Silicon photoelectrode support and silicon photoelectrode device

Abstract

The invention provides a silicon photoelectrode support and a silicon photoelectrode device, and belongs to the technical field of neuron detection. The silicon photoelectrode support is used for slowly implanting and fixing a silicon probe with a connector part and comprises a supporting base, the supporting base is of an integrally-formed structure, a channel for the silicon probe to penetrate through is formed in the supporting base, and the external end of the channel is used for fixing the connector part of the silicon probe. According to the silicon photoelectrode support and the silicon photoelectrode device, the supporting base is of an integrally-formed structure, and compared with a common main body and base split type design in the prior art, the mechanical rigidity and stability are more excellent; moreover, implantation is more flexible, a long-term, stable and repeatedly-recorded chronic implantation scheme can be carried out on a freely moving animal body, and recorded neurons are tracked across days; the silicon probe can be detached from the supporting base, and repeated use of the silicon probe is achieved.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of neuron detection, and more particularly relates to a silicon optical electrode support and a silicon optical electrode device. BACKGROUND

[0002] In neuroscience research, many basic cognitive processes, such as learning and memory, spatial navigation, and the like, have neural mechanisms that evolve across time scales of days or even longer. In order to thoroughly understand these processes, long-term, chronic neural activity recording must be performed on animal models (such as freely moving mice) in a natural behavior state.

[0003] At present, the mainstream in vivo neural activity recording technology mainly includes calcium imaging and electrophysiology. Although the calcium imaging technology can achieve chronic recording on freely moving animals, it has a low time resolution and cannot capture rapid neural dynamics. In addition, if deep brain nuclei are to be observed, a large range of invasive surgery is often required, which causes great damage to the animals.

[0004] The electrophysiology recording technology overcomes the above problems. It has a very high time resolution and can easily record the activities of neurons in deep brain regions, and is also suitable for freely moving animals. Therefore, researchers have invested a lot of effort to develop devices for chronic electrophysiology recording. However, the existing chronic implant devices generally have some problems: for example, many devices are permanently fixed with the electrodes after implantation, resulting in the inability to recycle the expensive electrodes; some devices are designed to be too heavy in order to pursue stability, which is not suitable for small experimental animals such as mice.

[0005] The commonly used probe performs well in acute recording, but acute recording cannot be performed on freely moving animals, nor can it track the activities of the same group of neurons across days. In order to apply the probe to chronic experiments such as learning and navigation that require long-term observation, the probe must be chronically implanted. The existing chronic implantation scheme adopts a split design, dividing the implant into a base permanently fixed on the skull and a main body carrying the probe joint part. This split design has a relatively complex structure, the manufacturing and assembly process is cumbersome, and the mechanical stability of the split structure connection cannot meet the experimental requirements in long-term recording. SUMMARY

[0006] The purpose of the embodiments of the present application is to provide a silicon optical electrode support and a silicon optical electrode device to solve the technical problem that the split design of the existing silicon probe chronic implantation device cannot meet the experimental requirements.

[0007] To achieve the above purpose, the technical scheme adopted by the present application is to provide a silicon optical electrode support for chronic implantation and fixation of a silicon probe with a joint part, comprising:

[0008] A support base, which is an integral structure, is provided with a channel for the silicon probe to pass through, and the outer end of the channel is used to fix the joint part of the silicon probe.

[0009] Optionally, the support base is 3D printed by using light-cured resin material.

[0010] Optionally, the implantation end of the support base has a retracted structure inwardly to reduce the impact on the surrounding tissue during implantation and facilitate fixation.

[0011] Optionally, the retracted structure is conical.

[0012] Optionally, the support base has a stepped surface, which divides the support base into a first seat body and a second seat body, the cross section of the first seat body is smaller than that of the second seat body, and the joint part is fixed to the second seat body.

[0013] The application also provides a silicon photoelectrode device, comprising:

[0014] The silicon photoelectrode support as described above;

[0015] A silicon probe, which is detachably mounted on the support base, and the joint part of the silicon probe is located at the outer end of the channel.

[0016] An optical fiber, which is fixedly connected with the joint part of the silicon probe, and the output tip of the optical fiber maintains a preset distance from the electrode recording site of the silicon probe to reduce the photoelectric effect interference on the electrode recording site when light stimulation is performed.

[0017] Optionally, the optical fiber is arranged obliquely relative to the axis of the silicon probe, and the distance between the output tip of the optical fiber and the nearest electrode recording site is 200-400 μm.

[0018] Optionally, the optical fiber forms an oblique angle of 5-15° relative to the axis of the silicon probe.

