- Email: [email protected]
Wearable and flexible oxygen sensor for transcutaneous oxygen monitoring
Sensors and Actuators B 95 (2003) 373–377
Wearable and flexible oxygen sensor for transcutaneous oxygen monitoring Kohji Mitsubayashi a,∗ , Yoshihiko Wakabayashi a , Daisuke Murotomi a , Takua Yamada a , Tatsuya Kawase a , Suketsune Iwagaki b , Isao Karube c b
a Department of Human and Information Science, Tokai University, 1117 Kitakaname, Hiratsuka, Kanagawa 259-1292, Japan Department of Physical Recreation, School of Physical Education, Tokai University, 1117 Kitakaname, Hiratsuka, Kanagawa 259-1292, Japan c Katayanagi Advanced Research Laboratories, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan
Abstract A wearable and flexible oxygen sensor with membrane structure was constructed by pouching KCl electrolyte solution by both non-permeable (metal weldable) sheet and gas-permeable membrane with Pt- and Ag/AgCl-electrode patterned by microfabrication techniques. The electrolyte solution was fastened only by heat-sealing the edges of the weldable membranes without any chemical adhesives. The wearable oxygen sensor (thickness: 84 m) was applied to the electrochemical measurement with a fixed potential of −600 mV vs. Ag/AgCl, thus obtaining the calibration range to dissolved oxygen (DO) from 0 to 8.0 mg/l and the quick response time (11 s to 90% of a steady-state current), which operate similarly to a commercially available oxygen electrode. By placing the wearable oxygen sensor onto the forearm skin surface of the subject inhaling various concentrations of oxygen the gas phase as the physiological application of it, the transcutaneous oxygen pressure was successfully monitored without any inconveniences such as skin inflammation, etc. © 2003 Elsevier B.V. All rights reserved. Keywords: Wearable oxygen sensor; Transcutaneous oxygen monitoring; Gas-permeable membrane; Metal weldable membrane
1. Introduction Several kinds of oxygen sensors has been used in many kinds of fields, not only for the measurement of oxygen concentration in the gas and in the liquid phases, but also for the medical, physiological and biological applications, i.e. transcutaneous monitoring of arterial oxygen pressure [1–3]. Some biosensors have been also constructed using the oxygen sensor monitoring the oxygen consumption induced by enzyme reaction [4]. In general, the transcutaneous oxygen sensor has been in use for monitoring arterial oxygen pressure in premature infants to prevent Retinopathy of Prematurely at NICU (neonatal intensive care unit) [5–8]. Commercially available sensors with a rigid cylindrical cell are fixed to the infant skin with adhesive plaster, thus resulting in common skin rashes and general discomforts on the infants. A new oxygen sensor with good flexibility and wearability, such as a clinical wet-pack, has been required for transcutaneous monitoring in comfort. ∗ Corresponding author. E-mail address: [email protected] (K. Mitsubayashi).
0925-4005/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0925-4005(03)00441-6
We previously reported some flexible chemical sensors, i.e. conductimetric [9], moisture, hygrometric and biosensors [10], which constructed by microfabrication techniques onto thinner polymer substrates. Those sensors were made it possible to monitor the chemical composition of biological fluids such as tears [11,12], airway mucus, sweat, saliva, etc. In this work, we have constructed the wearable oxygen sensor with good flexibility by laminating some functional polymer membranes such as gas-permeable and metal weldable membranes. After evaluating the characteristics of the device in vitro, the wearable sensor has been placed directly onto the subject’s skin surface for the transcutaneous oxygen measurement.
2. Experimental 2.1. Construction of a wearable oxygen sensor Fig. 1 illustrates the structure of the wearable oxygen sensor. The wearable oxygen sensor (width: 15 mm) was constructed using both non-permeable sheet (Surlyn IONOMER, thermoplastic sheet, 1652, poly(ethyleneco-methacrylic acid) (EMAA) ionomer-based materials,
374
K. Mitsubayashi et al. / Sensors and Actuators B 95 (2003) 373–377
Fig. 1. Structure of a wearable oxygen sensor with gas-permeable membrane coated electrodes and non-permeable membrane.
