質譜分析技術簡介
 

本實驗室(國立清華大學化學系綠色(化學)質譜(分析)實驗室,Green Chemistry & Mass Spectrometry Analytical Laboratory,GMLab)成立於1988年,現址於新竹市光復路上國立清華大學化學館三樓及高能材料館的二樓。使用的質譜儀包括:氣相層析-四極柱質譜儀(GC-QMS)、氣相層析-離子阱串聯質譜儀(GC-ITMS/MS)、液相層析離子阱串聯質譜儀(LC-ITMS/MS)、氣相層析-高解析質譜儀(GC-HRMS )、氣相層析-同位素比質譜儀(GC-IRMS)、感應耦合電漿質譜儀(ICP-MS)、飛行時間二次離子質譜儀 (ToF-SIMS)。GMLab以發展質譜分析技術,探求綠色化學潔淨方法,建立完整品保/品管系統,以解決實際應用問題為研究導向的專業分析化學實驗室,善用分析化學研究於社會公益議題為本實驗室之特色。研究領域涵蓋環境、生物基質、材料。

  • 在環境方面:

於90年間開發GC-QMS方法分析環境樣品中戴奧辛,首先發現台南二仁溪[1]、台南安順氯鹼工廠[2]遭戴奧辛嚴重汙染,之後陸續研究民生用品,發現學童工藝課用的紙黏土[3]含高量的戴奧辛,台灣中部地區的多氯聯苯毒油[4]事件(發生在70年代),主要元凶為戴奧辛。90年後期配合政府以焚化為主的垃圾處理政策,開發GC-HRMS方法分析環境樣品中戴奧辛,研究垃圾焚化廠之飛灰[5]、排氣[6]和周界空氣[7]中的戴奧辛。近年則擴充到分析多氯聯苯、多溴聯苯醚等其他持久性有機污染物(POPs)。

2000年起開始系統性的研究工業園區(傳統及科學)環境污染物對鄰近地區之影響,建立社區環境監測網,輔以LC-ITMS/MS分析水中之環境荷爾蒙(鄰苯二甲酸酯類、界面活性劑類),ICP-MS分析周界空氣、放流水中重金屬找出鎢、鎵、銦等標物種[8-10],結合電子鼻11和軟性游離法[12,13]GC-ITMS/MS方法分析異臭味,找出環境惡化原因,協助改善居民生活品質。2004年起開始開發GC-IRMS化合物別安定性同位素分析方法(CSIA),用13C/12C(‰)鑑識環境污染物之來源及關聯性,以釐清責任,諸如:廢棄有機溶劑、港口底泥中PAHs、地下水中有機氯溶劑等[14]。最近研究包括公共場所室內空氣品質調查、矽晶圓廠/面板廠的製程氣體及氣生分子污染物(AMC)偵錯,以及開發新穎奈米材料,配合質譜測定,達到綠色分析化學之目的。

  • 在生物基質方面:

在食品方面,於90年間開發GC-ECD定量GC-QMS確認之方法,分析食品中農藥及多氯聯苯,如魚肉中多氯聯苯[15]、蔬菜中除蟲菊精[16]、魚肉中有機氯農藥及多氯聯苯[17]、牡蠣中有機氯農藥及多氯聯苯[18]、中草藥中有機氯農藥[19],2000年開始研發環境荷爾蒙分析方法,應用到抽檢中、西式速食品中戴奧辛量,總膳食研究估算台灣居民從食品中攝入戴奧辛及戴奧辛類多氯聯苯量[20]。MALDI-MS以研究小分子為主,建立降低前處理時間達到快速分析之分析方法,使用第一代的MALDI-MS和紫質基質,可以同時定量分析豬肉中31種抗生素,使用簡易衍生法以進行確認分析[21],擴大紫質基質的應用到同時定量粉末、錠劑、膠曩等型態之多種水溶性維他命[22]。LC-ESI/MS也以研究小分子為主,建立摻雜/作假之黑心食品之分析方法,應用到鮮(羊)乳中摻雜(牛)乳[23],鮮(牛)乳中摻雜乳粉,以油脂判定素食加工食品中摻雜動物性成分、以脂肪判定魚油食品中摻雜植物油等定量分析為主。近年來開始研發GC-IRMS測定13C/12C(‰)、15N/14N(‰),以鑑定食品摻雜/作假之方法,如蜂蜜之摻糖、茶葉之作假等,為產源證明和履歷追蹤提供科學的依據。俗話說….民以食為天,吃甚麼像甚麼,藥補不如食補….,說明安全、營養、美味之食品,是健康生活的基本要件,食品安全一直是重要公共議題,嬰幼兒食品更是為人父母關心的焦點。

