Preparation method of breakable sectional multi-channel electric field sensor array and product and application thereof

Abstract

The invention discloses a preparation method of a breakable sectional multi-channel electric field sensor array. The preparation method comprises the following steps: stripping a first insulating layer of a first metal wire at a certain interval, and then welding a conductive material to form an electrode contact to obtain a second metal wire; a second metal wire penetrates into the insulating tube, and a window is formed in the area corresponding to the electrode contact; a second metal wire and an insulating tube are welded in a non-exposed area between the electrode contacts to form a weak interface insulating section; the area, corresponding to the windowing, of the insulating tube is wrapped with a reflecting layer, and light-cured resin is coated for curing to form a second insulating layer; a breaking guide groove is shallowly etched in the area, corresponding to the weak interface insulation section, of the second insulation layer, and curing is carried out to form a breakable sectional type probe; and arranging to form a multi-channel electric field sensor array. The invention further discloses the multi-channel electric field sensor array obtained by the method and application of the multi-channel electric field sensor array in an intracranial electric field intensity distribution measuring device. The multi-channel electric field sensor array has the advantages of high spatial resolution, high anti-interference capability and mechanical-electrical stability.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biomedical engineering, in particular to a preparation method of a breakable segmented multi-channel electric field sensor array, as well as products and applications thereof. BACKGROUND

[0002] Tumor electric field therapy is a new cancer treatment method that interferes with the mitotic process of cancer cells by applying a medium-frequency alternating electric field, thereby inhibiting tumor growth. In order to optimize the effect of this treatment method, it is necessary to accurately measure the distribution of the electric field in the target area.

[0003] A device and method for detecting intracranial vector electric field of transcranial electrical stimulation are disclosed in Chinese Patent No. CN120154340A, which belongs to the technical field of detecting intracranial electric field of transcranial electrical stimulation. The device inputs an individual head model in the stimulation system, sets a target point and calculates transcranial electrical stimulation parameters; the implantation position and angle of the vector detection electrode are planned through the navigation system, the target area of the brain is stimulated through the stimulation electrode, and the intracranial electric signal is collected in real time through the vector detection electrode; the weak signal collected is amplified with high precision and converted into a digital signal; the electric field signal collected is calculated and processed in real time, and the electric field distribution generated in the brain by transcranial electrical stimulation is analyzed and visualized; the electric signals before and after stimulation are analyzed in time and frequency domains, and the influence of stimulation on the neural signals in the detection area is evaluated. Through the design of high-precision, multi-level vector detection electrodes, the invention realizes high-precision measurement of three-dimensional electric field intensity and direction.

[0004] A measuring device for tumor electric field therapy animal experiment is disclosed in Chinese Patent No. CN114983610A, which is a device for measuring electric field intensity in animals during tumor electric field therapy (TTFields) experiments. It includes three parts: a multi-channel equidistant measuring probe, a positioner, and a channel selector. The positioner fixes and positions the experimental animal, maintaining a fixed body position. The multi-channel equidistant measuring probe enters the animal's body through the measuring hole on the positioner, and quantitatively measures the electric field intensity at different positions and depths. The channel selector selects different measurement channel signals and transmits them to the display recording equipment. The device has reasonable design, high measurement accuracy, strong practicality and reliability, and plays an important role in optimizing tumor electric field therapy-related animal experiment schemes and optimizing simulation models.

[0005] 1. The probe structure is fixed and cannot be adjusted in depth The "equidistant multi-channel probe" in CN114983610A has fixed detection point positions at the time of manufacture, and such a multi-wire design is prone to signal crosstalk between channels, cannot flexibly adjust the sampling depth according to experimental requirements, and may introduce signal noise. It cannot be personalized and accurately adjusted in depth, limiting its applicability in complex brain area or weak signal collection experiments.

[0006] 2. Insufficient accuracy, difficult to meet high spatial resolution requirements Existing probes are mostly assembled by traditional manual methods, with a large channel center spacing (usually > 2 mm), making it difficult to meet the high-resolution measurement requirements of the electric field gradient changes in the fine brain structure of small mammals (such as hippocampus, thalamic nuclei). In addition, there is a lack of control means for the reliability of micro-scale solder joints and the consistency of interface impedance, affecting the measurement accuracy and repeatability.

[0007] 3. Signal interference challenge not addressed Although some schemes mention electromagnetic shielding, the overall device is still susceptible to external and contact-to-contact electromagnetic noise interference, especially in high-frequency environments.

