单细胞光镊拉曼光谱在肿瘤诊断中的应用基础研究
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摘要
目的:研究同一恶性肿瘤的癌、癌旁、正常细胞的拉曼光谱与分子生物学变化之间的关系以及由正常组织→癌的发生发展过程中生物组分的变化与发病机理,以期建立癌细胞的特征拉曼光谱库。
方法:采取确诊为肝癌、胃癌、结肠癌、乳腺癌病人手术后的新鲜标本,用机械分散法制备正常、癌旁及癌组织的单细胞悬液,按照慢冻快融的原则进行细胞的冻存与复苏,然后通过光镊拉曼光谱技术测出正常、癌旁及癌组织的单细胞拉曼光谱。将细胞悬液离心15分钟后,取上清液以同样的激发功率和曝光时间采集背景光谱。最后把细胞的拉曼光谱减去背景的光谱,最终得到单细胞的拉曼光谱。所得数据用origin6.0软件进行处理。
结果:1.胃癌细胞的拉曼光谱的特征峰在883、1051、1089、1283cm-1,它们的相对强度改变与细胞内DNA含量、结构改变有关。胃癌的癌细胞与癌旁细胞、正常细胞在拉曼光谱的特征光谱带差异有显著意义(p<0.05)。2.结肠癌细胞的拉曼光谱的特征峰在1300、1350、1442、1458、1576、1662、1647和1739cm-1,它们的强度变化说明细胞中核酸含量增加,脂类的含量减少。结肠癌的癌细胞与癌旁细胞、正常细胞在拉曼光谱的特征光谱带差异有显著意义(p<0.05)。3.肝癌细胞的拉曼光谱特征峰在1040、1080、1182、1156、1241cm-1,它们的强度变化说明细胞中核酸含量增加,蛋白质的二级结构发生改变。肝癌的癌细胞与癌旁细胞在拉曼光谱的特征光谱带差异有显著意义(p<0.05)。因肝癌病人大多合并肝硬化,故肝正常细胞很难获得。4.乳腺癌细胞的拉曼光谱特征峰在782、979、1087、1155、1175cm-1,它们的强度改变说明细胞DNA的磷酸根骨架(主链)有一定的断裂,脂类含量有变化。乳腺癌的癌细胞与癌旁细胞、正常细胞在拉曼光谱的特征光谱带差异有显著意义(p<0.05)。5.在非特征性光谱带,胃癌、结肠癌、乳腺癌分别有不同例数的癌旁细胞与正常细胞的谱线差异无显著
Objective: The topic is to study the interaction between Raman spectrum of cancer、adjacent cancer、normal cells which were come from one patient and biological molecules,as well as the change and etiopathogenesis of biological tissue composition from normal tissue to carcinogenesis. In the end, characteristic Raman spectra of cancer cells are presented.
Methods: The fresh specimens of liver cancer、gastric cancer、colon cancer、breast cancer had been selected for this research after operation.Single cells suspension of normal、adjacent carcer、carcer tissues were made by mechanical dispersion method.According to the principle of the slow frozen and fast melt, the cells suspension were carried out to survive and anabiosis.Then the samples were detected by laser tweezers Raman spectra technique.After centrifugating cells suspension 15 minutes,the supernates were collected backgroud spectrum by means of the same provocation power and exposition time.At the last,single cells laser tweezers Raman spectrum were obtained by subtracting backgroud’s from cell Raman spectrum. All experiments datas were handled with the origin6.0 software.
