CN101999897A - Microelectrode propelling device and method - Google Patents

Abstract

The invention discloses a micro-electrode propulsion device and method. The device includes a gasket, a box body, a nut, a screw, a slide block and a bottom plate. The advancing method includes the following steps: the periphery of the base plate is arranged in a stepped shape, the positioning screws pass through two semicircular holes on the base plate as positioning references and the positioning holes at the corresponding positions on the skull to position the base plate on the skull, and the base plate and the skull are passed through dental The cement is bonded and fixed; the bottom plate and the box are connected by concave-convex grooves; the slideway of the box has a built-in slider, and the array plate is installed on the stepped groove of the slider to fix the microelectrode. The position of the hole on the array plate is specific to the brain area. The position of the intersecting axis of the sagittal plane and the coronal plane of the space encoding position, the horizontal position of the array board is the propulsion surface of the propeller, and the propeller performs EEG stimulation and EEG recording on the entire brain region. The device of the invention has the characteristics of simple operation and light structure, and is suitable for use in laboratories engaged in the research of animal brain regions.

Description

Microelectrode propulsion device and method thereof

technical field

The invention relates to a manual microelectrode propeller, which is used for feeding microelectrodes in the brain of a gecko that can move freely in a waking state.

Background technique

How the information of external things is encoded and transmitted in the brain has always been an important research topic in brain science. The encoding of neural information is a fundamental problem of the nervous system. The information of things is coded by neuron clusters. The use of cluster coding is conducive to the stability and accuracy of neural information expression, and through combination, more different representations than the number of neurons can be generated, thereby improving the expressive ability of the nervous system. It is a promising topic to study the high-order characteristics of expressing the interrelationships of multiple neurons in a cluster and then develop other more effective encoding modes.

A series of studies, such as the spatio-temporal encoding mode between neurons, the determination of the correlation between the EEG signal of the motor-related brain area and the motor behavior, and the change of the animal's motor behavior under the condition of external input stimulus signals, etc., all need to accurately place the microelectrode Put into the predetermined position. At present, there are three basic types of micro-drives used in animal information collection: hydraulic drive, gear transmission, and screw mechanism. Ranck (Ranck J.R. Brain Unit Activity During Behavior. 1973:76-79.) was one of the first to use screw mechanisms. His microdrive consists of two screws, one fitted in a hollow cavity in the other. The outer screws attach the microdrives to the animal's brain, and the inner screws hold the microelectrodes. When the screw inside is rotated, the microelectrode rotates with it. This kind of microelectrode thruster has a relatively rough structure and can only propel a single electrode.

Wang Julei (patent number: CN 201157420Y) of Tangdu Hospital of Fourth Military Medical University designed a manual microelectrode thruster for monkeys, cats and other large animals. This kind of micro propeller is provided with a propulsion rod on the base, the center of the propulsion rod is a screw rod, the rotation of the screw rod will drive the slider to move up and down, and the electrode plug can be fixed on the slider to realize the electrode advancement. The advantages of this manual microelectrode pusher are: there is a scale on the rotating ring, which can realize precise control, and the moving distance of the electrode can reach 4mm. Its disadvantages are: (1) The overall structure is large and heavy, and it is mainly suitable for large animals; (2) The connection with the skull is relatively simple and easy to fall off; (3) It can only be used for single-electrode recording and stimulation experiments.

MS. Fee of Bell Laboratories (MS Fee, A Leonardo. NEUROSCI METH 2001: (112) 83-94) designed a self-feeding electrode micro-thruster for brain signal acquisition of zebra finch. The microelectrode is mounted on a threaded slider that slides up and down a threaded cylinder. As the motor turns the cylinder, the slider moves the microelectrodes up and down. The advantages of this microelectrode thruster are: (1) The diameter is 6mm, the height is 17mm, the weight is less than 1.5g, and the structure is compact, which can be applied to small animals; (2) Each channel is controlled by a DC motor, which can realize three channels Feed separately, no influence on each other; (3) Driven by DC motor, the feeding accuracy is very high. The disadvantages of MS. Fee's propeller are: (1) the number of sites for collection is limited, and the utilization rate of animals is relatively low; (2) it is directly fixed to the skull, which is suitable for most animals, but for some Animals with special skull structures (such as large geckos) are not suitable; (3) Three DC motors with a diameter of 1.9mm and a weight of about 100mg are used, so the cost of the whole set of equipment is very high.

