Chip Fixing Device

Abstract

The present invention provides a chip fixing device, comprising: a fixing body, having a first plate body and a second plate body that are interlocked, the first plate body is provided with a first window for light source to enter, the second plate body is provided with a second window for collecting imaging, the first window and the second window are arranged opposite to each other; a clamping structure for clamping a sample to be tested, located in the second window, the clamping position of the clamping structure and the sample to be tested are arranged symmetrically relative to the center of the sample to be tested. The chip fixing device of the present invention can solve the technical problems of horizontal and vertical offset of the sample to be tested.

Description

Technical Field

[0001] The present invention relates to the field of chip technology, and in particular to a chip fixing device. Background Art

[0002] Tracking and observing a large number of single bacterial cells for a long time has become an important means of studying bacterial physiology. Single-cell time-lapse microscopy is one of the few technologies that can achieve the above goal. The core parts of this technology include: a) using a high-power oil objective (usually a 100x oil immersion objective with a numerical aperture of more than 1.5) for imaging; b) using a time-lapse shooting system (i.e. shooting the sample once every fixed time interval) to collect sample image data; c) using a high-precision electric displacement platform to achieve multi-point circular sampling; d) using an autofocus system to lock the sample focus to prevent image blur caused by loss of focus; e) using a microfluidic chip to provide cells with suitable growth conditions, including a continuous supply of fresh culture medium and a constant ambient temperature (usually 37°C).

[0003] At present, some high-end scientific research-grade commercial microscopes have integrated time-lapse shooting systems, high-precision electric displacement platforms, and autofocus systems while providing high-power oil immersion lenses. In addition, some commercial temperature control devices can be integrated into specific models of microscopes to control the temperature around the cell sample to a set value. For nutrient supply, some microfluidic devices can continuously provide fresh culture medium to cells by perfusion. Due to the development of the above-mentioned technologies, long-term tracking and observation of single bacterial cells has become quite convenient. However, the existing technical means also face two serious problems: one is the failure of the autofocus system, and the other is the offset of the sampling field of view. The failure of the autofocus system is mainly due to the displacement of the sample in the Z-axis direction, and the displacement exceeds the calibration range of the autofocus system. Even if the displacement does not exceed the calibration range, it will cause the autofocus time to be extended, greatly reducing the focusing rate. The sampling field of view offset is mainly due to the displacement of the sample in the X and Y axis directions. When the displacement exceeds the adaptability of the cell image recognition software, the subsequent image data analysis will be wrong, and even the serious consequence of the image being unable to be analyzed. The root cause of the above two problems is that the microfluidic chip needs to use a 0.17mm thick glass slide as the substrate during high-magnification imaging. This thickness of the glass slide is easy to deform and difficult to be firmly fixed on the electric translation stage. The main factors that cause the deformation and displacement of the glass slide include but are not limited to the following: a) thermal expansion and contraction of objects caused by temperature fluctuations; b) high-speed movement of the electric translation stage during multi-site cyclic sampling; c) changes in the tension of the immersion oil between the glass slide and the objective lens; d) mechanical vibration of the microscope during operation and external disturbances.

[0004] The existing technical solutions to the above problems include the following aspects. First, in order to avoid the impact of temperature fluctuations on image acquisition, the time-lapse microscopy system is often placed in a closed constant temperature room. The microscopy system is preheated for several hours before the experiment to make the system temperature the same as the room temperature. During the experiment, operators are prohibited from entering and leaving the constant temperature room to ensure the stability of the indoor temperature. This approach can also minimize the interference of mechanical vibrations in the environment to the system; second, in order to reduce the impact of high-speed movement of the electric translation stage and changes in the tension of the objective lens oil on the stability of image acquisition, the movement speed of the electric translation stage is usually reduced. In experiments with multi-site sampling, the number of sampling points will be limited, and the selected sampling points will be concentrated in a smaller area as much as possible to avoid sampling of large-scale and long-distance sites.

[0005] In addition to the above-mentioned technical solutions that can avoid the problems of single-cell time-lapse microscopy technology to a certain extent, there is currently no device specifically designed to prevent sample loss of focus and horizontal offset, which limits the scope of application of single-cell time-lapse microscopy technology to a certain extent. For example, most laboratories that do not have the conditions to set up a constant temperature chamber can only carry out single-cell time-lapse microscopy experiments on microorganisms cultured at room temperature to avoid sample loss of focus caused by temperature fluctuations. Or use a lower-magnification objective lens to conduct single-cell related research at the expense of resolution and imaging quality.

[0006] Therefore, the prior art has the following defects:

[0007] A) Constant temperature chamber technology solution: high space and operation costs, long waiting time to reach the preset temperature, long-term high temperature operation has a great impact on the instrument, increasing the instrument failure rate and shortening the instrument life;

[0008] B) Reduce the moving speed of the electric translation stage and limit the number and range of sampling points: the throughput of a single experiment is reduced, the overall experimental cost and time cost are increased, and it is difficult to meet the demand for large data volumes in single-cell experiments;

[0009] C) Use low-magnification objectives to reduce the need for autofocus system accuracy: imaging resolution and quality are sacrificed, and single cells cannot be accurately sampled and analyzed. Only cell group behavior can be sampled and analyzed. Summary of the invention

[0010] The purpose of the present invention is to provide a chip fixing device to solve the technical problems of horizontal and vertical deviation of a sample to be tested.

