CN101947115B - Implantable human blood glucose concentration continuous monitoring system based on optical fiber attenuation total reflection - Google Patents
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Abstract
The invention discloses an implantable human blood glucose concentration continuous monitoring system based on optical fiber attenuation total reflection, consisting of double optical paths and comprising a light source, an attenuator, a spectroscope, an optical fiber coupling device, an optical fiber ATR sensor, a measurement photodetector, a reference photodetector, a data collection system and a computer, wherein after being attenuated by the attenuator, the light source is divided into two optical paths formed by a measurement light and a reference light; in one optical path, the measurement light enters the optical fiber ATR sensor in a coupling way through a coupling method by the optical fiber coupling device and is received by the measurement photodetector via a transmission light of the optical fiber ATR sensor; in the other optical path, the reference light is directly received by the reference photodetector; signals recevied by the measurement photodetector and the reference photodetector are synchronously collected by the data collection system, are sent to the computer and are in analysis treatment, and the computer displays a measurement result and is also connected with the light source. The invention adopts a direct measurement in vivo method to directly measure the glucose concentration in a tissue fluid, thereby avoiding an error of measurement in vitro.
Description
Technical Field
The invention relates to a device for continuously monitoring blood sugar concentration of a human body. In particular to an implanted human blood glucose concentration continuous monitoring system based on optical fiber attenuation total reflection, which realizes the continuous detection of the blood glucose concentration of a human body by measuring the glucose concentration in subcutaneous tissue fluid by using an optical fiber ATR sensor implanted into the human body.
Background
Diabetes is a common disease and a frequently encountered disease of middle-aged and elderly people, the incidence rate of the diabetes is increasing day by day, and the diabetes is in the trend of being younger and more enlarged. The world health world organization lists it as three major difficult and complicated diseases together with tumors and cardiovascular and cerebrovascular diseases.
However, no medical means for completely curing diabetes is available in clinic at present, and the aim of curing diabetes is to realize insulin control as much as possible, avoid hyperglycemia of a human body, and prevent or relieve complications and treat the complications according to symptoms. The world health organization recommends the self-monitoring of blood sugar for diabetics, grasps the blood sugar condition in vivo at any time, and realizes the accurate control of insulin, which is significant for preventing and treating diabetes and complications thereof. Therefore, accurate detection of blood glucose concentration in humans is a prerequisite and basis for the prevention and treatment of diabetes and its complications.
The current diabetes detection mainly depends on invasive measurement, and blood sugar detection methods widely adopted internationally do not leave invasive blood taking processes. Consumables are needed in the invasive blood sugar detection process, and frequent blood sampling not only brings physiological and psychological pains to patients, but also has the risk of wound infection. Especially for clinical application, the method has the biggest defects that the dynamic and continuous detection of the blood sugar concentration of a human body cannot be realized, and the real-time change situation of the blood sugar concentration in the body of a patient cannot be reflected, so that the optimal clinical treatment effect cannot be achieved.
With the development of laser and detection technologies, various noninvasive blood glucose detection methods based on optical technologies, such as light transmission and reflection spectroscopy, raman spectroscopy, optical rotation, and photoacoustic spectroscopy, which utilize the absorption characteristics of glucose molecules for near-infrared light, and light polarization, which utilizes the polarization characteristics of glucose molecules for near-infrared light, have become the subject of intense research in the field of noninvasive blood glucose detection. The noninvasive blood sugar detection method does not need to extract substances in the body such as blood and the like, does not need to implant a sensor under the skin, can detect the change of the blood sugar concentration in the body of a patient by the interaction of light and tissues at specific parts of the human body, can dynamically and continuously detect the blood sugar concentration of the human body, and is the most ideal human blood sugar monitoring method. However, the noninvasive blood glucose detection technology is not mature, can not be applied to clinic in the experimental research stage, and can not meet the requirement of dynamically and continuously detecting the blood glucose concentration of a human body. Moreover, to date, there has not been any non-invasive blood glucose measurement instrument approved by the U.S. FDA.