[0019] Optionally, the joint part of the silicon probe is detachably mounted on the support base by a fastener.

[0020] Optionally, it further comprises a driving member and a screw rod, the joint part is connected with the screw rod, and the driving member is detachably mounted on the support base and drivingly connected with the screw rod to make the joint part move linearly with the driving of the driving member.

[0021] The silicon photoelectrode support and the silicon photoelectrode device provided by the application have the beneficial effects that, compared with the prior art, the support base is an integrally formed structure, and the mechanical rigidity and stability are more excellent than the split design of the main body and the base commonly used in the prior art; moreover, the implantation is more flexible, and the chronic implantation scheme of long-term, stable and repeatable recording can be performed on a freely moving animal, and the recorded neurons can be tracked for days; the silicon probe can be separated from the support base, and the silicon probe can be reused. BRIEF DESCRIPTION OF DRAWINGS

[0022] In order to more clearly illustrate the technical solutions in the embodiments of the application, the drawings needed to be used in the embodiments or the prior art description will be briefly introduced. Obviously, the drawings in the following description are only some embodiments of the application, and other drawings can be obtained by those skilled in the art without creative effort.

[0023] Figure 1 A perspective structural schematic diagram of the silicon photoelectrode support provided by the embodiments of the application;

[0024] Figure 2 A perspective structural schematic diagram of the silicon photoelectrode device provided by the embodiments of the application Figure 1 ;

[0025] Figure 3 A perspective structural schematic diagram of the silicon photoelectrode device provided by the embodiments of the application Figure 2 ;

[0026] Figure 4 An exploded structural schematic diagram of the silicon photoelectrode device provided by the embodiments of the application.

[0027] In the drawings, various reference signs represent:

[0028] 10, support base; 11, channel; 12, top wall; 13, bottom wall; 14, first side wall; 15, second side wall; 16, closing structure; 17, step surface; 171, first seat body; 172, second seat body;

[0029] 20, silicon probe; 21, joint part; 22, positioning step;

[0030] 30, optical fiber;

[0031] 40, fastener. DETAILED DESCRIPTION

[0032] In order to make the technical problems, technical solutions and beneficial effects of the application more clear, the application will be further described in detail in combination with the drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the application, and are not used to limit the application.

[0033] It is to be noted that when an element is referred to as being "fixed" or "set" on another element, it can be directly on the other element or indirectly on the other element. When an element is referred to as being "connected" to another element, it can be directly connected to the other element or indirectly connected to the other element.

[0034] It is to be understood that the terms "length", "width", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer" and the like, indicate directions or positions based on the directions or positions shown in the drawings, and are used for convenience of description and simplification of description only, and do not indicate or imply that the referred device or element must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be construed as limiting the application.

[0035] In addition, the terms "first", "second", "third", etc. are used only for descriptive purposes and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the technical features indicated. Therefore, the features defined with "first", "second", etc. can explicitly or implicitly include one or more of the features. In the description of the application, the meaning of "a plurality of" is two or more, unless otherwise specifically limited.

[0036] The embodiments of the present application provide a silicon photodetector support, as shown in the accompanying drawings, Figure 1 The silicon photodetector support includes a support base 10, which is an integral structure. The support base 10 is provided with a passage 11 for the silicon probe 20 to pass through. The outer end of the passage 11 is used to fix the joint part 21 of the silicon probe 20. As shown in the accompanying drawings, Figure 2 The silicon photodetector support is used for chronic implantation and fixation of the silicon probe 20 with the joint part 21.

[0037] The silicon probe 20 is installed on the silicon photodetector support, which is mainly used for chronic neurophysiological recording and optogenetic control of freely moving animals such as mice and rats.

[0038] The support base 10 is provided with a through passage 11 for accommodating and guiding the silicon probe 20. The silicon probe 20 can be a commercially available Neuropixels electrode, which includes an elongated probe handle and a joint part 21 at one end. The Neuropixels electrode is a high-density silicon probe that can increase the number of neurons that can be obtained in a single recording. When installed, the probe handle of the silicon probe 20 passes through the passage 11, and the joint part 21 is fixed at the outer end of the passage 11, i.e. the end away from the implanted animal's scalp.

