System for measuring NADH

Abstract

The utility model relates to the technical field of medical instruments, in particular to a system for measuring NADH, and the system comprises an NADH detection unit which comprises an excitation light source emitter, a detection port and a light source receiving part, the excitation light source emitter is communicated with the detection port through an emission optical fiber, and the light source receiving part is communicated with the detection port through a receiving optical fiber; the tissue blood oxygen detection unit comprises a near-infrared light emitter and a near-infrared light receiving part, the near-infrared light emitter is communicated with the detection port through an emitting optical fiber, and the near-infrared light receiving part is communicated with the detection port through a receiving optical fiber; the control processor is communicated with the signal outlet end of the light source receiving part and the signal outlet end of the near-infrared light receiving part; nADH content data of a to-be-detected tissue is measured through the NADH detection unit, tissue blood oxygen related data of the to-be-detected tissue is measured through the tissue blood oxygen detection unit, and then the data are collected and processed through the control processor so as to obtain accurate target NADH content data.

Description

Technical Field

[0001] The present application relates to the field of medical device technology, and in particular to a system 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 oxygen supply can be discovered more promptly, making it easier for medical staff to intervene and treat in a timely manner. The main place 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 imbalances within and between the microcirculation and mitochondrial dysfunction, both of which are directly related to organ dysfunction and poor prognosis. For example, microcirculatory dysfunction can prevent adequate oxygen delivery to parenchymal cells, while mitochondrial dysfunction can lead to abnormal energy metabolism, which in turn leads to impaired oxygen utilization in tissues and cells. Therefore, real-time mitochondrial function testing is a beneficial approach to understanding the patient's condition and buying time for treatment.

[0004] NADH (Nicotinamide adenine dinucleotide) is a chemical substance, generally referring to the reduced form of coenzyme I, and is a control marker in the energy production chain in mitochondria. Because NADH is primarily involved in cellular metabolism and energy production, and is produced in the citric acid cycle during glycolysis and cellular respiration, monitoring the redox state of NADH is the best parameter for characterizing mitochondrial function in vivo. Current NADH absorption spectrum analysis indicates that NADH absorbs light between 300 and 380 nm and emits fluorescence between 420 and 480 nm. Therefore, spectroscopic detection of NADH allows for real-time monitoring of mitochondrial function. However, current systems using spectroscopic NADH detection typically measure NADH in human cells. However, the presence of numerous interfering factors in the human body, such as the concentrations of hemoglobin and deoxyhemoglobin, can significantly interfere with detection accuracy. Utility Model Content

[0005] The present application provides a system for measuring NADH to solve the technical problem of poor accuracy of the existing system for detecting NADH in vivo based on optical principles.

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

[0007] The NADH detection unit includes an excitation light source transmitter, a detection port, and a light source receiving unit, wherein the excitation light source transmitter is connected to the detection port via a transmitting optical fiber, and the light source receiving unit is connected to the detection port via a receiving optical fiber to obtain primary NADH data;

[0008] a tissue blood oxygen detection unit, comprising a near-infrared light emitter and a near-infrared light receiving unit, wherein the near-infrared light emitter is connected to the detection port via the transmitting optical fiber, and the near-infrared light receiving unit is connected to the detection port via the receiving optical fiber, so as to detect local tissue blood oxygen saturation data and local tissue hemoglobin concentration index;

[0009] A control processor is connected to the signal output end of the light source receiving part and the signal output end of the near-infrared light receiving part, respectively, so as to perform data correction on the primary NADH data according to the local tissue blood oxygen saturation data and the local tissue hemoglobin concentration index.

[0010] Optionally, the excitation light source emitter is connected to the detection port through the emission optical fiber.

[0011] Optionally, the light source receiving part includes a filter, a photomultiplier tube and an amplifier; the detection port is connected to the filter through the receiving optical fiber, the filter is connected to the optical fiber multiplier tube through the receiving optical fiber, the photomultiplier tube is connected to the amplifier through the receiving optical fiber, and the amplifier is connected to the control processor.

