A system and method for measuring NADH

Abstract

This application relates to the technical field of medical devices, and particularly to a system and method for measuring NADH; the method includes: measuring the NADH content data of a tissue to be measured using an excitation light source and a receiving light source; measuring the tissue blood oxygen-related data of the tissue to be measured using a near-infrared light source; performing data correction on the NADH content data of the tissue to be measured and the tissue blood oxygen-related data of the tissue to be measured to obtain the target NADH content data; the formula used for data correction is: y = 0.575×A + 0.934×B + 40.298×C; where y is the value of the accurate NADH content data; A is the NADH content data of the tissue to be measured; B is the local tissue oxygen saturation data; C is the local tissue hemoglobin concentration index; this method can obtain accurate target NADH content data by using data correction to eliminate the tissue blood oxygen-related data in the NADH content data of the tissue to be measured.

Description

Technical Field

[0001] The present application relates to the field of medical device technology, and in particular to a system and method for measuring NADH. Background Art

[0002] When the body is short of oxygen, the body will distribute blood flow mainly to important organs (such as the brain and heart), while less important organs (such as the gastrointestinal tract or urogenital system) will experience insufficient blood perfusion, resulting in less oxygen entering these organs. Therefore, when the body is short of oxygen, non-vital organs are more sensitive to oxygen balance; and by monitoring non-vital organs, changes in patients can be observed at an earlier stage, so that changes in the patient's body's oxygen supply can be discovered more promptly, making it easier for medical staff to intervene and treat the condition in a timely manner. The main site closely related to changes in oxygen supply is the mitochondria, which are the main source of energy for living organisms. Their normal function is a prerequisite for the continuous supply of energy to perform all cellular functions.

[0003] In clinical intensive care, critical illness is often accompanied by hemodynamic imbalance between microcirculation and microcirculation, as well as mitochondrial dysfunction, both of which are directly related to organ dysfunction and poor prognosis: for example, microcirculatory dysfunction will not ensure sufficient oxygen delivery to parenchymal cells, while mitochondrial dysfunction will lead to abnormal energy metabolism, which in turn leads to oxygen utilization disorders in tissues and cells. Therefore, real-time mitochondrial function testing of patients is a favorable approach to understand the patient's condition and gain treatment time.

[0004] NADH (Nicotinamide adenine dinucleotide) is a chemical substance, generally referring to reduced coenzyme I, and is a control marker in the energy production chain in mitochondria. Since NADH is mainly involved in material and energy metabolism in cells, and NADH is produced in the citric acid cycle in glycolysis and cellular respiration, the data obtained by monitoring the redox state of NADH is the best parameter to characterize the mitochondrial function in vivo. At present, it is known from the absorption spectrum analysis of NADH that NADH can absorb light from 300nm to 380nm and emit fluorescence at 420 to 480nm. Therefore, mitochondrial function can be detected in real time by spectral detection of NADH. However, the current system using spectral detection of NADH generally chooses to detect NADH in human cells. However, since there are many interference items in the human body, such as the concentration of hemoglobin and deoxyhemoglobin, it will seriously interfere with the accuracy of the detection. Summary of the invention

[0005] The present application provides a system and method for measuring NADH to solve the technical problem of poor accuracy in detecting the presence of NADH in the body in the prior art.

[0006] In a first aspect, the present application provides a method for measuring NADH, the method comprising:

[0007] Determining the NADH content data of the tissue to be measured using an excitation light source and a receiving light source;

[0008] Determining the tissue blood oxygen related data of the tissue to be measured using a near-infrared light source;

[0009] Correcting the NADH content data of the tissue to be measured according to the tissue blood oxygen related data of the tissue to be measured to obtain the target NADH content data;

[0010] Wherein, the tissue blood oxygen related data includes local tissue blood oxygen saturation data and local tissue hemoglobin concentration index;

[0011] The formula used for the data correction is:

[0012] y = 0.575×A + 0.934×B + 40.298×C;

[0013] In the formula, y is the target NADH content data;

[0014] A is the NADH content data of the tissue to be measured;

[0015] B is the local tissue oxygen saturation data;

[0016] C is the local tissue hemoglobin concentration index.

[0017] Optionally, the correcting the NADH content data of the tissue to be measured according to the tissue blood oxygen related data of the tissue to be measured includes:

[0018] Determining the NADH content data of a standard NADH solution using the excitation light source and the receiving light source under colorless and constant temperature conditions, and constructing a standard curve for NADH measurement in combination with the concentration data of the standard NADH solution;

[0019] Obtaining the NADH content of the tissue to be measured according to the NADH content data of the tissue to be measured and the standard curve for NADH measurement;

[0020] Determining the tissue blood oxygen saturation of a standard tissue using a near-infrared light source and constructing a standard curve for blood oxygen saturation;

[0021] Respectively determining the local blood oxygen saturation and local hemoglobin concentration of a standard tissue using a near-infrared light source to construct a first standard curve for measuring local blood oxygen saturation and a second standard curve for measuring local hemoglobin concentration;

[0022] Based on the tissue oxygenation-related data of the tissue to be measured, the first standard curve, and the second standard curve, the local tissue oxygen saturation of the tissue to be measured and the local tissue hemoglobin concentration of the tissue to be measured are obtained;

[0023] According to the oxygen saturation of the tissue to be measured and the hemoglobin concentration of the tissue to be measured, and in combination with the data correction formula, the NADH content of the tissue to be measured is corrected to eliminate the local tissue oxygen saturation of the tissue to be measured and the local tissue hemoglobin concentration in the NADH content of the tissue to be measured, and the target NADH content data is obtained.

