WO2022073357A1 - Système de séquençage et appareil de support - Google Patents

Système de séquençage et appareil de support Download PDF

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Publication number
WO2022073357A1
WO2022073357A1 PCT/CN2021/099329 CN2021099329W WO2022073357A1 WO 2022073357 A1 WO2022073357 A1 WO 2022073357A1 CN 2021099329 W CN2021099329 W CN 2021099329W WO 2022073357 A1 WO2022073357 A1 WO 2022073357A1
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WO
WIPO (PCT)
Prior art keywords
reactor
base
flow channel
hole
positioning
Prior art date
Application number
PCT/CN2021/099329
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English (en)
Chinese (zh)
Inventor
张松振
姜泽飞
王光明
郑焦
赖林
Original Assignee
深圳市真迈生物科技有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CN202022251300.0U external-priority patent/CN213570512U/zh
Priority claimed from CN202022246419.9U external-priority patent/CN213924845U/zh
Priority claimed from CN202022251614.0U external-priority patent/CN213680707U/zh
Priority claimed from CN202110297328.4A external-priority patent/CN115109694A/zh
Application filed by 深圳市真迈生物科技有限公司 filed Critical 深圳市真迈生物科技有限公司
Publication of WO2022073357A1 publication Critical patent/WO2022073357A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence

Definitions

  • the present application relates to the field of biological sample detection equipment, and in particular, to a sequencing system and a carrying device.
  • the sequencing system is also constantly updated.
  • the sequencing system includes an imaging component, and the imaging component is used to perform a sequencing reaction on the nucleic acid in the reactor (for example, the flow cell flowc-ell or the chip). Molecules are photographed, and the resulting images are analyzed to obtain sequencing results.
  • a sequencing system includes a carrier device for carrying the chip and/or for adjusting the position of the chip.
  • biochemical reactions are often involved, especially those involving biocatalysts such as proteases, which are sensitive to temperature and generally need to control the temperature of the reaction environment, such as cooling the chip or The temperature is controlled to ensure the effective progress of the biochemical reaction on it.
  • Existing sequencing devices include temperature control components. For example, semiconductor cooling sheets are used to cool or heat the chips, and metal heat sinks or water cooling systems are used to dissipate heat.
  • the so-called temperature control component is in direct or indirect contact with the reactor to achieve refrigeration or heating. During the process of temperature change, the structure in contact with the temperature control component, such as the reactor, will deform, which may affect the biochemical reaction in the reactor. and/or increase the difficulty of focusing and tracking the signal acquisition.
  • Embodiments of the present application provide a sequencing system and a carrying device.
  • the sequencing system of the embodiment of the present application includes: a carrying device for carrying a reactor and adjusting the temperature of the reactor, a plurality of polynucleotides are connected to the reactor, and the carrying device includes: a base having a On the bearing surface that carries the reactor, the temperature control assembly includes a connected heat conduction plate, a refrigerator and a heat dissipation module.
  • the refrigerator is connected to the reactor through the heat conduction plate, and is placed on the bearing surface.
  • the thermally conductive plate is rigidly connected to the reactor, and a connecting component connects the base and the temperature control component, the connecting component includes a support seat, and the thermally conductive plate is connected to the
  • the base is connected through the support base;
  • a fluid device is connected with the carrying device for controllably moving one or more fluorescently labeled reagents to the reactor and the polynucleotide contacting;
  • an imaging device positioned above the carrier device for exciting and collecting fluorescence generated by the fluorescent label;
  • a computing device operably coupled to the imaging device, including means for acquiring fluorescence from the imaging device Signal instruction set.
  • the automation can be improved. Sequencing accuracy and instrument life.
  • Using the sequencing device for nucleic acid sequencing can better control the temperature of the reaction environment of the reactor to ensure the effective progress of the biochemical reaction in the reactor, and can also better achieve focusing and tracking, and quickly obtain a clear and clear view of the designated surface of the reactor. images, and then based on these clear images, the bases can be accurately identified, and the accurate determination of the nucleic acid sequence can be realized.
  • a bearing device in an embodiment of the present application includes: a base having a bearing surface for bearing a reactor; and a temperature control assembly, wherein the temperature control assembly includes a connected heat conducting plate, a refrigerator and a heat dissipation module.
  • the refrigerator is connected with the reactor through the heat-conducting plate, and when the reactor is placed on the bearing surface, the heat-conducting plate is rigidly connected with the reactor; and a connecting assembly, the base and The temperature control assembly is connected through the connection assembly, and the connection assembly includes a support seat, and the heat conduction plate and the base are connected through the support seat.
  • the bearing device including the above-mentioned structural composition and connection relationship, including that the heat-conducting plate and the reactor are arranged to be rigidly connected and/or that the heat-conducting plate and the base are not directly connected, can better control the influence of temperature changes on the structure and the connection relationship between the structures. , so that the carrying device can carry the reactor more stably all the time, including maintaining the position of the reactor in the moving process is always fast, and can achieve better heat transfer, which is conducive to the reaction in the carried reactor and the driving of the reactor. So that the detection device can continuously collect signals from different parts of the reactor, and stably realize the detection of the sample.
  • FIG. 1 is a schematic perspective view of a sequencing system according to an embodiment of the present application.
  • FIG. 2 is an exploded schematic view of a carrying device according to an embodiment of the present application
  • FIG. 3 is a schematic structural diagram of a mobile platform according to an embodiment of the present application when a base is carried;
  • FIG. 4 is a schematic structural diagram of a base according to an embodiment of the present application.
  • FIG. 5 is a schematic structural diagram of a reactor according to an embodiment of the present application.
  • FIG. 6 is a schematic structural diagram of a base according to an embodiment of the present application.
  • FIG. 7 is a schematic side view of the mobile platform according to the embodiment of the present application when the base is carried;
  • FIG. 8 is a partial enlarged schematic diagram of FIG. 7 according to an embodiment of the present application.
  • FIG. 9 is a schematic longitudinal cross-sectional view of the carrying device carrying the reactor according to the embodiment of the present application.
  • FIG. 11 is a schematic structural diagram of a water bath according to an embodiment of the present application.
  • FIG. 12 is a schematic structural diagram of a heat dissipation plate according to an embodiment of the present application.
  • FIG. 13 is a schematic structural diagram of a cover plate according to an embodiment of the present application.
  • FIG. 14 is another schematic structural diagram of the heat dissipation plate according to the embodiment of the present application.
  • 15 is a schematic longitudinal cross-sectional view of the carrying device from another perspective of an embodiment of the present application.
  • FIG. 16 is an enlarged schematic diagram of a part in FIG. 15 of an embodiment of the present application.
  • FIG. 17 is a schematic structural diagram of a support seat according to an embodiment of the present application.
  • FIG. 18 is a schematic structural diagram of a thermally conductive plate according to an embodiment of the present application.
  • FIG. 19 is a schematic structural diagram of the reactor according to the embodiment of the present application from another perspective.
  • 20 is a schematic longitudinal cross-sectional view of the carrying device according to the embodiment of the present application from another perspective;
  • 21 is a schematic longitudinal cross-sectional view of the carrying device according to the embodiment of the present application at the first manifold;
  • 22 is a partial cross-sectional view of a first manifold of an embodiment of the present application.
  • 23 is a schematic longitudinal cross-sectional view of the carrying device of the embodiment of the present application at the second manifold;
  • 24 is a schematic structural diagram of an imaging device according to an embodiment of the present application.
  • 25 is a schematic structural diagram of a first light source according to an embodiment of the present application.
