CN105249974A - Pressure-modulation-spectrum-technology-based noninvasive glucose detection system and method - Google Patents

Abstract

The invention discloses a non-invasive glucose detection system based on pressure modulation spectrum technology, which includes a light source, a power supply, a pressure modulator, a plurality of detectors and a computer. When the pressure modulator reaches the human tissue, the pressure modulator periodically presses the human tissue, and the light is reflected from the human tissue and then transmitted to the detector. There is a distance between the incident position of the light and the detection position of the detector, and the detector will collect The received data is sent to the computer for processing to extract the spectral information and concentration information of glucose. The non-invasive glucose detection system of the present invention can greatly enhance the glucose absorption signal, which makes the glucose detection more reliable and can perform repeated measurements.

Description

A non-invasive glucose detection system and method based on pressure modulation spectroscopy

technical field

The invention relates to the field of medical technology, in particular to a non-invasive glucose detection system and method based on pressure modulation spectroscopy technology.

Background technique

Diabetes is a disease that affects millions of people around the world, and the incidence is increasing day by day. People with diabetes need to control their blood sugar levels with frequent insulin injections, which are determined by taking blood samples several times a day. This invasive detection method usually uses some chemical additives to chemically react with blood sugar to generate some chemical components, and detecting these components is easier than directly measuring glucose, such as measuring color changes or oxidation currents. However, invasive testing not only brings considerable pain to patients, but also may bring some complications.

After a lot of research and attempts in recent years, the method of non-invasive blood glucose concentration detection has been gradually developed. These non-invasive detection methods do not require blood sampling and do not cause any trauma to the human body. Most of the non-invasive blood glucose detection methods are based on spectroscopic technology, and the absorption spectrum of glucose in the near-infrared or mid-infrared band is mainly used as the detection method. Glucose molecules have absorption peaks near the wavelengths of 1.59nm, 2.12nm, 2.27nm, 2.32nm and in the range of 9-10μm. Direct absorption spectroscopy or evanescent field-effect-based absorption spectroscopy (using implantable sensors), photoacoustic spectroscopy, and Raman spectroscopy have been successfully applied for noninvasive detection of blood glucose concentration.

Noninvasive detection of blood glucose in human tissue using spectroscopic methods still faces some major challenges. On the one hand, biological tissues contain many other physiological components (such as water, protein, fat, etc.) besides blood sugar. These components generally have more pronounced light absorption properties, far greater than that of glucose. Glucose, on the other hand, is found in very low levels in the blood, typically in the range of 30-500 mg/dl.

It is well known that gases have narrow absorption lines. When detecting weak gas signals, wavelength or frequency modulation technology is usually used to modulate the laser with a narrow-band emission line to detect the signal with a sharp change in the slope of the gas absorption line. Generally speaking, the magnitude of the modulation amplitude is on the order of the half-width of the signal or smaller. Subsequent sensitive frequency or phase-locked detection of the intensity-modulated signal using phase-locking techniques yields derivative spectral signals. Due to the influence of system 1/f noise, the signal is moved from the ground state to high frequency for detection, which can greatly reduce the noise and improve the signal-to-noise ratio. The absorption spectroscopy technique in scattering media (gasinscatteringmediaabsorptionspectroscopy, GASMAS) is mainly used to study the gas distribution in pores or cavities of scattering media (including fruits, tablets, ceramics, human tissue cavities, etc.). The solid medium has a strong broad absorption spectrum, while the gas distributed in the solid has a weak narrow absorption signal. Therefore, the phase-locking technique can be used to effectively isolate the gas absorption signal from the solid absorption spectrum.

On the contrary, isolating the weak target signal with broad absorption spectrum from the strong background signal with broad absorption spectrum is exactly the problem to be faced in the spectral detection of blood glucose concentration in tissue. At this point, commonly used spectral modulation techniques are no longer applicable.

Contents of the invention

The purpose of the present invention is to overcome the shortcomings and deficiencies of the prior art, and provide a non-invasive glucose detection system and method based on pressure modulation spectroscopy.