Results: 1.The characteristic peaks of gastric cancer cells spectrum are at 883,1051,1089,1283 cm-1,their strength changing relate to contents and construction of DNA inside cell. At the characteristic spectrum bands,the cancer,adjacent cancer,normal cells of gastric have notable distinctions(P<0.05).2.The characteristic peaks of colon cancer cells spectrum are at 1300、1350、1442、1458、1576、1662、1647和1739 cm-1,their strength changing relate to contents of nucleic acids and lipids inside cell. At the characteristic
方法:采取确诊为肝癌、胃癌、结肠癌、乳腺癌病人手术后的新鲜标本,用机械分散法制备正常、癌旁及癌组织的单细胞悬液,按照慢冻快融的原则进行细胞的冻存与复苏,然后通过光镊拉曼光谱技术测出正常、癌旁及癌组织的单细胞拉曼光谱。将细胞悬液离心15分钟后,取上清液以同样的激发功率和曝光时间采集背景光谱。最后把细胞的拉曼光谱减去背景的光谱,最终得到单细胞的拉曼光谱。所得数据用origin6.0软件进行处理。
结果:1.胃癌细胞的拉曼光谱的特征峰在883、1051、1089、1283cm-1,它们的相对强度改变与细胞内DNA含量、结构改变有关。胃癌的癌细胞与癌旁细胞、正常细胞在拉曼光谱的特征光谱带差异有显著意义(p<0.05)。2.结肠癌细胞的拉曼光谱的特征峰在1300、1350、1442、1458、1576、1662、1647和1739cm-1,它们的强度变化说明细胞中核酸含量增加,脂类的含量减少。结肠癌的癌细胞与癌旁细胞、正常细胞在拉曼光谱的特征光谱带差异有显著意义(p<0.05)。3.肝癌细胞的拉曼光谱特征峰在1040、1080、1182、1156、1241cm-1,它们的强度变化说明细胞中核酸含量增加,蛋白质的二级结构发生改变。肝癌的癌细胞与癌旁细胞在拉曼光谱的特征光谱带差异有显著意义(p<0.05)。因肝癌病人大多合并肝硬化,故肝正常细胞很难获得。4.乳腺癌细胞的拉曼光谱特征峰在782、979、1087、1155、1175cm-1,它们的强度改变说明细胞DNA的磷酸根骨架(主链)有一定的断裂,脂类含量有变化。乳腺癌的癌细胞与癌旁细胞、正常细胞在拉曼光谱的特征光谱带差异有显著意义(p<0.05)。5.在非特征性光谱带,胃癌、结肠癌、乳腺癌分别有不同例数的癌旁细胞与正常细胞的谱线差异无显著
Objective: The topic is to study the interaction between Raman spectrum of cancer、adjacent cancer、normal cells which were come from one patient and biological molecules,as well as the change and etiopathogenesis of biological tissue composition from normal tissue to carcinogenesis. In the end, characteristic Raman spectra of cancer cells are presented.
Methods: The fresh specimens of liver cancer、gastric cancer、colon cancer、breast cancer had been selected for this research after operation.Single cells suspension of normal、adjacent carcer、carcer tissues were made by mechanical dispersion method.According to the principle of the slow frozen and fast melt, the cells suspension were carried out to survive and anabiosis.Then the samples were detected by laser tweezers Raman spectra technique.After centrifugating cells suspension 15 minutes,the supernates were collected backgroud spectrum by means of the same provocation power and exposition time.At the last,single cells laser tweezers Raman spectrum were obtained by subtracting backgroud’s from cell Raman spectrum. All experiments datas were handled with the origin6.0 software.
Results: 1.The characteristic peaks of gastric cancer cells spectrum are at 883,1051,1089,1283 cm-1,their strength changing relate to contents and construction of DNA inside cell. At the characteristic spectrum bands,the cancer,adjacent cancer,normal cells of gastric have notable distinctions(P<0.05).2.The characteristic peaks of colon cancer cells spectrum are at 1300、1350、1442、1458、1576、1662、1647和1739 cm-1,their strength changing relate to contents of nucleic acids and lipids inside cell. At the characteristic
引文
1. 刘金绪,韩伟,彭英科等,关于癌变细胞红外光谱测定方法的研究,分析化学,1998,26(7), 883-885。
2. Pappas Dimitri , Smith Benjamin w ., Winefordner, et al. Raman Spectroscopy in bioanalysis.Talanta,2000,51(1),131-144
3. Duindam JJ, Tibbe AGJ, Ramanauskaite R, et al. Confocal Raman microscopy on eye lenses and single living cells, Progress in Biophysics and Molecular Biology, 1996, 65 (1) , 192-195.
4. Schrader B, Dippel B, Erb I, et al. NIR Raman spectroscopy in medicine and biology: results and aspects. Journal of Molecular Structure, 1999,480-481.
