WO2019126920A1

WO2019126920A1 - Cell stimulation device and cell stimulation method

Info

Publication number: WO2019126920A1
Application number: PCT/CN2017/118212
Authority: WO
Inventors: 李永川; 郭瑞彪; 唐彩云; 钱明; 蔡飞燕; 黄继卿; 郑海荣
Original assignee: 深圳先进技术研究院
Priority date: 2017-12-25
Filing date: 2017-12-25
Publication date: 2019-07-04

Abstract

Disclosed are a cell stimulation device and a cell stimulation method. The cell stimulation device comprises stimulation probes (1), a base (2) and a positioning socket (3) capable of sliding with respect to the base (2); the base (2) is provided with a plurality of hole sites (11) for mounting the stimulation probes (1); the positioning socket (3) has a positioning structure for positioning a culture dish (5); the stimulation probes (1) are mounted in the hole sites (11) and face towards the positioning socket (3); and a guide bar sliding structure is disposed between the base (2) and the positioning socket (3). The cell stimulation method is implemented by means of the cell stimulation device; the size of the area and the intensity of uniform ultrasonic stimulation received by cells in the culture dish (5) are controlled by adapting an array of stimulation probes (1) of different sizes and adjusting a height of the positioning socket (3), so as to stimulate cells; multiple groups of cells can be stimulated simultaneously; the experiment effect is excellent, the operation is precise, simple and fast, and the uniformity is good.

Description

Cell stimulation device and cell stimulation method

Technical field

The invention belongs to the technical field of cell stimulation, and in particular relates to a cell stimulation device and a cell stimulation method.

Background technique

With the development of science and technology, the understanding of neuroscience has deepened, and the research on neuroscience has become a hot spot in medical care. Nowadays, nerve stimulation mainly includes drugs and external stimulation methods. External stimulation methods include light stimulation and electrical stimulation. , magnetic stimulation and ultrasound stimulation. Ultrasound stimulation is gaining more and more attention due to its safety, non-invasiveness, effectiveness and real-time. Many laboratories in the world are currently conducting ultrasound-stimulated nerve cell research, and ultrasonic transducers are the core components. In the prior art, it is difficult to ensure that the ultrasound effect of cells received in each cell and group and between groups is Uniform, the experimental results are not good.

technical problem

The object of the present invention is to overcome the above deficiencies of the prior art, and to provide a cell stimulation device and a cell stimulation method, which have good experimental results, and are precise, simple, convenient, and uniform.

Technical solution

The technical solution of the present invention is: a cell stimulation device comprising a stimulation probe, a base and a positioning seat slidable relative to the base, the base being provided with a plurality of holes for mounting the stimulation probe, the positioning The seat has a positioning structure for positioning the culture dish, the stimulation probe is mounted on the hole position and faces the positioning seat, and a guide bar sliding structure is disposed between the base and the positioning seat.

Optionally, the guide bar sliding structure comprises a guiding rod, one end of the guiding rod is fixedly connected to the base, the positioning seat is provided with a sleeve hole, and the sleeve hole is sleeved on the guiding rod.

Optionally, the positioning seat or the guiding rod is provided with a positioning structure for locking the positioning seat.

Optionally, the positioning structure includes a threaded hole disposed on a side of the positioning seat and an adjusting bolt screwed to the threaded hole, the threaded hole is in communication with a side surface of the sleeve hole, and a front end of the adjusting bolt Abutting the side of the guide rod.

Optionally, the hole position is a stepped hole.

Optionally, the positioning structure is a receiving groove disposed on an upper surface of the positioning seat and configured to place the culture dish, and a bottom surface of the receiving groove is attached to a bottom surface of the culture dish.

Optionally, a side of the positioning seat is screwed with a fixing bolt for fixing the petri dish.

Optionally, the hole position is provided in plurality, and each of the hole positions is provided with an ultrasonic stimulation probe, and each of the ultrasonic stimulation probes is connected with a separate cable; the culture dish has an array hole The array aperture is disposed coaxially with the hole for mounting the stimulation probe.

Optionally, the side of the positioning seat is provided with a sound absorbing material for absorbing boundary ultrasonic waves.

The present invention also provides a cell stimulation method using the above cell stimulation device comprising the following steps:

Positioning the stimulation probe upward in the hole of the base and facing the positioning seat;

Placing a culture dish on the positioning seat;

Adjusting the culture dish to be coaxially aligned with the corresponding stimulation probe;

The distance of the positioning seat relative to the stimulation probe is adjusted by a guide bar sliding structure.