[0012] Optionally, the near-infrared light emitter is connected to the detection port via the emission optical fiber.

[0013] Optionally, the near-infrared light receiving unit includes a near-infrared light multiplier tube, the near-infrared light multiplier tube is connected to the detection port through the receiving optical fiber, and the near-infrared light multiplier tube is connected to the control processor.

[0014] Optionally, the system further includes:

[0015] The spectrometer includes a first spectrometer and a second spectrometer. One end of the first spectrometer is connected to the detection port through a transmitting optical fiber, and the other end of the first spectrometer is connected to the excitation light source emitter and the near-infrared light emitter respectively through a receiving optical fiber.

[0016] Optionally, the spectroscopic part further includes a second spectrometer, the second spectrometer is connected to the detection port via the receiving optical fiber, and the second spectrometer is respectively connected to the light source receiving part and the near-infrared light receiving part via the receiving optical fiber.

[0017] Optionally, the fiber diameters of the transmitting optical fiber and the receiving optical fiber are both ≤1 mm.

[0018] Optionally, the lengths of the transmitting optical fiber and the receiving optical fiber are both ≥1 m.

[0019] Optionally, the numerical apertures of the transmitting optical fiber and the receiving optical fiber are 0.20 to 0.23.

[0020] The above technical solution provided by the embodiment of the present application has the following advantages compared with the prior art:

[0021] An embodiment of the present application provides a system for measuring NADH. Since color and temperature changes of the tissue to be measured may interfere with the accuracy of the measurement results to a certain extent when measuring NADH, and excessive interfering substances in the tissue to be measured may also affect the accuracy of optical detection, the excitation light source of the excitation light source emitter and the receiving light source are used to first measure the NADH content data of the tissue to be measured in the detection port. Then, the near-infrared light emitter and the near-infrared light receiving part of the tissue blood oxygen detection unit cooperate to measure the local tissue blood oxygen saturation and tissue blood oxygen related data such as local tissue hemoglobin and deoxyhemoglobin in the tissue to be measured by near-infrared light. Finally, a control processor is used to collect and process these data, and the blood oxygen related data in the NADH content data of the tissue to be measured is eliminated through data correction, so as to obtain accurate target NADH content data. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present application and, together with the description, serve to explain the principles of the present application.

[0023] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0024] Figure 1 A schematic diagram of the system structure for measuring NADH provided in an embodiment of the present application;

[0025] Figure 2 A logic diagram of a system for measuring NADH provided in an embodiment of the present application;

[0026] Figure 3 A schematic diagram of the structure of the transmitting optical fiber and the receiving optical fiber provided in an embodiment of the present application;

[0027] Figure 4 Schematic diagram of the Israeli product system structure provided for Comparative Example 1 of this application;

[0028] Figure 5 This is a schematic diagram of the linear curve of the pure NADH solution provided in Example 2 of the present application;

[0029] Among them, 1-excitation light source emitter, 2-detection port, 3-light source receiving part, 31-filter, 32-photomultiplier tube, 33-amplifier, 4-emitting 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 spectrometer, 10-second spectrometer. DETAILED DESCRIPTION

[0030] To make the purpose, technical solutions, and advantages of the embodiments of this application more clear, the technical solutions in the embodiments of this application will be clearly and completely described below in conjunction with the drawings in the embodiments of this application. Obviously, the described embodiments are part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0031] It should be noted that all directional indications such as up, down, left, right, front, and back in the embodiments of the present invention are only used to explain the relative positional relationship and movement of the components in a specific posture (such as shown in the accompanying drawings). If the specific posture changes, the directional indication will also change accordingly.

[0032] In this utility model, unless otherwise specified or limited, the terms "connection" and "fixation" should be understood in a broad sense. For example, "fixation" can mean fixed connection, detachable connection, or integration; it can be mechanical connection or electrical connection; it can be direct connection or indirect connection through an intermediate medium; it can mean internal communication between two elements or interaction between two elements, unless otherwise specified. For those skilled in the art, the specific meanings of the above terms in this utility model can be understood according to specific circumstances.

