Chip sequencing device and sequencer

Abstract

The utility model discloses a chip sequencing device and a sequencer. The chip sequencing device comprises a chip flow cell piece and a temperature control part, the chip flow cell piece is provided with a reagent cavity, a first liquid inlet and a first liquid outlet, a reagent can be injected into the reagent cavity through the first liquid inlet, the reagent in the reagent cavity can be discharged through the first liquid outlet, the top of the reagent cavity is open, and the temperature control part is arranged on the top of the reagent cavity. A chip placing groove for placing an open type sequencing chip is formed in the bottom surface of the reagent cavity, and the temperature control component can heat or cool the chip flow cell piece. The chip sequencing device is provided with the chip flow cell piece used for installing the open type sequencing chip, so that the use of the immersed type objective lens becomes possible, the imaging module of the immersed type objective lens can extend into the reagent to carry out image acquisition on the open type sequencing chip, and the sequencing flux is improved. After sequencing is completed, the reagent can be discharged from the first liquid outlet, and waste liquid residues can be reduced. And the temperature control part can be used for heating and cooling the chip flow cell part.

Description

TECHNICAL FIELD

[0001] The utility model relates to chip detection technical field especially relates to a chip sequencing device and sequencer. BACKGROUND

[0002] At present, the sequencing technology has higher and higher requirements on flux, and the sequencing flux is mainly improved through two ways of improving chip density and using higher numerical aperture NA objective lens. Chip density improvement is difficult to realize, the reasons are as follows: firstly, because the chip density improvement will lead to the reaction groove on it to be reduced, so that the total energy received by the sample to be measured (such as nucleic acid) is reduced, which brings the problem of fluorescence signal drop; secondly, because the existing sequencing chip process is complex, it is difficult to further improve the chip density.

[0003] As for using higher numerical aperture NA objective lens, one way is to use immersion objective lens, but the existing sequencing chip often needs to package cover glass on the chip to form flow channel structure, and the packaged sequencing chip cannot use immersion objective lens for imaging, that is, the existing sequencing device cannot meet the working requirements of immersion objective lens.

[0004] Therefore, how to at least partially overcome the above problems is a technical problem that needs to be solved now. UTILITY MODEL CONTENT

[0005] The first purpose of the utility model is to provide a chip sequencing device, which can meet the working requirements of immersion objective lens and is beneficial to improve the sequencing flux of the chip.

[0006] To achieve this purpose, the utility model adopts the following technical scheme:

[0007] A chip sequencing device, comprising: a chip flow cell piece, the chip flow cell piece is provided with a reagent cavity, a first liquid inlet and a first liquid outlet which are in communication with the reagent cavity, the top of the reagent cavity is open, a chip placing groove is arranged on the bottom surface of the reagent cavity, and the chip placing groove is used for placing an open sequencing chip; a temperature control component, the temperature control component is arranged below the chip flow cell piece, and the temperature control component is used for heating or cooling the chip flow cell piece; wherein the reagent cavity is used for containing reagents, the reagent can be injected into the reagent cavity through the first liquid inlet, and the reagent in the reagent cavity can be discharged through the first liquid outlet.

[0008] As preferred, the open sequencing chip comprises a substrate layer, a feature array layer and a feature protection layer, the feature array layer and the feature protection layer are both arranged on the substrate layer, the feature array layer comprises a plurality of feature units arranged in rows and columns, the feature protection layer is arranged outside the feature units and is higher than the feature units to form a reaction groove for accommodating a sample to be tested.

[0009] As preferred, the chip flow cell further comprises a vacuum adsorption flow channel, one end of the vacuum adsorption flow channel is in communication with the chip placing groove, and the other end is used for external connection of a vacuum generator.

[0010] As preferred, at least part of the side wall surface of the reagent cavity is in an arc shape.

[0011] As preferred, an output flow channel is formed on the bottom surface of the reagent cavity and is in communication with the chip placing groove and the first liquid outlet.

[0012] As preferred, the chip sequencing device further comprises a heat dissipation component arranged below the temperature control component, the heat dissipation component comprises a liquid cooling component and a pump body, the liquid cooling component is internally provided with a liquid cooling flow channel, the liquid cooling flow channel is formed with a second liquid inlet and a second liquid outlet on the end surface of the liquid cooling component, and the pump body is used for pumping cooling liquid into the liquid cooling flow channel.

[0013] As preferred, the heat dissipation component further comprises a support limiting seat, a first connecting hole is arranged on the side of the support limiting seat; the chip sequencing device further comprises a connecting seat and a quick release connecting piece, a second accommodating space is arranged on the connecting seat, and the quick release connecting piece is connected in the first connecting hole through the second connecting hole.

[0014] As preferred, a first accommodating space is arranged through the support limiting seat, a second accommodating space is arranged on the connecting seat, and part of the structure of the liquid cooling component is arranged in the second accommodating space through the first accommodating space; and / or, the support limiting seat comprises two oppositely arranged airfoil sliding rails, the connecting seat comprises two oppositely arranged seat plates, a front-narrow-and-back-wide sliding groove is formed on the seat plate, and the two oppositely arranged airfoil sliding rails are slidably connected in the two sliding grooves one by one.

