A fractal structure microelectrode, its fabrication method, and a conduit.

Abstract

This invention provides a fractal structure microelectrode, its fabrication method, and a catheter. The microelectrode includes: a base layer with pads thereon; a conductive layer above the base layer, including electrode points electrically connected to the pads; each electrode point includes a central anode and an outer cathode, with interdigitated structures of the anode and cathode intersecting; an encapsulation layer above the conductive layer, exposing the electrode points and pads; and an electrode modification layer formed on the electrode points. An electrical pulse is applied to cardiac tissue through the anode and cathode, causing irreversible electroporation ablation of cardiac cells. The fractal structure microelectrode of this invention can increase the ratio of the length to area of ​​the insulating edge of the electrode points, facilitating current transfer from the electrode points to the cardiac tissue; it also reduces the distance between the anode and cathode, lowering the voltage required for irreversible electroporation of myocardial cells. The microelectrode is integrated into the catheter tip; the catheter can be inserted into the heart via a vein or artery in a biological body through minimally invasive interventional surgery.

Description

Technical Field

[0001] This invention relates to the field of biomedical engineering technology, specifically to a fractal structure microelectrode, its preparation method, and a conduit. Background Technology

[0002] Atrial fibrillation has become one of the most serious diseases in modern cardiology, with an incidence rate of approximately 2%. In severe cases, it can cause complications such as stroke and dementia, and even death. Pulsed field ablation involves applying high-intensity electric fields (400 V / cm for cardiomyocytes) and short-duration electrical pulses (in μs or ns), resulting in irreversible nanoscale pores in the cell membrane, known as irreversible electroporation. Due to its advantages of tissue specificity and fewer complications, irreversible electroporation ablation technology has become a novel ablation method for treating atrial fibrillation.

[0003] To facilitate the clinical application of irreversible electroporation ablation technology, researchers have developed several types of devices, which can be divided into two categories: rigid electrodes (such as Boston Scientific's Farawave) and flexible electrodes (such as flexible multilayer electron arrays). Rigid electrodes have a large electrode spacing, thus requiring electrical pulses with voltage amplitudes of up to several kilovolts. Flexible electrodes are typically fabricated using micro- and nano-fabrication processes, with small electrode spacing, avoiding the effects of high voltage. However, in current ablation procedures, the positional accuracy of flexible electrodes still needs improvement.

[0004] Based on the current state of technology and directions for improvement, designing and fabricating a catheter-mounted microelectrode for irreversible electroporation ablation has significant scientific research and clinical application value, and is of great importance for the clinical application of irreversible electroporation ablation. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a fractal structure microelectrode, its fabrication method, and a conduit.

[0006] According to one aspect of the present invention, a fractal structure microelectrode for irreversible electroporation ablation is provided, the microelectrode being a flexible electrode, comprising:

[0007] The base layer has pads on it;

[0008] A conductive layer is located above the substrate layer. The conductive layer includes electrode points that are electrically connected to the pads. Each electrode point includes a central anode and a cathode located around the anode. Both the anode and the cathode have interdigitated structures, and the interdigitated structures of the anode and the cathode are arranged in an intersecting manner.

[0009] An encapsulation layer is located above the conductive layer, and the encapsulation layer exposes the electrode points and the pads;

[0010] An electrode modification layer is formed on the electrode point and is used to modify the electrode point;

[0011] An electrical pulse is applied to the heart tissue through the anode and the cathode, causing irreversible electroporation ablation of the heart cells.

[0012] Furthermore, the interdigitated structure is a single-level or multi-level interdigitated structure to increase the ratio of the length to the area of ​​the insulating edge of the electrode point and reduce the distance between the anode and the cathode.

[0013] Furthermore, the applied electrical pulse is any one of a unipolar square pulse wave, a bipolar square pulse wave, or an exponentially decaying pulse.

[0014] Furthermore, the voltage of the applied electrical pulse is 10-1000V.

[0015] Furthermore, the thickness of the substrate layer and the encapsulation layer is 0.1-100 μm; the substrate layer and the encapsulation layer are made of the same or different materials, and the materials of the substrate layer and the encapsulation layer are any one of polyimide, parylene, SU-8 photoresist and silk protein.

[0016] Furthermore, the thickness of the conductive layer is 10-1000 nm.

[0017] Furthermore, the electrode modification layer covers the electrode point, and the material of the electrode modification layer is any one of platinum black, iridium oxide, MXenes, and polyethylene dioxythiophene-polystyrene sulfonic acid.