[0039] As shown in the accompanying drawings, Figure 1As shown, the silicon photoelectrode support includes a top wall 12, a bottom wall 13, a first side wall 14 and a second side wall 15, the top wall 12 and the bottom wall 13 are oppositely arranged, and the first side wall 14 and the second side wall 15 are separately arranged on opposite sides of the top wall 12. Thus, the first side wall 14, the top wall 12, the second side wall 15 and the bottom wall 13 are sequentially connected to form the channel 11. The through design of the channel 11 can reduce the weight of the silicon photoelectrode support, and avoid affecting the activity of the animal due to the excessive weight of the silicon photoelectrode support. The two ends of the channel 11 are open, one of which is an external end for inserting and fixing the joint part of the silicon probe 20, and the other is an implantation end for implanting into the scalp of the animal. The implantation end of the support base 10 is folded inward to form a folded edge.

[0040] As shown in Figure 3 and Figure 4 The joint part 21 of the silicon probe 20 is partially inserted into the channel 11, the shape of the channel 11 is adapted to the inserted part, and part of the joint part 21 is exposed and fixed at the end of the channel 11. After implanting into the animal body, the support base 10 protects and fixes the silicon probe 20. On the one hand, the top wall 12, the bottom wall 13, the first side wall 14 and the second side wall 15 surround the silicon probe 20 to protect the silicon probe 20, so that the silicon probe 20 will not be permanently damaged during use. On the other hand, the silicon photoelectrode support is a disposable product, which is discarded as a consumable product due to pollution after implanting into the animal body. The silicon probe 20 installed on the silicon photoelectrode support can be reused by cooperating with another silicon photoelectrode support after being cleaned by pancreatin, thereby improving the convenience of use.

[0041] The silicon photoelectrode support provided by the embodiment of the present application has an integrally formed support base 10, which has better mechanical rigidity and stability than the common split design of the main body and the base in the prior art. Moreover, the implantation is more flexible, and the long-term, stable and repeatable recording "chronic implantation" scheme can be performed on the freely moving animal to track the recorded neurons across days.

[0042] Optionally, the entire support base 10 can be 3D printed by a light-cured resin material, so as to realize lightweight while ensuring structural strength and reduce the burden on the animal's head. The light-cured resin can also be made of polyether ether ketone, medical-grade silicone, high-molecular polymer, titanium alloy or other biocompatible materials. The biocompatible material is non-toxic and does not cause strong and continuous immune rejection or inflammatory reactions and other foreign body reactions in animals, and can maintain good and stable physical and chemical properties in the animal body during tracking neurons.

[0043] As shown in Figure 1As shown, the implant end of the support base 10 has a tapered structure 16 to reduce the impact on the surrounding tissue and facilitate fixation.

[0044] The implant end of the support base 10 refers to the end implanted into the animal body during use. The implant end of the support base 10 is designed with a tapered structure 16. In this embodiment, the tapered structure 16 is conical. This design plays a guiding role during implantation and reduces damage to the soft tissue around the skull hole. At the same time, the tapered outer wall can increase the contact area, thereby providing better grip so that the support base 10 can be more firmly and permanently fixed on the skull of the animal. The tapered structure 16 can be conical or pyramidal.

[0045] As shown in FIG. 1, Figure 1 the first side wall 14 and the second side wall 15 are both bent inwardly towards the channel 11, forming a tapered structure 16 gradually narrowing along the axial cross-section of the channel 11. Of course, the top wall 12 and the side walls can also be bent, as long as the tapered structure 16 can be formed at the implant end of the support base 10.

[0046] As shown in FIG. 1, Figure 1 the support base 10 has a stepped surface 17, which divides the support base 10 into a first seat body 171 and a second seat body 172, the cross-section of the first seat body 171 being smaller than that of the second seat body 172, and the joint portion 21 being fixed to the second seat body 172. The stepped surface 17 is used to abut against the animal to limit the implantation depth of the support base 10.

[0047] As shown in FIG. 1, Figure 1 the bending positions on the first side wall 14 and the second side wall 15 are closer to the implant end of the support base 10 than the stepped surface 17. Of course, a bending portion can also be provided only on the first side wall 14 or the second side wall 15, as long as the tapered structure can be formed.

[0048] As shown in FIG. 1, Figure 2 , Figure 3 and Figure 4 The embodiment of the present application also provides a silicon optical electrode device, which comprises a silicon probe 20, an optical fiber 30 and the silicon optical electrode support as described above. The silicon probe 20 is detachably mounted on the support base 10, and the joint portion 21 of the silicon probe 20 is fixed to the outer end of the channel 11. The optical fiber 30 is fixed to the joint portion 21 of the silicon probe 20. The output tip of the optical fiber 30 and the electrode recording site of the silicon probe 20 maintain a predetermined distance therebetween to reduce the photoelectric effect interference on the electrode recording site during optical stimulation.

