簡易檢索 / 詳目顯示

研究生: 李宜庭
論文名稱: 人體揮發性有機物及飲食導致呼氣丙酮變化之研究
An Investigation on Volatile Organic Compounds from Human Body and Diet Influence on Breath Acetone
指導教授: 呂家榮
Lu, Chia-Jung
學位類別: 碩士
Master
系所名稱: 化學系
Department of Chemistry
論文出版年: 2020
畢業學年度: 108
語文別: 中文
論文頁數: 86
中文關鍵詞: 人體揮發性有機物呼氣丙酮micro-GC非侵入式檢測
英文關鍵詞: human VOCs, breath acetone, micro-GC, non-invasive test
DOI URL: http://doi.org/10.6345/NTNU202000870
論文種類: 學術論文
相關次數: 點閱:170下載:0
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 人體的代謝物一定程度上的反應了人體的生體狀態,而近幾年來,越來越來多學者在人體的揮發性有機化合物(VOCs)上進行了研究,其中,呼出氣體的分析為大宗。由於它的非侵入性和方便採樣的特點,使它具有在不同領域下運用的潛能。
    本論文主要是研究並排除外界的干擾,開發人體VOCs的採樣方式,並利用自行組裝的前濃縮系統進行分析物的收集,以氣相層析質譜儀來進行分析。本研究鑑定出50種以上在人體呼出氣體中的化合物,同時配合環境的檢測,比對呼出氣體和環境氣體的相關性。發現呼出氣體中烯類、醇類、酮類和含硫化合物較環境濃度高,而其中含硫類化合物主要來自飲食。而烷類、醛類、酯類、含苯化合物則是環境中含量較高。而在手心皮膚表面能夠偵測出15種左右的的化合物。另外,利用實驗室之前開發的微氣相層析儀能夠快速簡便的達成特定化合物的連續分析,在本研究中用來檢測不同飲食對人體呼氣丙酮濃度隨時間變化的趨勢,對五位健康的受試者進行測試,發現呼出丙酮的濃度會隨著攝取的食物而發生改變,它能一定程度上的反應人體的代謝狀態。

    One’s metabolites can reflect the state of himself in certain degree. In recent year, more and more researchers have conducted the research in human’s volatile organic compounds (VOCs), especially in breath analysis. Because its non-invasion and convenience, make it full of the potential in different area.
    This thesis aims to study and eliminate the interference when collecting the breath sample, develop a new method to sample human’s VOCs and collect the analytes by self -assembly preconcentrate system, analyze by Gas chromatography–mass spectrometry. With the method in this research, over 50 compounds in human breath can be detected. Also, by detecting the environment air to compare with the breath component. In these compounds, alkanes, alcohols, and ketones are found with higher concentration in human breath, whilst alkanes, aldehydes, esters and aromatic compounds have higher concentration in environment. In hand palm VOCs analysis, about 15 compounds can be found. Meanwhile, the influence of food intake on breath acetone was analysis by lab-made micro-GC, which can be used to analyze certain compound continuously. By analyzing five healthy subjects, finds out that the concentration of breath acetone changes after the food intake, which means breath acetone can reflect the metabolism in human in a certain way.

    摘要 I Abstract II 目錄 III 表目錄 VI 圖目錄 VIII 第一章 緒論 1 1.1. 前言 1 1.2. 人體呼吸作用和其所在的環境 4 1.3. 環境中的揮發性有機物 8 1.4. 呼氣中揮發性有機物的來源與其生理意義 10 1.4.1. 氨 11 1.4.2. 丙酮 12 1.4.3. 異戊二烯 15 1.4.4. 異丙醇 16 1.5. 人體皮膚揮發性有機物 18 1.6. 人體揮發性有機物採集方式 20 第二章 實驗部分 22 2.1. 實驗藥品與器材 22 2.1.1. 實驗藥品 22 2.1.2. 實驗儀器與器材 23 2.2. 前濃縮系統 24 2.2.1. 前濃縮系統介紹和其改良 24 2.2.2. 六向閥狀態 25 2.2.3. 前濃縮管 27 2.2.4. 前濃縮系統使用流程 29 2.3. 氣相層析-質譜儀 30 2.4. 採樣方式 31 2.4.1. 呼氣中揮發性有機物 31 2.4.2. 手心揮發性有機物 35 第三章 結果與討論 39 3.1. 採樣參數 39 3.1.1. 吸附劑效果比較 39 3.1.2. 氣體來源 40 3.1.3. 採樣袋與玻璃集氣管 41 3.1.4. 玻璃集氣管回收率 43 3.2. 手心揮發性有機物 44 3.3. 環境背景與呼氣中揮發性有機物 48 3.4. 食物與呼出丙酮 69 第四章 結果 78 參考資料 80

    1. Dweik, R. A.; Amann, A., Exhaled breath analysis: the new frontier in medical testing. J. Breath Res. 2008, 2 (3), 030301.
