CN101548892B - Implanted in-vivo continuous blood sugar monitor - Google Patents

Implanted in-vivo continuous blood sugar monitor Download PDF

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CN101548892B
CN101548892B CN2009100686848A CN200910068684A CN101548892B CN 101548892 B CN101548892 B CN 101548892B CN 2009100686848 A CN2009100686848 A CN 2009100686848A CN 200910068684 A CN200910068684 A CN 200910068684A CN 101548892 B CN101548892 B CN 101548892B
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laser
microcomputer
blood sugar
optical fiber
light
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CN101548892A (en
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徐可欣
曹玉珍
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Tianjin Xianyang Technology Development Co., Ltd.
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XIANSHI OPTICAL TECHNOLOGY Co Ltd TIANJIN CITY
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Abstract

The present invention provides an implanted in-vivo continuous blood sugar monitor. A laser generating and control unit is connected with a microcomputer for receiving the control command transmitted from the microcomputer. The output end divides the laser to two beams through a beam splitter. One beam is sampling light and is output to an optical power sampling unit. The other beam is output light and is output to an attenuation absorbing measuring unit. The optical power sampling unit detects and amplifies the sampling light, and then transmits the detected and amplified sampling light intoa microcomputer through a data collection module. The attenuation absorbing unit transmits the optical absorbing information of obtained tested medium into the microcomputer for executing data modeling through the data collection module. The invention adopts a CO2 laser as a light source. The measuring mode adopts background removal. The noise caused by environmental factor and influence caused byinstrumental shift are prevented. The measuring precision is increased. The accurate single wavelength absorbing amplitude can be obtained and more accurate absorbance value can be obtained. The power of laser is adjustable. The measuring precisions of system under different laser powers can be analyzed. A mode of multi-wavelength measurement can be adopted for increasing the modeling precision thereby increasing the prediction precision.

Description

Implanted is at the body continuous blood sugar monitor
Technical field
The present invention relates to a kind of blood sugar monitor.Particularly relate to a kind of novel Wicresoft based on the mid-infrared light spectral technology, continuously, the implanted of real time blood sugar monitoring is at the body continuous blood sugar monitor.
Background technology
Diabetes are second killers in the modern disease, and its harm to human body is only second to cancer, and as a kind of comparatively general endocrinopathy, it is increasing to people's physical and mental health harm, and the trend of extension and rejuvenation is arranged.Result of study shows: the main feature of diabetes is the blood sugar concentrations that slowly continue rising, when blood sugar concentration rises to certain height, is higher than renal glucose threshold and then can detects sugar in urine.Diabetics easily causes severe complications such as diabetes ketosis, cardio cerebrovascular affection, nephropathy, oculopathy, acromelic gangrene and infection owing to blood sugar concentration causes the internal metabolism disorder unusually.In addition, the rising of blood sugar concentration can cause the complication of retina, kidney and nervous system etc.Therefore, the main means and the target of treatment diabetes are exactly to keep the normal level of blood sugar concentration.
Since the complexity of life sciences, the present medical means that does not also have thoroughly to effect a radical cure diabetes.Treat diabetes now, mainly be to take blood sugar control concentration with prevention or alleviate the generation and the anti symptom treatment complication of complication, particularly by monitor continually blood sugar concentration and accurately, in time as according to the consumption of adjusting orally-taken blood sugar reducing medicine and insulin.There have been data to show that blood sugar control concentration can reduce the complication of I type and type ii diabetes.
In addition, keeping blood sugar content also is an important problem in serious symptom ward patient's nursing near normal level.Studies show that: ICU patient's blood sugar content is controlled near normal level, can significantly improves their clinical therapeutic efficacy.Yet the strictness control of blood glucose is unapproachable and requires quite frequent measurement.Therefore the continuous monitoring of blood glucose also will be a big progress in diabetics and patient with severe symptoms's monitoring.