[0033] Currently, the devices that use spectral detection for NADH include: (1) Israel CritiView, which measures from the urethral wall, uses a 375nm laser Doppler as the emission light source, a 450nm as the receiving unit, and uses multiple measurement wavelengths, which are combined through a dichroic beam splitter and coupled to a single excitation fiber. This product has been used in experiments on animals (rodents) and tissue cells. Because this product does not have a clinical registration certificate and cannot be used in clinical trials, it can only be used in the laboratory. At the same time, the results obtained by this product are only the electrical signals of the returned fluorescence, and many interference factors in the body (such as the concentration of hemoglobin and deoxyhemoglobin) are not removed. Therefore, the measured results cannot be used clinically.

[0034] (2) AngioExpert from Poland. This product is similar in shape to a sphygmomanometer and is used to measure NADH in epidermal cells of the upper arm. However, this product is rarely used, and the data it measures is not universally meaningful. Furthermore, the measured signal still does not eliminate the influence of interference factors in the human body.

[0035] Therefore, the current system for detecting NADH in the body based on optical principles has a problem of poor accuracy due to the presence of interference factors in the human body.

[0036] Figure 1 The following is a schematic diagram of the structure of a system for measuring NADH provided in an embodiment of the present application;

[0037] Figure 2 The following is an exemplary diagram of a system logic diagram for measuring NADH provided in an embodiment of the present application;

[0038] like Figure 1 and Figure 2 As shown, the embodiment of the present application provides a system for measuring NADH, the system comprising:

[0039] The NADH detection unit includes an excitation light source transmitter 1, a detection port 2, and a light source receiving unit 3. The excitation light source transmitter 1 is connected to the detection port 2 via a transmitting optical fiber 4, and the light source receiving unit 3 is connected to the detection port 2 via a receiving optical fiber 5 to obtain primary NADH data.

[0040] The tissue blood oxygen detection unit includes a near-infrared light emitter 6 and a near-infrared light receiving unit 7. The near-infrared light emitter 6 is connected to the detection port 2 through the transmitting optical fiber 4, and the near-infrared light receiving unit 7 is connected to the detection port 2 through the receiving optical fiber 5 to detect local tissue blood oxygen saturation data and local tissue hemoglobin concentration index;

[0041] A control processor 8 is 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, respectively, so as to perform data correction on the primary NADH data according to the local tissue blood oxygen saturation data and the local tissue hemoglobin concentration index.

[0042] 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.

[0043] 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 of the tissue to be tested.

[0044] It should be noted that the near-infrared light emitter 6 can be a near-infrared light emitted by an LED light source and transmitted by a near-infrared optical fiber.

[0045] It should be noted that the transmitting optical fiber 4 can cooperate with the LED laser transmitter and transmit ultraviolet light in the form of a pigtail; the end of the receiving optical fiber 5 can provide an FC interface to connect with the light receiving optical path.

[0046] It should be noted that the PLC processing chip in the control processor 8 can be written with the formula used for data correction:

[0047] y=0.575×A+0.934×B+40.298×C;

[0048] Wherein, y is the target NADH content data;

[0049] A is the NADH content data of the tissue to be tested;

[0050] B is the local tissue oxygen saturation data;

[0051] C is the local tissue hemoglobin concentration index.

[0052] 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 optical fiber multiplier 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.

[0053] In the embodiment of the present application, by refining the specific composition of the light source receiving part 3, the 450nm light signal in the receiving optical fiber 5 can be filtered out by means of the filter 31, and then the light signal is gradually amplified through the photomultiplier tube 32 and the amplifier 33. Therefore, it is convenient to control the processor 8 to collect and process the signal, so that the NADH content data of the tissue to be tested can be accurately detected.

[0054] In some optional embodiments, the near-infrared light receiving unit 7 includes a near-infrared light multiplier tube 71 , which is connected to the detection port 2 via the receiving optical fiber 5 , and the near-infrared light multiplier tube 71 is connected to the control processor 8 .