[0011] The above-mentioned purpose of the present invention can be achieved by adopting the following technical solutions:

[0012] The present invention provides a chip fixing device, comprising:

[0013] A fixed body, comprising a first plate body and a second plate body that are interlocked with each other, wherein the first plate body is provided with a first window for light source to enter, and the second plate body is provided with a second window for collecting images, and the first window and the second window are arranged opposite to each other;

[0014] A clamping structure for clamping the sample to be tested is located in the second window, and the clamping position of the clamping structure and the sample to be tested are symmetrically arranged relative to the center of the sample to be tested.

[0015] In an embodiment of the present invention, the clamping structure includes a plurality of elastic members connected to the first plate body, and a support frame connected to the second plate body, the sample to be tested is clamped between the plurality of elastic members and the support frame, and the abutting positions of the plurality of elastic members and the support frame are symmetrically arranged relative to the center of the sample to be tested.

[0016] In an embodiment of the present invention, the contact positions between the plurality of elastic members and the support frame are arranged to form a regular polygon, a circle or an ellipse.

[0017] In an embodiment of the present invention, the polygon is a quadrilateral, the number of the abutment positions is at least four, and one abutment position is provided at each diagonal corner of the quadrilateral.

[0018] In an embodiment of the present invention, the quadrilateral has four sides, and one abutment position is respectively provided at the center points of at least two of the opposite sides.

[0019] In an embodiment of the present invention, the support frame has two first support beams arranged opposite to each other, the two first support beams are connected to the inner wall of the second window, and at least one elastic member is arranged on the opposite sides of the first window. The elastic member can extend into the second window and elastically abut against the first support beam.

[0020] In an embodiment of the present invention, the support frame also includes two second support beams arranged opposite to each other, the two second support beams are connected to the two ends of the two first support beams, and at least one elastic member is respectively provided on the other opposite sides of the first window, and the elastic member can extend into the second window and elastically abut against the second support beam.

[0021] In an embodiment of the present invention, the elastic member includes a syringe and a needle movably disposed in the syringe, a spring is disposed in the syringe, the needle can be elastically moved by the spring, the syringe is connected to the first plate, and the needle can elastically abut against the sample to be tested.

[0022] In an embodiment of the present invention, one end of the first plate body is pivotally connected to one end of the second plate body, and / or the other end of the first plate body is detachably connected to the other end of the second plate body.

[0023] In an embodiment of the present invention, at least one first convex portion is respectively disposed at one end of the first plate body and at one end of the second plate body, and the first convex portion has a pivot hole, and a shaft rod is passed through the pivot hole.

[0024] In an embodiment of the present invention, at least one second convex portion is respectively disposed at the other end of the first plate body and the other end of the second plate body, and the second convex portion has a connecting hole, and a plug is inserted into the connecting hole.

[0025] In an embodiment of the present invention, a first card slot is provided on the other end surface of the first plate body, and a second card slot is provided on the other end surface of the second plate body. The first card slot is relatively connected to the second card slot, and a fixing rod is inserted therein. One end of the fixing rod can be pivotally connected to the first card slot or the second card slot, and a blocking block is formed on the other end of the fixing rod, and the blocking block can abut against the outer surface of the second plate body or the outer surface of the first plate body.

[0026] In an embodiment of the present invention, the inner diameter of the first window is not less than 15 mm.

[0027] In an embodiment of the present invention, the sample to be tested has a sampling area, and the distance between the outer edge of the sampling area and the edge of the second window is not less than 7.5 mm.

[0028] In an embodiment of the present invention, a diameter of the elastic member is the same as a width of the first support beam and a width of the second support beam.

[0029] In an embodiment of the present invention, the width of the first support beam and the width of the second support beam are 1 mm to 5 mm, respectively, and the thickness of the first support beam and the thickness of the second support beam are 0.5 mm to 3 mm, respectively.

[0030] The characteristics and advantages of the present invention are:

[0031] 1. The clamping structure of the chip fixing device of the present invention and the clamping position of the sample to be tested are designed to be symmetrical with the center of the sample to be tested, which can achieve a stable clamping of the sample to be tested on the one hand, and on the other hand, can ensure that the position of the sample to be tested relative to the fixed body does not change, that is, with the fixed body as a reference, the sample to be tested does not move horizontally and / or vertically. When the sample to be tested is a microfluidic chip, by using the present invention to fix the microfluidic chip, the chip fixing device can be stably integrated with the time-lapse microscopy imaging system. When performing single-cell time-lapse microscopy imaging, the deformation of the microfluidic chip caused by the environmental temperature difference and temperature change, the high-speed movement and mechanical vibration of the electric displacement stage, the change of the mirror oil tension, and other external environmental disturbances can be avoided to interfere with the cell sample, fundamentally solving the technical problems of automatic focus failure and sample horizontal displacement of the time-lapse microscopy imaging system.

