CN111227844B - Noninvasive blood glucose detection device and detection method based on Raman scattering spectrum - Google Patents
Noninvasive blood glucose detection device and detection method based on Raman scattering spectrum Download PDFInfo
- Publication number
- CN111227844B CN111227844B CN202010226749.3A CN202010226749A CN111227844B CN 111227844 B CN111227844 B CN 111227844B CN 202010226749 A CN202010226749 A CN 202010226749A CN 111227844 B CN111227844 B CN 111227844B
- Authority
- CN
- China
- Prior art keywords
- optical fiber
- human body
- blood
- raman scattering
- spectrum
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0033—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medical Informatics (AREA)
- Veterinary Medicine (AREA)
- Surgery (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Optics & Photonics (AREA)
- Emergency Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
Abstract
The invention discloses a noninvasive blood sugar detection device based on Raman scattering spectrum, which comprises a semiconductor laser, an optical fiber beam splitter, an optical fiber probe, an optical filter, a Raman spectrometer, a first circuit switch, a second circuit switch, a lock-in amplifier, a heart rate measuring instrument and a computer, wherein the optical fiber beam splitter is arranged on the upper surface of the semiconductor laser; the invention utilizes abundant molecular vibration information contained in Raman scattering light, and utilizes the characteristic that Raman scattering spectra of different molecules have different characteristics, so as to identify the molecules by virtue of the Raman scattering spectra, and the Raman scattering spectra in pure blood are 1125cm long‑1Characteristic peak of glucose to 1549cm‑1The relative value of the characteristic peak value of hemoglobin and the real-time blood sugar concentration data of the human body measured by the blood sugar biochemical analyzer are established to be 1125cm‑1The relation standard straight line L between the relative peak value of the characteristic peak of the glucose and the blood sugar concentration of the human body finally realizes the noninvasive and real-time detection of the blood sugar of the human body; the invention has the advantages of high precision, no pollution, no harm to human body and the like, and has wide application prospect in the field of biological non-invasive detection.
Description
Technical Field
The invention relates to the technical field of biological noninvasive detection, in particular to a noninvasive blood glucose detection device and a detection method based on Raman scattering spectrum.
Background
The population of the diabetics is increased greatly all over the world, and the population of the diabetics in China is more in the first three parts of the world. The harm of diabetes to human health includes: leading to islet failure, renal failure; so that a large amount of glucose is discharged out of the human body along with urine to cause osmotic diuresis, thereby causing a large amount of dehydration of the human body; damage blood vessels, cause other complications such as retinopathy, cardiovascular and cerebrovascular diseases, and the like; causing neuropathy. Diabetes is so dangerous that it is critical for the patient to find and seek medical advice in a timely manner, otherwise the patient will miss the best time to cure and reach a serious condition. Currently, because of limited medical level, diabetes cannot be cured radically, and patients can only control blood sugar by orally taking or injecting insulin, real-time detection of blood sugar is very important.
At present, invasive or minimally invasive methods are mainly adopted for detecting blood sugar, the methods consume a large amount of biochemical reagents and have long detection time, meanwhile, the sampling brings inevitable pain to patients, and more importantly, the sampling may cause infection. Currently, most of regular hospitals adopt a blood glucose biochemical analyzer for detecting blood glucose, blood plasma is obtained by centrifugally separating blood of a patient, then the blood plasma reacts with glucose oxidase, and the content of hydrogen peroxide generated by the reaction is measured, so that the content of the blood glucose is obtained. Although the method has high precision, the detection time is long, the cost is high, and the real-time detection of the blood sugar cannot be realized. In addition, some glucometers capable of realizing minimally invasive blood glucose detection, such as a Roche glucometer and a Qiangsheng glucometer, also exist in the market. These blood glucose meters need the patient to sample by oneself, utilize the test paper to realize the detection to the blood sugar, though the blood glucose meter compares to go to hospital to detect blood sugar convenient many, can realize the real-time detection to the blood sugar, but whether blood glucose meter itself has the calibration, whether test paper is overdue, external environment interference etc. factor often can lead to the measuring result inaccurate, and the credibility is lower.
Disclosure of Invention
The invention aims to solve the technical problem of providing a non-invasive blood sugar detection method based on Raman scattering spectrum, which can realize non-invasive and real-time detection of blood sugar of human body, has high precision, no pollution and no harm to human body.