    2. Taalman, R. D., Isoprene: background and issues. Toxicology 1996, 113 (1-3), 242-246.
    3. Haze, S.; Gozu, Y.; Nakamura, S.; Kohno, Y.; Sawano, K.; Ohta, H.; Yamazaki, K., 2-Nonenal newly found in human body odor tends to increase with aging. J. Invest. Dermatol. 2001, 116 (4), 520-524.
    4. Dormont, L.; Bessiere, J. M.; Cohuet, A., Human skin volatiles: a review. J. Chem. Ecol. 2013, 39 (5), 569-578.
    5. Wisthaler, A.; Weschler, C. J., Reactions of ozone with human skin lipids: sources of carbonyls, dicarbonyls, and hydroxycarbonyls in indoor air. Proc. Natl. Acad. Sci. U. S. A. 2010, 107 (15), 6568-6575.
    6. Pasini, E.; Corsetti, G.; Aquilani, R.; Romano, C.; Picca, A.; Calvani, R.; Dioguardi, F. S., Protein-Amino Acid Metabolism Disarrangements: The Hidden Enemy of Chronic Age-Related Conditions. Nutrients 2018, 10 (4).
    7. Hibbard, T.; Killard, A. J., Breath Ammonia Analysis: Clinical Application and Measurement. Crit. Rev. Anal. Chem. 2011, 41 (1), 21-35.
    8. Mürtz, M., Breath diagnostics using laser spectroscopy. Opt. Photonics News 2005, 16 (1), 30-35.
    9. Lindinger, W.; Hansel, A.; Jordan, A., On-line monitoring of volatile organic compounds at pptv levels by means of proton-transfer-reaction mass spectrometry (PTR-MS) medical applications, food control and environmental research. Int. J. Mass Spectrom. Ion Processes 1998, 173 (3), 191-241.
    10. Lindinger, W.; Hansel, A., Analysis of trace gases at ppb levels by proton transfer reaction mass spectrometry (PTR-MS). Plasma Sources Sci. Technol. 1997, 6 (2), 111-117.
    11. Warneke, C.; Kuczynski, J.; Hansel, A.; Jordan, A.; Vogel, W.; Lindinger, W., Proton transfer reaction mass spectrometry (PTR-MS): propanol in human breath. Int. J. Mass Spectrom. Ion Processes 1996, 154 (1-2), 61-70.
    12. Wang, Z.; Wang, C., Is breath acetone a biomarker of diabetes? A historical review on breath acetone measurements. J. Breath Res. 2013, 7 (3), 037109.
    13. Bajtarevic, A.; Ager, C.; Pienz, M.; Klieber, M.; Schwarz, K.; Ligor, M.; Ligor, T.; Filipiak, W.; Denz, H.; Fiegl, M., Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer 2009, 9 (1), 348-363.
    14. Allen, C. W.; Cox, A. N., Allen's astrophysical quantities. Springer Science & Business Media: New York, 2001.
    15. Haynes, W.; Lide, D.; Bruno, T., CRC Handbook of Chemistry and Physics, 97th edn, Vol. 2016–2017. CRC Press: 2017.
    16. Trends in Atmospheric Carbon Dioxide. https://www.esrl.noaa.gov/gmd/ccgg/trends/.
    17. Trends in Atmospheric Methane. https://www.esrl.noaa.gov/gmd/ccgg/trends_ch4/.
    18. UK Air DEFRA, Brief history of Monitoring Networks. https://uk-air.defra.gov.uk/networks/brief-history.
    19. Edwards, R. D.; Jurvelin, J.; Koistinen, K.; Saarela, K.; Jantunen, M., VOC source identification from personal and residential indoor, outdoor and workplace microenvironment samples in EXPOLIS-Helsinki, Finland. Atmos. Environ. 2001, 35 (28), 4829-4841.
    20. Wolkoff, P., Volatile organic compounds sources, measurements, emissions, and the impact on indoor air quality. Indoor air 1995, 5 (S3), 5-73.
    21. Brown, S.; Sim, M. R.; Abramson, M. J.; Gray, C. N., Concentrations of volatile organic compounds in indoor air–a review. Indoor air 1994, 4 (2), 123-134.
