Micro-nano electrode array for electrophysiological detection and electrical stimulation of spatially cognizant cells

Abstract

The application discloses a micro-nano electrode array for electrophysiological detection and electrical stimulation of spatial cognitive cells, comprising an electrophysiological detection site, an electrical shielding site, an electrical stimulation site, an electrophysiological lead, an electrical stimulation lead, a pad site, a pad lead and a substrate; the electrophysiological detection site is between the electrical stimulation site and the electrical shielding site; the electrophysiological detection site and the electrical stimulation site are arranged in the electrical shielding site; the pad lead is connected with the electrophysiological lead and the electrical stimulation lead; the electrophysiological detection site, the electrical shielding site, the electrical stimulation site, the electrophysiological lead, the electrical stimulation lead, the pad site and the pad lead are all on the substrate; the electrode array can synchronously perform electrophysiological detection and electrical stimulation of position cells; the electrical shielding site can control the range of electrical stimulation to be near the detection site; the electrophysiological detection site has low impedance; the electrical stimulation site can bear high voltage and current; the range of electrical stimulation is controllable; the brain tissue is less damaged; and the electrode array is suitable for electrophysiological detection and electrical stimulation of position cells of animals.

Description

Technical Field

[0001] This invention relates to the fields of neural signal detection and neuronal electrical stimulation, and in particular to a micro / nano electrode array for electrophysiological detection and electrical stimulation of spatial cognitive cells. Background Technology

[0002] Place cells are pyramidal neurons in the hippocampus of animals, believed to be directly involved in spatial navigation. Place cells become active when an animal enters a specific location in its environment. These active place cells are scattered throughout the hippocampus. To study the direct impact of place cells on spatial navigation, we need tools for precise stimulation of place cells. These tools must first detect place cells and then provide in-situ electrical stimulation. Electroencephalography (EEG) is one form of electrical stimulation. Currently available EEG methods include: transcranial electrostimulation (TCE), deep brain stimulation (DBS), transcranial direct current stimulation (TCD), electroconvulsive therapy (ECT), low-field magnetic stimulation (MRFS), functional electrical stimulation (FPS), magnetic stimulation, vagus nerve stimulation (VMS), deep transcranial magnetic stimulation (TMS), and reactive neurostimulation. These stimulation methods use millimeter- and centimeter-sized electrodes to stimulate the brain. These electrodes are much larger than the cells themselves, making it impossible to stimulate specific cells, and the effects of stimulation are difficult to assess, thus failing to meet the need for precise stimulation of single functional neurons.

[0003] Currently, the most effective technique for cellular-level stimulation is optogenetics. Optogenetics is a technique that uses light to control the activity of neurons or other cell types by specifically expressing light-sensitive photochannels, pumps, or enzymes in target cells. At the single-cell level, photoactivated enzymes and transcription factors can precisely control biochemical signaling pathways. Although optogenetics can provide millisecond-level temporal precision, and the required hardware (integrated optical fibers and solid-state light sources, etc.) is becoming increasingly smaller and even non-invasive, many technical challenges remain unresolved, such as: varying levels of opsin gene expression in microorganisms, unclear correlation with cellular electrical activity, difficulties in binding opsin activation to gene-encoding indicators, and spatial delays and uncontrollability.

[0004] Existing neurostimulation electrodes mostly adopt a three-dimensional structure, with large conductive and insulating wires that cause significant damage to brain tissue. They cannot achieve simultaneous electrophysiological detection and stimulation, nor can they identify specific spatial navigation cells or precisely stimulate specific cells.

[0005] Therefore, there is currently a lack of tools that can detect specific functional cells in the brain while simultaneously performing in situ electrical stimulation. Summary of the Invention

[0006] To address the aforementioned technical problems, this invention proposes a micro / nano electrode array for electrophysiological detection and electrical stimulation of spatial cognition cells, which solves the above-mentioned technical problems.

[0007] A micro / nano electrode array for electrophysiological detection and electrostimulation of spatial cognitive cells, comprising: electrophysiological detection sites, electro-shielding sites, electrostimulation sites, electrophysiological leads, electrostimulation leads, pad sites, pad leads, and a substrate. The electrophysiological detection sites are located between the electrostimulation sites and the electro-shielding sites; the electrophysiological detection sites and electrostimulation sites are disposed within the electro-shielding sites; the pad leads are respectively connected to the electrophysiological leads and the electrostimulation leads; the electrophysiological detection sites, electro-shielding sites, electrostimulation sites, electrophysiological leads, electrostimulation leads, pad sites, and pad leads are all located on the substrate.

