A flexible irreversible electroporation patch and methods of use thereof

Abstract

The application provides a flexible irreversible electroporation electrode patch for skin tumor treatment, which comprises a flexible electrode body, an electrode fixing adhesive, a release film, a cable fixing adhesive, a cable and a terminal. The flexible electrode body is composed of a 10-30 mu m thick polyimide film (PI) insulating substrate and a cover film clamping etched copper foil conductive circuit, the two ends of the circuit are respectively connected with a flexible conductive contact and a cable, the electrode fixing adhesive (diameter 50 mm with 3 split grooves) and the cable fixing adhesive respectively fix the patch and the cable, and the terminal is connected with a treatment host. The working electrode (4 evenly distributed in a 14-20 mm distribution circle) can be combined and switched in multiple groups, and is suitable for different sizes of skin tumors. The flexible electrode patch has good flexibility and stable fixation, can accurately control the electric field and the ablation range, avoids current mis-conduction, ensures safe and efficient treatment, and provides a special electrode scheme with strong adaptability and remarkable curative effect for irreversible electroporation treatment of skin tumors.

Description

Technical Field

[0001] This invention belongs to the field of skin tumor treatment technology, specifically relating to a flexible irreversible electroporation patch and its application method. Background Technology

[0002] The clinical treatment of benign and malignant skin tumors currently relies mainly on traditional methods such as surgical excision, radiotherapy, local chemotherapy, and photodynamic therapy. While surgical excision can directly remove the lesion, it presents problems such as significant trauma, postoperative scarring, and even functional limitations, especially for tumors on the face or joints, where the conflict between aesthetics and functional restoration is prominent. Radiotherapy, although non-invasive, carries the risk of complications such as skin fibrosis and depigmentation due to cumulative radiation dose, and requires multiple treatment cycles with low patient compliance. Local chemotherapy drugs (such as 5-fluorouracil ointment) can penetrate the epidermis to act on tumor cells, but the delivery efficiency is low due to the stratum corneum barrier, and it easily causes adverse reactions such as contact dermatitis. Photodynamic therapy relies on the synergistic effect of photosensitizers and specific wavelengths of light. Photosensitizers are metabolized slowly in the body, requiring patients to strictly avoid light for a period after treatment; otherwise, photosensitivity reactions may occur, causing significant inconvenience to daily life. Furthermore, photodynamic therapy typically only acts on the superficial layer of the skin (generally no more than 7 mm deep), and its effectiveness in treating deep or larger tumors is significantly limited.

[0003] The recently emerging technique of irreversible electroporation (IRE) offers a new approach to precision tumor treatment. It disrupts the integrity of tumor cell membranes through a high-voltage pulsed electric field, inducing selective apoptosis. This technique exhibits high selectivity in tissue damage, acting only on the cell membrane with minimal impact on normal tissue structures such as blood vessels, nerves, and connective tissue, thus meeting the need for protecting normal tissues in the treatment of skin tumors. IRE treatment avoids the collateral damage risks of traditional thermal ablation while effectively killing tumor cells, making it a commonly used treatment method in tumor research.

[0004] However, irreversible electroporation (IRE) still presents several challenges. First, the invasive nature of commonly used needle-like IRE electrodes can lead to bleeding, pain, and potential infection at the puncture site. Repeated punctures are necessary for multiple or large-area epidermal tumors, exacerbating patient suffering. Second, rigid electrodes struggle to adapt to dynamic curvature changes in the skin surface, especially in delicate anatomical areas like the eyelids and nose. Electrode positioning deviations can cause electric field distortion, resulting in insufficient treatment or damage to healthy tissue. Furthermore, prolonged wear can lead to electrode-tissue interface detachment due to skin deformation, and the lack of a real-time feedback mechanism for dynamic changes in epidermal impedance makes it difficult to maintain a stable electric field output. Third, the electric field parameters (such as pulse width and frequency) output by traditional IRE systems are often designed for deep solid tumors, making it difficult to flexibly adjust the ablation range based on tumor size. Direct application to skin tumors carries the risk of penetration depth overload, potentially damaging dermal collagen structures and subcutaneous nerve endings. Fourth, traditional IRE devices are bulky and can only be used in medical institutions, failing to meet the needs of continuous or repeated home treatment.

