Sample cell and droplet sample box suitable for biological analysis

Abstract

The utility model relates to a sample cell and a liquid drop sample box suitable for biological analysis, the sample cell comprises a first shell with a cavity and a separator arranged in the cavity and close to the side wall of the cavity, the separator divides the cavity into a main chamber and an overflow groove, and the overflow groove is communicated with the main chamber and the overflow groove. The center line of the main cavity is parallel to the center line of the overflow groove. During biological analysis, in the process of generating liquid drops in the main chamber or when the volume of liquid in the main chamber is increased due to other process steps, redundant liquid can overflow into the overflow groove from the main chamber, so that the liquid is prevented from overflowing.

Description

Technical Field

[0001] The utility model relates to a sample pool for biological analysis and a droplet sample box with the sample pool. Background Art

[0002] Polymerase chain reaction (PCR) technology is one of the most important tools in modern biology. Among them, droplet digital PCR (dPCR) developed based on microfluidics technology has been widely used due to its multiple advantages such as small reaction volume, fast reaction speed, low system noise and high sensitivity.

[0003] Droplet Digital PCR (DPCR) is a microfluidic chip-based, oil-in-water droplet technology. This encapsulates individual DNA molecules within individual droplets through the oil-in-water structure. The inertness of the oil isolates the DNA molecules from each other, confining each molecule to its own droplet for independent amplification, avoiding competition from other sequences. After DNA amplification is completed under appropriate temperature conditions, the total number of droplets and the number of droplets that detect a fluorescent signal are recorded, allowing precise quantification of DNA copy number using a Poisson distribution algorithm.

[0004] In the prior art, before optically imaging droplets, a liquid containing the droplets is typically placed in a droplet storage chamber, and the droplets in the droplet storage chamber are heated. However, after the droplets are placed in a sample box with a droplet storage chamber, some gas often remains between the first and second shells during the sealing process, resulting in trapped gas and causing test failure. Furthermore, dissolved gas may be present in the liquid that enters the droplet storage chamber. Upon heating, this gas rapidly expands, irregularly forming bubbles within the liquid storage chamber. These bubbles, unable to exit the droplet storage chamber, interfere with the desired fluorescence image of the microdroplets, reducing the accuracy of digital PCR detection.

[0005] It should be stated that the above background technology content is only used to assist in understanding the utility model concept and technical solution of this patent application. It does not necessarily belong to the prior art of this patent application. In the absence of clear evidence that the above content has been disclosed before the filing date of this patent application, the above background technology should not be used to evaluate the novelty and creativity of this application. Utility Model Content

[0006] The purpose of the utility model is to provide a sample pool suitable for biological analysis to solve one or more problems of the prior art.

[0007] To achieve the above-mentioned purpose, the technical solution adopted by the present invention is: a sample pool suitable for biological analysis, the sample pool comprising a first shell having a cavity, a separator arranged in the cavity and close to the side wall of the cavity, the separator dividing the cavity into a main chamber and an overflow trough, and the center line of the main chamber and the center line of the overflow trough are parallel to each other.

[0008] Preferably, the biological analysis comprises a PCR analysis, and the chamber is configured to generate microdroplets.

[0009] Preferably, the first shell includes a bottom extending in the horizontal direction and a peripheral side portion extending in the up-down direction, and at least a portion of the top surface of the peripheral side portion constitutes a sealing connection surface for sealing connection with components outside the first shell.

[0010] Preferably, the separator is connected to the bottom of the first shell, the extension direction of the separator is consistent with the extension direction of the peripheral side of the first shell, and the top surface of the separator is located below the horizontal plane where the sealing connection surface is located.

[0011] Preferably, the height of the cavity is 3-12 mm, the height of the separator is 1-8 mm, and the distance between the separator and the side wall of the cavity is 1-5 mm.

[0012] Preferably, the top surface of the separator is a horizontal top surface on a side close to the main chamber and an inclined top surface on a side close to the overflow trough, and the inclined top surface is inclined from top to bottom toward the inside of the overflow trough.

