A mobile diagnostics suite for the express quantitative determination of acetine in exhaled breath
Abstract
Analysis of volatile compounds in exhaled breath is the basis of non-invasive diagnostics based on the use of biomarkers of metabolic disorders and the identification of risk factors of the development of pathological processes performed for early diagnostics. Acetone in exhaled breath is a biomarker of diabetes. Concentrations of over 0.9 ррm indicate the development of the disease. The article presents a mobile diagnostics suite based on a portable gas chromatograph PIA and a method for the express quantitative determination of acetone in exhaled breath. The analytical system includes planar microfluidic columns with the internal section of 0.8 mm2, filled with a Carbopack B sorbent (80-100 mesh fraction), a thermocatalytic detector, and a thermal desorption unit. The suggested method can be used for quantitative determination of acetone in the concentration range from 0.1 ррm to 10 ррm. The analysis takes 3 minutes. We also assessed the possible sources of uncertainties during sampling, preparation, and calibration. In our study, we analysed the advantages and limitations of various calibration mixtures: control gas mixtures, gas mixtures prepared under static conditions by means of the analysis of equilibrium vapour phases, statistical volumetric analysis, and chromato-desorption method in a discrete mode. The study determined that it is advisable to prepare calibration mixtures immediately before the analysis. It also demonstrated that diagnostics of functional disorders (0.9-2 ррm) and neurotypical level (below 0.9 ррm) of acetone in exhaled breath requires the use of calibration gas mixtures obtained by means of volumetric or chromato-desorption methods, which decrease the impact of the calibration stage to the total level of uncertainty by 10-30%. The article also provides recommendations on the traceability and assessment of the mass fraction of acetone in calibration gas mixtures by means of a Microgas dynamic unit in the thermal diffusion mode with microflow sources. Methods for the reduction of uncertainty are suggested. The article also describes the prospects of using chromato-desorption systems for sample preparation and concentration of the samples of exhaled breath under conditions identical to the calibration conditions and reduction of the detection limit.
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References
Vsemirnaya organizaciya zdra-voohraneniya. Global'nyj doklad po dia-betu. ZHeneva, 2018, 88 p. (In Russ.)
Sagnik Das, Mrinal Pal. Non-Invasive Monitoring of Human Health by Exhaled Breath Analysis: A Comprehensive Re-view, Journal of The Electrochemical So-ciety, 2020; 167: 037562. https://doi.org/10.11491945-7111/ab67a6
Kopylov F.Yu., Syrkin A.L., Chomahidze P.Sh., Bykova A.A., Shaltaeva Yu.R., Belyakov V.V., Pershenkov V.S., Samotaev N.N., Golovin A.V., Vasil'ev V.K., Malkin E.K., Gromov E.A., Ivanov I.A., Lipatov D.YU., YAkovlev D.Yu.Perspektivy diagnostiki razlichnyh zabolevanij po sostavu vydyhaemogo vozduha, Klinicheskaya medicina. 2013; 10: 16-21. (In Russ.)
Kulikov V.Yu., Ruyatkina L.A., So-rokin M.Yu., Shabanova E.S., Baldin M.N., Gruznov V.M., Efimenko A.P., Petrovskij D.V., Shnajder E.P., Moshkin M.P. Vzai-mosvyaz' mezhdu soderzhaniem v vydy-haemom vozduhe acetona i osobenno-styami metabolicheskih narushenij u bol'n-yh saharnym diabetom pervogo i vtorogo tipov [Elektronnyj resurs] Medicina i obra-zovanie v Sibiri: elektronnyj nauchnyj zhurnal. 2011; 1: 2. (In Russ.)
Rydosz A. Micropreconcentrator in LTCC Technology with Mass Spectrometry for the Detection of Acetone in Healthy and Type-1 Diabetes Mellitus Patient Breath. Metabolites. 2014; 4(4): 921-931. https://doi.org/10.3390/metabo4040921
Toyooka T., Hiyama S., Yamada Y. A prototype portable breath acetone analyzer for monitoring fat loss. J Breath Res. 2013; 7(3): 036005. https://doi.org/10.1088/1752-7155/7/3/036005
Anderson J.C. Measuring breath ace-tone for monitoring fat loss: Review. Obe-sity (Silver Spring). 2015; 23(12): 2327-2334. https://doi.org/10.1002/oby.21242
Issitt Th., Wiggins L., Veysey M., Sweeney S.T., Brackenbury W.J., Redeker K. Volatile compounds in human breath: critical review and meta-analysis. Journal of Breath Research. 2022; 16(2): 024001. https://doi.org/10.1088/1752-7163/ac5230
Miekisch W., Schubert J.K., Noeldge-Schomburg G.F.E. Diagnostic potential of breath analysis--focus on volatile organic compounds. Clin Chim Acta. 2004; 347(1-2): 25-39. https://doi.org/10.1016/j.cccn.2004.04.023
Gashimova E.M., Temerdashev A.Z., Porhanov V.A., Polyakov I.S., Pe-runov D.V. Letuchie organicheskie soedi-neniya v vydyhaemom vozduhe kak bi-omarkery raka legkih. Dostizheniya i vozmozhnye problem. ZHurnal analitich-eskoj khimii. 2022; 77(7): 585-615. (In Russ.)