Beneficial effect

The invention provides a cell stimulation device and a cell stimulation method. By matching different sizes of stimulation probe arrays, by adjusting the height of the positioning seat, the cells can be stimulated by controlling the size and intensity of the uniform ultrasonic stimulation of the cells in the culture dish. The experiment has good effect, and the operation is precise, simple, convenient and quick, and can stimulate multiple groups of cells at the same time, and the uniformity is good.

DRAWINGS

In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings to be used in the embodiments will be briefly described below. It is obvious that the drawings in the following description are only some embodiments of the present invention. Those skilled in the art can also obtain other drawings based on these drawings without paying any creative work.

1 is a perspective exploded view of a cell stimulation device according to an embodiment of the present invention;

2 is a schematic diagram of circuit connection of a cell stimulation device according to an embodiment of the present invention;

3 is a three-dimensional assembly diagram of a base and a guide rod in a cell stimulation device according to an embodiment of the present invention;

4 is a schematic perspective view of a stimulation probe, a base, and a guide rod in a cell stimulation device according to an embodiment of the present invention;

5 is a three-dimensional assembly diagram of a stimulation probe, a base, a guide rod, and a positioning seat in a cell stimulation device according to an embodiment of the present invention;

FIG. 6 is a schematic perspective view of a cell stimulation device according to an embodiment of the present invention.

Embodiments of the invention

The present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It is understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

It is to be noted that when an element is referred to as being "fixed" or "in" another element, it can be directly on the other element or the central element. When an element is referred to as being "connected" to another element, it can be directly connected to the other element or the central element.

It should also be noted that the left, right, upper, lower, and the like orientations in the embodiments of the present invention are merely relative concepts or referenced to the normal use state of the product, and should not be considered as limiting. .

As shown in FIG. 1 to FIG. 6 , a cell stimulation device according to an embodiment of the present invention includes a stimulation probe 1 (ultrasonic stimulation probe), a base 2, a petri dish 5, and a positioning seat 3 that can slide relative to the base 2, and the base 2 A plurality of hole positions 11 for mounting the stimulation probe 1 are provided, and the stimulation probe 1 can be actively inserted into the hole position 11 and positioned by the hole position 11, that is, the stimulation probe 1 can be replaced. The hole positions 11 can be arranged in a matrix. The positioning seat 3 has a positioning structure for positioning the culture dish 5 so that the culture dish 5 can be smoothly placed on the positioning seat 3. The stimulation probe 1 is mounted on the hole position 11 and faces the bottom of the positioning seat 3 and the culture dish 5. The guide rod sliding structure is arranged between the base 2 and the positioning seat 3, so that the positioning seat 3 and the culture dish 5 can stably slide up and down. Thereby adjusting the distance between the culture dish 5 and the stimulation probe 1, the positioning seat 3 does not slide left and right or back and forth, by matching the array of stimulation probes 1 of different sizes, and by adjusting the height of the positioning seat 3, it can be controlled by the culture dish 5 The cells are stimulated by the size and intensity of the uniform ultrasonic stimulation. The culture dish 5 can be provided with a plurality of culture chambers 51, and the plurality of culture chambers 51 can correspond to the arrangement of the holes 11 and the array of stimulation probes 1, that is, the chambers 51 The bottom has a coaxial hole position 11 and a corresponding stimulation probe 1, so that multiple groups of cells can be stimulated at the same time, the uniformity is good, the operation is simple and convenient, and the scope of use is very wide.

Optionally, a plurality of hole positions 11 are provided, and one ultrasonic stimulation probe 1 is disposed in each hole position 11, and each (group) ultrasonic stimulation probe 1 is connected with a separate cable (coaxial cable). Each (group) of ultrasonic stimulation probes 1 is connected to a power amplifier, each power amplifier is connected to a frequency divider, the frequency divider is connected to a DA module (digital-to-analog conversion module), and the DA module is connected to a signal source.

