CN106479863B - Pusher for making monolayer cells - Google Patents

Abstract

The invention discloses a pusher device for making single-layer cells, which comprises: a base plate, on both sides of which are provided with guide rails; On; the push piece clamp, which is connected with the push piece; the first hinge assembly, which includes the first hinge mounting seat and the first hinge; the first hinge assembly is connected with the push piece clip through the fixing hole; the second hinge assembly, which It includes a second hinge mounting base and a second hinge; the second hinge assembly is connected to the first hinge assembly; the advancing directions of the first hinge and the second hinge are relatively vertical in space. In this case, the automatic fine-tuning technology of the pusher attitude on two degrees of freedom is used to realize the rapid and continuous single-layer spreading of one billion cells without the superposition of multiple layers of cells. The pushing device can be used in conjunction with imaging equipment to quickly find rare cells and diseased cells, which is of great significance to the early clinical detection of infectious diseases and tumor cancer.

Description

Pusher for making monolayer cells

technical field

The invention relates to a pushing device, in particular to a pushing device for making monolayer cells.

Background technique

How to quickly and accurately identify rare cells and trace pathogenic microorganisms among billions of cells in peripheral blood is an important research topic in the field of life sciences, and it is also an extremely effective means for early identification of infectious diseases, tumors and cancers, etc. Compared with traditional imaging detection, its detection time is greatly advanced, so it has very important significance for medical examination and clinical examination.

At present, the existing method for detecting peripheral blood cells is to use CTC cell flow cytometry for detection. The basic principle is to flow all the labeled cells through the detection area one by one, and detect rare cells or diseased cells through fluorescence detection. count. Because it adopts a single cell serial detection method, the detection cycle is long and the detection cost is high.

It is a new type of cell detection technology to spread the whole blood cells in a single layer on the glass slide by using the slide technology, and to identify rare cells or diseased cells by visual recognition or optical imaging for rapid cell screening and counting. Compared with the flow counting method, the speed is greatly improved, the detection time is short, and the cost is low.

The film pushing machines that have been used clinically include Sysmex's SP-1000i and Mindray's SC-120 film pushing machines, which are often used in conjunction with blood routine to detect the count of various white blood cells in the blood. The sample volume of these two instruments is 60μL-200μL. For cells that exist in large quantities in blood, such as eosinophils, lymphocytes, monocytes, etc., it can be detected more accurately. In clinical testing, it is better to only choose the pusher. The small parts of the small parts can only identify the approximate proportion of pathogenic cells.

However, these two models are powerless for the detection of rare cells and trace pathogenic microorganisms because:

1) The amount of samples is not enough. These two instruments do not have a device module for continuous nourishment, and can only push 60-200μL samples, while the detection of rare cells and trace pathogenic microorganisms requires 1 billion peripheral blood (about 7.5mL samples) Quickly and accurately identify dozens or even a few rare cells and trace pathogenic microorganisms among billions of cells.

2) The quality of the push film is not enough. Limited by application, Sysmex's SP-1000i and Mindray's SC-120 have no requirements for the head and tail of the push piece, they only need to have tiny monolayer cell fragments in the middle of the push piece, and the head and tail parts are Multiple layers of cells come together. For the rapid and accurate identification of dozens or even a few rare cells and traces of pathogenic microorganisms among billions of cells in 1 billion peripheral blood (7.5ml samples), it is obviously important for every part of the entire slide. Both require a single layer to ensure that rare cells are not missed due to cell stacking.

Contents of the invention

Aiming at the deficiencies in the prior art, this case proposes a pushing device for making monolayer cells.

Technical scheme of the present invention is summarized as follows:

A pusher for making monolayer cells, comprising:

The base plate is provided with rail bars on both sides;

A push piece, one end of which is used to contact the guide rail, and spread the cell solution on the substrate in a slidable manner on the guide rail;

Push piece clip, it is connected with described push piece;

A first hinge assembly, which includes a first hinge mounting base and a first hinge; the first hinge assembly is connected to the push clip through the first hinge;

a second hinge assembly, which includes a second hinge mount and a second hinge; the second hinge assembly is connected to the first hinge assembly;

Wherein, the advancing directions of the first hinge and the second hinge are relatively vertical in space.

Preferably, in the said pushing device for making monolayer cells, the height of the guide rails is 5-20 μm.

Preferably, in the pusher device for producing monolayer cells, a stopper for limiting the rotation angle of the pusher clamp is provided on the first hinge mount.

Preferably, in the said pusher device for producing monolayer cells, an elastic member is further arranged on the first hinge, and the elastic member generates a rebound force when the pusher clamp rotates.

Preferably, in the pusher device for making monolayer cells, there is also a flow channel for liquid injection inside the pusher.

Preferably, in the pusher device for producing monolayer cells, the pusher surface is further provided with a groove for accommodating a liquid injection tube.

Preferably, in the pusher device for making a monolayer of cells, the surface of the pusher is also provided with a wiring hole for the injection tube to pass through.