[0024] Optionally, the steps of measuring the NADH content data of the standard NADH solution by using the excitation light source and the receiving light source under colorless and constant temperature conditions, and constructing the standard curve for NADH measurement in combination with the concentration data of the standard NADH solution include:

[0025] Select a standard NADH solution, and perform concentration statistics on the standard NADH solution to obtain standard NADH solution concentration data;

[0026] Under colorless and constant temperature conditions, use the excitation light source and the receiving light source to measure the NADH content of the standard NADH solution to obtain standard NADH content data;

[0027] According to the standard NADH solution concentration data and the standard NADH content data, construct the standard curve of NADH.

[0028] Optionally, the wavelength of the excitation light source is 360 nm to 370 nm.

[0029] Optionally, the wavelength of the receiving light source is 450 m to 470 nm.

[0030] Optionally, the wavelength of the near-infrared light source is 600 nm to 660 nm.

[0031] In a second aspect, the present application provides a system for measuring NADH, the system being adapted to the method described in the first aspect, and the system includes:

[0032] The NADH detection unit includes an excitation light source emitter, a detection port, and a light source receiver. The excitation light source emitter is connected to the detection port through a transmission optical fiber, and the light source receiver is connected to the detection port through a receiving optical fiber to measure the NADH content data of the tissue to be measured;

[0033] The tissue blood oxygen detection unit includes a near-infrared light emitter and a near-infrared light receiver. The near-infrared light emitter is connected to the detection port through the emission optical fiber, and the near-infrared light receiver is connected to the detection port through the reception optical fiber to detect the local tissue blood oxygen saturation data and the local tissue hemoglobin concentration index of the tissue to be measured;

[0034] A control processor, which is respectively connected to the signal output end of the light source receiver and the signal output end of the near-infrared light receiver.

[0035] Optionally, the light source receiver includes a filter, a photomultiplier tube and an amplifier; the detection port is connected to the filter through the reception optical fiber, the filter is connected to the fiber multiplier tube through the reception optical fiber, the photomultiplier tube is connected to the amplifier through the reception optical fiber, and the amplifier is connected to the control processor.

[0036] Optionally, the near-infrared light receiver includes a near-infrared light multiplier tube, the near-infrared multiplier tube is connected to the detection port through the reception optical fiber, and the near-infrared light multiplier tube is connected to the control processor.

[0037] Optionally, the system further includes:

[0038] A beam splitting unit, including a first beam splitter and a second beam splitter. One end of the first beam splitter is connected to the detection port through an emission optical fiber, and the other end of the first beam splitter is respectively connected to the excitation light source emitter and the near-infrared light emitter through a reception optical fiber;

[0039] The second beam splitter is connected to the detection port through the reception optical fiber, and the second beam splitter is respectively connected to the light source receiver and the near-infrared light receiver through the reception optical fiber.

[0040] The above technical solution provided by the embodiment of the present application has the following advantages compared with the prior art:

[0041] A method for measuring NADH provided by the embodiment of the present application. Since when measuring NADH, the color change and temperature change of the tissue to be measured will both have a certain interference on the accuracy of the measurement result, and too many in-vivo interfering substances in the tissue to be measured will also affect the accuracy of optical detection. Therefore, the content data of NADH in the tissue to be measured is first measured by the excitation light source and the reception light source, and then the tissue blood oxygen saturation data in the tissue to be measured and the tissue blood oxygen-related data such as hemoglobin and deoxyhemoglobin in the tissue to be measured are measured by near-infrared light. Finally, the tissue blood oxygen-related data in the NADH content data of the tissue to be measured is corrected and removed by means of data correction, so as to obtain the target NADH content data. Description of the Drawings

[0042] The accompanying drawings here are incorporated into the specification and form a part of this specification, showing embodiments consistent with this application, and are used together with the specification to explain the principles of this application.

[0043] To more clearly illustrate the technical solutions in the embodiments of this application or in the prior art, the following will briefly introduce the accompanying drawings required for use in the description of the embodiments or the prior art. Obviously, for those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0044] Figure 1 Schematic flow diagram of a method for measuring NADH provided by an embodiment of this application;

[0045] Figure 2 Schematic detailed flow diagram of a method for measuring NADH provided by an embodiment of this application;

[0046] Figure 3 Schematic flow diagram of a method for constructing a standard curve for NADH measurement provided by an embodiment of this application;

[0047] Figure 4 Schematic structural diagram of a system for measuring NADH provided by an embodiment of this application;

[0048] Figure 5 Schematic logical diagram of a system for measuring NADH provided by an embodiment of this application;

[0049] Figure 6 Schematic structural diagram of the transmitting optical fiber and the receiving optical fiber provided by an embodiment of this application, where Figure 6 A is the schematic structural diagram of the transmitting optical fiber, Figure 6 B is the schematic structural diagram of the receiving optical fiber;

[0050] Figure 7 Schematic structural diagram of the Israeli product system provided in Comparative Example 1 of this application;

[0051] Figure 8 Schematic diagram of the linear curve of the NADH pure solution provided in Embodiment 3 of this application;

[0052] Among them, 1 - excitation light source emitter, 2 - detection port, 3 - light source receiving part, 31 - filter, 32 - photomultiplier tube, 33 - amplifier, 4 - transmitting optical fiber, 5 - receiving optical fiber, 6 - near-infrared light emitter, 7 - near-infrared light receiving part, 71 - near-infrared light multiplier tube, 8 - control processor, 9 - first beam splitter, 10 - second beam splitter. Detailed implementation manners

[0053] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions in the embodiments of this application will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of this application. Obviously, the described embodiments are part of the embodiments of this application, rather than all of them. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of this application without creative efforts fall within the scope of protection of this application.