In view of the defects of invasive blood glucose detection and the technical bottlenecks of noninvasive blood glucose detection, the current international research on continuous monitoring of human blood glucose concentration mainly focuses on the field of minimally invasive blood glucose detection. Medical studies have shown that glucose concentration in subcutaneous tissue fluid is closely related to glucose concentration in blood. Thus, glucose concentration in blood can be predicted by monitoring glucose concentration in interstitial fluid. Minimally invasive blood glucose detection techniques can be divided into two broad categories, according to the detection mode: one is to extract tissue fluid from the human body subcutaneously in a minimally invasive way and then detect the glucose concentration in vitro by an electrical, optical or chemical method; the other type is that the micro-sensor is directly implanted into the subcutaneous part, and the glucose concentration in the subcutaneous tissue fluid is detected in real time in vivo.
Compared with the near infrared band, glucose has a unique absorption spectrum called as a fingerprint spectrum in the middle infrared region, and the glucose absorbs much stronger in the near infrared band and has a narrow absorption peak. Therefore, the mid-infrared absorption spectrum contains more abundant quantitative information, and is easier to extract, and is more advantageous particularly when detecting low-content components. The mid-infrared ATR absorption spectrometry overcomes the disadvantage that the penetration depth of mid-infrared light is limited and is only about 10 mu m due to strong water absorption in the application of a transmission measurement method, and is concerned in the field of component measurement.
The basic principle of the intermediate infrared attenuated total reflection absorption spectrometry is as follows: under the condition of total reflection, the light is attenuated on the contact surface of the crystal and the sample. The degree of attenuation is related to the penetration depth of the evanescent wave in the sample, which is determined by the incident wavelength, the angle of incidence, the crystal and the refractive index of the sample. This property of attenuation at different wavelengths can be used to extract information about the components in the sample. Important characteristics of the ATR method compared to conventional infrared transmission measurements are: the possibility that the sample is damaged by heating after being irradiated with light is eliminated, and the thickness of the sample is not limited by the wavelength of light which must be more than three times. For the design of the optical fiber ATR probe, a working part optical fiber circular surrounding mode is adopted, so that the effective working length of the optical fiber ATR probe is expanded in a limited volume space, the optical path length of the optical fiber ATR probe can be developed according to requirements, the detection resolution of the optical fiber ATR sensor is further improved, and the requirement of the optimal optical path length of the system is met.
In 1998, Heise et al used mid-infrared ATR spectroscopy for clinical chemistry analysis. Lamb equals 2006 and published the research result of middle infrared ATR spectroscopy for blood sugar continuous monitoring, and the noise equivalent blood sugar concentration obtained from the in vitro experiment is 40 mg/dL. Heise, in its 2008 publication, also started to focus on the use of mid-infrared spectroscopy for blood glucose monitoring in intensive care, using microdialysis techniques to extract subcutaneous tissue fluid and a mid-infrared spectrometer to study the concentration of glucose in the tissue fluid. However, the defects and shortcomings of the interstitial fluid extraction type minimally invasive blood glucose detection method also make the Heise method finally incapable of being applied clinically.
Disclosure of Invention
The technical problem to be solved by the invention is to provide an implanted human blood glucose concentration continuous monitoring system based on optical fiber attenuation total reflection, which adopts an in-vivo direct measurement method to directly measure the glucose concentration in tissue fluid and can meet the real-time and continuous blood glucose detection requirements.
The technical scheme adopted by the invention is as follows: an implanted human blood glucose concentration continuous monitoring system based on optical fiber attenuation total reflection is composed of a double light path and comprises a light source, an attenuator, a spectroscope, an optical fiber coupling device, an optical fiber ATR sensor, a measuring light detector, a reference light detector, a data acquisition system and a computer, wherein the light source is attenuated by the attenuator and then is divided into two light paths consisting of measuring light and reference light by the spectroscope, one light path is that the measuring light adopts the optical fiber coupling device and is coupled into the optical fiber ATR sensor by a coupling method, and the transmitted light passing through the optical fiber ATR sensor is received by the measuring light detector; the other optical path is that the reference light is directly received by the reference light detector; the signals received by the measuring light detector and the reference light detector are synchronously acquired by a data acquisition system, and are sent to a computer for analysis and processing and displaying the measurement result, and the computer is also connected with the light source.
The light source outputs 1035 and 1080cm wavelengths including glucose mid-infrared band-1Miniaturized wavelength tunable CO with characteristic absorption peak2A laser.
The optical fiber coupling device is three-dimensionally adjustable.
The three-dimensional adjustable optical fiber coupling device comprises: the two micro lenses are respectively used for coupling a skin optical fiber path and a subcutaneous optical fiber path on an incident light path between the optical fiber coupling device and the optical fiber ATR sensor, and a skin optical fiber path and a subcutaneous optical fiber path on an emergent light path, and the three-dimensional adjustable clamping structure is used for fixing the two skin optical fiber paths.
The coupling method comprises a coupling method based on an optical window or an optical clear technology.
The optical window includes a cap structure for protecting the coupling ports of the subcutaneous optical fiber path and the subcutaneous optical fiber path.
The optical clearing technology is to smear biocompatible high-permeability preparation with set concentration on the skin surface so as to enhance the permeability of tissues to light.
The optical fiber ATR sensor is formed by a multimode optical fiber in a single-ring or multi-ring probe structure.
The optical fiber ATR measuring head of the optical fiber ATR sensor is arranged in the micro cavity, and the front end of the micro cavity is a semipermeable membrane with biocompatibility and selective permeability for molecules less than or equal to glucose.
The micro cavity is internally provided with a water-soluble polymer which has specific dynamic adsorption capacity and biocompatibility on glucose molecules.
The implanted human blood glucose concentration continuous monitoring system based on the optical fiber attenuation total reflection directly measures the glucose concentration in the tissue fluid by adopting an in-vivo direct measurement method, thereby avoiding in-vitro measurement errors. The method has the advantages that the measurement is carried out in vivo, the volume of the extracted tissue fluid does not need to be accurately calculated, and the possibility of introducing errors is further reduced. The implantable blood sugar continuous detection technology based on the mid-infrared optical fiber attenuated total reflection can meet the requirements of real-time and continuous blood sugar detection.
Has the following characteristics:
1. the ATR sensing probe is composed of optical fibers, the probe is designed in an annular mode, and the working length of the optical fiber ATR sensor is increased in a limited space. The probe has simple structure, small volume and easy manufacture, and can be implanted into the subcutaneous part of a human body to continuously monitor the glucose concentration in the body for 24 hours.
2. According to the invention, the optical fiber probe is arranged in the micro cavity, the front end of the cavity is provided with the semipermeable membrane with biocompatibility, only glucose and other small molecules are allowed to enter the cavity, the phenomenon that macromolecules are adsorbed on the surface of the optical fiber ATR sensor probe is avoided, the protection effect is achieved, and the service life of the probe is prolonged.
3. The invention utilizes the water-soluble polymer with specific dynamic adsorption capacity and biocompatibility on glucose molecules, reduces the interference of other substances in tissue fluid on measurement through the dynamic specific adsorption capacity of the water-soluble polymer on the glucose molecules, realizes the selective measurement of the glucose molecules and improves the measurement resolution.
4. The invention adopts a double-light-path structure, which comprises a reference light path and a measuring light path. The introduction of the reference light path eliminates the measurement error caused by the power fluctuation of the light source, and improves the stability and the resolution of the system.
5. The three-dimensional adjustable optical fiber coupling device of the invention separates the optical fiber ATR sensor from the detection system formed by the light source, the detector and the like, and lays a foundation for clinical application.
6. The invention provides a coupling method based on an optical clear technology, which enables an optical fiber to be embedded within 200 mu m of the subcutaneous tissue and reduces the possibility of infection.
7. The optical fiber probe, the micro cavity, the semipermeable membrane, the water-soluble polymer and the like are all made of biocompatible materials, and the optical fiber probe, the micro cavity, the semipermeable membrane, the water-soluble polymer and the like are safe and reliable and are harmless to human bodies.
Drawings
FIG. 1 is a schematic view of the overall structure of the present invention;
FIGS. 2(a) and 2(b) are schematic structural diagrams of an optical fiber ATR probe according to the present invention;
FIG. 3 is a schematic representation of the use of a semi-permeable membrane and a water-soluble polymer in a mid-infrared optical fiber ATR sensing probe;
FIG. 4 is a schematic diagram of a three-dimensional tunable fiber optic coupling device with a fiber ATR sensor separated from a detection system.
Fig. 5 is a schematic diagram of a system structure based on an optical window coupling method.
Fig. 6 is a schematic diagram of a system structure based on an optical clear coupling method.
Wherein,
1: light source 2: attenuator
3: spectroscope 4: optical fiber coupling device
5: optical fiber ATR sensor 6: measuring light path detector
7: reference optical path detector 8: data acquisition system
9: the computer 10: optical fiber path 1
11: single ring ATR probe 12: optical fiber path 2
13: multi-ring ATR probe 14: polymer solution
15: tissue 16: semipermeable biological membranes
17: optical fiber 18: optical fiber ATR probe
19: subcutaneous optical fiber path 20: subcutaneous optical fiber path
21: cap-like structure 22: optical fiber clamping structure
23: on-skin fiber path 24: micro-lens
25: fiber path on skin 26: skin(s)
27: micro-cavity 28: glucose molecules
29: polymer molecule 30: first mark
31: second mark
Detailed Description
The following describes the implantable human blood glucose concentration continuous monitoring system based on fiber-optic attenuated total reflection according to the present invention in detail with reference to the following embodiments and the accompanying drawings.
As shown in fig. 1, the implanted continuous monitoring system for blood glucose concentration of human body based on fiber attenuation total reflection of the present invention is composed of a dual optical path, including a light source 1, an attenuator 2, a spectroscope 3, a fiber coupling device 4, a fiber ATR sensor 5, a measuring photodetector 6, a reference photodetector 7, a data acquisition system 8 and a computer 9. The light source 1 is attenuated by an attenuator 2 and then is divided into two light paths consisting of measuring light and reference light by a spectroscope 3, wherein one light path is that the measuring light is coupled into an optical fiber ATR sensor 5 by an optical fiber coupling device 4 through a coupling method, the transmitted light passing through the optical fiber ATR sensor 5 is received by a measuring light detector 6, and the coupling method comprises a coupling method based on an optical window or an optical clear technology; the other optical path is that the reference light is directly received by the reference light detector 7; the signals received by the measuring light detector 6 and the reference light detector 7 are synchronously acquired by a data acquisition system 8, and are sent to a computer 9 for analysis and processing and displaying the measurement result, and the computer 9 is also connected with the light source 1. The invention utilizes the optical fiber ATR sensor implanted in the human body to realize the continuous monitoring of the concentration of the blood sugar of the human body by measuring the concentration of the glucose in the subcutaneous tissue fluid of the human body.
Namely, the optical system structure of the present invention is a dual optical path including a reference optical path and a measurement optical path. The detection signals of the reference light path detector and the measurement light path detector are synchronously acquired by a data acquisition system, and are analyzed, processed and displayed by a program in a computer. The ratio of the background detected by the two depth detectors to the reflection signal of the sample to be detected is converted into the absorbance of the sample to be detected according to the linear characteristics of the system. The dual optical path design, i.e. the introduction of the reference optical path, eliminates the light source CO2The influence of the power fluctuation of the laser on the measurement result improves the stability and the resolution of the system.
The light source 1 outputs 1035 and 1080cm wavelengths including glucose mid-infrared band-1Miniaturized wavelength tunable CO with equal characteristic absorption peak2And the line width of the output wavelength spectrum of the laser is narrow, which is beneficial to the detection and extraction of signals. The optical fiber coupling device 4 is a three-dimensional adjustable optical fiber coupling device. The attenuator 2 is continuously adjustable, and the adjusting range is 0.01% -100%, so that the power of the incident optical fiber ATR sensor is lower than the human body safety standard, and the requirement of the maximum power limit of the detector detection is met. Measuring light detector6 and reference light detector 7 are pyroelectric or tellurium cadmium mercury photoelectric detector suitable for the mid-infrared wave band, and tellurium cadmium mercury photoelectric detector has the liquid nitrogen refrigerating system, compares pyroelectric detector and can further improve measurement resolution ratio, but pyroelectric detector price is cheap relatively.
As shown in fig. 4, the implanted human blood glucose concentration continuous monitoring system based on fiber-optic attenuated total reflection is divided into three parts: a subcutaneously implanted optical fibre ATR sensor 5, as shown by the subcutaneous dashed box portion denoted by reference numeral 5 in fig. 4; a fiber coupling device 4, shown in phantom at 4 in FIG. 4; a light source and a detector. Therefore, the optical fiber ATR sensor is implanted subcutaneously, and a detection system consisting of a light source, a detector and the like is arranged outside without carrying about, thereby laying a foundation for clinical application. The three-dimensional adjustable optical fiber coupling device 4 comprises: two micro lenses 24 respectively used for coupling the skin optical fiber path 25 and the subcutaneous optical fiber path 19 on the incident optical path between the optical fiber coupling device 4 and the optical fiber ATR sensor 5 and the skin optical fiber path 23 and the subcutaneous optical fiber path 20 on the emergent optical path, and a three-dimensional adjustable clamping structure 22 used for fixing the two skin optical fiber paths 25 and 23.
As shown in fig. 5, the optical window based coupling technique, the optical fiber is implanted subcutaneously and the coupling ports 19, 20 are flat with the skin surface. The solution comprises a cap-like structure 21 for protecting the fiber paths 25, 23 on the skin and the coupling ports of the fiber paths 19, 20 under the skin flat with the skin surface, normally attached to the skin surface, open for measurement. In the application of the coupling method of the optical window, the optical fiber coupling port is exposed out of the skin surface, so that the inconvenience is caused, the possibility of infection is increased, and the coupling effect is good.
Fig. 6 is a schematic diagram of a coupling method based on the optical clear technology. The fibre coupling ports 19, 20 are located within 200 μm subcutaneously and do not require a cap-like structure to protect the fibre ports. Biocompatible high-permeability preparations (such as glycerol, ethylene glycol and the like or a mixture of two of the glycerol and the ethylene glycol) with set concentration are smeared at the first mark position and the second mark position 30 and 31 of the skin surface corresponding to the subcutaneous optical fiber, and after about 5 minutes, the high-permeability preparations on the skin surface are erased, so that the specular reflection on the skin surface and the scattering effect of subcutaneous components are eliminated, the light permeability of the measuring part corresponding to the subcutaneous optical fiber is enhanced, and the coupling effect is enhanced. The positioning device performs the septal butt joint of the skin optical fibers 25 and 23 and the subcutaneous optical fibers 19 and 20 according to the preset marks. The coupling method of the optical clear technology enables the optical fiber to be buried under the skin and not to be in contact with the outside, so that the possibility of infection is reduced, but the coupling effect is common.
As shown in fig. 2(a) and 2(b), the optical fiber ATR sensor 5 is formed by a multimode optical fiber in a single-ring or multi-ring probe structure, has a small ring design volume, meets the requirement of sensor implantation under the skin, expands the effective working length in a limited volume space, and improves the measurement resolution of the optical fiber ATR sensor. The multimode fiber material is silver halide which has small absorption in the middle infrared band and is easy to bend. According to the Lambert-beer law, the optimal optical path length under the glucose absorption peak can be derived, and higher sensitivity and smaller detection limit can be obtained under the optimal optical path. The optimal optical path at a single wavelength is given by formula l optimal1/∑ epsilon c, where Σ epsilon c refers to the sum of the extinction coefficient of all substances in the solution at this wavelength multiplied by their concentration. The linear optical fiber has limited total reflection times, so that the invention adopts the bending of the optical fiber according to a certain curvature to increase the total reflection times under the condition of meeting the total reflection, thereby achieving the purpose of increasing the optical path length, and the annular structure of the optical fiber ensures that the optical fiber obtains longer working length within the limited geometric dimension, thereby being possible to be implanted into the human body. Meanwhile, different optical path lengths can be obtained by adjusting the annular structure of the optical fiber ATR measuring head, such as radius, annular number and the like, so that the optimal optical path length required by system detection is met, and the measurement sensitivity and precision of the system are improved.
As shown in fig. 3, the optical fiber ATR probe 18 of the optical fiber ATR sensor 5 is disposed in a micro-chamber 27, and the front end of the micro-chamber 27 is a biocompatible semi-permeable membrane 16 having selective permeability to molecules equal to or less than glucose.
The micro-cavity 27 is internally provided with a water-soluble polymer which has specific dynamic adsorption capacity and biocompatibility on glucose molecules. The polymer can adsorb glucose molecules, has no effect on other molecules in tissue fluid, realizes selective measurement of the glucose molecules, enhances the intensity of spectral signals, and improves the measurement resolution.
That is, the optical fiber ATR probe 18 of the optical fiber ATR sensor 5 is placed in the micro-cavity, and the semi-permeable membrane with biocompatibility at the cavity port selectively passes through molecules less than or equal to glucose, so that the optical fiber ATR probe is protected from being adhered by macromolecules, and the service life of the optical fiber ATR probe is prolonged. In addition, a water-soluble polymer (represented by x) having a dynamic selective adsorption ability and biocompatibility to glucose molecules is placed in the micro-cavity. The interference of other substance components in the tissue fluid on the glucose detection process is weakened and eliminated on one hand by the dynamic balanced adsorption of the water-soluble polymer on glucose molecules, and the selective detection of spectral information is realized; on the other hand, due to the adsorption and combination of the glucose molecules and the polymer molecules, the attenuated total reflection absorption spectrum signal obtained when the glucose molecules are detected is enhanced and amplified, and the resolution and the sensitivity of the spectrum detection are improved, as shown in the polymer solution marked with 14 in fig. 3.
The structure of the implanted human blood glucose concentration continuous monitoring system based on the optical fiber attenuation total reflection adopts a double-light-path design, the double light-path eliminates the measurement error caused by the power fluctuation of a light source, and the system measurement principle is as follows:
1，t1at the moment, the signals detected by the reference and measurement optical paths are as shown in equation (1):
Is＝η1·Tb·I0formula (1)
Ir＝η2·I0
Wherein, IrAnd IsRespectively referencing and measuring the detection signals of the optical path at the moment; eta1And η2Linear transmission of the measuring and reference light paths, respectivelyA step coefficient; i is0The output light intensity of the laser at the moment; t isbThe transmittance of the sample was measured at this time.
2，t2At the moment, the signals detected by the reference and measurement optical paths are as shown in equation (2):
I′s＝η1·Ts·I′0formula (2)
I′r＝η2·I′0
Wherein, I'rAnd l'sRespectively referencing and measuring the detection signals of the optical path at the moment; i'0The output light intensity of the laser at the moment; t issThe transmittance of the sample was measured at this time.
The amount of change in the signal caused by the change in the measured sample at both times is determined by the following equation:
The parameters in the right term in the formula (3) are all parameters which can be directly measured, and the second term in the formula is when the laser is at t1And t2The output power at all times is the same, I'0＝I0Its value is zero. The meaning is that if the output power of the laser is stable, the detection result of the optical path is measured, namely, the first term of the formula (3) is the true value to be measured; if the output power of the laser fluctuates, the second term in the formula (3), namely the measurement result of the reference optical path is equivalent to the correction parameter of the power fluctuation, and the actual value to be measured can be obtained by combining the detection result of the measurement optical path. Therefore, the influence of the power fluctuation of the light source on the measurement result of the system is eliminated by introducing the reference light path, and the stability and the resolution of the system are improved.
All combinations of the invention disclosed and disclosed herein can be made by reference to the present disclosure, and although the combinations of the invention have been described in terms of detailed implementation, it will be apparent to those skilled in the art that splice modifications can be made to the apparatus described herein, or that certain elements can be added or subtracted, without departing from the spirit, scope and content of the invention. In particular, all such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and content of the invention.
Claims (8)
1. An implanted human blood glucose concentration continuous monitoring system based on optical fiber attenuation total reflection is characterized by comprising a light source (1), an attenuator (2), a spectroscope (3), an optical fiber coupling device (4), an optical fiber ATR sensor (5), a measuring light detector (6), a reference light detector (7), a data acquisition system (8) and a computer (9), and is characterized in that the light source (1) is attenuated by the attenuator (2) and then is divided into two light paths consisting of measuring light and reference light by the spectroscope (3), wherein one of the light paths is that the measuring light adopts the optical fiber coupling device (4), is coupled into the optical fiber ATR sensor (5) by a coupling method, and the transmitted light passing through the optical fiber ATR sensor (5) is received by the measuring light detector (6); the other optical path is that the reference light is directly received by a reference light detector (7); the signals received by the measuring light detector (6) and the reference light detector (7) are synchronously acquired by a data acquisition system (8), sent to a computer (9) for analysis and processing and display of a measurement result, the computer (9) is also connected with the light source (1), the optical fiber coupling device (4) is three-dimensionally adjustable, and the three-dimensionally adjustable optical fiber coupling device (4) comprises: the two micro lenses (24) are respectively used for a skin optical fiber path (25) and a subcutaneous optical fiber path (19) on an incident optical path between the optical fiber coupling device (4) and the optical fiber ATR sensor (5) and for coupling a skin optical fiber path (23) and a subcutaneous optical fiber path (20) on an emergent optical path, and the three-dimensional adjustable clamping structure (22) is used for fixing the two skin optical fiber paths (25, 23).
2. The implantable human blood glucose concentration continuous monitoring system based on the fiber-optic attenuated total reflection of claim 1, wherein the light source (1) is 1035 and 1080cm with output wavelengths including glucose mid-infrared band-1Miniaturized wavelength tunable CO with characteristic absorption peak2A laser.
3. The system of claim 1, wherein the coupling method comprises a coupling method based on an optical window or an optical clear technology.
4. The implantable human blood glucose concentration continuous monitoring system based on fiber-optic attenuated total reflection of claim 3, wherein said optical window comprises a cap-like structure (21) for protecting the coupling ports of the subcutaneous and the epithelial optical fiber paths (19, 20) and (25, 23).
5. The implantable human blood glucose concentration continuous monitoring system based on fiber-optic attenuated total reflection of claim 3, wherein the optical clearing technique is to coat a biocompatible high-permeability preparation with a set concentration on the skin surface to enhance the permeability of the tissue to light.
6. The implantable human blood glucose concentration continuous monitoring system based on the fiber attenuated total reflection of claim 1, wherein the fiber ATR sensor (5) is formed by a multimode fiber in a single-ring or multi-ring probe structure.
7. The implantable human blood glucose concentration continuous monitoring system based on the fiber attenuated total reflection of claim 6, wherein the fiber ATR probe (18) of the fiber ATR sensor (5) is arranged in a micro-cavity (27), and the front end of the micro-cavity (27) is a semi-permeable membrane (16) with biocompatibility and selective permeability for molecules less than or equal to glucose.
8. The implantable human blood glucose concentration continuous monitoring system based on the fiber-optic attenuated total reflection of claim 7, wherein the micro-cavity (27) is internally provided with a water-soluble polymer with specific dynamic adsorption capacity and biocompatibility on glucose molecules.
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| US20130060106A1 (en) | 2011-09-06 | 2013-03-07 | Medtronic Minimed, Inc. | Optical sensing systems and methods |
| CN205672030U (en) * | 2013-03-14 | 2016-11-09 | 贝克顿·迪金森公司 | For sensing the carry-on equipment of intravital analyte |
| JP2016523608A (en) * | 2013-06-06 | 2016-08-12 | プロフサ，インコーポレイテッド | Apparatus and method for detecting optical signal from embedded sensor |
| CN103637808B (en) * | 2013-11-18 | 2015-08-19 | 深圳先进技术研究院 | Opto-acoustic imaging devices |
| CN103919561B (en) * | 2014-03-25 | 2015-08-19 | 天津大学 | Based on the flattening type optical fiber ATR glucose sensor that metal nanoparticle strengthens |
| CN103919560A (en) * | 2014-03-25 | 2014-07-16 | 天津大学 | Bent optical fiber ATR (attenuated total reflectance) glucose sensor reinforced on basis of silver nanoparticles |
| DE102014210440B4 (en) * | 2014-06-03 | 2018-07-19 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | glucose sensor |
| CN104657576B (en) * | 2014-09-28 | 2017-09-22 | 东软熙康健康科技有限公司 | The rendering method and equipment of a kind of change of blood sugar |
| KR102491852B1 (en) * | 2015-08-28 | 2023-01-26 | 삼성전자주식회사 | Optical sensor and method of operating of the optical sensor |
| CN106037763B (en) * | 2016-07-04 | 2019-01-25 | 普乐药业有限公司 | A kind of fibre optical sensor syringe |
| ES2774983B2 (en) | 2019-01-22 | 2021-06-10 | Univ Sevilla | PORTABLE DEVICE AND METHOD FOR NON-INVASIVE ESTIMATION OF GLUCOSE LEVEL IN BLOOD |
| US11864906B2 (en) * | 2019-06-20 | 2024-01-09 | International Business Machines Corporation | LIDAR implantable biosensor for imaging biological tissue |
| CN110269627A (en) * | 2019-08-02 | 2019-09-24 | 普乐药业有限公司 | Blood sugar measuring system and method |
| CN110811639B (en) * | 2019-11-06 | 2023-11-21 | 浙江清华柔性电子技术研究院 | Total bilirubin detection patch and total bilirubin detection system |
| CN113567387A (en) * | 2021-08-24 | 2021-10-29 | 广东得语健康科技有限公司 | Cavity-enhanced infrared absorption spectrum sugar urine detection system and detection method thereof |
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