Yet, under the existence conditions, be to utilize biochemical reagents or enzyme and blood or blood plasma to have an effect to the detection method of blood sugar concentration in the hospital, the consumption by reagent or change to come qualitative or represent the height of blood sugar concentration quantitatively with shade after the enzyme effect.The shortcoming of this method is constantly to consume biochemical reagents, and measuring speed is slower, reagent and consumables associated therewith are dealt with improperly also and may be polluted, can not obtain successive blood glucose measurement result, sufferer by day, especially the blood glucose fluctuation situation during evening just may be left in the basket, yet have only lasting blood sugar monitoring just can guarantee best blood glucose regulation and control.
Now the great majority pick offs that can be used for the continuous blood sugar monitoring all is based on electrochemical principle or uses glucoseoxidase to carry out molecular recognition.One of them unfavorable conditions of these pick offs is their limited electrochemistry selectivitys, for example, and Ascorbate, acetaminophen or uric acid.For this reason, to be used in the severe case be breakneck to the glucose measurement that carries out based on electrochemistry on one's body.
Simultaneously, also have and studies show that concentration of glucose has certain relation in interior concentration of glucose of subcutaneous tissue liquid and the blood, therefore the developing direction of present most of pick offs all is the concentration of glucose that continues to detect in the interstitial fluid, thereby reflects the variation of blood sugar concentration indirectly.All equipment that is used for lasting glucose detection all is to change by the electric current that the reaction of measuring glucoseoxidase and hydrogen peroxide causes to realize.The pick off of this class is subjected to the influence that oxygen concentration changes in the body, also is subjected to the influence of carbamide, ascorbic acid electroactive species such as (vitamin C, uric acid) simultaneously.
Remove to develop an implantation glucose sensor although carried out sizable effort, up to now, continuous blood sugar monitoring notion almost is not applied to clinical.It is only position that pick off is implanted in subcutaneous tissue, because it can realize by surgical operation, and pick off is relatively easy the replacement under impaired situation.Though pick off in vivo can several thoughtful some months of continuous firing, can not be longer than more than the several hrs detection time of most of subcutaneous sensor, because sizable drift current is arranged in pick off.In general, can not find out the biological stability of pick off from the performance of external pick off.In fact, the performance of external pick off is not subjected to the influence of surrounding, and these characteristics play very big effect to the performance of implanted sensor.
The infrared spectrometry method is the main flow direction that carries out Wicresoft and Woundless blood sugar detection research as the representative of green test technology.Yet at present, it is not very high that the precision of wound blood-sample withdrawal measuring blood concentration method is arranged, Woundless blood sugar measuring apparatus is not also succeeded in developing, therefore the method for studying measuring blood concentration under Wicresoft's condition is very significant, it not only can replace traditional biochemistry detection method and reach the purpose of saving consumptive material and measuring fast, and be prerequisite and the basis that noinvasive detects blood sugar concentration, also be the important application basic research method of continuous monitoring blood sugar concentration in the art simultaneously.
Utilize CO 2The method that laser instrument is measured the biochemical indicator in the blood in conjunction with the ATR metering system as infrared light supply can be traced back to 1979, the Kaiser of Germany has at first proposed this kind method in then, and applied for patent (UnitedStates Patent 4169676), he has described ultimate principle, system constructing and the experimental technique of this method in this patent, and the qualitative experiment result of measuring blood concentration arranged, but do not do quantitative analysis, and tested blood is the blood sample that exsomatizes.
Summary of the invention
Technical problem to be solved by this invention is, provide a kind of implanted no consumption product based on the mid-infrared light spectral technology in real time, the implanted of continuous blood sugar monitoring is at the body continuous blood sugar monitor.