[0055] In the embodiment of the present application, by introducing a near-infrared light multiplier tube 71 into the infrared light receiving part, the light 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 tissue blood oxygen related data can be accurately detected.

[0056] In some optional embodiments, the system further comprises:

[0057] The optical splitter includes a first optical splitter 9 and a second optical splitter 10, one end of the first optical splitter 9 is connected to the detection port 2 through the transmitting optical fiber 4, and the other end of the first optical splitter 9 is connected to the excitation light source emitter 1 and the near-infrared light emitter 6 respectively through the receiving optical fiber 5;

[0058] The second optical splitter 10 is connected to the detection port 2 through the receiving optical fiber 5 , and the second optical splitter 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 .

[0059] In an embodiment of the present application, a spectroscopic part is introduced into the system, and the first spectrometer 9 is used to connect the excitation light source emitter 1 and the near-infrared light emitter 6 through the transmitting optical fiber 4, so as to realize time-sharing emission of different light sources. Then, the second spectrometer 10 is used to allow the optical signals coming out of the detection port 2 to enter the control processor 8 in batches, avoiding cross-influence between the optical signals of the transmitting optical fiber 4 and the receiving optical fiber 5, thereby facilitating subsequent data correction in the control processor 8 to obtain accurate target NADH content data.

[0060] In some optional embodiments, the fiber diameters of the transmitting optical fiber 4 and the receiving optical fiber 5 are both ≤1 mm.

[0061] In some optional embodiments, the lengths of the transmitting optical fiber 4 and the receiving optical fiber 5 are both ≥1 m.

[0062] In some optional embodiments, the numerical apertures of the transmitting optical fiber 4 and the receiving optical fiber 5 are 0.20 to 0.23.

[0063] In the embodiment of the present application, since the overall device needs to use spectral signals to achieve measurement, and the transmitting optical fiber 4 and the receiving optical fiber 5 can generally use quartz optical fiber, and are applicable from UV to visible, and the transmitting optical fiber 4 and the receiving optical fiber 5 need to transmit specific transmitting light and receiving light in an endoscopic manner, in order to meet the above requirements, the total diameter of the transmitting optical fiber 4 and the receiving optical fiber 5 needs to be controlled not to exceed 1 mm, and the length must be not less than 1 m, and at the same time, the numerical aperture of the transmitting optical fiber and the receiving optical fiber must be controlled to be 0.20~0.23.

[0064] It should be noted that, in order to obtain the best signal transmission effect, the core diameter / diameter of the transmitting optical fiber 4 and the receiving optical fiber 5 can be 192 μm / 200 μm respectively, and the NA thereof can be 0.22.

[0065] Figure 3 The schematic diagram of the structure of the transmitting optical fiber 4 and the receiving optical fiber 5 provided in the embodiment of the present application is exemplarily shown;

[0066] It should be noted that if Figure 3 As shown, the transmitting optical fiber 4 is concentrated in the central optical fiber and surrounded by a portion of the receiving optical fiber (the diameter of the central optical fiber can be 150 μm), and the receiving optical fiber filaments in the receiving optical fiber 5 are surrounded in a ring shape by the transmitting optical fiber in the center (the diameter of a single receiving optical fiber can be 200 μm).

[0067] Based on the above system, an embodiment of the present application further provides a method for measuring NADH, the method comprising:

[0068] S1. Determine the NADH content of the tissue under test using an excitation light source and a receiving light source;

[0069] S2. Using a near-infrared light source to measure tissue blood oxygenation data of the tissue under test;

[0070] S3. Select a standard NADH solution and perform concentration statistics on the standard NADH solution to obtain standard NADH solution concentration data;

[0071] S4. Determine 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;

[0072] S5. constructing a standard curve of NADH based on the standard NADH solution concentration data and the standard NADH content data;

[0073] S6. respectively measuring the local tissue oxygen saturation and the local tissue hemoglobin concentration of the standard tissue using a near-infrared light source 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;

[0074] S7. Obtaining the local tissue oxygen saturation and the local tissue hemoglobin concentration of the tissue to be tested based on the tissue oxygenation-related data of the tissue to be tested, the first standard curve, and the second standard curve;