於1999年比利時禽畜產品遭戴奧辛污染事件時,我們即開始從事食品中戴奧辛分析,從2000年起和環境品質文教基金會合作,每年調查市售鮮奶(嬰幼兒主要的戴奧辛攝入來源)戴奧辛含量,公佈檢測報告結果,以實測數據呼籲政府儘速實施乳品戴奧辛含量管制標準。2005和2006年抽檢市售魚油和魚肝油中戴奧辛,26件中有6件超出標準。2006年抽檢市售33種家用清潔劑中壬基酚類環境荷爾蒙物質含量,抽樣33件市售知名品牌,有11件超過歐盟標準。針對國際健康關切日深的常見的環境荷爾蒙-雙酚A進行調查。2007年抽檢市售國內市售19種PC嬰幼兒奶瓶中雙酚A的溶出濃度,2件超過歐盟標準。2008年抽檢市售進口與國產牛肉中戴奧辛,16件牛肉樣品,包括牛條肉、牛肋條、沙朗、及牛排,皆符合標準,發現來自不同國家的牛肉中戴奧辛濃度,存在明顯差異。經由平行監測調查,透過媒體公布結果,提供國際管制現況,民眾引為採購參考,所凝聚之共識及壓力,足以促使政府訂法及廠商改善,如衛生署於2006年4月間公告「食品中戴奧辛處理規範」例,為保障國民食品安全的高成效手段之一。

在藥物方面,以台灣地區之濫用藥物為研究對象,研發綠色前處理技術輔以GC-MS測定,如分析檳榔中(甲基)安非他命[24]、尿液中(甲基)安非他命[25、26]、尿液中(甲基)安非他命[27]、室內空氣中大麻菸的指標物種[28]。近年來,開始研發GC-IRMS測定13C/12C(‰)、15N/14N(‰),以為鑑定(甲基)安非他命濫用藥物來源、製程、使用者關聯性之方法[29],為防制濫用藥物提供嶄新的科學手段。在生醫方面,以建立ToF-SIMS分析方法提供縱深剖析、化學影像等資訊,如血袋(屬醫療器材)中鄰苯甲酸酯的移動和溶出[30],染髮劑在人髮(屬硬組織)中的擴散情況[31],評估睡眠剝奪對肝臟(屬軟組織)的影響[32]。最近開始以線上前處理ICP-MS測定方法,研究奈米粒子在皮膚及細胞中的宿命。

  • 在材料方面:

以電子材料/元件、光電半導體、顯示器材料、高分子材料、及奈米材料為主,包括進料分析、製程改善、偵錯分析等。90年代主要以扇形磁場式SIMS研究電子材料/元件[33-35, 39] 、光電半導體材料/元件[38]、高分子[40],也建立階段性熱裂解GC-QMS方法,研究高分子的熱穩定性[36,37]。2003年起,以建立ToF-SIMS分析方法為主,研究碳奈米管柱表面積覆聚苯胺薄膜的反應機制[41]、鉬酸鉍奈米桿的生成[42]、雙水合物醋酸鋅的熱裂解[43]、有機發光二極體的內部元素擴散對發光效率之影響[44]、量子點的原子組成分布[45]、塗布ZnO奈米粒子抗菌壁紙的功能[46]、古文物(西漢百官印)研究等[47]。

  • 展望:

質譜可提供民生議題、法規管制、研發及生產新興材料等,所需的低偵測極限與高確認能力之雙重要求,輔以簡便之綠色前處理方法,質譜分析的應用,勢必越發廣泛。結合質譜開發新穎先進的綠色分析化學方法,以解決實際問題,協助公共議題的化學分析工作,會是GMLab持續努力的目標。

參考文獻:

1.       Ling-YC Soong-DK Lee-MKPCDD/DFs and Coplanar PCBs in Sediment and Fish Samples from the Er-Jen River in TaiwanCHEMOSPHEREAugust 1995, Vol 31, Iss 3, pp 2863-2872.