[0032] 2. The chip fixing device of the present invention can realize a variety of single-cell imaging modes such as bright field, phase contrast incident light, laser excitation fluorescence, etc. through the design of the first window on the first plate and the second window on the second plate. The size of the first window meets the requirements of incident light illumination, and the size of the second window meets the requirements of sampling and shooting of at least 100 sites with a 100x magnification oil immersion objective. The present invention can simultaneously meet a series of experimental requirements such as high-throughput multi-site sampling, large-scale multi-site sampling, and high-magnification shooting, thereby improving the experimental throughput while ensuring data quality.

[0033] 3. In the chip fixing device of the present invention, the first plate and the second plate of the fixing body are connected by a shaft, the fixing body can be opened and closed by rotating the first plate, and the first plate and the second plate are locked by plugging. The present invention can achieve the same experimental purpose in a more convenient way, simplify the experimental operation, shorten the waiting time before the experiment, and reduce the damage to the instrument.

[0034] Fourth, in the chip fixing device of the present invention, a plurality of elastic members are distributed directly above the support frame, the shape of the support frame changes according to the change of the second window of the second plate body, and the layout of the plurality of elastic members changes with the structure of the support frame. The number of elastic members increases with the increase of the area of ​​the support frame, and the clamping degree of the chip fixing device on the microfluidic chip can be adjusted by adjusting the number of elastic members. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0036] Figure 1It is a structural schematic diagram of a first embodiment of a chip fixing device of the present invention in which a first plate body and a second plate body are buckled together.

[0037] Figure 2 It is a structural schematic diagram of the chip fixing device of the present invention in which the first plate body is opened relative to the second plate body.

[0038] Figure 3 It is a schematic diagram of the exploded structure of the chip fixing device of the present invention.

[0039] Figure 4 It is a structural schematic diagram of a second embodiment of a chip fixing device of the present invention in which the first plate body and the second plate body are buckled together.

[0040] Figure 5 It is an exploded schematic diagram of the first embodiment of the clamping structure of the present invention.

[0041] Figure 6 It is a cross-sectional view of the elastic member of the present invention in a first state.

[0042] Figure 7 It is a cross-sectional view of the elastic member of the present invention in the second state.

[0043] Figure 8 It is a cross-sectional view of a sample to be tested clamped on the chip fixing device of the present invention.

[0044] Fig. 9 It is an exploded schematic diagram of the second embodiment of the clamping structure of the present invention.

[0045] Fig.10 It is a schematic exploded view of a third embodiment of the clamping structure of the present invention.

[0046] Reference numerals and descriptions:

[0047] 1. Fixed body; 11. First plate; 111. First window; 112. First protrusion; 1121. Pivot hole; 113. Second protrusion; 1131. Connecting hole; 114. Gap; 115. Space; 116. First slot; 12. Second plate; 121. Second window; 122. First protrusion; 1221. Pivot hole; 123. Second protrusion; 1231. Connecting hole; 124. Second slot; 13. Axle; 14. Plug; 141. Insertion rod; 142. Plug head ; 151, fixing rod; 152, block; 2, clamping structure; 21, elastic member; 211, syringe; 212, needle; 213, spring; 22, support frame; 221, first support beam; 222, second support beam; 3, sample to be tested; 31, glass sheet; 32, surface sheet; 4, objective lens; 5, incident light source; 51, incident light; O, center; P, center; F1, width direction; F2, length direction; F3, height direction; F4, rotation direction; R, inner diameter; A, distance. DETAILED DESCRIPTION

[0048] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0049] Among them, the use of adjective or adverbial modifiers "upper" and "lower", "top" and "bottom", "inner" and "outer" is only to facilitate relative reference between multiple groups of terms, and does not describe any specific directional restrictions on the modified terms. In the description of the present invention, unless otherwise specified, "multiple" means two or more, and "at least one" means one or more.

[0050] like Figures 1 to 3 As shown, the present invention provides a chip fixing device, comprising a fixing body 1 and a clamping structure 2 for clamping a sample to be tested 3, wherein: the fixing body 1 has a first plate body 11 and a second plate body 12 that are interlocked, the first plate body 11 is provided with a first window 111 for light source to enter, the second plate body 12 is provided with a second window 121 for collecting imaging, and the first window 111 and the second window 121 are arranged opposite to each other; the clamping structure 2 for clamping the sample to be tested 3 is located in the second window 121, and the clamping position of the clamping structure 2 and the sample to be tested 3 is symmetrically arranged relative to the center O of the sample to be tested 3.