[0008] However, there is currently a lack of effective tools to accurately measure the spatial intensity distribution of intracranial electric fields, especially in complex brain tissue environments. Therefore, developing a device that meets the above requirements has important clinical value. SUMMARY

[0009] The purpose of the present application is to provide a preparation method of a breakable segmented multi-channel electric field sensor array, which realizes controllable breakage of the probe by segment, and the multi-channel electric field sensor array arranged has the advantages of high spatial resolution, strong anti-interference ability and mechanical-electrical stability when applied in the measurement device of intracranial electric field intensity distribution.

[0010] To achieve the above-mentioned purpose of the application, the present application provides the following technical solutions: A preparation method of a breakable segmented multi-channel electric field sensor array, the preparation method comprising: (1) a metal wire coated with a first insulating layer on the surface as a first metal wire, stripping the first insulating layer at a certain interval on the first metal wire, and welding a conductive material in the area after stripping the first insulating layer to form an electrode contact, obtaining a first metal wire with several electrode contacts as a second metal wire; (2) inserting the second metal wire into the insulating tube, the electrode contact is attached to the inner wall of the insulating tube, and the area corresponding to the electrode contact on the insulating tube is windowed to expose the electrode contact; (3) sealingly connecting the second metal wire and the insulating tube by fusion between the non-exposed areas of the electrode contacts to form a weak interface insulating section; (4) wrapping a reflective layer on the insulating tube corresponding to the windowed area, and then coating a light-cured resin to form a second insulating layer through a first light curing; (5) etching a breakage guide groove in the second insulating layer corresponding to the weak interface insulating section, and then performing a second light curing to form a breakable segmented probe; (6) arranging a plurality of breakable segmented probes to form a multi-channel electric field sensor array.

[0011] The multi-channel electric field sensor array provided by the application is composed of a plurality of breakable segmented probes arranged side by side; each probe is divided into a plurality of mechanically and electrically independently separable segmented units along the longitudinal axis direction, and a weakened connecting part is arranged between adjacent segmented units to adapt to the implantation requirements of different depths of rat brain regions; the sensing end of each probe is arranged along a preset spatial geometric layout to form a two-dimensional or three-dimensional sensing array structure, so as to realize the synchronous collection of intracranial multi-point electric field intensity. The multi-channel electric field sensor array provided by the application solves the key technical problems of fixed sensor channels, multi-channel signal crosstalk, and poor mechanical-electrical stability in the prior art.

[0012] The breakage mode of the breakable segmented probe can be: before the sensor is implanted, the position of the target breakage guide groove is located through microscopic vision or a displacement scale; an axial pressure is slowly applied to the root of the target breakage guide groove; when the stress exceeds the local fracture strength, brittle fracture occurs at the breakage guide groove, exposing the pre-welded electrode end point.

[0013] In step (1), a platinum-iridium alloy guide wire coated with a polyimide insulating layer is selected as the first metal wire; a silver-copper alloy is used as a welding conductive material to form a spherical electrode contact.

[0014] Preferably, the polyimide insulating layer is stripped at intervals of 1.0±0.05 mm on the first metal wire, the diameter of the metal wire is 0.20±0.02 mm, the surface width of the exposed metal wire after stripping the first insulating layer is 0.30±0.03 mm, and the diameter of the electrode contact is 0.3±0.03 mm.

[0015] In step (2), the insulating tube is a thermoplastic polyurethane (TPU) tube or a polyimide tube; the shape of the window is a V-shaped notch or a grid, and the width of the window is 110% to 180% of the width of the electrode contact.

[0016] Preferably, the inner diameter of the insulating tube is 0.32±0.02 mm, and the wall thickness is 0.1±0.01 mm.

[0017] Preferably, a thermoplastic elastomer (TPU) tube is selected, and reinforcing ribs (width 0.05±0.01 mm, spacing 0.50±0.05 mm) are arranged on both sides of the tube body.

[0018] In the present application, the width of the window is greater than the width of the electrode contact to ensure that the electrode is completely exposed and does not cause short circuit between adjacent conductive layers. If the window is too small (e.g. ≤ 100%): it may lead to incomplete etching, insufficient exposure of the electrode, increased contact resistance, and affect the quality of signal acquisition; if the window is too large (e.g. ≥ 200%): it may expose too much conductive layer under the insulating layer, increasing the risk of short circuit or reducing the mechanical strength; therefore, the reasonable range is usually 110% to 180% of the width of the electrode: it can ensure that the electrode is completely exposed, and avoid excessive etching.

[0019] In step (3), the closed insulating section corresponds to and completely covers the non-exposed area (i.e. the interval) between two adjacent electrode contacts, which functions to build a continuous, electrically insulating packaging structure on the guide wire, ensuring that only the metal surface at the predetermined position is exposed as a sensing electrode, and the rest (especially between electrodes) is reliably insulated.

[0020] In step (4), the reflective layer is aluminum foil, and the photocurable resin is polyurethane acrylate.