5. 陆逸仙, 张岳灿, 诸君浩等, 脑部恶性肿瘤组织切片的红外光谱研究,中国临床神经科学,2000, 8(4),278-279。
6. 彭卿, 徐惰庄, 李维红等, 胃肠道正常组织与相应肿瘤组织结构 FTIR 光谱研究,光谱学与光谱分析,1998,8(5), 528-531。
7. Fabian H, Jackson M, Murphy L, et al. A comparative infrared spectroscopic study of human breast tumors and breast tumor cell xenografts ,Biospectroscopy , 1995, 1(1), 37-45.
8. GAO Xiao-ling, Butler Ian S, Kremer Richard, A Novel Model of Assessment of Medical effect and Mechanisms of Anticancer DrugaRaman Spectroscopy, Acta Laser Biology Sinica, 1998,7(1) ,22.
9. SUN Chuan-wen , XU Yi-zhuang , SUN Kai-hua et al,A study of the diagnosis of salivary gland tumors by means of mid infrared optical fiber technique,Spectroscopy and Spectral Analysis, 1996, 16(5), 22.
10. 许以明, 张志义, 张伟, 竹红菌素以及其衍生物对脂质体空间结构的微观光敏损伤的Raman光谱特征, 中国科学C, 1998, 28(5), 417-419。
11. 许以明, 杨红英, 张志义, 竹红菌乙素敏化的人红细胞膜结构光损伤的Raman光谱特征, 中国科学C, 1999, 29(2), 138-140。
12. 许以明, 张志义, 徐国瑞, 治癌药物YHPD对DNA光敏损伤的激光拉曼光谱研究, 科学通报, 1989, 34(19), 1500-1502。
13. Li Wei-hong , XU Yi-zhuang , WENG Shi-fu, et al, FT-Raman and FTIR studies on the Normal and Maligant Tissues,Chinese Journal of Light Scattering, 1998, 10(3), 114-116.
14. Nicholas Stone , Catherine Kendall , Neil Shepherd et al. Near-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancers ,Journal of Raman Spectroscopy , 2002 , 33(7), 564-573.
15. Chang-an Xie ,Yong-qing Li, Confocal biological cell using optical trapping and shifted excitation difference techniques, Journal of Applied Physics, 2003, 93(5), 2982-2986.
16. Chang-an Xie , Yong-qing Li , Wei Tang , et al, Study of dynamical process of heat denaturation in optically trapped single microorganisms by near-infrared Raman spectroscopy, Journal of Applied Physics, 2003, 94(9), 6138-6142.
17. Chang-an Xie, Mumtaz Dinno, Yong-qing Li , Near-infrared Raman spectroscopy of single optically trapped biological cell. Optics Letters, 2002, 27(4), 249-251.
18.A. Ashkin, J. M. Dziedzic, J. E. Bjorkholm, et al, Observation of a single-beam gradient force optical trap for dielectric particles. Optics Letters, 1986, 11(5), 288-290.
19. Chang-an Xie , Yong-qing Li, Raman spectra and optical trapping of highly refractive and nontransparent particles. Applied Physics Letters, 2002, 81(6), 951-953.
20. 朱贵运,《激光拉曼光谱分析》,科学出版社,1991 年。
21. 陆同兴,路轶群,《激光光谱技术原理及应用》,中国科学技术大学出版社, 1999 年。
22. 郑顺旋,《激光拉曼光谱学》,上海科学技术出版社, 1985 年。
23. 赵南明,周海梦,《生物物理》, 高等教育出版社,施普林格出版社, 2000年。
24. P.R.Carey. Biochemical Applications of Raman and Resonance Raman Spectroscopics(1982)Academic Press,New York.
25. A.T.Tu,Raman Spectroscopy in Biology: Principles and Applications(1982). John Wiley&Sons , Inc New York.
26. 汪兆平,韩和相,李国华,拉曼光谱在癌症诊断中的应用,光散射学报,2000,11(4), 398-405
27. 余国滔,拉曼光谱在医学上的应用,光谱学与光谱学分析,1996, 16(8), 113-114。
28. Yao Hui-Lu, Wang Gui-Wen, HeBi-Juan et al. Study of Raman Spectra of single blood cells, Journal of Jinan University, 2005(4), 49-51.