    22. Weschler, C. J., Reactions among indoor pollutants. Sci. World J. 2001, 1, 443-457.
    23. Fan, Z.; Lioy, P.; Weschler, C.; Fiedler, N.; Kipen, H.; Zhang, J., Ozone-initiated reactions with mixtures of volatile organic compounds under simulated indoor conditions. Environ. Sci. Technol. 2003, 37 (9), 1811-1821.
    24. Thatcher, T. L.; Layton, D. W., Deposition, resuspension, and penetration of particles within a residence. Atmos. Environ. 1995, 29 (13), 1487-1497.
    25. Xu, Y.; Liu, Z.; Park, J.; Clausen, P. A.; Benning, J. L.; Little, J. C., Measuring and predicting the emission rate of phthalate plasticizer from vinyl flooring in a specially-designed chamber. Environ. Sci. Technol. 2012, 46 (22), 12534-12541.
    26. Destaillats, H.; Maddalena, R. L.; Singer, B. C.; Hodgson, A. T.; Mckone, T. E., Indoor pollutants emitted by office equipment: A review of reported data and information needs. Atmos. Environ. 2008, 42 (7), 1371-1388.
    27. Phillips, M.; Greenberg, J.; Awad, J., Metabolic and environmental origins of volatile organic compounds in breath. J. Clin. Pathol. 1994, 47 (11), 1052-1053.
    28. Voet, D.; Voet, J. G.; Pratt, C. W., Fundamentals of biochemistry: life at the molecular level. New Jersey, 2013.
    29. Ruzsanyi, V.; Peter Kalapos, M., Breath acetone as a potential marker in clinical practice. J. Breath Res. 2017, 11 (2), 024002.
    30. Laffel, L., Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes/Metab. Res. Rev. 1999, 15 (6), 412-426.
    31. Mohamed, E. I.; Linder, R.; Perriello, G.; Di, N. D.; Pöppl, S.; De, A. L., Predicting Type 2 diabetes using an electronic nose-based artificial neural network analysis. Diabetes, Nutr. Metab. 2002, 15 (4), 215-221.
    32. Rydosz, A., A negative correlation between blood glucose and acetone measured in healthy and type 1 diabetes mellitus patient breath. J. Diabetes Sci. Technol. 2015, 9 (4), 881-884.
    33. Taucher, J.; Hansel, A.; Jordan, A.; Fall, R.; Futrell, J. H.; Lindinger, W., Detection of isoprene in expired air from human subjects using proton‐transfer‐reaction mass spectrometry. Rapid Commun. Mass Spectrom. 1997, 11 (11), 1230-1234.
    34. Diskin, A. M.; Španěl, P.; Smith, D., Time variation of ammonia, acetone, isoprene and ethanol in breath: a quantitative SIFT-MS study over 30 days. Physiol. Meas. 2003, 24 (1), 107-119.
    35. Salerno-Kennedy, R.; Cashman, K. D., Potential applications of breath isoprene as a biomarker in modern medicine: a concise overview. Wien. Klin. Wochenschr. 2005, 117 (5-6), 180-186.
    36. Stone, B. G.; Besse, T. J.; Duane, W. C.; Dean Evans, C.; Demaster, E. G., Effect of regulating cholesterol biosynthesis on breath isoprene excretion in men. Lipids. 1993, 28 (8), 705-708.
    37. Euler, D. E.; Dave, S. J.; Guo, H., Effect of cigarette smoking on pentane excretion in alveolar breath. Clin. Chem. 1996, 42 (2), 303-308.
    38. Cailleux, A.; Allain, P., Isoprene and sleep. Life Sci. 1989, 44 (24), 1877-1880.
    39. Rao, K., The significance of the cholesterol biosynthetic pathway in cell growth and carcinogenesis. Anticancer Res. 1995, 15 (2), 309-314.
    40. Rieder, J.; Lirk, P.; Ebenbichler, C.; Gruber, G.; Prazeller, P.; Lindinger, W.; Amann, A., Analysis of volatile organic compounds: possible applications in metabolic disorders and cancer screening. Wien. Klin. Wochenschr. 2001, 113 (5-6), 181-185.
    41. Jones, A. E.; Summers, R. L., Detection of isopropyl alcohol in a patient with diabetic ketoacidosis. J. Emerg. Med. 2000, 19 (2), 165-168.
    42. Dwyer, J. B.; Tamama, K., Ketoacidosis and trace amounts of isopropanol in a chronic alcoholic patient. Clin. Chim. Acta 2013, 415, 245-249.