[0018] According to a second aspect of the present invention, a catheter is provided, wherein the head of the catheter is provided with the above-described fractal structure microelectrode for irreversible electroporation ablation, and the electrode point of the microelectrode is located at the center of the head of the catheter.

[0019] Furthermore, the microelectrode is attached to the head of the catheter using UV-curable adhesive. The catheter is inserted into the heart via a minimally invasive interventional procedure, and the microelectrode moves with the catheter.

[0020] According to a third aspect of the present invention, a method for fabricating the above-described fractal structure microelectrode for irreversible electroporation ablation is provided, the method comprising:

[0021] A substrate layer is fabricated on a silicon wafer, and pads are formed on the substrate;

[0022] An adhesive layer is formed on the substrate layer, and then a conductive layer is formed. The conductive layer is then patterned to form electrode points with fractal structures. The electrode points of the conductive layer include a central anode and a cathode located on the outer periphery of the anode. Both the anode and the cathode have interdigitated structures, and the interdigitated structures of the anode and the cathode are arranged intersectingly.

[0023] An encapsulation layer is fabricated on the conductive layer to obtain an electrode device;

[0024] Spin-coat photoresist, pattern the photoresist using photolithography, and use dry etching to etch and expose the electrode points, the pads, and the overall outline of the electrode device.

[0025] The electrode device is released from the silicon wafer, and an electrode modification layer is fabricated on the electrode point to obtain a fractal structure microelectrode for irreversible electroporation ablation.

[0026] Compared with the prior art, the present invention has at least one of the following beneficial effects:

[0027] 1. The microelectrode of the present invention is flexible as a whole. The flexible microelectrode can be integrated into the catheter tip, enabling ablation with high positional accuracy and high flexibility.

[0028] 2. This invention utilizes MEMS technology to fabricate microelectrodes with fractal structures, enabling irreversible electroporation ablation of the heart at lower voltages. It also features electrode-tissue contact detection and electrocardiogram signal recording functions, thereby improving the safety and efficiency of cardiac pulse field ablation. Attached Figure Description

[0029] Other features, objects, and advantages of the present invention will become more apparent from the following detailed description of non-limiting embodiments with reference to the accompanying drawings:

[0030] Figure 1 This is an exploded schematic diagram of a microelectrode according to an embodiment of the present invention;

[0031] Figure 2 This is a microelectrode with a first-order fractal structure according to an embodiment of the present invention;

[0032] Figure 3 This is a microelectrode with a second-order fractal structure according to an embodiment of the present invention;

[0033] Figure 4 This is a microelectrode with a three-level fractal structure according to an embodiment of the present invention;

[0034] Figure 5 This is a microelectrode with a four-level fractal structure according to an embodiment of the present invention;

[0035] Figure 6This illustrates the change in impedance between the microelectrode and cardiac tissue before ablation in one embodiment of the present invention.

[0036] Figure 7 This is a waveform diagram of an electrocardiogram signal recorded by a microelectrode in one embodiment of the present invention;

[0037] Figure 8 This is a schematic diagram of the integration of microelectrodes and conduits in one embodiment of the present invention;

[0038] Figure 9 This is a schematic diagram of a method for preparing a microelectrode according to an embodiment of the present invention.

[0039] In the diagram: 101 is the conduit, 102 is the microelectrode, 201 is the substrate layer, 202 is the conductive layer, 203 is the encapsulation layer, 204 is the electrode modification layer, 205 is the pad, A represents the anode, and B represents the cathode. Detailed Implementation

[0040] The present invention will now be described in detail with reference to specific embodiments. These embodiments will help those skilled in the art to further understand the present invention, but do not limit the invention in any way. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention. These all fall within the scope of protection of the present invention.

[0041] This invention provides a fractal structure microelectrode for irreversible electroporation ablation, wherein the microelectrode is a flexible electrode, as described above. Figure 1 The microelectrode includes a substrate layer 201, a conductive layer 202, an encapsulation layer 203, and an electrode modification layer 204. The substrate layer 201 has pads 205 located at the tail of the microelectrode for connection to leads. The conductive layer 202 is located above the substrate layer 201 and includes electrode points at its ends. The electrode points and pads are located at opposite ends of the microelectrode and are electrically connected to the pads 205. The electrode points have a fractal geometry, similar to the shape of snowflakes or the geometric shape of leaf veins. Each electrode point includes a central anode and a cathode located around the anode. Both the anode and cathode have interdigitated structures, which are intersecting. The encapsulation layer 203 is located above the conductive layer 202 and exposes the electrode points and pads 205. The electrode modification layer 204 is formed on the electrode points for modification. Electrical pulses are applied to the heart tissue through the anode and cathode, causing irreversible electroporation ablation of the heart cells. This flexible microelectrode can be integrated into the catheter tip, enabling ablation with high positional precision and offering great flexibility.

