Sequencing system and carrier device
By rigidly connecting the heat-conducting plate to the reactor, combined with the support base and heat dissipation module, the problem of structural deformation of the temperature control component during temperature changes is solved, which improves the accuracy and lifespan of the sequencing device and ensures the effective execution of biochemical reactions and the stability of image acquisition.
Patent Information
- Application Number
- CN202110297328.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2021-03-19
- Publication Date
- 2025-11-21
- Estimated Expiration
- 2041-03-19
AI Technical Summary
In existing sequencing devices, the structure in contact with the temperature control component and the reactor is prone to deformation during temperature changes, which affects the progress of biochemical reactions, makes it difficult to focus and track signals, and also affects the lifespan of the device.
A heat-conducting plate is rigidly connected to the reactor and connected to the base via a support base. Combined with a heat dissipation module and a cooler, a stable connection is formed, reducing the impact of temperature changes on the structure. The movement of reagents and the excitation and collection of fluorescent labels are controlled by a fluid device.
It improves the accuracy of automated sequencing and the lifespan of instruments, ensures the effective execution of biochemical reactions, and achieves stable focusing and tracking, rapidly acquiring clear images of the reactor surface and accurately identifying nucleic acid sequences.
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Figure CN115109694B_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of biological sample detection equipment, and in particular to a sequencing system and a bearing device. BACKGROUND
[0002] With the continuous development of nucleic acid sequencing technology, sequencing systems are also constantly updated. In a sequencing system / platform based on an optical imaging system to detect nucleic acid molecules in a chip, the sequencing system includes an imaging assembly, which is used to take pictures of nucleic acid molecules in a reactor (such as a flow cell or a chip) during a sequencing reaction, and analyze the pictures obtained by taking to obtain sequencing results.
[0003] Generally, to achieve focusing and / or tracking to collect images of one or more positions / fields of view on the chip at multiple time points, the chip installed on the sequencing platform and the imaging assembly are required to meet or maintain a relative positional relationship. Typically, the sequencing system includes a bearing device for bearing the chip and / or adjusting the position of the chip.
[0004] In the detection and analysis of the sample to be detected, biochemical reactions are often involved, especially biochemical reactions involving biological catalysts such as proteases, which are sensitive to temperature and generally require temperature control of the reaction environment, such as cooling or heating control of the chip to ensure the effective performance of the biochemical reaction thereon. The existing sequencing device includes a temperature control assembly, for example, a semiconductor refrigeration sheet is used to cool or heat the chip, and a metal heat sink or a water cooling system is used to remove heat. The temperature control assembly is in direct or indirect contact with the reactor to achieve refrigeration or heating. During temperature changes, structures in contact with the temperature control assembly, such as the reactor, will deform, which may affect the performance of the biochemical reaction in the reactor and / or increase the difficulty of focusing and tracking signal acquisition.
[0005] How to control the influence of temperature on related components / parts / structures, including how to reasonably arrange the related components / structures, to better achieve the function of the components / structures / devices and / or prolong their service life, is a problem to be solved or improved. SUMMARY
[0006] The present application provides a sequencing system and a bearing device.
[0007] The sequencing system of the embodiment comprises: a bearing device for bearing a reactor and adjusting the temperature of the reactor, the reactor being connected with a plurality of polynucleotides, the bearing device comprising: a base having a bearing surface for bearing the reactor, a temperature control assembly comprising a heat conduction plate, a refrigerator and a heat dissipation module connected in sequence, the refrigerator being connected with the reactor through the heat conduction plate, the heat conduction plate being rigidly connected with the reactor in the case that the reactor is placed on the bearing surface, and a connecting assembly connecting the base and the temperature control assembly, the connecting assembly comprising a support seat, the heat conduction plate being connected with the base through the support seat; a fluid device connected with the bearing device for controllably moving one or more reagents with fluorescent labels into contact with the polynucleotides in the reactor; an imaging device located above the bearing device for exciting and collecting fluorescence generated by the fluorescent labels; and a computing device operatively coupled with the imaging device and comprising an instruction set for acquiring fluorescence signals from the imaging device.
[0008] The sequencing device comprising the above structure, assembly or module and connection relationship of the embodiment can improve the precision of automatic sequencing and the service life of the instrument by reasonably arranging the mechanical hardware so that the relevant parts have less deformation and / or maintain a relatively stable connection relationship during temperature adjustment. Nucleic acid sequencing using the sequencing device can better control the temperature of the reactor reaction environment to ensure the effective performance of biochemical reactions in the reactor, and can better realize focusing and tracking to quickly obtain clear images of the specified surface of the reactor, and subsequent accurate identification of bases based on the clear images can achieve accurate determination of nucleic acid sequences.
[0009] The bearing device of the embodiment comprises: a base having a bearing surface for bearing a reactor; a temperature control assembly comprising a heat conduction plate, a refrigerator and a heat dissipation module connected in sequence, the refrigerator being connected with the reactor through the heat conduction plate, the heat conduction plate being rigidly connected with the reactor in the case that the reactor is placed on the bearing surface; and a connecting assembly connecting the base and the temperature control assembly, the connecting assembly comprising a support seat, the heat conduction plate being connected with the base through the support seat.
[0010] The bearing device comprising the above structure and connection relationship comprises the heat conduction plate being rigidly connected with the reactor and / or the heat conduction plate not being directly connected with the base, which can better control the influence of temperature changes on the structures and connection relationships thereof, so that the bearing device can always stably bear the reactor, including maintaining the position of the reactor being always fastened during movement, and can achieve better heat transfer, which is conducive to performing reactions in the reactor, driving the reactor to enable the detection device to continuously collect signals from different parts of the reactor, and stably realizing detection of samples.
[0011] Additional aspects and advantages of the application will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following and / or can be learned by practice of the application. BRIEF DESCRIPTION OF DRAWINGS
[0012] The foregoing and / or additional aspects and advantages of the present application are achieved by providing a sequencing system, which comprises a reaction device, a base, a heat dissipation module, a control module, a water bath chamber, a cover plate, and a moving platform.
[0013] Figure 1 is a perspective view of a sequencing system according to an embodiment of the present application;
[0014] Figure 2 is an exploded view of a carrier device according to an embodiment of the present application;
[0015] Figure 3 is a structural view of a moving platform carrying a base according to an embodiment of the present application;
[0016] Figure 4 is a structural view of a base according to an embodiment of the present application;
[0017] Figure 5 is a structural view of a reaction device according to an embodiment of the present application
[0018] Figure 6 is a structural view of a base according to an embodiment of the present application;
[0019] Figure 7 is a side view of a moving platform carrying a base according to an embodiment of the present application;
[0020] Figure 8 is a partial enlarged view of a reaction device according to an embodiment of the present application; Figure 7
[0021] Figure 9 is a longitudinal sectional view of a carrier device carrying a reaction device according to an embodiment of the present application;
[0022] Figure 10 is a working principle diagram of a heat dissipation module and a control module according to an embodiment of the present application;
[0023] Figure 11 is a structural view of a water bath chamber according to an embodiment of the present application;
[0024] Figure 12 is a structural view of a heat dissipation plate according to an embodiment of the present application;
[0025] Figure 13 is a structural view of a cover plate according to an embodiment of the present application;
[0026] Figure 14 is another structural schematic view of the heat dissipation plate of the embodiment of the present application;
[0027] Figure 15 is a longitudinal sectional schematic view of the bearing device of another perspective of the embodiment of the present application;
[0028] Figure 16 is a structural schematic view of the reactor of the embodiment of the present application; Figure 15 is a partial enlarged schematic view;
[0029] Figure 17 is a structural schematic view of the support seat of the embodiment of the present application;
[0030] Figure 18 is a structural schematic view of the heat conduction plate of the embodiment of the present application;
[0031] Figure 19 is a structural schematic view of the reactor of another perspective of the embodiment of the present application;
[0032] Figure 20 is a longitudinal sectional schematic view of the bearing device of another perspective of the embodiment of the present application;
[0033] Figure 21 is a longitudinal sectional schematic view of the bearing device at the first manifold of the embodiment of the present application;
[0034] Figure 22 is a partial sectional view of the first manifold of the embodiment of the present application;
[0035] Figure 23 is a longitudinal sectional schematic view of the bearing device at the second manifold of the embodiment of the present application;
[0036] Figure 24 is a structural schematic view of the imaging device of the embodiment of the present application;
[0037] Figure 25 is a structural schematic view of the first light source of the embodiment of the present application;
[0038] Figure 26 is a structural schematic view of the fluid device of the embodiment of the present application.
[0039] Main element symbol explanation:
[0040] Sequencing system 10000,
[0041] Bearing device 1000, base 100, bearing surface 120, accommodating groove 122, first through hole 124, gap 126, temperature control assembly 200, heat conduction plate 220, first hole 222, second hole 224,
[0042] Refrigerator 240, heat dissipation module 260, water bath room 262, first flow channel 262a, second flow channel 262b, third flow channel 262c, fourth flow channel 262d, liquid inlet 262e, liquid outlet 262f, heat dissipation plate 2622, first heat dissipation area 2622a, second heat dissipation area 2622b, cover plate 2624, flow channel 2626, sealing ring 2628, liquid component 264, pump 2642, cooler 2644, water reservoir 2646, control module 280, temperature sensor 282, microprocessor 284,
[0043] Reactor 300, chip frame 320, third hole 322, fourth hole 324, sheet layer 340, flow path 360, inlet 362, outlet 364, rigid plate 380,
[0044] Support seat 420, through slot 422, first protruding part 424, second protruding part 426, first positioning structure 440, first positioning column 442, first positioning ball 444, second positioning structure 460, second positioning column 462, second positioning ball 464, first connecting piece 480, second connecting piece 482,
[0045] First manifold 520, inlet flow channel 522, second groove 524, connecting part 526, fourth positioning structure 530, positioning groove 532, second manifold 540, outlet flow channel 542,
[0046] Support structure 600, support surface 620, first groove 640, second through hole 642, support piece 660, third positioning structure 680, positioning column 682,
[0047] Base 700, adjusting structure 720, fine adjustment nut 722, tension spring 724, moving platform 800, table top main body 820, first driving mechanism 840, first sliding rail 842, first sliding seat 844, second driving mechanism 860, second sliding rail 862, second sliding seat 864, first support part 864a, second support part 864b, third through hole 864c, guide piece 866,
[0048] Fluid device 2000, memory 60, multi-way valve 70, sample inlet 72, sample outlet 74, manifold 76, pump assembly 80, liquid collector 90,
[0049] Imaging device 3000, first light source 12, first light emitter 13, first light splitter 14, third lens 15, first lens 16, fourth lens 17, second lens 18, light splitting module 40, first reflecting surface 26, first camera 20, second camera 22. DETAILED DESCRIPTION
[0050] Embodiments of the present application are described below in detail with reference to the accompanying drawings, wherein the same or similar components are denoted by the same or similar reference numerals, and thus repeated description is omitted. The embodiments described below are examples for explaining the present application, and are not intended to limit the present application.
[0051] In the description of the present application, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", and the like indicate the orientation or positional relationship shown in the drawings, and are merely used for the purpose of facilitating the description of the present application and simplifying the description, and do not indicate or imply that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be construed as limiting the present application. In addition, the terms "first", "second" are only for descriptive purposes and cannot be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined as "first", "second" can explicitly or implicitly include one or more of the features. In the description of the present application, the meaning of "a plurality of" is two or more, unless otherwise explicitly specified and limited.