The technical scheme adopted by the invention for solving the technical problems is as follows: a non-invasive blood sugar detection device based on Raman scattering spectrum comprises a semiconductor laser, an optical fiber beam splitter, an optical fiber probe, an optical filter, a Raman spectrometer, a first circuit switch, a second circuit switch, a lock-in amplifier, a heart rate measuring instrument and a computer, wherein the optical fiber beam splitter comprises a total optical fiber beam, a first branched optical fiber and a second branched optical fiber, the first branched optical fiber and the second branched optical fiber are separated from the total optical fiber beam, the output end of the semiconductor laser is connected with the first branched optical fiber, the total optical fiber beam is connected with the optical fiber probe, the second branched optical fiber is connected with the signal input end of the Raman spectrometer through the optical filter, the Raman spectrometer is used for receiving Raman scattering optical signals, splitting light to obtain spectrum and converting the optical signals into electric signals, one signal output end of the Raman spectrometer is connected with the signal input end of the computer through the first circuit switch, the other signal output end of the Raman spectrometer is connected with the detection signal input end of the phase-locked amplifier through the second circuit switch, the reference signal input end of the phase-locked amplifier is connected with the signal output end of the heart rate measuring instrument, the amplification signal output end of the phase-locked amplifier is connected with the signal input end of the computer, the trigger signal output end of the computer is connected with the signal input end of the semiconductor laser, the optical fiber probe is used for collecting Raman scattering optical signals of blood at a human body detection part, and the heart rate measuring instrument is used for measuring the heart rate of a human body.
The optical fiber probe preferably comprises a hollow cylinder and a self-focusing lens, the hollow cylinder is a lighttight hollow cylinder, the self-focusing lens is embedded in the front end of a central hole of the hollow cylinder, the distance between the front end face of the self-focusing lens and the front end face of the hollow cylinder is 2-5 mm, a connecting optical fiber penetrates through the rear end of the central hole of the hollow cylinder, the connecting optical fiber is opposite to the rear end of the self-focusing lens, and the connecting optical fiber is connected with the total optical fiber bundle. The hollow cylinder can shield background light while playing a role in positioning the self-focusing lens, so that the signal-to-noise ratio is improved. The self-focusing lens can improve the energy density and the utilization rate of the laser, ensure that the laser can reach a certain depth under the skin and improve the accuracy of a detection result.
Further, the numerical aperture of the self-focusing lens is 0.25, and the focal length is 3 mm.
Preferably, the wavelength of the laser light emitted from the output end of the semiconductor laser is 532nm, the power is 280mW, and the line width is 0.3 nm.
Preferably, the optical fiber used by the optical fiber beam splitter is a quartz optical fiber, the transmittance of the quartz optical fiber is greater than or equal to 95%, the splitting ratio is 50:50, and the deviation of the splitting ratio is +/-8%; the optical filter is a high-pass optical filter with the light transmission range of 550-1000 nm, so that background light of 532nm and below is filtered out, and Raman scattering light is allowed to transmit, so that the influence of the background light is reduced, and the signal-to-noise ratio is improved.
Preferably, the Raman spectrometer adopts a grating with the line number of 800/mm as a light splitting element, the slit width of the system is 20 mu m, and the signal-to-noise ratio is higher than 6500: 1.
Preferably, the measurement range of the heart rate measuring instrument is 40-200 pulse times/minute, and the measurement error is +/-5%.
Preferably, the first circuit switch and the second circuit switch are both key switches.
Preferably, the human body detection site is a finger pulp of a human body.