[0021] In step (5), the depth of the breakage guide groove is 60-80% of the thickness of the second insulating layer, and the length of the breakage guide groove extends along the axial direction to cover the weak interface insulating section.

[0022] In step (6), the plurality of breakable segmented probes are arranged in an N×M matrix to form a multi-channel electric field sensor array, and the distance between adjacent probes is 500-1000 μm; or, the plurality of breakable segmented probes are distributed along a circular or arc trajectory to form a multi-channel electric field sensor array in a ring array; or, the plurality of breakable segmented probes are arranged in multiple columns to form a multi-channel electric field sensor array.

[0023] Among them, the matrix arrangement is suitable for the anatomical scale of rat hippocampus and cortex, the ring array is suitable for three-dimensional electric field monitoring around a specific brain area, and the insertion depth of each column of probes in the linear arrangement can be independently adjusted to realize cross-layer cortical electric field signal acquisition.

[0024] Preferably, the breakable segmented microprobe of the present application is prepared by the following steps: Electrode contact preparation: select a platinum-iridium alloy guide wire coated with a polyimide insulating layer, laser strip the insulating layer at an interval of 1.0±0.05 mm in the axial direction to expose the metal surface; weld silver-copper alloy solder in the exposed area to form a spherical electrode contact with a diameter of about 0.30±0.03 mm; Inserting the guide wire with electrodes into the TPU tube, ensuring that the electrodes are in contact with the tube wall; laser-cut a window at the corresponding electrode position on the TPU tube, in the shape of a V-shaped notch or grid, with a width of 150% (range: 110%–180%) of the electrode contact diameter, to fully expose the electrodes. Insulation segment formation: At the midpoint between adjacent electrodes (500 μm on each side), a 0.15 mm heating wire is used to heat at 120°C for 5 seconds to locally heat-fuse the TPU tube and the internal guide wire, forming a closed insulation segment with a length of 1.0 mm. Second insulation layer coating: After wrapping foil on the outside of the window area, a polyurethane acrylate light-curing resin is coated and cured by irradiation with ultraviolet light (365 nm) for 10 seconds to form a brittle outer insulation layer with a thickness of 30±5 μm. V-notch processing and reinforcement: A femtosecond laser was used to etch a V-shaped notch on the surface of the second insulating layer, corresponding to the weak interface region, with a depth of 21±3 μm (approximately 70% of the insulating layer thickness), a double-sided angle of 45°, and an axial length of 5.0 mm; then a second ultraviolet curing (365 nm, 20 seconds) was performed to improve the rigidity and stability of the insulating layer.

[0025] Functional verification and cutting: After the preparation of a single microprobe, the fracture performance was verified using a fracture sleeve.

[0026] Preferably, the breakable segmented probe provided by this invention is broken by a breakable sleeve. The breakable sleeve is a miniature axially slit metal or high-strength polymer tubular structure with an inner diameter slightly larger than the outer diameter of the microprobe. The axial slit facilitates insertion into and removal from the sensor. One end of the sleeve is equipped with an arc-shaped pressure head or an annular pressure ring, used to concentrate the force onto the root of the target V-shaped notch when axial pressure is applied.

[0027] Structural features of the break-off sleeve: Material: preferably stainless steel (such as 304L) or polyetheretherketone (PEEK), with sufficient rigidity and wear resistance; Inner surface: equipped with a low-friction coating (such as PTFE film) to reduce scratching of the outer photosensitive resin of the sensor; Front end structure: tapered or rounded transition to facilitate insertion and avoid damage to the sensor; Outer surface: equipped with anti-slip texture or connection interface for easy manual micro-operation.

[0028] The working principle of the break sleeve is as follows: Before sensor implantation, the break sleeve is axially fitted onto the outer layer of the sensor; the position of the target break guide groove is located by microscopic vision or displacement scale; axial pressure is slowly applied to the root of the target break guide groove; when the stress exceeds the local fracture strength, brittle fracture occurs at the break guide groove, exposing the pre-spot-welded electrode endpoints; then the pressure is removed, and the break sleeve is axially slid out.

[0029] The application also provides the breakable segmented multi-channel electric field sensor array prepared by the preparation method.

[0030] The application also provides application of the breakable segmented multi-channel electric field sensor array in a measurement device of intracranial electric field intensity distribution. The fixing device comprises a probe base and a multi-well plate installed on the probe base. The detection device comprises the multi-channel electric field sensor array, one end of which is fixed to the multi-well plate through the probe holder, and the other end is connected to the connector. The intracranial electric field intensity distribution measurement device based on the sensor array has the advantages of high spatial resolution, strong anti-interference ability, flexible operation, etc., can realize synchronous and accurate measurement of intracranial multi-point electric field intensity, and is suitable for animal experiment verification and individualized treatment parameter optimization of tumor electric field treatment.

