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 1 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

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 person’s 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.

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.

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IMCS 2012 – The 14th International Meeting on Chemical Sensors 490

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IMCS 2012 – The 14th International Meeting on Chemical Sensors 491

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eferences M. -H. Seo, MShimanoe, NChem., 200910.1016/j.snb

M. -H. Seo, MYamazoe, K.Chem., 201110.1016/j.snb

T. Kida, M. -HYamazoe, K.3315-3319.;

T. Kida, M.-HShimanoe, Adoi: 10.1039/

B. Zhu, Q. GWu, W. Huan217. doi: 10.

T. Kida, S. KYamazoe, J.J121. doi: 10

T. Kida, S. KSens. Lett., 210.1166/sl.20

r to detect 2r breath a2 nanotube-bal method. y to propofol,

method usation of prop

was detemO2 sensor catalyst. Tthat the d

he analysivolatile organ

M. Yuasa, T. KN. Yamazoe, S9, 137, 513-52b.2009.01.057

M. Yuasa, T. K Shimanoe, S, 154, 251-25b.2010.01.069

H. Seo, S. Kis Shimanoe, Adoi: 10.1021/a

H. Seo, S. KishAnal. Methods,/c1ay05223c

uo, X. Huang,ng, J. Mol. Cat1016/j.molcata

ishi, M. YuasaElectrochem.

0.1149/1.28890

ishi, N. Yamaz2011, 9, 288-2011.1466

2,6-diisopropanalysis, wbased gas sThe sensor, which was sing a liquidpofol in the mined by

combined The presen

eveloped syis and conic gases.

Kida, J. -S. HuSens. Actuator20.; doi: 7.

Kida, J. -S. HuSens. Actuator56.; doi: 9.

shi, Y. KanmurAnal. Chem., 2ac100123u.

hi, Y. Kanmura, 2011, 3, 188

, S. Wang, S. tal. A, 2006, 2a.2006.01.013

a, K. Shimano. Soc., 2008, 1011

zoe, K. Shima293. doi:

pylphenol we have sensor by r showed prepared sample. prepared a solid with a

nt study ystem is ontineous

uh, K. rs B:

uh, N. rs B:

ra, N. 2010, 82,

a, K. 7-1892.;

Zhang, S. 249, 211-3

oe, N. 155, J117-

anoe,

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IMCS 2012 – The 14th International Meeting on Chemical Sensors 492