29. 司徒镇强, 吴军正, 《细胞培养》(修订版),世界图书出版社, 2004 年。
30. Nicholas Stone, Catherine Kendall, Jenny Smith,et al, Raman spectroscopy for identification of epithelial cancers, Faraday Discuss. 2004,126-157.
31. 唐伟跃,王杰芳,徐平,胃癌组织拉曼光谱的研究,激光杂志, 2004, 25(1), 82-83。
32. M.S.Feld, R.Manoharan, J.Salenlus, et al, Detection and characterization of human tissue lesions with near-infrared Raman spectroscopy, Advances in Fluorescence Sensing Technology II,95,2 ,99-104,
33. YAN Xun-ling,DONG Rui-xin,WANG Qin-guo,Raman Spectra of Cell from Breast Cancer Patients,Spectroscopy and Spectral Analysis,2005,25(1), 58-61.
34. 汤钊猷,《现代肿瘤学》(第二版), 复旦大学出版社,2002 年。
35. 郭萍,易光辉,熊平等,癌症患者血清的激光拉曼光谱,光谱学与光谱学分析,2000,20(6), 844-846。
36. 存义,左健,紫外拉曼散射及其应用,物理,1999,28(4), 206-209。
37. 于世林,《波谱分析法》,重庆大学出版社,1991 年。
38. 彭燕,林三仁,血清自体荧光光谱检测诊断胃癌的初步研究,泸州医学院学报,1997, 20(1), 56-57。
39. 刘英俊, 侯晓华, 新的光学技术在内镜早期诊断胃肠道癌前病变中的作用, 临床消化病杂志, 2002, 3, 123-126。
40. 刘林森, 21 世纪的医学, 百科知识, 2003, 5, 14-15。
1. Mahadevan JA,Mitchell MF,Ramanujam N,et al,Near-infrared Raman spectroscopy for in vitro detection of cervical precancers,Photochem Photobiol, 1998, 68, 123-132.
2. Mahadevan JA,Mitchell MF,Ramanujam N,et al.Development of a fiber optic probe to measure NIR Raman spectra of cervical tissue in vivo, Photochem Photobiol, 1998,68, 427-431.
3. 姚淑霞,赵元黎,张录等,乳腺组织切片的拉曼光谱研究,河南预防医学杂志 2004,15(3), 132-134。
4. Zhao Yuan-Li, Lu Jing, Shen Pei-Hong, et al, Study of Laman Spectrum of Galactophore Tumour, Laser &Infrared, 2004, 34(6), 502-504.
5. Kendall C, Stone N, Shepherd, et al. Raman spectroscopy, a patential tool for the objective identification and classification of neoplasia in Barrett’s oesophagus, J Pathol, 2003 , 200(5), 602-609.
6. 凌晓峰,李维红,宋苑苑等, 胃癌组织的拉曼光谱初探.光谱学与光谱分析,2000,20, 692-693。
7. Xiao-feng Ling,Yuan-yuan Song ,Roger D,et al,Fourier trans-form Raman spectra can separate most normal and malignant tissue,Gastroenterology,2000,118, 398-399.
8. 闫循领,董瑞新,王秋国等,结肠癌病人几种细胞的 Raman 光谱,光谱学与光谱分析,2003,23(6), 1129-1131。
9. Boustany NN, Crawford JM, Manoharan R, et al. Analysis of nucleotides and aromatic amino acids in normal and neoplastic colon mucosa by ultraviolet reasonaree raman spectroscopy, Lab Invest,1999,79(10), 1201-1214.
10. R.H.Sharon, B.C.William, K.B.Andre, et al, cancer lett, 1996,35,110.
11. Lorinez A, Haddad D, Naik R, et al. Raman spectroscopy for neoplastic tissue differentiation:a pilot study, J Pediatr Surg , 2004, 396, 953-956.
12. M.Gniadecka, H.C.Wulf, N.Mortensen, et al, Diagnosis of Basal Cell Carcinoma by Raman Spectroscopy, Journal of Raman Spectroscopy, 1997, 28, 125-129.
