CN101819136A - Human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance - Google Patents

Human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance Download PDF

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CN101819136A
CN101819136A CN 201010153400 CN201010153400A CN101819136A CN 101819136 A CN101819136 A CN 101819136A CN 201010153400 CN201010153400 CN 201010153400 CN 201010153400 A CN201010153400 A CN 201010153400A CN 101819136 A CN101819136 A CN 101819136A
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optical fiber
glucose concentration
continuous monitoring
plasmon resonance
surface plasmon
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CN101819136B (en
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栗大超
伍鹏
刘同坤
徐可欣
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Tianjin University
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Abstract

The invention discloses a human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance. An optical fiber SPR (Surface Plasmon Resonance) probe is implanted in a human body; light emitted by a light source reaches the optical fiber SPR probe via an optical fiber coupler; after SPR attenuation, reflected light reaches a spectrograph through the optical fiber coupler; and a computer analyzes and processes data output by the spectrograph and displays monitoring results. A micro-cavity is fixed outside the optical fiber SPR probe, one side of the micro-cavity is a semitransparent film, and only glucose and other micromolecules can enter the micro-cavity. GGBP proteins or borate polymers are fixed on the goldfilm surface of the optical fiber SPR probe and can carry out specificity absorption to the glucose molecules, thereby improving the measurement sensitivity. The invention can realize human glucose concentration continuous monitoring by measuring the glucose concentration of human body tissue fluid, has high measurement precision and good stability and can realize 24-hour human glucose concentration continuous monitoring and provide comprehensive glucose concentration change data for better guiding the diabetes treatment.

Description

Human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance
Technical field
The present invention relates to a kind of human glucose concentration continuous monitoring device.Particularly relate to a kind of human glucose concentration continuous monitoring device that includes light source, fiber coupler, optical fiber probe, spectrometer and computing machine based on optical fiber surface plasmon resonance.
Background technology
Along with the raising of people's living standard, the variation of dietary structure and the change of life style, the increase of aging population and fat incidence, the incidence of disease of diabetes is ascendant trend year by year.The continuous blood sugar monitoring more and more is familiar with by people the significance of diabetes diagnosis and treatment.If can carry out painless and continual continuous blood sugar monitoring to the patient, the data that provide more close blood sugar drift to change, the blood sugar " overall picture " that just can reflect the patient, measure those uncared-for blood glucose information, disclose hiding blood sugar condition, find the peak value etc. of hypoglycemic episodes repeatedly, dawn phenomenon and the hyperglycaemia of those no conscious symptons, glucose-lowering treatment scheme reasonable more for drafting, individuation, valuable clinical foundation is provided, thereby instructs treatment of diabetes better.
Employed blood sugar test technology in the blood sugar monitoring process can be divided into by its wound degree to body and wound to be arranged, do not have wound and Wicresoft is detected.There is wound to be meant to touch in the testing process blood vessel and nerve to cause wound and causes and keenly feel; Not having wound is meant body without any damage; Though Wicresoft is meant little wound, do not touch blood vessel with neural, patient's no pain.
There is the wound blood sugar monitoring to adopt vein haemospasia and quick finger tip tip blood to detect blood sugar more.Because the restriction of detection method, blood sugar monitoring can only be finished at isolated time point, its result reflection be the moment blood sugar in certain several moment in one day, moment blood glucose value moved, all multifactor influences such as diet, medicine, anxious state of mind, exist certain one-sidedness and inaccuracy.And repeatedly blood drawing not only consumes a large amount of test paper, also brings certain psychological burden to the patient.
Along with the continuous development of laser and detection technique thereof, people's exploratory development multiple Woundless blood sugar detection method based on optical technology.Because except that glucose, water, fat and other mesostates in the body is to the absorption of spectrum; Changeable light scattering situation in the body; And the variation of aquation, volume of blood flow, temperature and other factors etc., the Woundless blood sugar detection technique exists the low and data reappearance of signal to noise ratio (S/N ratio), sensitivity, selectivity, to the relatively poor problems such as adaptability of individuality.To really realize practical application clinically, have got long long way to go.