  • FIG. 26 is a schematic structural diagram of a fluid device according to an embodiment of the present application.
  • the carrying device 1000 the base 100 , the carrying surface 120 , the accommodating groove 122 , the first through hole 124 , the gap 126 , the temperature control assembly 200 , the heat conduction plate 220 , the first hole 222 , the second hole 224 ,
  • Reactor 300 chip frame 320, third hole 322, fourth hole 324, sheet 340, flow path 360, inlet 362, outlet 364, rigid plate 380,
  • Base 700 adjustment structure 720, fine adjustment nut 722, tension spring 724, mobile platform 800, table top body 820, first drive mechanism 840, first slide rail 842, first slide seat 844, second drive mechanism 860, second The slide rail 862, the second slide seat 864, the first support portion 864a, the second support portion 864b, the third through hole 864c, the guide member 866,
  • Fluidic device 2000 reservoir 60, multi-port valve 70, sample inlet 72, sample outlet 74, manifold 76, pump assembly 80, liquid collector 90,
  • Imaging device 3000 first light source 12, first light emitter 13, first beam splitter 14, third lens 15, first lens 16, fourth lens 17, second lens 18, beam splitting module 40, first reflecting surface 26.
  • first and second are only used for descriptive purposes, and should not be construed as indicating or implying relative importance or implying the number of indicated technical features. Thus, features defined as “first”, “second” may expressly or implicitly include one or more of said features. In the description of the present application, “plurality” means two or more, unless otherwise expressly and specifically defined.
  • the terms “installed”, “connected” and “connected” should be understood in a broad sense, for example, it may be a fixed connection or a detachable connection Connection, or integral connection; it can be mechanical connection, electrical connection or can communicate with each other; it can be directly connected or indirectly connected through an intermediate medium, it can be the internal communication of two elements or the interaction of two elements relation.
  • installed should be understood in a broad sense, for example, it may be a fixed connection or a detachable connection Connection, or integral connection; it can be mechanical connection, electrical connection or can communicate with each other; it can be directly connected or indirectly connected through an intermediate medium, it can be the internal communication of two elements or the interaction of two elements relation.
  • a first feature "on” or “under” a second feature may include direct contact between the first and second features, or may include the first and second features Not directly but through additional features between them.
  • the first feature being “above”, “over” and “above” the second feature includes the first feature being directly above and obliquely above the second feature, or simply means that the first feature is level higher than the second feature.
  • the first feature is “below”, “below” and “below” the second feature includes the first feature being directly below and diagonally below the second feature, or simply means that the first feature has a lower level than the second feature.
  • the so-called chip refers to a solid-phase substrate and has a surface capable of connecting or immobilizing target biomolecules.
  • the surface can be a curved surface or a flat surface.
  • Such techniques include, for example, immobilizing a large number of probes, such as oligonucleotide fragments, on the surface of a support, and/or hybridizing probes immobilized on the surface of a support to DNA or other target molecules (such as proteins, factors or small molecules),
  • both the probe and the biomolecule to be tested are nucleic acid molecules, and at least a part of the probe can complementarily bind to the biomolecule to be tested (based on the principle of complementary base pairing), so that the target biomolecule can be linked or immobilized on the surface of the solid-phase substrate .
  • the Z-axis referred to in this application is the shooting direction of the imaging component
  • the imaging component may be, for example, an optical imaging component, wherein the Z-axis is the optical axis of the optical imaging component, and the Z-axis is perpendicular to the plane formed by the X-axis and the Y-axis.
  • the working distance of the objective lens referred to in this application refers to the distance between the front edge of the objective lens and the surface of the sample when the sample is in focus.
  • an embodiment of the present application provides a sequencing system 10000 for detecting biological samples.
  • the sequencing system 10000 includes a carrier device 1000 , a fluid device 2000 , an imaging device 3000 and a computing device (not shown).
  • the carrying device 1000 is used for carrying the reactor 300 and adjusting the temperature of the reactor 300, and the reactor 300 is connected with a plurality of polynucleotides.
  • this embodiment provides a carrying device 1000 , including two bases 100 , a base 700 and a mobile platform 800 . In other embodiments, more than two bases 100 may also be included.
  • each base 100 has a carrying surface 120 for carrying the reactor 300 , and the carrying surface 120 is provided with an accommodating groove 122 for accommodating the reactor 300 .
  • the reactor 300 when sequencing is performed, the reactor 300 is placed on the receiving tank 122, so that the reactor 300 placed on the base 100 is more stable during the process of being moved.
  • the reactor 300 can provide a space for biochemical reactions, and can also be called a reaction chamber, such as a chip.
  • the reactor 300 includes a chip frame 320 and a sheet layer 340 disposed in the chip frame 320 .
  • the shape of the accommodating groove 122 can match the shape of the chip frame 320 of the reactor 300 , which is a rectangular accommodating groove 122 in this embodiment.
  • the base 700 included in the carrying device 1000 may be a hollow structure, and the top of the base 700 may be provided with an opening. It can be easily understood that the base 700 with the hollow structure can accommodate other components provided on the base 100 .
  • two bases 100 are placed in parallel at the openings on the base 700 , and each base 100 is connected to the base 700 through an adjustment structure 720 , and the adjustment structure 720 can lengthen or shorten the space between the base 100 and the base 700 and the base 100 is disposed on the top of the base 700 , so the height of the base 100 can be changed by adjusting the structure 720 .
  • the adjustment structure 720 in this embodiment includes a fine adjustment nut 722 and a tension spring 724 , and a plurality of fine adjustment nuts 722 are connected between a base 100 and the base 700 .
  • the adjustment directions of the fine adjustment nut 722 are respectively perpendicular to the first direction and the second direction, wherein the first direction and the second direction are both horizontal directions, so in this embodiment, the direction of the fine adjustment nut 722 is the vertical direction.
  • One effect of setting the fine adjustment nut 722 may be that the overall height of the entire base 100 can be adjusted through the fine adjustment nut 722. Specifically, each fine adjustment nut 722 can be adjusted separately, and then the base 100 can be adjusted after rising to a certain height. Leveling is performed to ensure the imaging effect. Another effect can be to change the inclination of the base 100, for example, by adjusting only the fine adjustment nut 722 on one side of the base 100, so that the base 100 on this side is slightly raised or slightly descend, so that the base 100 has a certain inclination angle with respect to the horizontal position.
  • the height difference between the surfaces of the respective sheets 340 in the two reactors 300 can be made not greater than 20% of the working distance of the objective lens in the imaging assembly.
  • a plurality of tension springs 724 are connected between a base 100 and the base 700, and the elastic directions of the tension springs 724 are also perpendicular to the first direction and the second direction respectively, and the base 100 receives the force from the tension springs 724 all the time.
  • the fine adjustment nut 722 and the tension spring 724 cooperate with each other, 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 generates There is also little to no shaking.
  • the carrying device 1000 further includes a moving platform 800 .
  • the moving platform 800 is located below the base 700 and can be used to support and move the base 700 .
  • the mobile platform 800 includes a table top body 820, a first driving mechanism 840 and a second driving mechanism 860.
  • the table top body 820 is connected to the base 700.
  • the bottom of the base 700 is provided with threaded holes for threading with the table top body 820. connect.
  • 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, then the first driving mechanism 840 can drive the table top body 820 to move in the first direction, and the first sliding seat 844 is mounted on the first sliding rail 842 and is driven by the first motor Moving downward along the first slide rail 842 , the table top body 820 is connected with the first sliding seat 844 , and with the movement of the first sliding seat 844 , the table top body 820 drives the base 700 to move.
