DOI 10.5162/IMCS2012/5.5.

Propofol analysis using a TiO2 nanotube-based gas sensor and a solid electrolyte CO2 sensor
T. Kida1*, M.-H. Seo2, S. Kishi2, M. Yuasa1, Y. Kanmura3, N. Yamazoe1, and K. Shimanoe1 Department of Energy and Material Sciences, Faculty of Engineering Sciences, Kyushu University, Kasuga-shi, Fukuoka, Japan 2 Department of Molecular and Material Sciences, Interdisciplinary Graduate School of Engineering Science, Kyushu University, Kasuga-shi, Fukuoka, Japan 3 Department of Anesthesiology and Critical Care Medicine, Kagoshima University, Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan *Corresponding author: Email kida@mm.kyushu-u.ac.jp
1

Abstract For the development of gas sensors applied to organic gas detection, the preparation of sample gases containing organic vapors with controlled concentrations is sometime necessary in accurately evaluating the gas sensor properties. In this study, using a diffusion method where liquid samples were heated and vaporized under a carrier gas flow, we prepared standard sample gases containing 2,6-diisopropylphenol (propofol), which are breath markers for diabetes and anesthesia depth, respectively. We used a NASICON (Na3Zr2Si2PO12; Na+ conductor)-based CO2 sensor combined with a Pt/Al2O3 combustion catalyst to prepare propofol gases with known concentrations. We demonstrated that the prepared propofol gases with constant concentrations were effectively detected by Au loaded-TiO2 nanotube sensors. Key words: TiO2, Na3Zr2Si2PO12, semiconductor, solid electrolyte, propofol

Introduction Human breath analysis is a promising technique as a real-time medical diagnostics that allows noninvasive monitoring and detection of illnesses. Human breath contains a wide variety of compounds, including inorganic gases such as NO and volatile organic compounds (VOCs) such as ethanol and acetone. Their concentrations are closely associated with those in blood, and as such changes in the concentration are indicative of persons medical conditions. Recently, the analysis of 2,6-diisopropylphenol (propofol) in blood and breath has attracted considerable attention. Its chemical structure is shown in Fig. 1. Propofol is intravenously administered hypnotic agent used for induction and maintenance of anesthesia and for sedation of patients in intensive care units. The determination of propofol concentrations in expiratory air likely allows the real-time monitoring of changes in its concentration in blood during anesthesia. High-performance gas sensors with a compact size and low cost, if available, would provide an inexpensive and efficient way to rapidly screen for certain diseases.

OH
Fig. 1. Chemical structure of 2,6-diisopropylphenol (propofol).

However, existing sensors for VOC detection still have problems, i.e., low sensitivity, low selectivity, and interference from high humidity contained in breath. Thus, further sensor development is highly desirable. We have recently developed TiO2 nanotube-based gas sensors [1,2]. Nanostructured films made from TiO2 nanotubes provided effective pores in the films for gas diffusion and gave high sensitivity to VOCs like toluene and alchol. In this study, we applied this sensor for the detection of propofol.