[0054] Unless otherwise specifically stated, various raw materials, reagents, instruments, equipment, etc. used in this application can be obtained through market purchases or prepared by existing methods.

[0055] Currently, the devices for detecting NADH by spectroscopy include: (1) CritiView from Israel. This product measures from the urethral wall, uses a 375 nm laser Doppler as the emission light source, 450 nm as the receiving unit, and uses multiple measurement wavelengths. It is combined and coupled into a single excitation optical fiber through a dichroic beam splitter. This product has currently conducted experiments on animals (rodents) and tissue cells, etc. Since this product does not have a clinical registration certificate and cannot be applied to clinical experiments, it can only be used in the laboratory. At the same time, the results measured by this product only return the electrical signals of fluorescence and do not remove many interference items in the organism (such as the concentrations of hemoglobin and deoxyhemoglobin). Therefore, the measured results cannot be clinically applied.

[0056] (2) AngioExpert from Poland. This product is similar in shape to a sphygmomanometer and is used to measure NADH in the epidermal cells of the human upper arm. However, this product is less used, and the measured data does not have general significance. At the same time, the signals measured still do not remove the influence of interference factors in the human body.

[0057] Therefore, there is currently a problem that the accuracy of the system for detecting NADH in the body is poor due to the existence of interference factors in the human body.

[0058] Figure 1 Exemplarily shown is a schematic flowchart of a method for measuring NADH provided by the embodiments of this application;

[0059] As Figure 1 shown, the embodiments of this application provide a method for measuring NADH, and the method includes:

[0060] S1. Measuring the NADH content data of the tissue to be measured using an excitation light source and a receiving light source;

[0061] S2. Measuring the tissue blood oxygen-related data of the tissue to be measured using a near-infrared light source;

[0062] S3. Correct the NADH content data of the tissue to be measured according to the tissue oxygenation-related data of the tissue to be measured to obtain the target NADH content data;

[0063] Among them, the tissue oxygenation-related data includes local tissue oxygen saturation data and local tissue hemoglobin concentration index;

[0064] The formula used for the data correction is:

[0065] y = 0.575×A + 0.934×B + 40.298×C;

[0066] In the formula, y is the target NADH content data;

[0067] A is the NADH content data of the tissue to be measured;

[0068] B is the local tissue oxygen saturation data;

[0069] C is the local tissue hemoglobin concentration index.

[0070] In the embodiment of the present application, by introducing the specific formula for data correction, the relationship between the tissue oxygenation-related data of the tissue to be measured and the NADH content data of the tissue to be measured can be clarified. Therefore, through the data correction method, the tissue oxygenation-related data such as local tissue oxygen saturation and local tissue hemoglobin concentration can be directly removed from the NADH content data of the tissue to be measured, so as to obtain the target NADH content data.

[0071] It should be noted that the tissue to be measured refers to the tissue part in the body that needs to detect NADH, which can be the subcutaneous tissue part.

[0072] Figure 2 Exemplarily shows a detailed flowchart of a method for measuring NADH provided by the embodiment of the present application;

[0073] Such as Figure 2 As shown, in some optional embodiments, the correcting the NADH content data of the tissue to be measured according to the tissue oxygenation-related data of the tissue to be measured includes:

[0074] S301. Measure the NADH content data of the standard NADH solution by using the excitation light source and the receiving light source under colorless and constant temperature conditions, and construct a standard curve for NADH measurement in combination with the concentration data of the standard NADH solution;

[0075] S302. Obtain the NADH content of the tissue to be measured according to the NADH content data of the tissue to be measured and the standard curve for NADH measurement;

[0076] S303. Measure the local tissue oxygen saturation and local tissue hemoglobin concentration of the standard tissue using a near-infrared light source respectively to construct a first standard curve for measuring the local tissue oxygen saturation and a second standard curve for measuring the local tissue hemoglobin concentration;

[0077] S304. Obtain the content of interference factors of the tissue to be measured according to the tissue oxygen-related data, the first standard curve and the second standard curve;

[0078] S305. According to the local tissue oxygen saturation of the tissue to be measured and the local tissue hemoglobin concentration of the tissue to be measured, and in combination with the data correction formula, correct the NADH content data of the tissue to be measured to eliminate the local tissue oxygen saturation and the local tissue hemoglobin concentration in the NADH content of the tissue to be measured, and obtain the target NADH content data.

[0079] In the embodiment of the present application, by refining the specific steps of data correction, first construct a standard curve for NADH measurement, and through the NADH content data of the tissue to be measured, the NADH content in the tissue to be measured can be obtained. Then construct a first standard curve that can be used to measure the local tissue oxygen saturation and a second standard curve that can be used to measure the local tissue hemoglobin concentration. Finally, through the first standard curve, the second standard curve and the tissue oxygen-related data of the tissue to be measured, the local tissue oxygen saturation and the local tissue hemoglobin concentration in the tissue to be measured can be obtained. Finally, through the data correction formula, the influence of the local tissue oxygen saturation and the local tissue hemoglobin concentration in the NADH content data of the tissue to be measured can be eliminated, so as to obtain accurate target NADH content data.