  • the second driving mechanism 860 includes a second sliding rail 862, a second sliding seat 864 and a second motor (not shown in the figure).
  • the second sliding rail 862 is arranged in parallel with the second direction, then the second driving mechanism 860 can drive the table top body 820 to move in the second direction, and the second sliding seat 864 is mounted on the second sliding rail 862 and driven by the second motor Moving along the second sliding rail 862 , the first sliding rail 842 is disposed on the second sliding seat 864 .
  • the second sliding seat 864 in this embodiment includes a first support portion 864a and a second support portion 864b located on both sides of the first support portion 864a. One support portion 864a is connected to the other second support portion 864b in sequence.
  • the first support portion 864a has a cuboid structure
  • the first support portion 864a is provided with a slot along the first direction to form the first slide rail 842
  • the second support portion 864b has a slope, specifically the second support portion The greater the distance between the top of the 864b and the first support portion 864a along the second direction, the lower the height thereof, so the second sliding seat 864 is in the shape of a terrace as a whole.
  • a guide member 866 is provided in the second slide rail 862, and the guide member 866 is parallel to the second direction.
  • the second sliding seat 864 may include a first side and a second side opposite to the first side along the second direction.
  • the first side is the left side in FIG. 7
  • the second side is the right side in FIG. 7 .
  • the first side has a third through hole 864c matching with the guide member 866, and the guide member 866 extends through the third through hole 864c to the outside of the second sliding seat 864, of course, in other embodiments, the guide member 866 A matching third through hole 864c may also be provided on the second side.
  • the purpose of providing the guide member 866 is that compared with the first slide rail 842, the second slide rail 862 is longer in length and the weight of the components it carries is larger, the provision of the guide member 866 can make the second slide rail 862 longer.
  • the seat 864 can remain parallel to the second direction during movement so that the base 100 also remains stable during movement.
  • a plurality of pedestals 100 that can carry the reactors 300 can be arranged on the pedestal 700 , and the pedestal 700 is moved by the moving platform 800 to move the pedestals 100, multiple reactors 300 can be adjusted simultaneously.
  • the carrier device 1000 can better adjust the focal plane to meet the imaging requirements; by adjusting the base 100 and the base
  • the adjustment structure 720 between 700 can finely adjust, such as increasing or shortening the distance between the reactor 300 and the imaging component, and the imaging object such as the verticality of a certain field of view (FOV) on the reactor 300 and the optical axis.
  • the cooperation of the moving platform 800 and the adjustment structure 720 can easily and precisely realize the adjustment of the desired position/relationship of the reactor 300 and the imaging device 3000 .
  • biochemical reactions are generally involved, especially biochemical reactions involving biocatalysts such as proteases.
  • biocatalysts such as proteases.
  • Such biochemical reactions are sensitive to temperature, and generally it is necessary to control the temperature of the reaction environment, such as cooling or heating the chip, to ensure the effective progress of the biochemical reactions thereon.
  • the carrier device 1000 on the sequencing system 10000 in the present application further includes a temperature control assembly 200 for efficiently and stably controlling the temperature of the reactor 300, so that the biochemical reaction can be performed effectively.
  • the so-called semiconductor refrigeration sheet is based on the Peltier effect, so that the effect of cooling or heating can be achieved.
  • the principle of cooling or cooling is: when the current passes through the two phases When connecting conductors, there will be a temperature difference at the connection, that is, heat absorption and heat release at the connection.
  • the effect was discovered by the Frenchman Peltier (Jean-CharlesPeltier).
  • the amount of heat absorbed and released in the Peltier effect is determined by the magnitude of the current.
  • People have made cooling and heating elements based on the Peltier effect, such as Peltier cooling and heating fins. When the Peltier cooling and heating sheet is energized, one side absorbs heat (cooling) and the other side releases heat (heating).
  • the heat absorption surface and the heat release surface can be changed by changing the direction of the current.
  • the temperature control assembly 200 includes a refrigerator 240 , a heat dissipation module 260 and a control module 280 , and the refrigerator 240 has a first surface and a second surface opposite to each other.
  • the reactor 300 is placed on the bearing surface 120.
  • the bearing surface 120 is provided with an accommodating groove 122 for placing the reactor 300.
  • the bottom wall of the groove 122 is provided with a first through hole 124 . Then, when the bearing surface 120 carries the reactor 300 , the first surface of the refrigerator 240 is in contact with the reactor 300 through the first through hole 124 .
  • passing through the first through hole 124 means that the refrigerator 240 contacts the reactor 300 through the first through hole 124 from bottom to top, and the contact here includes both direct contact and indirect contact.
  • the reactor 300 is cooled or heated by direct contact heat transfer or indirect contact heat transfer.
  • the so-called direct contact is, for example, that the first surface of the refrigerator 240 is attached to the reactor 300
  • the indirect contact is, for example, the temperature control assembly 200 may further include a heat-conducting plate 220, so that the heat-conducting plate 220 abuts on the cooling plate 220.
  • a part of the heat-conducting plate 220 is located in the first through hole 124.
  • a heat-conducting adhesive with good thermal conductivity is used to bond the heat-conducting plate 220 and the refrigerator 240, so that the refrigerator 240 is connected to the refrigerator 240 through the heat-conducting plate 220.
  • Reactor 300 contacts.
  • the material of the heat conducting plate 220 is a metal material, such as a material containing silver or aluminum.
  • the heat-conducting plate 220 may be approximately in the shape of a cuboid, and the cross-sectional dimension of the heat-conducting plate 220 may be approximately the same as that of the refrigerator 240 , so that the structure between the heat-conducting plate 220 and the refrigerator 240 can be matched more compactly, which is conducive to efficient heat conduction.
  • the refrigerator 240 starts to work after being powered on. At this time, one of the first surface and the second surface starts to cool, and the other surface starts to heat. For example, after the refrigerator 240 works, the first side starts to cool, and the second side starts to heat. It can be understood that when the working current of the refrigerator 240 is different, the cooling type of the first side is different. For example, when the working current of the refrigerator 240 is forward, the first side cools; when the working current of the refrigerator 240 is reverse, the first side heats. Compared with other refrigeration elements, the refrigerator 240 has the advantages of being more environmentally friendly and not generating noise.
  • the heat dissipation module 260 is in contact with the second surface of the refrigerator 240 , for example, connected to the second surface through a paste-like substance with good thermal conductivity such as silicone grease, so as to take away the heat generated during the operation of the refrigerator 240 .
  • the heat dissipation module 260 includes a water bath 262 and a liquid component 264 .
  • the material of the water bath 262 can be a metal material, for example, the material of the water bath 262 is copper, aluminum and other materials.
  • the water bath 262 has a chamber for accommodating the cooling liquid, and the water bath 262 is provided with a liquid inlet 262e and a liquid outlet 262f which communicate with the chambers.
  • the water bath 262 includes a heat dissipation plate 2622 and a cover plate 2624 , a surface of the heat dissipation plate 2622 is provided with a flow channel 2626 for accommodating the cooling liquid, and the cover plate
  • the 2624 is sealed and closed on the flow channel 2626 to form a cavity.
  • a sealing ring 2628 is provided between the cover plate 2624 and the heat dissipation plate 2622, and the sealing ring 2628 can seal the gap between the cover plate 2624 and the heat dissipation plate 2622.
  • the flow channel 2626 is in a tortuous shape, which can further increase the circuit through which the cooling liquid flows, thereby enhancing the cooling effect of the water bath 262 .
