Liquid-interface assisted SERS could lead to earlier detection of Alzheimer’s

September 12, 2022 - 3 minutes
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In a new publication in Opto-Electronic Advances, Japanese researchers discussed label-free trace detection of bio-molecules by liquid-interface assisted surface-enhanced Raman scattering (SERS) using a microfluidic chip.

SERS has attracted attention in biotechnology. This is due to its high sensitivity to localized surface plasmon resonance of nanostructured metals. 

Trace detection of bio-molecules with large molecular weight remains challenging because treating SERS substrate using coupling or cross-linking agents is required. The researchers applied liquid-interface assisted SERS to realize label-free trace detection of bio-molecules. The results suggest it is promising for early-stage detection of virus infection and Alzheimer’s.

SERS, based on an optical near-field effect induced by the surface plasmon of noble metal nanoparticles or nanostructures excited by laser radiation, amplifies the Raman signals up to 1,014 times compared to regular Raman. Due to its enhanced intensity, the SERS technique continues to attract growing interest in trace-level detection and analysis of biomaterials. It has increased interest in fields such as imaging organelles in a single cell, cancer cell tracking, and biomarker identification.

Early diagnoses

The SERS technique may be used in the biomedical field for disease diagnosis at an early stage and also in tumor therapy. Although the enhancement factor of SERS typically ranges from 106 to 108 due to the use of novel SERS substrates and methods, single-molecule detection by label-free SERS is impracticable because of SERS-blinking. The origin of this phenomenon is due to the escape of analyte molecules from hotspots. Bio-molecules, including DNA and proteins, are difficult to detect directly by SERS. Additional treatments with a SERS substrate are needed to bind the bio-molecules.

The researchers, from the Advanced Laser Processing Research Team, RIKEN Center for Advanced Photonics, in Wakō and the Nano Medical Engineering Laboratory, RIKEN Cluster for Pioneering Research in Wakō proposed LI-SERS, which achieves a SERS enhancement factor greater than 1,014, higher than the regular SERS method. The microfluidic SERS chip featured an Ag-Cu SERS substrate integrated into an embedded glass microchannel. Hybrid femtosecond (fs) laser processing created the grass microchannel.

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The hybrid fs laser processing enables the creation of more complicated 3D structures with enhanced functionalities for biochips, sensors, and microelectronic devices. When the interface between the analyte solution and air on the SERS substrate in the microfluidic channel was irradiated by the Raman excitation laser, the LI-SERS intensity was increased by six orders of magnitude compared with regular SERS. 

The researchers said the study demonstrated that the LI-SERS method is applicable for more practical use. It is specifically useful for trace detection of label-free bio-molecules with large molecular masses, including DNA bases, DNA sequences and β-Amyloid (Aβ). Owing to the ultrahigh sensitivity and self-immobilization of LI-SERS, discrimination of DNA bases and DNA sequences with a detection limit of 1 fM was obtained without requiring additional treatments featuring coupling or cross-linking agents.

Early detection of Alzheimer’s disease

Also, the LI-SERS technique can detect label-free Aβ, a biomarker of Alzheimer’s disease, at levels below 1 pM. The label-free bio-sensing capability of LI-SERS offers great potential for the early-stage diagnosis of diseases in clinics.

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