[0042] In some implementations, the interdigitated structure is a single-level or multi-level interdigitated structure, forming fractal electrode points, such as... Figure 2 First-order fractal structure in Figure 3 Second-order fractal structure in Figure 4 The three-level fractal structure in Figure 5 The fourth-order fractal structure, etc. Figure 2-5 In this diagram, A represents the anode and B represents the cathode. In a first-order fractal electrode structure, both the central anode A and the peripheral cathode B have interdigitated structures. Figure 3 The second-order fractal structure in is Figure 2 Based on the first-order fractal structure, new interdigitated structures are added to the original interdigitated structure. Other levels of fractal structures follow the same principle. By designing the fractal structure of the electrode points, the ratio of the length to the area of ​​the anode (or cathode) geometry of the fractal structure can be increased, i.e., the ratio of the length to the area of ​​the insulating edge of the electrode point can be increased, thus facilitating the transmission of current from the electrode point to the heart tissue. Furthermore, the presence of the fractal structure reduces the distance between the anode and cathode, thereby lowering the voltage required for irreversible electroporation of cardiomyocytes, enabling the use of lower voltages for irreversible electroporation ablation of the heart.

[0043] In some embodiments, the applied electrical pulse is any one of a monopolar square wave pulse, a bipolar square wave pulse, or an exponentially decaying pulse. On the one hand, these types of electrical pulses have a very short duration, preventing excessive heating of cells or tissues. On the other hand, applying the electrical pulse to the phospholipid bilayer of the cell membrane for a short time leads to the formation of a transmembrane potential, resulting in an unstable potential and causing irreversible penetrating damage to the cell membrane (i.e., irreversible electroporation), creating nanoscale pores. This leads to changes in cell membrane permeability, disrupts intracellular homeostasis, and ultimately causes apoptosis, thus achieving an ablation effect. The applied electrical pulse voltage is 10-1000V. Compared to the thousands of volts of electrical pulses used by rigid electrodes in existing technologies, the microelectrode in this embodiment can achieve irreversible electroporation ablation of the heart at a lower voltage. The lower voltage reduces problems such as electric arcing, muscle tremors, and hydrolysis, thereby improving the safety of cardiac pulse field ablation. The pulse width ranges from 1 μs to 500 ms, and the short pulse duration prevents excessive heating of cells or tissues. To match the rhythm of the heartbeat, the pulse frequency ranges from 0.1 to 100 Hz. The number of pulses ranges from 1 to 100; using multiple pulses increases the ablation effect and ensures cell apoptosis. For example, a monopolar square wave pulse with a voltage of 300 V, a pulse width of 100 μs, a pulse frequency of 1 Hz, and 60 pulses can be used.

[0044] To achieve good insulation, in some embodiments, considering that too thin a layer might not provide insulation, while too thick a layer would reduce device flexibility, the thickness of the substrate layer 201 and the encapsulation layer 203 is 0.1-100 μm. The substrate layer 201 and the encapsulation layer 203 can be the same material or two different materials, such as polyimide, parylene, SU-8 photoresist, and silk fibroin, which are insulating materials. For example, the thickness of both the substrate layer 201 and the encapsulation layer 203 is 5 μm, and both are made of parylene. Because the substrate layer 201 and the encapsulation layer 203 are relatively thin and both are made of flexible materials, it is beneficial to form flexible electrodes.

[0045] To achieve good conductivity and facilitate micro / nano fabrication, in some embodiments, the thickness of the conductive layer 202 is 10-1000 nm. The material can be any of conductive materials such as gold, platinum, copper, graphene, and liquid alloys. For example, the conductive layer 202 of the microelectrode 102 has a thickness of 300 nm and is made of gold.