  • the water bath 262 may include a heat dissipation plate 2622 and a cover plate 2624, and 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
  • the second heat dissipation area 2622b is provided with a third flow channel 262c and a fourth flow channel 262d.
  • each flow channel has a first end and a second end facing different, the first end of the first flow channel 262a is communicated with the first end of the second flow channel 262b, and the second end of the first flow channel 262a is connected to the liquid inlet
  • the port 262e is in communication
  • the second end of the third flow channel 262c is in communication with the second end of the fourth flow channel 262d
  • the first end of the fourth flow channel 262d is in communication with the liquid outlet 262f
  • the second end of the second flow channel 262b It communicates with the first end of the third flow channel 262c.
  • FIG. 14 takes FIG. 14 as an example to illustrate a layout of the flow channels.
  • the flow channels may also be laid out in other ways.
  • the second heat dissipation area 2622b is located on the side where the first end of each flow channel in the first heat dissipation area 2622a is located.
  • the direction to the left in the figure is the direction of the first end of each flow channel, and the direction to the right in the figure is the direction of the second end of each flow channel.
  • the cover plate 2624 is connected to the cooling plate 2622 and covers the first flow channel 262a and the second flow channel. 262b, the third flow channel 262c and the fourth flow channel 262d.
  • first flow channel 262a, the second flow channel 262b, the third flow channel 262c and the fourth flow channel 262d flow in sequence, so it can also be considered that the entire flow channel is divided into four sections, so as to obtain the above four flow channels road.
  • At least one flow channel in the first heat dissipation area 2622a is in a tortuous shape
  • at least one flow channel in the second heat dissipation area 2622b is in a tortuous shape
  • the second flow channel 262b and the fourth flow channel 262d are respectively in a tortuous shape
  • the first flow channel 262a and the third flow channel 262c are respectively straight flow channels.
  • the tortuous flow channel can extend the length of the coolant flow path in a single flow channel.
  • the first flow channel 262a may also be in a zigzag shape
  • the third flow channel 262c may also be in a zigzag shape.
  • the liquid inlet 262e and the liquid outlet 262f are approximately located near the middle of the entire water bath 262, and the cooling liquid flows into the first end of the first flow channel 262a from the liquid inlet 262e, and passes through the first flow channel 262a It reaches the second end of the first flow channel 262a after a straight section of the first flow channel 262a, then enters the third flow channel 262c after passing through the tortuous second flow channel 262b, and then enters the tortuous fourth flow channel 262d after passing through a straight section of the third flow channel 262c. , and finally flows out from the liquid outlet 262f at the second end of the fourth flow channel 262d.
  • the above-mentioned flow channel design of the water bath 262 makes full use of the space of the water bath 262 and extends the length of the flow path of the cooling liquid under the same volume, thereby bringing about a better heat dissipation effect.
  • the liquid assembly 264 includes a connected pump 2642 and a cooler 2644, the pump 2642 is used to provide power to the cooling liquid, the cooler 2644 is used to cool the cooling liquid, and the pump 2642 is connected to the water through the liquid inlet 262e.
  • the bathroom 262 is connected, the cooler 2644 is connected to the water bathroom 262 through the liquid outlet 262f, that is, the pump 2642 is connected to the liquid inlet 262e through pipelines, and the cooler 2644 is connected to the liquid outlet 262f through other pipelines.
  • the cooling liquid is discharged from the liquid outlet 262f under the action of the pump 2642 and then cooled by the cooler 2644.
  • the cooler 2644 can use the existing cooling structure, for example, it can include a copper box, which is filled with refrigerant, the pipeline for the cooling liquid to flow through the box, and the cooling liquid flows in the pipeline and the box.
  • the coolant undergoes heat exchange, so as to achieve the purpose of cooling the coolant.
  • connection sequence of the cooler 2644 and the pump 2642 can also be changed.
  • the pump 2642 is connected to the water bath 262 through the liquid outlet 262f
  • the cooler 2644 is connected to the water bath 262 through the inlet port 262f.
  • the liquid port 262e is connected to the water bath 262.
  • the cooling liquid in the water bath 262 is discharged from the liquid outlet 262f under the action of the pump 2642, and passes through the cooler 2644 for heat dissipation before entering the water bath 262.
  • the liquid component 264 further includes a water reservoir 2644, and the water reservoir 2644 stores the cooling liquid, so as to provide the cooling liquid for the water bath 262.
  • the pump 2642 and the cooler 2644 are connected to the water tank 262 through pipelines, respectively. Reservoir 2644 is connected.
  • the cooling liquid is drawn out from the reservoir 2644 under the action of the pump 2642, passes through the pump 2642 and reaches the water bath 262 to absorb heat, and then passes through the cooler 2644 to dissipate heat and return to the reservoir 2644.
  • the cooling liquid in the water bath 262 is continuously pumped out under the action of the pump 2642, returns to the reservoir 2644 and flows through the cooler 2644 to be cooled, and then enters the water bath 262 to absorb heat.
  • the cooling liquid enters the first flow channel 262a from the liquid inlet 262e on the first flow channel 262a, and flows through the first flow channel 262a and the second flow channel 262b in sequence.
  • 2622a realizes multiple flows from one end of the flow channel to the other end, extending the flow path of the cooling liquid such as condensed water, which can improve the heat dissipation capacity, and at least one of the first flow channel 262a and the second flow channel 262b
  • the zigzag shape further extends the coolant flow path within the same volume/space.
  • the cooler 2644 further includes a cooling row, the cooling row is provided with a channel, and the channel is provided with a plurality of cooling fins for dissipating the cooling liquid flowing through the cooler 2644. Further, the cooler 2644 also A fan may be included that generates airflow towards the cooling row, resulting in better cooling.
  • control module 280 is connected to the refrigerator 240 and the heat dissipation module 260 for detecting the temperature of the reactor 300 and controlling the operation of the heat dissipation module 260 according to the detected temperature.
  • control module 280 controls the working state of the pump 2642 according to the temperature of the reactor 300 , so as to control the operation of the heat dissipation module 260 .
  • the temperature suitable for the reactor 300 has a preset range
  • the control module 280 detects that the temperature of the reactor 300 is much lower than the maximum temperature value within the preset range (still within the preset range)
  • the control module 280 can control the pump 2642 to stop working, so that the cooling liquid in the water bath 262 stops flowing.
  • the temperature of the reactor 300 is prevented from falling too low, and on the other hand, the energy consumption is also reduced.
  • the control module 280 detects When the temperature of the reactor 300 is much higher than the minimum temperature within the preset range (still within the preset range), the control module 280 can control the pump 2642 to start working again, drive the cooling liquid to flow, and improve the heat dissipation capacity.
  • the control module 280 includes a microprocessor 284 and a temperature sensor 282 electrically connected to the microprocessor 284 .
  • the temperature sensor 282 may be provided on the thermally conductive plate 220 for detecting the thermally conductive plate 220
  • the temperature of the reactor 300 is estimated by the temperature of the thermal conductive plate 220.
  • the microprocessor 284 can also be electrically connected to the pump 2642, and can control the pump 2642 to work or stop. For example, a relay controlled by the microprocessor 284 is set in the working circuit of the pump 2642, so as to control the closing or opening of the working circuit of the pump 2642. open.
  • the control module 280 may also control the working current of the refrigerator 240 according to the temperature sensed by the temperature sensor 282 .
  • the microprocessor 284 can control to increase the working current of the refrigerator 240 to increase the power of the refrigerator 240, so that the refrigerator 240 can improve the heat-conducting plate 220.