[0005] Therefore, there is a need to develop a novel electrode device that is flexible, deformable, adaptable to skin surface morphology, and combines non-invasiveness with precise treatment. Based on the aforementioned technical bottlenecks, this invention proposes a flexible wearable electrode patch, aiming to overcome the dual limitations of traditional treatment methods and existing IRE devices. Through the synergistic design of a biomimetic flexible structure and an intelligent control system, it achieves a unity of non-invasive application, surface adaptation, and precise energy delivery, compensating for the shortcomings of existing treatment methods, improving treatment effectiveness and safety, and showing broad application prospects as an alternative or supplementary treatment option. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides a flexible irreversible electroporation electrode patch and its application method. By attaching the irreversible electroporation patch to the skin and applying an electric field, the patch can achieve non-invasive adhesion to the tumor area and flexible adaptation to the skin curvature. Through precise electric field action, it achieves efficient and safe treatment of skin tumors while maximizing the protection of surrounding normal tissues, improving the patient's treatment experience and quality of life, and contributing to the further development of existing technologies.

[0007] To achieve the above objectives, the present invention adopts the following technical solution: This invention provides a flexible irreversible electroporation patch, comprising a flexible electrode body (01), an electrode fixing adhesive (02), a release film (03), a cable fixing adhesive (04), a cable (05), and a terminal (06); The flexible electrode body (01) comprises an insulating substrate (0101), a cover film (0102), a conductive line (0103) disposed between the insulating substrate (0101) and the cover film (0102), and a flexible conductive contact (0104); One end of the conductive line (0103) is provided with at least one working electrode (010301) penetrating the cover film (0102), and the flexible conductive contact (0104) is attached to the working electrode (010301); the other end of the conductive line (0103) is provided with a pad (010302) penetrating the insulating substrate (0101); the electrode fixing adhesive (02) is attached to the cover film (0102) side of the flexible electrode body (01), and the electrode fixing adhesive (02) has a through hole corresponding to the position of the working electrode (010301); The release film (03) covers the adhesive surface of the electrode fixing adhesive (02); one end of the cable (05) is electrically connected to the pad (010302), and the other end is connected to the terminal (06); the cable fixing adhesive (04) is used to fix a portion of the length of the cable (05) to the user's body surface.

[0008] Furthermore, both the insulating base (0101) and the cover film (0102) are made of polyimide film with a thickness of 10~30μm; the conductive line (0103) is formed on the rolled copper foil by etching process and is fixed to the insulating base (0101) and the cover film (0102) respectively by adhesive.

[0009] Furthermore, the number of the working electrodes (010301) is four, and they are arranged in a circular array; the electrode fixing adhesive (02) is circular with a diameter of 50 nm, and at least one dividing groove (0201) is provided on it, the center of which is concentric with the distribution circle of the working electrodes (010301).

[0010] Furthermore, the flexible conductive contact (0104) is a conductive gel or a conductive polyester fiber cloth.

[0011] Furthermore, the line width of the conductive line (0103) is 0.5-2mm; the diameter of the working electrode (010301) is 4mm, and the diameter of its distribution circle is 14-20mm; the diameter of the pad (010302) is 2mm, and the spacing between adjacent pads (010302) is not less than 10mm.

[0012] Furthermore, both the electrode fixing adhesive (02) and the cable fixing adhesive (04) are made of transparent polyurethane adhesive.

[0013] Furthermore, the terminal (06) is configured to be connected to the output port of the irreversible electroporation treatment host, and has conductive metal contacts and an insulating protective structure inside.

[0014] The present invention also provides a method for using the above-mentioned flexible irreversible electroporation patch, comprising the following steps: S1. Peel off the release film (03) covering the electrode fixing adhesive (02); attach the flexible electrode patch to the target position on the patient's body surface, and press to make the electrode fixing adhesive (02) adhere to the skin, wherein the dividing groove (0201) allows the electrode fixing adhesive (02) to adapt to uneven skin surfaces. S2. Flatten the cable (05) connected to the flexible electrode body (01) and fix it with the cable; S3. Use adhesive (04) to fix one end of the cable (05) to a non-treatment area on the patient's body surface; connect the terminal (06) at the end of the cable (05) to the treatment host.