[0051] In the chip fixing device of the present invention, the clamping position of the clamping structure 2 and the sample 3 to be tested is designed to be symmetrical with the center O of the sample 3 to be tested, so that the position of the sample 3 to be tested relative to the fixed body 1 does not change while firmly clamping the sample 3 to be tested. That is, with the fixed body 1 as a reference, the sample 3 to be tested does not change in the horizontal direction (such as Figure 1 and Figure 2 The movement along the width direction F1 of the fixed body 1 and along the length direction F2 of the fixed body 1) and / or the vertical direction (as shown in Figure 1 and Figure 2 The movement of the fixed plate 1 in the height direction F3 as shown. When the sample 3 to be tested is a microfluidic chip, the present invention is used to fix the microfluidic chip. After the chip fixing device is firmly integrated with the time-lapse microscopy system, when performing single-cell time-lapse microscopy, the deformation of the microfluidic chip caused by factors such as environmental temperature difference and temperature change, high-speed movement and mechanical vibration of the electric translation stage, and change in the tension of the mirror oil, as well as other external environmental disturbances can be avoided to interfere with the cell sample, thereby fundamentally solving the technical problems of automatic focus failure and sample horizontal deviation of the time-lapse microscopy system.

[0052] In the present invention, a first window 111 is formed on the first plate 11 , and a second window 121 is formed on the second plate 12 . After the first plate 11 is buckled onto the second plate 12 , the first window 111 and the second window 121 are disposed opposite to each other.

[0053] The fixed body 1 composed of the first plate body 11 and the second plate body 12 is provided with a first window 111. During time-lapse microscopic imaging, the first window 111 can allow the incident light 51 emitted by the incident light source 5 to irradiate the cell sample in the microfluidic chip. Figure 8 As shown, bright field imaging and phase contrast imaging are realized, and the area of ​​the first window 111 is slightly larger than the incident light spot size, avoiding the blocking of the incident light 51 and ensuring the quality of bright field and phase contrast imaging. Figure 2 In the present embodiment, the inner diameter R of the first window 111 is not less than 15 mm, where the inner diameter of the first window 111 refers to the minimum inner diameter of the first window 111; specifically, the shape of the first window 111 may be rectangular, square, circular or elliptical, etc. When the shape of the first window 111 is rectangular, the inner diameter of the first window 111 refers to the length of the short side of the rectangle; when the shape of the first window 111 is square, the inner diameter of the first window 111 refers to the length of the side of the square; when the shape of the first window 111 is circular, the inner diameter of the first window 111 refers to the diameter of the circle; when the shape of the first window 111 is elliptical, the inner diameter of the first window 111 refers to the length of the short axis of the ellipse.

[0054] The fixed body 1 composed of the first plate body 11 and the second plate body 12 is provided with a second window 121. During time-lapse microscopic imaging, the second window 121 can allow the laser to irradiate the cell sample in the microfluidic chip to achieve fluorescence imaging. At the same time, since an oil immersion objective lens is required for high-magnification imaging, the distance between the objective lens and the sample is only a few hundred microns, and there is immersion oil in the middle. Therefore, the size of the second window 121 is designed to provide sufficient activity space for the objective lens 4, ensuring the need for multi-point sampling in a wide range. In this embodiment, the sample 3 to be tested has a sampling area (such as the surface sheet 32 ​​described later), and the distance A between the outer edge of the sampling area and the edge of the second window 121 is not less than 7.5 mm, such as Figure 2 and Figure 8 shown.

[0055] The fixed body 1 of the present invention can realize a variety of single-cell imaging modes such as bright field, phase-contrast incident light, laser-excited fluorescence, etc. through the design of the first window 111 on the first plate 11 and the second window 121 on the second plate 12. The size of the first window 111 meets the illumination requirements of the incident light 51, and the size of the second window 121 meets the sampling and shooting requirements of at least 100 sites with a 100-fold magnification oil immersion objective. The present invention can simultaneously meet a series of experimental requirements such as high-throughput multi-site sampling, large-range multi-site sampling, and high-magnification shooting, thereby improving the experimental throughput while ensuring data quality.

[0056] Furthermore, in the present invention, the first plate body 11 and the second plate body 12 are connected in an openable and closable manner.

[0057] In a possible implementation, if Figure 2 As shown, one end of the first plate body 11 is pivotally connected to one end of the second plate body 12 . Specifically, at least one first convex portion 112 is provided at one end of the first plate body 11, and at least one first convex portion 122 is provided at one end of the second plate body 12. In the present embodiment, one first convex portion 112 is provided at one end of the first plate body 11, and two first convex portions 122 are provided at one end of the second plate body 12 along the width direction F1 of the fixed body 1. Of course, the present invention is not limited thereto. For example, two first convex portions 112 are provided at one end of the first plate body 11 along the width direction F1 of the fixed body 1, and one first convex portion 122 is provided at one end of the second plate body 12. Alternatively, one first convex portion 112 is provided at one end of the first plate body 11, and one first convex portion 122 is provided at one end of the second plate body 12. The number of the first convex portions 112 on the first plate body 11 and the number of the first convex portions 122 on the second plate body 12 can be selected according to the width direction F1 of the fixed body 1. When the width of the fixed body 1 is longer, the number of the first convex portions 112 and the first convex portions 122 is appropriately increased. Figure 3As shown, the first protrusion 112 has a pivot hole 1121, and the first protrusion 122 has a pivot hole 1221. Figure 2 As shown, when the first protrusion 112 of the first plate body 11 is inserted between the two first protrusions 122 of the second plate body 12, the shaft rod 13 is passed through the pivot hole 1121 and the pivot hole 1221, and the first plate body 11 can be freely opened and closed with the second plate body 12 by rotating around the shaft rod 13.

