Hamdi Melih SARAOĞLU Dumlupınar Üniversitesi Mühendislik Fakültesi

1. CAN LUNG DISEASES RECOGNIZED BY SMELLING? ELECTRONIC NOSE Assoc.Prof.Dr.Hamdi Melih Saraoğlu Dumlupınar University Faculty of Engineering Electrical and Electronics Engineering Kutahya Hamdi Melih SARAOĞLU Dumlupınar Üniversitesi Mühendislik Fakültesi Elektrik Elektronik Mühendisliği Bölümü Kütahya Türk Toraks Derneği 15. Yıllık Kongresi

2. FLOW of PRESENTATION • What is electronicnose? • Comparison of humannoseandelectronicnose • Thesensorsusedforelectronicnose • Applicationfields of electronicnose • Thegases in thehumanbreathandtheirformation • Can diseasesdiagnosedwithgases in breath? Nefesteki gazlardan hastalık tanısı konulabilir mi? • Samples of projects (Definingblood, glucoseand HbA1c valuesbyusingelectronicnose) Türk Toraks Derneği 15. Yıllık Kongresi

3. A New Discipline: Measurement of Smell Did you ever measure a smell? Can you tell whether one smell is just twice strong as another? Can you measure the difference between one kind of smell and another? It is very obvious that we have very many different kinds of smells, all the way from the odor of violets and roses to asafetida. But until you can measure their likeness and differences, you can have no science of odor. If you are ambitious to find a new science, measure a smell. Alexander Graham Bell (1914) Türk Toraks Derneği 15. Yıllık Kongresi

4. History of ElectronicNose The first studies related to electronic nose started at Warwick University in England in 1970. The study started in this University and the studies of a imitation nose machine continued in all over the world and the term of electronic nose was first seen in literature in 1990. The first prototype systems launched to the market in 1993 and the first commercial systems were launched to the market in 1994. Türk Toraks Derneği 15. Yıllık Kongresi

5. ElectronicNose; is a systemdevelopedforclassifyinganddetectingsteamandgasesautomaticallywhichimitatesthesmell organ of mammals. Electronicnose is not a prothesisdevelopedforthesmelldisabled. Türk Toraks Derneği 15. Yıllık Kongresi

6. ElectronicNoses; • arethedevicesthat can accuratelymeasurethesmellsthathumannose can not detect. • can sense towhatextent is eachsmellfoundwithinthemeasuredsubstance, whichclassthedetectedsmellbelongstoand at whichqualitylevel is it. • Objectively it givesrepetitiveresults. • It is usedforsmell, steamandgasanalysis. Türk Toraks Derneği 15. Yıllık Kongresi

7. HumanNose • When mammals take breath, together with the inhaled air, the smell molecules entering nose are kept and bind by receptors. Reaction of receptors is transmitted parallelly and this is coded in a combinational way. The signal formed as a result of this impulse is transmitted to olfactory (smell) bulbs and depending on learning, this recognition process occurs in the smell region of brain. • If the excitation signal is familiar recognition occurs in the brain. If it is the first signal then it is recorded as the first in the brain. If a reaction is necessary as a result of excitation signal, the reaction is decided in the brain. Türk Toraks Derneği 15. Yıllık Kongresi

8. Human nose has araound 1 000 000 receptor cells. For dogs this number is around 100 000 000 and comparing to an average human dogs can distinguish odors 100 times better. But it must be taught. • Human nose can distinguish around 2000 odors. By means of education this number can reach to 10 000. Türk Toraks Derneği 15. Yıllık Kongresi

9. Similarities of ElectronicNoseandMammalianNose Chemical sensors take the place of smell sensors and artificial neural network takes the place of olfactory (smell) bulbs. Türk Toraks Derneği 15. Yıllık Kongresi

10. Comparison of HumanNoseandElectronicNose • Electronic Nose System; Smell Identification Chemical Sensors Olfactory (Smell) Bulbs Electronic Decision Making System Türk Toraks Derneği 15. Yıllık Kongresi

11. DifferencesBetweenE-NoseandHumanNose • The most important specification of E-Nose system is, its ability to sensor, distinguish the types of smell in a very short time in the accuracy level of human nose and present the results in a very short time. • Human beings have the capability of distinguishing thousands of different odors • Human nose has some weaknesses: • It can never sense the smell of some gases like carbon monoxide and carbon dioxide. • It can not smell after some time (Fatigue). • Besides human nose has different accuracy levels personaly. Türk Toraks Derneği 15. Yıllık Kongresi

12. SmellDetectionwithElectronicNose Smell molecules are sent to chemical sensors in various ways. Each of these receivers are designed to sense different smells. The signals gathered by sensors from surroundings are transformed to binary codes via electronic systems and then sent to a computer. These electrical signals are processed with various pattern recognition methods and smell diagnosis is achieved. Türk Toraks Derneği 15. Yıllık Kongresi

