Implanted probe system for synchronous sampling of three-dimensional electric field vector detection and microdialysis

Abstract

The invention discloses a three-dimensional electric field vector detection and microdialysis synchronous sampling implanted probe system, and belongs to the technical field of neural electrophysiology detection. The system comprises a vector electric field detection module (containing multiple layers of platinum-iridium alloy contacts) and a microdialysis module (provided with a semi-permeable membrane window with high selectivity and biological compatibility) which are coaxially integrated, and spatial isolation and synchronous acquisition of electro-chemical signals are realized through an insulating support structure. The problems of separation and spatial dislocation of an electric field detection and biochemical sampling system in the prior art are solved, real-time association of three-dimensional electric field vector reconstruction and neurotransmitter analysis is supported, and accurate electro-chemical coupling data is provided for nerve regulation and control research.

Description

Technical Field

[0001] This invention belongs to the field of neurophysiological detection technology, specifically relating to an implantable probe system for simultaneous three-dimensional electric field vector detection and microdialysis sampling, which is suitable for real-time three-dimensional electric field measurement and simultaneous biochemical signal analysis in brain tissue or other tissue environments in vivo. Background Technology

[0002] With the advancement of technology, electric fields are widely used in research on regulating brain activity and assessing the state of neural networks. Especially in non-invasive or minimally invasive neuromodulation techniques, achieving high-precision sensing of local electric fields and combining this with analysis of neurotransmitter release based on changes in chemical signals is a crucial step in realizing closed-loop regulation.

[0003] Currently, microdialysis technology is widely used to collect small molecule components such as neurotransmitters and metabolites from local tissue fluid in vivo. However, electric field detection usually relies on uniaxial or biaxial electrode arrays, which can only obtain one-dimensional or two-dimensional potential information, making it difficult to achieve complete measurement of electric field vectors in three-dimensional space. In addition, the two systems are often arranged independently, with non-overlapping spatial positions and asynchronous signal acquisition, making it difficult to reveal the coupling mechanism between neurotransmitter changes and local electric field responses. For example, patents CN115103628 A and CN 216594878 U disclose brain tissue microdialysis probes with different structures, which can be used to collect biochemical substances such as neurotransmitters in the brain, but do not involve structures or methods for synchronous recording of electrical signals; patent CN120154340A discloses an implantable microelectrode array for monitoring brain region electrical activity, but its structure is limited to electrical signal acquisition and lacks chemical substance sampling capabilities. Similarly, the probe described in CN113367665A attempts to integrate two detection functions, but still does not achieve deep brain electric field vector measurement capabilities, nor does it have a structural registration and synchronization strategy with the microdialysis window.

[0004] Therefore, there is an urgent need for a novel probe system that integrates structure, synchronizes signals, and fuses functions, enabling simultaneous three-dimensional electric field vector detection and local neurotransmitter sampling within the same implanted structure, thereby providing more comprehensive and accurate data support for neuromodulation research. Summary of the Invention

[0005] To address the problems of separation, spatial misalignment, and asynchronous acquisition in existing technologies, the present invention proposes an implantable probe system for simultaneous three-dimensional electric field vector detection and microdialysis sampling. This system adopts a multi-layer coaxial integrated structure, integrating a three-dimensional electric field vector electrode array and a central axial microdialysis channel in a slender columnar probe structure. It can achieve high spatiotemporal accuracy of electrochemical signal co-monitoring within the target tissue and is suitable for biomedical scenarios such as animal experiments and deep brain implantation.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] An implantable probe system for simultaneous three-dimensional electric field vector detection and microdialysis sampling includes:

[0008] 1. The vector electric field detection module is located around the probe and has a slender columnar structure, which is bio-implantable and has a certain degree of mechanical rigidity;

[0009] 1a. Support structure, including a ring structure and longitudinal connecting pillars, used to fix each electrode layer and provide mechanical support to ensure implantation stability and deformation control.

[0010] Furthermore, the supporting structure material is a polymer material with good biocompatibility and insulation properties, such as polyimide (PI), to prevent electrical signal crosstalk and enhance probe implantation stability.

[0011] Furthermore, the support structure also serves to isolate the microdialysis fluid system from the electrical signal transmission path, avoiding electrochemical interference and signal crosstalk.

[0012] 1b. Detection contacts are set on the circumferential outer surface of the support structure, with multiple detection layers distributed along the axial direction. Each layer has at least three detection contacts evenly distributed in azimuth angles (preferably at 120° intervals) to solve for the electric field vector components in the XYZ directions, thereby realizing three-dimensional electric field vector calculation.

[0013] Furthermore, the preferred material for the detection contact is a platinum-iridium alloy, which possesses excellent conductivity, bioinertness, and long-term implantation stability.

[0014] Optionally, the interval between two adjacent detection contacts is 1 mm, which is adjustable to accommodate different tissue spatial scales and resolution requirements.