[0015] Compared with the prior art, the present invention has the following beneficial effects: 1. The flexible electrode patch prepared by the present invention has good flexibility and adhesion: by using flexible electrodes and release film, it can be closely attached to the skin surface, avoiding short circuits and discharges caused by poor contact, and improving the safety of treatment.

[0016] 2. The ablation range of the flexible electrode patch prepared by this invention is controllable: By different combinations of the four electrodes (1 positive and 1 negative, 1 positive and 2 negative, etc.), and by optimizing the electrode array arrangement and pulse parameters, the electric field distribution range can be precisely controlled, realizing non-invasive treatment of epidermal or superficial dermal tumors and avoiding trauma caused by invasive operations.

[0017] 3. The wearable design of the flexible electrode patch prepared by the present invention: The patch is lightweight and soft, and with the help of the insulating adhesive layer, it can be worn repeatedly to meet the needs of continuous treatment at home and improve patient compliance. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the flexible electrode patch structure in an embodiment of the present invention, wherein the flexible electrode body is 01, the electrode fixing adhesive is 02, the release film is 03, the cable fixing adhesive is 04, the cable is 05, and the terminal is 06. Figure 2 The diagram shows the composition of the flexible electrode body, where Figure A is a top view of the structure and Figure B is a layered structure diagram; the components are: insulating substrate 0101, covering film 0102, conductive line 0103, flexible conductive contact 0104, working electrode 010301, and pad 010302, with d being the diameter of the working electrode. Figure 3 Electrode fixing adhesive 02, partition groove 0201; Figure 4 For cable fixing adhesive 04, A is 160mm and B is 50mm; Figure 5 Figure 1 shows the simulated equipotential surface distribution of a 300V / cm electric field for different electrode combinations. Purple circles represent positive electrodes, and blue circles represent negative electrodes. From bottom to top, the applied voltage changes: 1000V, 2000V, and 3000V. From left to right, the electrode diameter changes: 2mm, 3mm, and 4mm. Figure A shows the equipotential surface distribution after applying the corresponding voltage to one adjacent positive and one negative electrode. Figure B shows the equipotential surface distribution after applying the corresponding voltage to one opposite positive and one negative electrode. Figure C shows the equipotential surface distribution after applying the corresponding voltage to one positive electrode and two adjacent negative electrodes. Figure D shows the equipotential surface distribution after applying the corresponding voltage to one positive electrode and three negative electrodes. Figure 6 This is an ultrasound measurement image showing the changes in tumor size in mice treated with flexible electrode patches according to an embodiment of the present invention. Detailed Implementation

[0019] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. When the following description relates to the drawings, unless otherwise indicated, the same numbers in different drawings represent the same or similar elements. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with this application. Rather, they are merely examples of apparatuses, systems, devices, and methods consistent with some aspects of this application.

[0020] The flexible electrode patch of the present invention, as shown in the figure Figure 1 As shown, the flexible electrode patch consists of a flexible electrode body 01, electrode fixing adhesive 02, release film 03, cable fixing adhesive 04, cable 05, and terminal 06. The flexible electrode body 01 is composed of a 10-30μm thick polyimide (PI) insulating substrate 0101 and a cover film 0102 sandwiching etched copper foil conductive lines 0103. The two ends of the conductive lines 0103 are respectively connected to the flexible conductive contact 0104 and the cable 05. The electrode fixing adhesive 02 (50mm in diameter, with 3 dividing grooves) and the cable fixing adhesive 04 fix the patch and the cable 05 respectively. The release film 03 covers the cable fixing adhesive 04, and the terminal 06 connects to the treatment host.

[0021] (1) The specific structure of the flexible electrode body 01 is as follows: Figure 2 As shown, it consists of an insulating substrate 0101, a cover film 0102, a conductive line 0103, and a flexible conductive contact 0104. The conductive line 0103 is provided with a working electrode 010301 and a solder pad 010302.

[0022] The insulating substrate 0101 is made of polyimide film (PI) with a preferred thickness of 10-30 μm. It provides mechanical support and electrical insulation for the electrode patch body, provides a flat and stable carrier for the subsequent preparation of conductive areas, and its softness and flexibility facilitate adhesion to tissues.