13. Gniadecka M, Philipsen PA, Sigurdsson S, et al.Melanoma diagnosis by Raman spectroscopy and neural networks:structure alterations in proteins and lipids in mtact cancer tissue,J Invest Dermatol,2004,122(20), 443-449.
14. A.Mizuno, H.Katajima, K.Kawauchi, et al, Near-infrared Fourier transform Raman spectroscopic study of human brain tissues, Journal of Raman Spectroscopy , 1994, 25, 25-29.
15. Koljenovic S, Choo Smith LP, Bakker Schat TC, et al. Discriminating Vital tumor from necrotic tissue in human glioblastoma tissue amples by Raman spectroscopy, Lab Invest, 2002, 82(10), 1265-1277.
16. 李维红,徐怡庄, 吴瑾光等,肿瘤和正常组织的 FT-Raman 与 FT-IR 研究,光散射学报,1998,10, 144。
17. 佟倜,叶松,安利民等.鳞癌及其癌旁组织的共聚焦激光拉曼光谱分析,吉林大学学报(医学版), 2001,30(6), 813-815。
18. 张镇西,刘德敏,拉曼光谱在癌症诊断中的应用,世界医疗器械,2004,5, 12-14。
19. CA Xie, YQ Li,Confocal micro-Raman spectroscopy of single biological cells using optical trapping and shifted excitation difference techniques,Journal of Applied Physics, 2003, 93, 2982-2986.
20. CA Xie, YQ Li,Raman spectra and optical trapping of highly refractive and nontransparent particles,Applied Physics Letters, 2002, 81, 951-953.
21. CA Xie, MA Dinno, YQ Li,Near-infrared Raman spectroscopy of single optically trapped biological cells, Optics Letters, 2002, 27, 249-251.
2. Pappas Dimitri , Smith Benjamin w ., Winefordner, et al. Raman Spectroscopy in bioanalysis.Talanta,2000,51(1),131-144
3. Duindam JJ, Tibbe AGJ, Ramanauskaite R, et al. Confocal Raman microscopy on eye lenses and single living cells, Progress in Biophysics and Molecular Biology, 1996, 65 (1) , 192-195.
4. Schrader B, Dippel B, Erb I, et al. NIR Raman spectroscopy in medicine and biology: results and aspects. Journal of Molecular Structure, 1999,480-481.
5. 陆逸仙, 张岳灿, 诸君浩等, 脑部恶性肿瘤组织切片的红外光谱研究,中国临床神经科学,2000, 8(4),278-279。
6. 彭卿, 徐惰庄, 李维红等, 胃肠道正常组织与相应肿瘤组织结构 FTIR 光谱研究,光谱学与光谱分析,1998,8(5), 528-531。
7. Fabian H, Jackson M, Murphy L, et al. A comparative infrared spectroscopic study of human breast tumors and breast tumor cell xenografts ,Biospectroscopy , 1995, 1(1), 37-45.
8. GAO Xiao-ling, Butler Ian S, Kremer Richard, A Novel Model of Assessment of Medical effect and Mechanisms of Anticancer DrugaRaman Spectroscopy, Acta Laser Biology Sinica, 1998,7(1) ,22.
9. SUN Chuan-wen , XU Yi-zhuang , SUN Kai-hua et al,A study of the diagnosis of salivary gland tumors by means of mid infrared optical fiber technique,Spectroscopy and Spectral Analysis, 1996, 16(5), 22.
10. 许以明, 张志义, 张伟, 竹红菌素以及其衍生物对脂质体空间结构的微观光敏损伤的Raman光谱特征, 中国科学C, 1998, 28(5), 417-419。
11. 许以明, 杨红英, 张志义, 竹红菌乙素敏化的人红细胞膜结构光损伤的Raman光谱特征, 中国科学C, 1999, 29(2), 138-140。
12. 许以明, 张志义, 徐国瑞, 治癌药物YHPD对DNA光敏损伤的激光拉曼光谱研究, 科学通报, 1989, 34(19), 1500-1502。
13. Li Wei-hong , XU Yi-zhuang , WENG Shi-fu, et al, FT-Raman and FTIR studies on the Normal and Maligant Tissues,Chinese Journal of Light Scattering, 1998, 10(3), 114-116.