The noninvasive blood glucose detection method implemented by the noninvasive blood glucose detection device comprises the following steps:
(1) selecting 30 healthy volunteers as measurement objects;
(2) 1 volunteer took 300mL of 25% glucose solution after fasting for 8 hours, and then measured the Raman scattering spectrum and the blood glucose concentration of human body in the pure blood of the volunteer every 30 minutes for 10 times in total, wherein each measurement process is as follows:
(2-1) ensuring that the external environment is stable and the human body is calm, selecting a human body detection part, fixing the optical fiber probe on the human body detection part, and enabling the optical fiber probe to be in contact with the skin of the human body detection part;
(2-2) triggering a semiconductor laser through a computer, wherein laser emitted by the semiconductor laser is emitted by a first bifurcated optical fiber, is irradiated to a human body detection part through an optical fiber probe after being combined by a main optical fiber bundle, reaches blood through skin of the human body detection part, is scattered by the blood to obtain a Raman scattering optical signal, enters a second bifurcated optical fiber through the main optical fiber bundle, and enters a signal input end of a Raman spectrometer after background light is filtered by an optical filter;
(2-3) dividing the output signal of the Raman spectrometer into two paths, closing the first circuit switch, disconnecting the second circuit switch, directly entering a signal input end of a computer by a path of signal sent by a signal output end of the Raman spectrometer, and processing by the computer to obtain a reference spectrum S10; closing the second circuit switch, disconnecting the first circuit switch, enabling another path of signal sent by another signal output end of the Raman spectrometer to enter a detection signal input end of a phase-locked amplifier, simultaneously measuring the heart rate of a human body by using a heart rate measuring instrument and inputting an obtained frequency signal to a reference signal input end of the phase-locked amplifier, amplifying a Raman scattering light signal in blood by using the frequency as a reference frequency by using the phase-locked amplifier, locking spectral information in the blood, inputting the spectral information to a signal input end of a computer in a signal form, and processing by the computer to obtain a spectrum S20;
(2-4) for spectrum S10, 1549cm was used by computer-1Normalizing the characteristic peak value of the hemoglobin to obtain a spectrum S1; for spectrum S20, 1549cm was used by computer-1Normalizing the characteristic peak value of the hemoglobin to obtain a spectrum S2; subtracting the spectrum S1 from the spectrum S2 to obtain a Raman scattering spectrum S3 in pure blood, namely S3 is S2-S1;
(2-5) sampling blood from the human body detection part selected in the step (2-1), and measuring blood glucose concentration data of the human body through a blood glucose biochemical analyzer;
(2-6) repeating the steps (2-1) to (2-5), summarizing the Raman scattering spectra in the pure blood and the human blood glucose concentration data obtained by 10 times of measurement, and obtaining 10 groups of Raman scattering spectra in the pure blood and the human blood glucose concentration data;
(2-7) 1125cm in Raman scattering spectrum in 10 groups of pure blood obtained-1Relative peak value of characteristic peak of glucose and blood glucose concentration data of human body are fitted by least square method to establish 1 1125cm-1A straight line of relation between the relative peak value of the characteristic peak of the glucose and the blood glucose concentration of the human body;
(3) repeating the step (2) to obtain 1125cm of another 29 volunteers-129 straight lines of the relation between the relative peak value of the characteristic peak of the glucose and the blood glucose concentration of the human body;
(4) for the obtained 30 1125cm strips-1Taking the average of the slope and intercept of the relative peak of the characteristic peak of glucose and the relation line of the blood glucose concentration of the human body to finally obtain a 1125cm line-1A standard straight line L of the relation between the relative peak value of the characteristic peak of the glucose and the blood glucose concentration of the human body;
(5) for the person to be measured needing non-invasive blood sugar detection, measuring in the steps (2-1) to (2-4) once to obtain the actually measured Raman scattering spectrum S of the pure blood of the person to be measured, and obtaining 1125cm in the Raman scattering spectrum S-1And (4) processing the relative peak value of the characteristic peak of the glucose, and finding the corresponding blood glucose concentration on the standard straight line L obtained in the step (2-6), namely obtaining the in-vivo blood glucose concentration value of the person to be tested.
Compared with the prior art, the invention has the following advantages:
the invention relates to a noninvasive blood sugar detection method based on Raman scattering spectrum, which utilizes abundant molecular vibration information contained in Raman scattering light and the characteristics that Raman scattering spectra of different molecules have different characteristics, identifies the molecules by virtue of the Raman scattering spectrum, measures the components and content of blood sugar and realizes noninvasive detection of blood sugar of a human body;
secondly, the invention passes 1125cm in Raman scattering spectrum in pure blood-1Characteristic peak of glucose to 1549cm-1The relative value of the characteristic peak value of the hemoglobin and the real-time blood glucose concentration data of the human body measured by the blood glucose biochemical analyzer are established to be 1125cm-1The relative peak value of the characteristic peak of the glucose and the standard straight line L of the relation of the blood glucose concentration of the human body are compared, and finally the noninvasive detection of the blood glucose of the human body is realized;
the invention has the advantages of high precision, no pollution, no harm to human body and the like, can realize non-invasive and real-time detection of the blood sugar of the human body, and has wide application prospect in the field of biological non-invasive detection.
