Breath Analysis For Medical Diagnosis Intelligent Systems-Books Pdf

Breath Analysis for Medical Diagnosis Intelligent Systems
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Darryl Hill and Russell Binions Breath Analysis for Medical Diagnosis. and make disease diagnosis from analysis of the collected data which compare favorably with. traditional medical diagnostic techniques, Sensors Breath Analysis Electronic Nose Cancer Detection. Introduction, Since the time of the ancient Greeks physicians have acknowledged the potential of. exhaled breath EB as a diagnostic tool for disease and underlying health conditions It is. possible through breath odour to identify the telltale sweet fruit like scent of acetone and. hence the underlying diabetes of a patient the stench attributable to a lung absyss and the. fumes of urine an indication of kidney disease 1, Contemporary research dawned with the identification of 250 common volatile. organic compounds VOC s in exhaled breath 2 Whilst the practicality of the study was. of low value the study group having to follow a severely restricted diet of simple molecules. for several days it was a first step in identifying potential bio markers of disease Initial. studies relied on simple gas chromatography GC sampling methods with no sample. fractionalisation of preconcentration Computational advancement through the 80 s and 90 s. made it possible for breath tests to be used routinely in clinical analysis for example to. identify blood ethanol levels and the diagnosis of a Helicobacter pylori bacterial infection. using 13 14C urea as a biomarker 3, Due to its non invasivity breath analysis is an attractive procedure for disease. diagnosis however challenges remain One of the biggest obstacles faced is linking the. suspected biomarkers back to the metabolic pathways that occur as a result of the underlying. health condition as many of these pathways are as of yet unkown Likewise technological. and procedural difficulties remain Standardization of sample collection preconcentration. and vapour desorption is key to making breath analysis both economical and practical in its. The Collection Preconcentration Desorption of Exhaled Breath. INTERNATIONAL JOURNAL ON SMART SENSING AND INTELLIGENT SYSTEMS VOL 5 NO 2 JUNE 2012. Over 1000 VOC s have been identified to date with most being in the ppmv down to. pptv concentrations as such it is essential that the sample collection and pre concentration are. required to make detection possible, Sample collection requires the distinction between dead air space representing the.
first 150ml of air collected originating from the mouth an upper airway where no exchange. is possible between the blood and breath and alveolar breath represented by the next. 350ml of exhaled breath 1 Studies have shown that whilst concentrations of some. chemical species and the pH are not vastly different between these two collections of. exhaled air cited adenosine hydrogen peroxide and 8 isoprostane other potential biomarker. concentrations vary according to the breath origin In one study it was found that the. concentration of ammonia was substantially lower in exhaled breath samples obtained. through tracheostomies than those collected via the mouth suggesting the origin of this. compound is in the upper airways 4 Hence depending on the biomarker being observed. inclusion of dead space air can be a contaminant or a necessity as is the case with nitrogen. oxide proposed as a biomarker of respiratory inflammation 5. The interaction of VOC s with water vapour comprising 99 by volume of liquid. exhalants is another important consideration when prescribing a standardized collection. method Studies have shown a reduced concentration of key VOC s due to their absorption. into water condensate in the collection apparatus 6 Further study found no significant loss. of VOC s in tedlar collection bags under typical conditions Loss of acetone and 2 butanone. were seen but only in conditions in which at least three times the normal volume of exhaled. water vapour was present 7 The study did find that water vapour impedes the functioning. and sensitivity of GC apparatus as a consequence water vapour collection was strongly. recommended before analyte concentration Further to this the effect of water vapour on. metal oxide sensor arrays has been documented Generally an increase in humidity has an. associated increase in conductivity decrease in resistivity This is believed to be due to. displacement of chemisorbed oxygen species by water molecules and hydroxyl species which. form at the sensor surface These lie higher in energy that the predecessor oxygen species. displaced 8, Preconcentration requires that the EB be passed through a chemical trap which. selectively absorbs analytes of interest Methods include chemical interaction resin. adsorption and cryogenic distillation cold trapping Ideal traps would completely adsorb. the volatile organic from the passing breath and then release completely upon desorption. Darryl Hill and Russell Binions Breath Analysis for Medical Diagnosis. usually via thermal decomposition with no loss or contamination Current devices fail to. meet these criteria Chemical trapping the process of passing the EB through a solution that. actively captures compounds is usually ultra specific This is advantageous when only one. analyte is being measured one case in point being acetone. Large concentrations of acetone have been identified in patients with acute diabetes. Techniques to quantify this presence involve bubbling the EB through an alkaline iodine. solution 9 and reacting the EB with 2 4 dinitrophenylhydrazine fig 1. Fig 1 Reaction of a ketone with 2 4 dinitrophenylhydrazine to give the corresponding hydrazone which can be. quantitatively measured to determine the original concentration of ketone Comparable to the measurement of. acetone in exhaled breath in diabetic patients 10, The above method has one critical limitation in that it requires breath sampling for. upwards of an hour Most recently research has involved basic salicylaldehyde SA. chemistry which has a measurement cycle of a more practical ten minutes with a detection. limit of just 14 ppbv for acetone The SA reaction requires initial basic conditions as treated. with NaOH 0 8M to prevent the water insoluble SA from forming a separated bilayer on. top of the water The reaction proceeds as an aldol condensation producing a blue product. which was measured using colorimetric diagnostic techniques 11. INTERNATIONAL JOURNAL ON SMART SENSING AND INTELLIGENT SYSTEMS VOL 5 NO 2 JUNE 2012. In contrast cold traps generally capture unwanted chemical compounds and as such. are generally too unspecific As a result adsorbent trapping is the most convenient and. widely used trapping technique It captures volatiles on an extracting phase polymer if liquid. sorbent is solid and then releases these as and when required into the separating apparatus. Solid Phase Microextraction SPME is such a technique developed by Dr Pawliszyne of the. University of Waterloo comparatively advantageous in that it requires no solvent and. importantly for practicality reasons can be done in field by non scientific staff Several days. can pass before the analysing process without significant loss of volatiles Concentrations as. low as pptv have been successfully adsorbed enhanced by the use of low temperature glassy. carbon LTGC microfibers, The selectivity and efficiency of commercially available poly dimethylsiloxane. divinylbenzene PDMS DVB fibers compared with LTGC fibers has been examined and the. following graph illustrates the enhancement gained when using the latter fig 2. Fig 2 Extraction recovery efficiencies of commercially available PDMS DVB with LTGC fibers in relation to. certain VOC s, As can be seen in all cases there was a dramatic increase in the extraction of VOC s. when the low temperature glassy carbon tubes were used an improvement by a factor of. approximately 5 Conclusions of the study reported that VOC s could be successfully. adsorbed in the subpicomolar concentrations more than adequate for the majority of VOC s. found in EB 12,Techniques for Breath Testing, Darryl Hill and Russell Binions Breath Analysis for Medical Diagnosis.