[0052] In the description of the present application, it should be noted that, unless otherwise explicitly specified and limited, the terms "mounting", "connecting", "connection" should be understood broadly, for example, it can be fixed connection, or detachable connection, or integrally connected; it can be mechanical connection, or electrical connection or can communicate with each other; it can be directly connected, or indirectly connected through an intermediate medium, or the internal communication of two elements or the interaction relationship between two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.
[0053] In the present application, unless otherwise explicitly specified and limited, the "upper" or "lower" of the first feature to the second feature can include that the first and second features are in direct contact, or that the first and second features are not in direct contact but are in contact through another feature between them. Moreover, the "upper", "above" and "on" of the first feature to the second feature includes that the first feature is directly above and obliquely above the second feature, or only indicates that the horizontal height of the first feature is higher than that of the second feature. The "under", "below" and "under" of the first feature to the second feature includes that the first feature is directly below and obliquely below the second feature, or only indicates that the horizontal height of the first feature is less than that of the second feature.
[0054] The following disclosure provides many different embodiments, or examples, for implementing different structures of the present application. For the purpose of simplification, the components and arrangements of the specific examples are described in the following. Of course, they are merely examples and are not intended to limit the present application. Moreover, the present application can repeatedly refer to reference numerals and / or reference letters in different examples, and such repetition is for the purpose of simplification and clarity, which does not indicate the relationship between the various embodiments and / or arrangements discussed. In addition, the present application provides various specific examples of processes and materials, but those of ordinary skill in the art can realize the application of other processes and / or the use of other materials.
[0055] It should be noted that, in the present application, the so-called chip refers to a solid-phase substrate having a surface capable of connecting or fixing target biomolecules, which can be a curved surface or a flat surface. The surface is curved, for example, also known as a microsphere. The technology, for example, includes fixing a large number of probes, such as oligonucleotide fragments, to the surface of the support, and / or hybridizing the probes fixed to the surface of the support with DNA or other target molecules (such as proteins, factors or small molecules). For example, the probe and the biological molecule to be tested are both nucleic acid molecules, and at least a part of the probe can be complementary to the biological molecule to be tested (based on the principle of base complementary pairing), so as to realize the connection or fixation of the target biomolecule to the surface of the solid-phase substrate.
[0056] In the present application, the Z-axis refers to the shooting direction of the imaging assembly, which can be, for example, an optical imaging assembly, wherein the Z-axis is the optical axis of the optical imaging assembly, and the Z-axis is perpendicular to the plane formed by the X-axis and the Y-axis.
[0057] In the present application, the working distance of the objective lens refers to the distance between the front edge of the objective lens and the surface of the sample when the sample is aligned with the focus point.
[0058] Please refer to Figure 1 With Figure 2 The embodiment of the present application provides a sequencing system 10000 for detecting a biological sample, which comprises a bearing device 1000, a fluid device 2000, an imaging device 3000 and a computing device (not shown in the figure).
[0059] The bearing device 1000 is used for bearing a reactor 300 and adjusting the temperature of the reactor 300, and the reactor 300 is connected with a plurality of polynucleotides.
[0060] Specifically, please refer to Figure 3 , Figure 4 With Figure 5The embodiment provides a bearing device 1000, which comprises two bases 100, a base 700 and a moving platform 800. In other embodiments, more than two bases 100 can be included. Each base 100 is provided with a bearing surface 120 for bearing a reactor 300, and the bearing surface 120 is provided with a containing groove 122 for containing the reactor 300.
[0061] For example, when sequencing is performed, the reactor 300 is placed on the containing groove 122, so that the reactor 300 placed on the base 100 is more stable during movement. The reactor 300 can provide a space for biochemical reactions, also known as a reaction chamber, for example, a chip. Generally, the reactor 300 comprises a chip frame 320 and a sheet layer 340 arranged in the chip frame 320, and the shape of the containing groove 122 can match the shape of the chip frame 320 of the reactor 300, and the containing groove 122 is rectangular in the embodiment.
[0062] Please refer to Figure 1 、 Figure 6 and Figure 7 The base 700 included in the bearing device 1000 can be a hollow structure, and the top of the base 700 can be provided with an opening. It can be easily understood that the hollow structure of the base 700 can accommodate other components arranged on the base 100. In the embodiment, the two bases 100 are placed in parallel at the opening of the base 700, and each base 100 is connected to the base 700 through an adjusting structure 720, which can increase or shorten the distance between the base 100 and the base 700, and the base 100 is arranged on the top of the base 700, so that the height of the base 100 can be changed by the adjusting structure 720.
[0063] Please refer to Figure 7 and Figure 8 The adjusting structure 720 in the embodiment comprises fine adjustment nuts 722 and tension springs 724, and a plurality of fine adjustment nuts 722 are connected between one base 100 and the base 700. The adjusting directions of the fine adjustment nuts 722 are perpendicular to the first direction and the second direction, respectively, wherein the first direction and the second direction are horizontal directions, so that the direction of the fine adjustment nuts 722 is vertical in the embodiment.
[0064] One function of the fine adjustment nuts 722 can be to adjust the height of the entire base 100 as a whole, and in particular, each fine adjustment nut 722 can be adjusted to a certain height, and then the base 100 can be leveled to ensure the imaging effect. Another function can be to change the inclination angle of the base 100, for example, by adjusting only the fine adjustment nuts 722 on one side of the base 100, so that the base 100 on that side is slightly raised or slightly lowered, so that the base 100 has a certain inclination angle relative to the horizontal position. Through the adjustment of the adjustment structure 720, the height difference between the surfaces of the respective sheets 340 in the two reactors 300 can be no more than 20% of the working distance of the objective lens in the imaging assembly.
[0065] Further, a plurality of tension springs 724 are connected between each base 100 and the base 700, and the elastic force direction of each tension spring 724 is perpendicular to the first direction and the second direction. The force on the base 100 from the tension spring 724 is always directed towards the base 700. The fine adjustment nut 722 cooperates with the tension spring 724, so that the base 100 is clamped in a position suspended from the base 700, and even if it is collided by other objects, the clamped base 100 has little or almost no shaking.
[0066] Please refer again to Figure 1 With Figure 7 , the carrier device 1000 further includes a moving platform 800 located below the base 700, which can be used to support and move the base 700. The moving platform 800 includes a table body 820, a first driving mechanism 840 and a second driving mechanism 860. The table body 820 is connected to the base 700. In this embodiment, the bottom of the base 700 is provided with a threaded hole for threaded connection with the table body 820.
[0067] Specifically, the first driving mechanism 840 includes a first sliding rail 842, a first sliding seat 844 and a first motor (not shown in the figure). The first sliding rail 842 is arranged parallel to the first direction, so that the first driving mechanism 840 can drive the table body 820 to move along the first direction. The first sliding seat 844 is installed on the first sliding rail 842 and moves along the first sliding rail 842 under the drive of the first motor. The table body 820 is connected to the first sliding seat 844, and moves with the first sliding seat 844.
[0068] The second driving mechanism 860 includes a second slide rail 862, a second slide base 864, and a second motor (not shown in the figure). The second slide rail 862 is arranged in parallel with the second direction, so that the second driving mechanism 860 can drive the table top body 820 to move along the second direction. The second slide base 864 is installed on the second slide rail 862 and moves along the second slide rail 862 under the drive of the second motor. The first slide rail 842 is arranged on the second slide base 864. In the embodiment, the second slide base 864 includes a first support part 864a and second support parts 864b arranged on both sides of the first support part 864a. Alternatively, one second support part 864b, the first support part 864a, and another second support part 864b are sequentially connected along the second direction.
[0069] It can be easily understood that the first support part 864a is a cuboid structure, and the first support part 864a is provided with a slot along the first direction, so as to form the first slide rail 842. The second support part 864b has a slope, specifically, the distance between the top of the second support part 864b and the first support part 864a along the second direction is greater, and the height is lower. Therefore, the second slide base 864 as a whole is in the shape of a stepped terrace.
[0070] In addition, in some embodiments, the second slide rail 862 is provided with a guide part 866 arranged in parallel with the second direction. The second slide base 864 along the second direction can include a first side and a second side opposite to the first side. In the embodiment, the first side is the left side of the second slide base 864, and the second side is the right side of the second slide base 864. Figure 7 Figure 7 The first side is provided with a third through hole 864c matched with the guide part 866. The guide part 866 extends to the outside of the second slide base 864 through the third through hole 864c. Of course, in other embodiments, the third through hole 864c matched with the guide part 866 can also be arranged on the second side.
[0071] In particular, the guide part 866 is arranged to make the second slide base 864 keep parallel to the second direction during movement, so as to keep the base 100 stable during movement.
[0072] According to the carrying device 1000 of any one of the above embodiments and the sequencing system 10000 in any one of the embodiments, a plurality of bases 100 capable of carrying the reactor 300 can be arranged on the base 700. The base 700 is moved by the moving platform 800 to move the base 100, so as to simultaneously adjust a plurality of reactors 300.
[0073] In a specific application scenario, for example, to image multiple reactors 300, different regions of multiple reactors 300, the carrier device 1000 can better adjust the focal plane to meet the imaging requirements; by adjusting the adjusting structure 720 between the base 100 and the base 700, the distance between the reactor 300 and the imaging assembly can be finely adjusted, such as increased or shortened, and the perpendicularity of the field of view (FOV) on the imaging object, for example, the reactor 300, and the optical axis. The cooperation of the moving platform 800 and the adjusting structure 720 can conveniently and finely adjust the expected position / relationship of the reactor 300 and the imaging device 3000.
[0074] It should be noted that in the detection and analysis of the sample to be tested, biochemical reactions are generally involved, especially biochemical reactions involving biological catalysts such as proteases and the like. Such biochemical reactions are sensitive to temperature, and generally require control of the temperature of the reaction environment, for example, cooling or heating control of the chip to ensure the effective performance of the biochemical reaction thereon.
[0075] In the carrier device 1000 on the sequencing system 10000 in the present application, a temperature control assembly 200 is further included for efficiently and stably controlling the temperature of the reactor 300, so that the biochemical reaction can be effectively performed.
[0076] Specifically, it should be noted that in the present application, the semiconductor refrigeration sheet is based on the Peltier effect, so as to achieve the effect of refrigeration or heating. The principle of refrigeration or heating is that when an electric current passes through two connected conductors, a temperature difference will be generated at the connection, that is, the connection will generate heat absorption and heat release phenomenon. This effect was discovered by the Frenchman Jean-Charles Peltier in 1834. The amount of heat absorption and heat release in the Peltier effect is determined by the size of the electric current. People have manufactured refrigeration and heating elements such as Peltier refrigeration and heating sheets based on the Peltier effect. When the Peltier refrigeration and heating sheet is powered, one side absorbs heat (refrigeration), and the other side releases heat (heating), and the heat absorption side and the heat release side can be changed by changing the direction of the electric current.
[0077] Please refer to Figure 4 and Figure 9 The temperature control assembly 200 includes a refrigerator 240, a heat dissipation module 260, and a control module 280, and the refrigerator 240 has opposite first and second faces. It can be understood that when sequencing is performed, the reactor 300 is placed on the carrier surface 120, and in order to make the reactor 300 more stable and not easy to deviate, the carrier surface 120 is provided with a containing groove 122 for placing the reactor 300, and the bottom wall of the containing groove 122 is provided with a first through hole 124. Then, in the case that the carrier surface 120 carries the reactor 300, the first face of the refrigerator 240 is in contact with the reactor 300 through the first through hole 124.
