CN102160791A - Self-mixing coherent laser radar invasive blood sugar measuring system - Google Patents

Abstract

The invention discloses a self-mixing coherent laser radar non-invasive blood sugar measurement system; it includes: a tunable semiconductor laser, a light detector, a signal processing circuit and the like. The photodetector is placed on the rear face of the laser or placed side by side with the laser, and the signal processing circuit is connected to the photodetector; the present invention replaces the movable mechanical arm with a non-mode-hopping tunable semiconductor laser to reduce the mechanical precision requirements of the system , so as to facilitate the development of the system towards miniaturization and portability; the self-mixing coherent method is used to further simplify the system, amplify the signal, and detect weak signals through simple components and structures.

Description

Self-mixing coherent lidar non-invasive blood glucose measurement system

technical field

The invention relates to a system capable of realizing non-invasive blood sugar measurement of human body, in particular to a system for non-invasive measurement of human blood sugar concentration by using frequency modulation continuous wave laser radar and self-mixing coherent process.

Background technique

Diabetes is a common and frequently-occurring disease. With the improvement of people's living standards, the incidence of diabetes is gradually increasing. In recent years, diabetes has become the third killer of modern diseases after cancer and cardiovascular diseases, and it is also listed as one of the three difficult diseases by the World Health Organization.

As people pay more and more attention to diabetes, how to realize accurate, convenient, continuous and non-invasive blood glucose measurement has also become a hot topic in research institutions. Among the many solutions, the optical method has attracted much attention.

The optical measurement method of blood glucose concentration can be divided into two methods in terms of detection objects: direct method and indirect method. The direct method is mainly to obtain the blood glucose concentration through the detection of the characteristics of the glucose molecule itself. Generally, the method of spectral analysis is selected, including near-infrared (NIR) spectral analysis method, optical polarization method and Raman (RAMAN) spectral analysis method, etc.; while the indirect method The concentration of blood sugar is calculated by detecting the influence of blood sugar on human blood and tissue characteristics. Generally, the method of scattering analysis is selected. The detection objects include the scattering coefficient of tissue to light, the refractive index of interstitial fluid, etc.

Near-infrared spectroscopic analysis, which has been widely studied at present, is mainly used to monitor blood sugar through the characteristic absorption peak intensity of glucose molecules. Although a great deal of research has been done and great progress has been made in this area for more than three decades, there is no credible working system so far. The main problems of this method are: the glucose molecule does not have a definite absorption form in the near-infrared spectral region; the spectrum contains the absorption spectra of other substances except glucose, and these signals will overlap and interfere with each other; the absorption signal will be affected by the scattering signal. great interference.

Another background technique utilizes the scattering properties of tissue for blood glucose analysis. In the near-infrared band, the light scattering of the tissue body is much stronger than the absorption. Through the analysis of the scattering spectrum, the information such as the refractive index and scattering coefficient of the tissue body can be obtained indirectly. After processing it with a suitable theory, the The corresponding blood glucose concentration can be obtained. The advantage of this method over near-infrared spectroscopy is that in the near-infrared band, the skin's light scattering is much greater than its absorption, so a higher signal-to-noise ratio can be obtained. Therefore, it can be considered to start with scattering analysis to find a non-invasive blood glucose measurement method that can meet the precision requirements.

A kind of background technology that utilizes the optical coherence tomography method to measure the blood glucose level of human body such as V. Larin, M. Motamedi, S. Eledrisi etc. in their article "Noninvasive Blood Glucose Monitoring With Optical Coherence Tomography", Diabetes Care, VOL. 25, pp.2263~2267, described in 2002. The system uses a 1300nm band superluminescent light-emitting diode (SLD) as a light source, and the core of the system is a Michelson interferometer. The light emitted by the light source passes through the beam splitter, and part of it is irradiated on the target detection object, and part of it is irradiated on a plane mirror as a reference beam, and the reflected detection light and reference light enter the photodetector at the same time for interference. The system modulates the optical path of the reference end through the mechanical arm to obtain different levels of information of the detected object, and establishes the relationship between the signal slope and the blood glucose concentration. The problem with this method of non-invasive blood glucose measurement is that a movable mechanical arm needs to be introduced into the system, and the scanning speed is slow and it is not conducive to the miniaturization and portability of the system; the strength of the system signal is related to the reflectivity of the detection object. When the reflectivity of the detected object is small, the obtained signal is very weak, so it is difficult to measure the extremely weak scattered light.