The technical solution adopted in the present invention is: a kind of implanted is at the body continuous blood sugar monitor, include: laser generation and control unit, beam splitter, luminous power sampling unit, decay absorptiometry unit, data acquisition module and microcomputer, described laser generation and control unit link to each other with microcomputer and accept the control command that microcomputer sends, outfan is divided into two bundles by beam splitter with laser, a branch ofly export to the luminous power sampling unit for sampled light, another bundle is exported to decay absorptiometry unit for output light; Described luminous power sampling unit with sampled light detection, amplification after data acquisition module is sent into microcomputer; Described decay absorptiometry unit is sent into microcomputer with the light absorption information of the measured medium of acquisition by data acquisition module and is carried out data modeling.
Described laser produces and control unit includes: RF driver, CO 2Laserresonator, length scanning and selected control module, wavelength and power stability control module and single-chip microcomputer, wherein, described RF driver drives CO 2Laserresonator produces laser and exports beam splitter to; Described length scanning and selected control module and CO 2Laserresonator links to each other, and is used to carry out the work spectral line of length scanning and selected laser instrument; Described wavelength and power stability control module and CO 2Laserresonator links to each other, and is used for the long and output of stable cavity; Described single-chip microcomputer is accepted the control command that microcomputer sends, the work of control wave long scan and selected control module and wavelength and power stability control module.
Described length scanning and selected control module are made of motor and driver thereof, by driven the work spectral line of grating deflection carrying out length scanning and selected laser instrument by Single-chip Controlling driver drives motor.
Described wavelength and power stability control module are to be made of piezoelectric ceramics and driver thereof, the size of the driving voltage by Single-chip Controlling driving pressure electroceramics, the long and output with the resonator cavity of stable laser.
Described length scanning and selected control module with the 9P06 spectral line as the reference spectral line, carrying out spectral line proofreaies and correct, determine the relative position of other spectral lines, laser works is at all spectral lines of 9R and 9P band, the user defines 9R and 9P is with many interior spectral lines as current work spectral line, and defines the time span of every work spectral line output.
Described decay absorptiometry unit includes: place the measuring probe of measured medium, convert the emergent light of measuring probe the photodetector of the signal of telecommunication to, to changing the lock-in amplifier of exporting to data acquisition module after the back signal of telecommunication amplifies.
Described measuring probe includes optical fiber ATR pick off, the temperature sensor that is arranged in the microdialysis pipe, described optical fiber ATR pick off comprises incident optical, prism, outgoing optical fiber and tinsel, and described temperature sensor is the full fiber type temperature sensor; The best effort length of optical fiber ATR pick off is L = Nd / ( 2 cos θ ) = l 0 d e · d 2 cos θ , Wherein: N is the total reflection number of times; D is a crystalline material thickness; θ is the crystalline material angle of incidence; d eBe the Effective depth penetration of light in test solution; The long l of optimum pathway 0Be 0.1mm.
Described laser produces and control unit includes: RF driver, CO 2Laserresonator, length scanning and selected control module, wavelength and power stability control module and single-chip microcomputer, wherein, described RF driver drives CO 2Laserresonator produces laser and exports beam splitter to; Described length scanning and selected control module and CO 2Laserresonator links to each other, and is used to carry out the work spectral line of length scanning and selected laser instrument; Described wavelength and power stability control module and CO 2Laserresonator links to each other, and is used for the long and output of stable cavity; Described single-chip microcomputer is accepted the control command that microcomputer sends, the work of control wave long scan and selected control module and wavelength and power stability control module.
Described length scanning and selected control module are made of motor and driver thereof, by driven the work spectral line of grating deflection carrying out length scanning and selected laser instrument by Single-chip Controlling driver drives motor.
Described wavelength and power stability control module are to be made of piezoelectric ceramics and driver thereof, the size of the driving voltage by Single-chip Controlling driving pressure electroceramics, the long and output with the resonator cavity of stable laser.
Described measuring probe also includes the miniflow siphunculus, be provided with in the described miniflow siphunculus with the microdialysis pipe in the identical pick off of optical fiber ATR pick off, have incident optical and outgoing optical fiber, described measuring probe is flexible form or rigid form.