The purpose of the present invention is achieved through the following technical solutions: a non-invasive glucose detection system based on pressure modulation spectroscopy, including a light source 1, a power supply 2, a pressure modulator 6, a plurality of detectors 8 and a computer 9; 2 Controlling the generation of light in the required wavelength band, the generated light is transmitted to the human tissue 4, the pressure modulator 6 periodically presses the human tissue 4, and the light reflected from the human tissue 4 is transmitted to multiple detectors 8 , wherein there is a distance between the incident position of the light and the detection positions of the plurality of detectors 8, and the plurality of detectors 8 send the collected data to the computer 9 for processing to extract the spectral information and concentration information of glucose.

When the number of the detector 8 is 1, an integrated optical fiber probe 5 is also included in the system, and the integrated optical fiber probe 5 is composed of an incident optical fiber 3 and a plurality of collection optical fibers 7 arranged in a ring, and the incident optical fiber 3 and the light source 2 connected, the light reaches the human tissue through the incident optical fiber, the collecting optical fiber 7 is connected to the detector 8, and the collecting optical fiber collects the light reflected from the human tissue and transmits it to the detector 8.

The distance between the incident position of the light and the detection position is between 0.5mm-10mm. The incident position is the position where the light emitted from the light source reaches the human tissue, or the corresponding position of the end of the incident optical fiber on the human tissue; The scattered light is received by the detector, or collected at the corresponding location on the tissue where the end of the fiber is located.

The light waveband of the light source 1 is 650nm-2500nm. Appropriate wavelengths were chosen for glucose measurement, including the two wavelengths (660nm and 910nm) used by standard pulse oximeters. Oxygenated and deoxygenated hemoglobin can be estimated using the wavelengths used by common pulse oximeters, thereby accurately canceling the effects of changes in blood oxygenation. This not only makes the blood glucose sensor more sensitive, but also makes the measurement of blood glucose more targeted. Blood oxygen is measured at two wavelengths, which are then fed into an algorithm for estimating glucose concentrations. This method can achieve higher accuracy than other possible methods.

The light source 1 is a combination of light-emitting diodes, diode lasers, or tungsten-halogen lamps and band-pass filters.

The periodic pressing of the human tissue 4 is realized by installing an electric motor or a magnetic device on a finger clip or an earlobe clip or a device capable of acting on other soft parts of the body.

The detection system also includes an implantable insulin injection device commanded to release an appropriate amount of insulin based on the measured glucose concentration. Moreover, a sufficient amount of insulin can be stored in the injection device for use.

Another object of the present invention is achieved through the following technical solutions: a non-invasive glucose detection method based on pressure modulation spectroscopy technology, using the light generated by the light source to detect the reflection spectrum of human tissue, and periodically compressing human tissue to eliminate background spectral signals, And the reflectance spectrum is recorded intermittently during compression/heartbeat pause and non-compression/heartbeat period, and the records are sequentially calculated for averaging, difference and ratio, so that the measured spectrum no longer depends on the intensity of incident light Finally, use the standard fitting method or multivariate analysis method to analyze and extract the spectral information of glucose.

Compared with the prior art, the present invention has the following advantages and beneficial effects:

1. The present invention greatly enhances the absorption signal of glucose by periodically compressing human tissue, which makes the detection of glucose more reliable and can be repeated.

2. The light wavelength selected by the light source of the present invention can estimate the content of oxygenated hemoglobin and deoxygenated hemoglobin, and then accurately eliminate the influence caused by the change of blood oxygen. This not only makes the blood glucose sensor more sensitive, but also makes the measurement of blood glucose more targeted.

Description of drawings

1 is a schematic diagram of a non-invasive glucose detection system based on pressure modulation spectroscopy according to the present invention;

Fig. 2 is the optical fiber probe structural diagram of system described in Fig. 1;

3 is a structural diagram of a detection device based on multiple detectors in an embodiment of the present invention;

Fig. 4 is the schematic diagram of the finger clip sensor adopted in the embodiment of the present invention;

Fig. 5 is the absorption spectrogram produced by the liquid component and the non-liquid component of the tissue in the embodiment of the present invention;

Fig. 6 is an absorption spectrum diagram of glucose extracted in the embodiment of the present invention.

detailed description

The present invention will be further described in detail below in conjunction with the embodiments and the accompanying drawings, but the embodiments of the present invention are not limited thereto.

