Nanoarchitecture Based SERS for Biomolecular Fingerprinting and Label-Free Disease Markers Diagnosis

Abstract

ConspectusSurface-enhanced Raman spectroscopy (SERS) fingerprinting is highly promising for identifying disease markers from complex mixtures of clinical sample, which has the capability to take medical diagnoses to the next level. Although vibrational frequency in Raman spectra is unique for each biomolecule, which can be used as fingerprint identification, it has not been considered to be used routinely for biosensing due to the fact that the Raman signal is very weak. Contemporary SERS has been demonstrated to be an excellent analytical tool for practical label-free sensing applications due its ability to enhance Raman signals by factors of up to 108–1014 orders of magnitude. Although SERS was discovered more than 40 years ago, its applications are still rare outside the spectroscopy community and it is mainly due to the fact that how to control, manipulate and amplify light on the “hot spots” near the metal surface is in the infancy stage.In this Account, we describe our contribution to develop nanoachitecture based highly reproducible and ultrasensitive detection capability SERS platform via low-cost synthetic routes. Using one-dimensional (1D) carbon nanotube (CNT), two-dimensional (2D) graphene oxide (GO), and zero-dimensional (0D) plasmonic nanoparticle, 0D to 3D SERS substrates have been designed, which represent highly powerful platform for biological diagnosis. We discuss the major design criteria we have used to develop robust SERS substrate to possess high density “hot spots” with very good reproducibility. SERS enhancement factor for 3D SERS substrate is about 5 orders of magnitude higher than only plasmonic nanoparticle and more than 9 orders of magnitude higher than 2D GO. Theoretical finite-difference time-domain (FDTD) stimulation data show that the electric field enhancement |E|2 can be more than 2 orders of magnitude in “hot spots”, which suggests that SERS enhancement factors can be greater than 104 due to the formation of high density “hot spots” in 3D substrate. Next, we discuss the utilization of nanoachitecture based SERS substrate for ultrasensitive and selective diagnosis of infectious disease organisms such as drug resistance bacteria and mosquito-borne flavi-viruses that cause significant health problems worldwide. SERS based “whole-organism fingerprints” has been used to identify infectious disease organisms even when they are so closely related that they are difficult to distinguish. The detection capability can be as low as 10 CFU/mL for methicillin-resistant Staphylococcus aureus (MRSA) and 10 PFU/mL for Dengue virus (DENV) and West Nile virus (WNV). After that, we introduce exciting research findings by our group on the applications of nanoachitecture based SERS substrate for the capture and fingerprint detection of rotavirus from water and Alzheimer’s disease biomarkers from whole blood sample. The SERS detection limit for β-amyloid (Aβ proteins) and tau protein using 3D SERS platform is several orders of magnitude higher than the currently used technology in clinics. Finally, w...

Intracellular and Cellular Detection by SERS‐Active Plasmonic Nanostructures

“…Spectroscopic methods have received increasing attention because quantitative molecular information of targets of interest can be revealed. Raman spectroscopy detects inelastic light scattering related to vibrational energy levels of the probed molecules, leading to molecularly specific Raman fingerprints . As such, Raman signals allow for specific identification of individual components from a complicated biological mixture; thus making it an ideal technique for multiplexed detection .…”

“…Raman spectroscopy detectsi nelastic light scattering relatedt ov ibrational energy levels of the probedmolecules, leading to molecularly specific Ramanf ingerprints. [2] As such, Ramans ignals allow for specific identification of individual components from ac omplicated biological mixture;t hus making it an ideal technique for multiplexed detection. [3] On the other hand, Raman scattering is ah ighly inefficient process that is ascribed to the small cross sections, which are typicallyi nt he order of 10 À30 cm 2 sr À1 molecule À1 ; [4] thus resultingi nw eak signals that are insufficient for sensitive analysis.…”

The Mechanism Research for the Surface Plasmon-Catalysed Reaction of the Mercapto Group Substituted Benzoic Acid

“…Thus, molecular symmetry, geometric structure formation and how atoms are arranged in molecules can be inferred using Raman spectroscopy. Since 1974, scientists have found that surfaceenhanced Raman scattering (SERS) technology [3][4][5] (based on its high sensitivity, little interference by water, formal research of interface effect, and so on) has played a powerful role in interface features and ultrathin membrane material research; it has thrived both in theory and experiment due to its extensive applications in fingerprint detection, even at the single molecule level [6][7][8][9]. SERS is the most extensive spatial location technique involving the adsorption process at solid or liquid interfaces because of its simplicity and ability to recognize the material structures rapidly, along with its ability to detect different types of supramolecular architectures as well as its ability to investigate distinct functional group adsorption phenomena [10][11][12].…”

Enhancements inside and outside the junctions of Ag colloidal dimers

“…1,2 This phenomenon is well-known as surface-enhanced Raman scattering (SERS). 3 Recently, SERS has received much attention as a probing technique for biosensors because of its high sensitivity; [4][5][6][7] it is known that SERS can detect even single molecules. [8][9][10] To achieve such high-sensitivity detection, a very high enhancementup to 10 11 for non-resonant molecules and 10 8 for resonant moleculesmay be required.…”