[0058] In this embodiment, the other end of the first plate body 11 is detachably connected to the other end of the second plate body 12 . Specifically, at least one second convex portion 113 is provided at the other end of the first plate body 11, and at least one second convex portion 123 is provided at the other end of the second plate body 12. In the present embodiment, two second convex portions 113 are provided at the other end of the first plate body 11 along the width direction F1 of the fixed body 1, and one second convex portion 123 is provided at the other end of the second plate body 12. Of course, the present invention is not limited thereto. For example, one second convex portion 113 is provided at the other end of the first plate body 11, and two second convex portions 123 are provided at the other end of the second plate body 12 along the width direction F1 of the fixed body 1. Alternatively, one second convex portion 113 is provided at the other end of the first plate body 11, and one second convex portion 123 is provided at the other end of the second plate body 12. The number of the second convex portions 113 on the first plate body 11 and the number of the second convex portions 123 on the second plate body 12 can be selected according to the width direction F1 of the fixed body 1. When the width of the fixed body 1 is longer, the number of the second convex portions 113 and the second convex portions 123 can be appropriately increased. Figure 2 and Figure 3 As shown, the second protrusion 113 has a connecting hole 1131, and the second protrusion 123 has a connecting hole 1231. When the first plate body 11 is rotated relative to the second plate body 12 and interlocked with each other, the second protrusion 123 on the second plate body 12 is embedded in the gap 114 between the two second protrusions 113 of the first plate body 11, and then the insertion rod 141 of the bolt 14 is inserted into the connecting hole 1131 and the connecting hole 1231 to achieve the locking of the first plate body 11 and the second plate body 12.

[0059] In this implementation, please refer to Figure 1As shown, two second protrusions 113 are formed on the other end surface of the first plate body 11 and are located on the same horizontal plane as the first plate body 11. The second protrusion 123 of the second plate body 12 is formed on the inner surface of the second plate body 12 near the other end edge thereof. After the first plate body 11 and the second plate body 12 are buckled together, the other end surface of the first plate body 11 and the other end surface of the second plate body 12 are located in the same plane, and the structure is more compact. In addition, a space 115 for accommodating the plug head 142 of the plug 14 is reserved at the corner of the other end surface of the first plate body 11, so that after the fixed body 1 of the present invention, the first plate body 11 is connected to the second plate body 12 through the plug 14, its overall outer contour shape is consistent along the height direction F3 of the fixed body 1, thereby improving the convenience of connecting the present invention with external structures such as an electric translation stage, and reducing the storage space.

[0060] In particular, when the present invention is applied to fix a microfluidic chip, the present invention is a microfluidic chip fixing device that is compatible with both a time-lapse microscopy system and a commercial microscope temperature control system, which can be stably integrated with the time-lapse microscopy system, effectively avoiding chip deformation caused by factors such as ambient temperature difference and temperature change, high-speed movement and mechanical vibration of the electric translation stage, and changes in mirror oil tension, as well as interference with the sample by other external environmental disturbances, fundamentally solving the technical problems of automatic focus failure and sample horizontal displacement of the time-lapse microscopy system. Compared with the prior art, the present invention can achieve the same experimental purpose in a more convenient way, simplify experimental operations, shorten waiting time before the experiment, reduce damage to the instrument, and can achieve a temperature of less than 40°C for 200 hours without loss of focus or horizontal position displacement of more than 2μm for time-lapse microscopy of bacterial single cells.

[0061] In another feasible embodiment, one end of the first plate body 11 is pivotally connected to one end of the second plate body 12, and this connection method is the same as the connection method in the above embodiment, except that: in this embodiment, the detachable connection method between the other end of the first plate body 11 and the other end of the second plate body 12 is different.

[0062] Specifically, Figure 4As shown, the other end surface of the first plate body 11 is provided with a first card slot 116, and the other end surface of the second plate body 12 is provided with a second card slot 124. After the first plate body 11 is buckled onto the second plate body 12, the first card slot 116 and the second card slot 124 are relatively connected along the height direction F3 of the fixed body 1. A fixing rod 151 is inserted into the first card slot 116 and the second card slot 124. One end of the fixing rod 151 is pivotally connected to the first card slot 116 or the second card slot 124. A card block 152 is formed at the other end of the fixing rod 151. The card block 152 can abut against the outer surface of the second plate body 12 or the outer surface of the first plate body 11. For example, the fixing rod 151 is rotatably connected to the second card slot 124 at a position close to the outer surface of the second plate body 12 through a pivot, toward the direction of the first plate body 11 (that is, Figure 4 When the fixing rod 151 is rotated in the first slot 116 and the second slot 124, the end surface of the block 152 connected to the fixing rod 151 contacts the outer surface of the first plate body 11, thereby realizing a locking connection between the first plate body 11 and the second plate body 12, and the connection is fast and the connection reliability is good.