Plexon offers two microelectrode thrusters, the MD-04 and MD-08, with 4 and 8 independently moving interface sliders, respectively. The interface slider is placed in the corresponding slideway of the cabinet. Each interface slider can hold 1-4 microelectrodes. There are threaded holes on the slider, and when the screw is turned clockwise, the slider will drive the microelectrodes to slide up and down. A guide hole is provided under the slider to guide the microelectrode to slide in the track. There are four screw connections between the box and the skull. The advantages of this thruster are: (1) multi-channel separate feeding; (2) light weight; (3) small size; (4) easy assembly; (5) cost-effective; (6) separate microelectrode transfer Interface; (7) It can realize 1/8 and 3/16 feed. Its disadvantages are: (1) The interface slider is one-time use and cannot be reused; (2) The implantation site is relatively fixed and difficult to change; (3) The fixation with the skull is not firm, especially not suitable for large gecko and other skulls An animal with a special structure.

Keith A. Stengel (patent number: US 7769421) designed the microelectrode thruster. The basic principle is also to use the screw thread to push manually. But in the slideway that is designed to be inclined 30° in the casing, the screw pushes the slide block to move along the slideway. A capillary is fixed on the slider, and the recording microelectrode is fixed on the capillary and moves up and down with the slider. A guide tube is provided at the bottom of the box, and the lower end of the capillary penetrates into the guide tube to ensure that the microelectrode moves up and down at the designated position. The bottom is directly cemented to the skull. The advantages of this thruster are: (1) 14 channels are fed separately; (2) The combination of capillary and guide tube is used to expand the design space; (3) The joint area between the bottom and the skull is small, which is convenient for fixing to the skull; Its disadvantages are: (1) The conventional fixation with the skull is not suitable for animals with special skull structures such as geckos; (2) The assembly is cumbersome, time-consuming and labor-intensive; (3) The processing cost is relatively high; (4) ) The implantation site is relatively fixed and difficult to change; (5) The slider is one-time use and cannot be reused.

Manuputy Ronald Jozef Domingus of the Netherlands (patent number: EP2135548 (A1) ) designed a microelectrode thruster. The basic principle is also to use the screw thread to push manually. He designed the shape of the six sliders into a 60° triangle, so that the six sliders can limit each other, and when the stud rotates, the sliders can only move up and down. Fix the recording microelectrode on the slider to realize the up and down feeding of the microelectrode. The advantages of this thruster are: (1) Realize 6-channel separate feed; (2) Directly connect the front-end amplifier with the microelectrode thruster; (3) Use the shape of the slider to directly limit the position, reducing the processing difficulty of the box ; (4) Simplified the overall structure, easy to use. Its disadvantages are: (1) The contact area with the skull is relatively large, which is not suitable for animals with special skull structures such as geckos; (2) The implantation site of the microelectrode is fixed, and the area where the microelectrode can be implanted is relatively small; (3) The slider is for one-time use and cannot be reused; (4) Compared with animals such as giant geckos, the structure is relatively large, which is not conducive to the free movement of animals.

Since the above microelectrode thrusters are mainly aimed at animals such as rats and cats, they are used in stimulation and recording experiments of large geckos. There are many problems, such as the inability to connect with the skull of large geckos, the area where microelectrodes can be implanted is relatively small, etc. wait. Therefore, we need to design a microelectrode thruster, which has a simple structure and light weight, can be perfectly fixed on the skull of the gecko, and can realize multi-site electrical brain stimulation and recording.

Contents of the invention

The object of the present invention is to provide a microelectrode propulsion device and method for in vivo recording and stimulation of large gecko in view of the defects in the prior art, which are used for in vivo recording and stimulation experiments of large gecko.

