Identifying endogenous volatile organic compounds(VOCs) as markers for different cancers currently requires time-consuming procedures and specialized operators.
OBJECTIVE:
The objective of this study was to develop a rapid and simple method for measuring VOCs at trace levels.
METHODS:
A simple vacuum ultraviolet photoionization mass spectrometer (VUV-PIMS) was used to detect trace levels of dimethyl trisulfide (DMTS), dimethyl sulfide (DMS), and 2-butanone, which correspond to volatile biomarker candidates present in the exhaled breath of patients with breast, liver, and lung cancers, respectively. The practicality of measuring endogenous VOCs using VUV-PIMS was confirmed by detecting them in cultured cell lines.
RESULTS:
The abovementioned VOCs were detected with high sensitivity by VUV-PIMS. The limits of detection (LODs) for DMTS, DMS, and 2-butanone were 3.1, 3.9, and 23.2 pptv, respectively, under ambient conditions, which surpass the sensitivity of nearly all other MS-based techniques. Moreover, relatively high concentrations of 2-butanone and DMS were observed in VOCs emitted from the A549 lung cancer cell line and the HepG2 liver cancer cell line, respectively.
CONCLUSIONS:
Our results show that VUV-PIMS may serve as a reliable method for real-time measurement of endogenous volatile cancer biomarkers.
van der ScheeM.P., PaffT., BrinkmanP., van AalderenW.M., HaarmanE.G. and SterkP.J., Breathomics in lung disease, Chest147 (2015), 224-31.
2.
QueraltoN., BerlinerA.N., GoldsmithB., MartinoR., RhodesP. and LimS.H., Detecting cancer by breath volatile organic compound analysis: A review of array-based sensors, J Breath Res8 (2014), 027112.
3.
ShirasuM. and TouharaK., The scent of disease: volatile organic compounds of the human body related to disease and disorder, J Biochem150 (2011), 257-66.
4.
ShirasuM., NagaiS., HayashiR., OchiaiA. and TouharaK., Dimethyl trisulfide as a characteristic odor associated with fungating cancer wounds, Biosci Biotechnol Biochem73 (2009), 2117-20.
5.
KingH.M., UnterkoflerJ., et al., lood and breath profiles of volatile organic compounds in patients with end-stage renal disease, BMC nephrology15 (2014), 43.
6.
KalluriU., NaikerM. and MyersM.A., Cell culture metabolomics in the diagnosis of lung cancer-the influence of cell culture conditions, J Breath Res8 (2014), 027109.
7.
MiekischW., SchubertJ.K. and Noeldge-SchomburgG.F., Diagnostic potential of breath analysis - focus on volatile organic compounds, Clin Chim Acta347 (2004), 25-39.
8.
FuX.A., LiM., KnippR.J., NantzM.H. and BousamraM., Noninvasive detection of lung cancer using exhaled breath, Cancer Med3 (2014), 174-81.
9.
WeisserO. and LandaS., Sulphide catalysts, their properties and applications, Academia, Prague, 1972.
10.
SilvaC.L., PassosM. and CâmaraJ.S., Solid phase microextraction, mass spectrometry and metabolomic approaches for detection of potential urinary cancer biomarkers - A powerful strategy for breast cancer diagnosis, Talanta89 (2012), 360-368.
11.
van den VeldeS., QuirynenM., van HeeP. and van SteenbergheD., Halitosis associated volatiles in breath of healthy subjects, J Chromatogr B Analyt Technol Biomed Life Sci853 (2007), 54-61.
12.
MochalskiP., SponringA., KingJ.L., UnterkoflerK., TroppmairJ. and AmannA., Release and uptake of volatile organic compounds by human hepatocellular carcinoma cells (HepG2) in vitro, Cancer Cell International13 (2013).
13.
HabeH., SatoS., MoritaT., FukuokaT., KirimuraK. and KitamotoD., Isolation and characterization of bacterial strains with the ability to utilize high concentrations of levulinic acid, a platform chemical from inedible biomass, Biosci Biotechnol Biochem (2015), 1-4.
14.
HabeH., SatoS., MoritaT., FukuokaT., KirimuraK. and KitamotoD., Bacterial production of short-chain organic acids and trehalose from levulinic acid: a potential cellulose-derived building block as a feedstock for microbial production, Bioresour Technol177 (2015), 381-6.
15.
FilipiakW., SponringA., MikovinyT., AgerC., SchubertJ., MiekischW., AmannA. and TroppmairJ., Release of volatile organic compounds (VOCs) from the lung cancer cell line CALU-1 in vitro, Cancer Cell Int8 (2008), 17.
16.
SponringA., FilipiakW., MikovinyT., AgerC., SchubertJ., MiekischW., AmannA. and TroppmairJ., Release of volatile organic compounds from the lung cancer cell line NCI-H2087 in vitro, Anticancer Res29 (2009), 419-26.
17.
UlanowskaA., KowalkowskiT., TrawinskaE. and BuszewskiB., The application of statistical methods using VOCs to identify patients with lung cancer, J Breath Res5 (2011), 046008.
18.
MazzatentaA., Di GiulioC. and PokorskiM., Pathologies currently identified by exhaled biomarkers, Respir Physiol Neurobiol187 (2013), 128-34.