[0063] Of course, the detachable connection between the other end of the first plate body 11 and the other end of the second plate body 12 can also be connected by bolts or pins. For example, threaded holes or through holes are respectively provided at the other end of the first plate body 11 and the other end of the second plate body 12. By connecting bolts in the threaded holes or connecting pins in the through holes, the first plate body 11 and the second plate body 12 can be locked together, thereby improving the convenience and speed of connection.

[0064] The sample to be tested 3 of the present invention is a microfluidic chip, which is made of a surface sheet 32 ​​made of polydimethylsiloxane (PDMS) material and a bottom glass sheet 31 with a thickness of 0.17 mm, which are sealed by oxygen plasma treatment. Of course, the material of the surface sheet 32 ​​can also be polycarbonate (PC), polymethyl methacrylate (PMMA) or pure glass, which is not limited here; wherein the area of ​​the surface sheet 32 ​​is smaller than the area of ​​the glass sheet 31. After the two are assembled, the surface sheet 32 ​​is located in the center of the glass sheet 31, and the empty areas around the glass sheet 31 are used for assembly with the fixed body 1. When using the fixed body 1, the microfluidic chip is placed in the second window 121 of the second plate body 12 of the fixed body 1. The shape and / or size of the second window 121 matches the outer contour shape and / or size of the glass sheet 31, and the tolerance between the two is no more than 0.1 mm. In this way, the position of the microfluidic chip installed each time can be fixed relative to the fixed body 1.

[0065] In one embodiment of the present invention, Figure 3 and Figure 5 As shown, the clamping structure 2 includes a plurality of elastic members 21 connected to the first plate body 11, and a support frame 22 connected to the second plate body 12, and the sample 3 to be tested is clamped between the plurality of elastic members 21 and the support frame 22, and the abutting positions of the plurality of elastic members 21 and the support frame 22 are symmetrically arranged relative to the center O of the sample 3 to be tested. Since the outer contour shape and size of the sample 3 to be tested are usually designed to be the same as the shape and size of the inner peripheral wall of the second window 121 of the second plate body 12, the abutting positions of the plurality of elastic members 21 and the support frame 22 are symmetrically arranged relative to the center O of the sample 3 to be tested, which can also be defined as that the abutting positions of the plurality of elastic members 21 and the support frame 22 are symmetrically arranged relative to the center P of the support frame 22, which can also meet the effect of preventing the sample 3 to be tested from being offset in the horizontal direction and / or the vertical direction. The sample 3 to be tested of the present invention is elastically pressed onto the support frame 22 by a plurality of elastic members 21, thereby achieving the purpose of fastening the sample 3 to be tested. In addition, due to the use of a plurality of elastic members 21, a uniform and gentle pressing and fixing method is provided for the sample 3 to be tested. When the sample 3 to be tested is a microfluidic chip, the elastic members 21 exert a uniform and gentle force on the glass sheet 31, thereby achieving reliable fastening while avoiding the breakage of the glass sheet 31 caused by rigid fastening. The present invention can particularly effectively avoid the breakage of a glass sheet 31 with a thickness of more than 0.1 mm when being pressed and fixed.

[0066] In the present invention, the contact positions of the plurality of elastic members 21 and the support frame 22 are arranged to form a regular polygon, a circle or an ellipse.

[0067] In a possible embodiment, if Figure 3 and Figure 5 As shown, the regular polygon formed by the abutting positions of the multiple elastic members 21 and the support frame 22 is a quadrilateral, and there are at least four abutting positions of the multiple elastic members 21 and the support frame 22, and one of the abutting positions is respectively provided at the diagonal points A of the quadrilateral.

[0068] Specifically, the support frame 22 has two first support beams 221 arranged opposite to each other, the two first support beams 221 are connected to the inner side wall of the second window 121, and at least one elastic member 21 is arranged on two opposite sides of the first window 111, and the elastic member 21 can extend into the second window 121 and elastically abut against the first support beams 221. For example, see Figure 5The four elastic members 21 indicated by the indicator lines are respectively provided at the ends of the two first support beams 221. When the sample 3 to be tested is placed in the second window 121, the two first support beams 221 receive the sample 3 to be tested, and the four elastic members 21 located at the ends of the first support beams 221 apply elastic pressure to the four sides of the sample 3 to be tested, so that the sample 3 to be tested is firmly combined with the fixed body 1. Of course, the elastic member 21 can also be pressed at any position in the middle of the two first support beams 221, as long as the position of the pressed elastic member 21 is symmetrically arranged relative to the center O of the sample 3 to be tested (or the center P of the support frame 22). For example, one elastic member 21 is pressed at the middle of each of the two first support beams 221. Among them, the number of elastic members 21 pressed on the first support beam 221 can be selected according to the length of the first support beam 221, or the clamping degree of the chip fixing device on the microfluidic chip can be adjusted by adjusting the number of elastic members 21 according to actual needs.