[0008] Preferably, the electrophysiological detection site, the electrical shielding site, and the electrical stimulation site are located at the tip of the front part of the micro-nano electrode array, the pad site is located at the rear part of the micro-nano electrode array, and the electrophysiological detection site is connected to the electrode pad site through an electrophysiological wire.

[0009] Preferably, there are two electrical stimulation wires. The electrical stimulation site is connected to the pad site through one of the electrical stimulation wires, and the electrical shielding site is connected to the pad site through the other electrical stimulation wire.

[0010] The electrophysiological detection sites are circular with a diameter of less than 20 micrometers and greater than 1 micrometer, and there are 16 of them, all located between the electrical stimulation sites and the electrical shielding sites.

[0011] The electrical shielding site is 50 micrometers wide and includes the electrophysiological detection site and the electrical stimulation site.

[0012] The electrical stimulation site is a circle with a diameter of 250 micrometers.

[0013] The electrophysiological leads are 5 micrometers wide and number equal to the electrophysiological detection sites.

[0014] The electrical stimulation wire is 50 micrometers wide and consists of two wires, one connected to the electrical stimulation site and the other connected to the electrical shielding site.

[0015] The pads are square and there are 18 of them.

[0016] The pad wires are connected to the electrophysiological wires and the electrical stimulation wires.

[0017] The electrophysiological detection sites, electrical shielding sites, electrical stimulation sites, electrophysiological leads, electrical stimulation leads, pad sites, and pad leads are all manufactured on a substrate using microelectromechanical processes, and the material is SOI.

[0018] The electrophysiological detection sites, electrical shielding sites, electrical stimulation sites, electrophysiological leads, electrical stimulation leads, pad sites, and pad leads are all made of platinum with a thickness of 250 nanometers.

[0019] The electrophysiological leads, electrical stimulation leads, and pad leads are covered with a silicon dioxide insulating layer with a thickness of 800 nm.

[0020] The electrophysiological detection site is modified by electroplating platinum nanoparticles on its surface, resulting in an impedance of less than 10 kiloohms.

[0021] Beneficial effects:

[0022] This invention proposes a micro / nano electrode array for electrophysiological detection and electrical stimulation of spatial cognition cells, with the following beneficial effects:

[0023] (1) It can meet the needs of detecting location cells and performing in situ electrical stimulation on the detected location cells;

[0024] (2) The integration of electrical stimulation and electrophysiological detection reduces damage to brain tissue and makes it more convenient to perform electrophysiological detection and electrical stimulation of cells.

[0025] (3) This electrode can stimulate position cells at close range and induce position fields more quickly;

[0026] (4) The electrode has good stability and impermeability;

[0027] (5) The electrode has high resolution and good repeatability. Attached Figure Description

[0028] To gain a more complete understanding of the invention and its advantages, reference will now be made to the following description taken in conjunction with the accompanying drawings, which are incorporated in and form part of this specification, wherein:

[0029] Figure 1 It is a micro / nano electrode array used for electrophysiological detection and precise electrical stimulation of cells at their location;

[0030] Figure 2 This is a magnified view of the detection and stimulation section of a micro / nano electrode array used for electrophysiological detection and precise electrical stimulation of cells.

[0031] Figure 3 It is a simulation of the electric field generated during the electrical stimulation of a micro / nano electrode array used for electrophysiological detection and precise electrical stimulation of cells.

[0032] In the figure, 1-electrophysiological detection site, 2-electrical shielding site, 3-electrical stimulation site, 4-electrophysiological lead, 5-electrical stimulation lead, 6-pad site, 7-pad lead, 8-substrate, 9-electrical field direction, 10-positive voltage. Detailed Implementation

[0033] Embodiments of the present invention will now be described with reference to the accompanying drawings. However, it should be understood that these descriptions are exemplary only and are not intended to limit the scope of the invention. In the following detailed description, numerous specific details are set forth to provide a thorough understanding of the embodiments of the invention for ease of explanation. However, it will be apparent that one or more embodiments may be practiced without these specific details. Furthermore, descriptions of well-known structures and techniques are omitted in the following description to avoid unnecessarily obscuring the concept of the invention.

