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Research on the Methods of Nasopharyngeal and Gastric Cancer Detection Based on Surface-enhanced Raman Spectroscopy

Author: FengShangYuan
Tutor: ChenRong;XieShuSen
School: Fujian Normal University
Course: Optical Engineering
Keywords: SERS Cell Tissue Plasma Cancer Detection Method Research
CLC: R739.63
Type: Master's thesis
Year: 2011
Downloads: 30
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Abstract

Surface-enhanced Raman spectroscopy has demonstrated great potential in the biomedical detection filed. In this thesis, we track the hot issue on SERS, combining the current research situation and clinical demand to develop nasopharyngeal and gastric cancer detection methods based on SERS technology. The main research results as follow:1) We use three methods to deliver nano-particle into living cell for SERS study, including "passive uptake", biological cell self-reduction and electroporation. After comparison of advantages and disadvantages of the three methods, we mainly research on the electroporation methods for fast delivery of silver nanoparticles into living cells for intracellular SERS spectroscopy. The new method for nanoparticle delivery averts the shortcoming of "passive uptake" and allows for quick acquisition of robust SERS spectra from living C666, A431, and CA46 cancer cell lines in our study. The whole-cell detection SERS spectra using electroporation delivery are more reproducible than for "passive uptake", thus are favored for practical applications. As a result, the process of SERS detection is accelerated significantly and the data reproducibility is improved as well, demonstrating great potential for biomedical applications, such as for high-throughput cancer cell screening.2) The capabilities of using gold nanoparticle based near-infrared surface enhanced Raman scattering (SERS) to obtain biochemical information from the normal and cancerous human nasopharyngeal tissue were firstly presented in this chapter. The SERS bands of nasopharyngeal tissue were assigned to known molecular vibrations. We discuss the blinking phenomenon at the tissue level when measuring the nasopharyngeal tissue SERS spectra. The blinking phenomenon is laser power density dependent. SERS imaging demonstrated great potential’for distinguishing cancerous and normal nasopharyngeal tissues without using any dye labeling or other chemical species as functionalized binding sites. Base on this, we further synthesize SERS immune probe to detect the EB virus. Experiment has proved the SERS immune probe feasible to detect EB virus with high performance. 3) A surface-enhanced Raman spectroscopy (SERS) method was firstly developed for blood plasma biochemical analysis with the aim to develop a simple blood test for non-invasive nasopharyngeal cancer detection. Blood plasma sample from nasopharyngeal cancer patients (n=43) and healthy subjects (n=33) were analyzed. Tentative assignments of the Raman bands in the measured SERS spectra suggest interesting cancer specific biomolecular differences. Principal component analysis (PCA) of the measured SERS spectra separated the spectral features of the two groups into two distinct clusters with little overlaps. Linear discriminate analysis (LDA) based on the PCA generated features differentiated the nasopharyngeal cancer SERS spectra from normal SERS spectra with high sensitivity (90.7%) and specificity (100%). The results from this exploratory study demonstrated great potentials for developing SERS blood plasma analysis into a novel clinical tool for non-invasive detection of nasopharyngeal cancers.4) The effect of different laser polarizations (non-polarized, linear-polarized, right-handed circularly polarized, and left-handed circularly polarized) on blood plasma SERS spectroscopy was explored for the first time. The aim of this study was to develop a more robust SERS spectroscopy based blood plasma analysis method for non-invasive gastric cancer detection. Blood plasma sample from gastric cancer patients (n=32) and healthy subjects (n=33) were analyzed. Compared with the non-polarized laser excitation and linear-polarized laser excitation, the use of circularly polarized laser excitation greatly improved the diagnostic sensitivity and specificity. The best diagnostic performance was achieved by left-handed circularly polarized laser excitation:a sensitivity of 100% and specificity of 97%, while with the non-polarized laser excitation, both the sensitivity and specificity were around 72%. The improvement may be related to the possibility that the left-handed circularly polarized laser light excitation was better in exploring the chirality of biomolecules in the gastric cancer blood plasma.5) Combining membrane electrophoresis with surface-enhanced Raman scattering (SERS), we have developed a novel method for blood plasma protein analysis for cancer detection applications. Compared to direct SERS analysis of untreated blood plasma, our new method significantly reduced the spectral variability of cancer patients due to the elimination of exogenous substances and the highly variable native plasma constituents other than albumin and globulin proteins. In this method, albumin and globulin proteins are first isolated from blood plasma by membrane electrophoresis and then mixed with silver nanoparticles to perform SERS spectral analysis. Blood plasma sample from nasopharyngeal cancer patients (n=43), gastric cancer patients (n=31) and healthy subjects (n=33) were analyzed in this chapter. Principal components analysis of the SERS spectra revealed that the data points for the cancer groups and the normal group form distinct, completely separated clusters with no overlap. Therefore, both gastric cancer group and the nasopharyngeal cancer group can be unambiguously discriminated from the normal group with both diagnostic sensitivity and specificity of 100%. These results are very promising for developing a label-free, non-invasive, and reliable clinical tool for rapid cancer detection and screening.

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