Thrombus real-time monitoring system and method for in-vitro life support equipment

Abstract

The invention provides a thrombus real-time monitoring system for in-vitro life support equipment. The thrombus real-time monitoring system comprises an impedance micro screen, an anti-blocking loop shaped like a Chinese character'ri ', an impedance analyzer and a PC. The combination and distribution mode of macroscopic flow holes and microcosmic capturing holes in the impedance micro screen is set, the macroscopic flow holes are used for improving the overall flow, and the microcosmic capturing holes are used for effectively capturing thrombus microemboli; under the condition that the overall working flow function of a circulation loop is not affected, combination between high flux and effective microembolus capture is achieved, and integration in an extracorporeal circulation system is facilitated; meanwhile, the micro matrix electrode is integrated on the composite aperture impedance micro sieve, quantitative thrombus bioelectrical impedance spectroscopy signal measurement can be achieved while thrombus microemboli are captured, quantitative analysis and determination of the thrombus microemboli content are achieved, and therefore real-time monitoring of the thrombus generation state is achieved.

Description

Technical Field

[0001] The present invention relates to the field of detection, in particular to a thrombus monitoring system for an extracorporeal life support device, and also to an extracorporeal life support device containing an impedance microsieve, and a method for real-time monitoring of thrombus formation. Background Art

[0002] Background: Thrombosis and its impact on outcome are significant in surgical patients, particularly when using extracorporeal life support (ECLS) devices such as cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), and left and right ventricular assist devices (LVADs and RVADs).

[0003] Due to the physiological / pathological reactions such as biocompatibility and inflammation caused by artificial materials used in large quantities in extracorporeal circulation systems (ECMO, LVAD, etc.), thrombosis and its complications have become serious diseases that threaten the lives and health of millions of circulatory failure patients receiving extracorporeal circulation system treatment worldwide. Therefore, the thrombosis state has become a strict monitoring indicator during the extracorporeal circulation treatment of serious diseases such as acute myocardial infarction, renal failure and even new coronavirus infection.

[0004] In order to achieve safer ECLS treatment, surgical patients need to monitor blood composition changes quickly and accurately. Therefore, under the characteristics of high hospitalization rate, high morbidity and high mortality caused by thrombosis, early warning and risk assessment of thrombosis have become important prerequisites for guiding treatment decisions and improving patient survival. Traditional methods for detecting thrombosis usually require the use of thromboelastographs, blood analyzers and other instruments, which collect blood samples intermittently and put them into the blood to detect relevant indicators such as active clotting time (ACT), activated partial thromboplastin time (APTT), prothrombin time (PT), D-dimer, etc., and finally judge the blood coagulation degree and thrombosis risk in this period of time to ensure whether anticoagulants are needed. Since the blood may change suddenly during the measurement interval, the use of a large amount of anticoagulants will increase coagulation complications such as intracranial hemorrhage and gastrointestinal bleeding. Therefore, the interval measurement is unreliable for real-time monitoring of thrombosis, and it is difficult to meet the application requirements under critical emergency or long-term operation conditions such as ECMO. Therefore, it is of great significance to establish a real-time thrombosis monitoring technology suitable for ECLS systems such as ECMO to minimize the risk of extracorporeal circulation.

[0005] In recent years, the research focus in the field of thrombosis status monitoring has gradually developed towards the direction of "rapid / in vivo targeting specific use environments and application objects". A new development trend in the research on thrombosis status monitoring of the extracorporeal circulation system is to begin to seek thrombosis-dominant markers to achieve rapid and direct thrombosis status monitoring, that is, to use biomedical diagnostic methods and technologies based on thrombosis-dominant markers to perform the most direct and effective monitoring of thrombosis in the extracorporeal circulation system. For example, dominant markers produced during thrombosis generation / degradation such as D-dimer and fibrinogen degradation products (FDP) have been used in the monitoring of thrombosis status in patients. At present, these thrombosis-dominant markers still require specific drug reactions. However, the above research has given us an important revelation: thrombosis-dominant markers are the most direct and effective characteristic parameters for characterizing the thrombosis status in the blood of in vivo patients. Thrombosis microemboli are a unique thrombosis-dominant marker, and their content can directly reflect the thrombosis status in the blood circulation circuit.