2.       Soong-DK Hou-PCC Ling-YCDioxins in Soil and Fish Samples from a Waste Pentachlorophenol Manufacturing PlantJOURNAL OF THE CHINESE CHEMICAL SOCIETYNovember 1997, Vol 44, Iss 5, pp 545-552.

3.       Soong-DK Ling-YCDetermination of PCDD/DFs in Paper Clay Samples CHEMOSPHEREMay 1995, Vol 30, Iss 9, pp 1799-1803.

4.       Soong-DK Ling-YCReassessment of PCDD/DFs and Co-PCBs Toxicity in Contaminated Rice-Bran Oil Responsible for the Disease Yu-ChengCHEMOSPHEREMarch 1997, Vol 34, Iss 5-7, pp 1579-1586.

5.       Ling-YC Hou-PCCA Taiwanese Study of 2,3,7,8-substituted PCDD/DFs and Coplanar PCBs in Fly ashes from IncineratorsJOURNAL OF HAZARDOUS MATERIALS February 1998 Vol 58, 83-91.

6.       廢棄物焚化爐有害空氣污染物及惡臭物質管理輔導計畫研究報告,桃園縣政府環境保護局,2003-2005

7.       Pai-Sheng Cheng, Ming-Sheng Hsu, Edward Ma, Ukai Chou, Yong-Chien Ling, Levels of PCDD/Fs in ambient air and soil in the vicinity of a municipal solid waste incinerator in HsinChu, Chemosphere 2003, 52(9), 1389-1396.

8.       科學工業園區污(雨)水下水道系統內污染物氣(臭、異)味探討計畫研究報告,新竹市政府環境保護局,2002

9.       新竹科學工業園區污水廠污泥乾燥焚化設施周界空氣及土壤中戴奧辛濃度資料之建立計畫研究報告,新竹科學工業園區管理局,2004

10.     新竹科學工業園區環境監測計畫品保查核工作計畫研究報告,新竹科學工業園區管理局,2007

11.    Shin-Hwa Tzing, Jia-Yaw Chang, Anil Ghule, Jia-Jiu Chang, Bertrand Lo, Yong-Chien Ling, A simple and rapid method for identifying the source of spilled oil using an electronic nose: Confirmation by gas chromatography with mass spectrometry, RAPID COMMUNICATIONS IN MASS SPECTROMETRY, August 2003, 17, 1873-1880.

12.    Shin-Hwa Tzing, Anil Ghule, Jia-Yaw Chang and Yong-Chien Ling, A Chemical Ionization of Substituted Naphthalenes using Tetrahydrofuran as a Reagent in Gas Chromatography with Ion Trap Mass Spectrometry, RAPID COMMUNICATIONS IN MASS SPECTROMETRY, March 2003, 17(8), 811-815.

13.    Shin-Hwa Tzing, Anil Ghule, Jia-Yaw Chang and Yong-Chien Ling, Selective adduct formation by furan chemical ionization reagent in gas chromatography ion trap mass spectrometry. Journal of Mass Spectrometry, April 2003, 38, 401-408.

14.    污染源同位素分析鑑識技術建立之研究及應用研究報告,環保署環境檢驗所,2005-2006

15.    Ling-YC Chang-MY Huang-IPMatrix Solid-Phase Dispersion Extraction and Gas-Chromatographic Screening of Polychlorinated-Biphenyls in FishJOURNAL OF CHROMATOGRAPHY AMay 1994, Vol 669, Iss 1-2, pp 119-124.

16.    Ling-YC Huang-IPMulti-Residue Matrix Solid-Phase Dispersion Method for the Determination of 6 Synthetic Pyrethroids in Vegetables Followed by Gas-Chromatography with Electron-Capture DetectionJOURNAL OF CHROMATOGRAPHY AMarch 1995, Vol 695, Iss 1, pp 75-82.

17.    Ling-YC Huang-IPMultiresidue-Matrix Solid-Phase Dispersion Method for Determining 16 Organochlorine Pesticides and Polychlorinated-Biphenyls in FishCHROMATOGRAPHIAMarch 1995, Vol 40, Iss 5-6, pp 259-266.

18.    Ling-YC Teng-HCSupercritical Fluid Extraction and Clean-up of Organochlorine Pesticides and Polychlorinated Biphenyls from MusselsJOURNAL OF CHROMATOGRAPHY ASeptember 1997, Vol 790, Iss 1-2, pp 153-160.