In order to achieve the above object, the present invention adopts the following technical solutions:

The microelectrode propulsion device of the present invention comprises a gasket, a box body, a nut, a screw, a slider and a bottom plate, wherein the bottom plate and the box body are connected by concave-convex matching grooves arranged correspondingly to each other, and the bottom plate is fixed on the skull. The slideway corresponding to the slider, the slider is provided with a stepped groove and a mounting hole, the array plate is installed on the stepped groove to fix the microelectrode, the nut is embedded in the mounting hole on the slider, and is firmly connected with the slider, the slideway is designed as The semicircular groove is used to limit the rotation of the slider so that it can only move up and down along the screw, and the gasket limits the up and down movement of the screw, so that the screw can only rotate in situ. Preferably, the concave-convex matching groove is a dovetail groove or a round groove.

Preferably, the array plate is a thin plate with a thickness of 300-500 μm, uniformly distributed through holes are opened on the array plate, and the hole spacing is in the range of 300-600 μm.

Preferably, the stroke of the slider is not less than 5 mm.

A propulsion method for a microelectrode propulsion device, comprising the following steps:

(1) The periphery of the bottom plate is set in a stepped shape. The positioning screws pass through the two semicircular holes on the bottom plate as the positioning reference and the corresponding positioning holes on the skull to position the bottom plate on the skull. The bottom plate and the skull are bonded and fixed by dental cement. ;

(2) The bottom plate and the box body are connected by concave and convex matching grooves;

(3) There is a built-in slider in the slideway of the box, and the array plate is installed on the ladder groove of the slider to fix the microelectrodes. The position of the hole on the array plate is the intersecting axis of the sagittal plane and the coronal plane of the specific spatial coding position of the brain region The horizontal position of the array board is the propulsion surface of the propeller, and the propeller performs EEG stimulation and EEG recording on the entire brain area.

The present invention has following beneficial effect:

(1) Determine the shape and fixation method of the bottom plate according to the shape and size of the parietal bone of the animal. The fixed position of the bottom plate determines the position of the entire microelectrode propulsion system relative to the brain area, so the position of the bottom plate needs to be determined first. In the present invention, two semicircular holes are opened on the bottom plate as the positioning reference of the bottom plate, and two positioning holes are punched in corresponding positions on the parietal bone, and positioning screws are implanted to determine the position of the bottom plate. In the experiment, the fixation between the dental cement and the parietal bone was not firm, and the implantation of set screws can significantly enhance the bonding strength between the base plate and the parietal bone. The size of the bottom plate determines the size of the overall structure to a certain extent. In order to reduce the design and manufacturing difficulty of the microelectrode propulsion system, the overall structure of the system should be as large as possible. On the other hand, the area that can be used to fix the bottom plate in the experiment is very small. This limits the size of the bottom plate to some extent. According to the shape and structure of the parietal bone, the present invention topologically derives the shape of the bottom plate and realizes the optimal design. The periphery of the bottom plate is designed into a stepped shape, which is beneficial to the coating and fixing of dental cement.

(2) Considering the convenience of processing and experimental assembly, the bottom plate and the box body are designed as separate structures, and the bottom plate and the box body are connected by dovetail grooves. Such a design is not only beneficial to the processing and manufacturing of each part, but also ensures the connection and positioning of the parts.

(3) There is a built-in slider in the slideway of the thruster, and the array plate is installed to fix the microelectrodes, and the electrodes are fixed with the holes on the array plate. The array board is processed with evenly spaced small holes. After the microelectrode passes through the small hole to the designated position, glue can be used to fix the microelectrode on the edge of the small hole. In the present invention, the hole array plate is used to fix the electrodes, which greatly increases the position of the electrodes that can be implanted, and can perform electrical stimulation and EEG recording on the entire experimental brain area. The position of the hole on the slider is determined by the coordinates of the sagittal and frontal planes according to the specific spatially encoded position of the brain region, and the position in the coronal plane is determined by the pusher. Thrusters allow for electrical brain stimulation and recording of the entire midbrain region.