  • 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 .
  • the temperature sensor 282 can be a non-contact temperature sensor 282, for example, the temperature sensor 282 is an infrared temperature sensor.
  • the cooling liquid in the above-mentioned water bath 262 may be water. In this way, the cost of the carrier device 1000 can be reduced.
  • the cooling liquid may be a specially made cooling liquid, without any limitation. The specially made coolant can ensure that the thermal conductivity can reach a more ideal state.
  • the temperature control component 200 included in the sequencing system 10000 can adjust the temperature of the reactor 300, for example, use a cooling sheet to cool or heat the chip, and then use a metal heat sink or a water cooling system to discharge the temperature. Take heat, etc.
  • the increase and decrease of temperature will cause deformation of the relevant mechanical firmware, such as thermal expansion and cooling contraction.
  • the temperature control assembly 200 and the structures directly connected or in contact with the above structures are easily affected, for example, the base 100 of the carrying device 1000 in the embodiment of the present application.
  • the entire temperature control assembly 200 can be in contact with the reactor 300 placed in the accommodating tank through the first through hole 124 from bottom to top.
  • a portion of the thermally conductive plate 220 is located in the first through hole 124 .
  • 15 and FIG. 16 in the horizontal direction shown in the figures, there is a certain gap between the edge of the heat-conducting plate 220 and the inner wall of the first through hole 124 , and the gap is used for the heat of the heat-conducting plate 220 .
  • Expansion and contraction provide enough deformation space.
  • the principle is similar to that there is a certain gap between the adjacent rails on the railway, leaving enough space for the deformation of the rails when the temperature changes, so as to avoid extrusion between the adjacent rails. Therefore, in this embodiment, the heat conduction plate 220 and the base 100 can be prevented from being pressed against each other as much as possible.
  • the carrying device 1000 further includes a connecting component, and the connecting component is used for connecting the base 100 and the temperature control component 200 .
  • the connection assembly includes a support base 420 , a first positioning structure 440 and a second positioning structure 460 .
  • the heat-conducting plate 220 and the base 100 are connected through the support seat 420, and the support seat 420 is made of a material whose thermal deformation degree is smaller than that of the heat-conducting plate 220, so that the deformation amount of the support seat 420 is smaller under the same temperature change condition.
  • the support base 420 is directly connected to the base 100 , so the influence on the base 100 is also small.
  • the support base 420 can be installed at the bottom of the base 100 , and a through groove 422 is provided in the center of the support base 420 , and the through groove 422 communicates with the first through hole 124 on the base 100 ,
  • the size of the through groove 422 may be smaller than the size 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 groove 422 .
  • the through grooves 422 can function as heat insulation.
  • the support base 420 may not be provided with the through slot 422, and the heat dissipation module 260 is located above the support base 420.
  • the groove of the temperature control component 200 located outside the first through hole 124 (in the case where a part of the temperature control component 200 is located in the first through hole 124 and a part is located outside the first through hole 124 ).
  • 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 positioning structures can pass through the first side.
  • the through hole 124 extends above the bottom wall of the receiving groove. In other embodiments, the two positioning structures may also directly pass through the base 100 and extend above the bottom wall of the accommodating groove.
  • the thermally conductive plate 220 is provided with a first hole 222 that can be matched with the first positioning structure 440 and a second hole 224 that can be matched with the second positioning structure 460 respectively.
  • the first hole 222 is a waist hole, and the waist hole is opposite to the waist hole. For the round hole, it has a higher deformation tolerance in its length direction.
  • the thermally conductive plate 220 expands under heat or shrinks under cold, it can deform along the length direction of the waist hole, and maintain the first hole 222 and the first position.
  • the matching relationship of the structures 440 ensures that the thermally conductive plate 220 is still closely matched with the positioning structure after being heated, and the position does not shift.
  • the first positioning structure 440 includes a first positioning post 442 that is matched with the first hole 222 .
  • the first positioning post 442 includes a first end and a second end opposite to the first end. The first end is connected to the support seat 420 , the second end of the first positioning post 442 is provided with a first positioning ball 444 , and the heat conducting plate 220 is located between the first positioning ball 444 and the support seat 420 .
  • the second positioning structure 460 includes a second positioning post 462 matched with the second hole 224 , the second positioning post 462 includes a first end and a second end opposite to the first end, and the first end of the second positioning post 462 is connected to the support
  • the seat 420 is connected, the second end of the second positioning post 462 is provided with a second positioning ball 464, the heat conducting plate 220 is located between the second positioning ball 464 and the support seat 420, and the reactor 300 is provided with a first positioning ball 444
  • the third hole for matching and the fourth hole for matching with the second positioning ball 464 is provided.
  • the two positioning posts cooperate with each other to position the heat-conducting plate 220 at the position to be in contact with the reactor 300 , and the arrangement of the two positioning balls, on the one hand, also positions the reactor 300 when it is placed, In addition, the placed reactor 300 is prevented from being displaced. On the other hand, the heat-conducting plate 220 cannot pass through the two positioning balls upward, and the heat-conducting plate 220 can be restricted between the positioning balls and the refrigerator.
  • one of the first positioning structure 440 and the second positioning structure 460 includes a positioning column, which can also meet the requirements of the present invention.
  • a thermally conductive adhesive with good thermal conductivity is used to bond the thermally conductive plate 220 and the refrigerator to further ensure that the thermally conductive plate 220 will not be separated from the refrigerator.
  • the first side of the support base 420 is provided with a first protruding portion 424 for supporting the thermally conductive plate 220 , the first protruding portion 424 is located in the first through hole 124 , and the top of the first protruding portion 424 is In contact with the bottom of the heat conducting plate 220 , there is also a gap between the first protruding portion 424 and the inner wall of the first through hole 124 , and the first positioning structure 440 is disposed on the first protruding portion 424 .
  • the second side of the support base 420 is provided with a second protruding portion 426 for supporting the thermally conductive plate 220 .
  • the second protruding portion 426 is located in the first through hole 124 and has a gap with the inner wall of the first through hole 124 .
  • the two positioning structures 460 are disposed on the second protruding portion 426 . In this way, the two protrusions can reduce the contact area between the heat-conducting plate 220 and the support seat 420 , and further reduce the influence of the heat-conducting heat of the heat-conducting plate 220 on the support seat 420 .
  • the heat-conducting plate 220 that is greatly deformed by the temperature is not directly in contact with or connected to the base 100, but is connected through the support seat 420.
  • the heat-conducting plate 220 is connected to the inner wall of the first through hole 124. There is a gap between them, so that even if the heat-conducting plate 220 is thermally expanded, it will not squeeze the base 100 , which can prolong the service life of the base 100 .
  • the increase and decrease of the temperature will not only deform the relevant mechanical firmware, but may also cause the temperature control assembly 200 to contact the reactor 300. part is deformed by heat.
  • a squeezing force will be generated on the reactor 300, so that the reactor 300 is also deformed, thereby causing the flow path 360 in the reactor 300 to deform, affecting the biochemical reaction and/or increasing the focus tracking signal. Difficulty of collection.
  • the reactor 300 further includes a rigid plate 380, the rigid plate 380 is arranged under the sheet layer 340, the rigid plate 380 can be a metal plate such as an aluminum plate, and the temperature control component 200 is in contact with reactor 300 through rigid plate 380 .