Preferably, in the said pusher device for producing monolayer cells, an elastic gasket is further provided between the pusher and the pusher clamp.

The beneficial effects of the present invention are: the device proposed in this case adopts the continuous sample injection technology, and utilizes the automatic fine-tuning technology of the push piece posture on the double degrees of freedom, which can realize the rapid and continuous single-layer spreading of 1 billion cells (7.5mL blood sample), And there will be no superposition of multiple layers of cells on the entire cell layer. The pusher device can be used in conjunction with large-field graphic imaging equipment, which can quickly identify individual rare cells and diseased cells in 1 billion cells (7.5mL blood sample), which is useful for early clinical detection of infectious diseases and tumors important meaning.

Description of drawings

Figure 1 is a schematic diagram of the structure of a pushing device for making monolayer cells.

Fig. 2 is a schematic structural view of the pusher device including the sections of the first hinge assembly and the second hinge assembly.

FIG. 3 is a partially enlarged view of A in FIG. 2 .

Fig. 4 is a schematic diagram of the structure of the tablet pushing device adopting the first method of sample injection and liquid injection.

Fig. 5 is a structural schematic diagram of the second method of sample injection and liquid injection in the pusher device.

Fig. 6 is a schematic structural view of the substrate in the chip pushing device.

Fig. 7 is a schematic diagram of the spatial dynamics when the first hinge and the second hinge rotate relative to each other.

Fig. 8 is a structural schematic diagram of multiple groups of tablet pushing devices being used in conjunction at the same time.

Detailed ways

The present invention will be further described in detail below in conjunction with the embodiments, so that those skilled in the art can implement it with reference to the description.

As shown in Figures 1-8, this case lists an embodiment of a pushing device for making monolayer cells, which includes:

The base plate 1 is provided with guide rail bars 2 on both sides;

Push piece 3, one end thereof is used for contacting with guide rail bar 2, and on guide rail bar 2, cell liquid is tiled on the substrate 1 in the mode of slidable movement; The effect of guide rail bar 2 is: 1) overcome blood sample viscosity, simultaneously Reduce the contact area between the pusher 3 and the substrate 1, thereby reducing the resistance when advancing on the substrate 1; 2) Control the gap between the pusher 3 and the substrate 1 to meet the needs of tiling of monolayer cells.

Push piece folder 4, it is connected with push piece 3;

The first hinge assembly includes a first hinge mount 5 and a first hinge 6; the first hinge assembly is connected to the push clip 4 through the first hinge 6;

The second hinge assembly includes a second hinge mount 7 and a second hinge 8; the second hinge assembly is connected to the first hinge assembly;

Wherein, the advancing directions of the first hinge 6 and the second hinge 8 are relatively vertical in space (as shown in FIG. 7 ). The first hinge 6 and the second hinge 8 are connection mechanisms capable of relative rotation, including but not limited to a "shaft-bearing" connection. The first hinge 6 is used to connect the push clip 4 and the first hinge mount 5 , and it can realize the relative rotation between the push clip 4 and the first hinge mount 5 along the X-axis direction. The second hinge 8 is used to connect the first hinge mounting base 5 and the second hinge mounting base 7 , and it can realize relative rotation between the first hinge mounting base 5 and the second hinge mounting base 7 along the Y-axis direction. The first hinge 6 and the second hinge 8 enable the push piece 3 to have two rotational degrees of freedom in the directions of the X and Y axes (as shown in FIG. 7 ).

Wherein, the height of the guide rail 2 is preferably 5-20 μm, and the diameter of the cells is 5-20 μm, so that the cells can be effectively protected during the pushing process.

Wherein, the first hinge mounting seat 5 is provided with a blocking member 9 for limiting the rotation angle of the pushing clip 4 . The stopper 9 can block the movement of the pusher clip 4, and its function is to limit the rotation angle between the pusher 3 and the first hinge mounting seat 5, so as to ensure that the moment when the pusher 3 is in contact with the substrate 1, The angle between the two will not exceed a fixed value (for example: 30 degrees), so as to protect the pushing piece 3 itself and improve the pushing quality.

Wherein, an elastic member 10 is also provided on the first hinge 6 , and the elastic member 10 generates a rebound force when the pushing clip 4 rotates. The elastic member 10 can apply an elastic force between the push piece clip 4 and the first hinge mounting seat 5, when the push piece clip 4 rotates relative to the first hinge mounting seat 5, the deformation of the elastic piece 10 makes it A certain amount of resilience can be generated. On the one hand, this force can constrain the angle between the push piece clip 4 and the first hinge mount 5 in a free state. On the other hand, when the push piece 3 is in contact with the base plate 1 and When pushing the piece, make the push piece 3 have a certain downward force to act on the guide rail bar 2 of the substrate 1, so as to ensure that the push piece 3 and the guide rail bar 2 are always in close contact during the piece pushing process. The elastic member 10 can be: a torsion spring, which is coaxial with the first hinge 6 (as shown in Figure 3), with one end abutting against the push piece clip 4 and the other end abutting against the first hinge mount 5; or stretching Spring, one end is fixed on the pusher clip 4, and the other end is fixed on the first hinge mount 5; or a compression spring, one end is fixed on the pusher clip 4, and the other end is fixed on the first hinge mount 5.

