MEMS electrode device for cardiac pulse field ablation and preparation method thereof

Abstract

The present invention provides a MEMS electrode device for cardiac pulse field ablation and a preparation method thereof, wherein the electrode device comprises a lower insulating layer, a temperature sensing layer, a middle insulating layer, an electrode layer, an upper insulating layer and an electrode modification layer arranged in sequence from bottom to top; wherein the electrode layer is used to apply pulsed electrical signals to cardiac tissue, and simultaneously record the electrical impedance of cardiac tissue before and after each pulse field ablation, and also to record the electrocardiographic signals of cardiac tissue before and after ablation; and the temperature sensing layer is used to record the dynamic temperature changes during the ablation process in situ. The present invention can improve the safety and efficiency of cardiac pulse field ablation.

Description

Technical Field

[0001] The present invention relates to the technical field of electrophysiological instruments, and in particular to a MEMS electrode device for cardiac pulse field ablation and a preparation method thereof. Background Art

[0002] Atrial fibrillation is the most common sustained arrhythmia in clinical practice. It has a high morbidity and mortality rate, and the risk of occurrence increases with age, affecting 1-2% of the population. About 90% of atrial fibrillation is due to abnormal electrical signals entering the atrium through the pulmonary veins, resulting in irregular electrocardiogram signals. To date, pulmonary vein isolation using catheter ablation technology is the cornerstone of interventional surgery for atrial fibrillation. Compared with drug therapy, catheter ablation has become the preferred treatment method due to its high safety, high efficiency and good results.

[0003] At present, catheter ablation technology generally uses radiofrequency ablation or cryoablation to achieve pulmonary vein isolation. The former causes cell death in the target area by applying radiofrequency energy, while the latter uses refrigerants such as N2O to cause cell death. Both technologies have obvious disadvantages. First, they are not specific to the damage of various tissues and cells in the pulmonary veins. Secondly, many surgical complications occur, such as pulmonary vein stenosis and phrenic nerve injury. In addition, radiofrequency ablation has high requirements for the surgeon and the operation time is long. Therefore, it is urgent to find a new ablation method to avoid the above problems.

[0004] Recently, a promising new ablation technique has emerged, known as pulsed field ablation. Compared with traditional radiofrequency ablation and cryoablation, it shows obvious advantages, including tissue specificity and non-thermal properties. Pulsed field ablation uses narrow pulses and high voltages to effectively induce nanoscale pores in cell membranes, leading to cell death, that is, irreversible electroporation. Several medical companies have developed ablation electrodes of various shapes, such as the ring-shaped 9-electrode ablation catheter of Medtronic, the basket-shaped 20-electrode ablation catheter and the lasso-shaped epicardial ablation catheter of Farapulse, and the lattice-tip catheter ablation system of Affera. However, there are still some common problems: (1) This type of ablation electrode cannot perform point-like ablation on the target point of the heart tissue to obtain ablation points of precise size, and often damages the entire area, which is bound to damage tissue in non-target areas; (2) Applying a high voltage of 1000-2500V may cause muscle contraction, resulting in electrode dislocation during treatment. High voltage may also cause serious electrolysis or arcing in the body; (3) The ablation effect cannot be quickly evaluated. CT, MRI and ultrasound examinations cannot effectively evaluate changes in the tissue level before and after ablation. If ablation is unsuccessful, a second operation is required; (4) The electrodes used are large in size and lack flexibility, and cannot be in close common contact with the surface of the heart; (5) The ability of a single catheter to integrate multiple sensors is insufficient, and it is impossible to simultaneously detect multiple physical parameters such as temperature and impedance.

[0005] Based on the above technologies and improvement directions, the design and preparation of a MEMS electrode device for cardiac pulsed field ablation and its preparation method have important scientific research and clinical application value, and are of great significance for the promotion and application of pulsed field ablation. Summary of the invention

[0006] In view of the defects in the prior art, an object of the present invention is to provide a MEMS electrode device for cardiac pulsed field ablation and a preparation method thereof.