A noninvasive glucose detection system based on pressure modulation spectroscopy technology, as shown in Figure 1, includes a light source 1, a power supply 2, an incident optical fiber 3, an integrated optical fiber probe 5, a pressure modulator 6, a collection optical fiber 7, a detector 8 and a computer 9, The light source 1 is controlled by the power supply 2 to generate light in the required band, and the generated light is transmitted to the human tissue 4 through the incident optical fiber 3, and the pressure modulator 6 controls the integrated optical fiber probe 5 to periodically press the human tissue 4, After the light is reflected from the human body tissue 4, it is received by the integrated optical fiber probe 5 and transmitted to the detector 8 by the collecting optical fiber 7. The detector 8 sends the collected data to the computer 9 for processing to extract the spectral information and concentration information of glucose.

The light waveband of the light source 1 is 650nm-2500nm. Select the appropriate wavelength for glucose measurement, including the two wavelengths used by standard pulse oximeters. Oxygenated and deoxygenated hemoglobin can be estimated using the wavelengths used by common pulse oximeters, thereby accurately canceling the effects of changes in blood oxygenation. This not only makes the blood glucose sensor more sensitive, but also makes the measurement of blood glucose more targeted. Blood oxygen is measured at two wavelengths, which are then fed into an algorithm for estimating glucose concentrations. This method can achieve higher accuracy than other possible methods.

The light source 1 is a combination of light-emitting diodes, diode lasers, or tungsten-halogen lamps and band-pass filters. The periodically modulated signal used to detect glucose concentration can be estimated by a method similar to that used by pulse oximeters.

There is a distance between the incident position of the integrated optical fiber probe 5 and the detection position. There are two detection methods for the non-invasive glucose detection system based on pressure modulation spectroscopy. The first way is to use an integrated optical fiber probe, which is composed of an incident optical fiber and multiple collection optical fibers arranged in a ring. The incident fiber is connected to the light source, and the collection fiber is connected to a detector. Another detection method is to use an integrated detection device, which includes a light source and multiple detectors, wherein the detectors are arranged in a ring around the light source. The common point of these two methods is the backscattering detection method, and there is a distance between the incident position of light and the detection position. The incident position is the position where the light emitted from the light source reaches the human tissue, or the corresponding position of the end of the incident optical fiber on the human tissue; The scattered light is received by the detector, or collected at the corresponding location on the tissue where the end of the fiber is located.

When the number of the detector 8 is 1, an integrated optical fiber probe 5 is also included in the system, and the integrated optical fiber probe 5 is composed of an incident optical fiber 3 and a plurality of collection optical fibers 7 arranged in a ring, and the incident optical fiber 3 is connected to the light source 2, The collecting optical fiber 7 is connected with the detector 8.

As shown in Figure 2, the fiber optic probe consists of an incident fiber and multiple collection fibers. Considering that water has a strong absorption of light, and to ensure that the detector can receive the maximum amount of diffuse reflected light, in most cases a suitable separation distance is necessary. Figure 2(a) is the detection system before pressure modulation, and Figure 2(b) is the detection system after pressure modulation Δx distance. Figure 2(c) is a cross-sectional view of the fiber optic probe.

The distance between the incident position and the detection position is between 0.5-10mm. As shown in Figure 3, it is a detection device with pressure modulation operation under the condition of using one incident optical fiber and multiple detectors. The detection device integrates the incident optical fiber and multiple detectors, all the detectors are arranged in a circular manner, and there is a distance between the optical fiber and the detectors. Figure 3(a) is the detection system before pressure modulation, Figure 3(b) is the detection system after pressure modulation Δx distance, and Figure 3(c) is a cross-sectional view of the detection device.

The detection system also includes an implantable insulin injection device 10 which commands the release of an appropriate amount of insulin based on the measured glucose concentration. And the dose of insulin in the injection device should be sufficient for a period of time.