IMCS 2012 The 14th International Meeting on Chemical Sensors

489

DOI 10.5162/IMCS2012/5.5.1
H However, continuous c preparation of standard d propofol gases g is nec cessary for the investiga ation of the properties of o the senso ors. Standard d propofol gases g are no ot commerci ally availavel. To prepar re standard propofol p gas ses, ed a simple e system of o determin ning we use organic gas concen ntrations in sample gas ses d by a diffus sion method where a liq quid prepared sample w was heated and vaporized [3,4]. In t this system, organic com mpounds in sample gas ses ecomposed to CO2 via cataly are de ytic combust tion and the e resulting CO C 2 is detec cted using a solid-state CO C 2 sensor. Organic va apor rations are determined from the C CO2 concentr concentr ration determ mined with the CO2 sen nsor accordin ng to their r stoichiome etric compllete combust tion reaction ns. We dem monstrated t that the syst tem could continuously y monitor a and determin ne the ethan nol vapor con ncentration i n a sample gas stream prepared by y heating liq quid e sample gas s thus prepa ared ethanol, and that the e used for the t accurate e evaluation n of could be gas sens sor propertie es for VOC de etection. I In this study y, we further r examined the feasibility y of our developed d system s for the determin nation of concentrations of o propofol. T The propofol gases thus prepared and concentrat tion d were used d to study th he properties s of analyzed TIO2 na anotube-based gas se ensors for the detection n of propofol. Experim mental T TiO2 nanotube-based sensors w were fabricate ed by a hyd drothermal process p and d a screen p printing meth hod [1]. A TiO2 commer rcial powder (P-25, Deg gussa) was hydrotherm ally OH solution (10 mol/L) at treated with a NaO or 24 h in a Teflon-lined T autoclave. a A After 230C fo the trea atment, the TiO2 powde er was wash hed n HCl solu ution (0.2 mol/L) un der with an ultrasoni ic irradiation for 1 h. The en, the obtain ned products s were caref fully washed with D.I. wa ater to remov ve Cl- ions, filtered, f and dried d to reco over TiO2 nan notubes. The e resulting nanotubes n w were calcined at 600C for 1 h, and then subjected d to ent using a planet-type p b balla ball-milling treatme anopaticles were w deposiited mill for 3 h. Gold na on TiO2 nanotubes by b a photoch hemical meth hod manner repo orted elsew where [5]. T The in a m prepared d nanotubes s (1.0 g) were dispersed d in D.I. wate er (100 mL) containing ethanol (10 m mL), and then n a designat ted amount of o HAuCl4 (0 0.52.0 wt%) ) was added d in the suspe ension. Etha anol was use ed as an ele ectron donor r. UV light (2 250 W) was irradiated to t the suspension for 3 h stirring. The obtained Au-loaded A T TiO2 under s nanotube shed with D.I. water, filte ered, es were was and dried d to recover Au-loaded TiO T 2 nanotub bes, which w were then ca alcined at 600C 6 for 1 h. Transmis ssion electro on microsco opy (TEM) w was used to observe the morp phology of deposited d Au u particles. The T loading amount of Au was tun ned by changing the con ncentration of o [AuCl4]in a precurso or solution and determ mined by ductively coupled plasm ma atomic emission ind spectroscopy (ICP-AES). The obtained TiO O2 nanotubes s coated wit th Au nanoparticles we ere deposite ed on an Al2O3 substrate with gold electrodes. The film wa as calcined at a 600C in air. The str ructure of the e fabricated sensor was shown in Fig. F 2 (a). Th he sensor re esponse of t the TiO2 sen nsor was defined as Rair/Rgas, whe re Rair and Rgas are the e electric res sistances in a air and in a test gas, res spectively. The T TiO2 sen nsor was operated at 450-550C.

Fig g. 2. The struc ctures of (a) TiO2-based sensor and (b) the CO2 sens sor.

The solid-state CO2 sens sor was fab bricated by depositing d a carbonate la ayer on a NA ASICON (N Na+ conduc ctor; Na3Zr2SiPO12) sin ntered disk. The T NASICO ON disk was prepared by a sol-gel method. As s an auxilia ary layer, ted on the NASICON N Li2CO3-BaCO3 was deposit dis sk. BiCuVOx x-based solid d reference electrode wa as attached to the N NASICON disk. The detailed fabrication proc cess was reported els sewhere [6, 7]. 7 The elect tromotive forc ce (EMF) of the devic ce was m measured with an ectrometer. The senso or was ope erated at ele 500C. The pr ropofol sens sing propertie es of the TiO O2 films were w measu ured in a gas-flow apparatus sho own in Fig . 3. Sampl le gases containing propofol in air were prepared by a ffusion met thod using a standa ard gas diff generator (Per rmeater PD-1B, GASTEC) [3, 4]. Liq quid propofo ol was pla aced in a capillary container and heated at t 50C to vaporize opofol. The generated g va apor was delivered to pro a chamber c where the TiO2 2 sensor was placed. Sy ynthetic air was used as a carrier gas.

IMCS 2012 The 14th International Meeting on Chemical Sensors

490

DOI 10.5162/IMCS2012/5.5.1

Fig. 3. E Experimental setup for measuring the sensing properties of o TiO2-based sensors a and preparing g standard pro opofol gases.

T The concen ntration of propofol p in the sample gas was de etermined by y decompos sing yst chamber shown in Fig g.3. propofol at the cataly tely A Pt/Al2O3 catalyst was used to complet decompo ose propofol l into CO2. The catalyst w was heated a at 500C wit th an electri ic furnace. T The resulting g CO2 contained in the sample gas w was delivered d to the cham mber where the CO2 sen nsor was plac ced. F Fig. 4 shows s a typical calibration cu urve of the CO2 sensor. The T EMF of the device w was o the logarit thm of CO2 concentratiion, linear to following g the Nernst behavior. From F this cur rve, the conc centration of f CO2 in sam mple gases c can be deter rmined.

Fig g. 5. Dynami ic transient o of the EMF of the CO2 sen nsor in response to propoffol gases with h different con ncentrations. The concentr rations of pro opofol was det termined from m the calibrattion curve of f the CO2 sen nsor.