Described measuring probe also comprises the used reference measure passage of promising standard sample spectral absorption measurement, with the measurement passage formation dual pathways reference measure of sample.
Optics connected mode between measuring probe and measuring device is in all bonding GRIN Lens of optical fiber connector, to dock by GRIN Lens.
Implanted of the present invention has following characteristics at the body continuous blood sugar monitor:
1, adopts CO 2Laser instrument is as light source, and laser output wavelength concentrates on 9.2~10.8 μ m, and glucose has a plurality of high absworption peaks at this spectral coverage, mainly utilizes 1035cm -1And 1080cm -1Two are carried out spectral measurement and analysis;
2, metering system is taked the metering system of background correction, and the influence that can avoid noise that environmental factors causes and instrumental shift to cause improves certainty of measurement;
3, lock-in detection, that is sent by single-chip microcomputer can well obtain direct current signal with the synchronous locking signal of laser modulation signal, thereby obtains accurate single wavelength absorption amplitude, obtains absorbance comparatively accurately;
4, laser power is adjustable, can analyze under the different laser powers, and the certainty of measurement of system is for suitable power output is determined in clinical practice;
5, laser instrument can be exported by multi-wavelength (maximum five wavelength), and the mode that can make us utilize multi-wavelength to measure improves modeling accuracy, thereby improves precision of prediction;
6, the real-time demonstration of computer can provide data image more intuitively for us.
Description of drawings
Fig. 1 is an entire block diagram of the present invention;
Fig. 2 is the spectrum in 9R and the 9P band;
Fig. 3 is control voltage and a laser output power curve of exporting piezoelectric ceramics when switching between certain five spectral line shown in Figure 2;
Fig. 4 is the structural representation of measuring probe of the present invention;
Fig. 5 is the A-A cut-away view of Fig. 4;
Fig. 6 is the structural representation of the temperature sensor among Fig. 5;
Fig. 7 is the generalized section of measuring probe second embodiment of the present invention;
Fig. 8 is the structural representation of terminal bonding GRIN Lens of the optical fiber of measuring probe;
Fig. 9 is the structural representation of the measuring probe of rigid form of the present invention;
Figure 10 is the structural representation of the optics connected mode between measuring probe and measuring device;
Structural representation when Figure 11 is to use temperature sensor to carry out thermometric.
Wherein:
11: laser produces and control unit: 12: beam splitter
13: luminous power sampling unit 14: decay absorptiometry unit
15: data acquisition module 16: microcomputer
111:RF driver 112:CO 2Laserresonator
113: length scanning and selected control module 114: wavelength and power stability control module
115: single-chip microcomputer 30: optical fiber ATR pick off
301: microdialysis pipe 311: temperature sensor
302: incident optical 303: tinsel
304: prism 305: outgoing optical fiber
306: polyimide tube 307: the miniflow siphunculus
308: incident optical 309: outgoing optical fiber
312: GRIN Lens 401: hollow needle
402: medical glue 403: base
404: lid 501: wideband light source
502: fiber optical circulator 503: wavelengt demodulator
A: control voltage b: output
The specific embodiment
Below in conjunction with embodiment and accompanying drawing implanted of the present invention is made a detailed description at the body continuous blood sugar monitor.
Implanted of the present invention is at the body continuous blood sugar monitor, with wavelength and amplitude programmable in infrared CO 2Tunable laser is as light source, and selected 9R, 9P bands of a spectrum are as key band; The Fibre Optical Sensor that employing designs based on attenuated total reflectance (ATR) mode; Constitute an incorporate gauge head with temperature sensor simultaneously; Gauge head is implanted in the subcutaneous tissue, surveys ATR absorption and the variations in temperature of interstitial fluid to mid-infrared light; By the photodetector receiving optical signals, convert the signal of telecommunication then to, adopt the locking amplifying technique to obtain the useful signal relevant with blood sugar concentration; Send light by wideband light source, Bragg grating fibre optic temperature sensor sensing temperature changes, and Wavelength demodulation obtains the signal of variations in temperature; Adopt the A/D conversion that useful signal and the signal relevant with variations in temperature are transferred to computer, show in real time and data storage, improve final blood sugar concentration precision of prediction thereby can effectively improve certainty of measurement by the locking amplification detection by computer.Algorithm by kinds of artificial intelligence filters out the combination of optimum measurement with spectral line, sets up the error compensation and the correction model of blood glucose forecast model, elimination variations in temperature factor affecting according to the response of a plurality of specific wavelengths.