[0015] Furthermore, the electrode signal leads are located within a rigid support structure, are made of highly conductive material, are covered with an insulating layer, and converge to the signal connector at the probe tail, connecting to the electrical signal acquisition module.

[0016] Optionally, the electrode array supports dual-function switching between detection and stimulation, enabling the design of a closed-loop neuromodulation system.

[0017] 2. The microdialysis module is located on the central axis of the probe body, running through the longitudinal axis of the probe. It is equipped with micro inlet and outlet channels for exchanging and sampling small molecules such as neurotransmitters in the target tissue.

[0018] The microdialysis channels (inlet channel 2a and outlet channel 2b) run through the entire probe axis and are used for the input of dialysis fluid and the output of samples.

[0019] Furthermore, the channel material is usually made of polymer tubing such as polyethylene or polyimide, with an inner diameter adapted to the microfluidic system.

[0020] Furthermore, the inlet and outlet channels of the microdialysis channel are also connected to an external micropump system via hoses or micro-connectors to control the dialysate flow rate and sampling rate.

[0021] Furthermore, all signal and fluid interfaces are concentrated at the probe tail, facilitating overall packaging and system integration.

[0022] 2c. Microdialysis membrane window, located at the front end of the microdialysis channel and aligned with the uncovered area between the electrode layer, is used to achieve diffusion exchange of small molecules in the dialysate and tissue fluid.

[0023] There is a non-overlapping area between the microdialysis membrane window and the electrode layer, achieving spatial separation of electrochemical functions.

[0024] Beneficial effects

[0025] 1. Achieve spatially overlapping and temporally synchronized three-dimensional electric field vector detection and microdialysis sampling within the same implanted probe;

[0026] 2. Avoid electrochemical interference and signal crosstalk between different functional modules to improve signal quality and biological safety;

[0027] 3. Enhance the ability to synchronously monitor and provide feedback on the "electrochemical" coupling mechanism in neural regulation;

[0028] 4. The probe has a compact structure and strong biocompatibility, making it suitable for deep brain implantation and animal model experiments;

[0029] 5. Supports the development of closed-loop stimulus feedback systems, adaptable to various neuromodulation experimental paradigms, such as: drug-electromodulation combined research and real-time correlation analysis of neurotransmitters-electrical signals. Attached Figure Description

[0030] Figure 1 : A schematic diagram of the overall structure of the implantation probe system of the present invention;

[0031] Figure 2 Perspective diagram of the electrode detection module;

[0032] Figure 3 Cross-sectional view of the microdialysis channel structure;

[0033] Figure 4 : Schematic diagram of an implantation probe according to another embodiment of the present invention;

[0034] Figure 5 : A perspective view of the implanted probe electrode detection module according to another embodiment of the present invention;

[0035] Reference numerals: 1. Vector electric field detection module; 1a. Support structure; 1b. Detection contact; 2. Microdialysis module; 2a. Inlet channel; 2b. Outlet channel; 2c. Microdialysis membrane window. Detailed Implementation

[0036] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments. However, the following embodiments are merely illustrative of the invention and not intended to limit its scope of protection. The scope of protection of the present invention should include all the contents of the claims, and through the description of the following embodiments, those skilled in the art can understand and implement the core content of the present invention.

[0037] Example

[0038] This embodiment proposes an implantable probe system for simultaneous three-dimensional electric field vector detection and microdialysis sampling. The probe system integrates a vector electric field detection module for electric field detection and a microdialysis probe for biochemical monitoring, allowing researchers or medical personnel to place the probe system in the target brain region or tissue and simultaneously perform electrophysiological and biochemical monitoring of regions of interest in the brain or spinal cord.

[0039] Reference Figure 1 , Figure 2 and Figure 3 The present invention provides an implantable probe system for simultaneous three-dimensional electric field vector detection and microdialysis sampling, which mainly includes:

[0040] 1) A vector electric field detection module 1 with a multi-layer electrode array on the periphery;

[0041] 2) The centrally located microdialysis module 2 includes an inlet channel 2a, an outlet channel 2b, and a microdialysis membrane window 2c.

[0042] Vector electric field detection module 1: This module includes an insulating support structure 1a and multiple detection contacts 1b, and has an overall columnar structure.

[0043] The support structure 1a is made of high-performance insulating and biocompatible materials such as polyimide to ensure no interference during high-precision signal acquisition. Internally, it incorporates longitudinal flexible reinforcing ribs to reduce bending deformation during implantation.

[0044] The multi-layer detection electrode consists of several layers of electrode array evenly arranged along the outer periphery of the probe. Each layer comprises detection contacts 1b in three directions (distributed at 120° intervals), enabling simultaneous acquisition of the local electric field distribution at multiple spatial points. Combined with vector analysis algorithms, the three-dimensional electric field vector information at the probe tip at any given time can be reconstructed. Platinum-iridium alloy is used as the detection contact material, exhibiting excellent conductivity and biocompatibility. The number of detection contacts depends on the specific application.