14. Nicholas Stone , Catherine Kendall , Neil Shepherd et al. Near-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancers ,Journal of Raman Spectroscopy , 2002 , 33(7), 564-573.
15. Chang-an Xie ,Yong-qing Li, Confocal biological cell using optical trapping and shifted excitation difference techniques, Journal of Applied Physics, 2003, 93(5), 2982-2986.
16. Chang-an Xie , Yong-qing Li , Wei Tang , et al, Study of dynamical process of heat denaturation in optically trapped single microorganisms by near-infrared Raman spectroscopy, Journal of Applied Physics, 2003, 94(9), 6138-6142.
17. Chang-an Xie, Mumtaz Dinno, Yong-qing Li , Near-infrared Raman spectroscopy of single optically trapped biological cell. Optics Letters, 2002, 27(4), 249-251.
18.A. Ashkin, J. M. Dziedzic, J. E. Bjorkholm, et al, Observation of a single-beam gradient force optical trap for dielectric particles. Optics Letters, 1986, 11(5), 288-290.
19. Chang-an Xie , Yong-qing Li, Raman spectra and optical trapping of highly refractive and nontransparent particles. Applied Physics Letters, 2002, 81(6), 951-953.
20. 朱贵运,《激光拉曼光谱分析》,科学出版社,1991 年。
21. 陆同兴,路轶群,《激光光谱技术原理及应用》,中国科学技术大学出版社, 1999 年。
22. 郑顺旋,《激光拉曼光谱学》,上海科学技术出版社, 1985 年。
23. 赵南明,周海梦,《生物物理》, 高等教育出版社,施普林格出版社, 2000年。
24. P.R.Carey. Biochemical Applications of Raman and Resonance Raman Spectroscopics(1982)Academic Press,New York.
25. A.T.Tu,Raman Spectroscopy in Biology: Principles and Applications(1982). John Wiley&Sons , Inc New York.
26. 汪兆平,韩和相,李国华,拉曼光谱在癌症诊断中的应用,光散射学报,2000,11(4), 398-405
27. 余国滔,拉曼光谱在医学上的应用,光谱学与光谱学分析,1996, 16(8), 113-114。
28. Yao Hui-Lu, Wang Gui-Wen, HeBi-Juan et al. Study of Raman Spectra of single blood cells, Journal of Jinan University, 2005(4), 49-51.
29. 司徒镇强, 吴军正, 《细胞培养》(修订版),世界图书出版社, 2004 年。
30. Nicholas Stone, Catherine Kendall, Jenny Smith,et al, Raman spectroscopy for identification of epithelial cancers, Faraday Discuss. 2004,126-157.
31. 唐伟跃,王杰芳,徐平,胃癌组织拉曼光谱的研究,激光杂志, 2004, 25(1), 82-83。
32. M.S.Feld, R.Manoharan, J.Salenlus, et al, Detection and characterization of human tissue lesions with near-infrared Raman spectroscopy, Advances in Fluorescence Sensing Technology II,95,2 ,99-104,
33. YAN Xun-ling,DONG Rui-xin,WANG Qin-guo,Raman Spectra of Cell from Breast Cancer Patients,Spectroscopy and Spectral Analysis,2005,25(1), 58-61.
34. 汤钊猷,《现代肿瘤学》(第二版), 复旦大学出版社,2002 年。
35. 郭萍,易光辉,熊平等,癌症患者血清的激光拉曼光谱,光谱学与光谱学分析,2000,20(6), 844-846。
36. 存义,左健,紫外拉曼散射及其应用,物理,1999,28(4), 206-209。
37. 于世林,《波谱分析法》,重庆大学出版社,1991 年。
38. 彭燕,林三仁,血清自体荧光光谱检测诊断胃癌的初步研究,泸州医学院学报,1997, 20(1), 56-57。
39. 刘英俊, 侯晓华, 新的光学技术在内镜早期诊断胃肠道癌前病变中的作用, 临床消化病杂志, 2002, 3, 123-126。
40. 刘林森, 21 世纪的医学, 百科知识, 2003, 5, 14-15。
1. Mahadevan JA,Mitchell MF,Ramanujam N,et al,Near-infrared Raman spectroscopy for in vitro detection of cervical precancers,Photochem Photobiol, 1998, 68, 123-132.