19.
VasG. and VekeyK., Solid-phase microextraction: a powerful sample preparation tool prior to mass spectrometric analysis, J Mass Spectrom39 (2004), 233-54.
20.
MesterZ.N., LamJ., SturgeonR. and PawliszynJ., Determination of methylmercury by solid-phase microextraction inductively coupled plasma mass spectrometry: a new sample introduction method for volatile metal species, Journal of Analytical Atomic Spectrometry15 (2000), 837-842.
21.
ArmentaS., AlcalaM. and BlancoM., A review of recent, unconventional applications of ion mobility spectrometry (IMS), Anal Chim Acta703 (2011), 114-23.
22.
RattrayN.J., HamrangZ., TrivediD.K., GoodacreR. and FowlerS.J., Taking your breath away: metabolomics breathes life in to personalized medicine, Trends Biotechnol32 (2014), 538-48.
23.
SaisonD., De SchutterD.P., DelvauxF. and DelvauxF.R., Optimisation of a complete method for the analysis of volatiles involved in the flavour stability of beer by solid-phase microextraction in combination with gas chromatography and mass spectrometry, J Chromatogr A1190 (2008), 342-9.
24.
MochalskiP., KingJ., KlieberM., UnterkoflerK., HinterhuberH., BaumannM. and AmannA., Blood and breath levels of selected volatile organic compounds in healthy volunteers, Analyst138 (2013), 2134-45.
25.
Grabowska-PolanowskaB., FaberJ., SkowronM., MiarkaP., PietrzyckaA., SliwkaI. and AmannA., Detection of potential chronic kidney disease markers in breath using gas chromatography with mass-spectral detection coupled with thermal desorption method, J Chromatogr A1301 (2013), 179-89.
26.
RiessU., TegtburU., FauckC., FuhrmannF., MarkewitzD. and SalthammerT., Experimental setup and analytical methods for the non-invasive determination of volatile organic compounds, formaldehyde and NOx in exhaled human breath, Anal Chim Acta669 (2010), 53-62.
27.
HansenM.J., LiuD., GuldbergL.B. and FeilbergA., Application of proton-transfer-reaction mass spectrometry to the assessment of odorant removal in a biological air cleaner for pig production, J Agric Food Chem60 (2012), 2599-606.
28.
JordanC., FitzE., HaganT., SiveB., FrinakE., HaaseK., CottrellL., BuckleyS. and TalbotR., Long-term study of VOCs measured with PTR-MS at a rural site in New Hampshire with urban influences, Atmospheric Chemistry And Physics9 (2009), 4677-4697.
29.
GrausM., MullerM. and HanselA., High resolution PTR-TOF: quantification and formula confirmation of VOC in real time, J Am Soc Mass Spectrom21 (2010), 1037-44.
30.
PengG., TrockE. and HaickH., Detecting simulated patterns of lung cancer biomarkers by random network of single-walled carbon nanotubes coated with nonpolymeric organic materials, Nano Lett8 (2008), 3631-5.
31.
PengG., TischU., AdamsO., HakimM., ShehadaN., BrozaY.Y., BillanS., Abdah-BortnyakR., KutenA. and HaickH., Diagnosing lung cancer in exhaled breath using gold nanoparticles, Nat Nanotechnol4 (2009), 669-73.
32.
SunJ.N.S.W.Q., ZhangP., LiZ., LiN.N., LiangM. and YangB., Real-time monitoring of trace-level VOCs by an ultrasensitive compact lamp-based VUV photoionization mass spectrometer, Atmospheric Measurement Techniques Discussions8 (2015), 5877-5894.
33.
ShuX., YangB., MengJ.W., WangY.F. and ShuJ.N., Vacuum Ultraviolet Photoionization Mass Spectra of Typical Organics Contained in Ambient Aerosols, Spectroscopy Letters46 (2013), 227-234.
34.
SalaunP., Planer-FriedrichB. and van den BergC.M., Inorganic arsenic speciation in water and seawater by anodic stripping voltammetry with a gold microelectrode, Anal Chim Acta585 (2007), 312-22.
35.
JordanA., HaidacherS., HanelG., HartungenE., HerbigJ., MärkL., SchottkowskyR., SeehauserH., SulzerP. and MärkT.D., An online ultra-high sensitivity Proton-transfer-reaction mass-spectrometer combined with switchable reagent ion capability (PTR+SRI-MS), International Journal of Mass Spectrometry286 (2009), 32-38.
36.
RudnickaJ., WalczakM., KowalkowskiT., JezierskiT. and BuszewskiB., Determination of volatile organic compounds as potential markers of lung cancer by gas chromatography - mass spectrometry versus trained dogs, Sensors and Actuators B: Chemical202 (2014), 615-621.
37.
CorradiM., PoliD., BandaI., BoniniS., MozzoniP., PinelliS., AlinoviR., AndreoliR., AmpolliniL., CasaliniA., CarbognaniP., GoldoniM. and MuttiA., Exhaled breath analysis in suspected cases of non-small-cell lung cancer: A cross-sectional study, J Breath Res9 (2015), 027101.
