CN102160791A - Self-mixing coherent laser radar invasive blood sugar measuring system - Google Patents
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Abstract
The invention discloses a self-mixing coherent laser radar invasive blood sugar measuring system, which comprises a tunable semiconductor laser, a photodetector, a signal processing circuit and the like. The photodetector is arranged on the rear end face of the laser or arranged in parallel with the laser; and the signal processing circuit is connected with the photodetector. The mode-hopping-free tunable semiconductor laser replaces a movable mechanical arm, the mechanical precision requirement of the system is reduced, and the system is miniaturized and portable; and the system is further simplified by a self-mixing coherent method, signals are amplified, and weak signals can be detected through simple elements and structures.
Description
Technical field
The present invention relates to a kind of system that can realize that the human body Woundless blood sugar is measured, relate in particular to and a kind ofly utilize the Continuous Wave with frequency modulation laser radar and mix the system of relevant process non-invasive measurement of blood sugar for human body concentration certainly.
Background technology
Diabetes are diseases of a kind of common pilosity, and along with the raising day by day of people's living standard, the sickness rate of diabetes is also increasing gradually.In recent years, diabetes have become the third-largest killer who is only second to cancer and cardiovascular disease in the modern disease, are also classified as one of three big difficult disease by World Health Organization (WHO).
Along with people to the increasing of diabetes attention rate, how to realize accurately, convenient, continuously, non-invasive measurement blood glucose also becomes the focus that research institution is discussed.In numerous schemes, optical means gets most of the attention.
The blood sugar concentration measuring method can be divided into dual mode from detected object: direct mode and indirect mode.Direct mode mainly is to obtain blood sugar concentration by the detection to the glucose molecule self character, and general selective light spectrum analysis method comprises near-infrared (NIR) spectra methods, rotatory polarization method and Raman (RAMAN) spectra methods etc.; Indirect mode then is by detecting blood glucose the concentration of blood glucose to be calculated in the influence of blood of human body and tissue characteristics, the method that general selective scattering is analyzed, and detected object comprises tissue to the scattering of light coefficient, the refractive index of tissue fluid etc.
The many near infrared spectroscopic methods of research mainly are to carry out blood sugar monitoring by the characteristic absorption peak intensity to glucose molecule at present.Although three during the last ten years, people have carried out big quantity research on the one hand at this, have also made significant headway, and up to the present go back the believable work system of neither one.The subject matter that this method exists is: the absorpting form that glucose molecule is determined near infrared spectrum district neither one; The phase mutual interference that can overlap of the absorption spectrum that comprises other material except glucose in the spectrum, these signals; Absorption signal can be subjected to the very big interference of scattered signal.
The scattering properties of another kind of background technology utilization tissue is carried out analysis of blood sugar.At the near infrared light wave band, organizer will be better than absorption far away to scattering of light, information such as the refractive index by can obtaining organizer indirectly to the analysis of scattering spectrum, scattering coefficient can obtain corresponding blood sugar concentration after with suitable theory it being handled.The advantage of the relative near infrared spectroscopic method of this method is near infrared band, skin to scattering of light much larger than absorption, thereby can obtain higher signal to noise ratio.Therefore can consider to start with and find a kind of Woundless blood sugar measuring method that can reach required precision from scattering analysis.
A kind of background technology such as V. Larin that utilizes optical coherence chromatography imaging method to measure the blood sugar for human body value, M. Motamedi, S. Eledrisi etc. is at their article " Noninvasive Blood Glucose Monitoring With Optical Coherence Tomography ", Diabetes Care, VOL.25, described in pp.2263 ~ 2267,2002.This system adopts the super-radiance light emitting diode (SLD) of a 1300nm wave band as light source, and the system core is a Michelson's interferometer.The light that light source sends is through beam splitter, and a part is radiated on the target acquisition thing, and part conduct is with reference on light beam irradiates to a plane mirror, and detection light that reflects and reference light enter photo-detector simultaneously and interfere.System modulates the information that obtains to survey the thing different levels by mechanical arm to the light path of reference edge, and sets up the relation between signal slope and the blood sugar concentration.The problem that the method that this Woundless blood sugar is measured exists is: need to introduce a movably mechanical arm in the system, scanning speed is slow and be unfavorable for miniaturization, the portability of system; The intensity of system signal is with to survey the thing reflectance relevant, and when being detected the thing reflectance less the time, the gained signal is very faint, therefore is difficult to realize the measurement to atomic weak scattering light.