  • the temperature control assembly 200 includes a heat conduction plate 220, a refrigerator 240 and a water bath 260 that are connected in sequence, and the heat conduction plate 220, the refrigerator 240 and the water bath 260 are stacked in sequence, and the entire temperature control assembly 200 can be worn from bottom to top
  • the first through hole 124 is in contact with the reactor 300 placed in the receiving groove 122 , wherein the thermally conductive plate 220 is in direct contact with the rigid plate 380 .
  • the connecting assembly further includes a first connecting member 480 and a second connecting member 482 which are connected.
  • the first connecting member 480 is connected to the base 100
  • the second connecting member 482 is connected to the water bath 260
  • the first connecting member 480 is a rigid connecting member
  • the second connecting member 482 is an elastic connecting member.
  • the first connecting member 480 is a screw rod
  • the second connecting member 482 is a spring
  • the screw rod and the spring are respectively arranged in the vertical direction.
  • the rod portion of the screw rod passes through the cover plate 264 and is threadedly connected to 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 head of the cover plate 264 .
  • an upward force is applied to the entire temperature control assembly 200 , and the cover plate 264 is pressed against the bottom of the support base 420 .
  • the reactor 300 is placed in the holding tank 122 .
  • the rigid plate 380 will first come into contact with the heat-conducting plate 220 .
  • the spring is compressed, and the temperature control assembly 200 moves downward until the chip frame 320 of the reactor 300 is in contact with the carrier. face 120 contacts.
  • the temperature control assembly 200 cools or heats the reactor 300
  • the top of the temperature control assembly 200 is in contact with the rigid plate 380.
  • the bottom is in contact with the spring, so the deformation is likely to occur downward, and the reactor 300 is not easily squeezed by the deformation.
  • the refrigerator 240 is flexibly connected to the water bath 262, so the extrusion of the refrigerator 240 towards the reactor 300 is also small; and the elastic force or extrusion can be transmitted downward to be released, showing These forces mainly cause the deformation and connection strength/strength of the refrigerator 240 and the water bath 262 under the carrying device 1000 , so that the carrying device 1000 can be stably and stably carried and moved, and the mechanical service life can be prolonged.
  • the support base 420 can be made of a relatively soft material.
  • the spring is compressed, and the temperature control assembly 200 moves downward.
  • the temperature control assembly 200 cannot continue to move downward after the thermal conductive plate 220 is in contact with the top of the support base 420 , so the reactor 300 stops moving.
  • the temperature control assembly 200 may stop moving after reaching the limit position connected to the base 100 .
  • the sequencing system 10000 and the carrying device 1000 include a temperature control assembly 200 for cooling or heating the reactor 300.
  • the temperature control assembly 200 and the reactor 300 are rigidly connected, so the temperature The temperature of the control assembly 200 and/or the deformation of the reactor 300 caused by heating will not basically affect the relative positional relationship between the two.
  • the device 1000 has less tolerance to the deformation of the supported and connected reactor 300 (reaction chamber), so that the reactor 300 placed therein can be tightly and firmly connected to the supporting device 1000; in this way, it is beneficial for the biochemical reaction process.
  • Accurate focusing and fast and stable focusing on the designated surface or part of the reactor 300 are beneficial to the acquisition of clear images of signals in the reactor and the realization of accurate sequencing based on the clear images.
  • imaging or cleaning or reaction reagents are usually passed into the reactor 300 to achieve the corresponding purpose. These reagents are generally placed in the reagent box.
  • 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 these reagents are introduced by the power device. into the reactor 300 flow path 360 of the reactor 300 for the corresponding process.
  • the flow path 360 of the sequencing system 10000 is established by connecting the various components with hoses, and in order to avoid liquid leakage and to connect more closely, a manifold is used with the reactor 300 including a plurality of flow paths 360 connect.
  • a manifold is used with the reactor 300 including a plurality of flow paths 360 connect.
  • the connection between the manifold and the reactor 300 will inevitably have different degrees of liquid leakage.
  • the support member 660 supporting the manifold is provided below the manifold, the support member 660 is easily damaged by the accumulation of fluid, which affects the performance stability of the carrying device 1000 and even the entire sequencing system 10000.
  • manifold mentioned in this application refers to the general name of the liquid inlet pipeline and the liquid outlet pipeline between the hose of the self-fluid system and the reactor 300 .
  • the carrying device 1000 in this embodiment further includes a fluid connector and a support structure 600 .
  • the reactor 300 has four flow paths 360, and the inlet and outlet of each flow path 360 may be located at the bottom of the reactor 300. In other embodiments, the reactor 300 may also be There is one or other number of flow paths 360 .
  • the base 100 includes a first side and a second side opposite to the second side.
  • the inlet of the flow path 360 in the reactor 300 may be close to the first side of the base 100
  • the flow path 360 of the reactor 300 may be close to the first side of the base 100
  • the outlet of the base 100 may be close to the second side.
  • the fluid connector communicates with the flow path 360 of the reactor 300, the fluid connector can pass through the base 100 from bottom to top, and the fluid connector is located in the reactor 300 and placed in the accommodating tank After 122 , the position that communicates with the inlet and outlet of the flow path 360 .
  • the fluid connection member includes a first manifold 520 and a second manifold 540 , and the first manifold 520 is located on the first side of the base 100 , as shown in FIGS. 21 and 21 .
  • FIG. 22 shows a schematic longitudinal cross-sectional view of a first manifold 520 of a structure, which has four inlet flow channels 522 for communicating with the inlets of the four flow channels 360 in the reactor 300 .
  • the second manifold 540 is located on the second side of the base 100 , as shown in FIG.
  • FIG. 23 which is a schematic longitudinal interface diagram of the second manifold 540 of a structure, which has an outlet flow channel 524 in which four branches merge into one main channel , the liquids discharged from the outlets of the four flow paths 360 of the reactor 300 converge on the main path of the outlet flow path 524 .
  • the internal flow channels are manifolds of other structures.
  • the support structure 600 is used to support the fluid connection.
  • the support structure 600 is located below the fluid connection and connected to the base 100 , so as to fix the fluid connection on the base 100 .
  • the fluid connector includes a first manifold 520 and a second manifold 540.
  • the supporting structure 600 also has two, which are respectively used to support the first manifold 520 and the second manifold 540, namely, the first manifold 520 and the second manifold 540.
  • the manifold 520 and the second manifold 540 are connected to the base 100 through the support structure 600 .
  • the following takes the support structure 600 under the first manifold 520 as an example for description, and the support structure 600 under the second manifold 540 is also the same.
  • the support structure 600 includes a support surface 620 for supporting the first manifold 520 and a support member 660 .
  • the support structure 600 may have a substantially U-shaped structure, and two ends of the U-shaped opening are screwed with the base 100 .
  • the bottom wall of the U-shaped structure can be used as the support surface 620 of the support structure 600.
  • the support surface 620 is provided with a first groove 640, one end of the support member 660 is set in the first groove 640, and the other end of the support member 660 is connected to the first groove
  • the manifold 520 is provided with a second through hole 624 in the first groove 640 .
  • the second through hole 624 is located on the bottom wall of the first groove 640 , and the radius of the second through hole 624 is smaller than the size that one end of the support member 660 can pass through, so the support member 660 will not slip from the second through hole 624 .
  • the bottom of the first manifold 520 has a second groove 524 matched with the other end of the support member 660 , and the other end of the support member 660 abuts in the second groove 524
  • the support member 660 is a spring and there may be a gap between the first manifold 520 and the support surface 620.
  • the first manifold 520 will press the spring downward.
  • the spring can elastically abut the first manifold 520 on the reactor 300 .
  • the two lateral sides of the first manifold 520 in the horizontal direction may have two connecting parts 526 respectively.