[0007] According to one aspect of the present invention, there is provided a MEMS electrode device for cardiac pulse field ablation, comprising a lower insulating layer, a temperature sensing layer, a middle insulating layer, an electrode layer, an upper insulating layer and an electrode modification layer arranged in sequence from bottom to top; wherein the electrode modification layer is used to reduce the electrochemical impedance of the electrode and improve the charge storage capacity; the electrode layer is used to apply a pulsed electrical signal to the cardiac tissue, and simultaneously record the electrical impedance of the cardiac tissue before and after each pulse field ablation, and is also used to record the electrocardiographic signal of the cardiac tissue before and after ablation; the temperature sensing layer is used to record in situ the dynamic temperature changes during the ablation process.

[0008] Furthermore, the electrode layer includes a circular electrode and an annular electrode located around the circular electrode, and the circular electrode and the annular electrode form a central radial electric field.

[0009] Furthermore, the radius of the circular electrode is 50-500 μm; the inner radius of the annular electrode is 100-1000 μm, and the outer radius is 150-1500 μm; and the distance between the circumference of the circular electrode and the inner circumference of the annular electrode is less than 1 mm.

[0010] Furthermore, the circular electrode and the annular electrode are respectively used to connect to two electrodes for transmitting pulse electrical signals; the pulse electrical signal applied to the electrode device meets the following conditions: the pulse waveform is a unipolar pulse square wave or a bipolar pulse square wave; the voltage is 10-500V; the pulse width is 1-100μs; the pulse frequency is 1-10Hz; and the number of pulses is 50-120.

[0011] Furthermore, the temperature sensing layer includes a temperature sensitive metal in a meandering shape.

[0012] Furthermore, the temperature sensing layer and the electrode layer are stacked up and down at the electrode end.

[0013] Furthermore, the thickness of the temperature sensing layer is 100-500 nm.

[0014] Furthermore, the lower insulating layer, the middle insulating layer and the upper insulating layer are formed of the same material, and the thickness of the lower insulating layer, the middle insulating layer and the upper insulating layer is 1-200 μm.

[0015] Furthermore, the electrode modification layer is formed by electroplating, and the material of the electrode modification layer is any one of platinum black, iridium oxide and polyethylene dioxythiophene-polystyrene sulfonic acid.

[0016] According to another aspect of the present invention, there is provided a method for preparing the above-mentioned MEMS electrode device for cardiac pulsed field ablation, the method comprising:

[0017] forming a lower insulating layer on the substrate;

[0018] sputtering an adhesion layer on the lower insulating layer, and then sputtering a first metal layer, and patterning the first metal layer by photolithography and photoresist to form a temperature sensing layer lead;

[0019] Above the temperature sensing layer leads, using photolithography and photoresist to form the outline of the temperature sensitive metal in the temperature sensing layer;

[0020] Sputter an adhesion layer, then sputter the temperature-sensitive metal;

[0021] removing the photoresist to leave a temperature-sensitive metal with a specified profile to form a temperature sensing layer;

[0022] Making a middle insulating layer above the temperature sensing layer;

[0023] sputtering an adhesion layer on the middle insulating layer, and then sputtering a second metal layer, and patterning the second metal layer by photolithography and photoresist to form an electrode layer;

[0024] forming an upper insulating layer on the electrode layer;

[0025] Spin-coat the photoresist, pattern the photoresist by photolithography, and use a dry etching method to etch and expose the electrode part, the pad part and the overall outline of the electrode device;

[0026] Release the electrode device.

[0027] Compared with the prior art, the present invention has at least one of the following beneficial effects:

[0028] 1. The present invention is processed using MEMS technology and can be used for cardiac pulse field ablation at a relatively low voltage. It also has impedance detection and electrocardiogram signal recording functions to evaluate the ablation effect. The temperature sensing layer can accurately measure the temperature in situ. The present invention can improve the safety and efficiency of cardiac pulse field ablation.