[0013] Another object of the present invention is to provide a liquid drop sample box suitable for biological analysis.

[0014] To achieve the above-mentioned purpose, the technical solution adopted by the present invention is: a droplet sample box suitable for biological analysis, comprising the sample pool as described above, and also comprising a second shell, wherein the first shell and the second shell can be sealedly connected and form a closed cavity after connection.

[0015] Preferably, a guide surface is provided at the bottom of the second shell, and the guide surface is configured to gradually move away from a horizontal plane upward in a direction from the main chamber toward the overflow trough.

[0016] In some embodiments, along the first direction of the sample box, the overflow groove is provided on both sides of the main chamber, and the guide surface has two arranged along the first direction, and the two guide surfaces extend from the middle to both sides respectively, wherein the first direction is the width direction or the length direction of the sample box.

[0017] In some embodiments, the guide surface is lower than the top surface of the partition in a vertical direction, and the guide surface is located inside the partition and has a distance from the partition in a horizontal direction.

[0018] In some embodiments, the second housing includes a top and a convex portion extending downwardly from a middle area of ​​the top, the peripheral edge of the top is sealedly connected to the first housing, and the guide surface is the bottom surface of the convex portion.

[0019] In some embodiments, the second shell further includes a limiting portion located on the circumferential outer side of the protrusion and extending downwardly, and a receiving groove is provided on the limiting portion, and the receiving groove is located above the overflow groove, wherein the bottom surface of the limiting portion is higher than the guide surface, and a guide slope is also provided on the outer circumference of the protrusion, and the guide slope connects the guide surface and the receiving groove.

[0020] In some embodiments, the guide surface is a plane, and the angle between the guide surface and a horizontal plane is 1° to 10°.

[0021] In some embodiments, a non-reflective film is fixedly provided on the bottom wall of the main chamber, and the second shell has a transparent area, and the orthographic projection of the transparent area on the horizontal plane covers the bottom wall of the main chamber.

[0022] Due to the application of the above-mentioned technical solution, the present invention has the following advantages compared with the prior art: when the sample cell suitable for biological analysis provided by the embodiment of the present invention is used for biological analysis, when droplets are generated in the main chamber or when the volume of liquid in the main chamber increases due to other process steps, excess liquid can overflow from the main chamber into the overflow tank, thereby avoiding liquid overflow. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Attachment Figure 1 This is a schematic diagram of the three-dimensional structure of the first shell in the sample pool of a specific embodiment of the utility model

[0024] Attachment Figure 2 For attachment Figure 1 A schematic diagram of the three-dimensional structure of the first shell from another perspective;

[0025] Attachment Figure 3 For attachment Figure 1 A schematic top view of the first shell;

[0026] Attachment Figure 4 For attachment Figure 1 A schematic diagram of the main structure of the first shell;

[0027] Attachment Figure 5 For the attachment Figure 4 Schematic diagram of the cross-sectional structure along the AA direction;

[0028] Attachment Figure 6 This is a schematic diagram of the three-dimensional structure of the second shell in the sample box of a specific embodiment of the utility model;

[0029] Attachment Figure 7 For attachment Figure 6 A schematic diagram of the three-dimensional structure of the second shell from another perspective;

[0030] Attachment Figure 8 For attachment Figure 6 A side structural schematic diagram of the second shell;

[0031] Attachment Figure 9 For attachment Figure 6 A schematic diagram of the main structure of the second shell;

[0032] Attachment Figure 10 For the attachment Figure 9 Schematic diagram of the cross-sectional structure along the BB direction;

[0033] Attachment Figure 11 This is a perspective structural diagram of a sample box according to a specific embodiment of the present invention from a top view;

[0034] Attachment Figure 12 For attachment Figure 11 A schematic side view of the structure of the sample box;

[0035] Attachment Figure 13 For the attachment Figure 12 Schematic diagram of the cross-sectional structure in the CC direction;

[0036] Attachment Figure 14 For attachment Figure 13 Enlarged schematic diagram of the middle D part;