(4). The present invention adopts the screw rod slider mechanism as the power propulsion system. The microelectrode thruster requires compact structure and flexible propulsion, so the simplest mechanism for the propulsion system in the thruster - the screw slider mechanism. At the same time, the upper and lower washers are used to limit the up and down movement of the screw, and the nut is embedded in the slider. In addition, standard screws and nuts are used in the present invention, which reduces the cost and difficulty of processing.

(5) The overall structure adopts a closed design. The particularity of the gecko's brain structure requires that when the microelectrode is implanted, a craniotomy is performed to remove part of the dura mater and arachnoid to expose the experimental brain area. However, the postoperative gecko brain must be isolated from the outside world, so the present invention adopts a closed design, and the feeding devices are all surrounded by casings. On the other hand, when the present invention is applied to the collection of EEG signals, it is required to shield the micro-electrodes leading out with signals, and the closed design can ensure a good shielding effect.

，仅相当于钢的60%，比强度很高，既能够保证整体结构重量轻，又能够保证薄壁零件的强度，保证在实际操作过程中整体结构不变形，提高微电极植入的位置精度。(6), the present invention uses titanium or aluminum alloy as the production material. The microelectrode propeller needs to be fixed on the skull of the gecko. If the weight is too heavy for the gecko to bear, it will affect the normal activities of the gecko. The density of titanium alloy is 4.5

, which is only equivalent to 60% of steel, and the specific strength is very high, which can not only ensure the light weight of the overall structure, but also ensure the strength of thin-walled parts, ensure that the overall structure does not deform during actual operation, and improve the position accuracy of microelectrode implantation .

Description of drawings

Figure 1 is a schematic diagram of a microelectrode pusher. (a) is a schematic view of the front view; (b) is a schematic view of the top view.

Figure 2 is a schematic diagram of the slider.

Figure 3 is a schematic diagram of the positioning of the gecko head position and the experimental area. Among them, (c) is a schematic diagram of front view; (d) is a schematic view of top view.

Designation of labels in Fig. 1: 1-gasket; 2-box; 3-nut; 4-screw; 5-slider; 6-bottom plate.

Label name in Fig. 2: 7-step groove.

Designation of labels in Fig. 3: 8-coronal suture; 9-anterior bregma; 10-parietal bone; 11-posterior bregma.

Detailed ways

Figure 1 is a schematic diagram of a microelectrode pusher. As shown in the figure, two gaskets 1 are used to limit the up and down movement of the screw 4, so the screw 4 can only rotate in situ, and the nut 3 is tightly connected with the slider 5. When the screw 4 is turned, the slider 5 is limited by the casing 2 to rotate, so the slider 5 can only move up and down along the screw 4 with the nut 3 . After the microelectrode is fixed on the hole array plate bonded to the slider 5, the microelectrode will also move up and down along with the slider 5.

Figure 2 is a schematic diagram of the slider. The area marked with in the figure is the stepped groove, which is used to bond the hole array plate.

Figure 3 is a schematic diagram of the positioning of the gecko head position and the experimental area. The area available for the experiment is the parietal bone between bregma and bregma, ie the area marked with a thick line, with a total area of about 90 mm ² .

Below in conjunction with Fig. 1, Fig. 2, Fig. 3, use a specific implementation example to illustrate the use method of the present invention.

The weight that can be carried by the head of the big gecko is limited. Considering the impact on the free movement of the big gecko, the weight of the thruster cannot exceed 5g, so the microelectrode thruster must be simple in structure and light in weight. The present invention adopts screw drive, and its structure is simple and handy, easy to operate. The experimental brain area is under the parietal bone, but there is a bony suture (coronal suture) between the parietal bone and the frontal bone of the big gecko. above, and not beyond the coronal suture.