Contents of the invention

The purpose of the present invention is to provide a self-mixing coherent laser radar non-invasive blood sugar measurement system for the deficiencies of the prior art.

The object of the present invention is achieved through the following technical solutions: a system for realizing non-invasive blood glucose measurement by using frequency-modulated continuous wave laser radar, which includes: tunable semiconductor laser, optical detector and signal processing circuit, etc. The photodetector is placed on the rear end face of the laser or placed side by side with the laser, and the signal processing circuit is connected to the photodetector; the light emitted by the tunable semiconductor laser is scattered by the subcutaneous tissue under test and then returned to be received by the photodetector. The detector detects the light intensity change signal and sends it to the signal processing circuit; the signal processing circuit includes a filtering module and a microprocessor module, the two modules operate independently in parallel, and the filtering module includes two filters of different frequencies; The signal processing circuit analyzes the spectrum information of the light intensity change signal, and calculates the blood sugar concentration according to the relationship between the light intensity and the frequency change.

Further, the detector is placed at the back end of the frequency-sweeping laser, and the light emitted by the tunable semiconductor laser is scattered by the measured tissue and returns to the laser to perform a self-mixing coherent process. The detector placed at the back end of the laser detects The resulting laser emits a light intensity change signal.

Further, the detector is placed side by side with the frequency-sweeping laser, and the detector detects a light intensity change signal caused by coherence between light reflected from the skin surface and scattered light from the subcutaneous tissue under test.

Further, the tunable semiconductor laser is a mode-hop-free tunable semiconductor laser.

Further, periodic frequency modulation is performed on the tunable laser, so that the frequency of the emitted light wave changes periodically and rapidly continuously.

Further, the periodic frequency modulation is a sawtooth or triangular wave function.

Further, the central wavelength of the tunable semiconductor laser is in the near-infrared band around 850nm.

Further, the filtering module includes two filters of different frequencies, and the filters filter the output light intensity change signal of the laser detected by the photodetector, according to the obtained signal intensities at the two different frequencies The difference is used to estimate the scattering coefficient of the tissue and the blood glucose concentration in the interstitial fluid.

Further, the microprocessor module performs fast Fourier transform on the laser output light intensity change signal detected by the photodetector to obtain the frequency spectrum of the output signal, and obtains the signal from the relationship between the signal frequency and the optical path length experienced by the signal. The change curve of the tissue, so as to further calculate the scattering coefficient of the tissue and the blood glucose concentration in the interstitial fluid.

The beneficial effect of the present invention is that the present invention replaces the movable mechanical arm with a non-mode-hopping tunable semiconductor laser, which reduces the mechanical precision requirements of the system, thereby facilitating the development of the system towards miniaturization and portability; the method of self-mixing coherence is further simplified The system amplifies the signal and detects weak signals through simple components and structures.

Description of drawings

Fig. 1 is a schematic structural diagram of an embodiment of the present invention: combining laser radar frequency modulation continuous wave and self-mixing coherent technology to realize non-invasive blood glucose measurement.

FIG. 2 is another embodiment of the present invention: a structural schematic diagram of non-invasive blood glucose measurement realized by laser radar frequency modulation continuous wave technology. The detector and the frequency-sweeping laser are placed side by side to detect the light intensity change signal caused by the coherence of the reflected light from the skin surface and the scattered light from the subcutaneous tissue under test.

Fig. 3 is a schematic diagram of the operation flow of the non-invasive blood glucose measurement system realized by combining laser radar frequency modulation continuous wave and self-mixing coherent technology.

Fig. 4 is a detailed schematic diagram of the working principle of the self-mixing coherent technology.

Fig. 5 is a simplified schematic diagram of frequency variation waveforms of the modulated signal and the signal beam reaching the detector. Figure (a).