[0015] As preferred, the chip sequencing device further comprises an adjusting base, the adjusting base is arranged below the connecting seat, and the inclination angle of the open sequencing chip can be adjusted through the adjusting base.

[0016] The second object of the utility model provides a sequencer, which can use an immersion objective lens, and the sequencing throughput is improved.

[0017] To achieve the object, the utility model adopts the following technical scheme.

[0018] A sequencer comprising an imaging module and the chip sequencing device, the imaging module comprising an immersion objective, the immersion objective being capable of extending into the reagent cavity.

[0019] The chip sequencing device has the advantages that:

[0020] The chip sequencing device provided by the utility model comprises a chip flow cell piece and a temperature control component, the chip flow cell piece is provided with a reagent cavity and a first liquid inlet and a first liquid outlet communicated with the reagent cavity, reagent can be injected into the reagent cavity through the first liquid inlet, and the reagent in the reagent cavity can be discharged through the first liquid outlet, the top of the reagent cavity is open, a chip placing groove is arranged on the bottom surface of the reagent cavity, the chip placing groove is used for placing an open sequencing chip, and the temperature control component is arranged below the chip flow cell piece, and the temperature control component is used for heating or cooling the chip flow cell piece. The chip sequencing device is provided with the chip flow cell piece used for mounting the open sequencing chip, so that the use of the immersion objective is possible, the imaging module of the immersion objective can extend into the reagent in the reagent cavity, image collection of the open sequencing chip is carried out, and the sequencing throughput is improved. After sequencing is completed, the reagent can be discharged from the first liquid outlet, and waste liquid residue can be reduced. The temperature control component can realize temperature rise and fall of the chip flow cell piece. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 It is a schematic view of the chip sequencing device provided by the utility model;

[0022] Figure 2 It is an exploded view of the chip sequencing device provided by the utility model;

[0023] Figure 3 It is a schematic view of the chip flow cell piece provided by the utility model;

[0024] Figure 4 It is a schematic view of the liquid cooling piece provided by the utility model;

[0025] Figure 5 It is a schematic view of the connecting seat provided by the utility model;

[0026] Figure 6 It is a schematic view of the adjusting base provided by the utility model;

[0027] Figure 7 It is a schematic view of the adjusting base provided by the utility model in another view;

[0028] Figure 8 It is a schematic view of the first module, the second module and the quick-release connecting piece provided by the utility model;

[0029] Figure 9 It is a schematic view of the second module forming a sliding groove provided by the utility model;

[0030] Figure 10 is a schematic view of the connecting seat in another perspective view provided by the utility model;

[0031] Figure 11 is a schematic view of the sequencer provided by the utility model;

[0032] Figure 12 is a schematic view of the open sequencing chip provided by the utility model;

[0033] Figure 13 is a relationship diagram of the height of the feature array layer and the absorption cross-sectional area provided by the utility model;

[0034] Figure 14 is a relationship diagram of the reaction groove aperture and the absorption cross-sectional area provided by the utility model.

[0035] In the figure:

[0036] 100, open sequencing chip; 1, base layer; 2, feature array layer; 3, feature protection layer;

[0037] 200, chip flow cell piece; 210, first main body part; 211, reagent cavity; 212, first liquid inlet; 213, first liquid outlet; 214, chip placing groove; 215, vacuum adsorption hole; 216, output flow channel; 220, first assembly part; 221, first assembly hole;

[0038] 300, temperature control part;

[0039] 400, heat dissipation part; 410, liquid cooling piece; 411, second main body part; 412, second assembly part; 413, first limiting groove; 414, second assembly hole; 415, third assembly hole; 416, liquid cooling flow channel; 417, second liquid inlet; 418, second liquid outlet; 420, support limiting seat; 421, first connecting hole; 422, fourth assembly hole; 423, wing-shaped slide rail; 424, first containing space;

[0040] 500, connecting seat; 501, second connecting hole; 502, second containing space; 503, seat plate; 504, third connecting hole; 505, sliding groove; 506, lifting surface;

[0041] 600, quick release connecting piece;

[0042] 700, adjusting base; 710, base body; 701, second limiting groove; 702, through hole; 703, fourth connecting hole; 704, fifth connecting hole;

[0043] 800, immersion objective; 900, reagent;

[0044] 10, first module; 20, second module. DETAILED DESCRIPTION

[0045] The utility model will be described in further detail below in connection with the drawings and embodiments. It can be understood that the specific embodiments described herein are merely used to explain the utility model and not limit the utility model. In addition, it should be noted that only the parts related to the utility model are shown in the drawings for ease of description, not all the structures.