[0078] Wherein, the first through hole 124 means that the refrigeration device 240 contacts the reactor 300 from bottom to top via the first through hole 124, and the contact herein includes both direct contact and indirect contact. Thus, the reactor 300 is refrigerated or heated in the manner of direct contact heat transfer or indirect contact heat transfer.
[0079] The direct contact is, for example, that the first face of the refrigeration device 240 is attached to the reactor 300, and the indirect contact is, for example, that the temperature control assembly 200 further comprises a heat conduction plate 220, and the heat conduction plate 220 is arranged on the first face of the refrigeration device 240, and a part of the heat conduction plate 220 is located in the first through hole 124, and the heat conduction plate 220 is bonded to the refrigeration device 240 by using a heat conduction adhesive with good heat conduction performance, so that the refrigeration device 240 contacts the reactor 300 through the heat conduction plate 220. Preferably, the material of the heat conduction plate 220 is a metal material, for example, a material containing silver or aluminum. The heat conduction plate 220 can be substantially cuboid, and the cross-sectional dimension of the heat conduction plate 220 can be substantially the same as the cross-sectional dimension of the refrigeration device 240, so that the structural cooperation between the heat conduction plate 220 and the refrigeration device 240 is more compact, which is beneficial to efficient heat conduction.
[0080] The refrigeration device 240 starts to work after being powered on, at this time, one of the first face and the second face starts to refrigerate, and the other one starts to heat. For example, after the refrigeration device 240 works, the first face starts to refrigerate, and the second face starts to heat. It can be understood that the refrigeration type of the first face is different when the working current of the refrigeration device 240 is different. For example, when the working current of the refrigeration device 240 is positive, the first face refrigerates; when the working current of the refrigeration device 240 is reversed, the first face heats. Compared with other refrigeration elements, the refrigeration device 240 has the advantages of being more environmentally friendly and not producing noise.
[0081] The heat dissipation module 260 contacts the second face of the refrigeration device 240, for example, is connected to the second face by using a paste-like substance with good heat conduction such as silicone grease, and is used to carry away the heat generated in the working process of the refrigeration device 240.
[0082] Please refer to Figure 10 , the heat dissipation module 260 comprises a water bath chamber 262 and a liquid assembly 264. The material of the water bath chamber 262 can be a metal material, for example, the material of the water bath chamber 262 is copper, aluminum or the like. The water bath chamber 262 has a cavity for containing cooling liquid, and the water bath chamber 262 is provided with a liquid inlet 262e and a liquid outlet 262f which communicate with the cavity.
[0083] In some embodiments, as Figure 11 、 Figure 12 and Figure 13As shown, the water bath chamber 262 comprises a heat dissipation plate 2622 and a cover plate 2624, the heat dissipation plate 2622 is provided with flow channels 2626 for containing cooling liquid on one surface thereof, and the cover plate 2624 is sealed to the flow channels 2626 to form a chamber, for example, a sealing ring 2628 is arranged between the cover plate 2624 and the heat dissipation plate 2622, which can seal the gap between the cover plate 2624 and the heat dissipation plate 2622. Preferably, the flow channels 2626 are in a meandering shape, which can further increase the loop of the cooling liquid, thereby enhancing the cooling effect of the water bath chamber 262.
[0084] For example, please refer to Figure 13 With Figure 14 , the water bath chamber 262 can comprise a heat dissipation plate 2622 and a cover plate 2624, the heat dissipation plate 2622 is provided with a first heat dissipation area 2622a and a second heat dissipation area 2622b. The first heat dissipation area 2622a is provided with a first flow channel 262a and a second flow channel 262b, and the second heat dissipation area 2622b is provided with a third flow channel 262c and a fourth flow channel 262d.
[0085] Wherein, each flow channel has a first end and a second end facing different directions, the first end of the first flow channel 262a and the first end of the second flow channel 262b are communicated, the second end of the first flow channel 262a is communicated with the liquid inlet 262e, the second end of the third flow channel 262c and the second end of the fourth flow channel 262d are communicated, the first end of the fourth flow channel 262d is communicated with the liquid outlet 262f, and the second end of the second flow channel 262b and the first end of the third flow channel 262c are communicated.
[0086] Next, take Figure 14 for example to describe a layout of flow channels, and in other embodiments, the flow channels can also be arranged in other ways.
[0087] Please refer to Figure 14 , the second heat dissipation area 2622b is located on the side of each flow channel first end in the first heat dissipation area 2622a. The left direction in the figure is the direction of the first end of each flow channel, and the right direction in the figure is the direction of the second end of each flow channel, and the cover plate 2624 connects the heat dissipation plate 2622 and covers the first flow channel 262a, the second flow channel 262b, the third flow channel 262c and the fourth flow channel 262d.
[0088] It should be noted that the first flow channel 262a, the second flow channel 262b, the third flow channel 262c and the fourth flow channel 262d are communicated in sequence, so it can also be considered that one entire flow channel is divided into four segments, thereby obtaining the above four flow channels.
[0089] At least one of the flow channels in the first heat dissipation region 2622a is meandering, and at least one of the flow channels in the second heat dissipation region 2622b is meandering, for example, the second flow channel 262b and the fourth flow channel 262d are meandering, while the first flow channel 262a and the third flow channel 262c are straight. The meandering flow channels can lengthen the flow path of the cooling liquid in a single flow channel. In other embodiments, the first flow channel 262a can also be meandering, and the third flow channel 262c can also be meandering.
[0090] The flow path of the cooling liquid in the water bath 262 of the embodiment shown will be described below: Figure 13 With reference to 14 The flow path of the cooling liquid in the water bath 262 of the embodiment shown will be described below:
[0091] Please continue to refer to Figure 13 With reference to Figure 14 The inlet 262e and the outlet 262f are located near the middle of the entire water bath 262, the cooling liquid flows into the first end of the first flow channel 262a from the inlet 262e, passes through a straight section of the first flow channel 262a to reach the second end of the first flow channel 262a, then enters the second flow channel 262b which is meandering, and then enters the third flow channel 262c which is straight, and then enters the fourth flow channel 262d which is meandering, and finally flows out of the outlet 262f at the second end of the fourth flow channel 262d.
[0092] The flow channel design of the water bath 262 described above makes full use of the space of the water bath 262, lengthens the flow path of the cooling liquid in the same volume, and thus brings better heat dissipation effect.
[0093] In addition, please refer again to Figure 10 The liquid assembly 264 includes a pump 2642 and a cooler 2644 connected in series, the pump 2642 is used to provide power to the cooling liquid, and the cooler 2644 is used to cool the cooling liquid. The pump 2642 is connected to the water bath 262 through the inlet 262e, and the cooler 2644 is connected to the water bath 262 through the outlet 262f, that is, the pump 2642 is connected to the inlet 262e through a pipeline, and the cooler 2644 is connected to the outlet 262f through another pipeline. The cooling liquid in the water bath 262 is discharged from the outlet 262f under the action of the pump 2642 and then cooled by the cooler 2644. The cooler 2644 can adopt existing cooling structure, for example, it can include a copper box filled with refrigerant, and the pipeline for the cooling liquid to flow through the box. When the cooling liquid flows in the pipeline, it exchanges heat with the coolant in the box, thereby achieving the purpose of cooling the cooling liquid.
[0094] In other embodiments, the order of the connections of the cooler 2644 and the pump 2642 can also be changed, in any of the above embodiments including the liquid assembly 264, the pump 2642 is connected to the water bath 262 through the liquid outlet 262f, and the cooler 2644 is connected to the water bath 262 through the liquid inlet 262e, the cooling liquid in the water bath 262 is discharged from the liquid outlet 262f under the action of the pump 2642, and is cooled by the cooler 2644 before entering the water bath 262.
[0095] In Figure 10 In the embodiments shown in FIG. 1, the liquid assembly 264 further includes a water storage pool 2644 in which cooling liquid is stored to provide cooling liquid for the water bath 262, and the pump 2642 and the cooler 2644 are respectively connected to the water storage pool 2644 through pipes. In the circuit shown by ①, the cooling liquid is pumped out of the water storage pool 2644 by the pump 2642, absorbs heat in the water bath 262 after passing through the pump 2642, and is cooled by the cooler 2644 before returning to the water storage pool 2644. In the circuit shown by ②, the cooling liquid in the water bath 262 is continuously pumped out by the pump 2642, cooled by the cooler 2644 after returning to the water storage pool 2644, and then enters the water bath 262 to absorb heat.
[0096] The temperature control assembly 200 and the system including the same in any of the above embodiments have a plurality of heat dissipation areas in the water bath 262 and each heat dissipation area includes a plurality of flow channels, which have a better heat dissipation effect. The temperature control assembly 200 or the system including the same can efficiently dissipate heat, so that the temperature of the internal environment of the device or system can be better controlled, and is particularly suitable for application to devices or systems that have strict requirements on temperature during operation, and also makes devices or systems that are easily affected by temperature particularly suitable for operation in seasons or regions with high temperature.
[0097] Specifically, for example, in the first heat dissipation area 2622a, the cooling liquid enters the first flow channel 262a from the liquid inlet 262e on the first flow channel 262a, and then flows through the first flow channel 262a and the second flow channel 262b, realizing multiple flows from one end of the flow channel to the other end in the first heat dissipation area 2622a, prolonging the flow path of the cooling liquid such as condensed water, and improving the heat dissipation capacity. In addition, at least one of the first flow channel 262a and the second flow channel 262b is in a zigzag shape, so that the flow path of the cooling liquid is further prolonged in the same volume / space.
[0098] In some embodiments, the cooler 2644 further includes a cooling radiator with channels and multiple heat sinks for dissipating heat from the coolant flowing through the cooler 2644. Furthermore, the cooler 2644 may also include a fan that generates airflow toward the cooling radiator, thereby providing a better cooling effect.
[0099] In some embodiments, the control module 280 is connected to the cooler 240 and the heat dissipation module 260 to detect the temperature of the reactor 300 and control the operation of the heat dissipation module 260 based on the detected temperature. For example, the control module 280 controls the operating state of the pump 2642 based on the temperature of the reactor 300, thereby controlling the operation of the heat dissipation module 260.
[0100] Specifically, for example, the suitable temperature for reactor 300 has a preset range. When the control module 280 detects that the temperature of reactor 300 is much lower than the maximum temperature value within the preset range (but still within the preset range), the control module 280 can control pump 2642 to stop working, so that the coolant in water bath 262 stops flowing. This avoids the temperature of reactor 300 from dropping too low and also reduces energy consumption. Conversely, if the control module 280 detects that the temperature of reactor 300 is much higher than the minimum temperature within the preset range (but still within the preset range), the control module 280 can control pump 2642 to start working again, driving the coolant to flow and improving heat dissipation capacity.