Drawings
FIG. 1 is a structural connection frame of the non-invasive blood glucose detecting device of the present invention;
FIG. 2 is an external view of the optical fiber probe of example 2;
FIG. 3 is a sectional view showing the structure of the optical fiber probe of example 2;
FIG. 4 shows 1125cm of the sample obtained in example 3-1And a standard straight line L of the relation between the relative peak value of the characteristic peak of the glucose and the blood glucose concentration of the human body.
Detailed Description
The invention is described in further detail below with reference to the accompanying examples.
Example 1: a noninvasive blood glucose detection device based on Raman scattering spectrum is disclosed, as shown in figure 1, comprising a semiconductor laser 1, an optical fiber beam splitter 2, an optical fiber probe 3, an optical filter 5, a Raman spectrometer 6, a first circuit switch 7, a second circuit switch 8, a phase-locked amplifier 9, a heart rate measuring instrument 10 and a computer 11, wherein the optical fiber beam splitter 2 comprises a total optical fiber bundle 22, a first branched optical fiber 21 and a second branched optical fiber 23 which are branched from the total optical fiber bundle 22, the output end of the semiconductor laser 1 is connected with the first branched optical fiber 21, the total optical fiber bundle 22 is connected with the optical fiber probe 3, the second branched optical fiber 23 is connected with the signal input end of the Raman spectrometer 6 through the optical filter 5, the Raman spectrometer 6 is used for receiving Raman scattering optical signals, splitting optical spectrum and converting optical signals into electrical signals, the first circuit switch 7 and the second circuit switch 8 are both key switches, one signal output end of the Raman spectrometer 6 is connected with the signal input end of a computer 11 through a first circuit switch 7, the other signal output end of the Raman spectrometer 6 is connected with the detection signal input end of a phase-locked amplifier 9 through a second circuit switch 8, the reference signal input end of the phase-locked amplifier 9 is connected with the signal output end of a heart rate measuring instrument 10, the amplification signal output end of the phase-locked amplifier 9 is connected with the signal input end of the computer 11, the trigger signal output end of the computer 11 is connected with the signal input end of a semiconductor laser 1, the optical fiber probe 3 is used for collecting Raman scattering light signals of blood of a human body detection part 4, the heart rate measuring instrument 10 is used for measuring the heart rate of the human body, so that the phase-locked amplifier 9 tracks the heart rate of the human body and uses the frequency as reference frequency to amplify the Raman scattering light signals in the blood and lock spectral information in the blood, the signal-to-noise ratio is improved.
In embodiment 1, the wavelength of the laser light emitted from the output end of the laser diode is 532nm, the power is 280mW, and the line width is 0.3 nm; the optical fiber used by the optical fiber beam splitter 2 is a quartz optical fiber, the transmittance of the optical fiber is greater than or equal to 95 percent, the splitting ratio is 50:50, and the deviation of the splitting ratio is +/-8 percent; the optical filter 5 is a high-pass optical filter 5 with the light transmission range of 550-1000 nm; the Raman spectrometer 6 adopts a grating with the line number of 800/mm as a light splitting element, the width of a slit of the system is 20 mu m, and the signal-to-noise ratio is higher than 6500: 1; the measurement range of the heart rate measuring instrument 10 is 40-200 pulse times/minute, and the measurement error is +/-5%.
The noninvasive blood glucose monitoring device based on raman scattering spectroscopy of embodiment 2 differs from embodiment 1 in that, in embodiment 2, as shown in fig. 2 and 3, the optical fiber probe 3 includes a hollow cylinder 31 and a self-focusing lens 32, the hollow cylinder 31 is a light-tight hollow cylinder 31, the numerical aperture of the self-focusing lens 32 is 0.25, the focal length is 3mm, the self-focusing lens 32 is embedded in the front end of the central hole 30 of the hollow cylinder 31, the distance between the front end face of the self-focusing lens 32 and the front end face of the hollow cylinder 31 is 3mm, the rear end of the central hole 30 of the hollow cylinder 31 is penetrated with a connecting optical fiber 33, the connecting optical fiber 33 faces the rear end of the self-focusing lens 32, the connecting optical fiber 33 is connected with the total optical fiber bundle 22, and a protective sleeve 34 is disposed outside the connecting optical fiber 33.