Summary of the invention
The objective of the invention is at the deficiencies in the prior art, provide a kind of from mixing coherent laser radar Woundless blood sugar measuring system.
The objective of the invention is to be achieved through the following technical solutions: one is utilized the Continuous Wave with frequency modulation laser radar to realize the system that Woundless blood sugar is measured, and it comprises: semiconductor laser with tunable, photo-detector and signal processing circuit etc.Described photo-detector places the rear end face of laser instrument or placed side by side with laser instrument, and signal processing circuit links to each other with photo-detector; The light that semiconductor laser with tunable sends returns by photo-detector after tested subcutaneous tissue scattering and receives, and described photo-detector is surveyed the light intensity variable signal and sent it to signal processing circuit; Described signal processing circuit comprises filtration module and microprocessor module, two parallel independent operatings of module, and described filtration module comprises the wave filter of two different frequencies; Signal processing circuit is analyzed the spectrum information of light intensity variable signal, calculates blood sugar concentration according to light intensity with the relation of frequency change.
Further, described detector places frequency sweep laser instrument rear end, the light that described semiconductor laser with tunable sends return laser light device after the tested tissue scattering carries out from mixing relevant process, places the detector of laser instrument rear end to survey by mixing the relevant laser instrument emission light intensity variable signal that causes certainly.
Further, described detector and frequency sweep laser instrument are placed side by side, and described detector is surveyed by skin surface reflected light and the relevant light intensity variable signal that causes of tested subcutaneous tissue scattered light.
Further, described semiconductor laser with tunable is no mode hopping semiconductor laser with tunable.
Further, tunable laser is carried out the periodic frequency modulation, make its emergent light wave frequency, be periodically fast variation continuously.
Further, described periodic frequency is modulated to sawtooth waveforms or triangular wave function.
Further, described semiconductor laser with tunable centre wavelength is positioned near the near infrared band of 850nm.
Further, described filtration module comprises the wave filter of two different frequencies, described wave filter carries out filtering to the laser instrument output intensity variable signal that photo-detector detects, and calculates the scattering coefficient of tissue and the blood sugar concentration in the tissue fluid according to the difference in signal strength at these 2 different frequencies that obtains.
Further, the laser instrument output intensity variable signal that described microprocessor module detects photo-detector carries out the frequency spectrum that fast fourier transform obtains output signal, by signal frequency and its light path that is experienced concern the change curve of picked up signal with the scattering optical path length, thereby further calculate the scattering coefficient of tissue and the blood sugar concentration in the tissue fluid.
The invention has the beneficial effects as follows that the present invention replaces movably mechanical arm with a no mode hopping semiconductor laser with tunable, reduce the mechanical precision requirement of system, thereby the system of being convenient to is toward small-sized, portability development; Adopt from mixing the relevant further simplified system of method, signal is amplified, just can detect small-signal by simple elements and structure.
Description of drawings
Fig. 1 is an embodiment of the present invention: the laser radar Continuous Wave with frequency modulation with combine and realize the structural representation that Woundless blood sugar is measured from mixing coherent technique.
Fig. 2 is an another embodiment of the invention: laser radar Continuous Wave with frequency modulation technology realizes the structural representation that Woundless blood sugar is measured.Detector and frequency sweep laser instrument are placed side by side, survey by skin surface reflected light and the relevant light intensity variable signal that causes of tested subcutaneous tissue scattered light.