As shown in Figure 1, implanted of the present invention is at the body continuous blood sugar monitor, include: laser produces and control unit 11, beam splitter 12, luminous power sampling unit 13, decay absorptiometry unit 14, data acquisition module 15 and microcomputer 16, described laser produces and control unit 11 links to each other with microcomputer 16, accept the control command that microcomputer 16 sends, outfan is divided into two bundles by beam splitter 12 with laser, a branch ofly export to luminous power sampling unit 13 for sampled light, another bundle is exported to decay absorptiometry unit 14 for output light; Described luminous power sampling unit 13 with sampled light detection, amplification after data acquisition module 15 is sent into microcomputer 16; Described decay absorptiometry unit 14 is sent into microcomputer 16 with the light absorption information of the measured medium of acquisition by data acquisition module 15 and is carried out data modeling.
Described laser produces and control unit 11 includes: RF driver 111, CO 2Laserresonator 112, length scanning and selected control module 113, wavelength and power stability control module 114 and single-chip microcomputer 115, wherein, described RF driver 111 drives CO 2Laserresonator 112 produces laser and exports beam splitter 12 to; Described length scanning and selected control module 113 and CO 2Laserresonator 112 links to each other, and is used to carry out the work spectral line of length scanning and selected laser instrument; Described wavelength and power stability control module 114 and CO 2Laserresonator 112 links to each other, and is used for the long and output of stable cavity; Described single-chip microcomputer 115 is control cores, carries out serial data communication with microcomputer 16, accepts the control command that microcomputer 16 sends, the work of control wave long scan and selected control module 113 and wavelength and power stability control module 114.CO 2Laserresonator 112 can multi-wavelength output.
Described length scanning and selected control module 113 are made of motor and driver thereof, by driven the work spectral line of grating deflection carrying out length scanning and selected laser instrument by single-chip microcomputer 115 control driver drives motors.The resolution 1.524um of motor, the resolution 5nm of piezoelectric ceramics.With all spectral lines of scanning step motor 9R and 9P band, the relative position of spectral line is very stable, nearest about 3 steps of separation of spectra, as shown in Figure 2.After in case a certain spectral line is identified, equal definable of every other spectral line and sign.
Described wavelength and power stability control module 114 are to be made of piezoelectric ceramics and driver thereof, the size of the driving voltage by single-chip microcomputer 115 control driving pressure electroceramics, the long and output with the resonator cavity of stable laser.
Microcomputer 16 sends instruction by the Labview program, single-chip microcomputer 115 is by the output of RF activator 111 control laser instrument, the output that the switch of the radiofrequency signal by adjusting the RF driver is controlled laser instrument with close the output of the dutycycle control laser instrument by adjusting radiofrequency signal.By the output of control step motor coarse adjustment wavelength, the output of control piezoelectric ceramics actuator fine tuning wavelength.
Described length scanning and selected control module 113 with 9P06 (9.433 μ m) spectral line as the reference spectral line, carrying out spectral line proofreaies and correct, determine the relative position of other spectral lines, laser works is at all spectral lines of 9R and 9P band, many spectral lines in user's definable 9R and the 9P band are as current work spectral line, and the time span of every of definable work spectral line output, the spectral line that the defines output of can automaticallying switch.The control voltage and the laser output power curve of piezoelectric ceramics when Fig. 3 switches between certain five spectral line for output.When the wavelength of selected spectral line and amplitude are stabilized locking output, indicate with corresponding signal.