[0101] In some embodiments, such as Figure 10 As shown, the control module 280 includes a microprocessor 284 and a temperature sensor 282 electrically connected to the microprocessor 284. The temperature sensor 282 can be disposed on the heat-conducting plate 220 to detect the temperature of the heat-conducting plate 220, thereby estimating the temperature of the reactor 300 using the temperature of the heat-conducting plate 220. The microprocessor 284 can also be electrically connected to the pump 2642 to control the operation or shutdown of the pump 2642. For example, a relay controlled by the microprocessor 284 can be provided in the operating circuit of the pump 2642 to control the closing or opening of the operating circuit of the pump 2642.
[0102] In some embodiments, the control module 280 can also control the operating current of the cooler 240 based on the temperature sensed by the temperature sensor 282. For example, when the temperature sensor 282 detects that the temperature of the heat-conducting plate 220 is lower than the target temperature, the microprocessor 284 can control an increase in the operating current of the cooler 240 to increase the power of the cooler 240, thereby causing the cooler 240 to raise the temperature of the heat-conducting plate 220. In this embodiment, the temperature sensor 282 is a contact temperature sensor 282, for example, the temperature sensor 282 is in contact with the heat-conducting plate 220. Of course, the temperature sensor 282 can also be a non-contact temperature sensor 282, for example, the temperature sensor 282 is an infrared temperature sensor.
[0103] In addition, the cooling liquid in the water bath 262 can be water. In this way, the cost of the bearing device 1000 can be reduced. In some embodiments, the cooling liquid can be a specially made cooling liquid, which is not limited herein. The specially made cooling liquid can ensure that the heat conduction capacity reaches a more ideal state.
[0104] From the above, it can be understood that the temperature control assembly 200 included in the sequencing system 10000 can regulate the temperature of the reactor 300, for example, using a refrigeration sheet to cool or heat the chip, and then using a metal heat sink or a water cooling system to remove heat. At this time, it needs to be noted that the increase and decrease of temperature will cause the deformation of related mechanical fixtures, such as thermal expansion and cold contraction. Among them, in particular, the temperature control object, the temperature control assembly 200 and the structure directly connected or contacted with the above structure are easily affected, for example, the base 100 of the bearing device 1000 in the embodiments of the present application.
[0105] In the present application, the entire temperature control assembly 200 can be in contact with the reactor 300 placed in the accommodating groove through the first through hole 124 from bottom to top, that is, it can be considered that the refrigerator is indirectly in contact with the reactor 300 through the heat conduction plate 220, and at this time part of the heat conduction plate 220 is located in the first through hole 124. And, please refer to Figure 15 With Figure 16 In the horizontal direction shown in the figure, there is a certain gap between the edge of the heat conduction plate 220 and the inner wall of the first through hole 124, which is used to provide enough deformation space for the thermal expansion and cold contraction of the heat conduction plate 220. The principle is similar to the gap left between adjacent rails on the railway to provide enough space for the deformation of the rails when the temperature changes to avoid extrusion between adjacent rails. Therefore, this embodiment can also achieve the purpose of avoiding mutual extrusion between the heat conduction plate 220 and the base 100 as much as possible.
[0106] Please refer to Figure 9 , Figure 15 With Figure 17 In some embodiments, the bearing device 1000 further comprises a connecting assembly for connecting the base 100 and the temperature control assembly 200. Among them, the connecting assembly comprises a support seat 420, a first positioning structure 440 and a second positioning structure 460. The heat conduction plate 220 is connected with the base 100 through the support seat 420, and the support seat 420 is made of a material with a thermal deformation degree smaller than that of the heat conduction plate 220, so that the deformation amount of the support seat 420 is smaller under the same temperature change condition, and the support seat 420 is directly connected with the base 100, so the influence on the base 100 is also smaller.
[0107] As Figure 15In the shown embodiment, the support base 420 can be mounted on the bottom of the base 100, and the support base 420 is provided with a through slot 422 in the center, which is in communication with the first through hole 124 on the base 100, and the size of the through slot 422 can be smaller than that of the first through hole 124, and a part of the refrigerator and the heat dissipation plate of the heat dissipation module 260 are located in the through slot 422. The through slot 422 can play a heat insulation role.
[0108] In other embodiments not shown in the figure, the support base 420 can also not be provided with a through slot 422, and the heat dissipation module 260 is located above the support base 420, for example, the side of the support base 420 close to the base 100 includes a groove for accommodating the temperature control assembly 200 located outside the first through hole 124 (the temperature control assembly 200 is partially located in the first through hole 124 and partially located outside the first through hole 124).
[0109] The support base 420 includes a first side and a second side opposite to the first side, the first side is provided with a first positioning structure 440, and the second side is provided with a second positioning structure 460, both of which can extend through the first through hole 124 to above the bottom wall of the accommodating groove. In other embodiments, the two positioning structures can also directly pass through the base 100 and extend to above the bottom wall of the accommodating groove.
[0110] Please refer to Figure 18 , the heat conduction plate 220 is provided with a first hole 222 capable of cooperating with the first positioning structure 440 and a second hole 224 capable of cooperating with the second positioning structure 460, the first hole 222 is a waist hole, which has higher deformation tolerance in the length direction compared with a round hole, when the heat conduction plate 220 is heated and expands or shrinks when cold, it can deform along the length direction of the waist hole, and maintain the cooperation between the first hole 222 and the first positioning structure 440, so that the heat conduction plate 220 still cooperates closely with the positioning structure after being heated, and the position does not deviate.
[0111] In the embodiment, the first positioning structure 440 includes a first positioning column 442 cooperating with the first hole 222, the first positioning column 442 includes a first end and a second end opposite to the first end, the first end of the first positioning column 442 is connected with the support base 420, and the second end of the first positioning column 442 is provided with a first positioning ball 444, and the heat conduction plate 220 is located between the first positioning ball 444 and the support base 420.
[0112] The second positioning structure 460 comprises a second positioning column 462 matched with the second hole 224, the second positioning column 462 comprises a first end and a second end opposite to the first end, the first end of the second positioning column 462 is connected with the support base 420, and the second end of the second positioning column 462 is provided with a second positioning ball 464, the heat conduction plate 220 is located between the second positioning ball 464 and the support base 420, and the reactor 300 is provided with a third hole capable of matching with the first positioning ball 444 and a fourth hole capable of matching with the second positioning ball 464.
[0113] In the embodiment, the two positioning columns can position the heat conduction plate 220 at the position to be contacted with the reactor 300, and the two positioning balls are arranged, on one hand, to position the reactor 300 when the reactor 300 is placed and prevent the reactor 300 from deviating after being placed, and on the other hand, the heat conduction plate 220 cannot pass through the two positioning balls upward, so that the heat conduction plate 220 is limited between the two positioning balls and the refrigerator.
[0114] In other embodiments, one of the first positioning structure 440 and the second positioning structure 460 comprises a positioning column, which can also meet the requirements of the present application.
[0115] In other embodiments, the heat conduction plate 220 and the refrigerator are bonded by using a heat conduction adhesive with good heat conduction performance, so as to further ensure that the heat conduction plate 220 will not be separated from the refrigerator.
[0116] In other embodiments, the first side of the support base 420 is provided with a first protruding part 424 for supporting the heat conduction plate 220, the first protruding part 424 is located in the first through hole 124, the top of the first protruding part 424 is in contact with the bottom of the heat conduction plate 220, there is also a gap between the first protruding part 424 and the inner wall of the first through hole 124, and the first positioning structure 440 is arranged on the first protruding part 424.
[0117] The second side of the support base 420 is provided with a second protruding part 426 for supporting the heat conduction plate 220, the second protruding part 426 is located in the first through hole 124 and has a gap with the inner wall of the first through hole 124, and the second positioning structure 460 is arranged on the second protruding part 426. In this way, the two protruding parts can reduce the contact area between the heat conduction plate 220 and the support base 420, and further reduce the influence of the heat conduction plate 220 on the support base 420.
[0118] In the bearing device 1000 of the above embodiment, the heat conduction plate 220 which is greatly deformed by temperature does not directly contact or connect with the base 100, but is connected through the support base 420, and there is a gap between the heat conduction plate 220 and the inner wall of the first through hole 124, so that even if the heat conduction plate 220 is expanded by heat, the base 100 will not be squeezed, and the service life of the base 100 can be prolonged.
[0119] In addition, it should be noted that in the process of temperature adjustment of the reactor 300 by the temperature control assembly 200, the temperature rise and fall will not only cause the deformation of the related mechanical fasteners, but also possibly cause the thermal deformation of the part of the temperature control assembly 200 in contact with the reactor 300. At this time, an extrusion force will be generated to the reactor 300 in the process of deformation, so that the reactor 300 also deforms, thereby causing the flow path 360 in the reactor 300 to deform and affecting the biochemical reaction and / or increasing the difficulty of collecting the focus pursuit focus signal.
[0120] Then, please refer to Figure 19 With Figure 20 In the embodiment of the present application, the reactor 300 further comprises a rigid plate 380, which is arranged below the sheet layer 340. The rigid plate 380 can be a metal plate such as an aluminum plate, and the temperature control assembly 200 contacts the reactor 300 through the rigid plate 380.
[0121] Specifically, the temperature control assembly 200 comprises a heat conduction plate 220, a refrigerator 240 and a water bath chamber 260 connected in sequence, and the heat conduction plate 220, the refrigerator 240 and the water bath chamber 260 are stacked in sequence. The entire temperature control assembly 200 can pass through the first through hole 124 from bottom to top and contact the reactor 300 placed in the accommodating groove 122, wherein the heat conduction plate 220 directly contacts the rigid plate 380.
[0122] As Figure 20 shown, the connecting assembly further comprises a first connecting piece 480 and a second connecting piece 482 connected. The first connecting piece 480 connects the base 100, and the second connecting piece 482 connects the water bath chamber 260. The first connecting piece 480 is a rigid connecting piece, and the second connecting piece 482 is an elastic connecting piece.
[0123] For example, the first connecting piece 480 is a screw rod, and the second connecting piece 482 is a spring. The screw rod and the spring are arranged in the vertical direction respectively. The rod part of the screw rod passes through the cover plate 264 and is threadedly connected with the support seat 420. The spring is sleeved on the screw rod, one end of the spring elastically abuts against the head of the screw rod, and the other end of the spring elastically abuts against the bottom of the cover plate 264. An upward force is applied to the entire temperature control assembly 200, and the cover plate 264 is pressed tightly on the bottom of the support seat 420.
[0124] The process of placing the reactor 300 on the bearing surface 120 in the embodiment will be described below:
[0125] The reactor 300 is placed in the accommodating groove 122. In the process of moving towards the accommodating groove 122, the rigid plate 380 will first contact the heat conduction plate 220. In the process of continuous movement, the spring is compressed, the temperature control assembly 200 moves downward, and the chip frame 320 of the reactor 300 contacts the bearing surface 120.
[0126] In the process of the temperature control assembly 200 cooling or heating the reactor 300, if the temperature control assembly 200 expands due to heat and deforms in the vertical direction, the top of the temperature control assembly 200 is in contact with the rigid plate 380, and the bottom is in contact with the spring, so the deformation is more likely to occur downward, and the reactor 300 is less likely to be squeezed by the deformation. In addition, in the temperature control assembly 200, the cooler 240 is flexibly connected to the water bath room 262, so the squeezing of the cooler 240 to the reactor 300 is also small; and the elastic force or squeezing can be transmitted downward to be released, which mainly causes the deformation and connection strength / force of the cooler 240 and the water bath room 262 located below the bearing device 1000, so as to make the bearing device 1000 stable and stable in bearing and movement, and prolong the mechanical service life.
