Development of SERS-based Microdevices for Rapid Bioassay

Abstract

Surface enhanced Raman Scattering (SERS) is a phenomenon where the Raman scattering signal of a molecule adsorbed on a rough metal surface is significantly amplified by 1011 – 1012 times. It was discovered in 1973 when the Raman scattering signal of pyridine molecules was observed on the rough silver electrode surface. Before its observation, a high-energy laser together with a signal amplification process was needed because the Raman scattering signal itself was so weak. However, the sensitivity of the Raman scattering were dramatically improved and single molecular-level substances could be detected using the SERS measurement. After the discovery of SERS, the research for the SERS application extensively increased, as a technology that could analyze with high sensitivity at the molecular level, as well as basic research to solve fundamental questions about the SERS phenomena. However, low signal reproducibility was a serious problem in SERS detection, making it difficult to apply it in wide ranges of areas such as medical diagnosis and environmental analysis. Recently, functional nanoparticles synthesis technology that can maximize the reproducibility and sensitivity of Raman scattering signals as well as applicable devices and platform technology have been developed. In this study, nanoparticles, which can be used for the quantitative analysis of various biomarkers and environmental materials, have been developed for the use of biomedical and environmental fields. In addition, various multi-functional devices for the use of SERS-based analysis have been also designed and manufactured.

In the first study, the quantitative analysis of PCA3 gene that could replace prostate specific antigen (PSA) were performed. Molecular diagnostics is usually done by amplifying genes in samples several times using PCR method. In this study, hollow gold nanoparticles were synthesized to maximize signal enhancement efficiency, and genes were detected without any amplification process. In addition, magnetic particles were used to select only genes in samples in a short period of time through magnetic fields. In the second study, we developed a microfluidic device that can automatically dilute and quantitatively analyze harmful environmental substances without any contact. In this study, the concentration gradient is formed by diluting the samples, and the diluted samples were mixed with metal nanoparticles in the microfluidic chip. Raman analysis was automatically conducted within the microfluidic circuit. We also used star shaped gold nanoparticles to detect trace environmental materials with high sensitivity. In the third study, we developed a paper chip that could directly diagnose diseases in the field. In this study, antibodies that can detect specific disease biomarkers were adsorbed on the paper chip in advance. When blood sample was injected with nanoparticles, Raman scattering signals from the test zone were analyzed to determine the presence of disease biomarker, as well as color change determination. In addition, for long-term storage in various environments, such as high temperature at a tropical region, chemical stability could be improved by coating the surface of gold nanoparticles with silica.

SERS technology has the advantages of good sensitivity and easy measurement of any type of samples. In this study, the functional nanoparticles that could be used for the reproducible analysis and the devices that perform most suitable functions were made to find a rapid, accurate and reproducible analytical method of targets. It is expected that SERS based analysis platforms will be available for a wide range of areas in the near future.