosen such that they either produce an additional optical signal, e.g., fluorescence and Raman scattering [186] or strongly modify the electrical conductivity of the sensor [173,187], allowing for the development of a multiplexed sensor platform design.…”

Multispectral transmission through phoxonic crystal slot-waveguide at midwave infrared frequencies

“…PxCs are recently known to form the basis for realizing various modern optical phenomena like slow and fast light, 23 zero refractive index, 16 chirality, 24 etc., and has proved to be a potential candidate in building nanoscale devices for measurements as precise as that of a small amount of mass or charge or even the ultra-short distance 25 – 27 While inserting defects into PxC arrays to form a cavity or a waveguide, 28 their ability to manipulate localized modes for both photons and phonons outshines. Such a possibility of high mode confinement within small volumes anticipates an ultra-strong nonlinear interaction for the purpose of the novel cavity-optomechanical (C-OM) devices and applications.…”