血糖检测仪论文中英文资料英文原文SICE Annual Conference 2011September 13-18, 2011, Waseda University, Tokyo, JapanBlood Glucose Level Measurement by Confocal ReflectionPhotodetection SystemYuki Miyauchi，Takuro Horiguchi, Hiroaki Ishizawa, Shin-ichirou Tezuka and Hitoshi Hara Interdisciplinary Graduate School of Science and Technology, Shinshu University, Nagano, Japan(Tel : +81-268-21-5400; E-mail: f09a212@shinshu-u.ac.jp)Graduate School of Science and Technology, Shinshu University, Nagano, Japan (Tel : +81-268-21-5400; E-mail: 10fa221b@shinshu-u.ac.jp)Faculty of Textile Science and Technology, Shinshu University, Nagano, Japan (Tel : +81-268-21-5400; E-mail: zawa@shinshu-u.ac.jp)Yokogawa Electric Corporation, Nagano, Japan(Tel : +81-265-85-5620; E-mail: Shin-ichirou.Tezuka@) Yokogawa Electric Corporation, Nagano, Japan(Tel : +81-265-85-5620; E-mail: Hitoshi.Hara@)Abstract:In the present study, the confocal optical system has been constructed by using the near-infrared laser, and the reflection photodetection system of the living body has been developed. This system reduces the influence of a complex light scatter by the skin tissue and achieves a highly accurate measurement byconfocal optical system. And the initial experiment for the development of the non-invasive blood glucose meter that presumed the blood glucose level by thenear-infrared absorption of the living body has been done. In this report, the principle of the blood glucose level measurement of this system has been confirmed. The light intensity of the reflection in the living body skin tissue has been measured in the constructed system, and it has been compared with the blood glucose level reference value. As a result, the absorption of the reflected light that depended on the blood glucose level has been confirmed. The possibility of measuring the blood glucose level has been shown.Keywords: Confocal Optical System, Non-invasive, Blood Glucose, Near-infrared.1. INTRODUCTIONRecently, the diabetic increases remarkably [1, 2]. The self-monitoring of blood glucose (SMBG) is necessary and indispensable to treat the diabetic. However, present SMBG has been limited to the measurement that needs collecting blood. The patient has loads of pain, stress, and costs, etc. Therefore, the non-invasive blood glucose meter to be able to measure the blood glucose level is strongly expected [3-5]. In the present study, the confocal optical system has been constructed by using the near-infrared laser, and the reflection photodetection system of the living body has been developed. And the initial experiment for the development of the non-invasive blood glucose meter that presumed the blood glucose level by the near-infrared absorption of the living body has been done. This system reduces the influence of a complex light scatter by the skin tissue and achieves a highly accurate measurement by confocal optical system [6, 7]. In this report, the focus depth by the confocal optical system of this system has been confirmed. And the principle of the blood glucose level measurement of this system was confirmed. The light intensity of the reflection in the living body skin tissue has been measured in the constructed system, and it has been compared with the blood glucose level reference value. As a result, the absorption of the reflected light that depended on the blood glucose level has been confirmed. The possibility of measuring the blood glucose level has been shown.2. EXPERIMENTAL METHOD2.1 Measuring systemFig. 1 shows the optical system for the system constructed in the present study.A near-infrared ray VCSEL (Vertical Cavity Surface Emitting Laser) [8] of wavelength 1.55 μm was used for the light source of this system, and PD (InGaAsPIN photodiode, FGA21; THORLABS) was used for the photo detector. This system is a confocal optical system [9] that has the depth resolution and high plane resolution. Intensity of the reflected light from the sample surface side to the inside of sample can be detected by moving the window up and down. The source of light has stabilized by the APC (Auto Power Control) circuit [10].Fig. 2 Appearance of the polycarbonate plate measurementFig. 3 Appearance of a living body blood glucose level measurement2.2 Polycarbonate plate measurementThe polycarbonate plate was set up in the vicinity of the focus of object lens. The thickness of the polycarbonate plate is 5.0 mm and refractive indexes are n = 1.5. The focus of object lens from the sample surface side to the bottom side was scanned at intervals of 0.1 mm, and the reflected light of each point was acquired. The aluminum plate was set up in the polycarbonate plate bottom as a reflector. When measuring it, the state to remove the confocal pinhole to compare it with the image optics system was measured.2.3 Living body blood glucose level measurementThe present study was approved because of regulations of the Shinshu University ethics committee. And it won consent from the subject by the document. The relation between the amount of near-infrared absorption measurements of this system and the reference value that depended on the living body blood glucose level was examined.The measuring object was made a palmar side of the left hand thumb root. The depth of the measurement skin tissue was assumed to be 0.5 mm, 1.0 mm, 1.5 mm, and the surface. And the living body was made to stick to the window material of this system, and the reflection light intensity in each depth was measured. Moreover, the blood glucose level reference value was measured by the enzyme electrode method at the same time.A male in his twenties and an able-bodied person were made a subject. They were measured twice when they were hungry, and they were measured 9 times at intervals of 5 minutes after glucose load.1.EXPERIMENTAL RESULT1.1Reflection light intensity through the polycarbonate plateFig. 4 The focus depth of the confocal reflection photodetection systemFig. 