[0006] Bioimpedance spectroscopy is an emerging biological tissue / cell monitoring parameter based on multi-frequency and complex impedance measurement. It has strong biological tissue penetration and sensitivity, no tissue damage, and can achieve rapid / high-frequency non-invasive monitoring of the physiological and pathological states of biological tissues. It has been successfully used in early diagnosis of tumors, brain edema, cerebral hemorrhage, lung failure, etc. and has achieved many valuable research results. It can be seen that bioimpedance spectroscopy measurement technology can reflect the high-recognition characteristics of cells / proteins at the microscopic level.

[0007] The bioimpedance spectrum characteristics of thrombus microemboli reflect the tissue dielectric frequency characteristics of thrombus microemboli. Since the tissue composition of thrombus is quite different from blood cells / red blood cell aggregation / gas particles / fat particles, the bioimpedance spectrum characteristics of thrombus microemboli are a highly specific characteristic parameter of thrombus microemboli. Therefore, the measurement of thrombus microemboli bioimpedance spectrum has become a new method for real-time monitoring of thrombus formation status in extracorporeal life support equipment. Summary of the invention

[0008] One of the purposes of the present invention is to provide a real-time thrombus monitoring system for extracorporeal life support equipment based on thrombus microembolus bioimpedance spectrum measurement, and a second purpose of the present invention is to provide a monitoring method for the real-time thrombus monitoring system for extracorporeal life support equipment.

[0009] The above-mentioned object of the present invention is achieved by the following technical solutions: A real-time thrombosis monitoring system for extracorporeal life support equipment includes an impedance microscreen and a "sun-shaped" anti-blocking circuit.

[0010] Preferably, the impedance micro - sieve of the present invention is composed of a composite - aperture impedance micro - sieve, a sealing ring, an inlet housing, and an outlet housing. The composite - aperture impedance micro - sieve is installed and connected to the housing through the sealing ring. The inlet housing and the outlet housing are respectively connected to pipelines, and the impedance micro - sieve is connected to the extracorporeal life - support device circulation loop through the inlet housing and the outlet housing. The composite - aperture impedance micro - sieve is provided with macroscopic flow holes and microscopic capture holes. The macroscopic flow holes are circular holes. Starting from the center of the composite - aperture impedance micro - sieve, multiple levels of different apertures are set and arranged in a radial radiation form. The microscopic capture holes are grid - type holes to effectively capture tiny thrombi. A micro - matrix electrode is integrated on the composite - aperture impedance micro - sieve. The electrode is a parallel interdigitated micro - electrode, evenly distributed on the surface of the impedance micro - sieve, arranged parallel to the grid - type holes, and converging to different - polarity electrodes H VC and L VC on both sides, and is connected to an impedance analyzer through a shielded lead wire.

[0011] Preferably, the "day - shaped" anti - clogging circuit of the present invention is composed of an upper branch, a lower branch, a middle main path, and six switching valves. The upper branch and the lower branch are respectively arranged on both sides of the middle main path. The first and last ends of the upper branch and the lower branch are connected and penetrate through the middle main path. The first ends of the upper branch and the lower branch are arranged staggeredly, and the last ends of the upper branch and the lower branch are arranged staggeredly. The impedance micro - sieve is arranged on the middle main path of the "day - shaped" anti - clogging circuit. The inlet and outlet of the impedance micro - sieve are respectively connected and penetrate through the middle main path. Switching valves are respectively arranged at the first and last ends of the upper branch, the lower branch, and the middle main path. The switching valve at the first end of the middle main path is arranged between the first ends of the upper branch and the lower branch, and the switching valve at the last end of the middle main path is arranged between the last ends of the upper branch and the lower branch.

[0012] The impedance micro - sieve is connected to an impedance analyzer, and the impedance analyzer is connected to a PC.

[0013] A method for real - time monitoring of thrombus formation by a thrombus real - time monitoring system for extracorporeal life - support devices: A blood sample is introduced into the impedance micro - sieve. The composite - aperture impedance micro - sieve captures thrombus micro - emboli. At the same time, the micro - matrix electrode integrated on the composite - aperture impedance micro - sieve measures the bio - impedance spectrum signal of the thrombus micro - emboli. The impedance micro - sieve bio - impedance spectrum signal collected is transmitted to the impedance analyzer, and the thrombus situation is judged through the processing and analysis of the impedance analyzer and the PC. The "day - shaped" anti - clogging circuit controlled by six switching valves usually only opens two switching valves of the main path to ensure the blood flow in the middle main loop. When the impedance micro - sieve is blocked, the six switching valves are opened in a specific order to realize the reverse blood flow to flush the thrombus micro - emboli blocking the micro - sieve.

[0014] The beneficial effects of the present invention are as follows: the present invention discloses a real-time thrombus monitoring system and method for extracorporeal life support equipment, wherein the thrombus monitoring system includes an impedance microscreen and a "sun-shaped" anti-blocking circuit; the constructed thrombus monitoring system is connected to the pipeline of the extracorporeal life support equipment, wherein the impedance microscreen combines a physical filter screen with a micro-matrix electrode to form an integrated device for capturing and detecting cells and microparticles, and thrombus microemboli are captured and detected. The impedance microscreen bioimpedance spectrum signal is processed and analyzed by an impedance analyzer and a PC to determine the thrombus situation. Thrombus microemboli are a unique thrombus-dominant marker, and their content directly reflects the state of thrombus formation in the blood circulation circuit. The bioimpedance spectrum characteristics of thrombus microemboli are a highly specific characteristic parameter of thrombus microemboli. Capturing and detecting thrombus microemboli can achieve highly sensitive and accurate monitoring of thrombi. Different apertures are arranged non-uniformly in the effective cross-section of the circulation pipeline to form a macro-micro composite structure. Microscopic capture holes (micrometer level) are used to effectively capture thrombus microemboli. At the same time, the macroscopic flow holes (millimeter level) are reasonably arranged to ensure high throughput and high flow rate of blood circulation. The size, area, position, and proportion of the apertures are controlled to easily achieve effective capture and fixation of particles of different particle sizes, and effectively eliminate interference such as air emboli / red blood cell aggregation. The macro-micro composite aperture can achieve real-time in vivo capture of microscopic thrombus microemboli under specific macro / high-throughput conditions of the extracorporeal circulation system, avoiding the uncertainty of in vitro measurement. Through the micro-matrix electrode integrated on the impedance microsieve, the content of thrombus microemboli on the impedance microsieve can be quickly measured to achieve fast and convenient detection; the impedance microsieve can effectively capture and measure the content of thrombus microemboli without the need to add additional coagulation / immune reaction drugs, achieving label-free, no biochemical reaction, and no effect on the original physiological characteristics of thrombus microemboli. The composite aperture design makes the impedance microsieve suitable for miniaturization / integration in the circulation pipeline, and the reverse flow impact can solve the problem of easy clogging of the filter screen, which is suitable for the long-term monitoring requirements of the extracorporeal circulation system. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The illustrations of the drawings herein are used to provide further understanding of the present invention and constitute a part of this application. The illustrative examples of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0016] Figure 1 It is a real-time thrombus monitoring system for extracorporeal life support equipment of the present invention; Figure 2 It is a structural diagram of the impedance microsieve of the present invention; Figure 3 Schematic diagram of the composite aperture impedance microsieve structure of the present invention; Figure 4 It is a schematic diagram of the macro flow hole of the present invention.

[0017] In the figure: 1. Impedance microsieve; 2. "日-shaped" anti-clogging circuit; 3. Impedance analysis; 4. PC; 5. Thrombus microembolus; 2-1. Upper branch; 2-2. Lower branch; 2-3. Middle main path; 2-4. Switch valve; 1-1. Introduction housing; 1-2. Discharge housing; 1-3. Composite-aperture impedance microsieve; 1-4. Sealing ring; 1-3-1. Macroscopic flow aperture; 1-3-2. Microscopic capture aperture; 1-3-3. Electrode H VC ; 1-3-4. Electrode L VC 。 Detailed implementation manners

[0018] The following further describes the detailed content and specific implementation manners of the present invention with reference to the accompanying drawings.

[0019] See Figures 1 to 4 As shown, a real-time thrombus monitoring system for an extracorporeal life support device includes an impedance microsieve and a "日-shaped" anti-clogging circuit.

[0020] The impedance microsieve is composed of a composite-aperture impedance microsieve, a sealing ring, an introduction housing, and a discharge housing. The composite-aperture impedance microsieve is installed and connected to the housing through the sealing ring. The introduction housing and the discharge housing are respectively connected to pipelines. The impedance microsieve is connected to the extracorporeal life support device circulation loop through the introduction housing and the discharge housing.

[0021] Macroscopic flow apertures and microscopic capture apertures are provided on the composite-aperture impedance microsieve. The macroscopic flow apertures are circular holes. Starting from the center of the composite-aperture impedance microsieve, multiple levels of different apertures are set and arranged in a radial and radiation form to increase the flow rate. In this application, larger millimeter-level flow apertures are used to increase the loop flow rate, ensure the rapid passage of blood flow, thus not affecting the overall performance of the extracorporeal circulation system, and facilitating integrated installation.