[0029] 2. The electrode of the present invention is flexible as a whole and can be directly attached to the surface of the heart, or attached to the end of a medical catheter using biological glue for ablation with the aid of interventional surgery. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Other features, objects and advantages of the present invention will become more apparent from the detailed description of non-limiting embodiments made with reference to the following drawings:

[0031] Figure 1 An exploded schematic diagram of a MEMS electrode device for cardiac pulsed field ablation according to an embodiment of the present invention;

[0032] Figure 2 is a schematic diagram of the structure of the electrode layer in an embodiment of the present invention;

[0033] Figure 3 Schematic diagram of a pulse electrical signal applied in an embodiment of the present invention;

[0034] Figure 4 This is a schematic diagram of the electrode electric field simulation in an embodiment of the present invention;

[0035] Figure 5 This is a schematic diagram of the structure of the temperature sensitive metal in the temperature sensing layer of an embodiment of the present invention;

[0036] Figure 6 It is a schematic flow chart of a method for preparing a MEMS electrode device for cardiac pulsed field ablation in an embodiment of the present invention.

[0037] In the figure: 1 is the lower insulating layer, 2 is the temperature sensing layer, 21 is the temperature sensitive metal, 3 is the middle insulating layer, 4 is the electrode layer, 41 is the circular electrode, 42 is the ring electrode, 5 is the upper insulating layer, and 6 is the electrode modification layer; A represents the potential distribution simulation result, and B represents the electric field intensity distribution simulation result. DETAILED DESCRIPTION

[0038] The present invention is described in detail below in conjunction with specific embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but do not limit the present invention in any form. It should be noted that, for those of ordinary skill in the art, several variations and improvements can also be made without departing from the concept of the present invention. These all belong to the protection scope of the present invention. In the description of the embodiments of the present invention, it should be noted that the terms "first", "second", etc. in the specification and claims of the present invention and the above-mentioned drawings are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. It should be understood that the data used in this way can be interchangeable where appropriate, so that the embodiments of the present invention described herein can be implemented in an order other than those illustrated or described herein.

[0039] The embodiment of the present invention provides a MEMS electrode device for cardiac pulse field ablation, referring to Figure 1 The device includes a lower insulating layer 1, a temperature sensing layer 2, a middle insulating layer 3, an electrode layer 4, an upper insulating layer 5 and an electrode modification layer 6 which are arranged in sequence from bottom to top; wherein the electrode modification layer 6 is used to reduce the electrochemical impedance of the electrode and improve the charge storage capacity; the electrode layer 4 is used to apply a pulsed electrical signal to the heart tissue and cause irreversible electroporation of the myocardial cells, while recording the electrical impedance of the heart tissue before and after each pulse field ablation, and also used to record the electrocardiogram signal of the heart tissue before and after ablation, so as to evaluate the ablation effect; the temperature sensing layer 2 is used to record the dynamic temperature changes during the ablation process in situ to obtain the best ablation parameters.

[0040] The electrode device in the embodiment of the present invention can be used for cardiac pulse field ablation, and has impedance detection function and ECG signal recording function to evaluate the ablation effect. The temperature sensing layer 2 can accurately measure the temperature in situ. The present invention can improve the safety and efficiency of cardiac pulse field ablation.

[0041] Reference Figure 2In some preferred embodiments, the electrode layer 4 includes a circular electrode 41 located at the center and an annular electrode 42 located around the circular electrode 41. The circular electrode 41 and the annular electrode 42 form a central radial electric field, thereby limiting the energy within the range of the electrodes. This structure can perform precise point-like ablation on cardiac tissue. The electrode layer 4 also includes electrode layer leads, which are respectively connected to the circular electrode 41 and the annular electrode 42. Preferably, the electrode layer leads are serpentine to prevent the leads from being easily broken during the deformation of the device.

[0042] The material of the electrode layer 4 needs to have good biocompatibility, and the thickness of the electrode layer 4 needs to be within the processable range of the MEMS process. In some preferred embodiments, the material of the electrode layer 4 is gold, platinum or carbon, etc., with a thickness of 100-500nm. The radius of the circular electrode 41, the inner radius and the outer radius of the annular electrode 42 are all set according to the size of the designed single ablation point to ensure that the ablation point size is accurately obtained. Preferably, the radius of the circular electrode 41 is 50-500μm; the inner radius of the annular electrode 42 is 100-1000μm, and the outer radius is 150-1500μm; the distance between the circumference of the circular electrode 41 and the inner ring circumference of the annular electrode 42 is less than 1mm, and the small spacing between the electrodes can realize low-voltage pulse field ablation, and the high electric field strength required for pulse field ablation can be achieved by applying a low voltage.