[0031] The specific introduction of each component in the measurement device is as follows: Probe base: as the basic framework of the whole device, used for installing other components and ensuring stable connection between all components; the base can be fixed on the rat skull by using skull screws to ensure the stability and accurate position of the base.

[0032] Multi-channel electric field sensor array: composed of multiple thin probes, each probe end is connected to the connector, and can simultaneously collect electric field intensity information from multiple points.

[0033] Connector: responsible for connecting the probe with the external data collection system to realize data transmission. Generally, a differential probe or an isolated oscilloscope will be connected later. In order to ensure that the connector will not have cable twisting and winding problems during the movement of the rat, a rotating disc and a telescopic wire are added in the design of the connector. The wire is allowed to freely stretch within a certain range to adapt to the movement range of the rat. At the same time, there is a anti-pulling protection to prevent the wire from being damaged due to excessive stretching.

[0034] Channel selector and differential probe connection: the channel selector receives signals from the probe and selects specific channels for measurement as needed, and the selected signals are transmitted to the differential probe, which is used to improve signal quality and reduce noise interference. By selecting specific probe channels for data reading, the experimental efficiency is improved.

[0035] Differential probe and oscilloscope connection: the signals processed by the differential probe are sent to the oscilloscope, and the oscilloscope displays the real-time electric field intensity change curve, which is convenient for researchers to observe and analyze data.

[0036] Synchronous triggering module and computer, signal generator connection: the synchronous triggering module is the core control unit of the whole system, which is connected with the computer and the signal generator through the cable; the computer is used for setting experimental parameters and controlling experimental process, and the signal generator generates the required electric field signal; the synchronous triggering module ensures the time synchronization between the treatment module and the measurement module, and allows the electric field intensity change and the physiological parameters to be recorded at the same time.

[0037] Signal generator and power amplifier connection: the electric field signal generated by the signal generator is transmitted to the power amplifier through the cable, and the power amplifier amplifies the signal to ensure that enough energy is applied to the experimental animal.

[0038] Power amplifier and transducer piece connection: the amplified electric field signal is output from the power amplifier, and after being adjusted by the hand-adjusted resistance, it is finally transmitted to the transducer piece. The transducer piece is attached to the skin of the experimental animal, and the electric signal is converted into an electric field to act on the intracranial.

[0039] Transducer piece and experimental animal connection: the transducer piece directly contacts the skin of the experimental animal, ensuring that the electric field can effectively penetrate the skull and reach the target area in the intracranial.

[0040] The connector is provided with a rotating disc and a telescopic lead wire, which is used for adjusting the extension and retraction of the lead wire.

[0041] The device comprises an electromagnetic shielding box, and the experimental animal is placed in the electromagnetic shielding box; during measurement, the fixing device and the detection device are located in the electromagnetic shielding box, and the signal acquisition device and the signal triggering device are located outside the electromagnetic shielding box.

[0042] Compartment design: in order to reduce external interference, the experimental animal is placed in an electromagnetic shielding box to form a compartment, so as to reduce the influence of external electromagnetic interference on the measurement result and ensure the accuracy of measurement.

[0043] The channel selector provided by the application has the following functions: Multi-channel selection: allows users to select specific probe channels for data reading, improving experimental efficiency.

[0044] Automatic switching: supports automatic channel switching for continuous data acquisition.

[0045] The connector is provided with a rotating disc and a telescopic lead wire, which is used for adjusting the extension and retraction of the lead wire.

[0046] The device comprises an electromagnetic shielding box, and the experimental animal is placed in the electromagnetic shielding box; during measurement, the fixing device and the detection device are located in the electromagnetic shielding box, and the signal acquisition device and the signal triggering device are located outside the electromagnetic shielding box.

[0047] Compared with the prior art, the application has the following excellent effects: The application realizes a single-wire multi-channel, high-density and step-by-step exposed sensor structure by means of a femtosecond laser precision machining V-shaped notch and a spot welding process; the mechanical strength and electrical stability of the micro-scale sensor are significantly improved by combining the photosensitive resin coating and the secondary curing process; in actual animal experiments, the spatial resolution reaches 1.0 mm, which is suitable for high-precision and dynamic measurement of intracranial electric field in tumor electric field treatment.

[0048] The application adopts a metal guide wire + local electrode welding + double-layer insulation packaging to construct a sensing unit; a mechanical weak interface structure (hot fusion closed section + femtosecond laser V-shaped notch) is arranged on the probe axis to realize step-by-step controllable breaking; a two-dimensional / three-dimensional array is formed by spatial arrangement of multiple probes to cover the target brain area; in combination with an electromagnetic shielding measurement system, low-noise and synchronous triggering electric field detection is realized. The sensor array can be selectively removed during implantation or after operation, and only the sensing section corresponding to the target brain area is retained, thereby significantly reducing tissue damage and signal interference.