Wicresoft's blood sugar test technology can either be avoided the limitation of wound blood sugar test to greatest extent, and its method detects more direct again than Woundless blood sugar, and it is also more easy to implement, and therefore has been subjected to giving more sustained attention of people.Wicresoft's blood sugar test technology has just changed measuring object into the tissue fluid relevant with blood level by the blood that has wound to detect still from the angle of direct measurement, by the method for Wicresoft's wound, at body or gather to vitro detection concentration of glucose wherein.To vitro detection, need the amount of tissue fluid bigger tissue fluid extracting, and need accurately know the extraction amount, increased the difficulty that extracts; In-vitro measurements also is subjected to influence extraneous and internal milieu difference, and measuring error is bigger; Because the restriction of instrument, in-vitro measurements are difficult to accomplish monitoring in real time in 24 hours.In bulk measurement is pick-up unit to be implanted to directly measure the tissue fluid concentration of glucose in the human body body, remedies the deficiency of above vitro detection, has very high using value.
Surface plasma body resonant vibration (SPR) is a kind of physical optics phenomenon, is interacted and is produced by the free electron on incident light wave and metallic conductor surface.Incident ray shines optically thinner medium from optically denser medium, when during greater than certain specific angle (critical angle), total reflection phenomenon taking place in incident angle.If between the two media interface, there is the metallic film of thickness tens nanometers, the P polarized component of the evanescent wave that produces during total reflection will enter metallic film so, interact with the free electron in the metallic film, inspire the surface plasma wave of propagating along the metallic film surface (SPW).When the angle of incident light or wavelength during to a certain particular value, the major part of incident light can convert the energy of SPW to, thereby the catoptrical energy of total reflection is descended suddenly, occurs resonance absorbing peak on reflectance spectrum, this moment incident light angle or wavelength, be called resonance angle or the resonant wavelength of SPR.The character on the resonance angle of SPR or resonant wavelength and metallic film surface is closely related, if metallic film surface attachment measured matter (being generally solution or biomolecule), can cause the variation of metallic film surface refractive index, thereby cause that the SPR optical signalling changes.According to this signal, just can obtain information such as the refractive index of glucose in the tissue fluid or concentration.Optical fiber is as a kind of transmission medium of light, and the singularity of its structure has determined it to be fit to be used to the making of surface plasma resonance sensor.The support of metallic film plated layer of metal film on the surface of fibre core when the fibre core of total internal reflection transmission light can be measured as SPR, and optical fiber just can be used as the Sensitive Apparatus that SPR measures.In recent ten years, many spr sensors based on optical fiber are studied use.The optical fiber probe volume is small and exquisite, portable strong, realizes the measurement of miniaturization and implanted easily.But present stage, the precision that has of optical fiber measurement mechanism was not high, can't reach and measure concentration of glucose requirement in the tissue fluid; The less stable that has can not long-time continuous be measured; What have measures owing to problems such as bio-compatibility can not be implanted in the human body body.
Summary of the invention
Technical matters to be solved by this invention is, a kind of measuring accuracy height, good stability is provided, has the human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance of bio-compatibility.
The technical solution adopted in the present invention is: a kind of human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance, by light source, fiber coupler, optical fiber probe, spectrometer and computing machine are formed, by measuring concentration of glucose realization human glucose concentration continuous monitoring in the tissue liquid, described light source arrives the interior optical fiber probe of implant into body body through fiber coupler, arrive spectrometer by fiber coupler again from the light of optical fiber probe reflection, described spectrometer output data is to computing machine, and described COMPUTER CALCULATION machine carries out analyzing and processing and shows measurement result the data of spectrometer output.
Described light source is a white light source, requires wavelength to change continuously in 400nm~900nm wavelength coverage, the smoothly stable nothing sudden change of wave spectrum.
Described fiber coupler is the one-to-two multimode optical fiber.
Described spectrometer wavelength sensing range covers 400~900nm, and detection sensitivity reaches 0.5nm.
The optical fiber of described optical fiber probe is multimode optical fiber, include fiber core, be plated in the metal film on the outer peripheral face of fiber core end, be plated in the catoptron of fiber core termination, be wrapped in optical fiber coating and covering on the outer peripheral face of fiber core except that metal-plated membrane from the inside to the outside.
Described golden film thickness is 45~55nm.
Described catoptron adopts gold or ag material, and thickness is 295~305nm.