  • the support surface 620 is provided with a third positioning structure 680
  • the first manifold 520 is provided with a fourth positioning structure 530.
  • the third positioning structure 680 includes positioning posts 682
  • the fourth positioning structure 530 includes The positioning grooves 532 matched with the positioning posts 682 , that is, the positioning posts 682 on the support structure 600 are inserted into the positioning grooves 532 on the first manifold 520 to complete the positioning.
  • the third positioning structure 680 includes positioning grooves 532
  • the fourth positioning structure 530 includes a positioning post 682 matched with the positioning groove 532 .
  • the supports 660 are two and symmetrically arranged so that the first manifold 520 is supported more stably.
  • the carrier device 1000 of any of the above-mentioned embodiments and the sequencing system 10000 including the carrier device 1000 are connected to the reactor 300 provided with the flow path 360 by including the fluid connector, so as to realize the fluid connector and the flow path 360 in the reactor 300 of connectivity.
  • the fluid connection is fixed in position through the cooperation of the support surface 620 in the support structure 600 and the support 660 .
  • the liquid flowing to the support member 660 along the fluid connection member can be discharged from the second through hole 624 in the first groove 640, thereby preventing One end of the support member 660 is immersed in the liquid, which ensures the normal use of the support structure 600 and makes the performance of the sequencing system 10000 more stable.
  • the present application also provides an imaging device 3000, which is located above the carrying device 1000, and is used to excite the reactor 300 to emit optical signals and collect at least a part of the optical signals.
  • the imaging device 3000 may include a laser generator and a camera, the laser generated by the laser generator is irradiated on the sheet layer 240 after reacting with the reagent on the reactor 300, and the camera collects the image information, and the image information includes the sheet layer 240.
  • the fluorescence information emitted by the layer 240 after being irradiated by the laser can be analyzed to obtain the sequencing result according to the fluorescence information.
  • an imaging device 3000 includes a first light source 12 , a first lens 16 and a beam splitting module 40 , and the beam splitting module 40 includes a first beam splitter 14 and a second lens 18 , a first camera 20 and a second camera 22 .
  • the first lens 16 is used for receiving the first light beam from the first light source 12 and collimating the light beam onto the reactor 300 , and for receiving and collimating the light beam from the reactor 300 .
  • 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 beam splitter 14 is used to split the focused beam from the second lens 18 into a second beam and a third 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.
  • the beam splitter 14 divides the light into the second beam and the third beam, which can reduce the use of optical elements and shorten the optical path length of the splitting light, so that the total optical path length of the imaging device 3000 is reduced.
  • the shortening is beneficial to the miniaturization of the imaging device 3000 and the industrialization.
  • the nucleic acid sample to be tested can be placed in the reactor 300, such as in a chip.
  • the first light source 12 may be a laser light source.
  • the chip includes a substrate, the substrate is provided with a flow channel, and the substrate is provided with glass.
  • the first beam splitter 14 splits the fluorescent convergent beam into a second beam and a third beam
  • the first camera 20 receives the second beam
  • the second camera 22 receives the third beam
  • a first image and a second image of the field of view are acquired respectively.
  • the first light source 12 may include a first light emitter 13 and a third lens 15 , and the first light beam is a light beam emitted by the first light emitter 13 passing through the third lens 15 After the collimated beam, the first beam is focused to the back focal plane of the first lens 16 through the fourth lens 17 , and then is collimated and incident on the reactor 300 through the first lens 16 .
  • the first light source 12 also includes a fiber optic coupler, such as a single mode light coupler.
  • 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 surface of the chip at a greater than critical angle, and total internal reflection occurs, which is generated on the lower surface of the chip glass.
  • Evanescent field evanescent wave. The fluorescence emitted by the excited fluorescent molecules in the evanescent field is received by the first lens 16 .
  • the light beam from the reactor 300 received by the first lens 16 is the light beam emitted by the sample under test in the reactor 300 .
  • the image sensors of the first camera 20 and the second camera 22 may adopt CCD or CMOS.
  • the image sensors used by the first camera 20 and the second camera 22 are of the same type, for example, both are CCD or both are CMOS.
  • the first beam splitter 14 may be a dichroic mirror.
  • the second beam is the transmitted beam of the first beam splitter 14
  • the third beam is the reflected beam of the first beam splitter 14 .
  • the first camera 20 and the second camera 22 are disposed at 90 degrees or 270 degrees. In this way, it is convenient to configure multiple cameras of the first camera 20 and the second camera 22 into the imaging device 3000 in a limited space.
  • the first beam splitter 14 has a first reflection surface 26 , the angle between the first reflection surface 26 and the horizontal plane is 45 degrees, and incident on a part of the first reflection surface 26 along the horizontal direction The light beam is reflected and turned by 90 degrees to reach the second camera 22 , while another part of the light beam incident on the first reflecting surface 26 in the horizontal direction passes through the first reflecting surface 26 and is incident on the first camera 20 .
  • the first camera 20 and the second camera 22 are arranged 90 degrees clockwise and 270 degrees counterclockwise.
  • the sample to be tested in the reactor 300 has two fluorescent labels, such as Cy3 and Atto647N, and the emission wavelengths of the two fluorescent molecules are 550-620 nm and 650-750 nm (the peaks are about 564 nm, respectively). and 670nm);
  • the first beam splitter 14 is a dichroic mirror, the dichroic mirror has a high transmittance for light with a wavelength of 550-620nm, and a high reflectance for light above 650nm.
  • the so-called fluorescently labeled nucleotide reagents include four types of nucleotide reagents, A, T, C and G, and different kinds of nucleotide reagents can be stored in different containers respectively.
  • four nucleotides carry the same fluorescent label, and during DNA sequencing, each round of sequencing reaction includes four base extension reactions, and the four base extension reactions are sequentially adding the four nucleotides and obtain the corresponding image.
  • each round of sequencing reaction includes two base extension reactions.
  • the nucleic acid to be tested, the enzyme, and the first fluorescent label and the second fluorescent are mixed in the flow path to react, and the first light source 12 simultaneously emits the first laser and the second laser to enter a specific field of view of the chip through the first lens 16, and the first fluorescent marker of the field of view is
  • the first and second fluorescent markers are excited by the first laser and the second laser to emit first and second fluorescence, respectively, and the first and second fluorescence are condensed to the first beam splitter 14 through the first lens 16 and the second lens 18 ( dichroic mirror), the dichroic mirror separates the converged first and 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, thus, respectively A first image and a second image formed by the first fluorescence and the second fluorescence of the field of view are obtained.
  • each round of sequencing reaction includes a base extension reaction.
  • the nucleic acid to be tested, the enzyme, and the above four nucleotide reagents The first light source 12 simultaneously emits the first laser and the second laser through the first lens 16 to enter the specific field of view of the chip, and the fluorescent markers in the field of view are excited by the first laser and the second laser respectively.
  • the fluorescence from fluorescent marker a is focused on the image plane of the first camera 20, and the fluorescence from fluorescent marker b is focused on the image plane of the second camera 22, thereby obtaining the first image and the second image of the field of view respectively.
  • Base calling/sequencing is achieved by combining first and second images of different rounds of sequencing reactions and merging information from the first and second images of the same round of sequencing reactions.
  • an embodiment of the present application provides a sequencing system 10000 , including a mobile platform 800 and an imaging device 3000 .
  • the mobile platform is used to carry the reactor 300
  • the imaging device 3000 is the imaging device 3000 in any of the above embodiments.