A non-invasive glucose detection method based on pressure-modulated spectroscopy technology, which uses light generated by a light source to detect the reflection spectrum of human tissue, and periodically compresses human tissue to eliminate background spectral signals, and during compression/heartbeat pauses and non-compression/heartbeat The reflectance spectrum is recorded intermittently during this period, and the records are sequentially calculated for averaging, difference and ratio, so that the measured spectrum no longer depends on the change of the incident light intensity, and finally the standard fitting method or multivariate The analytical method is used to analyze and extract the spectral information of glucose.

The periodic pressing of the human tissue 4 is realized by installing an electric motor or a magnetic device on a finger clip or an earlobe clip or a device capable of acting on other soft parts of the body. As shown in FIG. 4 , it is a finger clip 11 (or earlobe clip) sensing device. The incident optical fiber 12 and the detector 13 are integrated into the finger clip, and can be in direct contact with the finger 14 . The motor 17 drives the lift of the actuator 16 to achieve pressure modulation. The controller 18 is connected to the finger clip through a connector 15, which can not only control the motor drive 19 for pressure modulation, but also control the switch 20 of the light source, and control the data acquisition card 21 connected to the computer 22 to collect data.

As shown in Fig. 5, the absorption spectra produced by the liquid components and the non-liquid components of the tissue are described, wherein the absorption spectra of the liquid components can be modulated. The spectral shape of the modulated part is the same as that of the liquid component. A0 in the figure is the spectrum before pressure modulation, and A1 is the spectrum after pressure modulation.

As shown in Figure 6, where the spectrum depicted in Figure 6a depends only on the modulation, where ΔA=A1-A0. The difference in these spectra is largely due to the absorption of glucose, since the shift due to non-liquid components has been removed. The spectrum in Figure 6a contains the information of oxyhemoglobin and deoxygenated hemoglobin, and their spectral information can usually be obtained at corresponding wavelengths by using a pulse oximeter. Figure 6b depicts the spectrum of isolated glucose, which can be separated from the spectrum in Figure 6a using multivariate statistical analysis techniques.

Considering the possible effects of light incident position, detection position, detection method, tissue compression degree and modulation frequency, the device should be optimized through experiments in order to produce the optimal modulation and obtain the best glucose signal. In addition to the periodic compression that can be used to achieve modulation, the periodic stretch can also produce effective modulation.

Periodic tissue compression can be achieved using an electric motor or a magnetic device. The device can be attached to a finger clip, an earlobe clip (wearable device) or a device that acts on other soft parts of the body. Utilizing an integrated small-diameter fiber optic transmission/detection probe, modulation is conveniently performed by periodically moving the probe up and down (a few millimeters or so). As mentioned above, a sensor can be applied to the body at the beginning of the measurement, or periodically compressed by continuous wear. Of course, the modulation frequency must be kept low enough so that the tissue can be refilled with liquid tissue in the compressed gap. Nevertheless, background noise can still be reduced depending on 1/f.

Pulse oximeters use the beating of the heart to modulate the signal. Generally, light sources of two wavelengths (usually LED) are used for transmission measurement, the wavelengths are red light (660nm) and near-infrared light (910nm) near the isosbestic point (808nm). Oxyhemoglobin absorbs less at 660 nm than deoxyhemoglobin and absorbs more at 910 nm than oxyhemoglobin. The modulation of the beating heart produces a periodic waveform signal. By recording the plethysmographic waveform at two wavelength positions, the oxygen saturation in arterial blood can be calculated. Likewise, the present invention also uses modulation of heart beats to eliminate strong background signals caused by non-blood tissue components. However, an appropriate measurement wavelength should be chosen so that the signal related to the glucose concentration can be extracted. The selected wavelength should include the absorption peak of glucose. By recording the pulse intensity at the point of optimal glucose sensitivity, a pulse intensity function can be constructed. Alternatively, calibration can be performed through the results of invasive testing.

Oxygenated and deoxygenated hemoglobin can be estimated using the wavelengths used by common pulse oximeters, thereby accurately canceling the effects of changes in blood oxygenation. This not only makes the blood glucose sensor more sensitive, but also makes the measurement of blood glucose more targeted.