    43. Palmiere, C.; Sporkert, F.; Werner, D.; Bardy, D.; Augsburger, M.; Mangin, P., Blood, urine and vitreous isopropyl alcohol as biochemical markers in forensic investigations. Leg.Med. 2012, 14 (1), 17-20.
    44. Platteborze, P. L.; Rainey, P. M.; Baird, G. S., Ketoacidosis with unexpected serum isopropyl alcohol. Clin. Chem. 2011, 57 (10), 1361-1364.
    45. Li, W.; Liu, Y.; Liu, Y.; Cheng, S.; Duan, Y., Exhaled isopropanol: new potential biomarker in diabetic breathomics and its metabolic correlations with acetone. RSC Adv. 2017, 7 (28), 17480-17488.
    46. Chien, P. J.; Suzuki, T.; Tsujii, M.; Ye, M.; Minami, I.; Toda, K.; Otsuka, H.; Toma, K.; Arakawa, T.; Araki, K.; Iwasaki, Y.; Shinada, K.; Ogawa, Y.; Mitsubayashi, K., Biochemical Gas Sensors (Biosniffers) Using Forward and Reverse Reactions of Secondary Alcohol Dehydrogenase for Breath Isopropanol and Acetone as Potential Volatile Biomarkers of Diabetes Mellitus. Anal. Chem. 2017, 89 (22), 12261-12268.
    47. Goldsmith, L. A., Physiology, biochemistry, and molecular biology of the skin. Oxford University Press: New York, 1991; Vol. 2.
    48. Bolognia, J.; Jorizzo, J.; Schaffer, J., Dermatology. Elsevier Saunders: London, 2012.
    49. Labows, J. N., Perspectives on axillary odor. J. Soc. Cosmet. Chem 1982, 34, 193-202.
    50. Van Smeden, J.; Janssens, M.; Gooris, G. S.; Bouwstra, J. A., The important role of stratum corneum lipids for the cutaneous barrier function. BBA-MOL.CELL BIOL.L. 2014, 1841 (3), 295-313.
    51. Wang, Q.; Liu, X.; Jia, X., Progress in research work with respect to analysis method for composition of skin lipids. China Surfactant Deterg. Cosmet. 2014, 44, 226-230.
    52. Lawal, O.; Ahmed, W. M.; Nijsen, T. M. E.; Goodacre, R.; Fowler, S. J., Exhaled breath analysis: a review of 'breath-taking' methods for off-line analysis. Metabolomics 2017, 13 (10), 110-115.
    53. Lu, C. J.; Zellers, E. T., Multi-adsorbent preconcentration/focusing module for portable-GC/microsensor-array analysis of complex vapor mixtures. Analyst 2002, 127 (8), 1061-1068.
    54. Jian, R. S.; Sung, L. Y.; Lu, C. J., Measuring real-time concentration trends of individual VOC in an elementary school using a sub-ppb detection μGC and a single GC–MS analysis. Chemosphere 2014, 99, 261-266.
    55. Phillips, M.; Cataneo, R. N.; Greenberg, J.; Gunawardena, R.; Naidu, A.; Rahbari-Oskoui, F., Effect of age on the breath methylated alkane contour, a display of apparent new markers of oxidative stress. J. Lab. Clin. Med. 2000, 136 (3), 243-249.
    56. Fruekilde, P.; Hjorth, J.; Jensen, N.; Kotzias, D.; Larsen, B., Ozonolysis at vegetation surfaces: a source of acetone, 4-oxopentanal, 6-methyl-5-hepten-2-one, and geranyl acetone in the troposphere. Atmos. Environ. 1998, 32 (11), 1893-1902.
    57. Wells, J.; Morrison, G. C.; Coleman, B. K., Kinetics and reaction products of ozone and surface-bound squalene. J. ASTM Int. 2008, 5 (7), 1-12.
    58. Fujisaki, M.; Endo, Y.; Fujimoto, K., Retardation of volatile aldehyde formation in the exhaust of frying oil by heating under low oxygen atmospheres. J. Am. Oil Chem. Soc. 2002, 79 (9), 909-914.
    59. Frankel, E., Lipid oxidation. Prog. Lipid Res. 1980, 19 (1-2), 1-22.
    60. Dibble, T. S., A quantum chemical study of the C− C bond fission pathways of alkoxy radicals formed following OH addition to isoprene. J. Phys. Chem. 1999, 103 (42), 8559-8565.
    61. Poli, D.; Carbognani, P.; Corradi, M.; Goldoni, M.; Acampa, O.; Balbi, B.; Bianchi, L.; Rusca, M.; Mutti, A., Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study. Respir. Res. 2005, 6, 71-80.