[0127] In some embodiments, the support seat 420 can be made of a relatively soft material. During the continuous movement of the reactor 300, the spring is compressed, and the temperature control assembly 200 moves downward. Although the chip frame 320 of the reactor 300 is not in contact with the bearing surface 120, after the heat conduction plate 220 contacts the top of the support seat 420, the temperature control assembly 200 cannot continue to move downward, so the reactor 300 also stops moving. In other embodiments, the temperature control assembly 200 can also stop moving after reaching the limit position connected to the base 100.
[0128] According to the sequencing system 10000 and the bearing device 1000 of any of the above embodiments, the temperature control assembly 200 for cooling or heating the reactor 300 is rigidly connected between the temperature control assembly 200 and the reactor 300, so that the deformation of the temperature control assembly 200 and / or the reactor 300 caused by heating does not substantially affect the relative positional relationship between the two. In other words, the temperature control device 200 and the reactor 300 are tightly connected, and there is basically no physical space between the temperature control device 200 and the reactor 300 to accommodate deformation, so the position of the reactor 300 is basically not affected by the deformation. This can reduce the change in the position of the reactor 300 caused by the squeezing of the temperature control assembly 200 to the reactor 300, and the bearing device 1000 has less tolerance for the deformation of the connected reactor 300 (reaction chamber), so that the reactor 300 placed therein is tightly and stably connected to the bearing device 1000. In this way, it is beneficial to accurately focus and quickly and stably track the specified surface or part of the reactor 300 during the biochemical reaction process, to obtain clear images of the signals in the reactor, and to achieve accurate sequencing based on the clear images.
[0129] Further, during the sequencing process, imaging or washing or reaction reagents are usually introduced into the reactor 300 to achieve the corresponding purposes. These reagents are generally placed in a reagent box. During sequencing, the reactor 300 is first connected to the fluid device 2000 of the sequencing system 10000, so that the reactor 300 is connected to the liquid circuit of the sequencing system 10000, and then the power device is used to introduce these reagents into the reactor 300 flow path 360 of the reactor 300 to carry out the corresponding process.
[0130] Generally, the flow path 360 of the sequencing system 10000 is established by connecting each component by a hose, and in order to avoid liquid leakage and more closely connect, a manifold is used to connect the reactor 300 containing multiple flow paths 360. However, in actual operation, due to the change of liquid pressure at the connection, aging, and the connection between the manifold and the reactor 300 is inevitably leaked to different degrees. The leaked liquid is easy to drip from the manifold to the components below the manifold, especially when the support member 660 below the manifold is provided to support the manifold. The accumulated liquid is easy to cause damage to the support member 660 and affect the performance stability of the bearing device 1000 and even the entire sequencing system 10000
[0131] It should be noted that the manifold referred to in the present application refers to the inlet and outlet pipelines between the hoses of the fluid system and the reactor 300.
[0132] Please refer to Figure 21 The bearing device 1000 in the embodiment further includes a fluid connecting member and a support structure 600.
[0133] Specifically, as shown in Figure 5 and Figure 19 The reactor 300 has four flow paths 360, and the inlet and outlet of each flow path 360 can be located at the bottom of the reactor 300. In other embodiments, the reactor 300 can have one or other number of flow paths 360. In the present embodiment, the base 100 includes a first side and a second side opposite to the first side. For example, the inlet of the flow path 360 in the reactor 300 can be close to the first side of the base 100, and the outlet of the flow path 360 of the reactor 300 can be close to the second side of the base 100.
[0134] When the reactor 300 is carried on the bearing surface, the fluid connecting member communicates with the flow path 360 of the reactor 300. The fluid connecting member can pass through the base 100 from bottom to top, and the fluid connecting member is located at a position communicating with the inlet and outlet of the flow path 360 after the reactor 300 is placed in the accommodating groove 122.
[0135] Please refer to Figure 21 , Figure 22 and Figure 23In this embodiment, the fluid connection includes a first manifold 520 and a second manifold 540, the first manifold 520 is located at the first side of the base 100, as shown in Figure 21 As shown in Figure 22 Fig. 6 shows a longitudinal sectional view of a first manifold 520 of one structure, which has four inlet flow channels 522 for communicating with the inlets of the four flow paths 360 in the reactor 300. The second manifold 540 is located at the second side of the base 100, as shown in Figure 23 Fig. 7 shows a longitudinal sectional view of a second manifold 540 of one structure, which has an outlet flow channel 524 with four branches converging into one main branch, the liquid discharged from the outlets of the four flow paths 360 in the reactor 300 converges in the main branch of the outlet flow channel 524. Of course, in other embodiments, the internal flow channels can be manifolds of other structures.
[0136] As shown in Figure 21 As shown in Figure 22 The support structure 600 is used to support the fluid connection, for example, the support structure 600 is located below the fluid connection and connected with the base 100, so as to fix the fluid connection on the base 100. In this embodiment, the fluid connection includes a first manifold 520 and a second manifold 540, correspondingly, the support structure 600 also has two, which are used to support the first manifold 520 and the second manifold 540 respectively, that is, the first manifold 520 and the second manifold 540 are connected with the base 100 through the support structure 600.
[0137] The following takes the support structure 600 below the first manifold 520 as an example for description, the support structure 600 below the second manifold 540 is also the same.
[0138] The support structure 600 includes a support surface 620 for supporting the first manifold 520 and a support member 660, the support structure 600 can be a substantially U-shaped structure, the two ends of the opening of the U-shaped structure are threadedly connected with the base 100. The bottom wall of the U-shaped structure can be the support surface 620 of the support structure 600, the support surface 620 is provided with a first recess 640, one end of the support member 660 is arranged in the first recess 640, the other end of the support member 660 is connected with the first manifold 520, and a second through hole 624 is arranged in the first recess 640.
[0139] The second through hole 624 is located on the bottom wall of the first recess 640, and the radius of the second through hole 624 is smaller than the size through which the one end of the support member 660 can pass, so that the support member 660 cannot slide off from the second through hole 624. The bottom of the first manifold 520 has a second recess 524 matched with the other end of the support member 660, and the other end of the support member 660 is arranged in the second recess 524
[0140] In some embodiments, the first manifold 520 and the support surface 620 can have a gap therebetween, and the first manifold 520 is connected to the support surface 620 only through the support member 660, and liquid leakage on the first manifold 520 is more likely to flow into the first groove 640 through the support member 660.
[0141] In some embodiments, the support member 660 is a spring, and the first manifold 520 and the support surface 620 can have a gap therebetween, and when the reactor 300 is placed in the containing groove 122, the first manifold 520 can press the spring downward, and correspondingly, the spring can elastically abut the first manifold 520 on the reactor 300. Further, the first manifold 520 can have two connecting portions 526 on two sides in the horizontal direction, respectively, and when the reactor 300 is taken out of the containing groove 122, the spring pushes the first manifold 520 upward, and the top of the two connecting portions 526 can abut the bottom of the base 100, preventing the first manifold 520 from falling out.
[0142] In some embodiments, the support surface 620 is provided with a third positioning structure 680, and the first manifold 520 is provided with a fourth positioning structure 530, for example, the third positioning structure 680 includes a positioning column 682, and the fourth positioning structure 530 includes a positioning groove 532 matched with the positioning column 682, that is, the positioning column 682 on the support structure 600 is inserted into the positioning groove 532 on the first manifold 520 to complete positioning, of course, another way, for example, the third positioning structure 680 includes a positioning groove 532, and the fourth positioning structure 530 includes a positioning column 682 matched with the positioning groove 532, which is also feasible.
[0143] In some examples, the support member 660 has two and is symmetrically arranged, so that the first manifold 520 is more stably supported.
[0144] The second manifold 540 is also provided with a support structure 600 below, which is not described here.
[0145] The bearing device 1000 of any of the above embodiments and the sequencing system 10000 containing the bearing device 1000 are connected with the reactor 300 provided with the flow path 360 by containing the fluid connector, realizing the communication of the fluid connector and the flow path 360 in the reactor 300. The fluid connector realizes the position fixation through the cooperation of the support surface 620 and the support member 660 in the support structure 600. When liquid leakage occurs at the connection between the fluid connector and the flow path 360 in the reactor 300, the liquid flowing along the fluid connector to the support member 660 can be discharged from the second through hole 624 in the first groove 640, thereby avoiding the end of the support member 660 being soaked in the liquid, ensuring the normal use of the support structure 600, and making the performance of the sequencing system 10000 more stable.
[0146] Further, the present application also provides an imaging device 3000 located above the carrying device 1000, for exciting the reactor 300 to emit optical signals and collecting at least part of the optical signals. In the embodiment, the imaging device 3000 can include a laser generator and a camera. The laser generator generates laser light which irradiates the sheet layer 240 after reacting with the reagent on the reactor 300. The camera collects the image information, which includes the fluorescence information of the sheet layer 240 after being irradiated by the laser light. According to the fluorescence information, the sequencing result can be analyzed.
[0147] The imaging device 3000 of the present application can refer to the optical system, the method of calibrating the optical system and the sequencing system disclosed in the patent application CN111308726A, the content of which is incorporated herein by reference.
[0148] Specifically, referring to Figure 24 The imaging device 3000 of the present application includes a first light source 12, a first lens 16 and a light splitting module 40. The light splitting module 40 includes a first light splitter 14, a second lens 18, a first camera 20 and a second camera 22. The first lens 16 is used to receive the first light beam from the first light source 12 and to collimate the light beam to be incident on the reactor 300, and to receive the light beam from the reactor 300 and to collimate the light beam. The second lens 18 is used to focus the collimated light beam from the first lens 16 to the first camera 20 and the second camera 22. The first light splitter 14 is used to split the focused light beam from the second lens 18 into a second light beam and a third light beam. The first camera 20 is used to receive the second light beam. The second camera 22 is used to receive the third light beam.
[0149] The imaging device 3000 described above, since the second lens 18 focuses the light and then the light splitter 14 splits the light into a second light beam and a third light beam, which can reduce the use of optical elements, shorten the light splitting path length, shorten the total optical path length of the imaging device 3000, and facilitate the miniaturization and industrialization of the imaging device 3000.
[0150] In particular, the nucleic acid sample to be tested can be placed in the reactor 300, such as in a chip. The first light source 12 can be a laser light source. In one example, the chip comprises a substrate, a flow path is provided on the substrate, and a glass is provided on the substrate. When the sequencing system using the imaging device 3000 is used for sequencing, under certain conditions, the nucleic acid to be tested, enzymes, fluorescently labeled nucleotide reagents or solutions, etc. are mixed in the flow path to react, and then the first light source 12 emits laser light which is incident on the chip through the first lens 16. The fluorescent groups in the field of view are excited to emit fluorescence, and the fluorescence is focused by the first lens 16 and the second lens 18 to reach the first beam splitter 14. The first beam splitter 14 divides the convergent light beam into a second light beam and a third light beam. The first camera 20 receives the second light beam, and the second camera 22 receives the third light beam, and the first image and the second image of the field of view are collected respectively.