Example 3: a noninvasive blood glucose measuring method implemented by the noninvasive blood glucose measuring apparatus of embodiment 2 includes the steps of:
(1) selecting 30 healthy volunteers as measurement objects;
(2) 1 volunteer took 300mL of 25% glucose solution after fasting for 8 hours, and then measured the Raman scattering spectrum and the blood glucose concentration of human body in the pure blood of the volunteer every 30 minutes for 10 times in total, wherein each measurement process is as follows:
(2-1) ensuring the stability of the external environment and the calmness of the human body, selecting a human body detection part 4 (in the embodiment, the index finger and the finger abdomen of the human body), fixing the optical fiber probe 3 on the human body detection part 4, and enabling the optical fiber probe 3 to be in contact with the skin of the human body detection part 4;
(2-2) triggering the semiconductor laser 1 through the computer 11, wherein laser emitted by the semiconductor laser 1 is emitted from the first bifurcated optical fiber 21, is combined through the total optical fiber bundle 22, then is irradiated on the human body detection part 4 through the optical fiber probe 3, reaches blood through the skin of the human body detection part 4, is scattered by the blood to obtain a Raman scattering optical signal, enters the second bifurcated optical fiber 23 through the total optical fiber bundle 22, is filtered by the optical filter 5 to remove background light, and then enters the signal input end of the Raman spectrometer 6;
(2-3) dividing the output signal of the raman spectrometer 6 into two paths, closing the first circuit switch 7, opening the second circuit switch 8, directly entering a signal input end of the computer 11 through a path of signal sent by a signal output end of the raman spectrometer 6, and processing by the computer 11 to obtain a reference spectrum S10; closing the second circuit switch 8, opening the first circuit switch 7, enabling another path of signal emitted by another signal output end of the Raman spectrometer 6 to enter a detection signal input end of the phase-locked amplifier 9, simultaneously measuring the heart rate of the human body by using the heart rate measuring instrument 10, inputting the obtained frequency signal to a reference signal input end of the phase-locked amplifier 9, amplifying a Raman scattering light signal in blood by using the frequency as reference frequency by using the phase-locked amplifier 9, locking spectral information in the blood, inputting the spectral information to a signal input end of the computer 11 in a signal form, and processing by the computer 11 to obtain a spectrum S20;
(2-4) for spectrum S10, 1549cm was used by computer 11-1Normalizing the characteristic peak value of the hemoglobin to obtain a spectrum S1; 1549cm for spectrum S20 by computer 11-1Normalizing the characteristic peak value of the hemoglobin to obtain a spectrum S2; subtracting the spectrum S1 from the spectrum S2 to obtain a Raman scattering spectrum S3 in pure blood, namely S3 is S2-S1;
(2-5) sampling blood from the human body detection part 4 selected in the step (2-1), and measuring blood glucose concentration data of the human body through a blood glucose biochemical analyzer;
(2-6) repeating the steps (2-1) to (2-5), summarizing the Raman scattering spectra in the pure blood and the human blood glucose concentration data obtained by 10 times of measurement, and obtaining 10 groups of Raman scattering spectra in the pure blood and the human blood glucose concentration data;
(2-7) 1125cm in Raman scattering spectrum in 10 groups of pure blood obtained-1Relative peak value of characteristic peak of glucose and blood glucose concentration data of human body are fitted by least square method to establish 1 1125cm-1A straight line of relation between the relative peak value of the characteristic peak of the glucose and the blood glucose concentration of the human body;
(3) repeating the step (2) to obtain 1125cm of another 29 volunteers-129 straight lines of the relation between the relative peak value of the characteristic peak of the glucose and the blood glucose concentration of the human body;
(4) for the obtained 30 1125cm strips-1Taking the average of the slope and intercept of the relative peak of the characteristic peak of glucose and the relation line of the blood glucose concentration of the human body to finally obtain a 1125cm line-1The relative peak value of the characteristic peak of glucose and the standard straight line L (see FIG. 4) of the blood glucose concentration of the human body are to be noted, the 1125cm-1Once the relative peak value of the characteristic peak of glucose and the standard straight line L of the blood glucose concentration of the human body are established, the relative peak value and the standard straight line L do not need to be established repeatedly in the subsequent testing process;
(5) for the person to be measured needing non-invasive blood sugar detection, measuring in the steps (2-1) to (2-4) once to obtain the actually measured Raman scattering spectrum S of the pure blood of the person to be measured, and obtaining 1125cm in the Raman scattering spectrum S-1And (4) processing the relative peak value of the characteristic peak of the glucose, and finding the corresponding blood glucose concentration on the standard straight line L obtained in the step (2-6), namely obtaining the in-vivo blood glucose concentration value of the person to be tested.