[0080] Figure 3 Exemplarily shows a schematic flowchart of the method for constructing a standard curve for NADH measurement provided by the embodiment of the present application;

[0081] As Figure 3 shown, in some optional embodiments, the step of measuring the NADH content data of the standard NADH solution using the excitation light source and the receiving light source under colorless and constant temperature conditions, and constructing a standard curve for NADH measurement in combination with the concentration data of the standard NADH solution includes the steps:

[0082] S311. Select a standard NADH solution, and perform concentration statistics on the standard NADH solution to obtain standard NADH solution concentration data;

[0083] S312. Measure the NADH content of the standard NADH solution using the excitation light source and the receiving light source under colorless and constant temperature conditions to obtain standard NADH content data;

[0084] S313. Construct a standard curve of NADH based on the concentration data of the standard NADH solution and the content data of the standard NADH.

[0085] In the embodiments of the present application, by constructing a standard curve of NADH in the excitation light source and the receiving light source detection methods using a standard NADH solution, an accurate standard curve of NADH can be obtained, which facilitates accurately obtaining the NADH content of the tissue to be measured.

[0086] It should be noted that the standard NADH solution is prepared using a standard NADH kit. Based on the enzymatic digestion of the tissue, a uniformly dispersed tissue standard NADH solution can be obtained, thereby obtaining the concentration data of the standard NADH solution.

[0087] It should be noted that due to the characteristics of optical measurement, both color change and temperature change will cause certain interference to the measurement. Therefore, a standard NADH solution is first selected, and quantitative measurement is carried out using an excitation light source and a receiving light source under the conditions of being colorless and at a constant temperature, so as to determine the corresponding relationship between the measured reading of the system and the concentration of the standard NADH solution, which determines the relationship between the measured reading and the NADH concentration in other environments. In addition, at the tissue level, tissue blocks freshly taken from animals are selected, a standard NADH kit is used, and the enzymatic method is used to measure NADH at the tissue level, establishing the relationship between the measured value and the tissue NADH concentration. Therefore, it is convenient to perform quantitative processing on the tissue to be measured.

[0088] It should be noted that since the human body is a complex tissue containing many chemical substances, there must be other substances in the measurement wavelength band of NADH, and these substances will interfere with the measurement results. Therefore, in the actual measurement stage, the blood is decomposed in a way that continuously subdivides the blood, such as into plasma, serum, and red blood cells, etc., and the substances that cause greater interference to the measured value are determined in these components. At the same time, the mature oximeter (N17) produced by the applicant is used to measure the interfering substances, and then the change situation of the interfering substances measured by the oximeter is combined with the change situation of the NADH content data of the tissue to be measured measured by the system of the present application, and combined with algorithm correction, and calculations are carried out through the determined data correction related formula, which can improve the accuracy of the measured value. Therefore, decomposing the chemical components in the tissue to be measured and the blood can remove the interference of the interference factors on the reading, thereby making the measurement more accurate.

[0089] The oximeter N17 adopts a unique Spatial Resolution Algorithm (SAS), while the detection principle of other similar products is generally the modified Lambert-Beer law. The SAS spatial resolution algorithm can measure the local tissue oxygen saturation additionally compared with the modified Beer-Lambert law, and is not easily affected by the outer tissue. The oximeter N17 device obtained the CFDA certification in 2020. For the specific detection principle and the oximeter N17 device, refer to the relevant patents: CN201810481778.7 - Near-infrared non-invasive detection method for hemoglobin concentration index of human tissue; CN200310103053.8 - Non-destructive monitoring method and system for blood oxygen metabolism of biological tissue with diffused light; CN200610112598.9 - Detection method for absolute amounts of oxygenated and reduced hemoglobin concentrations in human tissue.

[0090] It should be noted that by determining the specific standard curve for blood oxygen saturation measurement and based on this standard curve, combined with the tissue blood oxygen-related data of the tissue to be measured, the specific local blood oxygen saturation and hemoglobin concentration content in the tissue to be measured can be deduced, so as to facilitate the subsequent elimination of the tissue blood oxygen-related data in the NADH content data of the tissue to be measured through data correction.

[0091] In some alternative embodiments, the wavelength of the excitation light source is 360nm to 370nm.

[0092] In some alternative embodiments, the wavelength of the received light source is 450m to 470nm.

[0093] In the embodiments of the present application, by defining the specific wavelength of the excitation light source and the specific wavelength of the received light source, since NADH can absorb light with a wavelength of 300nm to 380nm and emits fluorescence at 420nm to 480nm, setting the specific wavelengths of the excitation light source and the received light source can avoid the influence of interfering substances.

[0094] The wavelength of the excitation light source can be 360nm, 361nm, 362nm, 363nm, 364nm, 365nm, 366nm, 367nm, 368nm, 369nm or 370nm.

[0095] The wavelength of the received light source can be 450nm, 452nm, 454nm, 456nm, 458nm, 460nm, 462nm, 464nm, 466nm, 468nm or 470nm.

[0096] It should be noted that according to the operation and detection costs of the system and safety considerations, an LED light source with a wavelength of 365nm can be selected as the excitation light source, and 460nm can be selected as the received light source.

[0097] In some alternative embodiments, the wavelength of the near-infrared light source is 600nm to 660nm.

[0098] In the embodiments of the present application, by defining the specific wavelength of the near-infrared light, the blood oxygen saturation in the tissue can be detected more accurately, and at the same time, this wavelength has a good measurement effect on oxyhemoglobin in the tissue.