[0069] Furthermore, the support frame 22 also includes two second support beams 222 arranged opposite to each other, the two second support beams 222 are connected to the two ends of the two first support beams 221, and at least one elastic member 21 is respectively provided on the other opposite sides of the first window 111, and the elastic member 21 can extend into the second window 121 and elastically abut against the second support beams 222. For example, an elastic member 21 is respectively provided at the ends of the two second support beams 222, and when the sample 3 to be tested is placed in the second window 121, the two first support beams 221 and the two second support beams 222 jointly support the sample 3 to be tested, thereby improving the stability of supporting the sample 3 to be tested, and through the four elastic members 21 located at the ends of each first support beam 221 and the four elastic members 21 located at the ends of each second support beam 222, elastic pressure is applied to the four sides of the sample 3 to be tested, so that the sample 3 to be tested is firmly combined with the fixed body 1. Of course, the elastic member 21 can also be pressed at any position on the two second support beams 222, as long as the position of the pressed elastic member 21 is symmetrical with respect to the center O of the sample 3 to be tested (or the center P of the support frame 22), for example, one elastic member 21 is pressed at the middle of each of the two second support beams 222. The number of elastic members 21 pressed on the second support beams 222 can be selected according to the length of the second support beams 222, or the degree of clamping of the chip fixing device on the microfluidic chip can be adjusted by adjusting the number of elastic members 21 according to actual needs.

[0070] The support frame 22 composed of the first support beam 221 and the second support beam 222, and the multiple elastic members 21 apply pressure on the four sides of the sample 3 to ensure that the sample 3 is firmly combined with the fixed body 1, and can ensure that uniform and soft elastic pressure is applied to the sample 3 to prevent the sample 3 from being offset in the horizontal direction and / or vertical direction.

[0071] In another feasible embodiment, the contact positions of the plurality of elastic members 21 and the support frame 22 are arranged to form a circle or an ellipse. Fig. 9 As shown, the contact positions of the plurality of elastic members 21 and the support frame 22 are arranged to form a circle, and correspondingly, the shape of the support frame 22 is annular; Fig.10 As shown, the contact positions of the plurality of elastic members 21 and the support frame 22 are arranged to form an ellipse, and correspondingly, the shape of the support frame 22 is an elliptical ring shape.

[0072] The multiple elastic members 21 of the present invention are distributed directly above the support frame 22. The shape of the support frame 22 changes according to the change of the second window 121 of the second plate body, and the layout of the multiple elastic members 21 changes with the structure of the support frame 22. The number of elastic members 21 increases with the increase of the area of ​​the support frame 22, and the clamping degree of the chip fixing device on the microfluidic chip can be adjusted by adjusting the number of elastic members 21.

[0073] The present invention can fix microfluidic chips of different types and shapes by changing the size and shape of the support frame 22 of the chip fixing device. In addition, the present invention can also change the outer contour shape and size of the fixing body 1 to meet the assembly requirements with different types of stage adapters, including but not limited to multi-well plate stage adapters (86×128mm specifications), cell culture dish stage adapters (diameter 35mm, 60mm, 90mm, 100mm, 150mm, etc. specifications), multi-functional stage adapters, etc.

[0074] In the present invention, if Figure 6 and Figure 7 As shown, the elastic member 21 includes a syringe 211 and a needle 212 movably disposed in the syringe 211. A spring 213 is disposed in the syringe 211. The needle 212 can be elastically moved by the spring 213. The syringe 211 is connected to the first plate 11. The needle 212 can elastically abut against the sample 3 to be tested. Figure 8 Of course, the present invention can also use other components with elastic expansion and contraction characteristics to replace the structure of the combination of the syringe 211 and the needle 212, such as an elastic pressing sheet.

[0075] In this embodiment, if Figure 2 and Figure 8As shown, a plurality of connection holes or grooves are provided around the periphery of the first window 111 of the first plate body 11, and the syringe 211 of the elastic member 21 can be fixedly connected in the groove or the connection hole, for example, by bonding or welding, etc., and the connection is reliable and has good fixity. The arrangement positions of the elastic members 21 match the shape of the support frame 22, and the diameter of the elastic member 21 is the same as the width of the first support beam 221 and the width of the second support beam 222, so as to stably press the sample 3 to be tested; preferably, the width of the first support beam 221 and the width of the second support beam 222 are 1mm to 5mm respectively, and the thickness of the first support beam 221 and the thickness of the second support beam 222 are 0.5mm to 3mm respectively.