Fig. 3 for the laser radar Continuous Wave with frequency modulation with from mixing the combine operation workflow sketch map of realization Woundless blood sugar measuring system of coherent technique.
Fig. 4 is for mixing the operation principle detailed maps of coherent technique certainly.
Fig. 5 is modulation signal and the simple and easy sketch map of frequency change waveform that arrives the signal beams of detector.Figure (a).
Fig. 6 is for to do the later spectrogram of fast Fourier transform to the detector picked up signal.
Fig. 7 is the signal processing software flow pattern.
Fig. 8 is for mixing the FFT conversion figure of coherent laser radar Woundless blood sugar measuring system to the signal of the tissue liquid under the different concentration of glucose certainly.
The figure of Fig. 9 for the FFT signal is taken the logarithm.
Figure 10 is the comparison diagram of simulate signal slope and tissue scatter's coefficient.
The specific embodiment
The present invention is with laser radar Continuous Wave with frequency modulation technology and mix coherent technique certainly and be applied to the Woundless blood sugar measurement and come up, and has realized that finishing Woundless blood sugar concentration with simple system detects.
Not losing its versatility, will be the operation principle that example is come illustrative system as the semiconductor laser with tunable modulation signal with sawtooth waveforms below.
Fig. 4 is from the detailed maps that mixes relevant interference system operation principle.The frequency of laser emitting light wave can be expressed as:
In the following formula,
The slope of expression sawtooth modulation signal,
Expression modulation original frequency.
As shown in Figure 4, suppose that the experience light path is
Light wave, its backscattering light intensity is
, regard a virtual reflecting surface as with locating, then can introduce the reflectance notion:
In the following formula,
Be the initial light intensity of laser emitting, scattering coefficient is relevant with the decay of light in skin histology.
Just constituted a composite resonant cavity (compound cavity) between the rear end face of frequency sweep semiconductor laser so, front end face and the pairing virtual reflecting surface of the light of the different light paths of experience of returning by the skin histology scattering.According to mixing coherence theory certainly, back-scattering light can be expressed as the influence that laser emitting power is brought:
In the following formula
The gain for threshold value of laser instrument when stray light effects is arranged,
The gain for threshold value of laser instrument when representing no stray light effects,
The expression laser chamber is long,
Represent that the new resonator cavity chamber that above-mentioned virtual reflecting surface and laser instrument rear end face formed is long,
The frequency that the expression scattering enters the light wave of laser instrument,
Expression external feedback coefficient:
（5）
It is simplified and can obtain:
In the following formula
By the parameter decision of laser instrument own,
By the decision of laser modulation parameter,
Determine jointly by laser modulation parameter and light beam institute experience process.
This shows, the linear superposition that is changed to the different frequency cosine function of laser output power, frequency values is by the decision of light path that light beam experienced, and amplitude size that should frequency determine that by corresponding reflection coefficient system is determined by the parameter of laser instrument own the amplification of signal.According to above to the definition of reflection coefficient, the reflection coefficient here is relevant with the attenuation quotient that light is propagated in tissue, obtain signal spectrum by fast fourier transform so, just can analyze the relation between light path that light beam experiences and its light intensity attenuation amount, as shown in Figure 5 and Figure 6.
There are some researches show that the Beer-Lambert theorem is satisfied in the transmission of light in tissue:
In the following formula
The expression incident intensity,
The light intensity that expression reflects,
The light path that expression light is propagated in tissue,
Determine by following formula:
In the following formula
The absorptance of expression tissue,
The scattering coefficient of expression tissue.
The research of background technology proves that during near infrared light incident, absorptance is far smaller than scattering coefficient in skin histology, so the damped expoential of light in tissue influenced by scattering coefficient mainly.
According to the Mie scattering theory, when blood sugar concentration raises, the tissue scattering coefficient will reduce thereupon.Can get by aforementioned analysis, from from the signal of mixed phase dry systems gained, can extracting tissue scatter's coefficient, thereby demarcate by experiment can obtain that blood sugar concentration changes and the frequency-region signal slope between relation.