[0049] The foldable segmented multi-channel electric field sensor array and the intracranial electric field intensity distribution measuring device provided by the application not only realize accurate measurement of the spatial intensity distribution of the intracranial electric field, but also help to understand the mechanism of TTFields, and the simple and easy-to-use probe design and preparation method is easy to popularize and use; and the device has compact structure, flexible operation and strong adaptability, and can be widely used in research of various animal models, and has important clinical value. BRIEF DESCRIPTION OF DRAWINGS

[0050] Figure 1 It is a schematic diagram of the overall structure of the foldable segmented multi-channel electric field sensor array in the embodiments of the application; Figure 2 It is a local enlarged view of the foldable segmented probe, showing a V-shaped notch, a metal wire exposed end and a spot welding connection structure; Figure 3 It is an assembly drawing of the foldable segmented probe; Figure 4 It is a cross-sectional schematic view of the sensor array in an unbroken state, showing the layered structure of the metal wire, the TPU tube, the insulating layer and the external photosensitive resin coating layer; Figure 5 It is a schematic diagram of the three-dimensional structure of the measuring device, showing the layout relationship of the fixing device, the detection device, the electromagnetic shielding box and the signal acquisition / triggering equipment. DETAILED DESCRIPTION

[0051] In order to further illustrate the application, the specific embodiments of the application will be described in detail below in combination with the drawings and examples. The embodiments do not limit the technical scope of the application, but provide specific guidance for understanding and implementing the application.

[0052] Example 1: Preparation of breakable segmented multi-channel electric field sensor array Step (1): Guide wire substrate processing and electrode contact preparation Select a platinum-iridium alloy (PtIr, 90 / 10) guide wire with a diameter of 0.20±0.02 mm as the conductive substrate, and uniformly coat a layer of polyimide (PI) insulating layer with a thickness of 2±0.2 μm on its surface by spin coating process to form the first insulating layer 3, denoted as the first metal wire 1.

[0053] Use a laser to accurately strip the polyimide layer in the axial direction of the first metal wire 1 at an equal interval of 1.0±0.05 mm, exposing a metal surface with a width of 0.30±0.03 mm. The stripped area serves as the electrode welding site.

[0054] Fix the first metal wire 1 after stripping the electrode welding site in the groove of a quartz mold (groove diameter 0.25±0.03 mm, depth 0.15±0.02 mm), and place a silver-copper alloy (AgCu) solder ball (melting point about 250°C) with a diameter of 0.20±0.02 mm at each exposed area. Heat to 300°C under nitrogen protection for 5 seconds to melt the solder and form a firm metallurgical connection with the platinum-iridium guide wire, and after cooling, form a spherical electrode contact 2 with a diameter of about 0.30±0.03 mm, denoted as the second metal wire.

[0055] In this embodiment, the silver-copper alloy has excellent electrical conductivity and weldability, and the spherical structure is beneficial for stress dispersion and uniform signal collection.

[0056] Step (2): Insulating tube insertion and windowing processing Select a TPU tube as the outer support tube (insulating tube 4), with an inner diameter of 0.32±0.02 mm and a wall thickness of 0.10±0.01 mm, to ensure that the second metal wire can be inserted smoothly and that the electrode contacts are tightly attached to the tube wall of the insulating tube 4.

[0057] The TPU tube (insulating tube 4) has reinforcing rib structures (width 0.05±0.01 mm, spacing 0.50±0.05 mm) on both sides along the axial direction, which are used to improve the bending stiffness of the tube body and guide the breaking direction.

[0058] Insert the second metal wire into the TPU tube (insulating tube 4) and adjust the position so that all electrode contacts 2 are located in the corresponding area inside the TPU tube.

[0059] Use a laser to perform "windowing" processing on the outer wall of the TPU tube (insulating tube 4) corresponding to each electrode contact 2. The windowing shape is: V-shaped notch (opening angle 45°), preferably used for directional bending applications; or grid structure (strip width 0.05 mm, pitch 0.05 mm) for isotropic flexible scenarios; The width of the window 5 is 110% to 180% of the width of the electrode contact.

[0060] In this embodiment, the shape of the window 5 is a V-shaped notch, and the transverse width of the window 5 is 150% of the diameter of the electrode contact (i.e. about 0.45 mm), ensuring that the electrode is completely exposed and leaving a process tolerance.

[0061] In this embodiment, the TPU has both flexibility and hot welding performance; the window 5 design takes into account signal exposure and structural integrity.