[0049] As shown in FIG. 1, Figure 4As shown, the connector 21 of the silicon probe 20 has a positioning step 22. The connector 21 is inserted into the channel 11, and the silicon probe 20 and the support base 10 are quickly assembled by means of the positioning step 22 abutting against the external end of the support base 10. In addition, the positioning step 22 can also shield the internal structure of the silicon photoelectrode device.

[0050] like Figure 3 As shown, one end of the optical fiber 30 is fixed to the connector 21 of the silicon probe 20. The end of the optical fiber 30 inserted into the animal body is at a predetermined distance from the electrode recording site. The connector 21 of the silicon probe 20 is fixed to the support base 10 by screws or other detachable means. After the silicon photoelectrode device is installed on the animal, it is fixed to the animal by the support base, providing stable support. After the silicon photoelectrode device is removed from the animal, the optical fiber 30 and the silicon probe 20 can be removed from the support base, cleaned, and reused.

[0051] Both the output tip of the optical fiber 30 and the end of the silicon probe 20 are implanted into the animal's body. Part of the support base 10 is implanted and part is located outside the animal's body. The support base 10 supports and fixes the relative positions of the optical fiber 30 and the silicon probe 20. The entire silicon photoelectrode device does not affect the animal's free movement. Therefore, it can detect changes in neurons during complex behaviors. Compared with the traditional recording method of fixing the animal's head for acute implantation, it can achieve long-term observation and realize the learning and recording of complex behaviors.

[0052] The silicon photoelectrode device provided in this application embodiment allows the silicon probe 20 and the support base 10 to be detached, thereby enabling the silicon probe 20 to be reused and reducing detection costs. The silicon probe 20 can be implanted into an animal with the help of the support base 10, enabling a long-term, stable and reproducible chronic implantation program in freely moving animals.

[0053] The axis of the optical fiber 30 is at a specific angle of inclination relative to the axis of the silicon probe 20. Specifically, the angle of inclination of the optical fiber 30 relative to the axis of the silicon probe 20 is 5°-15°. For example, the angle of inclination is 5°, 15°, 10°, 13°, or any angle between 5° and 15°. The projection distance of the output tip of the optical fiber 30 on the probe axis from the electrode recording site on the silicon probe 20 is precisely controlled. The preset distance of the tip of the optical fiber 30 from the nearest electrode recording site is 200 μm-400 μm. For example, the preset distance of the tip of the optical fiber 30 from the nearest electrode recording site is 200 μm, 400 μm, or any value between 200 μm and 400 μm. For example, the preset distance of the tip of the optical fiber 30 from the nearest electrode recording site is set to 300 μm. By controlling the angle of inclination and the preset distance, the light spot emitted by the optical fiber 30 can effectively cover the target neuron group around the probe recording site, while the tip of the optical fiber 30 itself is kept at a sufficient distance from the sensitive electrode recording site, thereby significantly reducing the photoelectric effect generated by light stimulation and ensuring the purity of the recording signal. Specifically, the optical fiber 30 can be made of quartz optical fiber which has good flexibility and light transmission.

[0054] In some specific embodiments, as shown in Figure 3 The joint portion 21 of the silicon probe 20 is detachably mounted on the support base 10 by the fastener 40.

[0055] The number of fasteners 40 can be multiple to improve the stability of the connection and avoid loosening of the silicon probe 20 relative to the support base 10 due to movement of the animal. Optionally, the fastener 40 is a fixed screw. In order to achieve reusability, the joint portion 21 and the support base 10 are fixed in a detachable manner. As shown in Figure 1 and Figure 2 The joint portion 21 can be locked on the support base 10 by multiple fixed screws or other fasteners 40. After the experiment is completed, the experimenter only needs to loosen the fixed screw nut to completely remove the entire silicon probe 20 along with the functional components thereon from the support base 10 for the next experiment. Only the support base 10 which is low in cost is bonded to the skull of the animal.

[0056] In yet other specific embodiments, the silicon optoelectrode device further comprises a driving member and a screw rod, the joint portion 21 is connected to the screw rod, and the driving member is in transmission connection with the screw rod and is detachably mounted on the support base 10.

[0057] In order to avoid the weight of the silicon photoelectrode device from affecting the free activity of the animal, the driving member is a small steering engine which is directly connected with the screw rod to drive the screw rod to rotate. With the rotation of the screw rod, the joint part 21 is close to or away from the external end of the channel 11, so that the implantation depth of the silicon probe 20 and the optical fiber 30 in the animal body can be slightly adjusted.

[0058] The driving member is located at the external end of the support base 10 and can be removed from the support base 10 to realize repeated use and reduce the detection cost.

