基于光纤衰减全反射的植入式人体血糖浓度连续监测系统技术领域 本发明涉及一种人体血糖浓度连续监测装置。 The implantable human blood glucose concentration continuous monitoring system based on fiber ATR Technical Field  The present invention relates to a device for continuous monitoring of human blood glucose concentration. 特别是涉及一种利用植入人体的光纤ATR传感器，通过测量皮下组织液中的葡萄糖浓度，实现人体血糖浓度的连续检测的基于光纤衰减全反射的植入式人体血糖浓度连续监测系统。 In particular, it relates to a fiber optic ATR sensor implanted in the body, by measuring the glucose concentration in subcutaneous fluid, the implantable human blood glucose concentration to achieve a continuous monitoring system for continuous monitoring of human blood glucose concentration based on fiber attenuation of total reflection. 背景技术 糖尿病是中老年人的常见病和多发病，发病率日益上升，且呈年轻化和扩大化趋势。  Diabetes is a common disease in the elderly, the rising incidence of, and trends were younger and expansion. 世界卫生世界组织将它和肿瘤、心脑血管病一起列为范围内的三大疑难病症。 The World Health Organization World tumor and it, along with the three incurable diseases as a range of cardiovascular diseases.  然而目前临床上还没有彻底根治糖尿病的医学手段，现今治疗糖尿病的目标是尽可能实现胰岛素控制，避免人体血糖过高，预防或减轻并发症的发生并对症治疗并发症。  However, no clinical medical means to completely cure diabetes Currently, the goal now is to achieve the treatment of diabetes insulin to control as much as possible, avoid high blood sugar, prevent or reduce the incidence of complications and symptomatic treatment of complications. 世界卫生组织推荐对糖尿病患者进行血糖的自我监测，随时掌握体内的血糖情况，实现对胰岛素的准确控制，这对于预防和治疗糖尿病及其并发症意义重大。 World Health Organization recommended for patients with diabetes self-monitoring of blood glucose, to keep blood sugar in the body, to achieve precise control of insulin, which is great significance for the prevention and treatment of diabetes and its complications. 因此人体血糖浓度的精确检测是糖尿病及其并发症预防和治疗的前提和基础。 Therefore, accurate detection of human blood glucose concentration is the prerequisite and basis for diabetes and its complications, prevention and treatment. 目前的糖尿病检测主要依靠的是有创测量，国际上广泛采用的血糖检测方法都离不开有创的取血过程。  It diabetes relies mainly on the detection of invasive measurement, blood glucose testing methods are widely used international blood can not do without invasive procedure. 有创血糖检测过程中需要消耗品，且频繁采血不仅给病人带来生理和心理疼痛，还有伤口感染的危险。 Invasive blood glucose testing process required consumables, and frequent blood to the patient not only the physical and psychological pain, there is a danger of wound infection. 尤其是对于临床应用来讲，这种方法最大的缺点是不能实现对于人体血糖浓度的动态、连续检测，无法反映病人体内血糖浓度的实时变化情况，因此达不到最佳的临床治疗效果。 Especially for clinical application is concerned, the biggest drawback of this method is not possible for the dynamic human blood glucose concentration, continuous testing, can not reflect real-time changes in blood glucose concentration of the patient, and therefore less than optimal clinical effect.  随着激光和检测技术的发展，各种基于光学技术的无创血糖检测方法，例如，利用葡萄糖分子对近红外光吸收特性的光透射和光反射谱法、拉曼光谱法、旋光法、光声法等， 以及利用葡萄糖分子对近红外光偏振特性的光偏振法等，成为无创血糖检测领域的热门研究课题。  With the development of laser and detection techniques, various non-invasive blood glucose monitoring method based on optical techniques, e.g., glucose molecules using near-infrared light absorption characteristics of light transmission and light reflection spectroscopy, Raman spectroscopy, polarimetry, photoacoustic method, and the use of glucose molecules of light polarization properties of light polarization technique such as near infrared, non-invasive blood glucose monitoring has become a hot area of research. 无创血糖检测方法不需要提取血液等体内物质，不需要将传感器植入皮下，依靠光与人体特定部位组织的相互作用来检测病人体内血糖浓度的变化，可以动态、连续地检测人体血糖浓度，是最理想的人体血糖监测方法。 Non-invasive blood glucose testing methods not requiring the extraction of blood and other substances in the body, the sensor is implanted subcutaneously need not rely on the interaction of light with a specific portion of the body tissues to detect changes in the patient's blood glucose concentration may be dynamically, continuously detected human blood glucose concentration is the best blood sugar monitoring methods. 但无创血糖检测技术尚不成熟，处于实验研究阶段不能够应用于临床，无法满足动态、连续地检测人体血糖浓度的要求。 However, non-invasive blood glucose monitoring technology is not yet mature, in the experimental stage can not be used in clinical studies, can not meet the dynamic, continuously testing requirements human blood glucose concentration. 而且，至今仍没有任何无创血糖检测仪器通过美国FDA的认证。 