Claims (10)
1. A non-invasive blood sugar detection device based on Raman scattering spectrum is characterized by comprising a semiconductor laser, an optical fiber beam splitter, an optical fiber probe, an optical filter, a Raman spectrometer, a first circuit switch, a second circuit switch, a lock-in amplifier, a heart rate measuring instrument and a computer, wherein the optical fiber beam splitter comprises a total optical fiber beam, a first branched optical fiber and a second branched optical fiber, the first branched optical fiber and the second branched optical fiber are separated from the total optical fiber beam, the output end of the semiconductor laser is connected with the first branched optical fiber, the total optical fiber beam is connected with the optical fiber probe, the second branched optical fiber is connected with the signal input end of the Raman spectrometer through the optical filter, the Raman spectrometer is used for receiving Raman scattering optical signals, splitting light to obtain spectrum and converting the optical signals into electric signals, one signal output end of the Raman spectrometer is connected with the signal input end of the computer through the first circuit switch, the other signal output end of the Raman spectrometer is connected with the detection signal input end of the phase-locked amplifier through the second circuit switch, the reference signal input end of the phase-locked amplifier is connected with the signal output end of the heart rate measuring instrument, the amplification signal output end of the phase-locked amplifier is connected with the signal input end of the computer, the trigger signal output end of the computer is connected with the signal input end of the semiconductor laser, the optical fiber probe is used for collecting Raman scattering optical signals of blood at a human body detection part, and the heart rate measuring instrument is used for measuring the heart rate of a human body.
2. The device of claim 1, wherein the fiber optic probe comprises a hollow cylinder and a self-focusing lens, the hollow cylinder is an opaque hollow cylinder, the self-focusing lens is embedded in the front end of the central hole of the hollow cylinder, the distance between the front end face of the self-focusing lens and the front end face of the hollow cylinder is 2-5 mm, a connecting fiber is arranged at the rear end of the central hole of the hollow cylinder in a penetrating manner, the connecting fiber is opposite to the rear end of the self-focusing lens, and the connecting fiber is connected with the total fiber bundle.
3. The device of claim 2, wherein the self-focusing lens has a numerical aperture of 0.25 and a focal length of 3 mm.
4. The device as claimed in claim 1, wherein the output end of the semiconductor laser emits laser light with a wavelength of 532nm, power of 280mW, and line width of 0.3 nm.
5. The device for noninvasive glucose measurement based on Raman scattering spectroscopy of claim 1, wherein the optical fiber used in the optical fiber splitter is a quartz optical fiber, the transmittance of which is greater than or equal to 95%, the splitting ratio is 50:50, and the deviation of the splitting ratio is ± 8%; the optical filter is a high-pass optical filter with the light transmission range of 550-1000 nm.
6. The device for noninvasive glucose measurement based on Raman scattering spectroscopy of claim 1, wherein the Raman spectrometer uses a grating with a score of 800/mm as the light splitting element, the system has a slit width of 20 μm and a signal-to-noise ratio higher than 6500: 1.
7. The device for noninvasive glucose measurement based on Raman scattering spectroscopy of claim 1, wherein the heart rate measurement apparatus has a measurement range of 40-200 pulses/min and a measurement error of ± 5%.