[0075] S8. Correcting the NADH content of the tissue to be tested based on the local tissue oxygen saturation and the local tissue hemoglobin concentration of the tissue to be tested, in combination with a data correction formula, to eliminate the local tissue oxygen saturation and the local tissue hemoglobin concentration of the tissue to be tested from the NADH content of the tissue to be tested, thereby obtaining target NADH content data;

[0076] Wherein, the tissue blood oxygen related data includes local tissue blood oxygen saturation data and local tissue hemoglobin concentration index;

[0077] The formula used for data correction is:

[0078] y=0.575×A+0.934×B+40.298×C;

[0079] Wherein, y is the numerical value of the accurate NADH content data;

[0080] A is the numerical value of the primary NADH data;

[0081] B is the local tissue oxygen saturation data;

[0082] C is the local tissue hemoglobin concentration index.

[0083] In the embodiment of the present application, by introducing a specific formula used for data correction, the relationship between tissue blood oxygenation-related data and the NADH content data of the tissue to be measured can be clarified. Therefore, through data correction, tissue blood oxygenation-related data such as local tissue oxygen saturation and local tissue hemoglobin concentration can be directly eliminated from the NADH content data of the tissue to be measured, thereby obtaining accurate target NADH content data.

[0084] It should be noted that the tissue to be tested refers to the tissue site in the body where NADH needs to be detected, which can be the subcutaneous tissue site.

[0085] It should be noted that the NADH standard solution is prepared by enzymatically digesting tissue using a NADH standard kit to obtain a uniformly dispersed tissue standard NADH solution, thereby obtaining standard NADH solution concentration data.

[0086] It should be noted that due to the characteristics of optical measurement, both color and temperature changes can interfere with the measurement. Therefore, a standard NADH solution is first selected, and quantitative measurements are performed using an excitation light source and a receiving light source in a colorless and constant temperature environment. This establishes the corresponding relationship between the system's measured readings and the concentration of the standard NADH solution. This also determines the relationship between the readings and NADH concentrations measured under other conditions. Furthermore, at the tissue level, freshly sampled animal tissue blocks are selected, and an NADH standard kit is used. Enzymatic NADH measurements are performed at the tissue level. This establishes a relationship between the measured readings and tissue NADH concentrations, thus facilitating quantitative processing of the tissue being measured.

[0087] It should be noted that since the human body is a complex tissue containing many chemical substances, there must be other substances in the NADH measurement band, which will interfere with the measurement results. Therefore, in the actual measurement stage, a blood decomposition method is used to continuously subdivide the blood, for example, into plasma, serum, and red blood cells, and the substances that have a greater interference with the reading are determined among these components. At the same time, a mature oximeter (N17) produced by the applicant is used to measure the interfering substances. The changes in the interfering substances measured by the oximeter are then combined with the NADH content data of the tissue to be tested measured by the system of the present application, and combined with algorithm correction, the data correction related formula is calculated to improve the measurement reading accuracy. Therefore, decomposing the chemical components in the tissue to be tested and blood can remove the interference of tissue blood oxygen related data on the reading, thereby making the measurement more accurate.

[0088] The N17 oximeter uses a unique spatial resolution algorithm (SAS), while other similar products generally use a modified Beer-Lambert law. Compared to the modified Beer-Lambert law, the SAS spatial resolution algorithm can additionally measure local tissue oxygen saturation and is less susceptible to the influence of outer tissue layers. The device received CFDA certification in 2020. For specific detection principles and equipment, please refer to the following patents: CN201810481778.7 - Near-infrared non-invasive detection method for human tissue hemoglobin concentration index; CN200310103053.8 - Non-destructive monitoring method and system for blood oxygen metabolism in biological tissue using diffuse light; and CN200610112598.9 - Method for detecting the absolute concentration of oxygenated and reduced hemoglobin in human tissue.