And, still there is no non-invasive blood glucose monitoring equipment by the US FDA certification.  鉴于有创血糖检测的缺点以及无创血糖检测的诸多技术瓶颈，目前国际上人体血糖浓度连续监测的研究主要集中在微创血糖检测领域。  In view of the disadvantages of invasive blood glucose testing as well as many technical bottlenecks non-invasive blood glucose monitoring, research the current international human blood glucose concentration continuous monitoring focused on minimally invasive glucose detection. 医学研究表明，皮下组织液中的葡萄糖浓度与血液中的葡萄糖浓度是密切相关的。 Medical research shows that the glucose concentration in the subcutaneous tissue fluid glucose concentration in the blood are closely related. 因此，可以通过监测组织液中的葡萄糖浓度来预测血液中的葡萄糖浓度。 Thus, it is possible to predict the glucose concentration in the blood by monitoring the glucose concentration in the tissue fluid. 按检测方式，微创血糖检测技术可以分为两大类：一类是将组织液以微创的方式从人体皮下抽取出来，然后再通过电学、光学或化学的方法离体检测其葡萄糖浓度；另一类是将微型传感器直接植入皮下，在体实时检测皮下组织液中的葡萄糖浓度。 Detecting by way of minimally invasive glucose detection techniques can be divided into two categories: one is the tissue fluid extracted from a minimally invasive manner out of human skin, and then the glucose concentration detected by the method of electrical, optical or chemical in vitro; the other one is to directly implanted subcutaneously miniature sensors, real-time detection of the glucose concentration in the subcutaneous tissue of the liquid.  相比近红外波段，葡萄糖在中红外区有被称为“指纹谱”的独特吸收谱，其吸收较近红外波段强得多，且吸收峰窄。  compared to the near infrared region, a unique glucose absorption spectrum is called "fingerprinting" in the infrared region, which absorbs much stronger near infrared band and narrow absorption peak. 因此，中红外吸收光谱包含更丰富的定量信息，且提取更容易，特别是对于低含量组分进行检测时更具优势。 Thus, the infrared absorption spectrum containing quantitative information richer, and the extraction easier, especially advantages for detecting low levels of compounds. 中红外ATR吸收光谱法克服了中红外光在透射测量方法应用中，由于水强吸收造成的穿透深度有限，仅在ΙΟμπι左右这一劣势， 在成分测量领域备受关注。 ATR infrared absorption spectrometry overcome in the infrared transmittance measurement applications, since the penetration depth is limited due to the strong absorption of water, is only about ΙΟμπι this disadvantage, in the measurement field component of concern. 中红外衰减全反射吸收光谱法的基本原理为：全反射的条件下，光在晶体与样品接触表面发生衰减。  The basic principle of attenuated total reflection infrared absorption spectrometry is: under the condition of total reflection, evanescent light occurs in the crystal and the sample contacting surface. 衰减的程度与倏逝波在样品中的穿透深度有关，而穿透深度由入射波长、入射角、晶体和样品折射率决定。 The degree of attenuation and the penetration depth of the evanescent wave in the sample, whereas the depth of penetration, angle of incidence, the refractive index of the sample is determined by the crystal and the incident wavelength. 这种随波长不同而衰减程度不同的特性可用来提取样品中组分的信息。 Such different wavelengths with varying degrees of decay characteristics may be used to extract information components in the sample. 与传统的红外透射测量相比，ATR方法的重要特性在于：排除了样品被光照后加热而被破坏的可能，试样厚度不受必须大于三倍光波长的限制。 Compared with conventional infrared transmission measurements, the important characteristic is that the ATR method: The sample was ruled out after the light is destroyed in the heating, the thickness of the sample must not be greater than three times the wavelength of light limits. 对于光纤ATR探头设计，采用工作部分光纤圆形围绕形式，从而在有限的体积空间内扩展其有效工作长度，且其光程长可以根据需求研制，进而提高光纤ATR传感器的检测分辨率，以满足系统最优光程长的需求。 For fiber optic ATR probe design, the working portion of the fiber around a circular form, thereby extending its effective working length in a limited volume of space, and its optical path length can be developed according to the needs, and thus to improve the detection resolution of the optical fiber sensor ATR, to meet the the system optimal optical path length needs.  1998年，Heise等将中红外ATR光谱法用于临床化学分析。  In 1998, Heise like ATR infrared spectroscopy for the analysis of clinical chemistry. Lambrecht等于2006 年发表了中红外ATR光谱法进行血糖连续监测的研究成果，离体实验得到的噪声等效血糖浓度为40mg/dL。 Lambrecht equal to 2006 published the research results of the continuous monitoring of blood glucose ATR infrared spectroscopy, in vitro experiments of the noise equivalent glucose concentration of 40mg / dL. Heise在其2008年发表的文章中，也开始关注将中红外光谱法血糖监测用于重症监护中，采用微透析技术抽取皮下组织液，用中红外光谱仪研究组织液中葡萄糖的浓度。 