[0045] The outer layer of the vector electric field detection module 1 (excluding the detection contacts) is coated with parylene, a biocompatible material, as a protective layer to reduce tissue rejection. The portion in contact with the microdialysis probe isolates the electrical signal path from the microdialysis structure, preventing interference from the microdialysis liquid or electrochemical cross-contamination.

[0046] Reference Figure 1 , Figure 2 and Figure 3 The microdialysis module 2 is used to collect small molecules such as neurotransmitters from the target tissue. This module extends from the probe tail to the probe tip, and a microdialysis membrane window 2c is formed at the tip opening using a bio-inert semi-permeable membrane material (such as a polysulfone membrane) for the exchange of neurotransmitters and other molecules. The dialysate is supplied at a constant flow rate by an external micropump system, and the dialysis products are collected through the outlet for subsequent analysis.

[0047] Optionally, if a perfect correspondence between the electric field acquisition area and the biochemical substance acquisition area is not required, a different approach can be adopted. Figure 4 , Figure 5 The embodiments further reduce the impact of flow rate on electrical signal acquisition during biochemical substance collection.

[0048] In actual operation, the measurement process is as follows:

[0049] 1. After setting the stimulation or experimental conditions, implant the probe into the target tissue (such as the hippocampus, subthalamic nucleus, etc.).

[0050] 2. Start the microdialysis system and maintain a stable flow rate;

[0051] 3. Simultaneously activate the electrode signal acquisition module to record the potential of multiple detection contacts;

[0052] 4. Reconstruct the local three-dimensional electric field vector through mathematical modeling and calculation;

[0053] 5. Collect dialysis samples for neurotransmitter analysis;

[0054] 6. By jointly analyzing the electric field distribution and chemical signals, the electrochemical coupling mechanism in neural activity can be analyzed.

[0055] Through the above structure and operation, this invention constructs a composite probe system suitable for multifunctional detection, integrated implantation, and synchronous electrochemical acquisition, which has broad application potential in neural modulation, disease model research, and closed-loop feedback system development.

[0056] The above description is merely a specific embodiment of this application, enabling those skilled in the art to understand or implement this application. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of this application. Therefore, this application is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features claimed herein.

Claims

1. An implantable probe system for simultaneous three-dimensional electric field vector detection and microdialysis sampling, characterized in that... include: Vector electric field detection module: located around the probe, including: The insulating support structure (1a) is made of biocompatible polymer material; Multi-layer detection contacts (1b), each layer contains at least three detection contacts evenly distributed in azimuth angle, used for three-dimensional electric field vector calculation; Microdialysis module: located at the central axis of the probe, including: Inlet channel (2a) and outlet channel (2b); The microdialysis membrane window (2c) is aligned with the non-overlapping area of ​​the electrode layer; The vector electric field detection module is coaxially integrated with the microdialysis module to achieve synchronous acquisition of electrochemical signals.

2. The system according to claim 1, characterized in that: The detection contacts (1b) are distributed at 120° intervals, with a spacing of 1 mm between adjacent layers, and are made of platinum-iridium alloy.

3. The system according to claim 1, characterized in that: The supporting structure (1a) is made of polyimide, with built-in longitudinal flexible reinforcing ribs and an outer coating of parylene protective layer.

4. The system according to claim 1, characterized in that: The microdialysis membrane window (2c) is equipped with a semi-permeable membrane window (e.g., polysulfone semi-permeable membrane material) that has high selectivity and biocompatibility, and is spatially isolated from the detection contact layer.

5. The system according to claim 1, characterized in that: The electrode array supports dual-function switching of detection and stimulation, enabling closed-loop neural modulation.

6. The system according to claim 1, characterized in that: The inlet channel (2a) and outlet channel (2b) of the microdialysis module (2) are made of microtubes that are flexible, chemically inert and biocompatible. The material of the microtubes can be selected from polytetrafluoroethylene, polyetheretherketone, polyethylene or other materials suitable for microfluidic systems.

7. The system according to claim 1, characterized in that: All signal leads and fluid interfaces are located at the probe tail, which connects to an external acquisition system via connectors.

8. A method for synchronous detection of three-dimensional electric field and biochemical signal, characterized in that... The system according to any one of claims 1-7 comprises: The probe is implanted into the target tissue; Simultaneously start the microdialysis system and electrode signal acquisition module; Reconstructing three-dimensional electric field vectors based on multi-layer detection of contact potentials; Combined analysis of electric field distribution and neurotransmitter data in dialysis samples.

9. The method according to claim 8, characterized in that: The electric field vector is reconstructed based on the potential distribution of the detection contact using mathematical modeling methods.

10. A neural modulation closed-loop system, characterized in that... Integrating the probe system according to any one of claims 1-7, for: Real-time correlation between neurotransmitter release and electric field response; Stimulation parameters are dynamically adjusted based on the electrochemical coupling mechanism.

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