[0089] It should be noted that by determining a specific standard curve for blood oxygen saturation measurement, and based on this standard curve, combined with tissue blood oxygen related data, the specific content of interfering substances in the tissue to be tested can be deduced, thereby facilitating the subsequent elimination of tissue blood oxygen related data from the NADH content data of the tissue to be tested through data correction.

[0090] In some optional embodiments, the wavelength of the excitation light source is 360 nm to 370 nm.

[0091] In some optional embodiments, the wavelength of the receiving light source is 450 nm to 470 nm.

[0092] In the embodiment of the present application, the specific wavelength of the excitation light source and the specific wavelength of the receiving light source are limited. Since NADH can absorb light from 300nm to 380nm and emit fluorescence at 420nm to 480nm, setting the specific wavelength of the excitation light source and the specific wavelength of the receiving light source can avoid the influence of interfering substances.

[0093] The wavelength of the excitation light source may be 360 ​​nm, 361 nm, 362 nm, 363 nm, 364 nm, 365 nm, 366 nm, 367 nm, 368 nm, 369 nm or 370 nm.

[0094] The wavelength of the receiving light source may be 450 nm, 452 nm, 454 nm, 456 nm, 458 nm, 460 nm, 462 nm, 464 nm, 466 nm, 468 nm or 470 nm.

[0095] It should be noted that, based on the system's operation and detection costs as well as safety considerations, a 365nm LED can be selected as the excitation light source, while a 460nm LED can be selected as the receiving light source.

[0096] In some optional embodiments, the wavelength of the near-infrared light source is 600 nm to 660 nm.

[0097] In the embodiment of the present application, limiting the specific wavelength of near-infrared light can more accurately detect the local tissue oxygen saturation. At the same time, this wavelength has a better measurement effect on the local tissue oxygenated hemoglobin in the tissue.

[0098] The present application will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present application only and are not intended to limit the scope of the present application. The experimental methods in the following examples where specific conditions are not specified are generally measured according to industry standards. If there are no corresponding industry standards, then the methods are carried out according to general international standards, conventional conditions, or the conditions recommended by the manufacturer.

[0099] Example 1

[0100] like Figure 1 and Figure 2 As shown, a system for measuring NADH, the system comprising:

[0101] The NADH detection unit includes an excitation light source transmitter 1, a detection port 2, and a light source receiving unit 3. The excitation light source transmitter 1 is connected to the detection port 2 via a transmitting optical fiber 4, and the light source receiving unit 3 is connected to the detection port 2 via a receiving optical fiber 5.

[0102] The tissue blood oxygen detection unit includes a near-infrared light emitter 6 and a near-infrared light receiving unit 7. The near-infrared light emitter 6 is connected to the detection port 2 through the transmitting optical fiber 4, and the near-infrared light receiving unit 7 is connected to the detection port 2 through the receiving optical fiber 5.

[0103] The control processor 8 is 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 respectively.

[0104] 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 optical fiber multiplier 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.

[0105] The near-infrared light receiving unit 7 includes a near-infrared light multiplier tube 71 . The near-infrared light multiplier tube 71 is connected to the detection port 2 via the receiving optical fiber 5 . The near-infrared light multiplier tube 71 is connected to the control processor 8 .

[0106] The system also includes:

[0107] The optical splitter includes a first optical splitter 9 and a second optical splitter 10. One end of the first optical splitter 9 is connected to the detection port 2 through the transmitting optical fiber 4, and the other end of the first optical splitter 9 is connected to the excitation light source emitter 1 and the near-infrared light emitter 6 through the receiving optical fiber 5;

[0108] The second optical splitter 10 is connected to the detection port 2 through the receiving optical fiber 5 , and the second optical splitter 10 is connected to the light source receiving part 3 and the near-infrared light receiving part 7 through the receiving optical fiber 5 .

[0109] The diameter of the transmitting optical fiber and the receiving optical fiber is ≤1 mm. The length of the transmitting optical fiber and the receiving optical fiber is ≥1 m.

[0110] The numerical aperture of the transmitting fiber and the receiving fiber is 0.22.

