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Highly precise and real-time measurements of 13CO2/12CO2 isotopic ratio in breath using a 2 μm diode laser

Sun Ming-Guo Ma Hong-Liang Liu Qiang Cao Zhen-Song Wang Gui-Shi Liu Kun Huang Yin-Bo Gao Xiao-Ming Rao Rui-Zhong

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Highly precise and real-time measurements of 13CO2/12CO2 isotopic ratio in breath using a 2 μm diode laser

Sun Ming-Guo, Ma Hong-Liang, Liu Qiang, Cao Zhen-Song, Wang Gui-Shi, Liu Kun, Huang Yin-Bo, Gao Xiao-Ming, Rao Rui-Zhong
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  • Real-time breath gas analysis with high accuracy, precision and time resolution, as a promising, non-invasive, fast and reliable tool, is important in medical diagnostics. Especially stable isotopologues of carbon dioxide is applied to multiple research areas including the diagnosis of gastrointestinal diseases. Helicobacter pylori (H. pylori) is one of the most frequent bacterial infectious diseases in human beings and is now recognized as one of the key risk factors for chronic gastritis, peptic ulcers, stomach cancer and lymphoma. In contrast to traditional invasive tests, the most reliable non-invasive method in the diagnosis of the H. pylori infection is considered to be 13C-urea breath test which is implemented by measuring the 13CO2/12CO2 isotope ratio in human breath. Tunable diode laser absorption spectroscopy (TDLAS) has the advantages of fast response, low drift, good gas selectivity and high detection sensitivity, and it is very convenient to develop a high precision, real-time and online measurement system. A precision laser spectrometer for the measurement of CO2 isotope abundance in human breath (with CO2 concentration of 4%-5%) or high concentration gas is designed and evaluated based on TDLAS technology. The spectrometer contains a novel compact dense-pattern multipass cell with a small volume of 280 cm3 and an effective optical path length of 26. 4 m. The cell is in conjunction with a fiber-coupled distributed feedback diode laser operating at 2.008 μm. Wavelength modulation spectroscopy approach is used. The mass flow, pressure and temperature of the cell are actively controlled, and able to keep long-term stability. The influence of laser power fluctuation is eliminated by fitting the baseline with cubic polynomial to normalize the raw spectrum. Moving window regression is used to remove the influence of frequency drift on measuring isotope abundance. The system measurement precision is improved by wavelet denosing and Kalman filtering. The experimental results demonstrate that moving window regression method not only extends the stability time of the system but also improves the measurement precision of isotope abundance well, the wavelet denoising improves the signal-to-noise ratio by 2 times that by the method of multi-spectral average, the stability time of the system is 100 s given by Allan variance, and the measurement precision of CO2 isotope ratio is 0. 067‰ after Kalman filtering. The use of small multi-pass cell and the default of denoising devices make the system more portable and improve the real-time and online measurement performance of the system. In addition to the measurement of 13CO2/12CO2 isotope ratio in human breath, by replacing different lasers, the spectrometer can also be used to measure trace gas concentration and the stable isotope abundance of many gas molecules in atmosphere. Therefore, the spectrometer will have broad applications in the areas of medical diagnosis, carbon cycle study and environmental monitoring.
      Corresponding author: Cao Zhen-Song, zscao@aiofm.ac.cn
    • Funds: Project supported by the National Key Research and Development Program of China (Grant Nos. 2016YFC0303900, 2017YFC0209700), the National Natural Science Foundation of China (Grant No. 41405022), the Youth Innovation Promotion Association of Chinese Academy of Sciences Foundation (Grant No. 2015264), and the Natural Science Foundation of the Higher Education Institutions of Anhui Province, China (Grant No. TSKJ2016B12).
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    Andreev S N, Mironchuk E S, Nikolaev I V, Ochkin V N, Spiridonov M V, Tskhai S N 2011 Appl. Phys. B 104 73

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    Worle K, Seichter F, Wilk A, Armacost C, Day T, Godejohann M, Wachter U, Vogt J, Radermacher P, Mizaikoff B 2013 Anal. Chem. 85 2697

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    Wang Y, Jiang J C, Hua L, Hou K Y, Xie Y Y, Chen P, Liu W, Li Q Y, Wang S, Li H Y 2016 Anal. Chem. 88 9047

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    Kosterev A A, Curl R F, Tittel F K, Gmachl C, Capasso F, Sivco D L, Baillargeon J N, Hutchinson A L, Cho A Y 2000 Appl. Opt. 39 4425

    [18]

    Erdelyi M, Richter D, Tittle F K 2002 Appl. Phys. B 75 289

    [19]

    Richter D, Wert B P, Fried A, Weibring P, Walega J G, White J W C, Vaughn B H, Tittel F K 2009 Opt. Lett. 34 172

    [20]

    Li X X, Xu L, Gao M G, Tong J J, Feng M C, Liu J G, Liu W Q 2015 Acta Phys. Sin. 64 024217 (in Chinese) [李相贤, 徐亮, 高闽光, 童晶晶, 冯明春, 刘建国, 刘文清 2015 物理学报 64 024217]

    [21]

    Liu K, Wang L, Tan T, Wang G S, Zhang W J, Chen W D, Gao X M 2015 Sensors and Actuators B 220 1000

    [22]

    Tanaka K, Tonokura K 2011 Appl. Phys. B 105 463

    [23]

    Hoang V D 2014 Trends Analyt. Chem. 62 144

    [24]