Not losing its versatility, will be that example illustrates the advantage of this system on signal amplifies with sawtooth waveforms as the tunable laser modulation signal still below:
As above-mentioned derivation, mixing coherent laser radar Woundless blood sugar measuring method gained useful signal certainly can be expressed as:
In the following formula
The reflection coefficient of expression laser front facet,
Determine by the laser modulation parameter.
According to above-mentioned derivation method, introduce virtual reflecting surface equally, warble the optical coherent chromatographic imaging method described in the background technology when skin histology is surveyed, the gained signal can be expressed as follows:
In the following formula
The time delays of representing corresponding light wave experience light path,
Be correspondence
The reflection coefficient of virtual reflecting surface (
).
The resulting interference signal of detector can be expressed as so:
In the following formula
The frequency modulation(PFM) slope of expression light source,
Be the reference mirror reflection coefficient.
Relatively can derive from the mixed phase dry systems can be expressed as the amplification of signal:
This shows amplification
Mainly by the laser end face reflectance
Decision.
To with reference to the accompanying drawings below and embodiment, specify this invention, it is more obvious that purpose of the present invention and effect will become.
Fig. 1 is the sketch map of one embodiment of the present invention.As shown in Figure 1, of the present inventionly form by three parts from mixing coherent laser radar Woundless blood sugar measuring system: semiconductor laser with tunable, photo-detector and signal processing circuit.
Laser instrument can adopt near the long no mode hopping semiconductor laser with tunable of the coherence length of centre wavelength 850nm.
Laser instrument is fixed on skin histology to be measured top, makes its emitting laser can shine skin histology, and guarantee to enter laser instrument once more by the back scattered flashlight of skin histology.Photo-detector is placed on the rear end face of laser instrument, and the light intensity of monitoring laser instrument output light-wave changes.The signal of photo-detector output will carry out date processing by signal processing circuit.
Signal processing circuit comprises two modules: filtration module and microprocessor module, two parallel independent operatings of module.Filtration module comprises the wave filter of two different frequencies, respectively the output signal of photo-detector is carried out filtering; Microprocessor module carries out date processing by software to the output signal of photo-detector, and the software flow pattern of signal processing as shown in Figure 7.
The work process of this embodiment is as follows: tunable laser is carried out the periodic frequency modulation, and as the form modulation with sawtooth waveforms or triangular wave, fast linear changes continuously to make its emergent light wave frequency (wavelength) be periodically.The outgoing beam of laser instrument shines on the skin histology, has the part back-scattering light to return and is coupled in the laser cavity, finishes one from mixing relevant process in laser cavity, realizes the conversion of light path information to laser emitting light intensity frequency information.The detector that is placed on the laser instrument rear side this moment receives by mixing the relevant laser instrument emission light intensity variable signal that causes certainly, is converted into signal of telecommunication input signal treatment circuit.Filtration module in the signal processing circuit comprises the wave filter of two different frequencies, respectively the output signal of photo-detector is carried out filtering, obtains the signal intensity at two different frequencies.Aforementioned the analysis showed that, they represent the scattered signal of the different optical path lengths of experience respectively, can calculate the scattering coefficient of tissue and the blood sugar concentration in the tissue fluid by intensity difference between the two.Microprocessor module in the signal processing circuit carries out the frequency spectrum of fast fourier transform picked up signal at first to the received signal, and sets up the change curve of signal with the scattering optical path length by the relation of signal frequency and its light path that is experienced; Then to filter output signal with compare correction by fast fourier transform institute picked up signal frequency spectrum; At last set up corresponding relation between system signal and the human blood glucose concentration with reference to medical parameter.Whole system need not removable precision optical machinery parts, can satisfy the needs of instrument miniaturization, portability; According to aforementioned analysis, the certainly mixing of scattered light in laser cavity is relevant can amplify signal simultaneously, and amplification can be determined by the laser end face reflectance is carried out appropriate design, need not to add outside amplifying circuit again, has reduced the risk of introducing electrical noise.