2. Mahadevan JA,Mitchell MF,Ramanujam N,et al.Development of a fiber optic probe to measure NIR Raman spectra of cervical tissue in vivo, Photochem Photobiol, 1998,68, 427-431.
3. 姚淑霞,赵元黎,张录等,乳腺组织切片的拉曼光谱研究,河南预防医学杂志 2004,15(3), 132-134。
4. Zhao Yuan-Li, Lu Jing, Shen Pei-Hong, et al, Study of Laman Spectrum of Galactophore Tumour, Laser &Infrared, 2004, 34(6), 502-504.
5. Kendall C, Stone N, Shepherd, et al. Raman spectroscopy, a patential tool for the objective identification and classification of neoplasia in Barrett’s oesophagus, J Pathol, 2003 , 200(5), 602-609.
6. 凌晓峰,李维红,宋苑苑等, 胃癌组织的拉曼光谱初探.光谱学与光谱分析,2000,20, 692-693。
7. Xiao-feng Ling,Yuan-yuan Song ,Roger D,et al,Fourier trans-form Raman spectra can separate most normal and malignant tissue,Gastroenterology,2000,118, 398-399.
8. 闫循领,董瑞新,王秋国等,结肠癌病人几种细胞的 Raman 光谱,光谱学与光谱分析,2003,23(6), 1129-1131。
9. Boustany NN, Crawford JM, Manoharan R, et al. Analysis of nucleotides and aromatic amino acids in normal and neoplastic colon mucosa by ultraviolet reasonaree raman spectroscopy, Lab Invest,1999,79(10), 1201-1214.
10. R.H.Sharon, B.C.William, K.B.Andre, et al, cancer lett, 1996,35,110.
11. Lorinez A, Haddad D, Naik R, et al. Raman spectroscopy for neoplastic tissue differentiation:a pilot study, J Pediatr Surg , 2004, 396, 953-956.
12. M.Gniadecka, H.C.Wulf, N.Mortensen, et al, Diagnosis of Basal Cell Carcinoma by Raman Spectroscopy, Journal of Raman Spectroscopy, 1997, 28, 125-129.
13. Gniadecka M, Philipsen PA, Sigurdsson S, et al.Melanoma diagnosis by Raman spectroscopy and neural networks:structure alterations in proteins and lipids in mtact cancer tissue,J Invest Dermatol,2004,122(20), 443-449.
14. A.Mizuno, H.Katajima, K.Kawauchi, et al, Near-infrared Fourier transform Raman spectroscopic study of human brain tissues, Journal of Raman Spectroscopy , 1994, 25, 25-29.
15. Koljenovic S, Choo Smith LP, Bakker Schat TC, et al. Discriminating Vital tumor from necrotic tissue in human glioblastoma tissue amples by Raman spectroscopy, Lab Invest, 2002, 82(10), 1265-1277.
16. 李维红,徐怡庄, 吴瑾光等,肿瘤和正常组织的 FT-Raman 与 FT-IR 研究,光散射学报,1998,10, 144。
17. 佟倜,叶松,安利民等.鳞癌及其癌旁组织的共聚焦激光拉曼光谱分析,吉林大学学报(医学版), 2001,30(6), 813-815。
18. 张镇西,刘德敏,拉曼光谱在癌症诊断中的应用,世界医疗器械,2004,5, 12-14。
19. CA Xie, YQ Li,Confocal micro-Raman spectroscopy of single biological cells using optical trapping and shifted excitation difference techniques,Journal of Applied Physics, 2003, 93, 2982-2986.
20. CA Xie, YQ Li,Raman spectra and optical trapping of highly refractive and nontransparent particles,Applied Physics Letters, 2002, 81, 951-953.
21. CA Xie, MA Dinno, YQ Li,Near-infrared Raman spectroscopy of single optically trapped biological cells, Optics Letters, 2002, 27, 249-251.