[0037] Among them: 1. First shell; 11. Bottom; 12. Separator; 121. Horizontal top surface; 122. Inclined top surface; 13. Side portion; 14. Raised strip; 15. Main chamber; 16. Overflow groove; 17. Reaction area; 2. Second shell; 21. Top; 22. Raised portion; 23. Guide surface; 24. Limiting portion; 25. Accommodating groove; 26. Guide slope; 27. Chamfered surface. DETAILED DESCRIPTION

[0038] To make the purpose, technical solutions and advantages of the present application clearer, the embodiments of the present application will be described in further detail below with reference to the accompanying drawings. Terms such as "upper", "above", "lower", "below", "first end", "second end", "one end", "the other end" used in this application to express spatial relative positions are used to describe the relationship of one unit or feature relative to another unit or feature as shown in the accompanying drawings for the purpose of convenience of explanation. Terms of spatial relative position may be intended to include different orientations of the device in use or work other than the orientation shown in the figures. For example, if the device in the figure is turned over, the unit described as being "below" or "beneath" other units or features will be "above" the other units or features. Therefore, the exemplary term "below" can encompass both the above and below orientations. The device can be oriented in other ways (rotated 90 degrees or in other orientations), and the spatially related descriptive terms used herein are interpreted accordingly.

[0039] Furthermore, the terms "installed," "disposed," "provided with," "connected," "slidingly connected," "fixed," and "socketed" should be interpreted broadly. For example, "connected" can mean a fixed connection, a removable connection, or an integral structure; it can mean a direct connection, an indirect connection through an intermediary, or internal communication between two devices, elements, or components. Those skilled in the art will understand the specific meanings of these terms in this application based on the specific circumstances.

[0040] The technical solutions in the embodiments of the present application will be described clearly and completely below in conjunction with the accompanying drawings to make the advantages and features of the present invention easier for those skilled in the art to understand. Obviously, the embodiments described in this application are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without making creative efforts are within the scope of protection of this application.

[0041] See also Figures 1 to 5 A sample cell suitable for biological analysis is shown, which comprises a first shell 1 having a cavity. Here, the biological analysis suitable for the sample cell mainly refers to PCR analysis, and the cavity is configured to generate microdroplets.

[0042] The sample cell also includes a separator 12, which is disposed within the chamber and near the sidewall of the chamber. The separator 12 divides the chamber into a main chamber 15 and an overflow trough 16. The centerline of the main chamber 15 is parallel to the centerline of the overflow trough 16. When droplets are generated in the main chamber 15 or the volume of liquid in the main chamber 15 increases due to other process steps, excess liquid can overflow from the main chamber 15 into the overflow trough 16, preventing liquid from overflowing.

[0043] Specifically, the first shell 1 includes a bottom 11 extending in the horizontal direction and a peripheral side portion 13 extending in the up and down direction. At least a portion of the top surface of the peripheral side portion 13 constitutes a sealing connection surface for sealingly connecting with components outside the first shell 1, thereby closing the cavity to form a sealed chamber.

[0044] In this embodiment, the separator 12 is connected to the bottom 11 of the first shell 1, the extension direction of the separator 12 is consistent with the extension direction of the peripheral side 13 of the first shell 1, and the top surface of the separator 12 is located below the horizontal plane where the above-mentioned sealing connection surface is located. In this way, the inner side enclosed by the separator 12 forms a main chamber 15, and an annular overflow groove 16 is formed between the separator 12 and the peripheral side 13.

[0045] In a specific configuration, the separator 12 can be integrally formed on the first housing 1. The height of the cavity of the first housing 1 is 3 to 12 mm, preferably 6 to 8 mm; the height of the separator 12 is 1 to 8 mm, preferably 1.5 to 3 mm; and the distance between the separator 12 and the side wall of the cavity is 1 to 5 mm, preferably 2 to 3 mm.

[0046] See also Figure 5 As shown, the top surface of the separator 12 is a horizontal top surface 121 on the side near the main chamber 15 and an inclined top surface 122 on the side near the overflow trough 16. The inclined top surface 122 is inclined downward toward the interior of the overflow trough 16. When liquid overflows from the main chamber 15, the overflowing liquid will first pass over the horizontal top surface 121 and then flow along the inclined top surface 122 into the overflow trough 16. This top surface structure facilitates the overflow of excess liquid from the main chamber 15 into the overflow trough 16.