Accompanying drawing 8 and 9 has provided the simulation calculation result of this embodiment.Emulation adopt monte carlo method to photon the transmission in tissue follow the trail of, organize models selects tissue liquid parameter for use.As we can see from the figure, the attenuation slope of FFT signal reduced when concentration of glucose increased, and this illustrates that the slope of this system signal can reflect the variation of concentration of glucose in the solution.
When accompanying drawing 10 changed continuously for concentration of glucose, emulation gained signal slope and Mie scattering theory were calculated the comparison between the gained scattering coefficient.As can be seen from the figure signal slope reduces with concentration of glucose variation increase, meets substantially with Mie scattering theory value of calculation.When concentration of glucose changed 20mM, corresponding signal slope changed about 10dB/mm.Suppose that laser radar is 1mm in hypodermic effective range, the detection accuracy of detector is 0.1 dB, and then system's sensitivity that blood glucose is surveyed can reach 0.2mM in theory, and promptly 3.6mg/dL can satisfy the requirement of portable blood sugar monitoring.
Fig. 2 is the sketch map of second kind of embodiment of the present invention.As shown in Figure 2, this embodiment is made up of three parts: semiconductor laser with tunable, photo-detector and signal processing circuit.
Laser instrument can adopt near the long no mode hopping semiconductor laser with tunable of the coherence length of centre wavelength 850nm.
Laser instrument is fixed on skin histology to be measured top, makes its emitting laser can shine skin histology.Photo-detector and laser instrument are placed side by side, receive by the back scattered light beam that carries the blood glucose signal of skin.The signal of photo-detector output will carry out date processing by signal processing circuit.
The signal processing circuit of this embodiment is identical with first kind of embodiment.
The working method of this embodiment is as follows: tunable laser is carried out the periodic frequency modulation, and as the form modulation with sawtooth waveforms or triangular wave, fast linear changes continuously to make its emergent light wave frequency (wavelength) be periodically.The outgoing beam of laser instrument shines on the skin histology, and a part is reflected at skin surface as the reference light beam, and through the subcutaneous tissue scattering, flashlight and scattered light are received by photo-detector simultaneously a part as signal beams.Owing to have optical path difference between signal beams and the scattered beam, both interfere on detector mutually, and the light intensity signal that detector receives changes in time, and signal spectrum comprises blood sugar concentration information.The signal input signal treatment circuit that detector is received carries out data analysis.The signal processing circuit working method is identical with first kind of embodiment.
Simpler on the structure of the present invention, need not to set up specially reference mirror, make system structure compactness, simple, be fit to realize miniaturization, the portability of Woundless blood sugar measuring method; On the other hand, system amplifies signal from mixing to be concerned with, and need not to add outside amplifying circuit again when surveying small-signal, has reduced the risk of introducing electrical noise, has improved the sensitivity that blood glucose is surveyed.
Above content only is embodiments of the invention, and its purpose is not the restriction that is used for system and method proposed by the invention.In the protection domain of spirit of the present invention and claim, any modification and change to the present invention makes all fall into protection scope of the present invention.For example, the present invention also is applicable to the concentration of surveying solution, the application such as scattering coefficient of detecting material.
Claims (9)
1. one is utilized the Continuous Wave with frequency modulation laser radar to realize the system that Woundless blood sugar is measured, and it is characterized in that it comprises: semiconductor laser with tunable, photo-detector and signal processing circuit etc.; Described photo-detector places the rear end face of laser instrument or placed side by side with laser instrument, and signal processing circuit links to each other with photo-detector; The light that semiconductor laser with tunable sends returns by photo-detector after tested subcutaneous tissue scattering and receives, and described photo-detector is surveyed the light intensity variable signal and sent it to signal processing circuit; Described signal processing circuit comprises filtration module and microprocessor module, two parallel independent operatings of module, and described filtration module comprises the wave filter of two different frequencies; Signal processing circuit is analyzed the spectrum information of light intensity variable signal, calculates blood sugar concentration according to light intensity with the relation of frequency change.