[0034] According to one embodiment of the present invention, such as Figure 1 As shown, a micro / nano electrode array for electrophysiological detection and precise electrical stimulation of cells is disclosed. The micro / nano electrode array includes: an electrophysiological detection site 1, an electrical shielding site 2, an electrical stimulation site 3, an electrophysiological lead 4, an electrical stimulation lead 5, a pad site 6, a pad lead 7, and a substrate 8. The electrophysiological detection site 1 is located between the electrical stimulation site 3 and the electrical shielding site 2; the electrical shielding site 2 contains both the electrophysiological detection site 1 and the electrical stimulation site 3; the pad lead 7 is connected to the electrophysiological lead 4 and the electrical stimulation lead 5, respectively; and the electrophysiological detection site 1, the electrical shielding site 2, the electrical stimulation site 3, the electrophysiological lead 4, the electrical stimulation lead 5, the pad site 6, and the pad lead 7 are all located on the substrate 8.

[0035] The electrophysiological detection site 1, the electro-shielding site 2, and the electro-stimulation site 3 are located at the front tip of the micro-nano electrode array, and the pad site 6 is located at the rear of the micro-nano electrode array. The electrophysiological detection site 1 is connected to the electrode pad site 6 through the electrophysiological wire 4, the electro-stimulation site 3 is connected to the pad site 6 through the electro-stimulation wire 5, and the electro-shielding site 2 is connected to the pad site 6 through another electro-stimulation wire 5.

[0036] The electrophysiological detection sites are circular with a diameter of less than 20 micrometers and greater than 1 micrometer, and there are 16 of them, all located between the electrical stimulation site 3 and the electrical shielding site 2.

[0037] The electrical shielding site 2 has a width of 50 micrometers and includes the electrophysiological detection site 1 and the electrical stimulation site 3.

[0038] The electrical stimulation site 3 is a circle with a diameter of 250 micrometers.

[0039] The electrophysiological leads are 5 micrometers wide and number equal to the electrophysiological detection sites.

[0040] The electrical stimulation wire is 50 micrometers wide and there are two wires, one connected to the electrical stimulation site 3 and the other connected to the electrical shielding site 2.

[0041] The pads 6 are square and there are 18 of them.

[0042] The pad wire 7 is connected to the electrophysiological wire 4 and the electrical stimulation wire 5.

[0043] The electrophysiological detection site 1, the electrical shielding site 2, the electrical stimulation site 3, the electrophysiological lead 4, the electrical stimulation lead 5, the pad site 6, and the pad lead 7 are all manufactured on the substrate 8 using microelectromechanical processes, and the material is SOI.

[0044] The electrophysiological detection site 1, the electrical shielding site 2, the electrical stimulation site 3, the electrophysiological lead 4, the electrical stimulation lead 5, the pad site 6, and the pad lead 7 are all made of platinum, with a thickness of 250 nanometers.

[0045] The electrophysiological leads 4, the electrical stimulation leads 5, and the pad leads 7 are covered with silicon dioxide as an insulating layer with a thickness of 800 nm.

[0046] The electrophysiological detection site is modified by electroplating platinum nanoparticles on its surface, resulting in an impedance of less than 10 kiloohms.

[0047] like Figure 2 As shown, the electrostimulation site 3 is located at the circular center of the electro-shielding site 2, and 16 electrophysiological sites 1 are located around the electrostimulation site 3 and are surrounded by the electro-shielding site 2.

[0048] The microelectrode array in this invention is used as follows: Electrophysiological site 1 is used to detect spatial cognition cells such as place cells. While the place cells are detected, positive and negative bidirectional voltage or current pulses are applied between the electrical stimulation site 3 and the electrical shielding site 2 to stimulate the place cells.

[0049] Example 1

[0050] like Figure 3 As shown, the effect of electrical stimulation after applying a 1-volt voltage is shown. The black solid line is close to zero voltage, and the area inside the black solid line is a positive voltage of 10. The arrow points in the direction of the electric field 9. It can be seen that the electrical stimulation area is completely covered and limited to the vicinity of the electrophysiological detection site.