Heise in its 2008 article published in, begin to focus on the mid-infrared spectroscopy glucose monitoring for intensive care, the use of microdialysis technique to extract the subcutaneous tissue fluid, tissue fluid with a mid-infrared spectroscopy study of glucose concentration. 但组织液抽取式微创血糖检测方法的缺陷与不足，同样使得Heise的这种方法最终也无法走向临床应用。 However, lack of defects and the extracted tissue fluid minimally invasive glucose detection method, this method also makes Heise is not ultimately to clinical applications. 发明内容 本发明所要解决的技术问题是，提供一种采用在体直接测量方法，直接测量组织液中的葡萄糖浓度，能够满足实时、连续地血糖检测要求的基于光纤衰减全反射的植入式人体血糖浓度连续监测系统。 SUMMARY OF THE INVENTION  The present invention solves the technical problem, to provide a direct in vivo measurement method, direct measurement of the glucose concentration in the tissue fluid, to meet real-time, based on the implantation of an attenuated total reflection optical fiber is continuously blood glucose testing requirements type blood glucose concentration continuous monitoring system.  本发明所采用的技术方案是：一种基于光纤衰减全反射的植入式人体血糖浓度连续监测系统，由双光路构成，包括有光源、衰减器、分光镜、光纤耦合装置、光纤ATR传感器、 测量光探测器、参考光探测器、数据采集系统以及计算机，所述的光源经过衰减器衰减后， 经分光镜分为由测量光和参考光构成的两条光路，其中的一条光路是，所述的测量光采用光纤耦合装置，通过耦合方法耦合进入光纤ATR传感器，经光纤ATR传感器的透过光由测量光探测器接收；另一条光路是，所述的参考光由参考光探测器直接接收；所述的经测量光探测器和参考光探测器所接收的信号由数据采集系统同步采集，送往计算机进行分析处理并显示测量结果，所述的计算机还与光源相连接。  The technical proposal of the present invention is: An implantable human blood glucose concentration in a continuous monitoring system based on fiber optic attenuated total reflection, is constituted by a double optical path, comprising a light source, an attenuator, a beam splitter, the optical fiber coupling device, the optical fiber ATR sensor, the measurement light detector, a reference light detector, and a computer data acquisition system, said light source after attenuation of the attenuator, the dichroic mirror is divided into two optical paths by the measurement light and reference light composed of a light path therein that the measuring light using optical fiber coupling means, coupled into the fiber by ATR sensor coupling method, the probe is received by the measurement light transmitted through the optical fiber sensor ATR; the other optical path, said reference light by the reference light detection received directly; measured according to the reference photodetector and the photodetector signal received by the synchronous acquisition data acquisition system, sent to a computer for analysis and displays the measurement result of the processing, the computer is also connected to the light source.  所述的光源为输出波长包括葡萄糖中红外波段的1035和1080CHT1特征吸收峰的小型化波长可调谐CO2激光器。 Miniaturized wavelength light source  The output wavelength of 1035 and 1080CHT1 features include glucose absorption peak in the infrared band tunable CO2 laser.  所述的光纤耦合装置三维可调。  The three-dimensional optical fiber coupling device is adjustable.  所述的三维可调的光纤耦合装置包括有：分别用于光纤耦合装置与光纤ATR传感器之间的入射光路上的皮上光纤路径与皮下光纤路径，以及出射光路上的皮上光纤路径与皮下光纤路径耦合的两个微型透镜，用于固定两个皮上光纤路径的三维可调夹持结构。  The three-dimensional fiber coupler adjustable device comprising: respectively for the skin on the skin of the incident light path between the optical fiber coupling device and the optical path subcutaneous ATR sensor fiber path, and an exit optical path of the optical fiber two microlens fiber path subcutaneous path coupled, two-dimensional skin for fixing the optical fiber holding structure adjustable paths.  所述的耦合方法包括基于光学窗口或光学清透技术的耦合方法。 Said coupling method  includes an optical window or the optical coupling method Refreshing Technology.  所述的光学窗口包括用于保护皮上光纤路径与皮下光纤路径的耦合端口的帽状结构。  The optical window comprises a cap-like structure of the fiber path is coupled with a subcutaneous port fiber path on the protective sheath.  所述的光学清透技术是在皮肤表面涂抹设定浓度的生物兼容高渗制剂，以增强组织对光的通透性。 Refreshing the optical technology  is applied on the skin surface is set hypertonic concentration of biocompatible agents, to enhance the permeability of the tissue to light.  所述的光纤ATR传感器是由多模光纤采用单环或多环的探头结构构成。  The optical fiber sensor is employed by the ATR multimode optical fiber probe structure constituting a monocyclic or polycyclic.  所述的光纤ATR传感器的光纤ATR测头置于微型腔体内，所述的微型腔体的前端为对小于等于葡萄糖的分子有选择通过性的具有生物兼容性的半透膜。 Fiber optic ATR probe  The ATR sensor optical fiber is placed in a micro cavity, the distal end of the micro-cavity through a semipermeable membrane selective for the biocompatible properties of the molecules of glucose or less.  