4 showed the reflection light intensity in each point from the vicinity of the surface of the polycarbonate plate to the bottom. The peak of the scanning distance about 4.8 mm is a reflected light of the sample bottom. And it was confirmed by both of the image optics system and the confocal optical system. Moreover, the reflected light on the sample surface seen in the scanning distanceabout 1.4 mm was able to be confirmed only in the confocal optical system.3.2 Near-infrared absorption of a skin tissueThe logarithm value and the concentration of glucose of the skin tissue reflection light intensity are assumed to show a negative correlation from the Lambert-Beer law [11]. The reflection light intensity ratio on the inside and the surface of the skin tissue was used for the reflection light intensity. As a result, the fluctuation of the light intensity of the source of light is corrected. Fig. 5 showed the relation between the logarithm value and the blood glucose level reference value of the reflection light intensity ratio of each depth of 0.5 mm, 1.0 mm, and 1.5 mm. And the correlation coefficient and the standard error of each depth were shown in Table 1.Fig. 5 Near-infrared absorption of the skin tissue of each depth2.DISCUSSIO4.1 The focus depth of the confocal reflection photodetection systemThe reflection light intensity of the scanning in each point was overall large in the image optics system. Therefore, the reflection light peak on the sample surface was not able to be confirmed（Fig. 4）. It is shown that the reflection light intensity on the sample surface can be confirmed in the confocal optical system, and there is a depth resolution. Moreover, the distance between peaks of the reflected light of the sample surface and the bottom is about 3.4 mm. It is almost corresponding to optical distance t / n = 3.3 mm of t = 5.0 mm in thickness in refractive index n = 1.5. It was shown to be able to select the measurement depth according to the refractive index. The full width at half maximum of the peak of the reflected light in the confocal optical system is about 1mm. It can be said that the focus depth of the confocal reflection photodetection system is about 1.0 mm.Fig. 6 EGA result in relation between the reference values and the predictive values4.2 Near-infrared absorption of a skin tissueThe attenuation of the logarithm value of the reflection light intensity ratio that depended on the blood glucose level was confirmed in 0.5 mm and 1.5 mm in the depth of the measurement skin tissue. The possibility of presuming the blood glucose level from the reflection light intensity ratio logarithm value was shown from the logarithm value of the reflection light intensity ratio and the correlation of the bloodglucose level. However, the attenuation of the logarithm value of the reflection light intensity ratio thatdepended on the blood glucose level was not able to be confirmed by the depth of 1.0 mm. It is thought that this is because a steady measurement was not able to be done because the scattered structure of the skin tissue is organizing and it is not uniform. It will be necessary to examine the best measurement depth in detail in the future. The single regression analysis was done to the data of 1.5mm that the relation of the attenuation of the blood glucose reference value and the reflection light intensity was good in depth. Fig.6 showed the relation of the predictive value forecast by the reference value and the single regression analysis. And we used Error Grid Analysis (EGA). The EGA is developed a system for the evaluation of the clinical implications of patient generated blood glucose value, which takes into account the factors. A and B zone are clinical safety. C zone is a little danger. D and E zone are danger [12]. As a result of the single regression analysis, it was in the correlation with high blood glucose reference value and blood glucose forecast value. Moreover, all data was included in A and B zone in the result of EGA. The plot was distributed clinical within the effective range. Therefore, it was shown that the validity of the blood glucose level measurement by this system. And it is necessary to increase the number of measurements and to confirm the stability of the measurement.5. CONCLUSIONThe confocal optical system has been constructed by using the near-infrared laser, and the reflection photodetection system of the living body has been developed. The depth resolution of the system has been confirmed by measuring the polycarbonate plate. And it has been shown to be able to select the depth when the living body was measured. The possibility of presuming the blood glucose level from the reflection lightintensity ratio logarithm value has been shown from the logarithm value of the reflection light intensity ratio and the correlation of the blood glucose level. And EGA plot has been built by these data. The measurement of this system has been shown an effective possibility clinical. Therefore, the possibility of measuring the blood glucose level has been shown. However, the attenuation of the logarithm value of the reflection light intensity ratio that depended on the blood glucose level according to depth has been not able to be confirmed. This is because a steady measurement was not able to be done because the scattered structure of the skin tissue is organizing and it is not uniform. It will be necessary to examine the best measurement depth in detail in the future. And it is necessary to increase the number of measurements and to confirm the stability of the measurement. It is necessary to increase the number of subjects and to confirm the interindividual variation.REFERENCES[1] WHO 2010 Web Site, “http://www.who.int/diabetes/en/” [Accessed July 18, 2010].[2] 2009 International Diabetes Web Site, “http:/content/foreword/”. [Accessed July 18, 2010].[3] M. R. Robinson, R. P. Eaton, D. M. Haaland, G. W. Koepp, E. V. Thomas, B. R. Stallard, and P. L. Robinson, “Noninvasive Glucose Monitoring in Diabetic Patients: A Preliminary Evaluation”, CLIN. CHEM,38-9, pp.1618-1622,1992.[4] S. Koyama, Y. Miyauchi, H. Ishizawa, “Clinical Application of Non-invasive Blood Glucose Monitoring System”, J. Illum. Engng. Inst. Jpn., vol.95, no.5, 2011.[5] S. Koyama, Y. Miyauchi, T. Horiguchi, H. 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