[0151] In one example, please refer to Figure 25 , the first light source 12 can include a first light emitter 13 and a third lens 15. The first light beam is a collimated light beam of the light beam emitted by the first light emitter 13 after passing through the third lens 15. The first light beam is focused by the fourth lens 17 to the back focal plane of the first lens 16, and then collimated by the first lens 16 to be incident on the reactor 300. In one example, the first light source 12 further includes an optical fiber coupler, such as a single-mode optical fiber coupler. In particular, the imaging device 3000 is a total internal reflection imaging device 3000. The collimated light beam (parallel light beam) passing through the first lens 16 is incident on the chip surface at an angle greater than the critical angle, total internal reflection occurs, and an evanescent field (evanescent wave) is generated at the lower surface of the chip glass. The fluorescence emitted by the fluorescent molecules in the evanescent field is received by the first lens 16.
[0152] When the light beam emitted by the first light source 16 excites the fluorescent groups of the sample to be tested in the reactor 300 to emit light, the light beam received by the first lens 16 from the reactor 300 is the light beam emitted by the sample to be tested in the reactor 300.
[0153] The image sensors of the first camera 20 and the second camera 22 can be CCD or CMOS. Preferably, the types of image sensors used by the first camera 20 and the second camera 22 are the same, such as both being CCD or both being CMOS. The first beam splitter 14 can be a dichroic mirror.
[0154] In the illustrated embodiment, the second light beam is the transmitted light beam of the first beam splitter 14, and the third light beam is the reflected light beam of the first beam splitter 14.
[0155] In some embodiments, the first camera 20 and the second camera 22 are arranged at 90 degrees or 270 degrees. In this way, the first camera 20 and the second camera 22 can be arranged in the imaging device 3000 in a limited space. In particular, inFigure 24 In the shown orientation, the first beam splitter 14 has a first reflective surface 26, which forms a 45-degree angle with the horizontal plane, and a portion of the light beams incident on the first reflective surface 26 in the horizontal direction is reflected by 90 degrees to reach the second camera 22, while another portion of the light beams incident on the first reflective surface 26 passes through the first reflective surface 26 and is incident on the first camera 20. Figure 24 In one example, the sample to be measured in the reactor 300 is labeled with two fluorescent labels, for example, Cy3 and Atto647N, and the emission wavelength bands of the two fluorescent molecules are 550-620 nm and 650-750 nm (the peak wavelengths are about 564 nm and 670 nm, respectively); the first beam splitter 14 is a dichroic mirror, which has a high transmittance for light with a wavelength of 550-620 nm and a high reflectivity for light with a wavelength of 650 nm or more.
[0156] The fluorescently labeled nucleotide reagents include four types of nucleotide reagents A, T, C, and G, and different types of nucleotide reagents can be contained in different containers. In one example, the four types of nucleotide reagents are labeled with the same fluorescent label, and each round of sequencing reaction includes four base extension reactions, which are four times of sequentially adding the four types of nucleotide reagents and obtaining corresponding images.
[0157] In one example, the four types of nucleotide reagents are respectively labeled with a first fluorescent label and a second fluorescent label, and the first fluorescent label and the second fluorescent label can be excited to emit different fluorescent light. Two-color sequencing is performed using the four types of nucleotide reagents, and each round of sequencing reaction includes two base extension reactions. In sequencing using the sequencing system 10000 including the imaging device 3000, under certain conditions, the sample nucleic acid, the enzyme, and two types of nucleotide reagents or solutions labeled with the first fluorescent label and the second fluorescent label are mixed in the flow path to react, the first light source 12 simultaneously emits the first laser light and the second laser light, which are incident on the chip through the first lens 16, the first fluorescent label and the second fluorescent label in a certain field of view are excited by the first laser light and the second laser light to emit the first fluorescent light and the second fluorescent light, respectively, the first fluorescent light and the second fluorescent light are converged by the first lens 16 and the second lens 18 to the first beam splitter 14 (dichroic mirror), the dichroic mirror separates the first fluorescent light and the second fluorescent light, the first fluorescent light is focused on the image plane of the first camera 20, and the second fluorescent light is focused on the image plane of the second camera 22, thereby obtaining the first image and the second image formed by the first fluorescent light and the second fluorescent light in the field of view, respectively. Based on the first image and the second image information of the nucleotide addition sequence and different rounds of sequencing reaction, base recognition / sequencing is achieved.
[0158] In another example, four types of nucleotides are respectively labeled with fluorescent label a, fluorescent label b, double fluorescent label a-b, and no label, fluorescent label a and fluorescent label b can be excited to emit different fluorescence, four-color sequencing is performed using the four types of nucleotides, each round of sequencing reaction includes one base extension reaction, when sequencing is performed using a sequencing system comprising the imaging device 3000, under certain conditions, the nucleic acid to be tested, enzymes, and the above-mentioned four types of nucleotide reagents or solutions are mixed in the flow path to react, the first light source 12 simultaneously emits the first laser and the second laser which are incident on the chip through the first lens 16. The fluorescent labels in the field of view are excited by the first laser and the second laser to emit fluorescence, respectively. The fluorescence is converged to the first beam splitter 14 (dichroic mirror) through the first lens 16 and the second lens 18. The dichroic mirror separates the fluorescence from the fluorescent label a and the fluorescence from the fluorescent label b. The fluorescence from the fluorescent label a is focused on the image plane of the first camera 20, and the fluorescence from the fluorescent label b is focused on the image plane of the second camera 22. In this way, the first image and the second image of the field of view are obtained, respectively. Through the first image and the second image of different rounds of sequencing reactions and the information of merging the first image and the second image of the same round of sequencing reactions, base recognition / sequencing is realized.
[0159] Referring to Figure 1 The embodiment of the present application provides a sequencing system 10000, comprising a mobile platform 800 and an imaging device 3000, the mobile platform is used to carry a reactor 300, and the imaging device 3000 is the imaging device 3000 in any of the above-mentioned embodiments.
[0160] The above-mentioned sequencing system 10000 comprises the imaging device 3000 having any of the above-mentioned technical features and advantages, and has a compact structure, which is beneficial to miniaturization and industrialization.
[0161] Specifically, in the embodiment, the mobile platform 800 is movable. The mobile platform 800 can drive the reactor 300 to move relative to the imaging device 3000, for example, to move along a direction perpendicular to the optical axis of the first lens 16, or to move along a direction parallel to the optical axis of the first lens 16, or to move along a direction inclined to the optical axis of the first lens 16, so that different positions of the reactor 300 are located directly below the first lens 16. In this way, the imaging device 3000 comprising the sequencing system 10000 can be used to realize image acquisition of the reactor 300, and further realize sequence determination. It can be understood that the sequencing system 10000 of the embodiment of the present application can comprise the imaging device 3000 in any of the above-mentioned embodiments.
[0162] In addition, the sequencing system 10000 of the embodiments of the present application further comprises a computing device, which can be operatively coupled with the imaging device 3000 and can be used to obtain a set of instructions for the fluorescent signal from the imaging device 3000. Specifically, the fluorescent signal collected by the imaging device 3000 is, for example, an image, and the computing device obtains a set of images from the imaging device 3000, processes and identifies the information on the images to identify the sequence determination.
[0163] The embodiments of the present application provide a fluid device 2000, which is connected with the carrier device 1000 and is used to controllably move one or more reagents with fluorescent labels into contact with the polynucleotides in the reactor 300.
[0164] Specifically, please refer to Figure 26 In some embodiments, the fluid device 2000 comprises a reservoir 60 and a multi-way valve 70. The reservoir 60 is used to store solutions, and the solutions include a plurality of, for example, reaction solutions, buffer solutions, cleaning solutions and / or pure water, etc., including reagents for different reactions or different steps of one reaction; the multi-way valve 70 is provided with a plurality of sample inlets 72 and a sample outlet 74, wherein the sample inlets 72 are used for the reagents to enter the multi-way valve 70, and the sample outlet 74 is selectively communicated with one of the sample inlets 72, and then connected with a plurality of flow paths in the reactor 300 through the manifold 76 provided to move the reagents from the sample outlet 74 to the reactor 300 to contact with the polynucleotides.
[0165] It should be noted that the carrier device 1000 of the sequencing system 10000 can comprise a plurality of bases 100, and correspondingly, a plurality of reactors 300 can be provided. In this way, the plurality of sample inlets 72 of the multi-way valve 70 allows the plurality of reactors 300 to enter different liquids, so as to realize multiple rounds / repeated reactions, and the multi-way valve 70 can be provided to realize the sampling of a plurality of reagents to meet the biochemical process of sequencing, and can also avoid cross contamination between the reagents.
[0166] As Figure 26 shown, in some embodiments, the fluid device 2000 can further comprise a pump assembly 80 and a liquid collector 90. The pump assembly 80 is used as a negative pressure power source, so that the reagents flow into the flow paths of the reactor 300 under the action of negative pressure to perform biochemical reactions, and the liquid collector 90 can collect the liquids flowing out of the plurality of reactors 300.
[0167] In the description of the specification, reference to "one embodiment", "certain embodiments", "some embodiments", "exemplary embodiments", "a specific example", or "some examples" etc., mean that a particular feature, structure, material, or characteristic being described is included in at least one embodiment or example of the application. The appearances of the above expressions in various places in the specification are not necessarily referring to the same embodiment or example. Moreover, describing a particular feature, structure, material, or characteristic as included in an embodiment or example is intended to convey that the particular feature, structure, material, or characteristic is included in at least one embodiment or example of the application. Thus, appearances of the expressions "in one embodiment" or "in an embodiment" are not necessarily referring to the same embodiment.
[0168] Although the embodiments of the present application have been shown and described, it would be appreciated by those skilled in the art that changes, modifications, alternatives and variations to these embodiments could be made without departing from the principles and spirit of the application, the scope of which is defined by the claims and their equivalents.
Claims
1. A sequencing system, comprising: The application relates to a device for detecting a plurality of polynucleotides, comprising: a bearing device for bearing a plurality of reactors and adjusting the temperature of the reactors, the reactors being connected with a plurality of polynucleotides, the bearing device comprising, a base having a bearing surface for bearing the reactors, a temperature control assembly comprising a heat-conducting plate, a refrigerator and a heat dissipation module, the refrigerator being connected with the reactors through the heat-conducting plate, the heat-conducting plate being rigidly connected with the reactors in the case that the reactors are placed on the bearing surface, and a connecting assembly connecting the base and the temperature control assembly, the connecting assembly comprising a support seat, the heat-conducting plate being connected with the base through the support seat; a fluid device connected with the bearing device and used for controllably moving one or more reagents with fluorescent markers into contact with the polynucleotides, the fluid device further comprising a pump assembly and a liquid collector, the pump assembly being used as a negative pressure power source so that the reagents flow into flow paths of the reactors under the action of negative pressure to perform biochemical reactions, and the liquid collector being used for collecting liquid flowing out of the reactors; an imaging device located above the bearing device and used for exciting and collecting fluorescence generated by the fluorescent markers; and a computing device operatively coupled with the imaging device and comprising an instruction set for acquiring fluorescence signals from the imaging device. The fluid device comprises a multi-way valve provided with a plurality of liquid inlets and one liquid outlet, the liquid outlet being selectively communicated with one of the liquid inlets, the liquid inlets being used for allowing the reagents to enter the multi-way valve and move from the liquid outlet to the reactors. The imaging device comprises a first light source, a first lens and a light splitting module, the light splitting module comprising a first light splitter, a second lens, a first camera and a second camera, the first lens being used for receiving a first light beam from the first light source and collimating the first light beam to be incident on the reactors and receiving a light beam from the reactors and collimating the light beam, the second lens being used for focusing the collimated light beam from the first lens to the first camera and the second camera, and the first light splitter being used for splitting the focused light beam from the second lens into a second light beam and a third light beam, the first camera being used for receiving the second light beam, and the second camera being used for receiving the third light beam. The first light source comprises a first light emitter and a third lens, and the imaging device further comprises a fourth lens, the first light beam being a collimated light beam of a light beam emitted by the first light emitter after passing through the third lens, the first light beam being focused to a back focal plane of the first lens through the fourth lens and then collimated to be incident on the reactors through the first lens. The bearing surface is provided with a first through hole, the temperature control assembly passes through the first through hole and extends above the bearing surface, and the heat dissipation module comprises a water bath chamber, the heat-conducting plate, the refrigerator and the water bath chamber being sequentially stacked. 2. The sequencing system of claim 1, wherein, 3. The sequencing system of claim 1, wherein, 4. The sequencing system of claim 3, wherein, 5. The sequencing system of claim 1, wherein, 6. The sequencing system of claim 5, wherein, The heat-conducting plate is in contact with the reactor through the first through hole.