Optionally, the guiding rod sliding structure comprises a guiding rod 4, one end of the guiding rod 4 is fixedly connected to the base 2, the positioning seat 3 is provided with a sleeve hole 31, and the sleeve hole 31 is slidably sleeved on the guiding rod 4. The positioning seat 3 can be precisely slid up and down along the guide rod 4. The guide bar 4 can be provided with at least two. In the embodiment, the guide bar 4 is provided with four, and the positioning precision is high, the position is accurate, the force is balanced, and the operation is simple and convenient. The guide rod 4 can have a cylindrical shape. In a specific application, the number and shape of the guide bars 4 can be set according to actual conditions. Of course, the guide rod 4 can also be fixed to the positioning base 3 and slidably inserted into the base 2, and the positioning base 3 can also be adjusted to slide up and down with respect to the base 2.

Alternatively, the positioning seat 3 or the guide bar 4 is provided with a positioning structure for locking the positioning seat 3 so that the positioning seat 3 can be temporarily positioned to be maintained at a set height.

Optionally, the positioning structure includes a threaded hole disposed on the side of the positioning seat 3 and an adjusting bolt 61 threadedly connected to the threaded hole. The threaded hole communicates with the side surface of the sleeve hole 31, and the front end of the adjusting bolt 61 can abut against the side of the guiding rod 4. Therefore, the positioning seat 3 can be fixed relative to the guide rod 4. When the height of the positioning seat 3 needs to be adjusted again, the adjusting bolt 61 is reversely loosened to release the leading end of the adjusting bolt 61.

Alternatively, the hole position 11 may be a stepped hole to position the stimulation probe 1 of different specifications, and the cell stimulation device has wide applicability.

Optionally, the positioning structure is disposed on the upper surface of the positioning base 3 and is used for placing the accommodating groove 32 of the culture dish 5. The bottom surface of the accommodating groove 32 is attached to the bottom surface of the culture dish 5 to make the culture dish 5 and the stimulation probe. The surface of 1 is parallel. The bottom of the accommodating groove 32 is provided with a hollow hole 33, so that the stimulation probe 1 can directly face the bottom of the culture dish 5, and the energy loss is small.

Optionally, two opposite sides of the positioning seat 3 are screwed with fixing bolts 62 for fixing the culture dish 5 to adjust and fix the planar position of the culture dish 5, so that the central axis of the culture chamber 51 in the culture dish 5 and the stimulation probe The center axis of 1 coincides.

Optionally, the side of the positioning seat 3 is provided with a sound absorbing material for absorbing boundary ultrasound.

The embodiment of the invention further provides a cell stimulation method, which comprises the above cell stimulation device, comprising the following steps:

The stimulation probe 1 is disposed upward in the hole 11 of the base 2 and faces the positioning seat 3;

Placing the culture dish 5 on the positioning seat 3;

Adjusting the culture dish 5 to be coaxially aligned with the corresponding stimulation probe 1;

The distance of the positioning seat 3 relative to the stimulation probe 1 is adjusted by the sliding structure of the guide rod 4, and ultrasonic stimulation is applied to the culture dish 5 by the stimulation probe 1.

In a specific application, the guide rod 4 can be firstly fixed on the base 2, as shown in FIG. 3, the base 2 is provided with an array of hole positions 11, and the hole position 11 has a positioning step for mounting the stimulation probe 1 group to ensure The flatness and parallelism of the upper surface of the base 2 and the steps of the array holes. The guide rod 4 can be used to engage the positioning seat 3, so that the positioning seat 3 is not offset left and right, and does not rotate and can move up and down. The stimulation probe 1 is then mounted on the hole 11 of the base 2 as shown in FIG. The array of the stimulation probe 1 is installed in one-to-one correspondence with the hole position 11 of the array, and the stimulation probe 1 is matched with the step surface to ensure the parallelism between the probe surface and the upper surface of the base 2. Each of the stimulation probes 1 is led out by a coaxial cable. . The positioning seat 3 is then mounted on the guide bar 4 as shown in FIG. The boundary of the positioning seat 3 can use a sound absorbing material to absorb the boundary ultrasonic to ensure the consistency of the ultrasonic stimulation field, and the small gap between the sleeve hole 31 (round hole) of the positioning seat 3 and the guide rod 4 ensures the positioning seat 3 and The parallelism of the surface of the probe; the positioning seat 3 moves up and down along the upper surface of the guide rod 4 with respect to the base 2, and the relative height is positioned by the adjusting bolt 61 (screw). Finally, the cell culture dish 5 was installed as shown in FIG. The culture dish 5 is placed on the positioning base 3, and by moving left and right, the culture chamber 51 of the array on the culture dish 5 is in one-to-one correspondence with the hole position 11 of the array on the base 2, and the bottom surface of the culture dish 5 is matched with the surface of the positioning seat 3 to ensure The corresponding culture chamber 51 is coaxial with the stimulation probe 1. The culture dish 5 is secured by a fixing bolt 62 (screw). The parallelism of the base 2, the positioning block 3, the stimulation probe 1, and the culture dish 5 is good, and the ultrasonic field of the stimulation of the stimulation probe 1 is uniformly applied to the cells in the culture dish 5. In this embodiment, multiple sets of stimulation probes 1 are used, and each set of stimulation probes 1 is extracted by using a coaxial line. Each group of stimulation probes 1 can be connected with a power amplifier, which can stimulate multiple groups of cells at the same time, and the experiment is more convenient and quick. More sexual.