所述的微型腔体内设置有对葡萄糖分子具有特异性动态吸附能力和生物兼容性的水溶性聚合物。  The micro-cavity is provided with a specific dynamic adsorption capacity and biological compatibility of the water-soluble polymer of glucose molecules.  本发明的基于光纤衰减全反射的植入式人体血糖浓度连续监测系统，采用在体直接测量方法，直接测量组织液中的葡萄糖浓度，避免了离体测量误差。  The present invention is an implantable human blood glucose concentration in a continuous monitoring system based on fiber optic attenuated total reflection, direct in vivo measurement method, direct measurement of glucose concentration in the tissue fluid, ex vivo to avoid measurement errors. 其优势还在于在体测量，无需准确计算抽取的组织液体积，进一步减少了引入误差的可能性。 Its advantage lies in vivo measurements without accurately calculate the volume of the interstitial fluid extraction, further reducing the possibility of introducing errors. 本发明提出的基于中红外光纤衰减全反射的植入式血糖连续检测技术能够满足实时、连续地血糖检测要求。 The present invention proposes an implantable glucose based on attenuated total reflection FT-IR techniques to meet the continuously detected in real time, continuous blood glucose testing requirements.  具有如下特点： I.本发明ATR传感探头由光纤构成，探头采用环形设计，在有限的空间内增加了光纤ATR传感器的工作长度。  has the following characteristics:  I. ATR present invention is constituted by an optical fiber sensing probe, the probe design using an annular, increases the working length of the optical fiber sensor ATR in a limited space. 探头结构简单，体积小，易制造，能够植入到人体皮下进行葡萄糖浓度在体、24小时连续监测。 Probe simple structure, small volume, easy to manufacture, can be implanted subcutaneously into the glucose concentration in the human body, 24 hours of continuous monitoring.  2.本发明将光纤探头置于微型腔体中，腔体前端为具有生物兼容性的半透膜，只允许葡萄糖等小分子能够进入腔中，避免了大分子吸附于光纤ATR传感器探头表面，起到保护作用，延长了探头的使用寿命。  2. The present invention will miniature fiber optic probe in a semipermeable membrane cavity, the cavity having a front end biocompatible, allow only small molecules such as glucose to enter the chamber, avoiding the macromolecule adsorbed on the fiber optic sensor ATR probe surface, protect and prolong the life of the probe.  3.本发明利用对葡萄糖分子具有特异性动态吸附能力和生物兼容性的水溶性聚合物，通过其对葡萄糖分子的动态特异性吸附能力，减小了组织液中其他物质对测量的干扰，实现了葡萄糖分子的选择性测量，提高了测量分辨率。  3. The present invention utilizes water-soluble polymer having a specific dynamic adsorption capacity and biological compatibility on the glucose molecules, specifically by dynamic adsorption capacity of glucose molecules, other reducing interfering substances in the tissue fluid measurement , to achieve selective measurement of glucose molecules to improve the measurement resolution.  4.本发明专利采用双光路结构，包括参考光路和测量光路。 Patent  4. The dual optical structure, including a reference light path and the measuring optical path. 参考光路的引入消除了光源功率波动引起的测量误差，提高了系统的稳定性和分辨率。 Incorporated reference optical path to eliminate the measurement error caused by light power fluctuations, improve the stability and resolution of the system.  5.本发明专利的三维可调光纤耦合装置使光纤ATR传感器与光源和探测器等构成的检测系统分离，为临床应用奠定了基础。  5. The present invention is a three-dimensional patent tunable fiber coupling device with the optical fiber sensor ATR and the source detection system composed of detector separation etc., the foundation for clinical application.  6.本发明专利提出基于光学清透技术的耦合方法，使光纤埋入皮下200 μ m以内， 减少了感染的可能性。 Patent  6. The coupling method is proposed based on optical technology, perfectly clear, the optical fiber is embedded within the skin 200 μ m, reducing the possibility of infection.  7.本发明的光纤探头、微型腔体、半透膜和水溶性聚合物等均由生物兼容性材料制成，安全可靠，对人体无危害。 Made  7. The fiber optic probe of the present invention, the micro-cavity, the semipermeable membrane and water-soluble polymer by a biocompatible material, safe and reliable, no hazard to humans. 附图说明 图I是本发明的整体结构示意图； 图2 (a)、图2(b)是本发明光纤ATR探头结构示意图； 图3是半透膜和水溶性聚合物在中红外光纤ATR传感测头中的应用示意图； 图4是三维可调光纤耦合装置使光纤ATR传感器与检测系统分离示意图。 BRIEF DESCRIPTION  FIG. I is a schematic overall structure of the present invention;  FIG. 2 (a), FIG. 2 (b) is a schematic view of fiber optic ATR probe structure of the present invention;  FIG. 3 is a semipermeable membrane and a water-soluble application of polymer is a schematic view of an infrared fiber in the ATR sensor head;  FIG. 4 is a three dimensional tunable optical coupling means the optical fiber sensor ATR separate detection system schematic.  图5是基于光学窗口耦合方法的系统结构示意图。  