7. The sequencing system of claim 5, wherein, The part of the heat-conducting plate located in the first through hole has a gap between the inner wall of the first through hole.
8. The sequencing system of claim 5, wherein, The first face of the refrigerator is in contact with the reactor through the first through hole when the reactor is carried by the carrying face. The water bath is in contact with the second face of the refrigerator, and the water bath has a cavity for containing cooling liquid, and the water bath is provided with a liquid inlet and a liquid outlet communicating with the cavity.
9. The sequencing system of any one of claims 5-8, wherein, The water bath has a cavity for containing cooling liquid, and the water bath is provided with a liquid inlet and a liquid outlet communicating with the cavity, and the water bath is provided with a first heat dissipation area and a second heat dissipation area, and the first heat dissipation area is provided with a first flow channel and a second flow channel, and the second heat dissipation area is provided with a third flow channel and a fourth flow channel, and each flow channel has a first end and a second end facing different directions. The first end of the first flow channel and the first end of the second flow channel are communicated, and the second end of the first flow channel is communicated with the liquid inlet of the water bath. The second end of the third flow channel and the second end of the fourth flow channel are communicated, and the first end of the fourth flow channel is communicated with the liquid outlet of the water bath. The second end of the second flow channel and the first end of the third flow channel are communicated. At least one flow channel in the first heat dissipation area is in a zigzag shape, and at least one flow channel in the second heat dissipation area is in a zigzag shape.
10. The sequencing system of claim 9, wherein, The water bath further comprises a heat dissipation plate and a cover plate. The heat dissipation plate is provided with the first flow channel, the second flow channel, the third flow channel and the fourth flow channel, and the cover plate is connected to the heat dissipation plate and covers the first flow channel, the second flow channel, the third flow channel and the fourth flow channel to form the cavity.
11. The sequencing system of any one of claims 5-8, wherein, The heat dissipation module comprises the water bath and a liquid assembly, the liquid assembly comprises a pump and a cooler connected to each other, the pump is used to provide power to the cooling liquid, and the cooler is used to cool the cooling liquid, the pump is connected to the liquid inlet of the water bath, and the cooler is connected to the liquid outlet of the water bath.
12. The sequencing system of claim 11, wherein, The cooler comprises a cooling row, and the cooling row is provided with a channel, and the channel is provided with a plurality of cooling fins.
13. The sequencing system of claim 12, wherein, The cooler further comprises a fan capable of generating airflow towards the cooling row.
14. The sequencing system of claim 13, wherein, The liquid assembly further comprises a water storage pool for storing cooling liquid, and the pump and the cooler are connected through the water storage pool.
15. The sequencing system of claim 12, wherein, The temperature control assembly further comprises a control module connected to the refrigerator and the heat dissipation module, the control module is used to detect the temperature of the reactor and control the operation of the heat dissipation module according to the detected temperature.
16. The sequencing system of claim 15, wherein, The control module comprises a temperature sensor arranged on the heat-conducting plate for detecting the temperature of the heat-conducting plate.
17. The sequencing system of claim 10, wherein, The first ends of the first flow channel, the second flow channel, the third flow channel and the fourth flow channel face the same direction, and / or the second ends of the first flow channel, the second flow channel, the third flow channel and the fourth flow channel face the same direction.
18. The sequencing system of claim 5, wherein, The bearing surface is provided with a containing groove, and the first through hole is arranged in the containing groove.
19. The sequencing system of claim 5, wherein, The connecting assembly comprises a first connecting piece and a second connecting piece connected with each other, the first connecting piece is connected with the base through the support seat, one end of the second connecting piece is connected with the first connecting piece, and the other end of the second connecting piece is connected with the bottom of the water bath chamber, the first connecting piece is a rigid connecting piece, and the second connecting piece is an elastic connecting piece.
20. The sequencing system of claim 19, wherein, The second connecting piece is a spring.
21. The sequencing system of claim 1, wherein, The connecting assembly further comprises a first positioning structure and a second positioning structure, the support seat comprises a first side and a second side opposite to the first side, the first side of the support seat is provided with the first positioning structure, the second side of the support seat is provided with the second positioning structure, and the support seat is connected with the bottom of the base. The heat-conducting plate is provided with a first hole and a second hole capable of cooperating with the first positioning structure and the second positioning structure respectively.
22. The sequencing system of claim 21, wherein, The first hole is a waist hole.
23. The sequencing system of claim 21, wherein, The first positioning structure comprises a first positioning column matched with the first hole, the first positioning column comprises a first end portion and a second end portion opposite to the first end portion, the first end portion of the first positioning column is connected with the support seat, the second end portion of the first positioning column is provided with a first positioning ball with a radius larger than that of the first hole, and the heat-conducting plate is located between the first positioning ball and the support seat; and / or The second positioning structure comprises a second positioning column matched with the second hole, the second positioning column comprises a first end portion and a second end portion opposite to the first end portion, the first end portion of the second positioning column is connected with the support seat, the second end portion of the second positioning column is provided with a second positioning ball with a radius larger than the width of the second hole, and the heat-conducting plate is located between the second positioning ball and the support seat.
24. The sequencing system of claim 23, wherein, The reactor is provided with a third hole capable of cooperating with the first positioning ball and a fourth hole capable of cooperating with the second positioning ball.
25. The sequencing system of claim 21, wherein, The bearing surface is provided with a first through hole, the temperature control assembly passes through the first through hole and extends above the bearing surface, the first side of the support seat is provided with a first protruding portion for supporting the heat-conducting plate, and the first protruding portion has a gap between the first through hole and the inner wall of the first through hole; and / or The second side of the support seat is provided with a second protruding portion for supporting the heat-conducting plate, and the second protruding portion has a gap between the first through hole and the inner wall of the first through hole.
26. The sequencing system of claim 1, wherein, The reactor further comprises a rigid plate, and the temperature control assembly is rigidly connected with the reactor through the rigid plate.
27. The sequencing system of claim 26, wherein, The rigid plate is an aluminum plate.
28. The sequencing system of claim 1, wherein, The support seat is made of a material with a smaller degree of thermal deformation than that of the heat-conducting plate.
29. The sequencing system of claim 1, wherein, The bearing device further comprises a fluid connecting piece, the fluid connecting piece connects the fluid device, the reactor is provided with one or more flow paths, and in the case that the bearing surface bears the reactor, the fluid connecting piece communicates the reactor and the fluid device.
30. The sequencing system of claim 29, wherein, The bearing device further comprises a support structure for supporting the fluid connector, the support structure being located below the fluid connector and connected with the base; The support structure comprises a support surface for supporting the fluid connector and a support piece, the fluid connector being connected to the support surface through the support piece, the support surface being provided with a first groove, one end of the support piece being located in the first groove, and the other end of the support piece being connected with the fluid connector; The first groove is provided with a second through hole.
31. The sequencing system of claim 30, wherein, The fluid connector is provided with a second groove matched with the other end of the support piece, and the other end of the support piece is located in the second groove.
32. The sequencing system of claim 29, wherein, The flow path is provided with an inlet and an outlet, and the fluid connector comprises a first manifold and a second manifold; When the reactor is supported on the bearing surface, the first manifold is in communication with the inlet of the flow path, and the second manifold is in communication with the outlet of the flow path.
33. The sequencing system of claim 30 or 31, wherein, The support surface is provided with a third positioning structure, and the fluid connector is provided with a fourth positioning structure matched with the third positioning structure.
34. The sequencing system of claim 33, wherein, The third positioning structure comprises a positioning column, and the fourth positioning structure comprises a positioning groove matched with the positioning column; or The third positioning structure comprises a positioning groove, and the fourth positioning structure comprises a positioning column matched with the positioning groove.
35. The sequencing system of claim 30, wherein, There is a gap between the fluid connector and the support surface.
36. The sequencing system of claim 30, wherein, The support piece is a spring, so that the fluid connector elastically abuts on the reactor.
37. The sequencing system of claim 30, wherein, The number of support pieces is two, and the two support pieces are symmetrically arranged.
38. The sequencing system of claim 1, wherein, The bearing device further comprises a base, the base is used for accommodating a plurality of bases, a plurality of bases are arranged in parallel on the base, the base is provided with an adjusting structure, the base and the base are connected through the adjusting structure, and the adjusting structure is used for adjusting the distance between the base and the base.
39. The sequencing system of claim 38, wherein, The adjusting structure comprises a fine adjustment nut for adjusting the distance between the base and the base; A plurality of fine adjustment nuts are connected between one base and the base.
40. The sequencing system of claim 38, wherein, The adjusting structure further comprises a tension spring, and a plurality of tension springs are connected between one base and the base.
41. The sequencing system of claim 38, wherein, The base is a hollow structure, and the top of the base is provided with an opening; A plurality of bases are arranged at the opening of the base.
42. The sequencing system of claim 38, wherein, The bearing device further comprises a moving platform located below the base for supporting and moving the base.
43. The sequencing system of claim 42, wherein, The moving platform comprises a table top body, a first driving mechanism and a second driving mechanism, and the table top body is connected with the base; The first driving mechanism drives the table top body to move in a first direction, and the second driving mechanism drives the table top body to move in a second direction, and the first direction is perpendicular to the second direction.
44. The sequencing system of claim 43, wherein, The first driving mechanism comprises a first sliding rail, a first sliding seat and a first motor, the first sliding rail is arranged in parallel with the first direction, the first sliding seat is installed on the first sliding rail and moves along the first sliding rail under the drive of the first motor, and the table top body is connected with the first sliding seat.
45. The sequencing system of claim 44, wherein, The second driving mechanism comprises a second sliding rail, a second sliding base and a second motor, the second sliding rail is arranged in parallel with the second direction, the second sliding base is installed on the second sliding rail and moves along the second sliding rail under the driving of the second motor, and the first sliding rail is arranged on the second sliding base.
46. The sequencing system of claim 45, wherein, A guide member is arranged in the second sliding rail, and the guide member is parallel to the second direction. The second sliding base comprises a first side and a second side opposite to the first side along the second direction, one of the first side and the second side of the second sliding base has a third through hole matched with the guide member, and the guide member extends to the outside of the second sliding base through the third through hole.