[0043] The circular electrode 41 and the annular electrode 42 are respectively used to connect to two electrodes, namely the anode and the cathode, for transmitting pulsed electrical signals. The pulsed electrical signal applied to the electrode device meets the following conditions: the pulse waveform (i.e., the shape of the pulsed voltage signal) is a unipolar pulsed square wave or a bipolar pulsed square wave; the voltage (i.e., the peak value of the pulsed voltage signal) is 10-500V, which is used to achieve low-voltage pulsed field ablation; the pulse width (i.e., the duration of each pulse) is 1-100μs; the pulse frequency (i.e., the repetition frequency of the pulsed voltage signal) is 1-10Hz; the number of pulses (i.e., the number of pulses applied to each ablation position) is 50-120.

[0044] Preferably, refer to Figure 3 , is a schematic diagram of the applied pulse electrical signal, which meets the following conditions: the pulse waveform is a unipolar pulse square wave; the voltage is 100V; the pulse width is 100μs; the pulse frequency is 1Hz; and the number of pulses is 99.

[0045] Reference Figure 4 , which is an electrode electric field simulation diagram. After pulse electric signals are applied to the circular electrode 41 located in the center and the annular electrode 42 located at the periphery, the electric potential distribution simulation result A and the electric field intensity distribution simulation result B show that the two can form a central radial electric field, thereby limiting the energy within the range of the electrode. This structure can perform precise point ablation on cardiac tissue.

[0046] In some preferred embodiments, reference Figure 5 The temperature sensing layer 2 includes a temperature sensitive metal 21 in a meandering shape (i.e., a serpentine shape) to increase its effective length within a limited area, thereby obtaining a greater resistance change. The temperature sensitive metal 21 is made of a metal with a large temperature coefficient of resistance, such as platinum or gold, to obtain a greater sensitivity. The temperature sensing layer 2 also includes a temperature sensing layer lead wire led out from the temperature sensitive metal 21. Preferably, the temperature sensing layer lead wire is in a meandering shape (i.e., a serpentine shape) to prevent the lead wire from easily breaking during the deformation of the device. The thickness of the temperature sensing layer 2 is 100-500nm. If the thickness of the temperature sensing layer 2 is too small, it is easy to break and open the circuit. If the thickness is too large, its resistance value is reduced. The temperature sensing layer 2 and the electrode layer 4 are stacked up and down at the electrode end, and the electrode end and the lead end are respectively located at the two ends of the temperature sensing layer 2 or the electrode layer 4; preferably, the temperature sensing layer 2 and the end formed by the circular electrode 41 and the annular electrode 42 of the electrode layer 4 are stacked up and down, and the two are isolated only by the middle insulating layer 3 to realize in-situ accurate measurement of temperature.

[0047] In some preferred embodiments, the electrode modification layer 6 is formed by electroplating, and the material of the electrode modification layer 6 is any one of platinum black, iridium oxide and polyethylene dioxythiophene-polystyrene sulfonic acid, preferably platinum black, so as to reduce the electrochemical impedance of the electrode and improve the charge storage capacity.

[0048] To ensure that the electrode is flexible as a whole, in some preferred embodiments, the lower insulating layer 1, the middle insulating layer 3 and the upper insulating layer 5 are formed of the same material, which is convenient to process, and the same materials have good compatibility, good mutual bonding and sealing properties. The material of the insulating layer is a biocompatible material such as Parylene, polyimide or SU-8 photoresist. The thickness of the lower insulating layer 1, the middle insulating layer 3 and the upper insulating layer 5 is 1-200 μm. If the thickness of the insulating layer is too small, the device is easy to break, and if the thickness is too large, the flexibility of the device is reduced. The electrode device in the embodiment of the present invention is flexible as a whole and can be directly attached to the surface of the heart, or attached to the end of a medical catheter with biological glue for ablation with the help of interventional surgery.