[0062] Step (3): Weak interface insulation section formation At 500 μm on both sides of each electrode contact 2 (i.e. at the middle position of the two electrodes), a nickel-chromium heating wire with a diameter of 0.15 mm is used to heat at 120°C for 5 seconds to locally heat and fuse the TPU tube and the internal guide wire (second metal wire). During the fusion process, the TPU softens and forms a sealed connection with the surface of the guide wire, forming a closed insulation section 7 with a length of 1.0 mm.

[0063] In this embodiment, the hot welding achieves an airtight seal to prevent body fluids from seeping in; the 1.0 mm length matches the electrode spacing, and if necessary, the probe can be cut at the hot welding point.

[0064] Step (4): Second insulation layer coating and primary curing Outside the windowed area of the TPU tube, a layer of aluminum foil paper 9 (as a reflection layer to prevent excessive penetration of UV light and damage to the internal wire) with a thickness of 5 μm is wrapped first, and then a layer of polyurethane acrylate light-curing resin is uniformly coated.

[0065] This resin has low shrinkage, high hardness and brittleness (elongation at break < 3%), which is suitable for subsequent laser processing.

[0066] Under the irradiation of ultraviolet light with a wavelength of 365 nm for 10 seconds, the first light curing is performed, and a brittle second insulation layer 6 with a thickness of 30±5 μm is formed. This layer covers the entire probe surface, and only the electrode contact 2 is exposed through the window 5.

[0067] Step (5): V-shaped notch etching and secondary curing On the surface of the second insulation layer 6 after the primary curing (UV irradiation for 10 s), a femtosecond laser (wavelength 800 nm, pulse width 100 fs, repetition frequency 1 MHz) is used to etch a V-shaped notch structure as a breaking guide groove 8 in the corresponding area of the weak interface insulation section 7.

[0068] Depth: control for the second insulating layer 6 thickness of 70%, namely 21 ± 3 μm (not to penetrate, to retain the bottom layer integrity); Angle: bilateral tilt 45°, forming a sharp stress concentration point; Length: extend 5.0 mm along the axial direction, covering the entire weak interface region.

[0069] The V-shaped notch serves as a breaking guide groove 8, guiding the crack to propagate along the predetermined path when the bending force is applied.

[0070] Subsequently, secondary ultraviolet curing is carried out: irradiation under 365 nm UV for 20 seconds, so that the photocuring resin is fully crosslinked, the hardness and chemical stability of the second insulating layer 6 are improved, and the preparation of the single breakable segmented microprobe is completed.

[0071] In this embodiment, the femtosecond laser processing has high precision and small heat-affected zone; the secondary curing enhances the durability of the structure and improves the rigidity of the insulating layer.

[0072] Step (6): multi-channel array integration Fix 4-16 probes prepared above on the substrate in a 4x4 matrix or linear arrangement, with a probe spacing of 300-500 μm.

[0073] The overall structure of the breakable segmented multi-channel electric field sensor array in the embodiment of the application is shown in Figure 1 ; Figure 2 and Figure 3 is a local enlarged view and an assembly structure diagram of the breakable segmented probe, showing the V-shaped notch, the exposed end of the metal wire, and the spot welding connection structure; Figure 4 is a cross-sectional schematic view of the sensor array in an unbroken state, showing the layered structure of the metal wire, the TPU tube, the insulating layer, and the external photosensitive resin coating layer.

[0074] Example 2: Construction of an intracranial electric field intensity distribution measurement device Based on the sensor array prepared in Example 1, a complete intracranial electric field measurement system is constructed, including a fixing device, a detection device, a signal acquisition device, and a signal triggering device.

[0075] This embodiment provides an integrated device for measuring the intracranial electric field intensity distribution of rats, which combines a breakable segmented multi-channel electric field sensor array with a synchronous stimulation-acquisition system to achieve high spatiotemporal resolution, low noise, and dynamically adjustable intracranial electric field monitoring.

[0076] As shown in Figure 5 , the overall structure of the measurement device includes the following four core modules: Fixing device: for stabilizing the implanted probe and fixing it to the animal skull; Detection device: contains a breakable segmented multi-channel electric field sensor array, responsible for in-situ acquisition of intracranial electric field signals; Signal acquisition device: for selection, amplification and recording of multi-channel signals; Signal triggering device: for generating external electric stimulation signals and triggering synchronization with the acquisition system.

[0077] All modules work together to achieve high-fidelity, synchronized electric field measurement in an electromagnetic shielding environment.