Fig. 6 is a spectrogram after performing fast Fourier transform on the signal obtained by the detector.

Figure 7 is a software flow chart of the signal processing part.

Fig. 8 is the FFT transformation diagram of the signal of human interstitial fluid under different glucose concentrations by the self-mixing coherent lidar non-invasive blood glucose measurement system.

Fig. 9 is a graph of taking the logarithm of the FFT signal.

Fig. 10 is a comparison chart of the simulated signal slope and the tissue scattering coefficient.

Detailed ways

The invention applies laser radar frequency modulation continuous wave technology and self-mixing coherent technology to non-invasive blood sugar measurement, and realizes non-invasive blood sugar concentration detection with a simple system.

Without losing its versatility, the working principle of the system will be explained below by taking the sawtooth wave as the modulation signal of the tunable semiconductor laser as an example.

Fig. 4 is a detailed schematic diagram of the working principle of the self-mixing coherent interference system. The frequency of the light wave emitted by the laser can be expressed as:

                        _（1）

₍₁₎

表示锯齿调制信号的斜率，

表示调制初始频率。In the above formula,

Indicates the slope of the sawtooth modulated signal,

Indicates the modulation initial frequency.

的光波，其背向散射光强为

，将处看作一个虚拟的反射面，则可以引入反射率概念：As shown in Figure 4, it is assumed that the experienced optical path is

The light wave has a backscattered light intensity of

, and the point is regarded as a virtual reflective surface, then the concept of reflectivity can be introduced:

                      _（2）                             

₍₂₎

为激光器出射的初始光强，散射系数与光在皮肤组织中的衰减有关。In the above formula,

is the initial light intensity emitted by the laser, and the scattering coefficient is related to the attenuation of light in skin tissue.

Then, a compound cavity is formed between the rear end face and the front face of the frequency-sweeping semiconductor laser and the virtual reflection face corresponding to the light scattered back through the skin tissue and experiencing different optical paths. According to the self-mixing coherence theory, the influence of backscattered light on the output power of the laser can be expressed as:

      _（3）

₍₃₎

                     _（4）

₍₄₎

为有散射光影响时激光器的阈值增益，

表示无散射光影响时激光器的阈值增益，

表示激光器腔长，

表示上述虚拟反射面与激光器后端面所组成的新谐振腔腔长，

表示散射进入激光器的光波的频率，

表示外部反馈系数：In the above formula

is the threshold gain of the laser under the influence of scattered light,

Indicates the threshold gain of the laser without the influence of scattered light,

is the laser cavity length,

Indicates the cavity length of the new resonant cavity formed by the above-mentioned virtual reflector and the rear end face of the laser,

represents the frequency of light waves scattered into the laser,

Denotes the external feedback coefficient:

₍₅₎

表示激光器前端面的反射系数，表示前述虚拟反射面的反射系数。

Indicates the reflection coefficient of the front face of the laser, Indicates the reflection coefficient of the aforementioned virtual reflective surface.

Simplifying it gives:

          _（6）

₍₆₎

由激光器本身参数决定，

由激光器调制参数决定，

由激光器调制参数与光束所经历过程共同决定。In the above formula

Determined by the parameters of the laser itself,

Determined by the laser modulation parameters,

It is determined by the modulation parameters of the laser and the process experienced by the beam.

It can be seen from this that the change of the output power of the laser is a linear superposition of cosine functions of different frequencies, the frequency value is determined by the optical path experienced by the beam, and the amplitude corresponding to the frequency is determined by the corresponding reflection coefficient. It is determined by the parameters of the laser itself. According to the definition of reflection coefficient above, the reflection coefficient here is related to the attenuation coefficient of light propagating in tissue, then the signal spectrum can be obtained by fast Fourier transform, and the relationship between the optical path experienced by the beam and its light intensity attenuation can be analyzed , as shown in Figure 5 and Figure 6.

Existing studies have shown that the transmission of light in tissues satisfies the Beer-Lambert theorem:

                      _（7）

₍₇₎

表示入射光强，

表示反射回来的光强，

表示光在组织中传播的光程，

由下式决定：In the above formula

Indicates the incident light intensity,

Indicates the reflected light intensity,

Indicates the optical path of light propagating in the tissue,

It is determined by the following formula:

                       _（8）

₍₈₎

表示组织的吸收系数，

表示组织的散射系数。In the above formula

represents the tissue absorption coefficient,

Indicates the scattering coefficient of the tissue.