47. A bearing device characterized by comprising: Comprise: a base having a bearing surface for bearing a reactor; a temperature control assembly comprising a heat conduction plate, a refrigerator and a heat dissipation module connected in sequence, the refrigerator is connected with the reactor through the heat conduction plate, and the heat conduction plate is rigidly connected with the reactor when the reactor is placed on the bearing surface; and a connecting assembly, the base and the temperature control assembly are connected through the connecting assembly, the connecting assembly comprises a support seat, and the heat conduction plate is connected with the base through the support seat; The bearing device further comprises a fluid connecting piece connected with a fluid device, the reactor is provided with one or more flow paths, and the fluid connecting piece is connected with the reactor and the fluid device when the reactor is borne on the bearing surface, the flow path is provided with an inlet and an outlet, and the fluid connecting piece comprises a first manifold and a second manifold, the first manifold has an inlet flow channel for communicating with the inlet in the reactor, and the second manifold has an outlet flow channel with a plurality of branch channels converging into a main channel for communicating with the outlet of the reactor.
48. The load bearing device of claim 47, wherein, A first through hole is arranged on the bearing surface, the temperature control assembly passes through the first through hole and extends above the bearing surface, the heat dissipation module comprises a water bath chamber, and the heat conduction plate, the refrigerator and the water bath chamber are sequentially arranged; The refrigerator is flexibly connected with the water bath chamber, and the water bath chamber is connected with the base through the connecting assembly.
49. The load bearing device of claim 48, wherein, When the reactor is borne on the bearing surface, the heat conduction plate is in contact with the reactor through the first through hole, and the heat conduction plate is not in direct contact with the first through hole.
50. The load bearing device of claim 48, wherein, The part of the heat conduction plate located between the inner wall of the first through hole and the first through hole has a gap.
51. The load bearing device of claim 48, wherein, The refrigerator has a first face and a second face opposite to each other, and the first face of the refrigerator is in contact with the reactor through the first through hole when the reactor is borne on the bearing surface; The water bath chamber is in contact with the second face of the refrigerator, the water bath chamber has a cavity for containing cooling liquid, and the water bath chamber is provided with a liquid inlet and a liquid outlet communicating with the cavity.
52. The load bearing device of any of claims 48-50, wherein, The water bath has a chamber for containing cooling liquid, the water bath is provided with a liquid inlet and a liquid outlet which communicate with the chamber, the water bath is provided with a first heat dissipation area and a second heat dissipation area, the first heat dissipation area is provided with a first flow channel and a second flow channel, and the second heat dissipation area is provided with a third flow channel and a fourth flow channel, each of the flow channels has a first end and a second end which are directed to different directions; The first end of the first flow channel and the first end of the second flow channel are communicated, and the second end of the first flow channel is communicated with the liquid inlet of the water bath; The second end of the third flow channel and the second end of the fourth flow channel are communicated, and the first end of the fourth flow channel is communicated with the liquid outlet of the water bath; The second end of the second flow channel and the first end of the third flow channel are communicated; At least one of the flow channels in the first heat dissipation area is in a meandering shape, and at least one of the flow channels in the second heat dissipation area is in a meandering shape.
53. The load bearing device of claim 52, wherein, The water bath further comprises a heat dissipation plate and a cover plate; The heat dissipation plate is provided with the first flow channel, the second flow channel, the third flow channel and the fourth flow channel, and the cover plate is connected to the heat dissipation plate and covers the first flow channel, the second flow channel, the third flow channel and the fourth flow channel to form the chamber.
54. The load bearing device of claim 52, wherein, The heat dissipation module comprises the water bath and a liquid assembly, the liquid assembly comprises a pump and a cooler which are connected to each other, the pump is used to provide power to the cooling liquid, the cooler is used to cool the cooling liquid, the pump is connected to the liquid inlet of the water bath, and the cooler is connected to the liquid outlet of the water bath.
55. The load bearing device of claim 54, wherein, The cooler comprises a cooling row, the cooling row is provided with a channel, and the channel is provided with a plurality of cooling fins.
56. The load bearing device of claim 55, wherein, The cooler further comprises a fan, and the fan can generate an air flow towards the cooling row.
57. The load bearing device of claim 55, wherein, The liquid assembly further comprises a water storage pool, the water storage pool is used to store the cooling liquid, and the pump and the cooler are connected to each other through the water storage pool.
58. The load bearing device of claim 55, wherein, The temperature control assembly further comprises a control module, the control module is connected to the cooler and the heat dissipation module, the control module is used to detect the temperature of the reactor and control the operation of the heat dissipation module according to the detected temperature.
59. The load bearing device of claim 58, wherein, The control module comprises a temperature sensor, the temperature sensor is arranged on the heat conduction plate and is used to detect the temperature of the heat conduction plate.
60. The load bearing device of claim 52, wherein, The first ends of the first flow channel, the second flow channel, the third flow channel and the fourth flow channel are directed to the same direction, and / or the second ends of the first flow channel, the second flow channel, the third flow channel and the fourth flow channel are directed to the same direction.
61. The load bearing device of claim 48, wherein, The bearing surface is provided with a receiving groove, the first through hole is arranged in the receiving groove, and the receiving groove is used to accommodate the reactor.
62. The load bearing device of claim 48, wherein, The connecting assembly comprises a first connecting member and a second connecting member which are connected to each other, the first connecting member is connected to the base through the support seat, one end of the second connecting member is connected to the first connecting member, and the other end of the second connecting member is connected to the bottom of the water bath, the first connecting member is a rigid connecting member, and the second connecting member is an elastic connecting member.
63. The load bearing device of claim 62, wherein, The second connecting member is a spring.
64. The load bearing device of claim 47, wherein, The connecting assembly further comprises a first positioning structure and a second positioning structure, the support base comprises a first side and a second side opposite to the first side, the first side is provided with the first positioning structure, and the second side is provided with the second positioning structure, and the support base is connected to the bottom of the base; The heat-conducting plate is provided with a first hole and a second hole capable of cooperating with the first positioning structure and the second positioning structure respectively.
65. The load bearing device of claim 64, wherein, The first hole is a waist hole.
66. The load bearing device of claim 64, wherein, The first positioning structure comprises a first positioning column matched with the first hole, the first positioning column comprises a first end and a second end opposite to the first end, the first end of the first positioning column is connected to the support base, the second end of the first positioning column is provided with a first positioning ball with a radius larger than that of the first hole, and the heat-conducting plate is located between the first positioning ball and the support base; and / or The second positioning structure comprises a second positioning column matched with the second hole, the second positioning column comprises a first end and a second end opposite to the first end, the first end of the second positioning column is connected to the support base, the second end of the second positioning column is provided with a second positioning ball with a radius larger than the width of the second hole, and the heat-conducting plate is located between the second positioning ball and the support base.
67. The load bearing device of claim 66, wherein, The reactor is provided with a third hole capable of cooperating with the first positioning ball and a fourth hole capable of cooperating with the second positioning ball.
68. The load bearing device of claim 64, wherein, The bearing surface is provided with a first through hole, the temperature control assembly passes through the first through hole and extends above the bearing surface, the first side of the support base is provided with a first protruding part for supporting the heat-conducting plate, and the first protruding part is located in the first through hole and has a gap between the inner wall of the first through hole; and / or The second side of the support base is provided with a second protruding part for supporting the heat-conducting plate, and the second protruding part is located in the first through hole and has a gap between the inner wall of the first through hole.
69. The load bearing device of claim 47, wherein, The reactor further comprises a rigid plate, and the temperature control assembly is rigidly connected to the reactor through the rigid plate.
70. The load bearing device of claim 69, wherein, The rigid plate is an aluminum plate.
71. The load bearing device of claim 47, wherein, The support base is made of a material with a smaller degree of thermal deformation than that of the heat-conducting plate.
72. The load bearing apparatus of claim 47, wherein, The bearing device further comprises a support structure for supporting the fluid connecting piece, and the support structure is located below the fluid connecting piece and connected to the base; The support structure comprises a support surface for supporting the fluid connecting piece and a support piece, the fluid connecting piece is connected to the support surface through the support piece, the support surface is provided with a first groove, one end of the support piece is located in the first groove, and the other end of the support piece is connected to the fluid connecting piece; The first groove is provided with a second through hole.
73. The load bearing device of claim 72, wherein, The fluid connecting piece has a second groove matched with the other end of the support piece, and the other end of the support piece is located in the second groove.
74. The load bearing device of claim 72 or 73, wherein, The support surface is provided with a third positioning structure, and the fluid connecting piece has a fourth positioning structure matched with the third positioning structure.
75. The load bearing device of claim 74, wherein, The third positioning structure comprises a positioning column, and the fourth positioning structure comprises a positioning groove matched with the positioning column; or The third positioning structure comprises a positioning groove, and the fourth positioning structure comprises a positioning column matched with the positioning groove.
76. The load bearing device of claim 72, wherein, The fluid connector has a gap with the support surface.
77. The load bearing device of claim 72, wherein, The support is a spring, so that the fluid connector elastically abuts on the reactor.
78. The load bearing device of claim 72, wherein, The number of the supports is two, and the two supports are symmetrically arranged.
79. The load bearing device of claim 47, wherein, The bearing device further comprises a base for accommodating a plurality of the bases, the plurality of the bases being arranged in parallel on the base, and the base is provided with an adjusting structure for adjusting the distance between the base and the base.
80. The load bearing device of claim 79, wherein, The adjusting structure comprises a fine adjustment nut for adjusting the distance between the base and the base. A plurality of the fine adjustment nuts are connected between one of the bases and the base.
81. The load bearing device of claim 79, wherein, The adjusting structure further comprises a tension spring, and a plurality of the tension springs are connected between one of the bases and the base.
82. The load bearing device of claim 79, wherein, The base is a hollow structure, and the top of the base is provided with an opening. The plurality of the bases are arranged at the opening of the base.
83. The load bearing device of claim 79, wherein, The bearing device further comprises a moving platform located below the base for supporting and moving the base.
84. The load bearing device of claim 83, wherein, The moving platform comprises a table top body, a first driving mechanism and a second driving mechanism, and the table top body is connected with the base. The first driving mechanism drives the table top body to move in a first direction, and the second driving mechanism drives the table top body to move in a second direction, and the first direction is perpendicular to the second direction.
85. The load bearing device of claim 84, wherein, The first driving mechanism comprises a first sliding rail, a first sliding seat and a first motor, the first sliding rail is arranged in parallel with the first direction, the first sliding seat is installed on the first sliding rail and moves along the first sliding rail under the drive of the first motor, and the table top body is connected with the first sliding seat.
86. The load bearing device of claim 84, wherein, The second driving mechanism comprises a second sliding rail, a second sliding seat and a second motor, the second sliding rail is arranged in parallel with the second direction, the second sliding seat is installed on the second sliding rail and moves along the second sliding rail under the drive of the second motor, and the first sliding rail is arranged on the second sliding seat.
87. The load bearing device of claim 86, wherein, The second sliding rail is provided with a guide element, and the guide element is parallel to the second direction. The second sliding seat comprises a first side and a second side opposite to the first side in the second direction, one of the first side of the second sliding seat and the second side of the second sliding seat has a third through hole matched with the guide element, and the guide element extends to the outside of the second sliding seat through the third through hole.
Citation Information
Patent Citations
Optical system, method of adjusting the optical system, and sequencing system
CN111308726A
Optical detection system and sequencing system
CN207215686U
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Bearing system and sequencing device
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CN216585001U