FIG. 5 is a schematic diagram of the system configuration of an optical window based coupling method.  图6是基于光学清透耦合方法的系统结构示意图。  FIG. 6 is a diagram showing the system configuration of an optical coupling Refreshing Method. 其中， I :光源 2 :衰减器 3 :分光镜 4 :光纤耦合装置 5 ： 光纤ATR传感器 6 ： :测量光路探测器 7 ： 参考光路探测器 8 :数据采集系统  9 ： 计算机 10 :光纤路径I 11 :单环ATR探头 12 ：:光纤路径2 13 :多环ATR探头 14 ::聚合物溶液 15 :组织体 16 :生物半透膜 17 :光纤 18 :光纤ATR测头 19 :皮下光纤路径 20 :皮下光纤路径 21 :帽状结构 22 :光纤夹持结构 23 :皮上光纤路径 24 :微型透镜 25 :皮上光纤路径 26 :皮肤 27 :微型腔体 28 :葡萄糖分子 29 :聚合物分子 30 :第一标记 31 :第二标记 具体实施方式 下面结合实施例和附图对本发明的基于光纤衰减全反射的植入式人体血糖浓度连续监测系统做出详细说明。  wherein,  I: light 2: Attenuator  3: beam splitter 4: optical fiber coupling device  5: Fiber ATR sensor 6:: measuring optical path detector  7: reference path detection 8: data acquisition system  9: computer 10: optical path I  11: 12 :: monocyclic ATR probe fiber path 2  13: 14 :: polycyclic ATR probe polymer solution  15: organization 16: biological semipermeable membrane  17: optical fiber 18: ATR fiber probe  19: subcutaneous fiber path 20: subcutaneous fiber path  21: cap structure 22: optical fiber-holding structure [ 0048] 23: fiber path 24 on the skin: the micro lens  25: fiber path 26 on the skin: skin  27: microchamber 28: glucose molecules  29: 30 polymer molecules: first marker [ 0052] 31: second mark dETAILED DESCRIPTION  the following Examples and detailed description of the accompanying drawings to make implantable human blood glucose concentration in a continuous monitoring system based on fiber optic attenuated total reflection according to the present invention.  如图I所示，本发明的基于光纤衰减全反射的植入式人体血糖浓度连续监测系统，由双光路构成，包括有光源I、衰减器2、分光镜3、光纤耦合装置4、光纤ATR传感器5、测量光探测器6、参考光探测器7、数据采集系统8以及计算机9。  FIG I, the present invention is based on the optical attenuation fiber coupling device implantable human blood glucose concentration totally continuous monitoring system is constituted by a double optical path, comprising a light source I, the attenuator 2, a beam splitter 34 , fiber optic ATR sensor 5, measuring light detector 6, the reference light detector 7, 8 and a computer data acquisition system 9. 其中，所述的光源I经过衰减器2衰减后，经分光镜3分为由测量光和参考光构成的两条光路，其中的一条光路是，所述的测量光采用光纤耦合装置4，通过耦合方法耦合进入光纤ATR传感器5，经光纤ATR传感器5的透过光由测量光探测器6接收，所述的耦合方法包括基于光学窗口或光学清透技术的耦合方法；另一条光路是，所述的参考光由参考光探测器7直接接收；所述的经测量光探测器6和参考光探测器7所接收的信号由数据采集系统8同步采集，送往计算机9进行分析处理并显示测量结果，所述的计算机9还与光源I相连接。 Wherein said light source I after attenuation via attenuator 2, the beam splitter 3 into two optical paths configured by the measurement light and reference light, wherein the optical path is that the measuring light using optical fiber coupling device 4, by coupled into the optical fiber coupling method ATR sensor 5, the light transmitted through the optical fiber sensor ATR measuring light received by the detector 65 via the coupling comprising coupling method based on optical window or the optical technology perfectly clear; the other optical path is that the said reference light 7 is directly received by the reference light detector; measured according to the reference photodetector and the light detector 6 7 8 sync signal received by the data acquisition system acquisition, the computer 9 sent for analysis and display the measurement As a result, the computer 9 is also connected to the light source I. 本发明利用植入人体体内的光纤ATR传感器，通过测量人体皮下组织液中的葡萄糖浓度实现人体血糖的浓度连续监测。 The present invention utilizes fiber optic sensors implanted in the human body ATR continuously monitored by measuring the glucose concentration in subcutaneous tissue of the body fluid to achieve a concentration of blood sugar.  即本发明的光学系统结构为双光路，包括参考光路和测量光路。  That optical system according to the present invention is a dual optical path including the reference light path and the measuring optical path. 参考光路探测器与测量光路探测器的检测信号由数据采集系统同步采集，由计算机中的程序进行分析处理和显示。 The reference light path and the detection signal of the detector probe measuring optical path by the synchronous acquisition data acquisition system for display and analysis by a computer program. 通过两个深测器检测到的背景和待测样品的反射信号的比率，依据系统线性特点， 转化为待测样品的吸收度。 The ratio of the reflected signal detected by a deep detector background and two sample to be tested, according to the system of linear characteristic, is converted to absorbance of sample to be tested. 双光路设计即参考光路的引入消除了光源CO2激光器的功率波动性对测量结果的影响，提高了系统的稳定性和分辨率。 