Choose three spectral line 9R26 (9.2396um), 9R22 (9.2605um), 9R32 (9.6574um) experimentizes, obtain:
Polarization of laser output: vertically arrive level, polarization ratio:>20db (100: 1)
Spectral line is followed the tracks of: from 9R26 to 9R22, follow the tracks of stabilization time<0.2s;
From 9R22 to 9R32, follow the tracks of stabilization time<0.5s;
Wavelength reference precision: 5nm/mr.
Described decay absorptiometry unit 14 includes: the measuring probe 141 that places measured medium, convert the emergent light of measuring probe 141 photodetector 142 of the signal of telecommunication to, to changing the lock-in amplifier 143 of exporting to data acquisition module 15 after the back signal of telecommunication amplifies.
Described measuring probe 141 is flexible form or rigid form.Flexible probe can be implanted subcutaneous tissue by guid needle, and the rigidity gauge head then can directly thrust subcutaneous, easy to use.The test solution physical ability sees through and enters microdialysis pipe 301 inside, so that pick off fully contacts with liquid.
Optics connected mode between measuring probe 141 and measuring device is in all bonding GRIN Lens of optical fiber connector, to dock by GRIN Lens.
As Fig. 4, Fig. 5, shown in Figure 6, the measuring probe 141 of described flexible form, can be to include optical fiber ATR pick off 30, the temperature sensor 311 that is arranged in the microdialysis pipe 301, described optical fiber ATR pick off 30 is based on attenuated total reflectance (ATR) principle design, include incident optical 302, prism 304, outgoing optical fiber 305 and tinsel 303, has following feature: design based on the ATR mode, be used to survey the optical absorption of tested component, for not having reagent, non-maintaining optical pickocff fully; The active length of described Fibre Optical Sensor is according to the long design of optimum pathway.Described temperature sensor 311 is the full fiber type temperature sensor, as the Bragg grating fibre optic temperature sensor.By temperature survey, carry out measurement Error Compensation and correction, to improve certainty of measurement.
One section periphery adhesive in microdialysis pipe 301 close external measurement device is bonded with polyimide tube 306.
As Fig. 7, shown in Figure 8, described measuring probe 141 also comprises the used miniflow siphunculus 307 of promising standard sample spectral absorption measurement, be provided with in the described miniflow siphunculus 307 and the identical pick off of optical fiber ATR pick off 30 in the microdialysis pipe 301, promptly have optical fiber parameter design identical with incident optical 302, outgoing optical fiber 305 respectively incident optical 308 and outgoing optical fiber 309.Inject distilled water in the miniflow siphunculus, measure passage, so that the reflection temperature is to the influence of absorption spectrum as reference.At this moment, a terminal bonding GRIN Lens 312 of every optical fiber in the measuring probe 141.Incident beam is efficiently converged in the optical fiber, or make emergent light generate angle pencil of ray, make things convenient for the coupling of light.Described reference measure passage constitutes by measuring the identical two cover decay absorptiometry unit of passage with sample, carries out dual pathways reference measure, with the influence of factors such as elimination temperature to certainty of measurement.
Above-mentioned gauge head structure is called flexible probe, and the subcutaneous mode of its implantation is: the intravenous catheter with standard penetrates epidermis, dermal tissue, removes guid needle then, stays soft conduit.Shift gauge head onto the other end from an end of catheter lumen afterwards.Again that conduit is careful taking-up, gauge head is stayed in the dermal tissue, and the subcutaneous tissue interstitial fluid sees through Dialysis tubing 301 and enters its inside, so that optical fiber fully contacts with tissue fluid.