19.    Ling-YC Teng-HC Cartwright-C Supercritical fluid extraction and clean-up of organochlorine pesticides in Chinese herbal medicine JOURNAL OF CHROMATOGRAPHY AMarch 1999, 835(1-2), 145-157.

20.    Ming-Sheng Hsu, Kuang-Yi Hsu, Shih-Min Wang, Ukai Chou, Shih-Yun Chen, Nai-Chun Huang, Chia-Yi Liao, Tsae-Pyng Yu, Yong-Chien Ling, A total diet study to estimate PCDD/Fs and dioxin-like PCBs intake from food in Taiwan, Chemosphere, S65 – S70, April, 2007.

21.    Ling-YC Lin-LN Chen-YTQuantitative-Analysis of Antibiotics by Matrix-Assisted-Laser-Desorption/Ionization Time-of-Flight Mass-SpectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRYFebruary 1998, Vol 12, Iss 6, pp 317-327.

22.    Chen YT, Ling YC, Detection of Water-soluble Vitamins by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry using Porphyrin MatricesJournal of Mass Spectrometry, July 2002, 37(7), 716-730

23.    Chen RK, Chang LW, Chung YY, Lee MH, Ling YC , Quantification of cow milk adulteration in goat milk using high-performance liquid chromatography with electrospray ionization mass spectrometry, RAPID COMMUNICATIONS IN MASS SPECTROMETRY 18 (10): 1167-1171 2004..

24.    Wang-SM Ling-YC Tsai-LC Giang-YSHeadspace Sampling and Gas-Chromatographic Mass-Spectrometric Determination of Amphetamine and Methamphetamine in Betel, NovemberJOURNAL OF CHROMATOGRAPHY ANovember 1995, Vol 715, Iss 2, pp 325-331.

25.    Wang-SM Giang-YS Ling-YCSimultaneous supercritical fluid extraction and chemical derivatization for the gas chromatographic-isotope dilution mass spectrometric determination of amphetamine and methamphetamine in urine
JOURNAL OF CHROMATOGRAPHY B Au
gust 2001, 759: (1) 17-26.

26.    Tzing SH, Ghule A, Liu JY, Ling YC. On-line derivatization gas chromatography with furan chemical ionization tandem mass spectrometry for screening of amphetamines in urine. J. CHROMATOGRAPHY A. 1137 (1): 76-83 DEC 2006.

27.    Chou SL, Yang MH, Ling YC, Giang YS, Gas chromatography-isotope dilution mass spectrometry preceded by liquid-liquid extraction and chemical derivatization for the determination of ketamine and norketamine in urine, JOURNAL OF CHROMATOGRAPHY B 799 (1): 37-50 JAN 5 2004.

28.    Su-Lien Chou, Yong-Chien Ling, Mo-Hsiung Yang, Chung-Yen Pai, Determination of Δ9 -tetrahydrocannabinol in indoor air as an indicator of marijuana cigarette smoking using adsorbent sampling and in-injector thermal desorption gas chromatography–mass spectrometry, Analytica Chimica Acta 598, 103–109, 2007.

29.    疑似服用濫用藥物者尿液中(甲基)安非他命和愷它命之C-13/C-12N-15/N-14比值測定以為追踪來源參考用計畫報告,行政院衛生署管制藥品管理局,2007   

30.    Chen CY, Ghule AV, Chen WY, Wang CC, Chiang YS, Ling YC. Rapid identification of phthalates in blood bags and food packaging using ToF-SIMS, APPLIED SURFACE SCIENCE. 231-2: 447-451 Sp. Iss. SI, JUN 15 2004.

31.    Chen BJ, Lee PL, Chen WY, Mai FD, Ling YC, Hair Dye distribution in human hair by ToF SIMS, APPLIED SURFACE SCIENCE. 252-19: 6786-6788, JULY 30 2006.

32.    Chang, H. M.; Mai, F. D.; Wu, U. I.; Huang, Y. L.; Lan, C. T.; Ling, Y. C., Sleep Deprivation Predisposes Liver to Oxidative Stress and Phospholipid Damage – A Quantitative Molecular Imaging Study. Journal of Anatomy 2008, 212, 295-305,

33.    Liang-MK Ling-YCMicrostructural Dependence of Annealing Temperature in Magnetron-Sputtered Al-Si-Cu FilmsJOURNAL OF APPLIED PHYSICS September 1993, Vol 74, Iss 6, pp 3890-3898.