[0099] Figure 4 Exemplarily shown is a schematic structural diagram of a system for measuring NADH provided by an embodiment of the present application;

[0100] Figure 5 Exemplarily shown is a schematic logical diagram of a system for measuring NADH provided by an embodiment of the present application;

[0101] As Figure 4 and Figure 5 shown, based on a general inventive concept, the embodiments of the present application provide a system for measuring NADH, and the system includes:

[0102] The NADH detection unit includes an excitation light source emitter 1, a detection port 2, and a light source receiving part 3. The excitation light source emitter 1 is connected to the detection port 2 through an emission optical fiber 4, and the light source receiving part 3 is connected to the detection port 2 through a receiving optical fiber 5 to measure the NADH content data of the tissue to be measured;

[0103] The tissue blood oxygen detection unit includes a near-infrared light emitter 6 and a near-infrared light receiving part 7. The near-infrared light emitter 6 is connected to the detection port 2 through the emission optical fiber 4, and the near-infrared light receiving part 7 is connected to the detection port 2 through the receiving optical fiber 5 to detect the local tissue blood oxygen saturation data and the local tissue hemoglobin concentration index of the tissue to be measured;

[0104] A control processor 8, and the control processor 8 is respectively connected to the signal output end of the light source receiving part 3 and the signal output end of the near-infrared light receiving part 7.

[0105] This system is implemented based on the above method. The specific steps of the method can refer to the above embodiments. Since this system adopts some or all of the technical solutions of the above embodiments, it has at least all the beneficial effects brought by the technical solutions of the above embodiments, and will not be elaborated herein one by one.

[0106] It should be noted that the excitation light source emitter 1 can be an LED laser emitter, which mainly emits ultraviolet light with a wavelength of 360nm to 370nm.

[0107] It should be noted that a mature oximeter N17 is provided in the detection port 2 to measure the local tissue blood oxygen saturation data and the local tissue hemoglobin concentration index.

[0108] It should be noted that the near-infrared light emitter 6 can emit near-infrared light conducted by a near-infrared optical fiber from an LED light source.

[0109] It should be noted that both the transmitting optical fiber 4 and the receiving optical fiber 5 are made of quartz optical fibers, are applicable from UV to visible light, and both the transmitting optical fiber 4 and the receiving optical fiber 5 can conduct specific transmitted light and received light in an endoscopic manner. To meet the above requirements, the total diameter of the transmitting optical fiber 4 and the receiving optical fiber 5 should not exceed 1 mm, and the length should not be shorter than 1 m.

[0110] The core diameter / diameter of the transmitting optical fiber 4 and the receiving optical fiber 5 are 192 / 200 respectively, and its NA = 0.22.

[0111] It should be noted that the transmitting optical fiber 4 can cooperate with an LED laser emitter and conduct ultraviolet light in the form of a pigtail; the end of the receiving optical fiber 5 can provide an FC interface to connect to the optical receiving optical path.

[0112] Figure 6 The structural schematic diagrams of the transmitting optical fiber 4 and the receiving optical fiber 5 provided by the embodiments of the present application are exemplarily shown;

[0113] It should be noted that as Figure 6 shown, the transmitting optical fibers of the transmitting optical fiber 4 are concentrated in the central optical fiber and surrounded by some receiving optical fiber filaments on the periphery (the diameter of the central optical fiber can be 150 μm), and the receiving optical fiber filaments in the receiving optical fiber 5 are arranged in a ring around the central transmitting optical fiber filament (the diameter of a single receiving optical fiber filament can be 200 μm).

[0114] In some optional embodiments, the light source receiving part 3 includes a filter 31, a photomultiplier tube 32 and an amplifier 33; the detection port 2 is connected to the filter 31 through the receiving optical fiber 5, the filter 31 is connected to the photomultiplier tube through the receiving optical fiber 5, the photomultiplier tube 32 is connected to the amplifier 33 through the receiving optical fiber 5, and the amplifier 33 is connected to the control processor 8.

[0115] In the embodiments of the present application, by refining the specific composition of the light source receiving part 3, the optical signal of 450 nm in the receiving optical fiber 5 can be filtered out through the filter 31, and then the optical signal is gradually amplified by the photomultiplier tube 32 and the amplifier 33. Therefore, it is convenient for the control processor 8 to collect and process the signal, and thus the primary can be accurately detected.

[0116] In some optional embodiments, the near-infrared light receiving part 7 includes a near-infrared photomultiplier tube 71. The near-infrared photomultiplier tube is connected to the detection port 2 through the receiving optical fiber 5, and the near-infrared photomultiplier tube 71 is connected to the control processor 8.

[0117] In the embodiment of the present application, by introducing a near-infrared photomultiplier tube 71 into the infrared light receiving part, the optical signal of the receiving optical fiber 5 in the near-infrared light receiving part 7 can be amplified and processed in the control processor 8, so that the tissue blood oxygen saturation data can be accurately detected.

[0118] In some alternative embodiments, the system further includes:

[0119] A spectroscopic part, including a first spectroscope 9 and a second spectroscope 10. One end of the first spectroscope 9 is connected to the detection port 2 through the emission optical fiber 4, and the other end of the first spectroscope 9 is respectively connected to the excitation light source emitter 1 and the near-infrared light emitter 6 through the receiving optical fiber 5;

[0120] The second spectroscope 10 is connected to the detection port 2 through the receiving optical fiber 5, and the second spectroscope 10 is respectively connected to the light source receiving part 3 and the near-infrared light receiving part 7 through the receiving optical fiber 5.

[0121] In the embodiment of the present application, by introducing a spectroscopic part into the system and using the first spectroscope 9, the excitation light source emitter 1 and the near-infrared light emitter 6 can be connected through the emission optical fiber 4 to achieve time-division emission of different light sources. Then, using the second spectroscope 10, the optical signal from the detection port 2 can be divided into batches and enter the control processor 8, avoiding cross-interference between the optical signals of the emission optical fiber 4 and the receiving optical fiber 5, so that data correction can be conveniently performed in the control processor 8 later to obtain accurate target NADH content data.