thickness: 50 m, melt-point: 100 ◦ C, ion type: zinc, density: 0.94 g/cm3 , Mitsui Du-Pont Chemical Co. Ltd., Tokyo, Japan) and gas-permeable membrane (fluorinated ethylene-propylene [FEP], thickness: 25 m, Oriental Yeast Co. Ltd., Tokyo, Japan), which was coated with Pt-electrode (thickness: 2000 Å, width: 2.0 mm) and Ag/AgCl-electrode (thickness: 3000 Å, width: 5.0 mm) by microfabrication techniques, respectively. These membranes offer chemical stability, tear resistance, and flexibility. The patterning processes of the Pt- and Ag-electrode on the gas-permeable membrane are as follows. At first, a 2-strip mask pattern for Pt- and Ag-electrode was formed onto the permeable membrane as substrate by photolithography process using a spin coater (1H-D3, Mikasa Corp., Tokyo, Japan) and a mask aligner (MA-10, Mikasa Corp., Tokyo, Japan) with positive-type photo-resist resin. The Pt-layer was deposited by use of spattering (CFS-4ES-231, Shibaura Engineering Works Co. Ltd.) onto the patterned membrane. After the narrow layer for Pt-electrode on the membrane was covered with photo-resist resin, the Ag-layer was coated by spattering onto the Pt pre-coated strip. The photo-resin film was removed from the membrane substrate by rinsing with acetone solvent, thus obtaining the desired strip-shape electrodes onto the gas-permeable membrane. After washing with distilled water, the Ag-layer on the membrane was chloridized by electrochemical methods (110 mV, 4.5 min) with 0.1 mmol/l HCl solution [13], thus resulting in the Ag/AgCl layer as the counter/reference electrode. Then, the wearable oxygen sensor was constructed in a sandwich configuration with a membrane filter (IsoporeTM Membrane Filter, Polycarbonate, TKTP04700, pore size: 12 m, Nihon-Millipore, Tokyo, Japan) with electrolyte solution between the gas-permeable membrane with Pt- and Ag/AgCl-electrode and the non-permeable sheet. All the edges of the layer-built cell with 0.1 mmol/l KCl were fastened by heat-seal system (SURE Sealer, NL-201P, Ishizaki
Electricity Manufacturing Co. Ltd., Tokyo, Japan), thus obtaining the thinner Clark-type oxygen sensor with a bag-like electrolyte cell. The oxygen sensor was constructed only by heat-sealing even the metal deposited regions without any chemical adhesion because of excellent metal weldability of the non-permeable sheet, thus obtaining good flexibility and safety for the latter application onto the skin surface. Behavior of the wearable oxygen sensor was evaluated in the dissolved oxygen (DO) measurement and the calibration range was assessed using test solution of distilled water or sodium sulfite solution. A two-electrode electrochemical method was employed whereby the Pt-electrode on the gas-permeable membrane was used as the working electrode and the Ag/AgCl-electrode was used as the counter/reference electrode. A computer-controlled potentiostat (Potentiostat, Model 1112, Fusoseisakusho Inc., Kawasaki, Japan) was used for DO measurement at a fixed potential. The output current was continuously monitored on a computer graphic display and saved on the hard disk for later analysis. A commercially available DO sensor (B-505, Iijima Electronics Corp., Gamagori, Japan) was also used simultaneously in the measurement system, and the characteristics of the two devices were compared. 2.2. Transcutaneous oxygen measurement by the wearable sensor The transcutaneous oxygen measurement with the wearable sensor was conducted for healthy male volunteers with no history of skin diseases. They were instructed beforehand as to how the determination was to be performed and asked to behave naturally after obtaining their prior consent. The sensor was sterilized using a 70% ethanol solution before use. The tip of the wearable oxygen sensor was placed directly onto the forearm skin surface with a commercial available skin warmer (Elepuls HV-F303, OMRON, Kyoto,
K. Mitsubayashi et al. / Sensors and Actuators B 95 (2003) 373–377
Japan) and a thinner thermistor (103JT-050A, Ishizuka Electronics Corp. Tokyo, Japan), and fixed by an adhesive bandage. The outputs of the wearable oxygen sensor and the thermistor were monitored continuously for the subject inhaling various concentration of oxygen (21–60–21%) using a mouthpiece. A transcutaneous oxygen pressure (tcPO2 ) is related with the output current of the wearable sensor. The warmer temperature was controlled at 40 ◦ C for improving oxygen penetrability from an arterial blood to the skin surface, and for inhibiting a low-temperature skin-burn. The effect of the warming temperature on the sensor behavior was additionally evaluated from 37 to 42 ◦ C. The transcutaneous oxygen measurement with the wearable device was carried out onto various regions of human body (wrist, forearm, elbow, upper arm, chest wall and palm) in order to investigate the gas transmissibility and to obtain the suitable site for continuous monitoring.