Research on the background technology has proved that when near-infrared light is incident, the absorption coefficient in skin tissue is much smaller than the scattering coefficient, so the attenuation index of light in tissue is mainly affected by the scattering coefficient.

According to the Mie scattering theory, when the blood sugar concentration increases, the scattering coefficient of human tissue will decrease accordingly. From the foregoing analysis, it can be concluded that the tissue scattering coefficient can be extracted from the signal obtained from the self-hybrid coherent system, so that the relationship between the blood glucose concentration change and the signal slope in the frequency domain can be obtained through experimental calibration.

Without losing its versatility, the following will still take the sawtooth wave as the modulation signal of the tunable laser as an example to illustrate the advantages of the system in signal amplification:

As deduced above, the effective signal obtained by the self-hybrid coherent lidar non-invasive blood glucose measurement method can be expressed as:

             （9）

(9)

由激光器调制参数决定。In the above formula Indicates the reflection coefficient of the front face of the laser,

Determined by laser modulation parameters.

Also according to the above derivation method, a virtual reflection surface is introduced. When the chirped optical coherence tomography method described in the background technology detects skin tissue, the obtained signal can be expressed as follows:

         _（10）

₍₁₀₎

为对应

虚拟反射面的反射系数（

）。In the above formula Indicates the time delay of the corresponding light wave through the optical path,

for correspondence

The reflection coefficient of the virtual reflector (

).

Then the interference signal obtained by the detector can be expressed as:

   _（11）

₍₁₁₎

表示光源的频率调制斜率，

为参考镜面反射系数。In the above formula

Indicates the frequency modulation slope of the light source,

is the reference specular reflection coefficient.

Comparing the amplification factors that can be obtained from the hybrid coherent system to the signal can be expressed as:

                _（12）

₍₁₂₎

主要由激光器端面反射率

决定。It can be seen that the magnification

Mainly by the reflectivity of the laser end face

Decide.

The invention will be described in detail below according to the accompanying drawings and embodiments, and the purpose and effect of the invention will become more obvious.

Fig. 1 is a schematic diagram of an embodiment of the present invention. As shown in Figure 1, the self-mixing coherent lidar non-invasive blood glucose measurement system of the present invention consists of three parts: a tunable semiconductor laser, a light detector and a signal processing circuit.

The laser can adopt a non-mode-hopping tunable semiconductor laser with a center wavelength near 850nm and a long coherence length.

Fix the laser above the skin tissue to be tested, so that the laser light emitted by it can irradiate the skin tissue, and ensure that the signal light scattered by the skin tissue can enter the laser again. A photodetector is placed on the rear end face of the laser to monitor the light intensity change of the laser output light wave. The signal output by the light detector will be processed by the signal processing circuit.

The signal processing circuit includes two modules: a filter module and a microprocessor module, and the two modules run in parallel and independently. The filter module contains two filters with different frequencies, which respectively filter the output signal of the photodetector; the microprocessor module performs data processing on the output signal of the photodetector through software, and the software flow chart of signal processing is shown in Figure 7 .