8. The device of claim 1, wherein the first circuit switch and the second circuit switch are both push-button switches.
9. The apparatus of claim 1, wherein the human body detection site is a finger pulp of a human body.
10. A method of non-invasive blood glucose testing performed with the non-invasive blood glucose testing apparatus of any one of claims 1-9, comprising the steps of:
(1) selecting 30 healthy volunteers as measurement objects;
(2) 1 volunteer took 300mL of 25% glucose solution after fasting for 8 hours, and then measured the Raman scattering spectrum and the blood glucose concentration of human body in the pure blood of the volunteer every 30 minutes for 10 times in total, wherein each measurement process is as follows:
(2-1) ensuring that the external environment is stable and the human body is calm, selecting a human body detection part, fixing the optical fiber probe on the human body detection part, and enabling the optical fiber probe to be in contact with the skin of the human body detection part;
(2-2) triggering a semiconductor laser through a computer, wherein laser emitted by the semiconductor laser is emitted by a first bifurcated optical fiber, is irradiated to a human body detection part through an optical fiber probe after being combined by a main optical fiber bundle, reaches blood through skin of the human body detection part, is scattered by the blood to obtain a Raman scattering optical signal, enters a second bifurcated optical fiber through the main optical fiber bundle, and enters a signal input end of a Raman spectrometer after background light is filtered by an optical filter;
(2-3) dividing the output signal of the Raman spectrometer into two paths, closing the first circuit switch, disconnecting the second circuit switch, directly entering a signal input end of a computer by a path of signal sent by a signal output end of the Raman spectrometer, and processing by the computer to obtain a reference spectrum S10; closing the second circuit switch, disconnecting the first circuit switch, enabling another path of signal sent by another signal output end of the Raman spectrometer to enter a detection signal input end of a phase-locked amplifier, simultaneously measuring the heart rate of a human body by using a heart rate measuring instrument and inputting an obtained frequency signal to a reference signal input end of the phase-locked amplifier, amplifying a Raman scattering light signal in blood by using the frequency as a reference frequency by using the phase-locked amplifier, locking spectral information in the blood, inputting the spectral information to a signal input end of a computer in a signal form, and processing by the computer to obtain a spectrum S20;
(2-4) for spectrum S10, 1549cm was used by computer-1Normalizing the characteristic peak value of the hemoglobin to obtain a spectrum S1; for spectrum S20, 1549cm was used by computer-1Normalizing the characteristic peak value of the hemoglobin to obtain a spectrum S2; subtracting the spectrum S1 from the spectrum S2 to obtain a Raman scattering spectrum S3 in pure blood, namely S3 is S2-S1;
(2-5) sampling blood from the human body detection part selected in the step (2-1), and measuring blood glucose concentration data of the human body through a blood glucose biochemical analyzer;
(2-6) repeating the steps (2-1) to (2-5), summarizing the Raman scattering spectra in the pure blood and the human blood glucose concentration data obtained by 10 times of measurement, and obtaining 10 groups of Raman scattering spectra in the pure blood and the human blood glucose concentration data;
(2-7) 1125cm in Raman scattering spectrum in 10 groups of pure blood obtained-1Relative peak value of characteristic peak of glucose and blood glucose concentration data of human body are fitted by least square method to establish 1 1125cm-1A straight line of relation between the relative peak value of the characteristic peak of the glucose and the blood glucose concentration of the human body;
(3) repeating the step (2) to obtain 1125cm of another 29 volunteers-129 straight lines of the relation between the relative peak value of the characteristic peak of the glucose and the blood glucose concentration of the human body;
(4) for the obtained 30 1125cm strips-1Taking the average of the slope and intercept of the relative peak of the characteristic peak of glucose and the relation line of the blood glucose concentration of the human body to finally obtain a 1125cm line-1A standard straight line L of the relation between the relative peak value of the characteristic peak of the glucose and the blood glucose concentration of the human body;
(5) for the person to be measured needing non-invasive blood sugar detection, measuring in the steps (2-1) to (2-4) once to obtain the actually measured Raman scattering spectrum S of the pure blood of the person to be measured, and obtaining 1125cm in the Raman scattering spectrum S-1Finding out the corresponding blood glucose concentration on the standard straight line L obtained in the step (2-6) according to the relative peak value of the characteristic peak of the glucoseAnd obtaining the blood sugar concentration value in the body of the person to be tested.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010226749.3A CN111227844B (en) | 2020-03-27 | 2020-03-27 | Noninvasive blood glucose detection device and detection method based on Raman scattering spectrum |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010226749.3A CN111227844B (en) | 2020-03-27 | 2020-03-27 | Noninvasive blood glucose detection device and detection method based on Raman scattering spectrum |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111227844A CN111227844A (en) | 2020-06-05 |