Described fiber core is fixed with a miniature cavity in the periphery of metal-plated membrane part, and the end face of described miniature cavity is provided with the semi-permeable diaphragm that only has micromolecule to pass through.
Described golden film outer surface is fixed with one deck glucose molecule is had the specific adsorption characteristic, promptly very easily adsorbs in conjunction with glucose molecule and the adiaphorous D-galactose of other materials/D-grape carbohydrate-binding protein or borate polymkeric substance.Described GGBP albumen and borate polymkeric substance adopt the mode of covalent bonds or self assembly layer by layer to be fixed in golden film surface.
Human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance of the present invention has following characteristics:
1. sensing probe of the present invention is made of optical fiber, and is simple in structure, volume is small and exquisite, can be implanted to that human body is subcutaneous to carry out concentration of glucose continuous monitoring in 24 hours.Thereby the data that can provide comprehensive concentration of glucose to change provide valuable clinical foundation for drafting glucose-lowering treatment scheme reasonable more, individuation.
2. the present invention is fixed on miniature cavity outside the fibre-optical probe, can effectively protect probe, has improved measuring stability; Cavity one side has only micromolecule such as glucose can enter into cavity for semi-permeable diaphragm, reduced the influence of other materials to measuring in the hypodermis, has also played the effect of selective measurement.
3. the present invention utilizes covalent bonds or layer-by-layer that GGBP albumen or borate polymkeric substance are fixed on the sensor gold film surface.Because GGBP albumen, borate polymkeric substance have the specific adsorption characteristic to glucose molecule, make apparatus of the present invention compare other glucose measurement devices and have higher measurement sensitivity.
4. fibre-optical probe of the present invention, miniature cavity, semi-permeable diaphragm are made by biocompatible material, and be safe and reliable, can not produce harm to human body.
Description of drawings
Fig. 1 is based on the structural representation of the human glucose concentration continuous monitoring device of optical fiber;
Fig. 2 is the optical fiber probe structural representation that the present invention relates to;
Fig. 3 is the fixedly detecting head surface structural representation behind GGBP albumen or the borate polymkeric substance of covalent bond;
Fig. 4 is the processing procedure and the detecting head surface structural change process synoptic diagram of self assembly layer by layer.
Wherein:
1: light source 2: fiber coupler
3: optical fiber probe 4: computing machine
5: spectrometer 6: skin and hypodermis
7: spectrometer computing machine connecting line 8: optical fiber coating and covering
9: fiber core 10: golden film
11: micro-reflector 12:GGBP albumen or borate polymeric layer
13: miniature cavity 14: semi-permeable diaphragm
15: glucose molecule 16: the self assembly molecule layer
Embodiment
Below in conjunction with embodiment and accompanying drawing the human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance of the present invention is made a detailed description.
As shown in Figure 1, human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance of the present invention, form by light source 1, fiber coupler 2, optical fiber probe 3, spectrometer 5 and computing machine 4, by measuring concentration of glucose realization human glucose concentration continuous monitoring in the tissue liquid.Described optical fiber probe 3 adopts in the mode implant into body body of operation or syringe guiding.The optical fiber probe 3 that described light source 1 arrives in the implant into body body through fiber coupler 2, after the surface plasma resonance decay takes place, arrive spectrometer 5 by fiber coupler 2 again from the light of optical fiber probe 3 reflections, described spectrometer 5 output datas are to computing machine 4, and described computing machine 4 computing machines carry out analyzing and processing and show measurement result the data of spectrometer output.Computing machine can be calculated measured matter refractive index and concentration by the SPR opisometer, and can be shown result of calculation by input data fitting SPR curve.
Described light source 1 is a white light source, requires wavelength to change continuously in 400nm~900nm wavelength coverage, the smoothly stable nothing sudden change of wave spectrum.Described fiber coupler 2 is the one-to-two multimode optical fiber.Described spectrometer 5 wavelength sensing ranges cover 400~900nm, and detection sensitivity reaches 0.5nm.