The working process of this embodiment is as follows: periodic frequency modulation is performed on the tunable laser, such as in the form of a sawtooth wave or a triangular wave, so that the frequency (wavelength) of the outgoing light wave changes periodically, rapidly and linearly. The output beam of the laser is irradiated on the skin tissue, and some of the backscattered light will be coupled back into the laser cavity, and a self-mixing coherent process is completed in the laser cavity to realize the conversion from the optical path information to the frequency information of the laser output light intensity. At this time, the detector placed on the back side of the laser receives the light intensity change signal emitted by the laser caused by self-mixing coherence, and converts it into an electrical signal for input to the signal processing circuit. The filter module in the signal processing circuit includes two filters with different frequencies, which respectively filter the output signal of the photodetector to obtain signal strengths at two different frequencies. The above analysis shows that they respectively represent scattering signals with different optical path lengths, and the scattering coefficient of the tissue and the blood glucose concentration in the interstitial fluid can be estimated from the intensity difference between the two. The microprocessor module in the signal processing circuit first performs fast Fourier transform on the received signal to obtain the spectrum of the signal, and establishes the change curve of the signal with the scattered optical path length through the relationship between the signal frequency and the optical path it has experienced; The output signal of the filter is compared and corrected with the signal spectrum obtained by the fast Fourier transform; finally, the corresponding relationship between the system signal and the blood sugar concentration of the human body is established with reference to the medical parameters. The whole system does not need movable precision mechanical parts, and can meet the needs of miniaturization and portability of the instrument; at the same time, according to the above analysis, the self-mixing coherence of scattered light in the laser cavity can amplify the signal, and the magnification can be determined by the reflectivity of the laser end face It is determined by a reasonable design that there is no need to add an external amplifier circuit, which reduces the risk of introducing electrical noise.

Accompanying drawing 8 and 9 has provided the simulation calculation result of this embodiment. The simulation uses the Monte Carlo method to track the transmission of photons in the tissue, and the tissue model uses the parameters of human tissue fluid. It can be seen from the figure that the attenuation slope of the FFT signal decreases when the glucose concentration increases, which shows that the slope of the system signal can reflect the change of the glucose concentration in the solution.

Accompanying drawing 10 is the comparison between the signal slope obtained by simulation and the scattering coefficient calculated by Mie scattering theory when the glucose concentration changes continuously. It can be seen from the figure that the signal slope decreases with the increase of glucose concentration, which is basically consistent with the calculated value of Mie scattering theory. When the glucose concentration changes by 20mM, the corresponding signal slope changes by about 10dB/mm. Assuming that the effective measurement range of the lidar in the subcutaneous tissue is 1 mm, and the detection accuracy of the detector is 0.1 dB, the theoretical sensitivity of the system to blood sugar detection can reach 0.2 mM, that is, 3.6 mg/dL, which can meet the requirements of portable blood sugar monitoring.

Fig. 2 is a schematic diagram of a second embodiment of the present invention. As shown in Figure 2, this embodiment consists of three parts: a tunable semiconductor laser, a photodetector and a signal processing circuit.

The laser can adopt a non-mode-hopping tunable semiconductor laser with a center wavelength near 850nm and a long coherence length.

Fix the laser above the skin tissue to be tested so that the laser light emitted from it can irradiate the skin tissue. A photodetector is placed alongside the laser and receives the beam of light that carries the blood sugar signal scattered back from the skin. The signal output by the light detector will be processed by the signal processing circuit.

The signal processing circuit of this embodiment is the same as that of the first embodiment.

The working method of this embodiment is as follows: the tunable laser is periodically frequency modulated, such as in the form of a sawtooth wave or a triangular wave, so that the frequency (wavelength) of the outgoing light wave changes periodically, rapidly and linearly. The output beam of the laser is irradiated on the skin tissue, part of it is reflected on the skin surface as a reference beam, and part of it is scattered through the subcutaneous tissue as a signal beam, and the signal light and scattered light are received by the photodetector at the same time. Due to the optical path difference between the signal beam and the scattered beam, the two interfere with each other on the detector, the light intensity signal received by the detector changes with time, and the signal spectrum contains blood glucose concentration information. The signal received by the detector is input into the signal processing circuit for data analysis. The working mode of the signal processing circuit is the same as that of the first embodiment.

The present invention is simpler in structure, does not need to set up a special reference mirror, makes the system compact and simple, and is suitable for realizing the miniaturization and portability of the non-invasive blood glucose measurement method; There is no need to add an external amplifier circuit, which reduces the risk of introducing electrical noise and improves the sensitivity of blood glucose detection.

The above content is only an embodiment of the present invention, and its purpose is not to limit the system and method proposed by the present invention. Within the spirit of the present invention and the protection scope of the claims, any modifications and changes made to the present invention fall within the protection scope of the present invention. For example, the present invention is also applicable to applications such as detecting the concentration of a solution, detecting the scattering coefficient of a substance, and the like.

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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