| CN111227844B true CN111227844B (en) | 2022-05-20 |
Family
ID=70878867
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010226749.3A Active CN111227844B (en) | 2020-03-27 | 2020-03-27 | Noninvasive blood glucose detection device and detection method based on Raman scattering spectrum |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111227844B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111956233B (en) * | 2020-07-14 | 2022-07-19 | 中国科学院西安光学精密机械研究所 | Blood glucose measuring device and blood glucose measuring method |
| CN113208586A (en) * | 2021-03-01 | 2021-08-06 | 北京理工大学 | Noninvasive blood glucose rapid diagnosis differential Raman spectroscopy system |
| CN115120187A (en) * | 2021-03-29 | 2022-09-30 | 上海近观科技有限责任公司 | Device, system and method for detecting internal signal of biological tissue |
| CN113925504B (en) * | 2021-10-21 | 2024-02-13 | 浙江澍源智能技术有限公司 | Arterial blood Raman spectrum detection device and method based on pulse wave |
| CN114184899A (en) * | 2021-11-04 | 2022-03-15 | 中国工程物理研究院应用电子学研究所 | Strong-field light-emitting signal detector for micro-area closed space |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103505221A (en) * | 2012-06-28 | 2014-01-15 | 广西科学院 | Lossless method for quantitatively detecting blood glucose by utilizing Raman spectrum |
| EP3056141A1 (en) * | 2015-02-10 | 2016-08-17 | Politechnika Gdanska | A method of non-invasive measurement of blood glucose and optoelectronic system to non-invasive measurement of blood glucose |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10209192B2 (en) * | 2015-10-05 | 2019-02-19 | Nxgen Partners Ip, Llc | Spectroscopy with correlation matrices, ratios and glycation |
-
2020
- 2020-03-27 CN CN202010226749.3A patent/CN111227844B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103505221A (en) * | 2012-06-28 | 2014-01-15 | 广西科学院 | Lossless method for quantitatively detecting blood glucose by utilizing Raman spectrum |
| EP3056141A1 (en) * | 2015-02-10 | 2016-08-17 | Politechnika Gdanska | A method of non-invasive measurement of blood glucose and optoelectronic system to non-invasive measurement of blood glucose |
Non-Patent Citations (2)
| Title |
|---|
| 光学无创血糖浓度检测方法的研究进展;郭帅，等;《中国光学》;20191231;第12卷(第6期);第1235-1248页 * |
| 基于旋光法的无创血糖测量方法的研究;金海龙，等;《生物医学工程学杂志》;20091231;第26卷(第6期);第1391-1394页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111227844A (en) | 2020-06-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111227844B (en) | Noninvasive blood glucose detection device and detection method based on Raman scattering spectrum | |
| CA2045599C (en) | Non-invasive measurement of blood glucose | |
| US5383452A (en) | Method, apparatus and procedure for non-invasive monitoring blood glucose by measuring the polarization ratio of blood luminescence | |
| JP3643842B2 (en) | Glucose concentration testing device | |
| US7430445B2 (en) | Noninvasive blood analysis by optical probing of the veins under the tongue | |
| EP0548418B1 (en) | Non-invasive determination of glucose concentration in body of patient | |
| US20030176777A1 (en) | Method and device for detecting substances in body fluids by raman spectroscopy | |
| WO1996013202A1 (en) | Non-invasive determination of analyte concentration in body of mammals | |
| JP2013009963A (en) | Method for noninvasive human body component measurement with optional optical length | |
| CN111513728B (en) | Multi-technology fused noninvasive blood glucose detection device and measurement method | |
| CN106308814A (en) | Blood sugar non-invasive detection instrument based on near infrared spectrum analysis and realization method thereof | |
| CN108324286B (en) | Infrared noninvasive blood glucose detection device based on PCA-NARX correction algorithm | |
| CN110411947A (en) | Time gate determines the method and device of light path reference measure concentration | |
| US20230148312A1 (en) | Device for non-invasive blood glucose concentration measurement | |
| CN101435768B (en) | Apparatus and method for detecting specific substance concentration in solution by optical mode | |
| Priyoti et al. | Non-invasive blood glucose measurement using near infra-red spectroscopy | |
| CN203303031U (en) | Diabetes non-invasive detecting device based on glycation end product fluorescence spectrum | |
| Coleman et al. | Fiber optic based sensor for bioanalytical absorbance measurements | |
| Man | Noninvasive spectroscopic detection of blood glucose and analysis of clinical research status | |
| CN105232055A (en) | Noninvasive glucometer | |
| CN108634964A (en) | A kind of non-invasive blood sugar instrument based on spectrum | |
| CN111329492B (en) | Noninvasive blood lipid detection device and detection method based on near infrared spectrum | |
| JPH09187442A (en) | Non-invasion biochemical sensor | |
| CN113176229A (en) | Expiration detection method | |
| JP2004286475A (en) | Apparatus for measuring glucose concentration |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |