A dot matrix ablation system and method for cell atrial fibrillation model

Abstract

The application discloses a dot matrix ablation system and method for a cell atrial fibrillation model, which comprises a culture dish with constant temperature heating function, a dot matrix heating head composed of a plurality of heating points is arranged on the inner bottom of the culture dish, each heating point penetrates the bottom wall of the culture dish and is connected with a button switch through a control unit, each heating point corresponds to a button switch, and the opening and closing of the single heating point are controlled by pressing the corresponding button switch; the application can control the ablation position and reproduce the ablation scheme through the external keyboard button switch, solves the reproducibility defects of the existing ablation scheme, and solves the technical problems that the traditional manual ablation lacks standardized positioning and is extremely dependent on manual operation of experimenters; meanwhile, the application breaks through the double technical barriers of accurate modeling of electric turbulence and quantitative verification of ablation strategies in cell experiments through the modular electric excitation system and the dot matrix ablation executor, and provides a standardized and repeatable experimental platform for atrial fibrillation mechanism research.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical prediction model, and particularly relates to a dot matrix ablation system and ablation method for cell atrial fibrillation model. BACKGROUND

[0002] Atrial fibrillation (AF), also known as atrial fibrillation, is one of the most common arrhythmias in clinical practice, and has a huge socio-economic impact due to its associated morbidity, mortality, reduced quality of life and healthcare costs. At present, the etiology of atrial fibrillation is diverse, and a comprehensive understanding of the complex pathophysiological mechanisms is required for the rational development of new treatment methods. A monolayer of atrial cells represents a simplified substitute for atrial tissue and is very suitable for studying the mechanisms of atrial arrhythmias because they can be easily used in a standardized, systematic and controllable manner to study the role of specific pathways and processes in the initiation, perpetuation and termination of atrial arrhythmias. The existing research techniques have the following limitations: (1) Experimental model defects: although animal in vivo experiments (mice, monkeys, dogs, pigs and other mammals) can simulate real electrical conduction, they are costly and cannot achieve precise control of electrical signals; cell monolayer culture models simplify electrical signal monitoring (calcium fluorescence imaging resolution up to 50 μm), but the success rate of abnormal electrical signal induction is insufficient.

[0003] If there is a spiral wave in the heart, the spiral wave will interfere with the normal contraction of the heart, because the spiral wave itself has an intrinsic rotation frequency greater than the pacing frequency of the heart, causing the heart to contract faster, causing tachycardia. Repeated excitation of the myocardium not only reduces the pumping capacity of the heart, but also prevents the myocardium from getting enough rest, leading to myocardial infarction, stroke and other diseases. If the spiral wave breaks down into a spiral wave turbulent state, the electrical signals that spread like a tsunami will cause the heart to stop pumping blood, i.e. fibrillation.

[0004] Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, and has a huge socio-economic impact due to its associated morbidity, mortality, reduced quality of life and healthcare costs. At present, the etiology of atrial fibrillation is diverse, and a comprehensive understanding of the complex pathophysiological mechanisms is required for the rational development of new treatment methods. A monolayer of atrial cells represents a simplified substitute for atrial tissue and is very suitable for studying the mechanisms of atrial arrhythmias because they can be easily used in a standardized, systematic and controllable manner to study the role of specific pathways and processes in the initiation, perpetuation and termination of atrial arrhythmias. The existing research techniques have the following limitations: (1) Experimental model defects: animal in vivo experiments (mice, monkeys, dogs, pigs and other mammals) can simulate real electrical conduction, but are costly and cannot achieve precise control of electrical signals; cell monolayer culture models simplify electrical signal monitoring (calcium fluorescence imaging resolution up to 50 μm), but the success rate of abnormal electrical signal induction is insufficient.

[0005] (2) Induction technology bottleneck: traditional high-frequency stimulation easily leads to rapid apoptosis of cells and cannot control the propagation direction of spiral waves.

[0006] (3) Abnormal electrical signal induction efficiency is low: existing technologies are difficult to efficiently simulate the induction of abnormal electrical signals in cell experiments, and the simulation of atrial fibrillation ablation surgery is fast and low-cost. Existing methods for inducing abnormal electrical signals usually involve multiple high-frequency electrical signal stimulations at certain points in the culture dish to induce turbulent flow of electrical signals. However, for different types and batches of cells, the frequency and intensity of each stimulation are different, and need to be adjusted flexibly according to the characteristics of the cells in this experiment to successfully induce. After multiple inductions, strong stimulation significantly shortens the cell survival period, reducing the time window for doctors or experimenters to operate.

[0007] (4) Ablation operation is limited: after inducing turbulent flow, targeted ablation surgery treatment simulation needs to be carried out, and the problem of ablation scheme cannot be reproduced may also be encountered. Because most of the existing ablation schemes are still based on the hand operation of doctors or experimenters, first of all, due to technical reasons, that is, the calcium concentration in the cell needs to be observed by the camera to determine the excitation state of the cell fluorescence mapping system - MappingLab, the position of the key lesion needs to be judged manually and the ablation scheme is developed. The implementation of the ablation scheme also needs to be carried out manually, and the hand operation cannot observe the propagation of the electrical signal at the same time; therefore, the existing ablation relies on visual positioning of calcium fluorescence imaging and manual thermal ablation (energy fluctuation ± 25%), and due to the principle of calcium imaging, manual ablation and calcium imaging cannot be performed at the same time, and only after visual predetermination of the lesion position can manual blind operation be performed.

[0008] To solve the above technical problems, the present application provides a dot matrix ablation system and ablation method for a cell atrial fibrillation model, which breaks through the dual technical barriers of precise modeling of electrical turbulence and quantitative verification of ablation strategies in cell experiments, and provides a standardized and repeatable experimental platform for atrial fibrillation mechanism research. SUMMARY

[0009] In view of the defects in the prior art, the purpose of the present application is to provide a dot matrix ablation system and ablation method for a cell atrial fibrillation model, which can control the ablation position and reproduce the ablation scheme by using an external keyboard button switch, thereby solving the reproducibility defect of the existing ablation scheme, and the technical problem that traditional hand-operated ablation lacks standardized positioning and is extremely dependent on manual operation of experimenters.

[0010] Specifically, the technical problem to be solved by the present application is to solve the problems in the prior art. In a first aspect, the present application provides a dot-matrix ablation system for a cell atrial fibrillation model, comprising a culture dish with constant temperature heating function, a dot-matrix heating head composed of a plurality of heating dots is arranged at the inner bottom of the culture dish, each heating dot penetrates the bottom wall of the culture dish and is connected to a button switch through a control unit, each heating dot corresponds to a button switch, and the opening and closing of each heating dot are controlled by pressing the corresponding button switch.

[0011] Preferably, the shape of all the button switches is the same as that of the dot-matrix heating head.

[0012] Preferably, the position of each heating dot in the dot-matrix heating head is the same as the position of the button switch for controlling the opening and closing of the heating dot in the shape formed by all the button switches.

[0013] Preferably, the dot-matrix heating head is an N*N square matrix.

[0014] Preferably, an LED dot-matrix is arranged in the control unit, the shape of the LED dot-matrix is the same as that of the dot-matrix heating head, and the position of each LED dot in the LED dot-matrix is the same as the position of each heating dot in the dot-matrix heating head.

[0015] Preferably, the constant temperature heating temperature of the culture dish is 37℃.

[0016] Preferably, the opening of each heating dot is controlled by pressing the corresponding button switch, at which time the LED dot at the corresponding position is brightened; the closing of each heating dot is controlled by pressing the corresponding button switch, at which time the LED dot at the corresponding position is extinguished.

[0017] In a second aspect, the present application provides a dot-matrix ablation method for a cell atrial fibrillation model, which adopts the dot-matrix ablation system for a cell atrial fibrillation model as described above to perform dot-matrix ablation on the cell atrial fibrillation model, and the ablation method comprises the following steps: first, placing myocardial cells in the middle of the inside of the culture dish.

[0018] Second, placing an abnormal electrical signal inducing device in the culture dish and exciting it by a signal generator to form a spiral electrical signal (spiral wave) in the myocardial cells, and then taking out the abnormal electrical signal inducing device.

[0019] Third, when a rotating center of the spiral electrical signal or a propagation path of the spiral electrical signal is observed at a certain dot-matrix position in the dot-matrix heating head, an ablation plan is made and the button switch at the corresponding position is pressed to start the heating dot at the corresponding position, the generated heat burns the myocardial cells at the corresponding position to prevent the propagation of the spiral electrical signal, thereby achieving the ablation effect.

[0020] Preferably, the ablation plan is in a ring-shaped blocking mode for the rotation center of the spiral electric signal, and in a linear blocking mode for the propagation path of the spiral electric signal.

[0021] Compared with the prior art, the positive effects of the present application are that the dot-matrix ablation system and ablation method of the cell atrial fibrillation model in the present application can quickly formulate and execute an ablation scheme for the position of a key lesion after artificial judgment through a dot-matrix ablation executor, can control the ablation position and reproduce the ablation scheme through an external keyboard button switch, solve the reproducibility defect of the existing ablation scheme, and solve the technical problem that traditional manual ablation lacks standardized positioning and is extremely dependent on manual operation of experimenters; at the same time, the dot-matrix ablation executor aims to break through the technical barriers of quantitative verification of ablation strategies in cell experiments, and provides a standardized and repeatable experimental platform for atrial fibrillation mechanism research. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 Fig. 1 is a schematic diagram of the dot-matrix ablation system in the present application Figure 1 .

[0023] Figure 2 Fig. 2 is a schematic diagram of the dot-matrix ablation system in the present application Figure 2 .

[0024] Figure 3 Fig. 3 is a schematic diagram of the dot-matrix ablation system in the present application.

[0025] Figure 4 Fig. 4 is a circuit schematic of the dot-matrix ablation system in the present application Figure 1 .

[0026] Figure 5 Fig. 5 is a schematic diagram of the position relationship between the rotation center of the spiral wave and the dot matrix in the present application.

[0027] Figure 6 Fig. 6 is a schematic diagram of the position relationship between the spiral wave and the dot matrix in the present application.

[0028] Fig. 7 is a schematic diagram of the position relationship between the button switch and the spiral wave in Example 1 of the present application; Fig. (a), Fig. (b), Fig. (c), Fig. (d) and Fig. (e) respectively represent the distribution of the spiral wave after execution of the ablation scheme.

[0029] Fig. 8 is a schematic diagram of the position relationship between the button switch and the spiral wave in Example 2 of the present application; Fig. (a), Fig. (b), Fig. (c), Fig. (d) and Fig. (e) respectively represent the distribution of the spiral wave after execution of the ablation scheme.

[0030] Figure 9 is a schematic diagram of the positional relationship between the push button switch and the spiral wave in Example Three of the present application; Figure (a), Figure (b), Figure (c), Figure (d), Figure (e) respectively represent the distribution of the spiral wave after the ablation scheme is executed.

[0031] Figure 10 Figure 1 is a schematic diagram of the physical object of the prior art fluorescent mapping system.

[0032] The markers in the drawing are: 1-plastic ring, 3-culture dish, 4-cardiomyocytes, 6-dot matrix heating head, 7-push button switch, 8-spiral wave, 9-heating plate, 10-LED dot matrix, 11-key matrix, 12-OLED, 13-temperature and humidity sensor, 14-single-chip microcomputer, 15-relay switch array, 16-calcium camera. DETAILED DESCRIPTION

[0033] The following Figure 1 Figure 9 and the detailed description further illustrate the present application.

[0034] Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, which has a huge socio-economic impact due to its associated morbidity, mortality, reduced quality of life and healthcare costs. At present, the etiology of atrial fibrillation is diverse, and a comprehensive understanding of the complex pathophysiological mechanisms is needed for the rational development of new treatment methods. The monolayer of atrial cells represents a simplified substitute for atrial tissue, which is very suitable for studying the mechanism of atrial arrhythmia because they can be easily used in a standardized, systematic and controllable way to study the role of specific pathways and processes in the occurrence, continuation and termination of atrial arrhythmia. However, the existing cell atrial fibrillation model research technology has three limitations: experimental model defects: although animal in vivo experiments (mice, monkeys, dogs, pigs and other mammals) can simulate real electrical conduction, they are costly and cannot achieve precise electrical signal control; cell monolayer culture model simplifies electrical signal monitoring (calcium fluorescence imaging resolution up to 50 μm), but the success rate of abnormal electrical signal induction is insufficient.

[0035] Induction technology bottleneck: traditional high-frequency stimulation easily leads to rapid apoptosis of cells and cannot control the propagation direction of spiral waves.

[0036] Ablation operation limitations: existing ablation relies on visual positioning with calcium fluorescence imaging and manual thermal ablation (energy fluctuation ± 25%), and due to the principle of calcium imaging, manual ablation and calcium imaging cannot be performed simultaneously, so it can only be performed manually after visually predicting the lesion location. It uses a fluorescent mapping system - MappingLab, as shown in Figure 10 , which involves a calcium camera 16.

[0037] In view of the above defects, the cell atrial fibrillation model dot matrix ablation system conceived in the application includes a culture dish 3 with constant temperature heating function, a dot matrix heating head 6 composed of multiple heating points is arranged at the inner bottom of the culture dish 3, each heating point penetrates the bottom wall of the culture dish 3 and is connected to a button switch through a control unit, each heating point corresponds to a button switch, and the opening and closing of the single heating point are controlled by pressing the corresponding button switch.

[0038] The shape of all the button switches is the same as that of the dot matrix heating head 6.

[0039] The position of each heating point in the dot matrix heating head 6 is the same as that of the button switch for controlling the opening and closing of the heating point in the shape composed of all the button switches.

[0040] The dot matrix heating head 6 is an N*N square matrix.

[0041] An LED dot matrix is arranged in the control unit, the shape of the LED dot matrix is the same as that of the dot matrix heating head 6, and the position of each LED dot in the LED dot matrix is the same as that of each heating point in the dot matrix heating head 6.

[0042] Preferably, the constant temperature heating temperature of the culture dish is 37℃.

[0043] The opening of the single heating point is controlled by pressing the corresponding button switch, at this time, the LED dot at the corresponding position is brightened; the closing of the single heating point is controlled by pressing the corresponding button switch, at this time, the LED dot at the corresponding position is extinguished.

[0044] The physical schematic diagram of the cell atrial fibrillation model dot matrix ablation system in the application is shown in Figure 3 It includes a culture dish 3, a dot matrix heating head 6, a heating plate 9, an LED dot matrix 10, a key matrix 11, an OLED 12, a temperature and humidity sensor 13, a single-chip microcomputer 14 and a relay switch array 15.

[0045] The ablation method for the cell atrial fibrillation model dot matrix ablation system to perform dot matrix ablation on the cell atrial fibrillation model includes the following steps: first step: placing myocardial cells 4 in the middle of the inside of the culture dish 3.

[0046] Second step: placing an abnormal electrical signal inducing device in the culture dish and exciting it through a signal generator to form a spiral electrical signal (spiral wave) in the myocardial cells 4, and then taking out the abnormal electrical signal inducing device.

[0047] Third step: when the rotating center of the spiral electric signal or the propagation path of the spiral electric signal is observed in a certain dot array position of the dot array heating head 6, an ablation plan is made and the corresponding position button switch is pressed to start the heating point of the corresponding position, the generated heat burns the myocardial cells of the corresponding position to prevent the propagation of the spiral electric signal, so as to achieve the ablation effect.

[0048] The ablation plan is to adopt a ring-shaped blocking method surrounding the rotating center of the spiral electric signal, and a linear blocking method blocking the propagation of the electric signal for the propagation path of the spiral electric signal.

[0049] In order to further illustrate the above ablation method, the following three embodiments are listed: Embodiment one: referring to the figures (a), (b), (c), (d), (e) in FIG. 7, the spiral electric signal 8 is a single spiral wave starting from a rotating center and spiraling in one direction.

[0050] The induction of the above-mentioned spiral wave is to induce an abnormal electric signal by a signal generator control point to generate an S1 electric signal with a certain frequency and wave width, and after N cycles of the S1 electric signal, another S2 electric signal with a certain frequency and wave width is generated by a signal generator control electric field.

[0051] The process of the method for generating and ablation of the above-mentioned spiral wave in the cell fibrillation model includes the following steps: first step: placing the myocardial cells 4 in the middle of the culture dish 3 with constant temperature heating function.

[0052] Second step: placing the abnormal electric signal induction device in the culture dish and forming the spiral electric signal 8 in the myocardial cells 4 by exciting the signal generator, and then taking out the abnormal electric signal induction device.

[0053] Third step: when the propagation path of the spiral electric signal 8 is observed in a certain dot array position of the dot array heating head 6, an ablation plan is made by adopting a linear blocking method blocking the propagation of the electric signal, and the corresponding position button switch 7 is pressed to start the heating point of the corresponding position, the generated heat burns the myocardial cells of the corresponding position to prevent the propagation of the spiral electric signal 8, so as to achieve the ablation effect.

[0054] The linear blocking method is to press four button switches 7 connected in a straight line on the propagation path of the electric signal to block the propagation of the spiral electric signal 8, when the heating points in the straight line composed of the four button switches 7 burn the myocardial cells of the corresponding position to prevent the propagation of the spiral electric signal 8, the spiral electric signal 8 gradually spreads to the edge, and finally achieves the ablation effect.

[0055] Example two: see figure (a), (b), (c), (d), (e) in figure 8, the helical electrical signal 8, which is from two rotating center, respectively, in the opposite two directions for the double helix wave.

[0056] The above-mentioned helical wave is induced by using abnormal electrical signal induction device, through signal generator control electric field excitation first produces a frequency and wave width of S1 electrical signal, after N cycles of S1 electrical signal, through signal generator control electric field excitation produces another frequency and wave width of S2 electrical signal.

[0057] The process of the above-mentioned helical wave in the cell room fibrillation model and ablation method includes the following steps: first step: the myocardial cells 4 are placed in the middle of the culture dish 3 with constant temperature heating function.

[0058] Second step: abnormal electrical signal induction device is placed in the culture dish and formed helical electrical signal 8 in myocardial cells 4 by signal generator excitation, and then the abnormal electrical signal induction device is taken out.

[0059] Third step: when the rotating center of helical electrical signal 8 is observed in a certain dot matrix position of dot matrix heating head 6, the ablation plan of ring isolation mode surrounding the rotating center is made, and the corresponding position button switch 7 is pressed according to the ablation plan, the heating point of the corresponding position is started, the heat generated by heating is burned to death the myocardial cells of the corresponding position to prevent the propagation of helical electrical signal 8, so as to achieve the ablation effect.

[0060] The ring isolation mode is to block the propagation of helical electrical signal 8 by pressing a plurality of button switches 7 connected on the electrical signal propagation path to form a ring and surround the center of the rotating center, when the heating points on the ring formed by a plurality of button switches 7 are heated, the heat generated by heating is burned to death the myocardial cells of the corresponding position to prevent the propagation of helical electrical signal 8, helical electrical signal 8 gradually spreads to the edge, and finally achieves the ablation effect.

[0061] Example three: see figure (a), (b), (c), (d), (e) in figure 9, the helical electrical signal 8, which is from two rotating center, respectively, in the opposite two directions for the double helix wave.

[0062] The above-mentioned helical wave is induced by using abnormal electrical signal induction device, through signal generator control electric field excitation first produces a frequency and wave width of S1 electrical signal, after N cycles of S1 electrical signal, through signal generator control electric field excitation produces another frequency and wave width of S2 electrical signal.

[0063] The process of the method for generating and ablation of the spiral wave in the cell atrial fibrillation model comprises the following steps: first step: placing the myocardial cells 4 in the middle of the inside of the culture dish 3 with constant temperature heating function.

[0064] Second step: placing the abnormal electrical signal inducing device in the culture dish and exciting by the signal generator to form the spiral electrical signal 8 in the myocardial cells 4, and then taking out the abnormal electrical signal inducing device.

[0065] Third step: when it is observed that there is a propagation path of the spiral electrical signal 8 in a certain dot matrix position of the dot matrix heating head 6, an ablation plan of linear blocking mode of blocking the propagation of the electrical signal is made, and the corresponding position button switch 7 is pressed according to the ablation plan, the heating point of the corresponding position is started, the heat generated by heating is used to burn the myocardial cells of the corresponding position to prevent the propagation of the spiral electrical signal 8, so that the ablation effect is achieved.

[0066] The linear blocking mode is that four button switches 7 connected on the propagation path of the electrical signal are pressed to form a straight line to block the propagation of the spiral electrical signal 8, when the heat generated by the heating points of the straight line formed by the four button switches 7 burns the myocardial cells of the corresponding position to prevent the propagation of the spiral electrical signal 8, the spiral electrical signal 8 gradually diffuses to the edge, and finally the ablation effect is achieved.

[0067] Compared with the prior art, the positive effects of the present application are that the ablation position and the reproducible ablation scheme can be controlled by the external keyboard type button switch, the reproducibility defect of the existing ablation scheme is solved, and the technical problems of traditional manual ablation due to lack of standardized positioning and extremely dependent on manual operation of experimental personnel are solved; at the same time, the modular electric excitation system and the dot matrix ablation executor are used to break through the double technical barriers of accurate modeling of electrical turbulence and quantitative verification of ablation strategy in cell experiments, and to provide a standardized and repeatable experimental platform for atrial fibrillation mechanism research.

[0068] As described above, only the preferred technical scheme of the present application is embodied, and some changes made by the person skilled in the art to some parts of the present application also embody the principle of the present application, and should be the technical scope of the present application.

Claims

1. A matrix ablation system for a cellular atrial fibrillation model, characterized in that, The system includes a petri dish (3) with a constant temperature heating function. A dot matrix heating head (6) consisting of multiple heating points is set at the bottom of the petri dish (3). Each heating point penetrates the bottom wall of the petri dish (3) and is connected to a button switch through a control unit. Each heating point corresponds to a button switch. Pressing the corresponding button switch controls the opening and closing of a single heating point.

2. The fractional ablation system for a cellular atrial fibrillation model as described in claim 1, characterized in that, The shape of all the push-button switches is the same as that of the dot matrix heating head (6).

3. The fractional ablation system for a cellular atrial fibrillation model as described in claim 2, characterized in that, The position of each heating point in the dot matrix heating head (6) is the same as the position of the button switch that controls its opening and closing in the shape composed of all the button switches.

4. The fractional ablation system for a cellular atrial fibrillation model as described in claim 3, characterized in that, The dot matrix heating head (6) is an N*N square matrix.

5. The fractional ablation system for a cellular atrial fibrillation model as described in claim 4, characterized in that, The control unit is provided with an LED dot matrix, the shape of which is the same as that of the dot matrix heating head (6), and the position of each LED dot in the LED dot matrix is ​​the same as the position of each heating point in the dot matrix heating head (6).

6. The fractional ablation system for a cellular atrial fibrillation model as described in claim 5, characterized in that, Pressing the corresponding button switch turns on a single heating point, at which point the corresponding LED light up; pressing the corresponding button switch turns off a single heating point, at which point the corresponding LED light goes out.

7. The fractional ablation system for a cellular atrial fibrillation model as described in claim 1, characterized in that, The constant temperature heating temperature of the culture dish (3) is 37°C.

8. A method for fractional ablation of a cellular atrial fibrillation model, comprising fractional ablation of the cellular atrial fibrillation model using the fractional ablation system for the cellular atrial fibrillation model as described in any one of claims 1-7, characterized in that, The ablation method includes the following steps: First step: Place the cardiomyocytes (4) in the middle of the culture dish (3); Second step: Place the abnormal electrical signal induction device in the culture dish and generate a spiral electrical signal in the cardiomyocytes (4) by a signal generator, and then remove the abnormal electrical signal induction device; Third step: When a spiral electrical signal rotation center is observed at a certain point in the dot matrix heating head (6), formulate an ablation plan with an annular partition surrounding the rotation center; When a spiral electrical signal propagation path is observed at a certain point in the dot matrix heating head (6), formulate an ablation plan with a linear partition blocking the propagation of the electrical signal; Press the button switch at the corresponding position according to the above ablation plan to start the heating point at the corresponding position. The heat generated by the heating will burn the cardiomyocytes at the corresponding position and prevent the propagation of the spiral electrical signal, thereby achieving the ablation effect.

9. The fractional ablation method for a cellular atrial fibrillation model as described in claim 7, characterized in that, The ablation plan employs a ring-shaped isolation method surrounding the rotation center of the spiral electrical signal, and a linear isolation method to block the propagation path of the spiral electrical signal.

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