Indeed, when mechanical modulation is used, the glucose signal can be extracted by comparing the plethysmographic modulated signal waveforms recorded at two or more wavelength positions, in an approach similar to that taken by standard pulse oximeters.

Glucose signaling is thought to be specific relative to other major tissue components. Through the combination of external mechanical modulation and heartbeat modulation, useful information can be extracted at the double frequency of two different modulation frequencies, and then an enhanced glucose signal can be obtained.

It is worth mentioning that although tissue absorption (diffuse reflectance detection in the case of lower penetration depths) is the preferred method, given that Raman spectroscopy is very sensitive to the Raman transition of glucose, Raman spectroscopy The method can also be used in the measurement of pressure-modulated glucose spectroscopy. At this point, a laser source with a fixed frequency will be used to excite the Raman transition.

The above-mentioned embodiment is a preferred embodiment of the present invention, but the embodiment of the present invention is not limited by the above-mentioned embodiment, and any other changes, modifications, substitutions, combinations, Simplifications should be equivalent replacement methods, and all are included in the protection scope of the present invention.

Claims (9)

1. the noinvasive glucose detection systems based on pressure modulation spectral technique, it is characterized in that: comprise power supply (1), light source (2), pressure modulator (6), multiple detector (8) and computer (9), described light source (2) controls via power supply (1) light producing required wave band, the light produced arrives tissue (4), described pressure modulator (6) periodically presses tissue (4), light is transferred to multiple detector (8) after reflecting from tissue (4), wherein there is a distance between the incoming position of light and the detecting location of multiple detector (8), the data collected are sent to computer (9) and carry out processing thus the spectral information and the concentration information that extract glucose by multiple detector (8).

2. the noinvasive glucose detection systems based on pressure modulation spectral technique according to claim 1, it is characterized in that: when described detector (8) quantity is 1, integrated optical fiber probe (5) is also comprised in system, described integrated optical fiber probe (5) is made up of the collection optical fiber (7) of incident optical (3) and many annular array, described incident optical (3) is connected with light source (2), light arrives tissue by incident optical, described collection optical fiber (7) is connected with detector (8), described collection optical fiber is collected and be transferred to detector (8) after the light after tissue reflection.

3. the noinvasive glucose detection systems based on pressure modulation spectral technique according to claim 1 and 2, is characterized in that: the distance between the incoming position of described light and detecting location is 0.5mm-10mm.

4. the noinvasive glucose detection systems based on pressure modulation spectral technique according to claim 1 and 2, is characterized in that: the optical band of described light source (1) is 650nm-2500nm.

5. the noinvasive glucose detection systems based on pressure modulation spectral technique according to claim 1 and 2, is characterized in that: the combination that described light source (1) is halogen tungsten lamp and band pass filter, light emitting diode or diode laser.

6. the noinvasive glucose detection systems based on pressure modulation spectral technique according to claim 1 and 2, is characterized in that: described tissue (4) is carried out periodically to realize pressed through electro-motor or magnetic device.

7. the noinvasive glucose detection systems based on pressure modulation spectral technique according to claim 1 and 2, is characterized in that: described electro-motor or magnetic device are installed to finger clamp or ear lobe clamp or can act on the equipment of other softs of health.

8. the noinvasive glucose detection systems based on pressure modulation spectral technique according to claim 1 and 2, it is characterized in that: also comprise a transplantable insulin injection device (10), described insulin injection device (10) discharges appropriate insulin according to the concentration of glucose instruction of measuring.

9. the noinvasive glucose sensing approach based on pressure modulation spectral technique, it is characterized in that: the reflectance spectrum of the optical detection tissue utilizing light source to produce, background spectrum signal is eliminated by periodically compressing tissue, and between compression/heart beating interval and uncompressed/heart beat period, intermittently record is carried out to reflectance spectrum, described record is averaged successively, the calculating of difference and ratio, the spectrum measured is made no longer to depend on the change of incident intensity, finally re-use standard fit method or multivariable technique carries out analyzing and extracts the spectral information of glucose.