[0023] The conductive line 0103 is made of rolled copper foil, and the circuit image is formed by etching process. The line thickness is preferably in the range of 0.3-1 ounce, and the line width is preferably in the range of 0.5-2 mm. The conductive line is fixed by adhesive and insulating substrate 0101.

[0024] The conductive line 0103 has a working electrode 010301 at one end. The working electrode is preferably 4mm in diameter, with four electrodes evenly distributed on a circumference of diameter d, which is preferably between 14-20mm. It passes through the covering film 0102 and connects to the flexible conductive contact 0104 to transmit energy to the patient. By switching the electrode combination (1 positive electrode and 1 negative electrode, 1 positive electrode and 2 negative electrodes, etc.), the electric field distribution range can be changed, precisely controlling the ablation area. For example, for small tumors (approximately 1cm in diameter), a compact arrangement of 1 positive electrode and 1 negative electrode is used to focus the electric field; for large tumors (2cm in diameter and above), an extended arrangement of 2 positive electrodes and 2 negative electrodes is used to expand the ablation area.

[0025] The other end of the conductive line 0103 is provided with a pad 010302, the pad diameter is preferably 2mm and the pad spacing L is not less than 10mm; it passes through the insulating substrate 0101 and is welded to the cable 05.

[0026] The cover film 0102 is made of polyimide film (PI) with a preferred thickness of 10-30 μm; it covers the conductive line 0103 and is fixed by adhesive, serving the same function as the insulating substrate 0101.

[0027] The flexible conductive contact 0104 is made of conductive gel or conductive polyester fiber cloth. One side is attached to the working electrode 01030, and the other side is attached to the target skin. Its flexible surface can better fit the skin, reduce interfacial resistance, and make the user comfortable.

[0028] (2) such as Figure 3 The electrode fixing adhesive 02 uses transparent PU adhesive to attach the working electrode to the skin surface. It is circular, with a diameter D preferably 50mm, concentric with the distribution circle d of the working electrodes. It has three dividing grooves 0201 between the electrodes to facilitate adhesion to uneven skin surfaces. It adheres to the non-conductive contact area of ​​the flexible base layer surface (i.e., the part where the electrode does not contact the skin), isolating the electrode from other parts of the skin to prevent misconduct of current; and using double-sided adhesive, it fixes the patch to the skin surface, ensuring that the patch does not shift during treatment.

[0029] (3) Release film 03, made of fluorine film, plastic film, etc., is covered on the fixed adhesive 02; its extremely low surface energy can be easily removed without damaging the adhesive itself.

[0030] (4) such as Figure 4 Cable fixing adhesive 04 is made of the same material as electrode fixing adhesive 02. It is used to attach the cable to the appropriate position on the patient and prevent the cable from pulling on the working electrode. Its dimensions are A = 160mm and B = 50mm.

[0031] (5) Cable 5 is used to connect the flexible electrode body 01 and terminal 06 to transmit energy.

[0032] (6) Terminal 6 is used to connect to the main unit and is matched with the output terminal of the external irreversible electroporation current transmitter. The port has built-in conductive metal contacts and an insulating protective structure. After being inserted into the main unit, it quickly establishes an electrical connection and avoids short circuits caused by external impurities and moisture. This ensures safe and stable current transmission during the treatment process and realizes energy transfer.

[0033] like Figure 5 The simulation of the equipotential surface distribution of a 300V / cm electric field for different electrode combinations is used to select appropriate electrodes and electric field parameters and control the electric field distribution after assessing tumor size and morphology. After assessing the tumor size and shape, the electrode combination is pre-selected and the equipotential surface is simulated to ensure that the tumor area is completely covered by the electric field, while reducing the voltage intensity within a certain range to minimize the occurrence of electric sparks, muscle tremors, etc.

[0034] In one possible implementation, the insulating substrate 0101 is selected as polydimethylsiloxane (PDMS), the cover film 0102 is selected as polydimethylsiloxane (PDMS), and the conductive line 0103 is selected as conductive ink. The conductive ink is attached to the insulating substrate by screen printing or a microelectronic circuit direct writing molding machine.

[0035] In one possible implementation, cables and terminals are removed, the main unit is miniaturized (and can be integrated with the power supply), and flexible electrodes are integrated, making it easy to carry and wear, suitable for patients who need to use it frequently for a long time.

