Table Of ContentBioanalytical Reviews
Stefan Weigl Editor
Breath
Analysis
An Approach for Smart Diagnostics
4
Bioanalytical Reviews
SeriesEditors
Frank-MichaelMatysik,InstituteofAnalyticalChemistry,UniversityofRegensburg,
Regensburg,Germany
JoachimWegener,DepartmentofChemistry,UniversityofRegensburg,Regensburg,
Germany
Bioanalytical Reviews is the successor of the former review journal with the same
name, and it complements Springer’s successful and reputed review book series
programintheflourishingandexcitingareaoftheBioanalyticalSciences.
Bioanalytical Reviews (BAR) publishes reviews covering all aspects of
bioanalytical sciences. It therefore is a unique source of quick and authoritative
information for anybody using bioanalytical methods in areas such as medicine,
biology,biochemistry,genetics,pharmacology,biotechnology,andthelike.
Reviewsofmethodsincludeallmoderntoolsapplied,includingmassspectrom-
etry, HPLC (in its various forms), capillary electrophoresis, biosensors,
bioelectroanalysis, fluorescence, IR/Raman, and other optical spectroscopies,
NMR radiometry, and methods related to bioimaging. In particular the series
volumes provide reviews on perspective new instrumental approaches as they
apply to bioanalysis, and on the use of micro-/nano-materials such as micro- and
nanoparticles.Articlesonμ-totalanalyticalsystems(μ-TAS)andonlabs-on-a-chip
alsofallintothiscategory.
Intermsofapplications,reviewsonnovelbioanalyticalmethodsbasedontheuse
of enzymes, DNAzymes, antibodies, cell slices, to mention the more typical ones,
are highly welcome. Articles on subjects related to the areas including genomics,
proteomics, metabolomics, high-throughput screening, but also bioinformatics and
statisticsastheyrelatetobioanalyticalmethodsareofcoursealsowelcome.Reviews
coverbothfundamentalaspectsandpracticalapplications.
Reviews published in BAR are (a) of wider scope and authoratively written
(rather than a record of the research of single authors), (b) critical, but balanced
and unbiased; (c) timely, with the latest references. BAR does not publish (a)
reviews describing established methods of bioanalysis; (b) reviews that lack wider
scope,(c)reviewsofmainlytheoreticalnature.
Stefan Weigl
Editor
Breath Analysis
An Approach for Smart Diagnostics
With contributions by
(cid:1) (cid:1) (cid:1)
R. Abozaid M. Aufderhaar M. Cánovas Díaz
(cid:1) (cid:1) (cid:1)
T. de Diego Puente J. Gallego-Jara M. Hlavatsch
(cid:1) (cid:1) (cid:1) (cid:1)
S. Karan S. Klingler G. Lozano-Terol A. Meister
(cid:1) (cid:1) (cid:1) (cid:1)
B. Mizaikoff M. Müller R. Myers K. Nandigam
(cid:1) (cid:1) (cid:1) (cid:1)
G. Nosovitskiy P. Nosovitskiy J. Pangerl T. Rück
(cid:1) (cid:1) (cid:1)
D. M. Ruszkiewicz R. A. Sola-Martínez P. Sukul
(cid:1)
P. Trefz S. Weigl
Editor
StefanWeigl
OstbayerischeTechnischeHochschule
Regensburg
Regensburg,Germany
ISSN1867-2086 ISSN1867-2094 (electronic)
BioanalyticalReviews
ISBN978-3-031-18525-0 ISBN978-3-031-18526-7 (eBook)
https://doi.org/10.1007/978-3-031-18526-7
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I dedicate this book to Prof. Dr. Rudolf Bierl
and Prof. Dr. Frank-Michael Matysik. Thank
you for your trust, the instructive discussions
and your support, not only on my academic
path.
Preface
Itisthefirstthingwedouponarrivalinthisworld,thelastthingwhenitistimeto
leaveandjustlikeaperson’sheartbeat,itisasignoflife—breathing.
But breathing is more than simply the process of moving air in and out of the
lungs.Withoutbreathing,wewouldnotbeabletospeakoreventolaugh.Therefore,
withouttheabilitytobreath,wewouldbedeprivedoftheexpressionofmanyofour
emotions.Moreover,breathexhaleprovidesamirrortothebiochemicalprocesses,
occurring not only in the lungs but in the whole body, thanks to the gas exchange
betweenlungsandbloodtakingplaceatthealveoli.Itisthereforenotsurprisingthat,
since ancient times, analysing breath is a popular diagnostic tool for systemic
disordersanddiseases.
There is evidence that already the ancient Greeks and the Chinese people
analysedbreath.WithinthefifthandfourthcenturyBC,theperiodofHippocrates,
breath odour was used to diagnose kidney failure, lung abscess, diabetic
ketoacidosis,liverdiseaseandhalitosisinGreece.Onemilestoneofbreathanalysis
was reached in 1780, when Antoine Laurent Lavoisier, accompanied by Pièrre
Simon de Laplace and Armand Séguin, was able to describe the metabolism of a
guinea pig, discovering the metabolization of oxygen to carbon dioxide under the
emission of heat. Lavoisier’s pioneering work in this field also included the first
attempttodescribethehumanrespiratorygasmetabolism,thusmakinganimportant
contribution tothe development of respiratoryphysiology. At thebeginning ofthe
nineteenth century, it was A. Nebelthau who invented one of the first colorimetric
breath tests. With his test, he was able to detect breath acetone of people suffering
fromDiabetes Mellitus.In1874,FrancisEdmundAnstie,aBritishdoctor,usedan
acidic chrome solution changing its colour from red-brown to green upon contact
withethanol,representingthefirstalcoholbreathtest.Aboutonecenturylater,inthe
1970s, the age of modern breath analysis was heralded by the studies of Linus
Pauling. Using gas-liquid partition chromatography, he was able to quantitatively
determineabout250differentsubstancesinhumanbreathexhale.