Gashimova E.M., Temerdashev A.Z., Porhanov V.A., Polyakov I.S., Pe-runov D.V., Osipova A.K., Dmitrieva E.V. Ocenka vozmozhnosti differencirovaniya gi-stologicheskogo tipa i lokalizacii opuholi u pacientov s rakom legkih po sostavu vydyhaemogo vozduha. ZHurnal analiticheskoj khimii. 2021; 76(8): 723-729. (In Russ.)
Ryabtsev S.V., Shaposhnick A.V., Lukin A.N., Domashevskaya E.P. Applica-tion of semiconductor gas sensors for med-ical diagnostics. Sensors and Actuators B: Chemical. 1999; 59(1): 26-29.
Shaposhnik A., Zviagin A., Sizask E., Vasiliev A. Acetone and Ethanol Selec-tive Detection by a Single MOX-sensor. Procedia Engineering. 2014; 87: 1051-1054.
Zvyagin A.A., SHaposhnik A.V., Ryabcev S.V., SHaposhnik D.A., Vasil'ev A.A., Nazarenko I.N. Opredelenie parov acetona i etanola poluprovodnikovymi sen-sorami. ZHurnal analiticheskoj khimii. 2010; 65(1): 96-100. (In Russ.)
Saasa V., Malwela Th., Beukes M., Mokgotho M., Liu Ch.-P., Mwakikunga B. Sensing Technologies for Detection of Acetone in Human Breath for Diabetes Diag-nosis and Monitoring. Diagnostics. 2018; 8 (1): 12. https://doi.org/10.3390/diagnostics8010012
Hashoul D, Haick H. Sensors for de-tecting pulmonary diseases from exhaled breath. Eur Respir Rev. 2019; 28: 190011. https://doi.org/10.1183/16000617.0011-2019
Malysheva A.O., Baldin M.N., Gruznov V.M., Blinova L.V. Vnelaboratornyj ekspressnyj gazohromatograficheskij metod analiza vydyhaemogo chelovekom vozduha s avtomatizirovannoj graduirovkoj. Analitika i kontrol'. 2018; 22(2): 177-185. (In Russ.)
Gashimova E.M., Temerdashev A.Z., Porhanov V.A., Polyakov I.S., Pe-runov D.V., Azaryan A.A., Dmitrieva E.V. Ocenka vozmozhnosti gazohromato-graficheskogo opredeleniya letuchih organicheskih soedinenij v vydyhaemom vozduhe dlya neinvazivnoj diagnostiki raka legkih. ZHurnal analiticheskoj khimii. 2019; 74(5): 365-372. (In Russ.)
Gashimova E.M., Temerdashev A.Z., Porhanov V.A., Polyakov I.S., Pe-runov D.V., Azaryan A.A., Dmitrieva E.V. Primenenie analiza vydyhaemogo vozduha dlya identifikacii markerov raka legkih. Zlokachestvennye opukholi. 2019; 9(3): 1-66. (In Russ.)
Baldin M.N., Simakov V.A., Gruz-nov V.M., Moshkin M.P., Kozlov V.A., Firsov A.P. Probootbornik dlya gazovogo analiza vydyhaemogo vozduha. Patent na poleznuyu model' RU 117078 U1, 20.06.2012. Zayavka № 2012106953/15 ot 27.02.2012.