    62. Miyazawa, M.; Shindo, M.; Shimada, T., Metabolism of (+)-and (−)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Drug Metab. Dispos. 2002, 30 (5), 602-607.
    63. Frye, R. F.; Zgheib, N. K.; Matzke, G. R.; Chaves‐Gnecco, D.; Rabinovitz, M.; Shaikh, O. S.; Branch, R. A., Liver disease selectively modulates cytochrome P450–mediated metabolism. Clin. Pharmacol. Ther. 2006, 80 (3), 235-245.
    64. Mcdonald, J. D.; Zielinska, B.; Fujita, E. M.; Sagebiel, J. C.; Chow, J. C.; Watson, J. G., Fine particle and gaseous emission rates from residential wood combustion. Environ. Sci. Technol. 2000, 34 (11), 2080-2091.
    65. Salthammer, T.; Uhde, E., Organic indoor air pollutants: Occurrence, measurement, evaluation. John Wiley & Sons: Weinheim, 2009.
    66. Weschler, C. J.; Hodgson, A. T.; Wooley, J. D., Indoor chemistry: ozone, volatile organic compounds, and carpets. Environ. Sci. Technol. 1992, 26 (12), 2371-2377.
    67. Ruzsanyi, V.; Peter Kalapos, M.; Schmidl, C.; Karall, D.; Scholl-Burgi, S.; Baumann, M., Breath profiles of children on ketogenic therapy. J. Breath Res. 2018, 12 (3), 036021.
    68. Galassetti, P. R.; Novak, B.; Nemet, D.; Rose-Gottron, C.; Cooper, D. M.; Meinardi, S.; Newcomb, R.; Zaldivar, F.; Blake, D. R., Breath ethanol and acetone as indicators of serum glucose levels: an initial report. Diabetes Technol. Ther. 2005, 7 (1), 115-123.
    69. Van Den Velde, S.; Quirynen, M.; Van Steenberghe, D., Halitosis associated volatiles in breath of healthy subjects. J. Chromatogr. B 2007, 853 (1-2), 54-61.
    70. Jiang, L.; Shen, J.; Li, H.; Wang, Q.; Shen, X., Effects of volatile organic compounds released by different decorative particleboards on indoor air quality. BioResources 2018, 13 (4), 7595-7605.
    71. Taucher, J.; Hansel, A.; Jordan, A.; Lindinger, W., Analysis of compounds in human breath after ingestion of garlic using proton-transfer-reaction mass spectrometry. J. Agric. Food Chem. 1996, 44 (12), 3778-3782.
    72. Votto, A. P.; Domingues, B. S.; De Souza, M. M.; Da Silva Júnior, F. M.; Caldas, S. S.; Filgueira, D.; Clementin, R. M.; Primel, E. G.; Vallochi, A. L.; Furlong, E. B., Toxicity mechanisms of onion (Allium cepa) extracts and compounds in multidrug resistant erythroleukemic cell line. Biol. Res. 2010, 43 (4), 429-437.
    73. Puri, B.; Hall, A., Phytochemical dictionary: a handbook of bioactive compounds from plants. CRC press: London, 1998.
    74. Tamaki, K.; Sonoki, S.; Tamaki, T.; Ehara, K., Measurement of odour afterin vitroorin vivoingestion of raw or heated garlic, using electronic nose, gas chromatography and sensory analysis. Int. J. Food Sci. Technol. 2008, 43 (1), 130-139.
    75. Ludwig, I. A.; Sánchez, L.; De Peña, M. P.; Cid, C., Contribution of volatile compounds to the antioxidant capacity of coffee. Food Res. Int. 2014, 61, 67-74.
    76. Dorsey, A., Toxicological profile for toluene. 2000.
    77. Jordan, A.; Hansel, A.; Holzinger, R.; Lindinger, W., Acetonitrile and benzene in the breath of smokers and non-smokers investigated by proton transfer reaction mass spectrometry (PTR-MS). Int. J. Mass Spectrom. Ion Processes 1995, 148 (1-2), L1-L3.
    78. Beauchamp, J., Inhaled today, not gone tomorrow: pharmacokinetics and environmental exposure of volatiles in exhaled breath. J. Breath Res. 2011, 5 (3), 037103.
    79. Mitchell, G.; Kassovska-Bratinova, S.; Boukaftane, Y.; Robert, M.; Wang, S.; Ashmarina, L.; Lambert, M.; Lapierre, P.; Potier, E., Medical aspects of ketone body metabolism. Clin. Invest. Med. 1995, 18 (3), 193-216.

    無法下載圖示 本全文未授權公開
    QR CODE