[0111] The wavelength of the excitation light source of the excitation light source transmitter 1 is 365 nm, and the wavelength of the receiving light source in the light source receiving part 3 is 460 nm.

[0112] The wavelength of the near-infrared light source is 600nm to 660nm.

[0113] Example 2

[0114] In the system disclosed in Example 1, further specific detection is performed:

[0115] Have the patient lie flat on his back and keep the body as still as possible, because this system is mainly used for patients in intensive care units, who rarely move. At the same time, a catheter is generally placed in the patient's urethra area, and the function of the catheter itself is to assist the patient in urination. Therefore, when there is no need to urinate, the system can be used for monitoring.

[0116] Since the maximum width of the catheter is about 1 cm, and the inner diameter width of the transmitting optical fiber 4 used in the system is about 0.52 cm, and the total width including the outer shell is about 0.86 cm, the transmitting optical fiber 4 is inserted into the catheter and the top end contacts the mucosa of the patient's urethral wall. After the transmitting optical fiber 4 is fixed on the mucosa, the LED excitation light source transmitter 1 is turned on to generate light to optically irradiate the area of ​​the patient, and the signal is recovered through the receiving optical fiber 5 in a specific band. The control processor 8 can instantly calculate the patient's NADH content, and a long-term monitoring method is used to observe the changes in NADH in the patient's non-vital organs over a long period of time.

[0117] 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 blood oxygen saturation related data and the NADH related data are independent of each other without interference.

[0118] In the control processor 8, the measured NADH content data and tissue blood oxygen related data of the tissue to be tested will undergo the following processing:

[0119] First, referring to the NADH concentration in human tissue, a pure NADH solution with a concentration close to that in human tissue was prepared. Then, while maintaining a voltage of 3V in the system of the present application, the concentration of the pure NADH solution was adjusted as shown in Table 1. The readings were measured at different concentrations (retaining 3 decimal places) as shown in Table 1. At the same time, a linear curve was drawn using linear regression to obtain the formula and correlation coefficient of the curve, as shown in Table 1. Figure 5 As shown, its linear curve is: y = 48.716x + 14.329, where R 2 =0.8816, which shows that the correlation of the linear curve is good.

[0120] Table 1 Linear curve data of NADH pure solution

[0121]

[0122] Then, fresh blood was continuously added to the pure NADH solution, and the NADH values ​​at different blood concentrations were measured. Finally, using Aegean Medical's blood oxygen detection device N17, the device readings, local tissue oxygen saturation (TOI), and local tissue hemoglobin concentration index (THI) of the newly added blood at different concentrations were measured. The device readings, TOI, and THI at the same concentration were fitted using a linear model to obtain the revised NADH value formula:

[0123] y=0.575×A+0.934×B+40.298×C.

[0124] Where y is the numerical value of the accurate NADH content data;

[0125] A is the value of primary NADH data;

[0126] B is the local tissue oxygen saturation data;

[0127] C is the local tissue hemoglobin concentration index.

[0128] The specific operation of the above process is as follows: First, without adding blood, in the presence of pure NADH solution, the value of the oximeter N17 device is measured as the standard value. Then, blood is gradually added proportionally to measure the oximeter N17 device value, local tissue oxygen saturation (TOI), and 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, linear regression is used to derive the model formula, and the model prediction accuracy is calculated. The results are shown in Table 3.

[0129] Table 2 Oximeter N17 device readings, local tissue oxygen saturation and local tissue hemoglobin concentration index under different blood concentration conditions

[0130]

[0131] Table 3 Accuracy calculation results

[0132] NADH readings TOI (%) THI y y_linear_model Accuracy (%) 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

[0133] Comparative Example 1

[0134] Comparing Comparative Example 1 with Example 1, the difference between Comparative Example 1 and Example 1 is:

[0135] Figure 4 The schematic diagram of the structure of the Israeli product system provided in Comparative Example 1 of the present application is shown as an example;

[0136] Israeli products such as Figure 4As shown, during the study in the laboratory, optical fibers were placed in the brains of gerbils and the animals were deprived of oxygen. It was found that after oxygen was cut off, the amount of NADH measured in the animals changed rapidly.