[0078] Among them, the fixing device includes a probe base and a multi-well plate installed thereon. The probe base is made of biocompatible polyether ether ketone (PEEK) material through precise injection molding or machining molding, with a size of 12 mm × 12 mm × 3 mm, and four threaded holes are provided at the bottom, which can be firmly fixed to the rat skull surface (such as 2 mm behind the anterior fontanel, 1.5 mm apart) through skull screws, to ensure long-term implant stability. The multi-well plate is integrated above the base and is a through-hole structure (pore diameter 0.35±0.02 mm, hole spacing 500 μm) arranged in a 3×3 or 4×4 array, which is used to accurately guide and position the implantation angle and depth of each microprobe. The multi-well plate is also equipped with a probe fixer (miniature compression clamp) that can lock the position after the probe is inserted to prevent postoperative displacement.

[0079] Among them, the detection device includes a breakable segmented multi-channel electric field sensor array prepared in Example 1, which is composed of 8-16 microprobes, each with a length of 6-10 mm and an electrode spacing of 1.0±0.05 mm, forming independent sensing channels. The distal end of the probe is inserted vertically into the rat brain tissue (such as the cortex, hippocampus or thalamus) through the multi-well plate, and the proximal end of the lead is connected to a miniature connector after being led out; the connector is fixed to the side of the probe base and has the following design features: rotating disc structure: built-in precision bearing, allowing the connector housing to rotate freely in the horizontal plane ±360°, preventing the lead from winding when the rat is free to move; telescopic lead assembly: internal spiral spring lead, suitable for animal movement range; anti-pulling protection mechanism: mechanical limiting structure is set, which automatically releases when the pulling force exceeds 0.5 N, avoiding the probe being pulled out; during the experiment, the probe can be segmented under a microscope by an external breaking sleeve (stainless steel microforceps), only retaining the sensing segment corresponding to the target brain area, achieving "on-demand sensing".

[0080] The signal acquisition device is used for receiving, selecting and recording weak electrophysiological signals from the sensor array, and includes the following components connected in sequence: a connector: transmitting the probe array output signal to an external system; a multi-channel selector (an 8x8 analog switch array): supporting a maximum of 32 channels of input, which can be remotely controlled by a computer software, selecting any single channel or multiple channels for synchronous output; supporting an automatic scanning mode, which cyclically switches channels at a rate of 10 Hz to achieve continuous monitoring of the entire array; a differential probe (such as a gain of 50x and an input impedance of 16 MΩ): differentially amplifying the selected signal to effectively suppress common-mode noise (such as 50 Hz power frequency interference); an oscilloscope or data acquisition card: a sampling rate of 2 GSa / s, a resolution of 12 bits, and a bandwidth of 0.1-10 kHz, which is used for real-time display and storage of the electric field intensity change curve.

[0081] All signal acquisition devices are placed outside the electromagnetic shielding box and connected with the devices inside the box through a shielding feedthrough interface.

[0082] The signal triggering device is used for applying a controllable external electric field stimulation and achieving time synchronization with the acquisition system, and includes: a synchronous triggering module: as the timing control center of the system, receiving the experiment start instruction from the computer, and sending a trigger pulse (TTL signal) to the signal generator, and sending an acquisition start signal to the oscilloscope, to ensure synchronization of stimulation and recording; a signal generator (such as Keysight 33600A): generating sine wave, square wave or pulse sequence signals, with a frequency range of 0.1-100 Hz and an amplitude of 0.1-5 Vpp, which can simulate different types of electric stimulation paradigms; a power amplifier (such as ATA-2031): amplifying the low-power signal to ±20 V RMS output capability to ensure sufficient driving strength; a current-limiting resistor (100 Ω): connected in series in the output loop to limit the current to ensure animal safety; a transducer sheet: using a niobium-magnesium-lead-lead titanate [PMN-PT] electrode (diameter 8 mm) attached to the surface of the rat skull (such as the forehead or parietal bone) to convert the electric signal into an intracranial electric field. The transducer sheet is in close contact with the skin through medical conductive paste, which reduces impedance and improves the penetration efficiency of the electric field.

[0083] In order to eliminate environmental electromagnetic interference, the entire measurement system is integrated in an electromagnetic shielding box: the shielding box is composed of double-layer copper mesh (aperture < 1 mm) and is grounded; the experimental animal is placed in the internal compartment of the shielding box, and the fixing device and the detection device are located inside the box; the signal acquisition device and the signal triggering device are located outside the box and are connected through a shielded cabin terminal to avoid signal leakage; the box body is provided with an observation window (conductive glass) to support long-term conscious animal experiments.

[0084] Example 3: Measurement of Intracranial Electric Field Intensity Distribution in Rats After the experimental mice are anesthetized, they are fixed on the head fixation support for skull exposure and drilling; The sensor array is installed on the multi-well plate, and initially all V-shaped notches are not broken; The next V-shaped notch is broken by the breaking sleeve as needed, exposing the next electrode end point, and achieving different depth measurements; Slowly insert the sensor into the target brain area (such as subcortical 1.0 mm); Start the signal trigger device to apply a 200 kHz, 2 V / cm electric field; Read the current electric field signal through the channel selector, and record it on the oscilloscope after differential amplification; Upload data to the host computer to generate a three-dimensional electric field distribution map for verifying the TTFields simulation model or optimizing the treatment parameters.

