Liquid interface-assisted SERS could see early


image: Figure 1. Schematic of the laser fabrication system for microfluidic SERS chips.
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Credit: OAE

A new publication from Advances in optoelectronics; DOI 10.29026/oea.2022.210121 discusses label-free trace detection of biomolecules by liquid interface-assisted surface-enhanced Raman scattering using a microfluidic chip.

Surface-enhanced Raman scattering (SERS) has attracted attention in biotechnology. This is due to its high sensitivity to localized surface plasmon resonance of nanostructured metals. The detection of traces of high molecular weight biomolecules remains difficult because the treatment of the SERS substrate using coupling or crosslinking agents is necessary. Researchers applied liquid interface-assisted SERS to achieve label-free trace detection of biomolecules. The results suggest that it holds promise for the early diagnosis of viral infection and Alzheimer’s disease.

Surface Enhanced Raman Scattering (SERS), based on a near-field optical effect induced by the surface plasmon of noble metal nanoparticles or nanostructures excited by laser radiation, amplifies Raman signals up to 1014 times compared to ordinary Raman. Due to its increased intensity, the SERS technique continues to attract growing interest in trace detection and analysis of biomaterials. It has generated increased interest in areas such as imaging organelles in a single cell, tracking cancer cells and identifying biomarkers.

The SERS technique can be used in the biomedical field for the diagnosis of disease at an early stage and also in the treatment of tumors. Although the SERS improvement factor typically ranges from 106 – ten8 due to the use of new SERS substrates and methods, detection of a single molecule by SERS without a label is impractical due to SERS blinking, the origin of this phenomenon being due to the leakage of analyte molecules from the dots hot. Additionally, biomolecules, including deoxyribonucleic acid (DNA) and proteins, are difficult to detect directly by SERS. Additional treatments with a SERS substrate are required to bind the biomolecules.

The research team came up with LI-SERS, which achieves an SERS improvement factor greater than 1014, much higher than the usual SERS method. The microfluidic SERS chip featured an Ag-Cu SERS substrate embedded in an embedded glass microchannel. Femtosecond (fs) hybrid laser processing created the grass microchannel.

fs hybrid laser processing enables the creation of more complex 3D structures with enhanced functionality for biochips, sensors and microelectronic devices. When the interface between the analyte solution and the air on the SERS substrate in the microfluidic channel was irradiated with the Raman excitation laser, the intensity of the LI-SERS was increased by six orders of magnitude compared to to ordinary SERS. The mechanism of LI-SERS has been attributed to the synergistic effect of Marangoni flux induced by laser irradiation and optical trapping. This laser irradiation would direct the analyte molecules to the hotspots where the collected molecules are trapped by the optical force. Therefore, the analyte molecules were immobilized on the SERS substrate with the realization of strong Raman scattering.

This study demonstrated that the LI-SERS method is applicable for more practical use. It is particularly useful for trace detection of unlabeled biomolecules with large molecular masses, including DNA bases, DNA sequences, and β-amyloid (Aβ). Due to the ultra-high sensitivity and self-immobilization of LI-SERS, discrimination of DNA bases and DNA sequences with a detection limit of 1 fM was achieved without the need for additional treatments involving coupling or cross-linking agents. In addition, the LI-SERS technique can detect unlabeled Aβ, a biomarker of Alzheimer’s disease, at levels below 1 pM, and with a linear correlation between the Raman signal and the concentration of Aβ in the range 1 nM-1 pM being reached. The label-free biosensing capability of LI-SERS offers great potential for early disease diagnosis in clinics.

In conclusion, the researchers gave an overview of the scope of the LI-SERS method for the detection of traces of biomolecules in microfluidic SERS chips with particular reference to the detection of ultra-traces of DNA bases and Aβ. A liquid interface may have formed in the microchannel. Marangoni flux and LI-SERS-induced optical trapping effects demonstrated a detection limit of 1 fM for untagged DNA bases. Notable features of the LI-SERS method, including ultra-high sensitivity and versatility coupled with the collection and self-immobilization of analyte molecules at hotspots, will be beneficial for disease diagnostics at a early stage such as viral infections and Alzheimer’s disease.

Article reference: Bai S, Ren XL, Obata K, Ito Y, Sugioka K. Label-free trace detection of biomolecules by liquid interface-assisted surface-enhanced Raman scattering using a microfluidic chip. Opto-Electron Adv 5, 210121 (2022). doi: 10.29026/oea.2022.210121

Key words: femtosecond laser treatment / LI-SERS / microfluidic chip / DNA / β-Amyloid

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Advances in optoelectronics (OEA) is a high-impact, open-access, peer-reviewed SCI monthly journal with an impact factor of 8.933 (Journal Citation Reports for IF2021). Since its launch in March 2018, OEA has been indexed in SCI, EI, DOAJ, Scopus, CA and ICI databases over time and has expanded its editorial board to 36 members from 17 countries and regions (average h-index of 49).

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