13. SensorsUsed in ElectronicNose • Quartz Crystal Microbalance Sensors (QCM) • Surface Acoustic Wave Devicies (SAW) • Metal Oxide Semiconductors (MeOX) • Inter Digital Transducer (IDT) • Optical Sensors Türk Toraks Derneği 15. Yıllık Kongresi

14. SurfaceAcousticWaveDevicies (SAW) Türk Toraks Derneği 15. Yıllık Kongresi

15. Inter DigitalTransducer-IDT • Interdigital Transducer is a micro electronic device, it is covered by detector materials and conductivity and capacity changes are measured. For gas sensor prototype an IDT was developed whose electrode linewidth is 10 m and width is 3 mm, length is 5 mm and formed by 125 pairs of electrode. Conductivity and capacity changes Δσ, ΔC The system used with the measurements carried out with alternating current and direct current (on the left) Türk Toraks Derneği 15. Yıllık Kongresi

16. Quartz Crystal Microbalance (QCM) Sensör A QCM sensor is a quartz resonator, covered with detector chemical formed by detectors. Owing to perception of gas molecules by QCM sensors, the relation between Δm(g) mass differences are turned to Δf(Hz) frequency changes by means of Sauerbey equity. A(cm²) : Perception surface areaCf : Mass perception stable of quartz crystal Δf (Hz) : Frequency changeΔm (g) : Mass change Türk Toraks Derneği 15. Yıllık Kongresi

17. QCM Piezoelectric crystal Crystal center plated with gold and polymeric material Back electrod Front electrod Crystal holder Türk Toraks Derneği 15. Yıllık Kongresi

18. Sensor Row Used in Quartz Crystal Microbalance (QCM) Elektronic Nose Türk Toraks Derneği 15. Yıllık Kongresi

19. QCM Sensor Smell Detection Türk Toraks Derneği 15. Yıllık Kongresi

20. DesignandSynthesis of DetectorMolecules • Size of perception is measured by deviation portion of transducine from the basic point when the gas or the group of gas is sent to detector. This deviation is provided by chemical detector covered over transducer. This process is carried out in this sequence. • 1. Between the molecul or molecule group we want to perceive and chemical detector interactions are seen among the molecules like • Hydrogen bond • - interaction • Self assembly • while the chemical detectors are designed it is • designed to form these interactions. Türk Toraks Derneği 15. Yıllık Kongresi

21. DesignandSynthesis of DetectorMolecules Theinteractionbetweenthechemicaldetectorandanalytematerial (moleculorgroup of moleculesthataredesiredto be perceived) causes an increase of massovertransducer. Theincrease of massresults a decrease of maintransducerfrequency in otherwords a deviancefromthemaincondition. It can be saidthatthegreater is extent of deviationthehighertheperceptionwill be. Concerningtheoccurance of perceptionandexisting in greatnumber it is completleyrelatedtospecification of chemicaldetector. Hence, thedesignandsynthesisprocess of detectorchemical is extremelyimportant. Türk Toraks Derneği 15. Yıllık Kongresi

22. DesignandSynthesis of DetectorMolecules • After the design of molecules, the proces of synthesis requires a long time. This process includes; • Design of molecule • Determination and purchase of necessary material to synthesize the designed molecule • Synthesize and structure characterization Türk Toraks Derneği 15. Yıllık Kongresi

23. DesignandSynthesis of DetectorMolecules An example of synthesizing process Seperation of synthesized detectors with a colon Detector molecules whose synthesizing process is completed. Türk Toraks Derneği 15. Yıllık Kongresi

24. Transducer Covering and Obtaining Detectors System of sensor covering Türk Toraks Derneği 15. Yıllık Kongresi

25. Türk Toraks Derneği 15. Yıllık Kongresi

26. Metals Pt, Pd, Ni, Ag, Au, Sb, Rh, ... Semi conductors Si, GaAs, InP, ... Ionic compounds Electronic conductors(SnO2, TiO2, Ta2O5, IrOx, In2O5, . Blending conductors(SrTiO3, La1-xSrxCo1-yNiyO3, perovskites Ga2O3, ...) Ionic conductors(SrTiO3(ZrO2, LaF3, CeO2, CaF2, Na2CO3, ß-alumina, Molecular crystal Phtalocyanine (PbPc, LuPc2, LiPc, (PcAlF)n, (PcGaF)n, ...) Alkanethiols, dialkilsulphur, (alkoxy-)silanes, carboxylic acid, ... Self-editing layers Langmuir-Blodgett films Phthalocyanine, Polydiacetylene, Cd-Arachidatphthalocyanines, polydiacetylenes, Cd-arachidat,... Clathrate compounds zeolites, calixarenes, resorcinarenes, cyclodextrines, crown-ethers, cyclophanes, cyclopeptides, ... Polimers polyethers, polyurethanes, polysiloxanes, polypyrroles, polythiophenes, polyfluorocarbons, polyolefines, PTFE, nafion, ... Biomolecules functional compounds synthetic: phospholipides, FMD- and AIDS-virus-epitopes, ...natural: glucose-oxidase, lactose-permease, bacterial cellulose, E. coli-cellmembranes, more general: enzymes, receptors, transport-proteins, membranes, cells, ... ChemicalSensorMaterials Türk Toraks Derneği 15. Yıllık Kongresi