[0085] Data analysis: Use computer software to process the collected data and draw an electric field intensity distribution map. Analyze the differences in electric field intensity at different depths and positions to evaluate the effectiveness of electric field therapy. Specifically, the following steps are included: (1) Data preprocessing Data import: Import the collected electric field intensity data into the computer. Use data processing software (such as MATLAB, Python, etc.) to read the data file.

[0086] Data arrangement: Arrange the data into a format suitable for drawing. Usually, the data needs to be classified by position and depth to form a multi-dimensional array or table.

[0087] (2) Data visualization Scatter plot: Use a scatter plot to show the electric field intensity values at each probe position. The coordinates of each point represent the position of the probe, and the color or size represents the electric field intensity; Heat map: Use a heat map to show the distribution of electric field intensity. The heat map can more intuitively display the trend of electric field intensity changes.

Claims

1. A method of making a breakable segmented multi-channel electric field sensor array, characterized by, The preparation method comprises: (1) taking a metal wire coated with a first insulating layer as a first metal wire, peeling off the first insulating layer at intervals on the first metal wire, and welding a conductive material on the area after the first insulating layer is peeled off to form an electrode contact, thereby obtaining a first metal wire with several electrode contacts as a second metal wire; (2) inserting the second metal wire into an insulating tube, with the electrode contacts adhering to the inner wall of the insulating tube, and opening a window on the insulating tube corresponding to the area of the electrode contacts to expose the electrode contacts; (3) sealingly connecting the second metal wire and the insulating tube at the non-exposed area between the electrode contacts to form a weak interface insulating section; (4) wrapping a reflective layer on the area of the insulating tube corresponding to the window, and then coating a light-cured resin for one light curing to form a second insulating layer; (5) shallowly etching a breakage guide groove in the area of the second insulating layer corresponding to the weak interface insulating section, and performing secondary light curing to form a breakable segmented probe; (6) arranging several breakable segmented probes to form a multi-channel electric field sensor array.

2. The method of claim 1, wherein the method further comprises: In step (1), a platinum-iridium alloy guide wire coated with a polyimide insulating layer is selected as the first metal wire; and silver-copper alloy is used as the conductive material for welding to form a spherical electrode contact.

3. The method of claim 1, wherein the method further comprises: In step (2), the insulating tube is a thermoplastic polyurethane (TPU) tube or a polyimide tube; the shape of the window is a V-shaped notch or a grid, and the width of the window is 110% to 180% of the width of the electrode contact.

4. The method of claim 1, wherein the method further comprises: In step (4), the reflective layer is aluminum foil, and the light-cured resin is polyurethane acrylate.

5. The method of claim 1, wherein the method further comprises: In step (5), the depth of the breakage guide groove is 60-80% of the thickness of the second insulating layer, and the length of the breakage guide groove extends along the axial direction to cover the weak interface insulating section.

6. The method of claim 1, wherein the method further comprises: In step (6), the several breakable segmented probes are arranged in an N×M matrix to form a multi-channel electric field sensor array, and the distance between adjacent probes is 500-1000 μm; or, the several breakable segmented probes are distributed along a circumferential or arc trajectory to form a ring array to constitute a multi-channel electric field sensor array; or, the several breakable segmented probes are arranged in multiple linear arrays to form a multi-channel electric field sensor array.

7. A breakable segmented multi-channel electric field sensor array obtained by the preparation method of any one of claims 1-6.

8. Use of the breakable segmented multi-channel electric field sensor array according to claim 7 in a device for measuring the intracranial electric field intensity distribution, characterized in that, The measuring device comprises: a fixing device comprising a probe base and a multi-well plate mounted on the probe base; a detection device comprising the multi-channel electric field sensor array, one end of which is fixed to the multi-well plate through a probe holder, and the other end is connected to a connector; a signal acquisition device comprising a connector, a channel selector, a differential probe, and an oscilloscope connected in sequence; a signal triggering device comprising a synchronous triggering module, a signal generator, a power amplifier, a resistor, and a transducer sheet connected in sequence.

9. Use according to claim 8, characterized in that, The connector is provided with a rotating disc and a telescopic lead wire for adjusting the extension of the lead wire.

10. Use according to claim 8, characterized in that, The device comprises an electromagnetic shielding box, and the fixing device and the detection device are located in the electromagnetic shielding box, and the signal acquisition device and the signal triggering device are located outside the electromagnetic shielding box.

Images