[0047] The first housing 1 is also provided with a rectangular ridge 14 extending upward from the upper surface of the bottom 11. This ridge 14 is substantially lower than the height of the separator 12. This ridge 14 is located within the main chamber 15 and forms a reaction area 17 therein for generating and depositing droplets. Multiple ridges 14 are arranged in an array, correspondingly forming multiple reaction areas arranged in an array within the main chamber 15. Each reaction area 17 is horizontally spaced a certain distance from the separator 12 on each side.

[0048] A non-reflective film (not shown in the figure) is also fixedly provided on the bottom groove wall of the main chamber 15. The non-reflective film can be fixed to the bottom wall of the main chamber 15 by gluing, or it can be a film layer formed by spraying, so that the bottom wall of the main chamber 15 is smooth and opaque for optical photography detection.

[0049] See also Figures 11 to 14A droplet sample box suitable for biological analysis is shown, which includes the sample pool as described above and a second shell 2. The second shell 2 can be sealed and connected with the first shell 1 to form a closed cavity after connection, so that the sample can be stored therein for biological analysis.

[0050] The detailed structure of the second housing 2 is as follows Figures 6 to 10 As shown, the bottom of the second shell 2 is also provided with a guide surface 23, which is constructed to gradually move upward away from the horizontal plane in the direction from the main chamber 15 toward the overflow groove 16. That is, along the direction from the main chamber 15 toward the overflow groove 16, the height of the guide surface 23 from the liquid level in the main chamber 15 gradually increases.

[0051] The main purpose of this arrangement is: on the one hand, in the process of closing the second shell 2 onto the first shell 1, the lowest position of the guide surface 23 at the bottom of the second shell 2 contacts the liquid surface of the liquid in the main chamber 15, which can make the contacted liquid be discharged toward the overflow groove 16, so that the excess liquid can be discharged into the overflow groove 16, avoiding the generation of trapped air between the liquid and the test failure during the sealing process; on the other hand, in the process of testing and analyzing the biological analysis samples in the sample box, they are usually heated. During heating, the volume of the liquid increases due to thermal expansion, and the excess liquid can also enter the overflow groove 16 from the main chamber 15. At the same time, during the heating process, the bubbles inside the liquid can also contact the guide surface 23 and be guided into the overflow groove 16 and the space above it under the action of the guide surface 23, avoiding the bubbles in the liquid from affecting the subsequent detection and photography.

[0052] As shown in the accompanying drawings, along the first direction of the sample box, a separator 12 is provided on both sides of the main chamber 15, so that an overflow groove 16 is provided on both sides of the main chamber 15, and there are two guide surfaces 23 arranged along the first direction. The two guide surfaces 23 extend from the middle to both sides respectively, so as to guide the excess liquid or generated bubbles to the overflow grooves 16 on both sides. Here, the guide surface 23 is a smooth plane, and the angle between the guide surface 23 and the horizontal plane is preferably 1° to 10°. The above-mentioned first direction can be the width direction or the length direction of the sample box. In this embodiment, the first direction is the width direction of the sample box, such as Figures 8 to 10 As shown, when viewed from the side of the sample box, the two guide surfaces 23 are in the shape of an inverted triangle on the bottom surface of the second shell 2 .

[0053] In this embodiment, Figures 1 to 5The sample pool shown, wherein the separator 12 is circumferentially arranged in a closed shape, and both sides of the main chamber 15 in the first direction and the second direction have overflow grooves 16, all of the overflow grooves 16 are interconnected to form an annular groove, and the liquid overflowing from the main chamber 15 will pass through the separators 12 on all sides and overflow into the overflow grooves 16. The above-mentioned second direction is perpendicular to the first direction, and the second direction here refers to the length direction of the sample box. Of course, in other embodiments, the first direction can also be the width direction of the sample box, and in this case, the second direction is the length direction of the sample box. In some other embodiments, the shape of the sample box can also be different from the rectangular structure shown in this embodiment, but can adopt a circular or other shape, which is not limited here.