3. Results and discussion 3.1. Evaluation of the wearable oxygen sensor The sensor with the thinner structure (thickness: 84 m) possessed flexibility, tear resistance and chemical stability. Prior to evaluating the sensor performance in the DO measurement, the device was applied to the cyclic voltammography analysis. Fig. 2 illustrates the cyclic voltammogram (CV) of the wearable device by potential sweeping by the potentiostat (CV-50W, Bioanalytical System Inc., Tokyo, Japan) from 0 to −1000 mV vs. Ag/AgCl. As the figure indicates, a peak current was observed at the reduction potential of −600 mV, which is consistent with the existing commercial available oxygen electrode. Based on the result of CV, the fixed potential of −600 mV vs. Ag/AgCl was applied
Fig. 2. CV of the wearable oxygen sensor with Pt-working and Ag/AgCl-counter/reference electrodes.
375
Fig. 3. Typical response of the sensor output by applying nitrogen gas (99%).
by the computer-controlled potentiostat to the Pt working electrode of the oxygen sensor in later experiments. By applying nitrogen gas (99%) in the gas phase or sodium sulfite solution without DO in the liquid phase, the current output of the wearable oxygen sensor decreased rapidly (Fig. 3). The response time for output current to reach 90% of the steady-state value was 11 s on equality with that of the commercial one. The wearable sensor calibration plots are shown in Fig. 4. In this figure, the sensor output is presented as a displacement of current value. The current output of the sensor device was linearly related to the concentration of the DO over a range 0.0–8.0 mg/l, with a correlation coefficient of 0.999 deduced by regression analysis, as shown by the following equation: sensor output (A) = 0.24 + 5.11[DO (mg/l)] As just described, the wearable device constructed by the microfabrication techniques with the functional membranes has indicated satisfactory performances as the oxygen sensor in the liquid- and gas-phase. We then applied the sensor for the transcutaneous oxygen measurement.
Fig. 4. Calibration curve of the wearable sensor for the DO measurement.
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Fig. 5. Typical output of the transcutaneous oxygen measurement by the wearable sensor attached onto the forearm skin of the subject inhaling the controlled oxygen (21–60–21%, sequentially).
3.2. Transcutaneous oxygen measurement by the wearable sensor Fig. 5 shows the typical response for transcutaneous oxygen pressure and the skin temperature. The oxygen concentration supplied through the mouthpiece was controlled from 21 to 60% (10 min) to 21%. As the figure indicates, the output current of the wearable sensor related tcPO2 value was rapidly increased by the inhalation of 60% oxygen air, and after keeping the steady-state current, then decreased by 21% oxygen air. The skin surface was controlled at approx. 40 ◦ C as indicate in the figure. The application of the wearable oxygen sensor caused no physical discomfort, i.e. skin rashes and skin-burn, to the subjects. Thus, the wearable sensor was successfully monitored the transcutaneous oxygen measurement. The oxygen transmissibility from the arterial blood to the skin surface was reported to depend on the body regions [7,14]. Fig. 6 shows the output increases of the device attached various regions in subject body, by changing the concentration of inhaling oxygen from 21 to 60%. The skin temperature was controlled at 40 ◦ C in all experiments. As the comparison of the body regions, the high outputs were observed at the arm regions, especially inside the wrist and forearm. From the experimental point of view, the forearm has been considered to be well-suited region for the wearable device application. Fig. 7 shows the effect of the warming temperature at the forearm skin on the output increase of the wearable sensor by changing the concentration of inhaling oxygen from 21 to 60%. As this figure indicates, the output increment after 60% oxygen inhalation was enlarged by increasing in skin temperature because the skin warming induces the oxygen transmissibility from the arterial blood to the skin surface as noted above. The wearable oxygen sensor, however, could be used for transcutaneous monitoring at 37 ◦ C, in which the low-temperature skin-burn is not induced and the warming apparatus is not required for non-invasive measurement.