Withinthelastdecades,highlysensitiveandselectiveofflineandreal-timemass
spectrometryemergedandopenednewopportunities.Researchwasmainlyfocusing
vii
viii Preface
onthediscoveryofbiomarkers,whichcouldbeusedforearlydetectionofdiseases.
However,untilnow,exceptfornitrogenmonoxide,whichisanapprovedbiomarker
for asthma, no “magic” biomarker or breath print has been discovered. Besides,
manyresourceshavebeeninvestedinthedevelopmentofpoint-of-caredevicesfor
potentialbiomarkersbutbreathanalysisisstillfailingtoproceedfrombenchtobed
andbecomepartoftheeverydaydiagnosticroutineinclinicsordoctoraloffices.
Thisbook therefore addressesthemistakes that have beenmade in thepast and
offers answers on how to take breath analysis to the next level. Besides, real-time
and offline analysis methods based on spectrometers as well as reviews about
differentsensingapproachesfortargetedpoint-of-caredevicesarepresented.More-
over,thisbookdiscussespulmonaryfunctionanalysisanditsroleinmodernbreath
analysis.
The first chapter deals with the physio-metabolic monitoring of breath exhale
using real-time mass spectrometry. It describes the complexity of breath analysis
since many factorscan easily change thecomposition ofbreathincluding different
respiratorypatternsorrhythmsaswellaspostureorexhalingflowrates.Ontheone
hand, the chapter deals with the challenges and pitfalls coming along with current
breath analysis research, but on the other hand highlights its importance and
potentialsformoderndiagnostics.
Within the second chapter, offline breath analysis using gas chromatography
coupledwithmassspectrometryandtheroleofstandardizationofbreathsampling
aswellasdataanalysisarediscussed.Furthermore,thechapteraddressesinnovative
algorithms and how they improve the analytical performance of the measurement
device.
Inthethirdchapter,gaschromatographycoupledwithionmobilityspectrometry
forthedetectionofvolatilebreathcompoundsinclinicalandemergencysettingsis
presented. It focuses on the potentials of this real-time measurement technique for
rapid testing, diagnosis and biomarker discovery. In addition, it addresses the
remaininglimitationsincurrentapplicationsandhowtomeetremainingchallenges.
Thefourthchapterisconcernedwiththeapplicabilityofopticalsensingstrategies
intheinfra-redregion.Differentmeasurementmethodsandcurrentapplicationsare
reviewedprovidinganoverviewonthefundamentalprinciplesandrecentdevelop-
mentsinthisemergingfield.
Theapplicabilityofphotoacousticspectroscopyisaddressedinthe fifthchapter
of this book. The measurement principle is described in detail highlighting the
potentialsandpitfalls.Besides,theapplicationofinnovativealgorithmsisdiscussed
to employ this technology in complex measurement matrices like breath. Finally,
recent applications of photoacoustic spectroscopy in breath analysis are reviewed
withinthechapter.
Within the sixth chapter of this book, sensor-array-based devices for breath
analysisarediscussed,highlightingelectronicnoses.Thechapterincludesmaterial
design advances, material selections and innovative sensor structures. Besides, a
discussion of parametric resonance and excitation applied to sensor-based breath
analysisdevicesispresented.Ananalysisofareviewonthedevelopmentofcarbon
nanomaterialsconcludesthechapterbydiscussingthecurrentchallengesrelatedto
Preface ix
sensor array devices, machine-learning algorithms and the application of breath
analysis.
The final chapter of the book addresses modern pulmonary function diagnosis
highlighting its importance for reliable breath analysis. The techniques described
includespirometry,bodyplethysmographyandavarietyofothercommontestsused
toassessapatient’srespiratorystatus.Furthermore,thechapterdealswithbloodgas
analysis, capnometry and capnovolumetry and the analysis of nitrogen oxide in
humanbreathexhaleforasthmadetection.
Although this book covers many aspects of breath analysis, it is not all-
encompassing since this would go far beyond the scope of this book. However, it
provides a good overview and addresses the most important aspects of modern
breathanalysisincludingtheadvantagesanddisadvantagesofofflineandreal-time
massspectrometers,thescopesandlimitsoftargetedsensingapproachesaswellas
the importance of pulmonary function diagnostics in the field of breath analysis.
Besides, the challenges and pitfalls of breath analysis are addressed and potential
solutionslikeimprovedstandardizationsandinnovativealgorithmsarepresented.
Atthispoint,Iwouldliketoexpressmydeepestgratitudetoallauthorsandco-
authors.Withoutyourfinework,thisbookwouldnothavebeenpossible.Ihopeyou
allagreethatthisbigeffortandthelonghoursofworkhavebeenworthwhile.The
bookwillbeofinterestnotonlyforexpertsinthefieldbutalsotostudentsandtheir
teachersinvariousinterdisciplinaryresearchfieldsencompassedbymodernbreath
analysis.
Regensburg,Germany StefanWeigl