In addition, this device can also realize continuous sample injection, which can be realized in various forms:

Mode 1: The inside of the push piece 3 is provided with a flow channel 11 for liquid injection, as shown in FIG. 4 .

Method 2: The surface of the push piece 3 is also provided with a groove 12 for accommodating the liquid injection tube. The surface of the push piece 3 may also preferably be provided with a wiring hole 13 for the insertion of the liquid injection tube, as shown in FIG. 5 .

In addition, an elastic gasket 14 is provided between the push piece 3 and the push piece clip 4 to realize the elastic connection between the push piece 3 and the push piece clip 4, so as to ensure that the push piece 3 will not be damaged during the installation process.

The second hinge mounting base 7 and the base plate 1 can be externally connected to a driving device, such as a linear motor or a rotary motor+screw, to generate relative motion under this action, including the Z-axis direction and the Y-axis direction (marked in FIG. 7 Orientation as the reference) translational motion. The driving device can include one or more linear motors or rotary motors + screw driving devices. In order to improve throughput and efficiency, the film pushing device can include multiple bodies to perform film pushing operations simultaneously, as shown in FIG. 8 .

The above relative movement can be realized in the following ways:

A) The substrate 1 is fixed, and the second hinge mount 7 is driven by an external drive device to perform translational motions in the Z and Y directions.

B) The base plate 1 performs translational movement in the Y direction by the driving system of the external driving device, and the second hinge mount 7 performs translational movement in the Z direction under the drive of the external driving device.

C) The substrate 1 is driven by an external drive device to perform translational motions in the Z and Y directions, while the second hinge mount 7 remains fixed.

The basic operation process of the pushing device is as follows:

1) Place the substrate 1;

2) Driven by an external drive device, the push piece 3 slowly moves in a direction perpendicular to the substrate 1 and gradually approaches the substrate 1;

3) During the contact process between the push piece 3 and the substrate 1, the first hinge 6 and the second hinge 8 will automatically fine-tune the state of the push piece according to the contact force between the push piece 3 and the substrate 1, so that the edge of the push piece 3 is in line with the substrate. 1 tight fit;

4) Driven by the external drive device, the push piece 3 continues to move in the direction perpendicular to the substrate 1, and at this time the elastic member 10 starts to act, so that the push piece 3 acts on the substrate 1 with a certain pressure, ensuring that the push piece 3 close contact with

5) Slowly inject the sample into the sample injection channel through an external power source. The sample is dispersed on the edge of the substrate 1 under the action of capillary force. At the same time, under the drive of the external drive device, the push piece 3 is translated along the length direction of the substrate 1, and the sample is continuously and evenly spread on the substrate 1 in a single layer;

6) After pushing the film, under the drive of the external driving device, the pushing film 3 will move away from the substrate 1 vertically and parallel to the direction of the substrate 1, and then automatically return to the original position. At the same time, the external power source cleans the injection flow To ensure no cross-contamination.

Although the embodiment of the present invention has been disclosed as above, it is not limited to the use listed in the specification and implementation, it can be applied to various fields suitable for the present invention, and it can be easily understood by those skilled in the art Therefore, the invention is not limited to the specific details without departing from the general concept defined by the claims and their equivalents.

Claims (7)

1. a kind of for making the pushing device of cell monolayer characterized by comprising

Substrate, two sides are equipped with guide rail bar；

Push jack, one end for being contacted with the guide rail bar, and in the guide rail bar in a manner of slidable movement by cell Liquid tiles on the substrate；

Push jack folder, connect with the push jack；

First axle component comprising have first axle mounting base and first axle；The first axle component passes through described the One hinge and push jack folder realize connection；

Second hinge component comprising have second hinge mounting base and second hinge；The second hinge component and described first Hinge component connection；

Wherein, the direction of propulsion of the first axle and the second hinge spatially Relative vertical；

Wherein, the height of the guide rail bar is 5-20 μm.

2. according to claim 1 for making the pushing device of cell monolayer, which is characterized in that the first axle peace The block piece for limiting the push jack folder rotation angle is provided on dress seat.

3. according to claim 1 for making the pushing device of cell monolayer, which is characterized in that in the first axle On be additionally provided with elastic component, the elastic component the push jack press from both sides rotate when generate screen resilience.

4. according to claim 1 for making the pushing device of cell monolayer, which is characterized in that inside the push jack also Offer the runner for fluid injection.

5. according to claim 1 for making the pushing device of cell monolayer, which is characterized in that the push jack surface is also Offer the groove for accommodating liquid injection pipe.

6. according to claim 5 for making the pushing device of cell monolayer, which is characterized in that the push jack surface is also Offer the routing hole interted for liquid injection pipe.

7. according to claim 1 for making the pushing device of cell monolayer, which is characterized in that the push jack and push jack Elastomeric pad is additionally provided between folder.