[0122] The following further elaborates the present application in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present application and not to limit the scope of the present application. The experimental methods without specific conditions noted in the following embodiments are usually measured according to industry standards. If there is no corresponding industry standard, they are carried out according to general international standards, conventional conditions, or conditions recommended by the manufacturer.

[0123] Embodiment 1

[0124] As Figure 4 shown, a system for measuring NADH, the system includes:

[0125] An NADH detection unit, including an excitation light source emitter 1, a detection port 2 and a light source receiving part 3. The excitation light source emitter 1 is connected to the detection port 2 through the emission optical fiber 4, and the light source receiving part 3 is connected to the detection port 2 through the receiving optical fiber 5;

[0126] The tissue blood oxygen detection unit includes a near-infrared light emitter 6 and a near-infrared light receiver 7. The near-infrared light emitter 6 is connected to the detection port 2 through the emission optical fiber 4, and the near-infrared light receiver 7 is connected to the detection port 2 through the reception optical fiber 5;

[0127] A control processor 8, and the control processor 8 is respectively connected to the signal outlet end of the light source receiver 3 and the signal outlet end of the near-infrared light receiver 7.

[0128] The light source receiver 3 includes a filter 31, a photomultiplier tube 32 and an amplifier 33; the detection port 2 is connected to the filter 31 through the reception optical fiber 5, the filter 31 is connected to the photomultiplier tube through the reception optical fiber 5, the photomultiplier tube 32 is connected to the amplifier 33 through the reception optical fiber 5, and the amplifier 33 is connected to the control processor 8.

[0129] The near-infrared light receiver 7 includes a near-infrared photomultiplier tube 71. The near-infrared photomultiplier tube is connected to the detection port 2 through the reception optical fiber 5, and the near-infrared photomultiplier tube 71 is connected to the control processor 8.

[0130] The system further includes:

[0131] A beam splitting unit, including a first beam splitter 9 and a second beam splitter 10. One end of the first beam splitter 9 is connected to the detection port 2 through the emission optical fiber 4, and the other end of the first beam splitter 9 is respectively connected to the excitation light source emitter 1 and the near-infrared light emitter 6 through the reception optical fiber 5;

[0132] The second beam splitter 10 is connected to the detection port 2 through the reception optical fiber 5, and the second beam splitter 10 is respectively connected to the light source receiver 3 and the near-infrared light receiver 7 through the reception optical fiber 5.

[0133] Embodiment 2

[0134] Based on the system obtained in Embodiment 1, the system is further refined:

[0135] As Figure 3 shown, a method for measuring NADH, the method includes:

[0136] S1. Measuring the NADH content of the tissue to be measured by using an excitation light source and a reception light source to obtain the NADH content data of the tissue to be measured;

[0137] S2. Measuring the tissue blood oxygen related data of the tissue to be measured by using a near-infrared light source;

[0138] S311. Selecting a standard NADH solution and performing concentration statistics on the standard NADH solution to obtain the standard NADH solution concentration data;

[0139] S312. Measure the NADH content of the standard NADH solution using an excitation light source and a receiving light source under colorless and constant temperature conditions to obtain the standard NADH content data;

[0140] S313. Construct a standard curve of NADH based on the standard NADH solution concentration data and the standard NADH content data;

[0141] S302. Obtain the NADH content of the tissue to be measured based on the NADH content data of the tissue to be measured and the standard curve of NADH measurement;

[0142] S303. Measure the tissue oxygen saturation and hemoglobin concentration of the standard tissue using a near-infrared light source respectively, and construct a first standard curve for tissue oxygen saturation measurement and a second standard curve for hemoglobin concentration measurement;

[0143] S304. Obtain the local tissue oxygen saturation of the tissue to be measured and the local tissue hemoglobin concentration of the tissue to be measured according to the tissue oxygen-related data of the tissue to be measured, the first standard curve and the second standard curve;

[0144] S305. According to the local tissue oxygen saturation of the tissue to be measured and the local tissue hemoglobin concentration of the tissue to be measured, and combined with the data correction formula, correct the NADH content of the tissue to be measured to eliminate the local tissue oxygen saturation of the tissue to be measured and the local tissue hemoglobin concentration of the tissue to be measured in the NADH content of the tissue to be measured, and obtain the target NADH content data.

[0145] Wherein, the tissue oxygen-related data includes local tissue oxygen saturation data and local tissue hemoglobin concentration index.

[0146] The wavelength of the excitation light source is 365 nm, and the wavelength of the receiving light source is 460 nm.

[0147] The wavelength of the near-infrared light source is 600 nm to 660 nm.

[0148] Example 3

[0149] In the system disclosed in Example 1 and the method disclosed in Example 2, further specific detections are carried out:

[0150] Let the patient lie flat in a supine position, and keep the body as still as possible. Since this system is mainly applied to patients in the intensive care unit, and such patients have a very low movement frequency. At the same time, a urinary catheter is generally placed in the urethral area of the patient, and the function of the urinary catheter itself is to assist the patient in urination. Therefore, when urination is not required, the system can be used for monitoring.

[0151] Since the maximum width of the catheter is about 1 cm, while the inner diameter width of the emission optical fiber 4 used in this system is about 0.52 cm, and the total width including the outer shell is about 0.86 cm. Insert the emission optical fiber 4 into the catheter and make the top contact the mucosa of the patient's urethral wall. After the emission optical fiber 4 is fixed on the mucosa, turn on the LED excitation light source emitter 1 to emit light, so as to irradiate this area of the patient optically, and recover the signal through the receiving optical fiber 5 at a specific wavelength band. The control processor 8 can immediately calculate the content of NADH in the patient, and adopt a long-term monitoring method to observe the change of NADH in the patient's non-vital organs over a long period of time.

