Development of measurement technology of surface-enhanced Raman spectroscopy for detection of biomolecules

Project: A - Government Institutionb - Ministry of Science and Technology


Structures and reactions of electrode/liquid interfaces play an increasingly important role in electrochemistry (EC). Generally, vibrational spectroscopic methods such as infrared (IR) and Raman have been widely employed to identify the molecules and the nature of the chemisorption bond. Although each technique alone has its strengths and limitations, combined developments culminate in producing a wealth of excellent information leading to a better understanding of the complexity of interfacial electrochemistry. The detection sensitivity and resolution are two very important criteria for comparing these techniques in terms of their capability in providing high quality information from interfaces. Existing electrochemical techniques generally have a very high sensitivity capable of detecting a molecular or atomic change in the interface at the submonolayer quantity. However, they have a poor time resolution at milliseconds unless microelectrodes or ultra-microelectrodes are used. Raman spectroscopy can be conveniently applied not only to in situ measurements of solid-liquid interfaces in fundamental as well as practical studies, but also to the porous and rough surfaces with high surface areas that are very difficult to study using many other surface techniques. With the development of technologies of surface-enhanced Raman scattering (SERS), Raman signals of analytes now can be significantly enhanced by fourteen orders of magnitudes. Theses enhancements come not only from the increased surface areas of noble metals (Au, Ag and Cu), but also from the surface plasmon resonance of noble metals. Therefore, SERS spectroscopies can be widely used in biomedicine fields, like encoding approach for DNA and RNA detection, and for single-molecule detection. In spite of the fact that thousands of papers on SERS have been published, the development of SERS into a widely used tool has been slow. There are two major obstacles hampering the development of EC-SERS. First, only three noble metals (Au, Ag, and Cu) provide the large enhancement needed, which severely limited the range of SERS’s practical applications. Second, the high SERS-active substrates normally suffer from instability, which leads to poor reversibility during EC-SERS measurements. In our laboratory, we got bounteous experiment experiences and satisfactory relative results on the preparations of noble metal nanoparticles (NPs) and SERS-active metal substrates based on EC methods. This plan aims to develop SERS-active array metal substrates for improving sensitivity, resolution, reproducibility and stability in Raman detections based on EC methods. Meanwhile, the developed SERS measurement technologies are applied in biomedicines and further development of biosensors. In the first year, SERS-active substrates are electrochemically prepared based on highly qualitative nanotemplates of anodic aluminum oxide (AAO). The prepared SERS-active substrates are employed in detection of biomolecules. In the second year, SERS-active like-array metal substrates with high sensitivity and resolution are developed based on new strategy of EC methods. Meanwhile, SERS-active Pt NPs are prepared and investigated. The prepared SERS-active substrates are employed in detection of cancer cells. In the third year, the developed SERS techniques with higher sensitivity and resolution in the first two years are combined and used in encoding approach to DNA and RNA detection, and to single-molecule detection. Finally, biosensors are developed based on prepared SERS-active array substrates. (1) Establishment of the key technique in preparation of highly qualitative AAO templates based on different EC methods and electrolytes. (2) Establishment of the mechanisms of electromagnetic and chemical enhancements in detection of biomolecules based on SERS-active array metal substrates. (3) Establishment of the key technique in preparation of highly qualitative SERS-active like-array metal substrates based on new EC strategies. (4) Establishment of the key techniques in preparation of SERS-active Pt NPs based on EC methods and in measurement of cancer cells by SERS spectroscopy. (5) Combining the developed techniques in preparing SERS-active array substrates to improve the SERS spectra having higher sensitivity and resolution. (6) Using developed SERS techniques in encoding approach to DNA and RNA detection, and to single-molecule detection and in developing biosensors based on EC-SERS.
Effective start/end date8/1/137/31/14


  • Surface-enhanced Raman scattering
  • Sonoelectrochemical methods
  • Limit of detection