In the specific application, the size of the base 2, the positioning seat 3 and the like are not limited, and the size of the probe is not limited. With the probes of different sizes, by adjusting the height of the positioning seat 3, the area of the cells in the culture dish 5 subjected to uniform ultrasonic stimulation can be controlled. The intensity, the experimental effect is good, and the operation is precise, simple, convenient and fast, and can stimulate multiple groups of cells at the same time, and the uniformity is good.

The cell stimulation device and the cell stimulation method provided by the embodiments of the present invention can control the area of the cells in the culture dish 5 to be uniformly stimulated by adjusting the height of the positioning block 3 by matching the arrays of the stimulation probes 1 of different sizes. And the intensity to stimulate the cells, the culture dish 5 can be provided with a plurality of culture chambers 51, and the plurality of culture chambers 51 can correspond to the arrangement of the holes 11 and the array of stimulation probes 1, that is, the coaxial holes are arranged under the respective culture chambers 51. 11 and the corresponding stimulation probe 1, so that multiple groups of cells can be stimulated at the same time, the uniformity is good, the operation is simple and convenient, and the application range is wide.

The above is only the preferred embodiment of the present invention, and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and scope of the present invention should be included in the scope of the present invention. Inside.

Claims

A cell stimulation device, comprising: a stimulation probe, a base and a positioning seat slidable relative to the base, the base being provided with a plurality of holes for mounting the stimulation probe, the positioning seat having a The positioning structure of the culture dish is positioned, the stimulation probe is mounted on the hole position and faces the positioning seat, and a guiding rod sliding structure is disposed between the base and the positioning seat.
The cell stimulating device according to claim 1, wherein the guide bar sliding structure comprises a guiding rod, one end of the guiding rod is fixedly connected to the base, and the positioning seat is provided with a sleeve hole, The sleeve hole is sleeved on the guide rod.
A cell stimulation device according to claim 2, wherein said positioning seat or said guide bar is provided with a positioning structure for locking said positioning seat.
A cell stimulation device according to claim 3, wherein said positioning structure comprises a threaded hole provided on a side of said positioning seat and an adjusting bolt screwed to said threaded hole, said threaded hole and said The sides of the sleeve are communicated, and the front end of the adjusting bolt abuts against the side of the guide rod.
A cell stimulation device according to claim 1, wherein said hole position is a stepped hole.
The cell stimulating device according to claim 1, wherein the positioning structure is a receiving groove disposed on an upper surface of the positioning seat and for placing the petri dish, the receiving groove The bottom surface is attached to the bottom surface of the culture dish.
A cell stimulation apparatus according to claim 6, wherein a side of said positioning seat is screwed with a fixing bolt for fixing said petri dish.
A cell stimulation device according to claim 1, wherein said plurality of hole positions are provided, and each of said holes is provided with an ultrasonic stimulation probe, and each of said ultrasonic stimulation probes is connected There is a separate cable; the culture dish has an array of holes that are coaxially disposed with the hole for mounting the stimulation probe.
A cell stimulation device according to claim 1, wherein a side of said positioning block is provided with a sound absorbing material for absorbing boundary ultrasonic waves.
A cell stimulation method, characterized by using a cell stimulation device according to any one of claims 1 to 9, comprising the steps of:

Positioning the stimulation probe upward in the hole of the base and facing the positioning seat;

Placing a culture dish on the positioning seat;

Adjusting the culture dish to be coaxially aligned with the corresponding stimulation probe;

The distance of the positioning seat relative to the stimulation probe is adjusted by a guide bar sliding structure.