[0022] The microscopic capture apertures are grid-shaped holes. The grid-shaped holes have unique advantages in capturing cells. By using grid-shaped holes, effective capture of microthrombi can be achieved. The diameter of thrombus microemboli in the extracorporeal circulation system targeted by this application is mainly 20μm - 40μm. Due to the deformation of blood cells, grid-shaped holes with a width of 6.5μm - 8μm can ensure the smooth passage of larger blood cells such as white blood cells. Therefore, the width of the grid-shaped holes can be set to 8μm - 20μm.

[0023] A micro matrix electrode is integrated on the composite-aperture impedance microsieve. The electrodes are parallel finger microelectrodes, evenly distributed on the surface of the impedance microsieve, arranged parallel to the grid-shaped holes, and converge on different-polarity electrodes H VC 、L VC on both sides of the impedance microsieve, and are connected to an impedance analyzer through shielded leads.

[0024] The "day-shaped" anti-blocking circuit consists of an upper branch, a lower branch, a middle main path, and six switching valves. The upper branch and the lower branch are respectively arranged on both sides of the middle main path. The head and tail ends of the upper branch and the lower branch are connected and communicated with the middle main path. The head ends of the upper branch and the lower branch are arranged staggeredly, and the tail ends of the upper branch and the lower branch are arranged staggeredly. The impedance micro-sieve is arranged on the middle main path of the "day-shaped" anti-blocking circuit. The inlet and outlet of the impedance micro-sieve are respectively connected and communicated with the middle main path. Switching valves are respectively arranged at the head and tail ends of the upper branch, the lower branch, and the middle main path. The switching valve at the head end of the middle main path is arranged between the head ends of the upper branch and the lower branch, and the switching valve at the tail end of the middle main path is arranged between the tail ends of the upper branch and the lower branch.

[0025] The impedance micro-sieve is connected to an impedance analyzer, and the impedance analyzer is connected to a PC.

[0026] A method for the real-time monitoring of thrombus formation by a thrombus real-time monitoring system for an extracorporeal life support device: A blood sample is passed into the impedance micro-sieve. The composite-aperture impedance micro-sieve captures thrombus micro-emboli. At the same time, the micro-matrix electrodes integrated in the composite-aperture impedance micro-sieve measure the bioelectrical impedance spectrum signal of the thrombus micro-emboli. The impedance micro-sieve bioelectrical impedance spectrum signal collected is transmitted to the impedance analyzer, and the thrombus situation is judged through the processing and analysis by the impedance analyzer and the PC. For the "day-shaped" anti-blocking circuit controlled by six switching valves, usually only two switching valves of the main path are opened to ensure the blood flow in the middle main circuit. When the impedance micro-sieve is blocked, the six switching valves are opened in a specific order to realize the reverse blood flow to flush the micro-emboli blocking the micro-sieve.

[0027] See Figures 1 to 4 As shown, the specific working process of the present invention is as follows: An artificial heart pump drives the blood to operate in the circulation circuit at a specific controllable flow rate / velocity, and the flow rate is monitored by an ultrasonic flowmeter; water bath heating is used to ensure that the blood in the circulation circuit is at body temperature; the impedance micro-sieve is integrated into the circulation circuit of the extracorporeal circulation system through the inlets and outlets on both sides, and the standard anti-disconnection connections at both ends of the housing can be directly connected to the general pipeline of the circulation circuit; the blood flows into the housing through the blood inlet, and after being captured by the composite-aperture impedance micro-sieve, some thrombus micro-emboli remain on the impedance micro-sieve; the quantitative measurement of the bioelectrical impedance spectrum of the thrombus micro-emboli is realized through the matrix electrode circuit integrated in the impedance micro-sieve. The impedance analyzer and the PC are used for the acquisition, processing, and analysis of the impedance micro-sieve bioelectrical impedance spectrum signal; for the "day-shaped" branch controlled by six switching valves, usually only two switching valves of the main path are opened to ensure the blood flow in the middle main circuit. When the impedance micro-sieve is blocked, the six switching valves are opened in a specific order, the switching valves on the upper branch and the lower branch are opened, and the switching valves on the middle main path are closed, to realize the reverse blood flow to flush the micro-emboli blocking the micro-sieve. To improve blood compatibility and reduce the generation of self-thrombus, a heparin anticoagulant coating is adopted inside the overall structure of the impedance micro-sieve.