[0046] In some embodiments, the electrode modification layer 204 covers the electrode points. The material of the electrode modification layer 204 is any one of platinum black, iridium oxide, MXenes, and polyvinyl dioxythiophene-polystyrene sulfonic acid, and is applied by electroplating, thermal evaporation, sputtering, spin coating, etc. For example, the electrode modification layer 204 of the microelectrode 102 covers the electrode points and is applied by electroplating. The material is platinum black, which can reduce the interfacial impedance of the electrode points and improve the charge storage capacity of the electrode points, thereby facilitating the recording of electrical signals and electrical stimulation by the electrode points.

[0047] The microelectrode in the above embodiments can perform multiple functions in cardiac ablation surgery: determining the contact between the electrode on the catheter and the heart tissue before ablation, performing irreversible electroporation ablation on the heart tissue, and recording electrocardiogram waveforms. A single device possesses multiple functions, reducing the need for multiple catheters with different functions during surgery. Multiple functions can be accomplished with a single catheter, thereby improving surgical efficiency, reducing surgical time, and ultimately enhancing the safety and efficiency of cardiac pulse field ablation. (Refer to...) Figure 6 When using microelectrodes to determine the contact between the microelectrode and cardiac tissue before ablation, the difference in conductivity between cardiac tissue and blood causes a change in impedance. The AC impedance values ​​measured by the electrode differ depending on whether the electrode and tissue are in contact or separated. (Refer to...) Figure 7 Microelectrodes can be used to record electrocardiogram signal waveforms. After forming an electrode modification layer on the electrode point, the signal-to-noise ratio of the recorded signal can be increased.

[0048] Another embodiment of the present invention provides a catheter, referring to Figure 8The head of the catheter 101 is equipped with a fractal microelectrode 102 for irreversible electroporation ablation as described in the above embodiment, which can move with the movement of the catheter 101. The electrode point of the microelectrode 102 is located at the center of the head of the catheter 101, ensuring that the tissue contacted by the catheter head is the ablation site, facilitating control of the ablation position by controlling the end of the catheter. Because the microelectrode 102 is flexible and integrated into the head of the catheter 101, it allows for highly precise ablation through flexible manipulation of the catheter, exhibiting high flexibility.

[0049] In some embodiments, the microelectrode 102 is attached to the head of the catheter 101 by UV-curing adhesive, thereby integrating the microelectrode 102 into the head of the catheter 101. The catheter 101 is inserted into the heart via a vein or artery of the organism through a minimally invasive interventional procedure, and the microelectrode 102 moves with the movement of the catheter 101.

[0050] Another embodiment of the present invention also provides a method for preparing the above-mentioned fractal structure microelectrode for irreversible electroporation ablation, referring to... Figure 9 The method includes:

[0051] S1. Fabricate a substrate layer on a silicon wafer and form pads on the substrate;

[0052] S2. An adhesive layer is made on the substrate layer, and then a conductive layer is made. The conductive layer is then patterned to form electrode points with fractal structures. The electrode points of the conductive layer include an anode in the center and a cathode located on the outer periphery of the anode. Both the anode and the cathode have interdigitated structures, and the interdigitated structures of the anode and the cathode are arranged in an intersecting manner.

[0053] S3. Fabricate an encapsulation layer on the conductive layer to obtain the electrode device;

[0054] S4. Spin-coating photoresist, patterning the photoresist through photolithography, and using dry etching to etch and expose the electrode points, pads and overall outline of the electrode devices.

[0055] S5. Release the electrode device from the silicon wafer and fabricate an electrode modification layer on the electrode point to obtain a fractal structure microelectrode for irreversible electroporation ablation.

[0056] In one specific embodiment, the method for fabricating the microelectrode includes:

[0057] S1, such as Figure 9 As shown in (a), a 5 μm thick layer of parylene-C was deposited on a 4-inch silicon wafer using chemical vapor deposition as the underlying substrate layer.

[0058] S2, such as Figure 9As shown in (b), a 20 nm thick chromium layer is sputtered onto the substrate as an adhesion layer, followed by a 300 nm thick gold layer; Figure 9 As shown in (c), photoresist is spin-coated and then patterned using photolithography; as... Figure 9 As shown in (d), chromium / gold is patterned using wet etching to form electrode points with fractal structures, and then the photoresist is washed away with acetone.

[0059] S3, such as Figure 9 As shown in (e), a 5 μm thick layer of parylene-C was deposited using chemical vapor deposition as the upper encapsulation layer.

