CN202051710U - Noninvasive blood glucose measurement system employing self-mixing coherent laser radar - Google Patents

Abstract

The utility model discloses a noninvasive blood glucose measurement system employing a self-mixing coherent laser radar, the system comprising a tunable semiconductor laser, an optical detector, a signal processing circuit and the like. The optical detector is placed on the rear end face of the laser or arranged side by side with the laser, and the signal processing circuit is connected with the optical detector. By replacing a moveable mechanical arm with a mode jump-free tunable semiconductor laser, the noninvasive blood glucose measurement system is reduced in mechanical precision requirement, thus facilitating the miniaturized and portable development of the system; by employing the self-mixing coherence method, the system is further simplified, signals are amplified, and feeble signals can be detected by simple elements and simple structures.

Description

A kind of from mixing coherent laser radar Woundless blood sugar measuring system

Technical field

This utility model relates to a kind of system that can realize that the human body Woundless blood sugar is measured, and relates in particular to a kind ofly to 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.

The utility model content

The purpose of this utility model is at the deficiencies in the prior art, provides a kind of from mixing coherent laser radar Woundless blood sugar measuring system.

The purpose of this utility model is achieved through the following technical solutions: a kind of Continuous Wave with frequency modulation laser radar that utilizes is realized 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.

The beneficial effects of the utility model are that this utility model replaces movably mechanical arm with a no mode hopping semiconductor laser with tunable, the mechanical precision requirement of reduction system, thereby past small-sized, the portability development of the system of being convenient to; 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 this utility model embodiment: 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 kind of embodiment of the present utility model: 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.

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

This utility model 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:

f(t)＝αt+f ₀ (1)

In the following formula, α represents the slope of sawtooth modulation signal, f ₀Expression modulation original frequency.

As shown in Figure 4, suppose that the experience light path is L _iLight wave, its backscattering light intensity is I _i, with z=L _iThe place regards a virtual reflecting surface as, then can introduce the reflectance notion:

$r_{2\mathrm{ext}}^i=\sqrt{I_i/I_0}---\left(2\right)$

In the following formula, I ₀Be 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:

$\mathrm{\&Delta;P}~g_c-g_{\mathrm{th}}=-\underset{i}{\mathrm{\&Sigma;}}\frac{{\mathrm{\&kappa;}}_i}{L}\cos \left(2\mathrm{\&pi;}{f}_i{\mathrm{\&tau;}}_{\mathrm{ext}}^i\right)...({\mathrm{\&kappa;}}_1<<1)---\left(3\right)$

${\mathrm{\&tau;}}_{\mathrm{ext}}^i=\frac{2(L_i-L)}{c}---\left(4\right)$

G in the following formula _cThe gain for threshold value of laser instrument when stray light effects is arranged, g _ThThe gain for threshold value of laser instrument when representing no stray light effects, L represents that laser chamber is long, L _iRepresent that the new resonator cavity chamber that above-mentioned virtual reflecting surface and laser instrument rear end face formed is long, f _i=α (t-τ _i) the expression scattering frequency that enters the light wave of laser instrument, κ _iExpression external feedback coefficient:

${\mathrm{\&kappa;}}_i=\frac{r_{2\mathrm{ext}}^i}{r_{2s}}(1-{\left|r_{2s}\right|}^2)---\left(5\right)$

r _2sThe reflection coefficient of expression laser front facet,

The reflection coefficient of representing aforementioned virtual reflecting surface.It is simplified and can obtain:

$\mathrm{\&Delta;P}~A\&CenterDot;r_{2\mathrm{ext}}^i\&CenterDot;\cos (2\mathrm{\&pi;}\&CenterDot;B\&CenterDot;t_{\mathrm{ext}}^i\&CenterDot;t+C)---\left(6\right)$

A is by the parameter decision of laser instrument own in the following formula, and B is by the decision of laser modulation parameter, and C is determined 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:

I＝I ₀exp(-μ _tl) (7)

I in the following formula ₀The expression incident intensity, I represents the light intensity that reflects, l represents the light path that light is propagated, μ in tissue _tDetermine by following formula:

μ _t＝μ _a+μ _s (8)

μ in the following formula _aThe absorptance of expression tissue, μ _sThe 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:

$\mathrm{\&Delta;P}~A\&CenterDot;r_{2\mathrm{ext}}^i\&CenterDot;\cos (2\mathrm{\&pi;}\&CenterDot;B\&CenterDot;{\mathrm{\&tau;}}_{\mathrm{ext}}^i\&CenterDot;t+C)---\left(9\right)$

A＝(1-|r ^2s| ²)/r _2s

R in the following formula _2sThe reflection coefficient of expression laser front facet, B is determined 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:

$E_{\mathrm{sig}}=\underset{i}{\mathrm{\&Sigma;}}{r}_{\mathrm{sig}}^i\&CenterDot;\exp \left\{j\right[2\mathrm{\&pi;}\&CenterDot;f\&CenterDot;(t-{\mathrm{\&tau;}}_i)+\mathrm{\&phi;}\left({\mathrm{\&tau;}}_i\right)\left]\right\}---\left(10\right)$

τ in the following formula _iThe time delays of representing corresponding light wave experience light path,

Be corresponding τ _iThe reflection coefficient of virtual reflecting surface

The resulting interference signal of detector can be expressed as so:

$I({\mathrm{\&tau;}}_1,...,{\mathrm{\&tau;}}_m,t)={\left|\underset{i=1}{\overset{m}{\mathrm{\&Sigma;}}}{E}_i({\mathrm{\&tau;}}_i,t)\right|}^2\&Proportional;\underset{i}{\mathrm{\&Sigma;}}{r}_{\mathrm{ref}}\&CenterDot;r_{\mathrm{sig}}^i\&CenterDot;\cos [2\mathrm{\&pi;}\&CenterDot;B\&CenterDot;{\mathrm{\&tau;}}_i\&CenterDot;t-\mathrm{\&phi;}\left({\mathrm{\&tau;}}_i\right)]---\left(11\right)$

α represents the frequency modulation(PFM) slope of light source, r in the following formula _RefBe the reference mirror reflection coefficient.

Relatively can derive from the mixed phase dry systems can be expressed as the amplification of signal:

$M=\frac{(1-{\left|r_{2s}\right|}^2)/r_{2s}}{r_{\mathrm{ref}}}>1---\left(12\right)$

This shows that amplification M is mainly by laser end face reflectance r _2sDecision.

To with reference to the accompanying drawings below and embodiment, specify this utility model, it is more obvious that the purpose of this utility model and effect will become.

Fig. 1 is the sketch map of a kind of embodiment of the present utility model.As shown in Figure 1, of the present utility modelly 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 0.1dB, 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 utility model.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 this utility model structure, 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 embodiment of the present utility model, and its purpose is not the restriction that is used for system and method that this utility model is proposed.In the protection domain of spirit of the present utility model and claim, any modification and change to this utility model is made all fall into protection domain of the present utility model.For example, this utility model also is applicable to the concentration of surveying solution, the application such as scattering coefficient of detecting material.

Claims (1)

1. one kind is mixed coherent laser radar Woundless blood sugar measuring system certainly, it is characterized in that it comprises: semiconductor laser with tunable, photo-detector and signal processing circuit; 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; Described signal processing circuit comprises filtration module and microprocessor module, two parallel independent operatings of module, and described filtration module is made up of the wave filter of two different frequencies.

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