[0049] The embodiment of the present invention further provides a method for preparing the above-mentioned MEMS electrode device for cardiac pulsed field ablation, the method comprising:

[0050] S1. Making a lower insulating layer on a substrate;

[0051] S2, sputtering an adhesion layer on the lower insulating layer, the material of the adhesion layer may be titanium or chromium, and then sputtering a first metal layer, and patterning the first metal layer by photolithography and photoresist, specifically, spin coating photoresist, patterning the photoresist by photolithography, and patterning the metal layer by wet etching or dry etching to form a temperature sensing layer lead;

[0052] S3, forming the outline of the temperature sensitive metal in the temperature sensing layer by photolithography and photoresist above the lead of the temperature sensing layer;

[0053] S4, sputtering an adhesion layer, the material of the adhesion layer may be titanium or chromium, and then sputtering a temperature sensitive metal;

[0054] S5, removing the photoresist to leave a temperature sensitive metal with a specified profile, specifically, soaking in hot acetone and removing the photoresist by ultrasonic vibration to form a temperature sensing layer;

[0055] S6. Making a middle insulating layer above the temperature sensing layer;

[0056] S7, sputtering an adhesion layer on the middle insulating layer, the material of the adhesion layer may be titanium or chromium, and then sputtering a second metal layer, and patterning the second metal layer by photolithography and photoresist, specifically, spin coating the photoresist, patterning the photoresist by photolithography, and patterning the metal layer by wet etching or dry etching to form an electrode layer;

[0057] S8, making an upper insulating layer on the electrode layer;

[0058] S9, spin-coating photoresist, patterning the photoresist by photolithography, and etching and exposing the electrode part, the pad part and the overall outline of the electrode device by dry etching method;

[0059] S10. Release the electrode device.

[0060] Preferably, refer to Figure 6 The preparation method of a MEMS electrode device for cardiac pulsed field ablation comprises the following steps:

[0061] S1, such as Figure 6 As shown in (a), on a 4-inch silicon wafer, a 5 μm thick polyparaxylene (Parylene-C) is deposited by chemical vapor deposition as a lower insulating layer;

[0062] S2, such as Figure 6 As shown in (b), a 20nm thick chromium layer is sputtered on the lower insulating layer as an adhesion layer, and then a 400nm thick gold layer is sputtered; Figure 6 As shown in (c), spin-coating photoresist, patterning the photoresist by photolithography, and patterning chromium / gold by wet etching to form temperature sensing layer leads;

[0063] S3, such as Figure 6 As shown in (d), a photoresist is spin-coated and patterned by photolithography to form the outline of the temperature sensitive metal in the temperature sensing layer;

[0064] S4, such as Figure 6 As shown in (e), a 20nm thick layer of chromium is sputtered as an adhesion layer, and then a 400nm thick layer of platinum is sputtered as a temperature-sensitive metal;

[0065] S5, such as Figure 6 As shown in (f), the photoresist is removed by immersion in hot acetone and ultrasonic vibration, leaving behind temperature-sensitive metal platinum with a specific profile;

[0066] S6, such as Figure 6 As shown in (g), a 5 μm thick polyparaxylene (Parylene-C) is deposited by chemical vapor deposition as a middle insulating layer;

[0067] S7, such as Figure 6 As shown in (h), a 20nm thick chromium layer is sputtered on the middle insulating layer as an adhesion layer, and then a 400nm thick gold layer is sputtered; Figure 6 As shown in (i), a photoresist is spin-coated, the photoresist is patterned by photolithography, and gold is patterned by wet etching to form an electrode layer;

[0068] S8, such as Figure 6 As shown in (j), a 5 μm thick polyparaxylene (Parylene-C) is deposited by chemical vapor deposition as an upper insulating layer;

[0069] S9, such as Figure 6 As shown in (k), the photoresist is spin-coated and patterned by photolithography; Figure 6 As shown in (l), a reactive ion etching method is used to etch and expose the electrode portion, the pad portion and the overall outline of the electrode device;

[0070] S10, such as Figure 6 As shown in (m), the electrode device is released.