[0060] S4, such as Figure 9 As shown in (f), photoresist is spin-coated and then patterned using photolithography; as... Figure 9 As shown in (g), the electrode point portion, the pad portion and the overall outline of the electrode device are etched and exposed using reactive ion etching, and then the photoresist is washed away with acetone.

[0061] S5. Remove the electrode devices from the silicon wafer and electroplate platinum black onto the electrode points using an electroplating method.

[0062] The fractal structure microelectrode and its preparation method for irreversible electroporation ablation in the above embodiments of the present invention are fabricated using MEMS technology. They can be used for cardiac pulse field ablation at lower voltages and have electrode and tissue contact detection and electrocardiogram signal recording functions. The ablation position accuracy is also greatly improved. The present invention can improve the safety and efficiency of irreversible electroporation ablation of the heart.

[0063] Specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art can make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention. The above preferred features can be used in any combination without conflict.

Claims

1. A fractal structure microelectrode for irreversible electroporation ablation, characterized in that, The microelectrode is applied to a catheter, and the microelectrode is a flexible electrode, comprising: The base layer has pads on it; A conductive layer is located above the substrate layer. The conductive layer includes electrode points that are electrically connected to the pads. Each electrode point includes a central anode and a cathode located around the anode. Both the anode and the cathode have interdigitated structures, and the interdigitated structures of the anode and the cathode are arranged in an intersecting manner. An encapsulation layer is located above the conductive layer, and the encapsulation layer exposes the electrode points and the pads; An electrode modification layer is formed on the electrode point to modify the electrode point; the electrode modification layer covers the electrode point, and the material of the electrode modification layer is any one of platinum black, iridium oxide, MXenes, and polyvinyl dioxythiophene-polystyrene sulfonic acid. An electrical pulse is applied to the heart tissue through the anode and the cathode, causing irreversible electroporation ablation of the heart cells. The interdigitated structure is a single-level or multi-level interdigitated structure. Through the fractal structure design of the electrode points, the ratio of the length to the area of ​​the geometric shape of the anode or cathode of the fractal structure is increased, thereby increasing the ratio of the length to the area of ​​the insulating edge of the electrode point. The fractal structure reduces the distance between the anode and cathode, thereby reducing the voltage required to cause irreversible electroporation of myocardial cells.

2. The fractal structure microelectrode for irreversible electroporation ablation according to claim 1, wherein, The applied electrical pulse can be any one of a unipolar square pulse, a bipolar square pulse, or an exponentially decaying pulse.

3. The fractal structure microelectrode for irreversible electroporation ablation according to claim 1, wherein, The applied electrical pulse has a voltage of 10-1000 V.

4. The fractal structure microelectrode for irreversible electroporation ablation according to claim 1, characterized in that, The thickness of the substrate layer and the encapsulation layer is 0.1-100 μm; the substrate layer and the encapsulation layer are made of the same or different materials, and the materials of the substrate layer and the encapsulation layer are any one of polyimide, parylene, SU-8 photoresist and silk protein.

5. The fractal structure microelectrode for irreversible electroporation ablation according to claim 1, characterized in that, The thickness of the conductive layer is 10-1000 nm.

6. A catheter, characterized in that, The head of the catheter is provided with a fractal structure microelectrode for irreversible electroporation ablation as described in any one of claims 1-5, wherein the electrode point of the microelectrode is located at the center of the head of the catheter.

7. The catheter according to claim 6, characterized in that, The microelectrode is attached to the head of the catheter using UV-curable adhesive. The catheter is inserted into the heart via a minimally invasive interventional procedure, and the microelectrode moves with the catheter.

8. A method for preparing a fractal structure microelectrode for irreversible electroporation ablation according to any one of claims 1-5, characterized in that, include: A substrate layer is fabricated on a silicon wafer, and pads are formed on the substrate; An adhesive layer is formed on the substrate layer, and then a conductive layer is formed. The conductive layer is then patterned to form electrode points with fractal structures. The electrode points of the conductive layer include a central anode and a cathode located on the outer periphery of the anode. Both the anode and the cathode have interdigitated structures, and the interdigitated structures of the anode and the cathode are arranged intersectingly. An encapsulation layer is fabricated on the conductive layer to obtain an electrode device; Spin-coat photoresist, pattern the photoresist using photolithography, and use dry etching to etch and expose the electrode points, the pads, and the overall outline of the electrode device. The electrode device is released from the silicon wafer, and an electrode modification layer is fabricated on the electrode point to obtain a fractal structure microelectrode for irreversible electroporation ablation.

Images