2. the Continuous Wave with frequency modulation laser radar that utilizes as claimed in claim 1 is realized the system that Woundless blood sugar is measured, it is characterized in that, described detector places frequency sweep laser instrument rear end, the light that described semiconductor laser with tunable sends return laser light device after the tested tissue scattering carries out from mixing relevant process, places the detector of laser instrument rear end to survey by mixing the relevant laser instrument emission light intensity variable signal that causes certainly.
3. the Continuous Wave with frequency modulation laser radar that utilizes as claimed in claim 1 is realized the system that Woundless blood sugar is measured, it is characterized in that, described detector and frequency sweep laser instrument are placed side by side, and described detector is surveyed by skin surface reflected light and the relevant light intensity variable signal that causes of tested subcutaneous tissue scattered light.
4. the Continuous Wave with frequency modulation laser radar that utilizes as claimed in claim 1 is realized the system that Woundless blood sugar is measured, and it is characterized in that described semiconductor laser with tunable is no mode hopping semiconductor laser with tunable.
5. the Continuous Wave with frequency modulation laser radar that utilizes as claimed in claim 4 is realized the system that Woundless blood sugar is measured, and it is characterized in that, tunable laser is carried out the periodic frequency modulation, makes its emergent light wave frequency, is periodically to change continuously fast.
6. the Continuous Wave with frequency modulation laser radar that utilizes as claimed in claim 5 is realized the system that Woundless blood sugar is measured, and it is characterized in that described periodic frequency is modulated to sawtooth waveforms or triangular wave function.
7. the Continuous Wave with frequency modulation laser radar that utilizes as claimed in claim 1 is realized the system that Woundless blood sugar is measured, and it is characterized in that described semiconductor laser with tunable centre wavelength is positioned near the near infrared band the 850nm.
8. the Continuous Wave with frequency modulation laser radar that utilizes as claimed in claim 1 is realized the system that Woundless blood sugar is measured, it is characterized in that, described filtration module comprises the wave filter of two different frequencies, described wave filter carries out filtering to the laser instrument output intensity variable signal that photo-detector detects, and calculates the scattering coefficient of tissue and the blood sugar concentration in the tissue fluid according to the difference in signal strength at these 2 different frequencies that obtains.
9. the Continuous Wave with frequency modulation laser radar that utilizes as claimed in claim 1 is realized the system that Woundless blood sugar is measured, it is characterized in that the laser instrument output intensity variable signal that described microprocessor module detects photo-detector carries out the frequency spectrum that fast fourier transform obtains output signal, by signal frequency and its light path that is experienced concern the change curve of picked up signal with the scattering optical path length, thereby further calculate the scattering coefficient of tissue and the blood sugar concentration in the tissue fluid.
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| CN106166072B (en) * | 2015-05-19 | 2021-02-09 | 萨姆特得有限责任两合公司 | Method and device for non-invasive determination of a measured variable of an analyte in a biological body |
| CN106137218A (en) * | 2016-07-30 | 2016-11-23 | 哈尔滨工业大学 | A kind of method of non-intruding infrared composite absorption accurate measurement change of blood sugar |
| CN106889993A (en) * | 2017-04-11 | 2017-06-27 | 郜键 | FM/cw laser imaging non-blood sampling type blood sugar detection method based on light intensity modulation |
| CN106889993B (en) * | 2017-04-11 | 2020-05-15 | 郜键 | FM/cw laser imaging non-blood sampling type blood sugar detection method based on light intensity modulation |
| CN107865664A (en) * | 2017-09-22 | 2018-04-03 | 郜键 | A kind of non-blood sampling formula blood sugar detecting method of laser imaging |
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