The concentration c n of propo ofol was successfully co ontrolled by changing th he mixing te of the par rent propofoll gas and a synthetic rat air r. According gly, the res sponse of the CO2 sensor chang ged as sho own in Fig.5. It is at the presen nt method allowed for noteworthy tha the e continuous s generation of propofol gas and in-situ determination of its concentration in sample gases. Fig. 6 shows s the S SEM and TEM M images of TiO2 nanotubes de ecorated with w Au nanoparticles. The SEM image shows the porous structu ure of the sensing film. This str ructure allow ws for the dif ffusion of lar rge sized gas such as propofol p dee ep inside the e sensing film m. The hig ghly anisotro ropic shape e of the nanotubes suc ccessfully fo ormed the observed porous structure. The T TEM image e clearly showed that Au A nanoparti cles were lo oaded on e nanotubes. . An average e particle size e was ca. the 20-50 nm at 0.92 wt % . Increasing g the Au ading amount led to an in ncrease in the particle loa siz ze of Au.

Fig. 4. C Calibration cu urve of the CO2 sensor.

Results and Discus ssion W We first analyzed the propo ofol concentr ration in sample gases with the C CO2 sensor. Fig. 5 show ws the respon nse of the C CO2 to CO2 formed after the combustion n of sensor t propofol gases pr repared by the diffus sion centration w was method. The propofol conc ned accordin ng to the simple compllete determin combust tion reaction of propofol.

IMCS 2012 The 14th International Meeting on Chemical Sensors

491

DOI 10.5162/IMCS2012/5.5.1
Co onclusion Inorder r to detect 2 2,6-diisoprop pylphenol (pr ropofol) for r breath a analysis, we w have fab bricated TIO2 nanotube-b based gas sensor s by a hydrotherma al method. The sensor r showed gh sensitivity y to propofol, , which was prepared hig by a diffusion method us sing a liquid sample. he concentra ation of prop pofol in the prepared Th sample gas was detem mined by a solid ectrolyte CO O2 sensor combined with a ele combustion catalyst. c T The presen nt study ystem is demonstrated that the d eveloped sy useful for the analysiis and co ontineous v organ nic gases. generation of volatile Re eferences
[1] M. -H. Seo, M. M Yuasa, T. K Kida, J. -S. Hu uh, K. Shimanoe, N. N Yamazoe, S Sens. Actuator rs B: Chem., 2009 9, 137, 513-52 20.; doi: 10.1016/j.snb b.2009.01.057 7. M Yuasa, T. K Kida, J. -S. Hu uh, N. [2] M. -H. Seo, M. Yamazoe, K. Shimanoe, S Sens. Actuator rs B: Chem., 2011, 154, 251-25 56.; doi: 10.1016/j.snb b.2010.01.069 9. H. Seo, S. Kis shi, Y. Kanmur ra, N. [3] T. Kida, M. -H Yamazoe, K. Shimanoe, A Anal. Chem., 2010, 2 82, 3315-3319.; doi: 10.1021/a ac100123u. H. Seo, S. Kish hi, Y. Kanmura a, K. [4] T. Kida, M.-H Shimanoe, Anal. A Methods,, 2011, 3, 1887-1892.; doi: 10.1039/ /c1ay05223c [5] B. Zhu, Q. Guo, X. Huang,, S. Wang, S. Zhang, S. Wu, W. Huan ng, J. Mol. Cattal. A, 2006, 249, 2 211217. doi: 10.1016/j.molcata a.2006.01.013 3 a, K. Shimano oe, N. [6] T. Kida, S. Kishi, M. Yuasa Yamazoe, J. Electrochem.. Soc., 2008, 155, 1 J117J121. doi: 10 0.1149/1.28890 011 zoe, K. Shima [7] T. Kida, S. Kishi, N. Yamaz anoe, Sens. Lett., 2011, 2 9, 288-2 293. doi: 10.1166/sl.20 011.1466

Fig. 6. S SEM and TE EM images of f TiO2 nanotu ubes loaded wi ith Au.

F Fig. 7 shows s the depend dence of sen nsor response e of the TiO O2-based ga as sensor. T The device r responded well w to chang ges in propo ofol concentr ration, demo onstrating its high sensitiv vity to propo ofol. The sens sor response e was improv ved ositing Au na anoparticles on nanotub bes. by depo An impr rovement of f catalytic activity a of T TIO2 nanotube es is possi ibly due to the observ ved increase e in the sen nsor response. The hig ghly disperse ed state of o Au nan noparticles on nanotube es may als so contribute to the h high sensitivit ty.

Fig. 7. D Dependence of sensor responses of T TiO2 nanotube e devices on propofol p conce entration at 50 0C (a) TiO2 n nanotubes, (b) ) loaded with Au A at 0.92 wt. %.

IMCS 2012 The 14th International Meeting on Chemical Sensors

492