[0071] The MEMS electrode device for cardiac pulse field ablation and the preparation method thereof in the above-mentioned embodiments of the present invention are processed using MEMS technology, can be used for cardiac pulse field ablation at a relatively low voltage, and have impedance detection function and electrocardiogram signal recording function to evaluate the ablation effect. The temperature sensing layer can accurately measure the temperature in situ. The present invention can improve the safety and efficiency of cardiac pulse field ablation.

[0072] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art can make various modifications or variations within the scope of the claims, which does not affect the essence of the present invention. The above preferred features can be used in any combination without conflicting with each other.

Claims

1. A MEMS electrode device for cardiac pulsed field ablation, characterized in that: It includes a lower insulating layer, a temperature sensing layer, a middle insulating layer, an electrode layer, an upper insulating layer and an electrode modification layer which are arranged in sequence from bottom to top; Wherein, the electrode modification layer is used to reduce the electrochemical impedance of the electrode and improve the charge storage capacity; The electrode layer is used to apply pulsed electrical signals to the cardiac tissue, and simultaneously record the electrical impedance of the cardiac tissue before and after each pulse field ablation, and is also used to record the electrocardiogram signal of the cardiac tissue before and after ablation; The temperature sensing layer is used to in-situ record the dynamic temperature changes during the ablation process; The electrode layer includes a circular electrode and an annular electrode located around the circular electrode, and the circular electrode and the annular electrode form a central radial electric field; The circular electrode and the annular electrode are respectively used to connect with two electrodes for transmitting pulse electrical signals; the pulse electrical signal applied to the electrode device meets the following conditions: the pulse waveform is a unipolar pulse square wave or a bipolar pulse square wave; the voltage is 10-500V; the pulse width is 1-100μs; the pulse frequency is 1-10Hz; and the number of pulses is 50-120.

2. The MEMS electrode device for cardiac pulsed field ablation according to claim 1, characterized in that: The radius of the circular electrode is 50-500 μm; the inner radius of the annular electrode is 100-1000 μm, and the outer radius is 150-1500 μm; the distance between the circumference of the circular electrode and the inner circumference of the annular electrode is less than 1 mm.

3. The MEMS electrode device for cardiac pulsed field ablation according to claim 1, characterized in that: The temperature sensing layer includes a temperature sensitive metal in a meandering shape.

4. The MEMS electrode device for cardiac pulsed field ablation according to claim 1, characterized in that: The temperature sensing layer and the electrode layer are stacked up and down at the electrode end.

5. The MEMS electrode device for cardiac pulsed field ablation according to claim 1, characterized in that: The thickness of the temperature sensing layer is 100-500 nm.

6. The MEMS electrode device for cardiac pulsed field ablation according to claim 1, characterized in that: The lower insulating layer, the middle insulating layer and the upper insulating layer are formed of the same material, and the thickness of the lower insulating layer, the middle insulating layer and the upper insulating layer is 1-200 μm.

7. The MEMS electrode device for cardiac pulsed field ablation according to claim 1, characterized in that: The electrode modification layer is formed by electroplating, and the material of the electrode modification layer is any one of platinum black, iridium oxide and polyethylene dioxythiophene-polystyrene sulfonic acid.

8. A method for preparing a MEMS electrode device for cardiac pulsed field ablation according to any one of claims 1 to 7, characterized in that: include: forming a lower insulating layer on the substrate; sputtering an adhesion layer on the lower insulating layer, and then sputtering a first metal layer, and patterning the first metal layer by photolithography and photoresist to form a temperature sensing layer lead; Above the temperature sensing layer leads, using photolithography and photoresist to form the outline of the temperature sensitive metal in the temperature sensing layer; Sputter an adhesion layer, then sputter the temperature-sensitive metal; removing the photoresist to leave a temperature-sensitive metal with a specified profile to form a temperature sensing layer; Making a middle insulating layer above the temperature sensing layer; sputtering an adhesion layer on the middle insulating layer, and then sputtering a second metal layer, and patterning the second metal layer by photolithography and photoresist to form an electrode layer; forming an upper insulating layer on the electrode layer; Spin-coat the photoresist, pattern the photoresist by photolithography, and use a dry etching method to etch and expose the electrode part, the pad part and the overall outline of the electrode device; Release the electrode device.

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