[0076] Please refer to Figure 8 As shown, the working principle of the chip fixing device is as follows: the first window 111 of the first plate body 11 of the chip fixing device meets the requirements of bright field and phase difference incident light illumination imaging, and the incident light 51 emitted by the incident light source 5 passes through the sample to be tested 3 and enters the objective lens 4 to realize illumination imaging; the design of the second window 121 of the second plate body 12 of the chip fixing device meets the requirements of laser excitation fluorescence imaging. The laser is emitted by the objective lens 4, and after being irradiated onto the sample to be tested 3, the sample emits fluorescence, and the fluorescence signal is then collected and imaged by the objective lens 4; the size design of the second window 121 of the second plate body 12 of the chip fixing device simultaneously meets the requirements that the high-power oil immersion objective lens and the imaging sample need to be very close, and the objective lens 4 needs to move within a larger range to achieve large-scale multi-point sampling.

[0077] The above are only several embodiments of the present invention. Those skilled in the art may make various changes or modifications to the embodiments of the present invention based on the contents disclosed in the application documents without departing from the spirit and scope of the present invention.

Claims

1. A chip fixing device, characterized in that: include: A fixed body, comprising a first plate body and a second plate body that are interlocked with each other, wherein the first plate body is provided with a first window for light source to enter, and the second plate body is provided with a second window for collecting images, and the first window and the second window are arranged opposite to each other; A clamping structure for clamping the sample to be tested is located in the second window, and the clamping position of the clamping structure and the sample to be tested are symmetrically arranged relative to the center of the sample to be tested; wherein, the sample to be tested includes a glass sheet and a surface sheet located at the center of the glass sheet, and the clamping structure includes a plurality of elastic members connected to the first plate body, and a support frame connected to the second plate body, the glass sheet is clamped between the plurality of elastic members and the support frame, and the abutting positions of the plurality of elastic members and the support frame are symmetrically arranged relative to the center of the sample to be tested; wherein the abutting positions of the plurality of elastic members and the support frame are arranged to form a regular polygon, a circle or an ellipse.

2. The chip fixing device according to claim 1, characterized in that: The polygon is a quadrilateral, the number of the abutment positions is at least four, and one abutment position is respectively provided at the diagonal corners of the quadrilateral.

3. The chip fixing device according to claim 2, characterized in that: The quadrilateral has four sides, and at least one abutment position is respectively provided at the center point of each of the two opposite sides.

4. The chip fixing device according to claim 1, 2 or 3, characterized in that: The support frame has two first support beams arranged opposite to each other, the two first support beams are connected to the inner side walls of the second window, and at least one elastic member is arranged on opposite sides of the first window. The elastic member can extend into the second window and elastically abut against the first support beam.

5. The chip fixing device according to claim 4, characterized in that: The support frame also includes two second support beams arranged opposite to each other, the two second support beams are connected to the two ends of the first support beams, and at least one elastic member is respectively provided on the other two opposite sides of the first window, and the elastic member can extend into the second window and elastically abut against the second support beam.

6. The chip fixing device according to claim 1, characterized in that: The elastic member includes a syringe and a needle movably arranged in the syringe. A spring is arranged in the syringe. The needle can be elastically moved by the spring. The syringe is connected to the first plate body. The needle can elastically abut against the sample to be tested.

7. The chip fixing device according to claim 1, characterized in that: One end of the first plate body is pivotally connected to one end of the second plate body, and / or the other end of the first plate body is detachably connected to the other end of the second plate body.

8. The chip fixing device according to claim 7, characterized in that: At least one first convex portion is respectively disposed at one end of the first plate body and one end of the second plate body. The first convex portion has a pivot hole, and a shaft rod is passed through the pivot hole.

9. The chip fixing device according to claim 7 or 8, characterized in that: The other end of the first plate body and the other end of the second plate body are respectively provided with at least one second convex portion, the second convex portion has a connecting hole, and a plug is inserted into the connecting hole.

10. The chip fixing device according to claim 7 or 8, characterized in that: A first card slot is provided on the other end surface of the first plate body, and a second card slot is provided on the other end surface of the second plate body. The first card slot is relatively connected to the second card slot, and a fixing rod is inserted therein. One end of the fixing rod can be pivotally connected to the first card slot or the second card slot, and a blocking block is formed on the other end of the fixing rod, and the blocking block can abut against the outer surface of the second plate body or the outer surface of the first plate body.

11. The chip fixing device according to claim 1, characterized in that: The inner diameter of the first window is not less than 15 mm.

12. The chip fixing device according to claim 1, characterized in that: The sample to be tested has a sampling area, and the distance between the outer edge of the sampling area and the edge of the second window is not less than 7.5 mm.

13. The chip fixing device according to claim 5, characterized in that: The diameter of the elastic member is the same as the width of the first support beam and the width of the second support beam.

14. The chip fixing device according to claim 13, characterized in that: The width of the first support beam and the width of the second support beam are 1 mm to 5 mm respectively, and the thickness of the first support beam and the thickness of the second support beam are 0.5 mm to 3 mm respectively.

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