Dual optical design that is incorporated by reference optical path to eliminate the influence of power fluctuation of the CO2 laser light source on the measurement results, improves the stability and resolution of the system.  所述的光源I为输出波长包括葡萄糖中红外波段的1035和lOSOcnT1等特征吸收峰的小型化波长可调谐CO2激光器，且其输出波长谱线线宽窄，有利于信号的检测和提取。 Source I  The output wavelength is in the infrared region include glucose lOSOcnT1 1035 and the like wherein the absorption peak wavelength miniaturized tunable CO2 laser, the output wavelength and spectral line width, and extracted facilitate detection signal. 所述的光纤耦合装置4是三维可调的光纤耦合装置。 The optical fiber coupling means 4 is a three-dimensional fiber coupler means adjustable. 衰减器2连续可调，调节范围为O. 01%〜100%，以保证入射光纤ATR传感器的功率低于人体安全标准和满足探测器检测最大功率限制的要求。 Continuously adjustable attenuator 2 is adjusted in the range of O. 01% ~100%, to ensure that the incident optical power sensor is lower than human ATR and meet the requirements of safety standards probe detects a maximum power limit. 测量光探测器6和参考光探测器7为适用于中红外波段的热释电或碲镉汞光电探测器，碲镉汞光电探测器带有液氮制冷系统，相比热释电探测器可进一步提高测量分辨率，但热释电探测器价格相对便宜。 Measurement light detector 6 and the reference light detector 7 is applied to the pyroelectric infrared or mercury cadmium telluride photodetector, pyroelectric detector HgCdTe photodetector with a liquid nitrogen cooling system, may be compared further improve the measurement resolution, but pyroelectric detector is relatively cheap.  如图4所示，基于光纤衰减全反射的植入式人体血糖浓度连续监测系统分为三部分：植入皮下的光纤ATR传感器5,如图4中标注5所表不的皮下虚框部分所不；光纤I禹合装置4，如图4中标注4所表示的虚框部分所示；光源和探测器等构成的检测系统。  As shown, the implantable human blood glucose concentration in a continuous monitoring system based on fiber optic attenuated total reflection 4 divided into three parts: the fiber implanted subcutaneously ATR sensor 5 denoted by 5 in the virtual table without subcutaneous FIG. 4 the frame portion is not; I Yu fiber bonding apparatus 4 are denoted by the imaginary frame portion 4 as shown in FIG. 4 represented; detection system including a light source and detectors. 从而使得光纤ATR传感器植入皮下，光源和探测器等构成的检测系统置外，不需随身携带，为临床应用奠定了基础。 ATR sensor is implanted so that the fiber composed of the detection system facing the skin, the light source and detectors, the need to carry the foundation for clinical application. 所述的三维可调的光纤耦合装置4包括有：分别用于光纤耦合装置4与光纤ATR传感器5之间的入射光路上的皮上光纤路径25与皮下光纤路径19，以及出射光路上的皮上光纤路径23与皮下光纤路径20耦合的两个微型透镜24，用于固定两个皮上光纤路径25、23的三维可调夹持结构22。 The three-dimensional tunable fiber coupler means 4 comprises: an optical fiber path 25, respectively, and subcutaneous skin incident optical path between the optical path 4 and the optical fiber coupling device ATR sensor 519, and the outgoing light path of the skin the optical fiber path 23 and two micro-lens coupling the optical fiber path 20 subcutaneous 24 for fixing the skin two-dimensional fiber path 25, 23 adjustable holding structure 22.  如图5所不,基于光学窗口的稱合技术,光纤植入皮下,稱合接口19、20与皮肤表面平。  FIG. 5 is not based on optical window, said bonding technique, fiber implanted under the skin, said bonding interfaces 19, 20 and the flat surface of the skin. 方案包括用于保护皮上光纤路径25、23和与皮肤表面平的皮下光纤路径19、20耦合端口的帽状结构21,平时贴附于皮肤表面,测量时打开。 Scheme 25, 23 includes a skin and a flat surface on the optical path of the optical fiber path subcutaneous protective skin cap structure 19, 20 coupled to port 21, usually attached to the skin surface, measuring the open. 光学窗口的稱合方法应用中,光纤耦合端口露出皮肤表面，造成不便的同时也增加了感染的可能性，但其耦合效果较好。 Methods bonding said optical window, the optical fiber coupling port exposed skin surface, inconvenience but also increases the possibility of infection, but better coupling.  如图6所示，基于光学清透技术耦合方法的系统示意图。 As shown in  FIG 6, a schematic diagram of an optical system based on a method coupling techniques perfectly clear. 光纤耦合接口19、20位于皮下200 μ m以内，不需要用以保护光纤接口的帽状结构。 Fiber coupling interface 19, 20 are located inside the skin 200 μ m, it is not required to protect the optical interface cap structure. 在皮下光纤对应的皮肤表面第一、第二标记处30、31涂抹设定浓度的生物兼容高渗制剂（如甘油，乙二醇等，或者某两种混合），约5分钟后，擦除皮肤表面的高渗制剂，从而消除皮肤表面镜面反射及皮下成分的散射作用，使皮下光纤所对应的测量部位对光的通透性增强，增强耦合效果。 