[0051] The detailed experimental steps are as follows:

[0052] Train mice to run in an open field, allowing their movement trajectories to cover the entire open field;

[0053] The microelectrode array was implanted into the hippocampus or entorhinal cortex of mice, which are related to spatial cognition. Electrophysiological site 1 was used to detect spatial cognition cells such as place cells in the mice.

[0054] After detecting spatial cognition cells such as position cells, positive and negative bidirectional voltage or current pulses are applied between electrical stimulation site 3 and electrical shielding site 2 to stimulate spatial cognition cells such as position cells.

[0055] Those skilled in the art will understand that although the invention has been shown and described with reference to specific exemplary embodiments thereof, they should understand that various changes in form and detail may be made to the invention without departing from the spirit and scope of the invention as defined by the appended claims and their equivalents. Therefore, the scope of this disclosure should not be limited to the above embodiments, but should be determined not only by the appended claims but also by their equivalents.

Claims

1. A micro / nano electrode array for electrophysiological detection and electrical stimulation of spatial cognition cells, characterized in that, The micro / nano electrode array includes: an electrophysiological detection site (1), an electrical shielding site (2), an electrical stimulation site (3), an electrophysiological lead (4), an electrical stimulation lead (5), a pad site (6), a pad lead (7), and a substrate (8); the electrophysiological detection site (1) is located between the electrical stimulation site (3) and the electrical shielding site (2); the electrical shielding site (2) contains the electrophysiological detection site (1) and the electrical stimulation site (3); the pad lead (7) is connected to the electrophysiological lead (4) and the electrical stimulation lead (5) respectively; the electrophysiological detection site (1), the electrical shielding site (2), the electrical stimulation site (3), the electrophysiological lead (4), the electrical stimulation lead (5), the pad site (6), and the pad lead (7) are all on the substrate (8); The electrophysiological detection site (1), the electrical shielding site (2), and the electrical stimulation site (3) are located at the tip of the front part of the micro-nano electrode array, and the pad site (6) is located at the rear part of the micro-nano electrode array. The electrophysiological detection site (1) is connected to the electrode pad site (6) through the electrophysiological wire (4). There are two electrical stimulation wires (5). The electrical stimulation site (3) is connected to the pad site (6) through one electrical stimulation wire (5), and the electrical shielding site (2) is connected to the pad site (6) through another electrical stimulation wire (5).

2. The micro / nano electrode array according to claim 1, characterized in that, The electrophysiological detection sites (1) are circular with a diameter of less than 20 micrometers and greater than 1 micrometer, and there are 16 of them, all located between the electrical stimulation sites (3) and the electrical shielding sites (2).

3. The micro / nano electrode array according to claim 1, characterized in that, The width of the electrical shielding site (2) is 50 micrometers.

4. The micro / nano electrode array according to claim 1, characterized in that, The electrostimulation site (3) is a circle with a diameter of 250 micrometers.

5. The micro / nano electrode array according to claim 1, characterized in that, The electrophysiological lead wire (4) has a width of 5 micrometers and the number is equal to that of the electrophysiological detection sites (1).

6. The micro / nano electrode array according to claim 1, characterized in that, The electrical stimulation lead (5) has a line width of 50 micrometers.

7. The micro / nano electrode array according to claim 1, characterized in that, The pads (6) are square and there are 18 of them.

8. The micro / nano electrode array according to claim 1, characterized in that, The electrophysiological detection site (1), the electrical shielding site (2), the electrical stimulation site (3), the electrophysiological lead (4), the electrical stimulation lead (5), the pad site (6), and the pad lead (7) are all fabricated on the substrate (8) using microelectromechanical processes, and the material is SOI.

9. The micro / nano electrode array according to claim 1, characterized in that, The electrophysiological detection site (1), the electrical shielding site (2), the electrical stimulation site (3), the electrophysiological lead (4), the electrical stimulation lead (5), the pad site (6), and the pad lead (7) are all made of platinum and have a thickness of 250 nanometers.

10. The micro / nano electrode array according to claim 1, characterized in that, The surfaces of the electrophysiological leads (4), the electrical stimulation leads (5), and the pad leads (7) are all covered with silicon dioxide as an insulating layer, with an insulating layer thickness of 800 nm. The electrophysiological detection site (1) is modified by electroplating platinum nanoparticles on its surface, and the impedance after modification is less than 10 kiloohms.

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