[0059] Specifically, the support base 10 is provided with a threaded hole, the adjusting screw is connected in the threaded hole through the joint part 21 of the silicon probe 20, the adjusting screw is driven to rotate by the driving member, the depth of the adjusting screw inserted into the threaded hole is changed, so that the silicon probe 20 is driven to move axially (advance or retreat) by micrometers relative to the fixed support base 10 by the adjusting screw, which enables the researchers to fine-tune the depth of the silicon probe 20 after implantation to record different brain layers or healthier neurons. In addition, the screw rod can also be a rod body of a linear module, the joint part 21 is fixed on the sliding block of the screw rod, and the driving member drives the screw rod to rotate to drive the insertion depth of the joint part 21, so as to fine-tune the depth of the silicon probe 20.

[0060] The silicon photoelectrode device provided by the embodiment of the application is manufactured by using a parameterized modeling software to perform three-dimensional design and using a light-curing 3D printing technology to integrally form and manufacture the support base 10. When the three-dimensional design is performed by using the parameterized modeling software, the implantation depth, the implantation angle, and the relative position of the optical fiber 30 and the silicon electrode need to be considered. After the support base 10 is 3D printed, the optical fiber 30 is fixed to the joint part 21 of the silicon probe 20 at a preset angle and position. Then, the silicon probe 20 passes through the channel 11 of the support base 10, and the joint part 21 is locked on the support base 10 by using a fixing screw or other ways, to form a complete silicon photoelectrode device. The craniotomy is performed on the animal, the implantation end of the support base 10 is implanted into a target brain area, the silicon probe 20 is inserted into a target position, and then the support base 10 is fixed on the skull of the animal. The data acquisition system and the laser are connected, and the long-term electrophysiological recording and optogenetic stimulation under free activity are performed. After the experiment is completed, the silicon probe 20 and the optical fiber 30 are completely taken out from the support base 10, and are cleaned and stored for next use.

[0061] The above merely describes the preferred embodiments of the application and is not used to limit the application, and any modification, equivalent replacement, and improvement made within the spirit and principle of the application should be included in the protection scope of the application.

Claims

1. A silicon photoelectrode holder, characterized by: A silicon probe (20) with a joint part (21) is chronically implanted and fixed, comprising: A support base (10) is integrally formed, and a channel (11) is arranged on the support base (10) for the silicon probe (20) to pass through, and the outer end of the channel (11) is used to fix the joint part (21) of the silicon probe (20).

2. The silicon photoelectrode holder of claim 1, wherein: The support base (10) is 3D printed by using a light-cured resin material.

3. The silicon photoelectrode holder of claim 1, wherein: The implantation end of the support base (10) has a retracted structure (16) inwardly retracted to reduce the influence on the surrounding tissue during implantation and facilitate fixation.

4. The silicon photoelectrode holder of claim 3, wherein: The retracted structure (16) is tapered.

5. The silicon photoelectrode holder of claim 1, wherein: The support base (10) has a stepped surface (17) that divides the support base (10) into a first seat body (171) and a second seat body (172), the cross section of the first seat body (171) is smaller than that of the second seat body (172), and the joint part (21) is fixed in the second seat body (172).

6. A silicon photoelectrode device, characterized by: Comprise: The silicon electrode support of any one of claims 1 to 5; A silicon probe (20) is detachably mounted on the support base (10), and the joint part (21) of the silicon probe (20) is located at the outer end of the channel (11); An optical fiber (30) is fixedly connected with the joint part (21) of the silicon probe (20), and the output tip of the optical fiber (30) maintains a predetermined distance from the electrode recording site of the silicon probe (20) to reduce the photoelectric effect interference on the electrode recording site when performing optical stimulation.

7. The silicon photoelectrode device of claim 6, wherein: The optical fiber (30) is inclined relative to the axis of the silicon probe (20), and the distance between the output tip of the optical fiber (30) and the nearest electrode recording site is 200-400 μm.

8. The silicon photoelectrode device of claim 7, wherein: The optical fiber (30) forms an inclination angle of 5-15° relative to the axis of the silicon probe (20).

9. The silicon photoelectrode device of claim 6, wherein: The joint part (21) of the silicon probe (20) is detachably mounted on the support base (10) by a fastener (40).

10. The silicon photoelectrode device of claim 6, wherein: Further comprising a driving member and a screw rod, the joint part (21) is connected with the screw rod, and the driving member is detachably mounted on the support base (10) and is in transmission connection with the screw rod, so that the joint part (21) moves linearly with the driving of the driving member.

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