    Li Z B, Ma H L, Cao Z S, Sun M G, Huang Y B, Zhu W Y, Liu Q 2016 Acta Phys. Sin. 65 053301 (in Chinese) [李志彬, 马宏亮, 曹振松, 孙明国, 黄印博, 朱文越, 刘强 2016 物理学报 65 053301]

    [25]

    Wu T, Chen W D, Kerstel E, Fertein E, Gao X M, Koeth J, Robner K, Bruckner D 2010 Opt. Lett. 35 634

  • [1]

    Wang C J, Sahay P 2009 Sensors 9 8230

    [2]

    Wojtas J, Bielecki Z, Stacewicz T, Mikolajczyk J, Nowakowski M 2012 Opto-Electron. Rev. 20 26

    [3]

    Braden B, Lembcke B, Kuker W, Caspary W F 2007 Dig. Liver. Dis. 39 795

    [4]

    Logan R P H, Dill S, Bauer F E, Walker M M, Hirschl A M, Gummett P A, Good D, Mossi S 1991 Eur. J. Gastroenterol. Hepatol. 3 915

    [5]

    Cooper D E, Martinelli R U, Carlisle C B, Riris H, Bour D B, Menna R J 1993 Appl. Opt. 32 6727

    [6]

    Crosson E R, Ricci K N, Richman B A, Chilese F C, Owano T G, Provencal R A, Todd M W, Glasser J, Kachanov A A, Paldus B A, Spence T G, Zare R N 2002 Anal. Chem. 74 2003

    [7]

    Wahl E D H, Fidric B, Rella C, Koulikov S, Kharlamov B, Tan S, Kachanov A A, Richman B A, Crosson E R, Paldus B A, Kalaskar S, Bowling D R 2006 Isot. Environ. Health Stud. 42 21

    [8]

    Kasyutich V L, Martin P A, Holdsworth R J 2006 Appl. Phys. B 85 413

    [9]

    Mironchuk E S, Nikolaev I V, Ochkin V N, Rodionova S S, Spiridonov M V, Tskhai S N 2009 Quantum Electron. 39 388

    [10]

    Andreev S N, Mironchuk E S, Nikolaev I V, Ochkin V N, Spiridonov M V, Tskhai S N 2011 Appl. Phys. B 104 73

    [11]

    Worle K, Seichter F, Wilk A, Armacost C, Day T, Godejohann M, Wachter U, Vogt J, Radermacher P, Mizaikoff B 2013 Anal. Chem. 85 2697

    [12]

    Kääriäinen T J, Hietala E, Aikio R, Vasama H, Suopajärvi P, Richmond C, Manninen A 2016 Conference on Lasers and Electro-Optics:Applications and Technology paper ATu1O.1

    [13]

    Wang Y, Jiang J C, Hua L, Hou K Y, Xie Y Y, Chen P, Liu W, Li Q Y, Wang S, Li H Y 2016 Anal. Chem. 88 9047

    [14]

    Zhou Q H, Li E Y, Wang X, Gong Y L, Hua L, Wang W G, Qu T S, Li J H, Liu Y P, Wang C S, Li H Y 2014 Anal. Methods 6 698

    [15]

    Zhou C, Liu N W, He T B, Zhou S, Zhang L, Li J S 2017 Chin. J. Lasers 44 1111003 (in Chinese) [周超, 刘宁武, 何天博, 周胜, 张磊, 李劲松 2017 中国激光 44 1111003]

    [16]

    Gao Y W, Zhang Y J, Chen D, He Y, You K, Chen C, Liu W Q 2016 Acta Opt. Sin. 36 0330001 (in Chinese) [高彦伟, 张玉钧, 陈东, 何莹, 尤坤, 陈晨, 刘文清 2016 光学学报 36 0330001]

    [17]

    Kosterev A A, Curl R F, Tittel F K, Gmachl C, Capasso F, Sivco D L, Baillargeon J N, Hutchinson A L, Cho A Y 2000 Appl. Opt. 39 4425

    [18]

    Erdelyi M, Richter D, Tittle F K 2002 Appl. Phys. B 75 289

    [19]

    Richter D, Wert B P, Fried A, Weibring P, Walega J G, White J W C, Vaughn B H, Tittel F K 2009 Opt. Lett. 34 172

    [20]

    Li X X, Xu L, Gao M G, Tong J J, Feng M C, Liu J G, Liu W Q 2015 Acta Phys. Sin. 64 024217 (in Chinese) [李相贤, 徐亮, 高闽光, 童晶晶, 冯明春, 刘建国, 刘文清 2015 物理学报 64 024217]

    [21]

    Liu K, Wang L, Tan T, Wang G S, Zhang W J, Chen W D, Gao X M 2015 Sensors and Actuators B 220 1000

    [22]

    Tanaka K, Tonokura K 2011 Appl. Phys. B 105 463

    [23]

    Hoang V D 2014 Trends Analyt. Chem. 62 144

    [24]

    Li Z B, Ma H L, Cao Z S, Sun M G, Huang Y B, Zhu W Y, Liu Q 2016 Acta Phys. Sin. 65 053301 (in Chinese) [李志彬, 马宏亮, 曹振松, 孙明国, 黄印博, 朱文越, 刘强 2016 物理学报 65 053301]

    [25]

    Wu T, Chen W D, Kerstel E, Fertein E, Gao X M, Koeth J, Robner K, Bruckner D 2010 Opt. Lett. 35 634

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Publishing process
  • Received Date:  18 August 2017
  • Accepted Date:  13 November 2017
  • Published Online:  20 March 2019

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