Fiber skin on the skin surface corresponding to the first and second mark 30 and 31 apply the set concentration biocompatible hypertonic agents (such as glycerol, ethylene glycol, etc., or a mixture of two), after about 5 minutes, erasing hypertonic formulations of the skin surface, the skin surface to eliminate specular reflection and scattering component subcutaneous, subcutaneous fiber measurement site corresponding light permeability enhancement, enhanced coupling effect. 定位装置将皮上光纤25、23与皮下光纤19、20按照预先设定的标记进行隔皮对接。 The skin on the optical fiber positioning means 25, 23 for compartment 19, 20 to the subcutaneous fiber according to a predefined docking skin tag. 光学清透技术的耦合方法使光纤埋入皮下，不与外界接触，降低了感染的可能性，但其耦合效果一般。 A method of optically coupling optical fiber technology Refreshing subcutaneously implanted not in contact with the outside world, the possibility of infection, but its effect is generally coupled.  如图2(a)、图2(b)所示，所述的光纤ATR传感器5是由多模光纤采用单环或多环的探头结构构成，环形设计体积小，满足传感器植入皮下的要求，在有限的体积空间内扩展了有效工作长度，提高了光纤ATR传感器的测量分辨率。  FIG. 2 (a), FIG. 2 (b), the optical fiber of the ATR sensor 5 is employed by the multi-mode fiber probe structure monocyclic or ring configuration, the small volume of annular design, implantation of the sensor satisfies subcutaneous required, in a limited volume of space expand the effective working length, the measurement resolution of the fiber optic ATR sensor. 多模光纤材料选择卤化银，卤化银在中红外波段吸收很小，易弯曲。 Multimode fiber material selection halide, the silver halide in the infrared absorption is small, easy to bend. 根据朗伯-比尔定律可导出葡萄糖吸收峰下的最佳光程长，最佳光程下可获得较高的灵敏度和较小的探测极限。 According to Lambert - Beer law can be derived glucose absorption optimum optical path length, the optimum optical path can obtain higher sensitivity and lower detection limits of smaller peaks. 单波长下的最佳光程由公式Itwtimal =I/ Σ ε c决定，其中Σ ε c指溶液中所有物质在此波长的消光系数与其浓度乘积之和。 The optimum optical path at a single wavelength is determined by the formula Itwtimal = I / Σ ε c, where Σ ε c refers to the extinction coefficient of all the substances in solution at this wavelength, and its concentration of the product. 直线型光纤全反射次数有限，因此本发明采用将光纤按一定的曲率弯曲，在满足全反射条件下，增加全反射次数，从而达到增加光程长的目的，光纤的环形结构使其在有限的几何尺寸内获得较长的工作长度，使其植入人体成为可能。 A limited number of the total reflection type linear optical fiber, thus the present invention employs an optical fiber is bent by a certain curvature, to meet the condition of total reflection, increasing the number of total reflection, so as to achieve the purpose of increasing the optical path length, so that the optical fiber ring in a limited obtain longer within the geometry of the working length, making it possible to implant the human body. 同时通过调整光纤ATR测头的环形结构，如半径、环形数等，可以获得不同的光程长，以满足系统检测需要的最佳光程长，从而提高系统测量灵敏度和精度。 While the optical fiber by adjusting the ATR probe ring structure, such as the radius, the number of the ring, etc., can obtain different optical path lengths, to meet the optimum optical path length required for the detection system, thereby improving measurement sensitivity and accuracy of the system.  如图3所示，所述的光纤ATR传感器5的光纤ATR测头18置于微型腔体27内，所述的微型腔体27的前端为对小于等于葡萄糖的分子有选择通过性的具有生物兼容性的半透膜16。  As shown in FIG. 3, the fiber optic probe ATR ATR sensor fiber 5 is placed within 18 27, the distal end 27 of the micro-cavity is by selective properties of the molecules of glucose less micro-cavity the biocompatible semipermeable membrane 16.  所述的微型腔体27内设置有对葡萄糖分子具有特异性动态吸附能力和生物兼容性的水溶性聚合物。  provided with a dynamic adsorption capacity and the specific biocompatible polymer to the water-soluble glucose molecules 27 within the micro-cavity. 该聚合物可以吸附葡萄糖分子，对于组织液中其它分子无作用，实现了葡萄糖分子的选择性测量，同时增强了光谱信号强度，提高了测量分辨率。 The polymer can adsorb glucose molecules for other molecules in the tissue fluid has no effect, to achieve the selective measurement of glucose molecules, while enhancing the strength of the signal spectrum, the measurement resolution.  S卩，光纤ATR传感器5的光纤ATR测头18置于微型腔体中，腔体端口具有生物兼容性的半透膜对小于等于葡萄糖的分子选择性通过，保护光纤ATR探头不被大分子粘附， 延长其使用寿命。  S Jie, fiber optic ATR probe ATR sensor fiber 5 is placed in the molecular semipermeable membrane 18 micro cavity, the cavity having a port for biocompatibility or less by selective glucose, to protect the fiber ATR probe is not adhesion molecules, extending its life. 此外，微型腔体中置有对葡萄糖分子具有动态选择性吸附能力和生物兼容性的水溶性聚合物（X表示）。 In addition, micro-cavity having a set of dynamic adsorption capacity and selectivity of biocompatible water-soluble polymer (X represents a) glucose molecules. 