As shown in Figure 9, the measuring probe 141 of described rigid form is that the pick off of Fig. 4, Fig. 5, Fig. 6 or structure shown in Figure 7 is packed in the hollow needle 401, and hollow needle 401 is fixed on the base 403, and is 90 ° of angles with base 403.Hollow needle 401 is made by rustless steel, with the corresponding position of optical fiber ATR active length on pin be the band micropore, can make tissue fluid penetrate pin and enter in the needle tubing.When using this gauge head, stick a needle into subcutaneously lightly, treat that the medical glue 402 under the base 403 is pasted till the tight skin.The structure of base 403 for reducing the position accuracy demand of multifiber butt joint, in all bonding GRIN Lens of optical fiber connector, and makes each lens by fixed positional alignment as shown in figure 10.Optical fiber shown in Figure 8 is packed into wherein, and lid 404 can be opened when connecting measuring device, so that another union joint butt joint identical with the structure of base 403.
As shown in figure 11, when using Bragg grating fibre optic temperature sensor 311 to carry out thermometric, Bragg grating fibre optic temperature sensor 311 is to be connected with wideband light source 501 that sends broadband spectral and wavelengt demodulator 503 respectively by fiber optical circulator 502.
The design of Fibre Optical Sensor active length L of the present invention shown in Fig. 4:
The design of Fibre Optical Sensor active length L (being the bare fibre part that optical fiber does not have clad) is according to the long design of optimum pathway of relevant spectral measurement.
Every generation attenuated total reflectance once, the light Effective depth penetration d in test solution eFor:
d e = d e ⊥ + d e / / 2
Wherein: the Effective depth penetration d of vertical and horizontal polarized light E ⊥, d E//Be respectively:
d e ⊥ = n 1 n 2 cos θ n 1 2 - n 2 2 · λ 0 π sin 2 θ - ( n 2 / n 1 ) 2
d e / / = n 1 n 2 cos θ n 1 2 - n 2 2 · 2 n 1 2 sin 2 θ - n 2 2 ( n 1 2 - n 2 2 ) sin 2 θ - n 2 2 · λ 0 π sin 2 θ - ( n 2 / n 1 ) 2
Wherein: λ 0Be light wavelength in a vacuum; λ N1For light at medium n 1In wavelength; θ is the angle of incidence of light;
n 1Be medium n 1Refractive index; n 2Be medium n 2Refractive index.
Through an attenuated total reflectance, light penetrates that the degree of depth of sample is limited, and sample is less to light absorption, so beam energy changes also very for a short time, and gained spectral absorption band is weak, poor signal to noise.In order to increase absorption peak strength, improve and measure signal to noise ratio, adopt the method that increases the total reflection number of times to make absorption band strengthen promptly multiple attenuated total reflectance.Total reflection times N and crystalline material (optical fiber sensitizing range) length 2L and thickness (diameter) d and the angle of incidence θ of light in crystal (optical fiber) has following relation:
N=(2L/d)cosθ
Long according to Mark with the optimum pathway of the relevant spectral measurement of Griffiths:
l 0 = 1 / Σ i = 1 n α i c i
Because main component is a water in the blood, and water is very strong in the absorption of middle-infrared band, therefore can be with each composition in the blood
Figure G2009100686848D00082
The value α of water 1c 1The value approximate substitution.Record by experiment, in middle-infrared band 1080 -1Near, α 1c 1=10.3085.So long l of optimum pathway 0About 0.1mm.
Optical fiber sensitizing range best effort length L is:
L = Nd / ( 2 cos θ ) = l 0 d e · d 2 cos θ
After fiber optic materials, diameter and angle of incidence are selected, just can obtain its best effort length L.