Di Francesco F., Loccioni C., Fio-ravanti M., Russo A., Pioggia G., Ferro M., Roehrer I., Tabucchi1 S., Onor M. Imple-mentation of Fowler’s method for endtidal air sampling. Journal of Breath Research. 2008; 2(3): 037009. https://doi.org/10.1088/1752-7155/2/3/037009
Di Gilio A., Palmisani J., Ventrella G., Facchini L., Catino A., Varesano N., Pizzutilo P., Galetta D., Borelli M., Barbie-ri P., Licen S., de Gennaro G. Breath Anal-ysis: Comparison among Methodological Approaches for Breath Sampling. Mole-cules. 2020; 25(24): 5823. https://doi.org/10.3390/molecules25245823
Harshman S.W., Pitsch R.L., Da-vidson C.N., Lee E.M., Scott A.M., Hill E.M., Mainali P., Brooks Z.E., Strayer K.E., Schaeublin N.M., Wiens T.L., Broth-ers M.C., Drummond L.A., Yamamoto D.P., Martin J.A. Evaluation of a Standard-ized Collection Device for Exhaled Breath Sampling onto Thermal Desorption Tubes. Journal of Breath Research. 2020; 14: 036004. https://doi.org/10.1088/1752-7163/ab7e3b
Chuchalin A.G., Kudryavcev V.B., Alekseev D.V., Anaev E.H., Anohina T.N., Nosov M.V., Revel'skij A.I., Revel'skij I.A., Rodionov A.A. Matematiko-komp'yuternaya obrabotka kvveksperimentov po raspoznavaniyu legochnyh zabolevanij. Intellektual'nye sistemy. 2011; 15(1-4): 265-290. (In Russ.)
Malysheva A.O., Baldin M.H., Gruznov B.M. Opredelenie koefficientov raspredeleniya letuchih organicheskih veshchestv v sisteme zhidkost'vozduh dlya sozdaniya graduirovochnyh gazoobraznyh obrazcov so sledovymi koncentraciyami veshchestv. ZHurnal analiticheskoj khimii. 2017; 72(10): 867-871. (In Russ.)
Španěl P., Dryahina K., Smith D. A quantitative study of the influence of in-haled compounds on their concentrations in exhaled breath. Journal of Breath Re-search. 2013; 7(1): 017106. https://doi.org/10.1088/1752-7155/7/1/017106
Herbig J. Buffered end–tidal (BET) sampling – a novel method for real–time breath–gas analysis. Journal of Breath Re-search. 2008; 2(3):037008. https://doi.org/
1088/1752-7155/2/3/037008
Anderson J. Modeling soluble gas exchange in the airways and alveoli. An-nals of Biomedical Engineering. 2003; 31(11): 1402-22. https://doi.org/10.1114/1.1630600
Schubert J. CO2-controlled sampling of alveolar gas in mechanically ventilated patients. Journal of Applied Physiology. 2001; 90(2): 486-492.
Phillips M. Method for the Collec-tion and Assay of Volatile Organic Com-pounds in Breath. Analytical Biochemistry. 1997; 247(2): 272-278.
Miekisch W. Impact of sampling procedures on the results of breath analysis. Journal of Breath Research. 2008; 2(2): 026007. https://doi.org/10.1088/1752-7155/2/2/026007
Sukul P. Immediate effects of breath holding maneuvers onto composition of exhaled breath. Journal of Breath Re-search. 2014; 8(3): 037102. https://doi.org/10.1088/1752-7155/8/3/037102
Rodinkov O.V., Bugajchenko A.S., Moskvin L.N. Staticheskij parofaz-nyj ana-liz i ego sovremennoe sostoyanie. ZHurnal analiticheskoj khimii. 2020; 75(1): 3-23. (In Russ.)
GOST R ISO 6144-2008. Nacional'nyj standart rossijskoj federacii analiz gazov. Prigotovlenie graduirovochnyh gazovyh smesej. Staticheskij ob"emnyj metod. Gas analysis. Preparation of calibra-tion gas mixtures. Static volumetric meth-od. (In Russ.)
Platonov I.A., Kolesnichenko I.N., Novikova E.A., Pavlova L.V. Ispol'zovanie sorbcionnyh mikrosistem dlya sozdaniya obrazcov sostava letuchih organicheskih soedinenij. Izmeritel'naya tekhnika. 2019; 7: 62-66. (In Russ.)
Platonov I.A., Kolesnichenko I.N., Novikova E.A., Muhanova I.M. po-luchenie gazovyh smesej izvestnogo sosta-va dinamicheskimi metodami. Sorbtsionnye i khromatograficheskie protsessy. 2017; 17(3): 378-387. https://doi.org/10.17308/sorpchrom.2017.17/391 (In Russ.)
ZHuravleva G.A. Zakonomernosti uderzhivaniya N, O, S-soderzhashchih or-ga-nicheskih soedinenij iz gazovoj fazy sorbentami na osnove solej perekhodnyh metallov // Sorbtsionnye i khromatograficheskie protsessy. 2017; 17(5): 750-755. https://doi.org/10.17308/sorpchrom.2017.17/435 (In Russ.)
Vitenberg A.G., Konopel'ko L.A. Parofaznyj gazohromatograficheskij analiz: metrologicheskie prilozheniya. ZHurnal analiticheskoj khimii. 2011; 66(5): 452-472. (In Russ.)