[0137] In summary, the embodiment of the present application provides a system for measuring NADH, which first measures the NADH content data of the tissue to be measured in the detection port 2 through the excitation light source and the receiving light source of the excitation light source transmitter 1, and then uses the near-infrared light transmitter 6 and the near-infrared light receiving part 7 in the tissue blood oxygen detection unit to measure the local tissue blood oxygen saturation in the tissue to be measured and measure the tissue blood oxygen related data such as local tissue hemoglobin and deoxyhemoglobin in the tissue to be measured by near-infrared light. Finally, the control processor 8 is used to collect and process these data, and the tissue blood oxygen related data in the NADH content data of the tissue to be measured is eliminated through data correction, so as to obtain accurate target NADH content data.

[0138] At the same time, the embodiment of the present application provides a system for measuring NADH, and the accuracy of the data correction formula constructed by the system can reach 95.1% or above.

[0139] The foregoing is merely a list of specific embodiments of the present application, intended to enable those skilled in the art to understand or implement the present application. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application is not limited to the embodiments shown herein, but is intended to conform to the broadest scope consistent with the principles and novel features of the present application.

Claims

1. A system for measuring NADH, the system comprising: NADH detection unit, tissue blood oxygen detection unit and control processor (8); characterized in that, The NADH detection unit comprises an excitation light source transmitter (1), a detection port (2) and a light source receiving part (3), wherein the excitation light source transmitter (1) is connected to the detection port (2) via an emitting optical fiber (4), and the light source receiving part (3) is connected to the detection port (2) via a receiving optical fiber (5) to obtain primary NADH data; A tissue blood oxygen detection unit comprises a near-infrared light emitter (6) and a near-infrared light receiving unit (7), wherein the near-infrared light emitter (6) is connected to the detection port (2) via the transmitting optical fiber (4), and the near-infrared light receiving unit (7) is connected to the detection port (2) via the receiving optical fiber (5), so as to detect local tissue blood oxygen saturation data and local tissue hemoglobin concentration index; a control processor (8), wherein the control processor (8) is connected to a signal output end of the light source receiving part (3) and a signal output end of the near-infrared light receiving part (7) respectively, so as to perform data correction on the primary NADH data according to the local tissue blood oxygen saturation data and the local tissue hemoglobin concentration index; The transmitting optical fiber (4) has its transmitting optical fiber concentrated in the center and partially surrounds the receiving optical fiber on the periphery, and the receiving optical fiber in the receiving optical fiber (5) surrounds the central transmitting optical fiber in a ring shape; The fiber diameters of the transmitting optical fiber (4) and the receiving optical fiber (5) are both ≤1 mm; The numerical apertures of the transmitting optical fiber (4) and the receiving optical fiber (5) are 0.20 to 0.

23.

2. The system according to claim 1, 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 optical fiber multiplier 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).

3. The system according to claim 1, wherein: The near-infrared light receiving unit (7) comprises a near-infrared light multiplier tube (71), the near-infrared light multiplier tube is connected to the detection port (2) via the receiving optical fiber (5), and the near-infrared light multiplier tube (71) is connected to the control processor (8).

4. The system according to claim 1, wherein: The system further comprises: The spectroscopic part includes a first spectrometer (9). One end of the first spectrometer (9) is connected to the detection port (2) through a transmitting optical fiber (4), and the other end of the first spectrometer (9) is connected to the excitation light source emitter (1) and the near-infrared light emitter (6) through a receiving optical fiber (5).

5. The system according to claim 4, characterized in that The optical splitter further comprises a second optical splitter (10), the second optical splitter (10) being connected to the detection port (2) via the receiving optical fiber (5), and the second optical splitter (10) being connected to the light source receiving part (3) and the near-infrared light receiving part (7) respectively via the receiving optical fiber (5).

6. The system according to claim 1, wherein: The lengths of the transmitting optical fiber (4) and the receiving optical fiber (5) are both ≥1 m.

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