[0036] Application Example 1 The prepared electrode patch was applied to mice. First, a skin tumor was implanted subcutaneously on the right back of the mouse. Seven days post-implantation, irreversible electroporation using a flexible electrode patch was performed. The size and morphology of the skin tumor were assessed to determine the number and location of the positive and negative electrodes. During treatment, the release film 03 of the patch was first removed, and then the electrode adhesive 02 was applied to the mouse skin tumor, with the flexible conductive contacts aligned with the tumor surface to ensure relatively complete coverage. The electric field range was simulated based on the tumor size to determine the number and polarity of electrodes used, and appropriate field strength parameters were selected to achieve good and complete tumor coverage. Figure 6 The ultrasound measurement diagram showing the change in mouse tumor size over time illustrates that after treatment with the electrode patch prepared in this invention, the mouse tumor gradually shrinks, demonstrating significant effectiveness in practical applications.

Claims

1. A flexible irreversible electroporation patch, characterized in that, Includes flexible electrode body (01), electrode fixing adhesive (02), release film (03), cable fixing adhesive (04), cable (05), and terminal (06); The flexible electrode body (01) comprises an insulating substrate (0101), a cover film (0102), a conductive line (0103) disposed between the insulating substrate (0101) and the cover film (0102), and a flexible conductive contact (0104); One end of the conductive line (0103) is provided with at least one working electrode (010301) penetrating the cover film (0102), and the flexible conductive contact (0104) is attached to the working electrode (010301); the other end of the conductive line (0103) is provided with a pad (010302) penetrating the insulating substrate (0101); the electrode fixing adhesive (02) is attached to the cover film (0102) side of the flexible electrode body (01), and the electrode fixing adhesive (02) has a through hole corresponding to the position of the working electrode (010301); The release film (03) covers the adhesive surface of the electrode fixing adhesive (02); one end of the cable (05) is electrically connected to the pad (010302), and the other end is connected to the terminal (06); the cable fixing adhesive (04) is used to fix a portion of the length of the cable (05) to the user's body surface.

2. The flexible irreversible electroporation patch according to claim 1, characterized in that, The insulating base (0101) and the cover film (0102) are both made of polyimide film with a thickness of 10~30μm; the conductive line (0103) is formed on the rolled copper foil by etching process and is fixed to the insulating base (0101) and the cover film (0102) respectively by adhesive.

3. The flexible irreversible electroporation patch according to claim 1, characterized in that, The number of working electrodes (010301) is four, and they are arranged in a circular array; the electrode fixing adhesive (02) is circular with a diameter of 50 nm, and at least one dividing groove (0201) is provided on it, the center of which is concentric with the distribution circle of the working electrodes (010301).

4. The flexible irreversible electroporation patch according to claim 1, characterized in that, The flexible conductive contact (0104) is a conductive gel or a conductive polyester fiber cloth.

5. The flexible irreversible electroporation patch according to claim 1, characterized in that, The conductive line (0103) has a line width of 0.5-2mm; the working electrode (010301) has a diameter of 4mm and a distribution circle diameter of 14-20mm; the pad (010302) has a diameter of 2mm and the spacing between adjacent pads (010302) is not less than 10mm.

6. The flexible irreversible electroporation patch according to claim 1, characterized in that, The electrode fixing adhesive (02) and the cable fixing adhesive (04) are both made of transparent polyurethane adhesive.

7. The flexible irreversible electroporation patch according to claim 1, characterized in that, The terminal (06) is configured to be connected to the output port of the irreversible electroporation treatment host, and has conductive metal contacts and an insulating protective structure inside.

8. A method of using a flexible irreversible electroporation patch according to any one of claims 1-7, characterized in that, Includes the following steps: S1. Peel off the release film (03) covering the electrode fixing adhesive (02); attach the flexible electrode patch to the target position on the patient's body surface, and press to make the electrode fixing adhesive (02) adhere to the skin, wherein the dividing groove (0201) allows the electrode fixing adhesive (02) to adapt to uneven skin surfaces. S2. Straighten the cable (05) connected to the flexible electrode body (01) and fix it using the cable; S3. Adhesive backing (04) fixes one end of the cable (05) to a non-treatment area on the patient's body surface; and connects the terminal (06) at the end of the cable (05) to the treatment host.

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