[0152] The other end of the receiving optical fiber 5 is connected to a data transmitter, which can calculate and display the acquired data in real time, and the data related to blood oxygen saturation and the data related to NADH are independent and interference-free from each other.

[0153] In the control processor 8, the NADH content data of the tissue to be measured and the tissue blood oxygen related data of the tissue to be measured will go through the following processing process:

[0154] First, refer to the NADH concentration in human tissues, configure a NADH pure solution with a concentration similar to it. Then, under the condition that the voltage of this application system is maintained at 3 V, adjust the concentration of the NADH pure solution as shown in Table 1, and measure the readings (retained to 3 decimal places) at different concentrations as shown in Table 1. At the same time, use the linear regression method to draw a linear curve, and obtain the formula and correlation coefficient of the curve, as Figure 8 shown. Its linear curve is: y = 48.716x + 14.329, where R 2 = 0.8816, which indicates that the correlation of this linear curve is good.

[0155] Table 1 Data table of the linear curve of NADH pure solution

[0156]

[0157] Then, continuously add fresh blood to this NADH pure solution to measure the NADH values of this application system at different blood concentrations respectively.

[0158] Finally, use the blood oxygen detection device N17 of Aegean Medical to detect the device readings, local tissue oxygen saturation (TOI) and local tissue hemoglobin concentration index (THI) of the freshly added blood at different concentrations respectively. Fit the three indicators of device reading, TOI and THI at the same concentration using a linear model to obtain a modified NADH value formula:

[0159] y = 0.575×A + 0.934×B + 40.298×C.

[0160] In the formula, y is the target NADH content data;

[0161] A is the NADH content data of the tissue to be measured;

[0162] B is the local tissue oxygen saturation data;

[0163] C is the local tissue hemoglobin concentration index.

[0164] The specific operation of the above process is as follows: First, without adding blood and in the case of a pure NADH solution, measure the value of the N17 device of the oximeter as the standard value, and then gradually increase the blood proportionally to measure the value of the N17 device of the oximeter, the local tissue oxygen saturation (TOI), and the local tissue hemoglobin concentration index (THI) under different blood concentration conditions. The results are shown in Table 2. Under the assumption of a linear model, use linear regression to deduce the model formula and calculate the prediction accuracy of the model. The results are shown in Table 3.

[0165] Table 2 Readings of the N17 device of the oximeter, local tissue oxygen saturation, and local tissue hemoglobin concentration index under different blood concentration conditions

[0166]

[0167] Table 3 Calculation results of accuracy

[0168] NADH reading TOI (%) THI y y_linear_model Accuracy rate (%) 62 95.60 1.152 174 171.452 94.536 86 93.20 0.965 174 175.498 95.139 102 91.80 0.724 174 173.694 94.163 125 84 0.663 174 177.196 95.416 146 74.5 0.529 174 175.016 95.416 157 71.6 0.381 174 172.678 95.240 167 70.10 0.264 174 172.322 95.036

[0169] Comparative Example 1

[0170] Compare Comparative Example 1 with Example 1. The differences between Comparative Example 1 and Example 1 are as follows:

[0171] Figure 7 Exemplarily shows the schematic diagram of the Israeli product system provided by Comparative Example 1 of the present application;

[0172] The Israeli product is as Figure 7 shown. When conducting research in the laboratory, place the optical fiber in the gerbil's brain and isolate the animal from oxygen. It is found that after oxygen deprivation, the measured change in NADH of the animal shows a rapid change.

[0173] In summary, a method for measuring NADH provided by an embodiment of the present application first measures the NADH content data of the tissue to be measured in the tissue to be measured through an excitation light source and a receiving light source, and then measures the tissue oxygen saturation in the tissue to be measured through near-infrared light, and can measure tissue oxygen-related data such as hemoglobin and deoxyhemoglobin in the tissue to be measured. Finally, use the data correction method to correct the tissue oxygen-related data in the NADH content data of the tissue to be measured, so as to obtain accurate target NADH content data.

[0174] Meanwhile, a method for measuring NADH provided by an embodiment of the present application can achieve an accuracy rate of 95.1% or more for the data correction formula constructed by this method.

[0175] Various embodiments of the present application may exist in the form of a range; it should be understood that the description in the form of a range is only for convenience and brevity, and should not be construed as a rigid limitation on the scope of the present application; therefore, it should be considered that the range description has specifically disclosed all possible sub-ranges and individual values within that range. For example, it should be considered that the range description from 1 to 6 has specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and individual numbers within that range, such as 1, 2, 3, 4, 5, and 6, and this applies regardless of the range. Additionally, whenever a numerical range is indicated herein, it means including any cited number (fraction or integer) within the indicated range.

[0176] In the present application, unless otherwise stated, the orientation terms such as "upper" and "lower" specifically refer to the drawing directions in the drawings. Additionally, in the description of the specification of the present application, the terms "comprising", "including", etc. mean "including but not limited to". In this text, relational terms such as "first" and "second" are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. In this text, "and / or" describes the association relationship of associated objects and indicates that three relationships may exist. For example, A and / or B may represent: A exists alone, A and B exist simultaneously, and B exists alone. Where A and B may be singular or plural. In this text, "at least one" means one or more, and "multiple" means two or more. "At least one kind", "at least one of the following items (pieces)" or similar expressions refer to any combination of these items, including any combination of single item (piece) or plural items (pieces). For example, "at least one of a, b, or c", or, "at least one of a, b, and c" can both represent: a, b, c, a - b (i.e., a and b), a - c, b - c, or a - b - c, where a, b, and c can be single or multiple respectively.