As shown in Figure 2, the optical fiber of described optical fiber probe 3 is multimode optical fiber, includes fiber core 9, is plated in the metal film 10 on the fiber core 9 end outer peripheral faces, and described golden film 10 thickness are 45~55nm.Be plated in the catoptron 11 of fiber core 9 terminations, described catoptron 11 adopts gold or ag material, and thickness is 295~305nm.Be wrapped in optical fiber coating and covering 8 on the outer peripheral face of fiber core 9 except that metal-plated membrane 10 from the inside to the outside.Described golden film 10 outside surfaces are fixed with one deck D-galactose/D-glucose in conjunction with Protein G GBP or borate polymkeric substance, D-galactose/D-glucose has the specific adsorption characteristic in conjunction with Protein G GBP or borate polymkeric substance to glucose molecule, and promptly very easily adsorbing in conjunction with glucose molecule does not have effect with other materials.Described GGBP albumen and borate polymkeric substance adopt the mode of covalent bonds or self assembly layer by layer to be fixed in golden film surface.Described fiber core 9 is fixed with a miniature cavity 13 in the periphery of metal-plated membrane 10 parts, and the end face of described miniature cavity 13 is provided with the semi-permeable diaphragm 14 that only has the glucose micromolecule to pass through.
The method for making of optical fiber probe 3 of the present invention is: (1) is that (NA 0.36 for multimode optical fiber with a core diameter 600um, refractive index 1.458) fiber core 9, with sulfuric acid corrosion coat and covering 8, the barish fiber core that the end of multimode optical fiber is stayed polishes this end end face then and polishes; (2) with vacuum coating equipment fiber end face is plated metal film (gold or silver) the formation micro-reflector that thickness reaches 295~305nm, the outer peripheral face at exposed fiber core plates the golden film that thickness is 45~55nm then; (3) fix a miniature cavity in the transducing part periphery, the semi-permeable diaphragm that the one side of cavity can be passed through for micromolecule such as glucose only.
Glucose had the GGBP albumen of specific adsorption characteristic or mode that the borate polymkeric substance is fixed on optical fiber probe 3 gold medal films 10 surfaces is divided into two kinds: 1) covalent bonds; 2) self assembly layer by layer.
Covalent bonds is meant that the mode that adopts the chemical bond combination forms the self assembly molecule layer on optical fiber probe gold film surface, makes GGBP albumen or borate polymkeric substance react formation strong covalent bond (as amido link) with it and is fixed on golden film surface.The optical fiber probe surface structure as shown in Figure 3 after fixing: 16 is the self assembly molecule layer, and an end generates being connected of Au-S key with golden film, and the other end forms strong covalent bond with GGBP albumen or borate polymkeric substance and combines.The covalent bonds mode mainly contains the amine coupling and mercaptan is coupled two kinds.The flow process of amine coupling is: it is the flow cell of 85nL that optical fiber probe is placed volume, and the flow velocity that various solution feed flow cell is 5ul/min.1) logical 10mmol/L NAC solution is about 3 hours, generates the self assembly molecule layer on the optical fiber probe surface, makes up Au-S key layer; 2) logical PBS damping fluid (PH7.4) is 2 minutes, the NAC that flush away is residual; 3) mix the EDC of 0.4M and the NHS of 0.1M by 1: 1 volume ratio, obtain the EDC/NHS mixed liquor.The EDC/NHS mixed liquor was fed 7 minutes, and the self assembly molecule layer reaction fixing with the optical fiber probe surface generates active ester; 4) logical PBS damping fluid is 2 minutes, removes the mixed liquor of residual EDC/NHS; 5) GGBP protein or borate polymer solution were fed 20 minutes, the active ester reaction that generates with EDC/NHS forms covalent bonds.6) logical deionized water is 2 minutes, removes residual GGBP albumen or borate polymkeric substance; 7) monoethanolamine-hydrochloric acid solution with 1M fed 5 minutes, sealed unnecessary fixedly site; 8) logical PBS damping fluid is 5 minutes, removes remaining monoethanolamine-hydrochloric acid solution.The mercaptan coupling principle is similar to the amine coupling with flow process: after having led to the EDC/NHS mixed liquor, (80mM gathers N to feed PDEA, the N-diethyl is acrylamide to be that 8.5 phosphate buffer mixes with pH value 0.1M) about 4 minutes, form disulfide bond, feed then GGBP protein or borate polymer solution 20 minutes with it reaction form covalent bond, use the unnecessary site of sodium acetate mixed liquor (pH value is 4) sealing of Nacl, 0.1M of halfcystine, the 1M of 50mM at last.
Self assembly layer by layer is to construct multi-layer film structure as expulsive force at optical fiber probe gold film surface alternating deposit with weak interaction (interionic electrostatic interaction, hydrogen bond etc.), and GGBP albumen or the introducing of borate polymkeric substance wherein are fixed on golden film surface.With reference to Fig. 4, self assembly processing procedure layer by layer is as follows: (a) optical fiber probe is immersed in the said polycation solution, take out after leaving standstill a period of time, absorption one deck polycation on the optical fiber probe.At this moment, on the optical fiber probe with electric charge just become owing to the absorption of polycation; (b) water washes the optical fiber probe surface, removes the polycation of excessive adsorption, and optical fiber probe is carried out drying; (c) above-mentioned optical fiber probe is transferred in electronegative GGBP albumen or the borate polymer solution, the optical fiber probe surface charge reverts to negative; (d) washing, drying.The operation that repeats (a)-(d) just can obtain the polycation/polyanion ultrathin membrane of multilayer.
Human glucose concentration continuous monitoring device measuring process based on optical fiber surface plasmon resonance of the present invention is as follows:
1) the mode implant into body hypodermis that optical fiber probe is adopted operation or syringe guide; 2) light that sends of light source arrives optical fiber probe through fiber coupler, and the surface plasma resonance decay takes place at the probe place; 3) light reflects at the micro-reflector place; 4) reflected light arrives spectrometer by fiber coupler again; 5) data of spectrometer are imported computing machine into, and computing machine carries out analyzing and processing and shows measurement result data.Because optical fiber probe is very responsive to the solution refractive index, reflectance spectrum is not with difference simultaneously for glucose solution concentration, so tissue liquid can obtain corresponding data result when changing.Before implanting optical fiber probe, using glucose solution is demarcated measurement mechanism.In this example, light source is the halogen tungsten lamp light source of wavelength coverage 400nm-900nm, and there are heat radiation and stable-pressure device in the light source outside, can guarantee the light continous-stable that light source sends.Fiber coupler is the y-type optical fiber of an one-to-two, and fibre diameter is 600um, and interface is SMA905.The wavelength resolution of spectrometer reaches 0.5nm.
The data processing method of the human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance of the present invention is as follows:
Generally speaking, using the SPR technology is the corresponding relation that obtains SPR angle and strength of fluid by experiment to the measurement of strength of fluid, obtains concentration value by methods such as interpolation, matches then.But the SPR method is used for the measurement of concentration still has certain theoretical foundation, and these theoretical applied computing formula are according to the difference of the complexity of solution composition and difference.If the refractive index of medium is n, film thickness is d, and absorption coefficient is k, and under the condition of k=0, spr signal (variation of resonant wavelength or resonance angle) is relevant with the n and the d of medium, and n is relevant with the amount (concentration) of measured matter with d.The n of medium is directly relevant with the mass density ρ and the Substance Properties of medium, and following fundamental relation is arranged between these parameters:
ρ=MN=M/A[(n 2-1)/(n 2+2)] (1)
In the formula, M represents molecular weight, and N represents the molal quantity of unit volume material, the Lorentz-Lorenz molar refraction of A representative species, ρ has reflected the amount of substance of studying, in fact A has reflected Substance Properties, it is the attribute of material itself, and is less with the variation of condition in the ordinary course of things.By the potpourri that two kinds or two or more material are formed, the material molal quantity sum of its unit volume is
N=N 1+N 2+N 3+… (2)
And potpourri unit volume Lorentz-Lorenz molar refraction A equals the mean value of each material unit's Lorentz-Lorenz molar refraction, promptly
A=(A 1N 1+A 2N 2+A 3N 3+…)/(N 1+N 2+N 3+…) (3)
Equally, the molecular weight M of potpourri equals the mean value of each molecular weight of material, that is:
M=(M 1N 1+M 2N 2+M 3N 3+…)/(M 1+M 2+M 3+…) (4)
With formula (2), (3), (4) formula substitution formula (1) Shi Kede
(n 2-1)/(n 2+2)=A 1N 1+A 2N 2+A 3N 3+… (5)
For polyatomic molecule, the A of molecule mLorentz-Lorenz molar refraction A by each atom nForm
A m=n 1A a1+n 2A a2+n 3A a3+… (6)
N represents the number of contained atom in the molecule respectively in the formula.
For being adsorbed on optical fiber probe surface thickness is the pure material of d (nm of unit), and the available following formula of the quality m of its absorption (μ g/cm2) calculates
M=ρd=0.1M/Ad[(n 2-1)/(n 2+2)] (7)
If the medium of absorption is potpourri (object of SPR research substantially all is a potpourri in actual applications), then following formula will become comparatively complicated form.At this moment, can be the refractive index of an individual system with the refractive index set of All Media, as the formula (5).For example, suppose that potpourri is a perfect condition, promptly is made of two kinds of materials.A kind of for refractive index is the glucose of n, another kind is n for refractive index 0Damping fluid, be in the mixed membranous layer of d then at thickness, the glucose quality of absorption is
Figure GDA0000020827760000061
In the formula,
Figure GDA0000020827760000062
Ap, Mp are respectively the Lorentz-Lorenz molar refraction and the molal weight of glucose, and Vp is the partial specific volume of glucose.
The present invention is open and that disclose, and all combinations can produce by using for reference this paper disclosure, although combination of the present invention is described by detailed implementation process, but those skilled in the art obviously can be spliced device as herein described in not breaking away from content of the present invention, spirit and scope or change, or increase and decrease some parts, more particularly, the replacement that all are similar and change apparent to those skilled in the artly, they are regarded as being included among spirit of the present invention, scope and the content.

Claims (10)

1. human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance, by light source (1), fiber coupler (2), optical fiber probe (3), spectrometer (5) and computing machine (4) are formed, by measuring concentration of glucose realization human glucose concentration continuous monitoring in the tissue liquid, it is characterized in that: described light source (1) arrives the interior optical fiber probe (3) of implant into body body through fiber coupler (2), arrive spectrometer (5) by fiber coupler (2) again from the light of optical fiber probe (3) reflection, described spectrometer (5) output data is to computing machine (4), and described computing machine (4) computing machine carries out analyzing and processing and shows measurement result the data of spectrometer output.
2. the human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance according to claim 1, it is characterized in that, described light source (1) is a white light source, requires wavelength to change continuously in 400nm~900nm wavelength coverage, the smoothly stable nothing sudden change of wave spectrum.
3. the human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance according to claim 1 is characterized in that, described fiber coupler (2) is the one-to-two multimode optical fiber.
4. the human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance according to claim 1 is characterized in that, described spectrometer (5) wavelength sensing range covers 400~900nm, and detection sensitivity reaches 0.5nm.
5. the human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance according to claim 1, it is characterized in that, the optical fiber of described optical fiber probe (3) is multimode optical fiber, include fiber core (9), be plated in the metal film (10) on the outer peripheral face of fiber core (9) end, be plated in the catoptron (11) of fiber core (9) termination, be wrapped in optical fiber coating and covering (8) on the outer peripheral face of fiber core (9) except that metal-plated membrane (10) from the inside to the outside.
6. the human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance according to claim 5 is characterized in that, described golden film (10) thickness is 45~55nm.
7. the human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance according to claim 5 is characterized in that, described catoptron (11) adopts gold or ag material, and thickness is 295~305nm.
8. the human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance according to claim 5, it is characterized in that, described fiber core (9) is fixed with a miniature cavity (13) in the periphery of metal-plated membrane (10) part, and the end face of described miniature cavity (13) is provided with the semi-permeable diaphragm (14) that only has micromolecule to pass through.
9. the human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance according to claim 5, it is characterized in that, described golden film (10) outside surface is fixed with one deck glucose molecule is had the specific adsorption characteristic, promptly very easily adsorbs in conjunction with glucose molecule and the adiaphorous D-galactose of other materials/D-grape carbohydrate-binding protein (GGBP) or borate polymkeric substance.
10. the human glucose concentration continuous monitoring device based on optical fiber surface plasmon resonance according to claim 5, it is characterized in that described GGBP albumen and borate polymkeric substance adopt the mode of covalent bonds or self assembly layer by layer to be fixed in golden film surface.
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