[0054] Specifically, see Figures 6 to 14 As shown, the second shell 2 is an integrally formed component, which includes a top 21 and a protrusion 22 extending downward from the middle area of ​​the top 21. The top 21 is used to be sealedly connected to the first shell 1. Specifically, the bottom surface of the outer peripheral portion of the top 21 and the top surface of the peripheral side portion 13 fit each other, and the two can be sealed by using a method such as double-sided tape for sticking.

[0055] The guide surface 23 is the bottom surface of the protrusion 22. After the second shell 2 is connected to the first shell 1, the protrusion 22 is located above the main chamber 15, and the guide surface 23 is lower than the top surface of the partition 12 in the vertical direction. The positive projection of the guide surface 23 in the horizontal plane is located in the main chamber 15, that is, the guide surface 23 is located on the inner side of the partition 12. At the same time, there is a gap between the outer edge of the protrusion 22 and the partition 12 in the horizontal direction, so that there is a gap between the guide surface 23 and the partition 12 in the horizontal direction.

[0056] The second shell 2 is also provided with a receiving groove 25, which is located outside the protrusion 22 and above the overflow groove 16. The setting of the receiving groove 25 allows more receiving space above the overflow groove 16, thereby being able to accommodate gas overflowing from the liquid.

[0057] In this embodiment, the second shell 2 also includes a limiting portion 24 located on the outer side of the protrusion 22 and extending downwardly. The limiting portion 24 is located in the closed cavity formed by the first shell 1 and the second shell 2. The receiving groove 25 is provided on the limiting portion 24 and its opening is arranged downward. In the vertical direction, the bottom surface of the limiting portion 24 is higher than the guide surface 23. A guide slope 26 is also provided on the outer peripheral portion of the protrusion 22. The guide slope 26 connects the guide surface 23 and the receiving groove 25, and can further guide the gas generated by the bubbles generated in the main chamber 15 and escaped into the receiving groove 25. The outer peripheral edge of the limiting portion 24 is also provided with a chamfered surface 27 to facilitate insertion into the first shell 1.

[0058] The second housing 2 has a transparent area whose horizontal projection covers the bottom wall of the main chamber 15, thereby facilitating the capture of liquid droplets at the bottom by an optical camera. The second housing 2 can be made of transparent acrylic or PC (polycarbonate).

[0059] When using this sample box, a predetermined amount of formula oil is first added to the main chamber 15 of the first shell 1, and then the generating gun head of the droplet generating device is extended to below the oil liquid surface to generate droplets, so that the droplets are spread flat in each reaction area 17. Subsequently, the second shell 2 is installed on the first shell 1. Specifically, the protective film of the double-sided tape attached to the bottom surface of the outer edge of the top 21 is torn off, and the second shell 2 is installed on a dedicated bracket. Subsequently, a dedicated mechanical device is used to contact the second shell 2 from one end to the first shell 1 and start to press downward until the installation of the second shell 2 is completed. At this time, the double-sided tape sticks and fixes the top 21 and the top surface of the peripheral side 13 of the first shell 1 and seals them, that is, the second shell 2 is fixed on the first shell 1 and sealed between the first shell 1, and a closed cavity is formed between the first shell 1 and the second shell 2. The biological sample to be tested is immersed in the formula oil in the form of droplets and spread flat on the bottom of the main chamber 15. During the above process, the bottom surface of the second shell 2, that is, part of the guide surface 23 contacts the liquid surface of the formula oil, so that the excess formula oil is discharged into the overflow groove 16, so that the gas in the main chamber 15 is driven out as much as possible to avoid the phenomenon of trapped gas.

[0060] Next, the thermal module heats the bottom of the first housing 1 to perform PCR cycles. After the thermal cycle is complete, the optical module takes fluorescent images from above the second housing 2 for data analysis. During the heating process, the formulated oil in the main chamber 15 increases in volume and overflows into the overflow trough 16. Simultaneously, the resulting bubbles rise and contact the guide surface 23, where they are drawn into the holding groove 25. These bubbles avoid remaining above the main chamber 15 and thus preventing interference with the fluorescence photography.