[0177] The above description is only the specific embodiments of the present application, enabling those skilled in the art to understand or implement the present application. Various modifications to these embodiments will be obvious to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to these embodiments shown herein, but rather to the broadest scope consistent with the principles and novel features claimed herein.

Claims

1. A method for measuring NADH, characterized in that, The method includes: Measuring the NADH content data of the tissue to be measured using an excitation light source and a receiving light source; Measuring the tissue blood oxygen related data of the tissue to be measured using a near-infrared light source; Data-correcting the NADH content data of the tissue to be measured according to the tissue blood oxygen related data of the tissue to be measured to obtain the target NADH content data; Wherein, the tissue blood oxygen related data includes local tissue blood oxygen saturation data and local tissue hemoglobin concentration index; The formula used for the data correction is: y = 0.575×A + 0.934×B + 40.298×C; In the formula, y is the target NADH content data; A is the NADH content data of the tissue to be measured; B is the local tissue blood oxygen saturation data; C is the local tissue hemoglobin concentration index.

2. The method according to claim 1, wherein The data-correcting the NADH content data of the tissue to be measured according to the tissue blood oxygen related data of the tissue to be measured includes: Measuring the NADH content data of a standard NADH solution using the excitation light source and the receiving light source under colorless and constant temperature conditions, and constructing a standard curve for NADH measurement in combination with the concentration data of the standard NADH solution; Obtaining the NADH content of the tissue to be measured according to the NADH content data of the tissue to be measured and the standard curve for NADH measurement; Measuring the local tissue blood oxygen saturation and local tissue hemoglobin concentration of a standard tissue using a near-infrared light source respectively to construct a first standard curve for measuring local tissue blood oxygen saturation and a second standard curve for measuring local tissue hemoglobin concentration; Obtaining the local tissue blood oxygen saturation of the tissue to be measured and the local tissue hemoglobin concentration of the tissue to be measured according to the tissue blood oxygen related data of the tissue to be measured, the first standard curve and the second standard curve; Data-correcting the NADH content of the tissue to be measured according to the local tissue blood oxygen saturation of the tissue to be measured and the local tissue hemoglobin concentration of the tissue to be measured, and in combination with the data correction formula to eliminate the local tissue blood oxygen saturation of the tissue to be measured and the local tissue hemoglobin concentration of the tissue to be measured in the NADH content of the tissue to be measured to obtain the target NADH content data.

3. The method according to claim 2, wherein The measuring the NADH content data of a standard NADH solution using the excitation light source and the receiving light source under colorless and constant temperature conditions, and constructing a standard curve for NADH measurement in combination with the concentration data of the standard NADH solution includes the steps: Selecting a standard NADH solution and performing concentration statistics on the standard NADH solution to obtain standard NADH solution concentration data; Measuring the NADH content of the standard NADH solution using the excitation light source and the receiving light source under colorless and constant temperature conditions to obtain standard NADH content data; Constructing a standard curve for NADH according to the standard NADH solution concentration data and the standard NADH content data.

4. The method according to claim 1, wherein The wavelength of the excitation light source is 360nm - 370nm.

5. The method according to claim 1, wherein The wavelength of the receiving light source is 450m - 470nm.

6. The method according to claim 1, wherein The wavelength of the near-infrared light source is 600nm to 660nm.

7. A system for measuring NADH, characterized in that, The system is adapted to the method according to any one of claims 1-6, and the system includes: An NADH detection unit, including an excitation light source emitter (1), a detection port (2), and a light source receiving part (3). The excitation light source emitter (1) is connected to the detection port (2) through a transmission optical fiber (4), and the light source receiving part (3) is connected to the detection port (2) through a receiving optical fiber (5) to measure the NADH content data of the tissue to be measured; A tissue blood oxygen detection unit, including a near-infrared light emitter (6) and a near-infrared light receiving part (7). The near-infrared light emitter (6) is connected to the detection port (2) through the transmission optical fiber (4), and the near-infrared light receiving part (7) is connected to the detection port (2) through the receiving optical fiber (5) to detect the local tissue blood oxygen saturation data and the local tissue hemoglobin concentration index of the tissue to be measured; A control processor (8), and the control processor (8) is respectively connected to the signal output end of the light source receiving part (3) and the signal output end of the near-infrared light receiving part (7).

8. The system according to claim 7, wherein The light source receiving part (3) includes a filter (31), a photomultiplier tube (32), and an amplifier (33); the detection port (2) is connected to the filter (31) through the receiving optical fiber (5), the filter (31) is connected to the photomultiplier tube through the receiving optical fiber (5), the photomultiplier tube (32) is connected to the amplifier (33) through the receiving optical fiber (5), and the amplifier (33) is connected to the control processor (8).

9. The system according to claim 7, wherein The near-infrared light receiving part (7) includes a near-infrared light multiplier tube (71). The near-infrared light multiplier tube is connected to the detection port (2) through the receiving optical fiber (5), and the near-infrared light multiplier tube (71) is connected to the control processor (8).

10. The system according to claim 9, wherein The system further includes: A spectroscope part, including a first spectroscope (9) and a second spectroscope (10). One end of the first spectroscope (9) is connected to the detection port (2) through a transmission optical fiber (4), and the other end of the first spectroscope (9) is respectively connected to the excitation light source emitter (1) and the near-infrared light emitter (6) through a receiving optical fiber (5); The second spectroscope (10) is connected to the detection port (2) through the receiving optical fiber (5), and the second spectroscope (10) is respectively connected to the light source receiving part (3) and the near-infrared light receiving part (7) through the receiving optical fiber (5).

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