Fig. 6. Effect of skin surface sites (wrist, forearm, elbow, upper arm, chest wall and palm) on the output increase of the wearable sensor for the transcutaneous measurement by applying from 21 to 60% oxygen.
Fig. 7. Effect of the warming temperature (37, 41, 42 ◦ C) at the skin surface on the output increase of the wearable sensor for the transcutaneous measurement by applying from 21 to 60% oxygen.
4. Conclusions The flexible and wearable oxygen sensor was constructed in a sandwich configuration with membrane filter with KCl electrolyte solution between the non-permeable (metal weldable) sheet and the gas-permeable membrane coated with Pt- and Ag/AgCl-electrode by the photolithograph approach. The electrolyte solution was enclosed only by heat-seal on the edges of the weldable membranes. The wearable oxygen sensor (thickness: 84 m) was calibrated against DO from 0 to 8.0 mg/l being equivalent to the commercially available oxygen electrode. By applying the device onto the forearm skin surface, the wearable sensor
K. Mitsubayashi et al. / Sensors and Actuators B 95 (2003) 373–377
was successfully used to monitor the transcutaneous oxygen pressure without any inconveniences such as skin inflammation, etc. Potential application of the wearable oxygen sensor include not only the safe transcutaneous measurement without the warming apparatus, but also the development of a new wearable biosensor for attached directly to body surfaces for monitoring the chemical composition of biological fluids such as tears, airway mucus, sweat, saliva, etc.
References [1] L.C. Clark, Monitor and control of blood and tissue oxygen tension, Trans. Am. Soc. Art. Int. Org. 2 (1956) 41–52. [2] N.T.S. Evans, P.F.F. Naylor, The oxygen tension gradient across human epidermis, Resp. Physiol. 3 (1967) 38–42. [3] R. Huch, D.W. Lubbers, A. Huch, Reliability of transcutaneous monitoring of arterial PO2 in newborn infants, Arch. Dis. Child. 49 (1974) 213–218. [4] K. Mistubayashi, K. Yokoyama, T. Takeuchi, I. Karube, Gas-phase biosensor for ethanol, Anal. Chem. 66 (1994) 3297–3302. [5] R. Huch, A. Huch, D.W. Lubbers, Transcutaneous measurement of blood PO2 (tcPO2 ), J. Perinat. Med. 1 (1973) 183–191. [6] D.W. Lubbers, A. Huch, R. Huch, Unblutige kontinuierliche erfassung des Saure-Basen-Status beim Menschen durch transcutane Messung des arteriellen PO2 und PCO2 sowie der Hamoglobinkonzentration bei Korpertemperatur, Klin. Wschr. 51 (1973) 411–420. [7] S. Imura, K. Baba, Continuous transcutaneous PO2 measurement in newborn infant, Resp. Circulation 23 (1975) 53–59. [8] G. Duc, Is transcutaneous PO2 reliable for arterial oxygen monitoring in newborn infants? Pediatrics 55 (1975) 55–63. [9] K. Mitsubayashi, K. Yokoyama, T. Takeuchi, E. Tamiya, I. Karube, Flexible conductimetric sensor, Anal. Chem. 65 (1993) 3586–3590. [10] K. Mitsubayashi, K. Yokoyama, T. Takeuchi, I. Karube, A flexible biosensor for glucose, Electroanalysis 7 (1) (1995) 83–87. [11] K. Mitsubayashi, K. Ogasawara, K. Yokoyama, T. Takeuchi, T. Tsuru, I. Karube, Measurement of tear electrolyte concentration, Tech. Health Care 3 (1995) 117–121.
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[12] K. Ogasawara, K. Mitsubayashi, K. Miyata, T. Tsuru, I. Karube, Concentration of tear electrolytes and tear turnover rate by flexible conductimetric sensor in Keratoconjunctivitis sicca patients and normal healthy subjects, Jpn. J. Clin. Opthal. 49 (4) (1995) 779–783. [13] H. Suzuki, I. Watanabe, Y. Kikuchi, Measurement of PO2 using a micromachined oxygen electrode, Chem. Sens. B 15 (1999) 34–36. [14] B. Hagihara, Development and application of blood gas monitoring, Jpn. J. Clin. Pathol. 32 (1984) 1065–1075.
Biographies Kohji Mitsubayashi is an associate professor at Tokai University (Department of Human and Information Science). His research interests include a newly olfactometric system using biological materials, wearable chemical sensors for human monitoring, biomolecular devices, microsystem technology, etc. Yoshihiko Wakabayashi is a graduate student at Tokai University (Mitsubayashi Lab.). He has investigated wearable sensor and monitoring system. Daisuke Murotomi had been a graduate student at Tokai University (Mitsubayashi Lab.) from 1998 to 2000. He had investigated wearable oxygen and biosensor devices. Takua Yamada had been an undergraduate student at Tokai University (Mitsubayashi Lab.) from 1999 to 2000. He had investigated wearable sensor and monitoring system. Tatsuya Kawase had been an undergraduate student at Tokai University (Mitsubayashi Lab.) from 1999 to 2000. He had investigated wearable sensor and physiological monitoring system. Suketsune Iwagaki is a professor of Tokai University (Department of Physical Recreation, School of Physical Education) and a doctor of medicine. Isao Karube is a professor of Tokyo University of Technology and the head of Research Laboratory for Advanced Bioelectronics, National Institute of Advanced Industrial Science and Technology (AIST) after he retired as professor of University of Tokyo in April 2002.
Wearable and flexible oxygen sensor for transcutaneous oxygen monitoring Kohji Mitsubayashi a,∗ , Yoshihiko Wakabayashi a , Daisuke Murotomi a , Takua Yamada a , Tatsuya Kawase a , Suketsune Iwagaki b , Isao Karube c b
a Department of Human and Information Science, Tokai University, 1117 Kitakaname, Hiratsuka, Kanagawa 259-1292, Japan Department of Physical Recreation, School of Physical Education, Tokai University, 1117 Kitakaname, Hiratsuka, Kanagawa 259-1292, Japan c Katayanagi Advanced Research Laboratories, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan
Abstract A wearable and flexible oxygen sensor with membrane structure was constructed by pouching KCl electrolyte solution by both non-permeable (metal weldable) sheet and gas-permeable membrane with Pt- and Ag/AgCl-electrode patterned by microfabrication techniques. The electrolyte solution was fastened only by heat-sealing the edges of the weldable membranes without any chemical adhesives. The wearable oxygen sensor (thickness: 84 m) was applied to the electrochemical measurement with a fixed potential of −600 mV vs. Ag/AgCl, thus obtaining the calibration range to dissolved oxygen (DO) from 0 to 8.0 mg/l and the quick response time (11 s to 90% of a steady-state current), which operate similarly to a commercially available oxygen electrode. By placing the wearable oxygen sensor onto the forearm skin surface of the subject inhaling various concentrations of oxygen the gas phase as the physiological application of it, the transcutaneous oxygen pressure was successfully monitored without any inconveniences such as skin inflammation, etc. © 2003 Elsevier B.V. All rights reserved. Keywords: Wearable oxygen sensor; Transcutaneous oxygen monitoring; Gas-permeable membrane; Metal weldable membrane
1. Introduction Several kinds of oxygen sensors has been used in many kinds of fields, not only for the measurement of oxygen concentration in the gas and in the liquid phases, but also for the medical, physiological and biological applications, i.e. transcutaneous monitoring of arterial oxygen pressure [1–3]. Some biosensors have been also constructed using the oxygen sensor monitoring the oxygen consumption induced by enzyme reaction [4]. In general, the transcutaneous oxygen sensor has been in use for monitoring arterial oxygen pressure in premature infants to prevent Retinopathy of Prematurely at NICU (neonatal intensive care unit) [5–8]. Commercially available sensors with a rigid cylindrical cell are fixed to the infant skin with adhesive plaster, thus resulting in common skin rashes and general discomforts on the infants. A new oxygen sensor with good flexibility and wearability, such as a clinical wet-pack, has been required for transcutaneous monitoring in comfort. ∗ Corresponding author. E-mail address: [email protected] (K. Mitsubayashi).
0925-4005/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0925-4005(03)00441-6
We previously reported some flexible chemical sensors, i.e. conductimetric [9], moisture, hygrometric and biosensors [10], which constructed by microfabrication techniques onto thinner polymer substrates. Those sensors were made it possible to monitor the chemical composition of biological fluids such as tears [11,12], airway mucus, sweat, saliva, etc. In this work, we have constructed the wearable oxygen sensor with good flexibility by laminating some functional polymer membranes such as gas-permeable and metal weldable membranes. After evaluating the characteristics of the device in vitro, the wearable sensor has been placed directly onto the subject’s skin surface for the transcutaneous oxygen measurement.
2. Experimental 2.1. Construction of a wearable oxygen sensor Fig. 1 illustrates the structure of the wearable oxygen sensor. The wearable oxygen sensor (width: 15 mm) was constructed using both non-permeable sheet (Surlyn IONOMER, thermoplastic sheet, 1652, poly(ethyleneco-methacrylic acid) (EMAA) ionomer-based materials,
374
K. Mitsubayashi et al. / Sensors and Actuators B 95 (2003) 373–377
Fig. 1. Structure of a wearable oxygen sensor with gas-permeable membrane coated electrodes and non-permeable membrane.
thickness: 50 m, melt-point: 100 ◦ C, ion type: zinc, density: 0.94 g/cm3 , Mitsui Du-Pont Chemical Co. Ltd., Tokyo, Japan) and gas-permeable membrane (fluorinated ethylene-propylene [FEP], thickness: 25 m, Oriental Yeast Co. Ltd., Tokyo, Japan), which was coated with Pt-electrode (thickness: 2000 Å, width: 2.0 mm) and Ag/AgCl-electrode (thickness: 3000 Å, width: 5.0 mm) by microfabrication techniques, respectively. These membranes offer chemical stability, tear resistance, and flexibility. The patterning processes of the Pt- and Ag-electrode on the gas-permeable membrane are as follows. At first, a 2-strip mask pattern for Pt- and Ag-electrode was formed onto the permeable membrane as substrate by photolithography process using a spin coater (1H-D3, Mikasa Corp., Tokyo, Japan) and a mask aligner (MA-10, Mikasa Corp., Tokyo, Japan) with positive-type photo-resist resin. The Pt-layer was deposited by use of spattering (CFS-4ES-231, Shibaura Engineering Works Co. Ltd.) onto the patterned membrane. After the narrow layer for Pt-electrode on the membrane was covered with photo-resist resin, the Ag-layer was coated by spattering onto the Pt pre-coated strip. The photo-resin film was removed from the membrane substrate by rinsing with acetone solvent, thus obtaining the desired strip-shape electrodes onto the gas-permeable membrane. After washing with distilled water, the Ag-layer on the membrane was chloridized by electrochemical methods (110 mV, 4.5 min) with 0.1 mmol/l HCl solution [13], thus resulting in the Ag/AgCl layer as the counter/reference electrode. Then, the wearable oxygen sensor was constructed in a sandwich configuration with a membrane filter (IsoporeTM Membrane Filter, Polycarbonate, TKTP04700, pore size: 12 m, Nihon-Millipore, Tokyo, Japan) with electrolyte solution between the gas-permeable membrane with Pt- and Ag/AgCl-electrode and the non-permeable sheet. All the edges of the layer-built cell with 0.1 mmol/l KCl were fastened by heat-seal system (SURE Sealer, NL-201P, Ishizaki
Electricity Manufacturing Co. Ltd., Tokyo, Japan), thus obtaining the thinner Clark-type oxygen sensor with a bag-like electrolyte cell. The oxygen sensor was constructed only by heat-sealing even the metal deposited regions without any chemical adhesion because of excellent metal weldability of the non-permeable sheet, thus obtaining good flexibility and safety for the latter application onto the skin surface. Behavior of the wearable oxygen sensor was evaluated in the dissolved oxygen (DO) measurement and the calibration range was assessed using test solution of distilled water or sodium sulfite solution. A two-electrode electrochemical method was employed whereby the Pt-electrode on the gas-permeable membrane was used as the working electrode and the Ag/AgCl-electrode was used as the counter/reference electrode. A computer-controlled potentiostat (Potentiostat, Model 1112, Fusoseisakusho Inc., Kawasaki, Japan) was used for DO measurement at a fixed potential. The output current was continuously monitored on a computer graphic display and saved on the hard disk for later analysis. A commercially available DO sensor (B-505, Iijima Electronics Corp., Gamagori, Japan) was also used simultaneously in the measurement system, and the characteristics of the two devices were compared. 