通过水溶性聚合物对葡萄糖分子的动态平衡式吸附，一方面削弱和排除了组织液中其他物质成分对葡萄糖检测过程的干扰，实现了光谱信息的选择性检测；另一方面由于葡萄糖分子和聚合物分子的吸附结合，如图3中标注14所示的聚合物溶液，使得检测葡萄糖分子时获得的衰减全反射吸收光谱信号得到了增强和放大，提高了光谱检测的分辨率和灵敏度。 By dynamic equilibrium adsorption of the water-soluble polymer of glucose molecules, and the weakening of the tissue fluid exclude interfering components other substances glucose detection process, to achieve selective detection of the spectral information; other hand, because the glucose molecules and polymers adsorbed molecules bound, labeled 3 in a polymer solution shown in FIG. 14, when detecting that the obtained attenuated total reflection absorption spectrum of glucose molecule has been enhanced signal amplification and improved spectral resolution and sensitivity of detection.  本发明的基于光纤衰减全反射的植入式人体血糖浓度连续监测系统结构采用双光路设计，双光路消除光源功率波动引起的测量误差和系统测量原理如下所述： 1，h时刻，参考和测量光路检测到的信号如公式⑴所示： Is= Ill .Tb· I。  The present invention is based on fiber attenuation of totally implantable human blood glucose monitoring system for continuous dual structure of optical design, the optical path bis eliminate measurement errors and system fluctuations measurement principle of the power source as follows:  1, signal h time point, the reference path and the measuring light detected as shown ⑴ formula:  is = Ill .Tb · I. 公式（I) Ir = n2 · I0 其中，L和Is分别为此时刻参考和测量光路的检测信号；Il1和Π2分别为测量和参考光路的线性传递系数；Ιο为激光器此时的输出光强；Tb为此时的测量样品的透过率。 Equation n2 · wherein, L and Is, respectively, the time reference and measurement light path detection signal for this I0  (I)  Ir =; Il1 and Π2, respectively, for the measurement and reference optical path linear transfer coefficient; Ιο a laser this output light intensity; Tb transmittance measurement sample at that time.  2，t2时刻，参考和测量光路检测到的信号如公式⑵所示： Γ s = η i · Ts · Γ。  2, t2 time, the reference path and the measuring light detection signal as shown in Equation ⑵:  Γ s = η i · Ts · Γ. 公式（2) Γ r = n2 · Γ 0 其中，I' jPI' 3分别为此时刻参考和测量光路的检测信号；Γ。 Equation (2)  Γ r = n2 · Γ 0  wherein, I 'jPI' 3 respectively for this measurement optical path and the reference timing detection signal; Γ. 为激光器此时的输出光强；TS为此时刻测量样品的透过率。 At this time, as the output of the laser light intensity; the TS transmittance measurement sample for this time.  则两个时刻由测量样品的变化引起的信号变化量由下式决定： Ag = Ιηφ == Ιηφ) + ln(f)公式⑶s s r 公式（3)中的右项中的参数均为可以直接测量的参数，公式第二项当激光器在h 和七2时刻输出功率相同，既Γ ^时，其值为零。  The time variation of the two signals caused by changes in the measurement sample is determined by the following formula:  Ag = Ιηφ == Ιηφ) + ln (f) formula ⑶s sr  Equation (right 3) items parameters are parameters can be measured directly, when the second term in equation the same as the laser output power in time of 2 h and seven, both Γ ^, its value is zero. 其含义为，若激光器输出功率稳定，则测量光路的检测结果，既公式（3)的第一项既为待测量的真实值；若激光器输出功率波动， 公式（3)中的第二项，既参考光路的测量结果相当于功率波动的校正参量，结合测量光路的检测结果，可获得待测量的真实值。 Its meaning is, if the laser output power is stable, the detection result of the measurement light path, both Equation (3) both the first item is the true value to be measured; if the laser output power fluctuation, the second term formula (3), both the measurement results corresponding to the reference optical path power fluctuations correction variables, combined detection result of the measurement light path, the true value to be measured can be obtained. 从而，参考光路的引入消除了光源的功率波动对系统测量结果的影响，提高了系统的稳定性和分辨率。 Thus, the introduction of the reference optical path to eliminate the influence of fluctuations in the power source system of the measurement results, improves the stability and resolution of the system.  本发明公开和揭示的所有组合可以通过借鉴本文公开内容产生，尽管本发明的组合已通过详细实施过程进行了描述，但本领域技术人员明显能在不脱离本发明内容、精神和范围内对本文所述的装置进行拼接改动，或增减某些部件。  All combinations of the disclosed invention and disclosed by reference the disclosure herein to produce, although the combination of the present invention have been described in the detailed implementation, those skilled in the art will clearly be able to without departing from the spirit, the spirit and scope of the invention the apparatus for splicing alterations described herein, or changes in certain components. 具体地说，所有相类似的替换和改动对本领域技术人员来说是显而易见的，他们都被视为包括在本发明精神、范围和内容之中。 Specifically, all similar substitutions and modifications to the skilled artisan will be apparent, they are regarded as included within the spirit of the present invention, the scope and content.