34.    Lin-YP Ling-YCSurface Study of Polymers by Static Secondary-Ion Mass-Spectrometry Using a Magnetic-Sector Mass-SpectrometerJOURNAL OF THE CHINESE CHEMICAL SOCIETYJune 1993, Vol 40, Iss 3, pp 229-240.

35.    Ling-YC Wang-JP Yeh-MH Liu-KS Lin-INSecondary-Ion Mass-Spectrometric Studies of SrTiO3, Buffering Effect on (Pb1-XLaX)(Zr1-YTiY)1-X/4O3 Thin-Films Prepared by Pulsed-Laser Deposition APPLIED PHYSICS LETTERSJanuary1995, Vol 66, Iss 2, pp 156-158.

36.    Tsai-CJ Perng-LH Ling-YCA Study of Thermal-Degradation of Poly(Aryl-Ether-Ether-Ketone) Using Stepwise Pyrolysis-Gas Chromatography Mass-SpectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRYNovember 1997, Vol 11, Iss 18, pp 1987-1995.

37.    Perng LH, Tsai CJ, Ling YC, Wang SD, Hsu CY, Thermal decomposition characteristics of poly[diethyl-2-(methacryloyloxy)ethyl phosphate] using thermogravimetric analysis/mass spectrometry, JOURNAL OF APPLIED POLYMER SCIENCE, July 2002, 85 (4): 821-830 JUL 25 2002.

38.    C.Y. Chiou, C.C. Wang, Y.C. Ling, C.I. ChiangSecondary Ion Mass Spectrometry Analysis of in Doped P-type GaN FilmsApp. Surf. Sci. January 2003, 203-204, 482-485.

39.    C.Y. Chen, Y.C. Ling, J.F. Hwang, J.H. Lee, M.L. Wen, M.C. Hwang, G.C. Lin, R.C. DengRound Robin Study of Chlorine, Sulfur and Carbon in  Copper Films from Taiwan SIMS UserApp. Surf. Sci. January 2003, 203-204, 461-464.

40.    Lin HC, Tsai IF, Yang ACM, Hsu MS, Ling YC, Chain diffusion and microstructure at a glassy-rubbery polymer interface by SIMS, MACROMOLECULES, April 2003, 36 (7): 2464-2474

41.    Chen WY, Chen CY, Hsu KY, Wang CC, Ling YC, Reaction monitoring of polyaniline film formation on carbon nanotubes with TOF-SIMS, APPLIED SURFACE SCIENCE 231-2: 845-849 Sp. Iss. SI, JUN 15 2004.

42.    Ghule AV, Chen CY, Mei FD, Ling YC, TOF-SIMS study of pyridine intercalated nanorods of bismuth molybdate, APPLIED SURFACE SCIENCE 231-2: 840-844 Sp. Iss. SI, JUN 15 2004.

43.    Ghule AV, Ghule K, Chen CY, Chen WY, Tzing SH, Chang H, Ling YC , In situ thermo-TOF-SIMS study of thermal decomposition of zinc acetate dehydrate, JOURNAL OF MASS SPECTROMETRY 39 (10): 1202-1208 OCT 2004.

44.    Chen WY, Ling YC, Chen BJ, Shih HH, Cheng CH, Diffusion study of multi-organic layers in OLEDs by ToF-SIMS, APPLIED SURFACE SCIENCE. APPLIED SURFACE SCIENCE. 252-19: 6594-6596, JULY 30, 2006.

45.    Chen WY, Ling YC, Chen BJ, Wang CC, Atomic distribution in quantum dots - a ToF-SIMS study. APPLIED SURFACE SCIENCE. 252-19: 7003-7005, JULY 30, 2006.

46.    Ghule K, Ghule A, Chen BJ, Ling YC. Preparation and characterization of ZnO nanoparticles coated paper and its antibacterial activity study. GREEN CHEMISTRY 8 (12): 1034-1041 Dec. 2006.

47.  Yin YS, Chen BJ, Ling YC, ToF-SIMS study of official seals from Han Dynasty, APPLIED SURFACE SCIENCE. 2008 in pres