2.2. Transcutaneous oxygen measurement by the wearable sensor The transcutaneous oxygen measurement with the wearable sensor was conducted for healthy male volunteers with no history of skin diseases. They were instructed beforehand as to how the determination was to be performed and asked to behave naturally after obtaining their prior consent. The sensor was sterilized using a 70% ethanol solution before use. The tip of the wearable oxygen sensor was placed directly onto the forearm skin surface with a commercial available skin warmer (Elepuls HV-F303, OMRON, Kyoto,
K. Mitsubayashi et al. / Sensors and Actuators B 95 (2003) 373–377
Japan) and a thinner thermistor (103JT-050A, Ishizuka Electronics Corp. Tokyo, Japan), and fixed by an adhesive bandage. The outputs of the wearable oxygen sensor and the thermistor were monitored continuously for the subject inhaling various concentration of oxygen (21–60–21%) using a mouthpiece. A transcutaneous oxygen pressure (tcPO2 ) is related with the output current of the wearable sensor. The warmer temperature was controlled at 40 ◦ C for improving oxygen penetrability from an arterial blood to the skin surface, and for inhibiting a low-temperature skin-burn. The effect of the warming temperature on the sensor behavior was additionally evaluated from 37 to 42 ◦ C. The transcutaneous oxygen measurement with the wearable device was carried out onto various regions of human body (wrist, forearm, elbow, upper arm, chest wall and palm) in order to investigate the gas transmissibility and to obtain the suitable site for continuous monitoring.
3. Results and discussion 3.1. Evaluation of the wearable oxygen sensor The sensor with the thinner structure (thickness: 84 m) possessed flexibility, tear resistance and chemical stability. Prior to evaluating the sensor performance in the DO measurement, the device was applied to the cyclic voltammography analysis. Fig. 2 illustrates the cyclic voltammogram (CV) of the wearable device by potential sweeping by the potentiostat (CV-50W, Bioanalytical System Inc., Tokyo, Japan) from 0 to −1000 mV vs. Ag/AgCl. As the figure indicates, a peak current was observed at the reduction potential of −600 mV, which is consistent with the existing commercial available oxygen electrode. Based on the result of CV, the fixed potential of −600 mV vs. Ag/AgCl was applied
Fig. 2. CV of the wearable oxygen sensor with Pt-working and Ag/AgCl-counter/reference electrodes.
375
Fig. 3. Typical response of the sensor output by applying nitrogen gas (99%).
by the computer-controlled potentiostat to the Pt working electrode of the oxygen sensor in later experiments. By applying nitrogen gas (99%) in the gas phase or sodium sulfite solution without DO in the liquid phase, the current output of the wearable oxygen sensor decreased rapidly (Fig. 3). The response time for output current to reach 90% of the steady-state value was 11 s on equality with that of the commercial one. The wearable sensor calibration plots are shown in Fig. 4. In this figure, the sensor output is presented as a displacement of current value. The current output of the sensor device was linearly related to the concentration of the DO over a range 0.0–8.0 mg/l, with a correlation coefficient of 0.999 deduced by regression analysis, as shown by the following equation: sensor output (A) = 0.24 + 5.11[DO (mg/l)] As just described, the wearable device constructed by the microfabrication techniques with the functional membranes has indicated satisfactory performances as the oxygen sensor in the liquid- and gas-phase. We then applied the sensor for the transcutaneous oxygen measurement.
Fig. 4. Calibration curve of the wearable sensor for the DO measurement.
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K. Mitsubayashi et al. / Sensors and Actuators B 95 (2003) 373–377
Fig. 5. Typical output of the transcutaneous oxygen measurement by the wearable sensor attached onto the forearm skin of the subject inhaling the controlled oxygen (21–60–21%, sequentially).