1. According to the assembly diagram in Figure 1, fix the nut 3 and the hole array plate in a proper position. It is used to fix the nut 3 in the slot of the slider 5 through 502 glue. It is necessary to control the nut to be coaxial with the upper and lower holes, otherwise it will affect the thread

Transmission of the rod-slider mechanism. The hole array plate is fixed in the stepped groove 7 reserved in the slider 5 . First, grind the hole array plate according to the size of the stepped groove 7 to ensure smooth edges. Then, using the step as the positioning reference, press the hole array plate on the stepped groove 7 with 502 glue. After the 502 glue is solidified, polish the glued part to ensure that the slider 5 can slide smoothly in the box body 2. Finally, the slider is assembled in the box.

2. Anesthetize the gecko and fix it on the locator, so that its brain is in a standard positioning state. With the bregma as the positioning reference, two positioning holes were symmetrically drilled in the appropriate position of the parietal bone with a positioning high-speed cranial drill, and positioning screws were screwed in. Roughing the parietal bone 10 to be coated with dental cement in the next step is beneficial to enhance the bonding strength between the dental cement and the parietal bone 10 . A craniotomy was performed on the gecko, the dura mater and arachnoid were cut off, and the experimental brain area was exposed.

3. Since the parietal bone 10 is uneven, first apply a small amount of dental cement to the joint area between the parietal bone 10 and the bottom plate 6 to ensure that the bottom plate 6 is placed horizontally. A small amount of dental cement is coated on the front and back of the base plate 6 to fix the base plate 6 on the parietal bone 10 . After the dental cement solidifies, match the assembled box body 2 with the bottom plate 6 . Apply dental cement around the casing 2 and base plate 6, and pay attention to the dental cement not exceeding the coronal joint 8.

4. According to the position of bregma 9, implant microelectrodes at the required points, and fix them on the hole array plate. Finally, seal all unused holes with 502 glue.

5. Disinfect the exposed skin and muscle tissue, suture the skin of the gecko's head, connect the microelectrodes to the stimulation interface, and perform chronic experiments after recovery.

6. Three to four days after the big gecko recovers, conduct postoperative electrical stimulation or EEG recording experiments on the big gecko. If the effect is not satisfactory at the point where it is located, you can turn the screw 4 to realize the advancement of the microelectrode in vivo.

Claims (5)

1. microelectrode propulsion plant, it is characterized in that comprising pad (1), casing (2), nut (3), screw (4) slide block (5) and base plate (6), wherein base plate (6) is connected by the mutual corresponding concavo-convex groove that matches that is provided with casing (2), base plate (6) is fixed on the skull, be provided with in the casing (2) and the corresponding slideway of slide block (5), step trough (7) and installing hole are set on the slide block (5), step trough (7) go up to be installed array board with fixing microelectrode, nut (3) embeds the installing hole on the slide block (5), and with fastening linking to each other of slide block (5), ramp design becomes semi-circular groove to be used to limit slide block (5) rotation, it can only be moved up and down along screw (4), pad (1) has limited moving up and down of screw (4), and screw (4) can only rotate in the original place.

2. microelectrode propulsion plant according to claim 1 is characterized in that the described concavo-convex groove that matches is dovetail groove or circular groove.

3. microelectrode propulsion plant according to claim 1 is characterized in that described array board is the thin plate of thickness 300～500 μ m, has equally distributed through hole on the array board, and the pitch of holes scope is at 300～600 μ m.

4. microelectrode propulsion plant according to claim 1 is characterized in that described slide block (5) stroke is not less than 5mm.

5. propulsion method based on the described microelectrode propulsion plant of claim 1 is characterized in that may further comprise the steps:

(1), base plate (6) around be arranged to stepped, dog screw is positioned base plate (6) on the skull jointly by the locating hole of two semicircle orifices on the base plate (6) as relevant position on location benchmark and the skull, and base plate (6) and skull are cement-bonded and fixing by dentistry;

(2), base plate (6) adopts the concavo-convex groove that matches to be connected with casing (2);

(3), casing (2) slideway built-in sliding block (5), array board is installed with fixing microelectrode on slide block (5) step trough, the position in the hole on the array board is the sagittal plane of specific space encoding position, brain interval and the concurrent aces position of coronal plane, the horizontal level of array board is angle of rake pressure surface, and propeller carries out electrical brain stimulation and eeg recording to whole brain zone.

Images