[0061] The above embodiments are only for illustrating the technical concept and features of the present invention. Their purpose is to enable people familiar with this technology to understand the content of the present invention and implement it. They are not intended to limit the scope of protection of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the scope of protection of the present invention.

Claims

1. A sample cell suitable for biological analysis, characterized in that: The sample pool includes a first shell having a cavity, and a separator arranged in the cavity and close to the side wall of the cavity, wherein the separator divides the cavity into a main cavity and an overflow trough, and the center line of the main cavity and the center line of the overflow trough are parallel to each other.

2. The sample cell suitable for biological analysis according to claim 1, characterized in that: The biological analysis includes a PCR analysis, and the chamber is configured to generate microdroplets.

3. The sample cell suitable for biological analysis according to claim 1, characterized in that: The first shell includes a bottom extending in a horizontal direction and a peripheral side portion extending in an up-down direction. At least a portion of a top surface of the peripheral side portion constitutes a sealing connection surface for sealingly connecting with components outside the first shell.

4. The sample cell suitable for biological analysis according to claim 3, characterized in that: The separator is connected to the bottom of the first shell, the extension direction of the separator is consistent with the extension direction of the peripheral side of the first shell, and the top surface of the separator is located below the horizontal plane where the sealing connection surface is located.

5. The sample cell suitable for biological analysis according to any one of claims 1 to 4, characterized in that: The height of the cavity is 3-12 mm, the height of the separator is 1-8 mm, and the distance between the separator and the side wall of the cavity is 1-5 mm.

6. The sample cell suitable for biological analysis according to any one of claims 1 to 4, characterized in that: The top surface of the separator is a horizontal top surface on a side close to the main chamber and an inclined top surface on a side close to the overflow trough, and the inclined top surface is inclined from top to bottom toward the inside of the overflow trough.

7. A droplet sample box suitable for biological analysis, characterized by: The sample cell according to any one of claims 1 to 6 further comprises a second shell, wherein the first shell and the second shell can be sealedly connected to form a closed cavity after being connected.

8. The droplet sample box suitable for biological analysis according to claim 7, characterized in that: A guide surface is provided on the bottom of the second shell, and the guide surface is configured to gradually move away from a horizontal plane upward in a direction from the main chamber toward the overflow tank.

9. The droplet sample box suitable for biological analysis according to claim 8, characterized in that: Along the first direction of the sample box, the overflow groove is provided on both sides of the main chamber, and the guide surface has two arranged along the first direction, and the two guide surfaces extend from the middle to both sides respectively, wherein the first direction is the width direction or length direction of the sample box.

10. The droplet sample box suitable for biological analysis according to claim 8, characterized in that: The guide surface is lower than the top surface of the partition in a vertical direction, and is located inside the partition with a distance from the partition in a horizontal direction.

11. The droplet sample box suitable for biological analysis according to claim 8, characterized in that: The second shell includes a top and a convex portion extending downward from a middle area of ​​the top. The peripheral side edge of the top is sealedly connected to the first shell, and the guide surface is the bottom surface of the convex portion.

12. The droplet sample box suitable for biological analysis according to claim 11, characterized in that: The second shell also includes a limiting portion located on the circumferential outside of the protrusion and extending downwardly, and a receiving groove is provided on the limiting portion, and the receiving groove is located above the overflow groove, wherein the bottom surface of the limiting portion is higher than the guide surface, and a guide slope is also provided on the outer circumference of the protrusion, and the guide slope connects the guide surface and the receiving groove.

13. The droplet sample box suitable for biological analysis according to claim 8, characterized in that: The guide surface is a plane, and the angle between the guide surface and the horizontal plane is 1° to 10°; And / or, a non-reflective film is fixedly provided on the bottom wall of the main chamber, and the second shell has a transparent area, and the orthographic projection of the transparent area on the horizontal plane covers the bottom wall of the main chamber.

Images