[0028] The present invention provides a real-time thrombus monitoring system for extracorporeal life support equipment, including an impedance microsieve, a "Japanese-shaped" anti-blocking circuit, an impedance analyzer and a PC. By designing the combination and distribution of macroscopic flow holes (millimeter level) and microscopic capture holes (micrometer level) on the impedance microsieve, the macroscopic flow holes are used to increase the overall flow, and the microscopic capture holes are used to effectively capture thrombus microemboli; the combination of high flux and effective capture of microemboli is achieved without affecting the overall working flow function of the circulation loop, which is conducive to integration into the extracorporeal circulation system; at the same time, the micro-matrix electrode is integrated on the composite aperture impedance microsieve, and quantitative thrombus bioelectrical impedance spectrum signal measurement can be achieved while capturing thrombus microemboli, and quantitative analysis and determination of thrombus microemboli content can be achieved, which can be applied to the real-time monitoring system of thrombus formation status of extracorporeal life support equipment.

Claims

1. A real-time thrombus monitoring system for extracorporeal life support equipment, characterized in that: It includes an impedance micro - sieve and a "day - shaped" anti - clogging circuit. The impedance micro - sieve is connected to an impedance analyzer, and the impedance analyzer is connected to a PC.

2. The real-time thrombus monitoring system for extracorporeal life support equipment according to claim 1, characterized in that: The impedance micro - sieve is composed of a composite - aperture impedance micro - sieve, a sealing ring, an inlet housing, and an outlet housing. The composite - aperture impedance micro - sieve is installed and connected to the housing through the sealing ring. The inlet housing and the outlet housing are respectively connected to pipelines, and the impedance micro - sieve is connected to the extracorporeal life - support device circulation loop through the inlet housing and the outlet housing.

3. The real-time thrombus monitoring system for extracorporeal life support equipment according to claim 2, characterized in that: The composite - aperture impedance micro - sieve is provided with macro - flow holes and micro - capture holes. The macro - flow holes are round holes. Starting from the center of the composite - aperture impedance micro - sieve, multiple levels of different apertures are set and arranged in a radial and radiating form. The micro - capture holes are grid - shaped holes.

4. The real-time thrombus monitoring system for extracorporeal life support equipment according to claim 2, characterized in that: The composite aperture impedance microsieve is integrated with micro-matrix electrodes, wherein the electrodes are parallel interdigitated micro-electrodes, evenly distributed on the surface of the impedance microsieve, arranged parallel to the grid-shaped holes, and converged on electrodes H of different polarities on both sides of the impedance microsieve. VC , L VC and connected to the impedance analyzer through shielded leads.

5. The real-time thrombus monitoring system for extracorporeal life support equipment according to claim 1, characterized in that: The "day - shaped" anti - clogging circuit consists of an upper branch, a lower branch, a middle main path, and six switching valves. The upper branch and the lower branch are respectively arranged on both sides of the middle main path. The beginning and the end of the upper branch and the lower branch are connected and penetrate through the middle main path. The beginning ends of the upper branch and the lower branch are arranged staggeredly, and the end ends of the upper branch and the lower branch are arranged staggeredly. The impedance micro - sieve is arranged on the middle main path of the "day - shaped" anti - clogging circuit. The inlet housing and the outlet housing of the impedance micro - sieve are respectively connected and penetrate through the middle main path. Switching valves are respectively arranged at the beginning and the end of the upper branch, the lower branch, and the middle main path. The switching valve at the beginning of the middle main path is arranged between the beginning ends of the upper branch and the lower branch, and the switching valve at the end of the middle main path is arranged between the end ends of the upper branch and the lower branch.

6. A method for real-time monitoring of thrombus formation using the real-time thrombus monitoring system for extracorporeal life support equipment according to any one of claims 1 to 5, characterized in that: Blood samples are passed into the impedance micro - sieve. The composite - aperture impedance micro - sieve captures thrombus micro - emboli. At the same time, the micro - matrix electrodes integrated in the composite - aperture impedance micro - sieve measure the bio - impedance spectrum signals of the thrombus micro - emboli. The impedance micro - sieve bio - impedance spectrum signals collected are transmitted to the impedance analyzer, and the thrombus condition is judged through the processing and analysis of the impedance analyzer and the PC. The "day - shaped" anti - clogging circuit controlled by six switching valves usually only opens the two switching valves of the main path to ensure the blood flow in the middle main loop. When the impedance micro - sieve is blocked, the six switching valves are opened in a specific order to realize the reverse blood flow to flush the thrombus micro - emboli blocking the micro - sieve.

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