3.2. Transcutaneous oxygen measurement by the wearable sensor Fig. 5 shows the typical response for transcutaneous oxygen pressure and the skin temperature. The oxygen concentration supplied through the mouthpiece was controlled from 21 to 60% (10 min) to 21%. As the figure indicates, the output current of the wearable sensor related tcPO2 value was rapidly increased by the inhalation of 60% oxygen air, and after keeping the steady-state current, then decreased by 21% oxygen air. The skin surface was controlled at approx. 40 ◦ C as indicate in the figure. The application of the wearable oxygen sensor caused no physical discomfort, i.e. skin rashes and skin-burn, to the subjects. Thus, the wearable sensor was successfully monitored the transcutaneous oxygen measurement. The oxygen transmissibility from the arterial blood to the skin surface was reported to depend on the body regions [7,14]. Fig. 6 shows the output increases of the device attached various regions in subject body, by changing the concentration of inhaling oxygen from 21 to 60%. The skin temperature was controlled at 40 ◦ C in all experiments. As the comparison of the body regions, the high outputs were observed at the arm regions, especially inside the wrist and forearm. From the experimental point of view, the forearm has been considered to be well-suited region for the wearable device application. Fig. 7 shows the effect of the warming temperature at the forearm skin on the output increase of the wearable sensor by changing the concentration of inhaling oxygen from 21 to 60%. As this figure indicates, the output increment after 60% oxygen inhalation was enlarged by increasing in skin temperature because the skin warming induces the oxygen transmissibility from the arterial blood to the skin surface as noted above. The wearable oxygen sensor, however, could be used for transcutaneous monitoring at 37 ◦ C, in which the low-temperature skin-burn is not induced and the warming apparatus is not required for non-invasive measurement.
Fig. 6. Effect of skin surface sites (wrist, forearm, elbow, upper arm, chest wall and palm) on the output increase of the wearable sensor for the transcutaneous measurement by applying from 21 to 60% oxygen.
Fig. 7. Effect of the warming temperature (37, 41, 42 ◦ C) at the skin surface on the output increase of the wearable sensor for the transcutaneous measurement by applying from 21 to 60% oxygen.
4. Conclusions The flexible and wearable oxygen sensor was constructed in a sandwich configuration with membrane filter with KCl electrolyte solution between the non-permeable (metal weldable) sheet and the gas-permeable membrane coated with Pt- and Ag/AgCl-electrode by the photolithograph approach. The electrolyte solution was enclosed only by heat-seal on the edges of the weldable membranes. The wearable oxygen sensor (thickness: 84 m) was calibrated against DO from 0 to 8.0 mg/l being equivalent to the commercially available oxygen electrode. By applying the device onto the forearm skin surface, the wearable sensor
K. Mitsubayashi et al. / Sensors and Actuators B 95 (2003) 373–377
was successfully used to monitor the transcutaneous oxygen pressure without any inconveniences such as skin inflammation, etc. Potential application of the wearable oxygen sensor include not only the safe transcutaneous measurement without the warming apparatus, but also the development of a new wearable biosensor for attached directly to body surfaces for monitoring the chemical composition of biological fluids such as tears, airway mucus, sweat, saliva, etc.
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Biographies Kohji Mitsubayashi is an associate professor at Tokai University (Department of Human and Information Science). His research interests include a newly olfactometric system using biological materials, wearable chemical sensors for human monitoring, biomolecular devices, microsystem technology, etc. Yoshihiko Wakabayashi is a graduate student at Tokai University (Mitsubayashi Lab.). He has investigated wearable sensor and monitoring system. Daisuke Murotomi had been a graduate student at Tokai University (Mitsubayashi Lab.) from 1998 to 2000. He had investigated wearable oxygen and biosensor devices. Takua Yamada had been an undergraduate student at Tokai University (Mitsubayashi Lab.) from 1999 to 2000. He had investigated wearable sensor and monitoring system. Tatsuya Kawase had been an undergraduate student at Tokai University (Mitsubayashi Lab.) from 1999 to 2000. He had investigated wearable sensor and physiological monitoring system. Suketsune Iwagaki is a professor of Tokai University (Department of Physical Recreation, School of Physical Education) and a doctor of medicine. Isao Karube is a professor of Tokyo University of Technology and the head of Research Laboratory for Advanced Bioelectronics, National Institute of Advanced Industrial Science and Technology (AIST) after he retired as professor of University of Tokyo in April 2002.