27. Δm Mass change Q Reaction heat change σ Conductivity resulting from voltage, heat and frequency dependent changes, photoconductivity changes C Capacitance changes ΔE, I(η) Electrochemical potantial differance changes and frequency function changesη ε(η) Optical absorption and reflection changes MeasurementParameters of Transducers Türk Toraks Derneği 15. Yıllık Kongresi

28. Electronicnosedetectionareas Türk Toraks Derneği 15. Yıllık Kongresi

29. ElectronicNoseApplicationsin FoodIndustry • Determining freshness of products like fish and meat • Determining the food bacteria or mould growth • Classification of aromatic drinks • Quality classification of coffee and cereals • Determining fruit ripening Türk Toraks Derneği 15. Yıllık Kongresi

30. ElectronicNoseApplicationsin EnvironmentalHealthArea • Environmental pollution monitoring • Monitoring biochemical condition of waste water • Quality control of drinking water • Indoor air quality monitoring • Airport luggage check Türk Toraks Derneği 15. Yıllık Kongresi

31. ElectronicNoseApplicationsin Military • Detecting the place of military mines • Detecting the gases used with chemical weapons Türk Toraks Derneği 15. Yıllık Kongresi

32. ElectronicNoseApplicationsin Medicine • Detecting respiratory tract infections with breath samples • Diagnosing diabete • Diagnosing lung cancer • Diagnosing nephropathy • Diagnosing urinary tract infection • Determining the level of anaesthezia gas Türk Toraks Derneği 15. Yıllık Kongresi

33. ElectronicNoseApplicationsin Bacteriology • Classification of micro-organisms • Identification of infections in hospitals • Classification of bacterias causing ear, nose, throat and eye infection • Classification and distinguishing various bacterias like (Coliform, Anaerob) • Quantifying glucose and HbA1c amount in blood with smell of breath Türk Toraks Derneği 15. Yıllık Kongresi

34. Türk Toraks Derneği 15. Yıllık Kongresi

35. DUMLUPINAR UNIVERSITY GAS and SMELL IDENTIFICATION LABORATORY Türk Toraks Derneği 15. Yıllık Kongresi

36. Sensor Test System Türk Toraks Derneği 15. Yıllık Kongresi

37. Network Analizörü Mass Flow Kontrolörü PC Azot Uçucu organikler Sensör Hücresi Sensor Test System Uçucu organikler Türk Toraks Derneği 15. Yıllık Kongresi

38. Sensor Test System Türk Toraks Derneği 15. Yıllık Kongresi

39. HumanBreath • In human breath, 3481 volatile organic compounds were identified using Gas Chromotography and Mass Spectrometry • In healthy human breath, there are 200–400 different gases found. • On the condition of an illness, in relation to the reason of disease, the ratio of gases found in the breath differs. This is a symptom of the disease and if the ratio change of these gases can be defined, the disease can be diagnosed. • Using elecronic nose technology, gases in the breath can be detected and diseases can be diagnosed. Türk Toraks Derneği 15. Yıllık Kongresi

40. Volatilecompounds in humanbreathwhoseamountdiffersin variousdiseases Türk Toraks Derneği 15. Yıllık Kongresi

41. Volatilecompounds in humanbreathwhoseamountdiffersin variousdiseases

42. RelationshipBetweenBreathOdor-Disease • Parameters produced by human body, sheds light on diagnosing illnesses. Odors produced by various organs lead these parameters produced by human body. In this context, some diseases may be diagnosed with human breath odor. Türk Toraks Derneği 15. Yıllık Kongresi

43. How do thegases in breath form? • While blood is getting cleared in lungs, gases in the blood pass to breath via alveoli. Consequently, many parameters related to body are found in breath. The gases exhaled with breath consist of various alkalic and aromatic compounds. Each of these gas compounds (volatile chemicals) may point out information about diseases. Türk Toraks Derneği 15. Yıllık Kongresi

44. TÜBİTAK Project with number 104E053 Diagnostic System Design for Medical Applications using QCM-SSC Gas Sensor Serial ____________________________________ QCM sensors used in this project; are produced by TÜBİTAK Marmara Research Center Materials Institute Group. Türk Toraks Derneği 15. Yıllık Kongresi

45. Project Sub-Title • Quantifyingglucoseand HbA1c parametersamount in bloodwithsmell of humanbreath Türk Toraks Derneği 15. Yıllık Kongresi

46. Breathstoragebag Türk Toraks Derneği 15. Yıllık Kongresi

47. MeasurementSystem Türk Toraks Derneği 15. Yıllık Kongresi

48. DesignedSystem Türk Toraks Derneği 15. Yıllık Kongresi

49. DesignedSystem

50. ExperimentationProtocol-1