Claims (7)

1. an implanted is at the body continuous blood sugar monitor, include: laser generation and control unit (11), beam splitter (12), luminous power sampling unit (13), decay absorptiometry unit (14), data acquisition module (15) and microcomputer (16), described laser produces and control unit (11) links to each other with microcomputer (16) accepts the control command that microcomputer (16) sends, outfan is divided into two bundles by beam splitter (12) with laser, a branch ofly export to luminous power sampling unit (13) for sampled light, another bundle is exported to decay absorptiometry unit (14) for output light; Described luminous power sampling unit (13) with sampled light detection, amplification after data acquisition module (15) is sent into microcomputer (16); Described decay absorptiometry unit (14) is sent into microcomputer (16) with the light absorption information of the measured medium of acquisition by data acquisition module (15) and is carried out data modeling, it is characterized in that, described decay absorptiometry unit (14) includes: the measuring probe (141) that places measured medium, the emergent light of measuring probe (141) is converted to the photodetector (142) of the signal of telecommunication, to changing the lock-in amplifier (143) of exporting to data acquisition module (15) after the back signal of telecommunication amplifies, described measuring probe (141) includes the optical fiber ATR pick off (30) that is arranged in the microdialysis pipe (301), temperature sensor (311), described optical fiber ATR pick off (30) includes incident optical (302), prism (304), outgoing optical fiber (305) and tinsel (303), described temperature sensor (311) is the full fiber type temperature sensor; The best effort length of optical fiber ATR pick off (30) is Wherein: N is the total reflection number of times; D is a crystalline material thickness; θ is the crystalline material angle of incidence; d eBe the Effective depth penetration of light in test solution; The long l of optimum pathway 0Be 0.1mm.
2. implanted according to claim 1 is characterized in that at the body continuous blood sugar monitor described laser produces and control unit (11) includes: RF driver (111), CO 2Laserresonator (112), length scanning and selected control module (113), wavelength and power stability control module (114) and single-chip microcomputer (115), wherein, described RF driver (111) drives CO 2Laserresonator (112) produces laser and exports beam splitter (12) to; Described length scanning and selected control module (113) and CO 2Laserresonator (112) links to each other, and is used to carry out the work spectral line of length scanning and selected laser instrument; Described wavelength and power stability control module (114) and CO 2Laserresonator (112) links to each other, and is used for the long and output of stable cavity; Described single-chip microcomputer (115) is accepted the control command that microcomputer (16) sends, the work of control wave long scan and selected control module (113) and wavelength and power stability control module (114).
3. implanted according to claim 2 is at the body continuous blood sugar monitor, it is characterized in that, described length scanning and selected control module (113) are made of motor and driver thereof, by driven the work spectral line of grating deflection carrying out length scanning and selected laser instrument by single-chip microcomputer (115) control driver drives motor.
4. implanted according to claim 2 is at the body continuous blood sugar monitor, it is characterized in that, described wavelength and power stability control module (114) are to be made of piezoelectric ceramics and driver thereof, the size of the driving voltage by single-chip microcomputer (115) control driving pressure electroceramics, the long and output with the resonator cavity of stable laser.
5. implanted according to claim 1 is at the body continuous blood sugar monitor, it is characterized in that, described measuring probe (141) also includes miniflow siphunculus (307), be provided with in the described miniflow siphunculus (307) with microdialysis pipe (301) in the identical pick off of optical fiber ATR pick off (30), have incident optical (308) and outgoing optical fiber (309), described measuring probe (141) is flexible form or rigid form.
6. implanted according to claim 1 is at the body continuous blood sugar monitor, it is characterized in that, described measuring probe (141) also comprises the used reference measure passage of promising standard sample spectral absorption measurement, with the measurement passage formation dual pathways reference measure of sample.
7. implanted according to claim 1 is characterized in that at the body continuous blood sugar monitor optics connected mode between measuring probe (141) and measuring device is in all bonding GRIN Lens of optical fiber connector, to dock by GRIN Lens.
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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
CN106159668B (en) * 2016-09-07 2019-01-01 上海理工大学 A kind of repetition rate locking device and method
CN107242855A (en) * 2017-06-05 2017-10-13 天津大学 A kind of biological tissue's dynamic modulation spectral measurement device and method
CN109965886A (en) * 2019-03-21 2019-07-05 邓庆平 A kind of hurtless measure Intelligent blood sugar measuring instrument
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