Currently instrumental detection of breath biomarkers can be split into two subgroups. Conventional methods that utilise GC usually coupled with a form of mass spectroscopy. MS and electronic analysis via the use of sensors commonly found in the form of. electronic noses or e noses Electronic noses consist of sensor arrays that are usually specific. in response to certain gases and aim to mimic biological olfactory systems through. determination of concentration of gases Generally e noses are cheaper portable and faster. commonly requiring less than 30 minutes to analyse a sample Whilst e noses are already. deployed in industry from fields as diverse as food fragrances chemistry and the. environment 13 The use of e noses in medical diagnosis has shown promising results in the. fields of renal disease lung cancer and diabetes however the devices tend to be too specific. and lack cross compatibility suitable for one particular disease only. The former technique involves injecting the analyte onto the head of the. chromatographic column and then passed through the column under the continuous pressure. from an inert gaseous phase As the analyte travels through the column the different. constituents separate out in an order largely dependant upon the material used to pack the. column Silicones tend to separate analytes according to boiling point whereas polar packing. materials instead separate according to the relative polarities of the species 14. Further analysis most commonly employs mass spectroscopy MS to identify the. separated species using the difference in mass to charge ratio m e to define ions or charged. molecular fragments Currently this method of determination is the primary procedure. utilised to identify VOC s in human breath Comparative studies have shown however that. there is little difference in accuracy of determination even with low concentration ppbv. organics compared with other detection techniques 15 The study involved the detection of. 108 organics in human breath using both real time and canister analysis It was found that. many of the analytes where present in too low concentrations to be detected by either method. of detection MS and Flame Ionized Detection FID noting that preconcentration of the. sample is therefore a stringent requirement Hence the sample study was reduced to just a. few organics including isoprene and prinene biological hydrocarbons benzene and. toluene anthropogenic hydrocarbons within that subset The study found that there was no. significant difference in the accuracy s of either method the extent of agreement described as. excellent an observation even more prominent when both MS and FID were independently. calibrated, INTERNATIONAL JOURNAL ON SMART SENSING AND INTELLIGENT SYSTEMS VOL 5 NO 2 JUNE 2012. FID exploits the phenomenon whereby charged ions and electrons are released upon. igniting organic compounds that have been mixed with hydrogen and air These charged. species are able to carry charge which is measured and calibrated to detect the species. present 16 One severe limitation over MS that cannot be overcome is that during the. detection process FID destroys the sample making subsequent or indeed more in depth. analysis impossible, Another analysis method is Ion Mobility Spectrometry IMS This method calibrates. the relative delay in reaching a detector of charged ions and molecules Such species travel at. velocities proportional to their size shape mass and charge hence individual identification is. possible The ion mobility K is defined as the proportionality factor of an ion s drift velocity. vd in a gas and an electric field of strength E eq 1. vd KE eq 1, The ion mobility K can be experimentally determined by measuring the drift time tD of an ion. travelling within a homogeneous electric field with potential difference U in the drift length L. The ion mobility K can also be calculated by the Mason equation eq 3. where Q is the ion charge n is the drift gas number density is the reduced mass of the ion. and the drift gas molecules k is Boltzmann constant T is the drift gas temperature and is. the ion s collision cross section with the drift gas This relation holds approximately at a low. electric field limit where the ratio of E n is small at 2 x 10 17 C cm2 17. IMS can be integrated with MS IMMS with each complementing and enhancing the. others accuracy and efficiency Together it becomes a power analytical tool for identifying. molecular structure and separating complex samples which MS alone might not be able to. Darryl Hill and Russell Binions Breath Analysis for Medical Diagnosis. distinguish Studies have found the resolving power of IMMS to be in the region of 50 120. which is similar to capillary gas chromatography 18. Proton Transfer Mass Spectrometry PMT MS is another promising field able to. analyze analyte concentrations as low as a few pptv This relies on protonation of the. chemical species coming from a transfer from protonated water Almost all VOC s have. proton affinities greater than water hence there is complete transfer 19 The technique is. particularly advantageous for breath analysis as large volumetric contributions from N2 O2. CO2 and water do not interfere with measurement Like MS species identification is done. purely on an m e ratio meaning that mass overlapping is possible when fragmentatio. Sensors Breath Analysis Electronic Nose Cancer Detection Introduction Since the time of the ancient Greeks physicians have acknowledged the potential of exhaled breath EB as a diagnostic tool for disease and underlying health conditions It is possible through breath odour to identify the telltale sweet fruit like scent of acetone and

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