  • the above-mentioned sequencing system 10000 since it includes the imaging device 3000 having any of the above-mentioned technical features and advantages, has a compact structure, which is favorable for miniaturization and industrialization.
  • the mobile platform 800 is movable.
  • the moving platform 800 can drive the reactor 300 to move relative to the imaging device 3000 , for example, move along the direction perpendicular to the optical axis of the first lens 16 , or move along the direction parallel to the optical axis of the first lens 16 , or move along the direction inclined to the first lens 16 .
  • 16 moves in the direction of the optical axis, so that different positions of the reactor 300 are located directly under the first lens 16, so that the sequencing system 10000 including the imaging device 3000 can be used to realize the image acquisition of the reactor 300, thereby realizing sequence determination.
  • the sequencing system 10000 according to the embodiment of the present application may include the imaging device 3000 according to any of the foregoing embodiments.
  • the sequencing system 10000 of the embodiment of the present application further includes a computing device, the computing device can be operably coupled with the imaging device 3000 , and the computing device can be used to obtain an instruction set of the fluorescence signal from the imaging device 3000 .
  • the fluorescence signal collected by the imaging device 3000 is, for example, an image
  • the computing device acquires the image set from the imaging device 3000, processes and recognizes the information on the image to recognize the sequence determination.
  • Embodiments of the present application provide a fluidic device 2000, which is connected to the carrier device 1000 and used to controllably move one or more fluorescently labeled reagents to the reactor 300 to contact the polynucleotide.
  • the fluid device 2000 includes a reservoir 60 and a multi-port valve 70 .
  • the storage 60 is used to store solutions, and the solutions include a variety of solutions, such as reaction solutions, buffer solutions, cleaning solutions and/or purified water, etc., including reagents for different reactions or different steps of a reaction;
  • the multi-port valve 70 is provided with multiple A sample inlet 72 and a sample outlet 74, wherein the sample inlet 72 is used for the reagent to enter the multi-port valve 70, and the sample outlet 74 can be selectively communicated with one of the sample inlets 72, and is then realized through the set manifold 76 Connections to multiple flow paths within the reactor 300 for reagents to move from the sample outlet 74 to the reactor 300 to contact the polynucleotides.
  • the carrier device 1000 of the sequencing system 10000 may include multiple bases 100, and correspondingly, multiple reactors 300 may also be provided.
  • the multiple injection ports 72 of the multi-port valve 70 allow multiple Each of the reactors 300 can enter different liquids, thereby realizing multiple rounds/repeated reactions, and the setting of the multi-port valve 70 can realize the injection of multiple reagents to meet the biochemical process of sequencing, and also avoid cross-contamination between reagents.
  • the fluidic device 2000 may also include a pump assembly 80 and a sump 90 .
  • the pump assembly 80 is used as a negative pressure power source, so that the reagent flows into the flow path of the reactor 300 under the action of negative pressure to carry out a biochemical reaction, and the liquid collector 90 can collect the liquid flowing out of the multiple reactors 300.

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Abstract

Système de séquençage comprenant un appareil de support utilisé pour supporter un réacteur et ajuster la température du réacteur, le réacteur étant relié à une pluralité de polynucléotides, l'appareil de support comprenant : une base présentant une surface de support pour supporter le réacteur; un ensemble de régulation de température comprenant une plaque de transfert de chaleur, un réfrigérateur et un module de dissipation de chaleur qui sont tous reliés les uns aux autres, le réfrigérateur étant relié au réacteur au moyen de la plaque de transfert de chaleur, et, lorsque le réacteur est placé sur la surface de support, la plaque de transfert de chaleur étant reliée de manière rigide au réacteur; et un ensemble de liaison reliant la base à l'ensemble de régulation de température, l'ensemble de liaison comprenant un siège de support, et la plaque de transfert de chaleur étant reliée à la base au moyen du siège de support; et le système de séquençage comprenant en outre un appareil de fluide relié à l'appareil de support et utilisé pour déplacer de manière contrôlée un ou plusieurs réactifs marqués par fluorescence vers le réacteur pour entrer en contact avec les polynucléotides; un appareil d'imagerie positionné au-dessus de l'appareil de support et utilisé pour exciter et collecter la fluorescence générée par des marqueurs fluorescents; et un appareil informatique fonctionnellement couplé à l'appareil d'imagerie, et comprenant un ensemble d'instructions pour acquérir un signal de fluorescence à partir de l'appareil d'imagerie.
PCT/CN2021/099329 2020-10-10 2021-06-10 Système de séquençage et appareil de support WO2022073357A1 (fr)

Applications Claiming Priority (8)

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CN202022251300.0 2020-10-10
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116769591A (zh) * 2023-08-28 2023-09-19 四川杰莱美科技有限公司 一种实时荧光定量pcr仪
CN118090608A (zh) * 2024-04-22 2024-05-28 深圳市真迈生物科技有限公司 分析仪和分析系统

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007149696A1 (fr) * 2006-06-23 2007-12-27 Applera Corporation Systèmes et procédés de refroidissement dans des instruments d'analyses biologiques
CN102533526A (zh) * 2011-12-31 2012-07-04 盛司潼 一种基因测序仪
CN207215686U (zh) * 2017-09-20 2018-04-10 深圳市瀚海基因生物科技有限公司 光学检测系统及序列测定系统
CN108018195A (zh) * 2018-01-23 2018-05-11 深圳市瀚海基因生物科技有限公司 承载模块、核酸加载装置及用途
CN208938659U (zh) * 2018-09-13 2019-06-04 深圳市瀚海基因生物科技有限公司 测序系统
CN110904206A (zh) * 2019-12-18 2020-03-24 深圳市真迈生物科技有限公司 液路系统、生物分子分析系统及核酸序列测定系统
CN111308726A (zh) * 2018-12-12 2020-06-19 深圳市真迈生物科技有限公司 光学系统、调校光学系统的方法和测序系统
CN211111948U (zh) * 2018-09-13 2020-07-28 深圳市真迈生物科技有限公司 承载装置和测序系统

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007149696A1 (fr) * 2006-06-23 2007-12-27 Applera Corporation Systèmes et procédés de refroidissement dans des instruments d'analyses biologiques
CN102533526A (zh) * 2011-12-31 2012-07-04 盛司潼 一种基因测序仪
CN207215686U (zh) * 2017-09-20 2018-04-10 深圳市瀚海基因生物科技有限公司 光学检测系统及序列测定系统
CN108018195A (zh) * 2018-01-23 2018-05-11 深圳市瀚海基因生物科技有限公司 承载模块、核酸加载装置及用途
CN208938659U (zh) * 2018-09-13 2019-06-04 深圳市瀚海基因生物科技有限公司 测序系统
CN211111948U (zh) * 2018-09-13 2020-07-28 深圳市真迈生物科技有限公司 承载装置和测序系统
CN111308726A (zh) * 2018-12-12 2020-06-19 深圳市真迈生物科技有限公司 光学系统、调校光学系统的方法和测序系统
CN110904206A (zh) * 2019-12-18 2020-03-24 深圳市真迈生物科技有限公司 液路系统、生物分子分析系统及核酸序列测定系统

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116769591A (zh) * 2023-08-28 2023-09-19 四川杰莱美科技有限公司 一种实时荧光定量pcr仪
CN116769591B (zh) * 2023-08-28 2023-10-31 四川杰莱美科技有限公司 一种实时荧光定量pcr仪
CN118090608A (zh) * 2024-04-22 2024-05-28 深圳市真迈生物科技有限公司 分析仪和分析系统

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