[0046] In the description of the utility model, unless otherwise explicitly specified and limited, the terms "connected", "connected", "fixed" should be understood broadly, for example, it can be fixedly connected, or it can be detachably connected, or it can be integrated; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium; it can be the communication between two elements or the interaction relationship between two elements. For ordinary skilled in the art, the specific meaning of the above terms in the utility model can be understood according to the specific circumstances.

[0047] In the utility model, 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 the first and second features are not in direct contact but are in contact through another feature between them. Moreover, the "upper", "upper" and "upper" of the first feature to the second feature include 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 "below", "below" and "below" of the first feature to the second feature include 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.

[0048] In the description of the embodiment, the terms "upper", "lower", "right", etc. orientation or position relationship is based on the orientation or position relationship shown in the drawings, only for the convenience of description and simplification of operation, and does not indicate or imply that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, therefore cannot be understood as a limitation on the utility model. In addition, the terms "first", "second" are only used to distinguish in description, and have no special meaning.

[0049] The utility model discloses a chip sequencing device, such as Figures 1 to 11As shown, the chip sequencing device comprises an open sequencing chip 100, a chip flow cell piece 200 for containing reagents 900 and placing the open sequencing chip 100, and a temperature control component 300. Specifically, the chip flow cell piece 200 is provided with a reagent cavity 211, and a first liquid inlet 212 and a first liquid outlet 213 in communication with the reagent cavity 211. The reagent 900 can be injected into the reagent cavity 211 through the first liquid inlet 212, and the reagent 900 in the reagent cavity 211 can be discharged through the first liquid outlet 213. The top of the reagent cavity 211 is open, and the bottom surface of the reagent cavity 211 is provided with a chip placing groove 214 for placing the open sequencing chip 100. The temperature control component 300 is arranged below the chip flow cell piece 200, and is used to heat or cool the chip flow cell piece 200.

[0050] It should be noted that the reagents 900 herein include reaction reagents and photographing reagents. The sequencing of the sample to be tested involves many rounds of biochemical reactions. Reaction reagents need to be added to the reagent cavity 211 for each round of biochemical reaction, and the types of reaction reagents can be the same or different. After the biochemical reaction of the sample to be tested is completed, photographing is performed, at which time the photographing reagents need to be added to the reagent cavity 211, and then photographing is performed. After the photographing of the sample to be tested is completed, the photographing reagents in the reagent cavity 211 can be discharged to enter the next round of biochemical reaction, so as to realize the cycle.

[0051] Compared with the sequencing chip packaged with a glass cover plate in the prior art, the chip sequencing device of the present application adopts an open sequencing chip 100, and through the arrangement of the chip flow cell piece 200, the open sequencing chip 100 can be fixed and immersed in the reagents 900. Such an arrangement makes it possible to use a submerged objective lens. The temperature control component 300 can realize temperature rise and fall of the chip flow cell piece 200.

[0052] In order to improve the stability of the open sequencing chip 100 in the chip placing groove 214, in some embodiments, the opening shape of the chip placing groove 214 is basically the same as the shape of the open sequencing chip 100, and the opening size of the chip placing groove 214 is slightly larger than the size of the open sequencing chip 100. Alternatively, the chip placing groove 214 is a rectangular groove, and the open sequencing chip 100 is a rectangular block. In order to facilitate the extraction of the open sequencing chip 100 from the chip placing groove 214, a communicating hand pulling groove is further arranged beside the chip placing groove 214.

[0053] In some embodiments, a vacuum suction flow channel is further provided on the chip flow cell piece 200, one end of the vacuum suction flow channel is communicated with the chip placing groove 214, and the other end is used for connecting a vacuum generator (not shown in the figure). Specifically, one end of the vacuum suction flow channel forms a vacuum suction hole 215 on the bottom surface of the chip placing groove 214, and the other end of the vacuum suction flow channel forms an air hole on the side wall of the chip flow cell piece 200, and the pipeline of the vacuum generator is communicated at the air hole, so as to form a negative pressure environment below the open sequencing chip 100 and adsorb the open sequencing chip 100 in the chip placing groove 214. Of course, in addition to using vacuum suction, other ways can also be used to fix the open sequencing chip 100, for example, using a spring sheet to press the open sequencing chip 100.

[0054] In some embodiments, a first pipe joint is communicated at the first liquid inlet 212, and the first pipe joint is used to conveniently connect an inlet pipe. In some embodiments, a second pipe joint is communicated at the first liquid outlet 213, and the second pipe joint is used to conveniently connect an outlet pipe.

[0055] Continuing to refer to Figure 3 As shown, the chip flow cell piece 200 includes a first main body part 210 and a plurality of first assembly parts 220 arranged in a circumferential direction around the first main body part 210, the first main body part 210 is provided with a reagent cavity 211, the first assembly part 220 is provided with a first assembly hole 221, and a first connecting piece (not shown in the figure) passes through the first assembly hole 221 to fix the chip flow cell piece 200 on other structures. In one specific embodiment, the first main body part 210 is a rectangular block, and the first assembly part 220 is provided with four first assembly parts 220, two of which are arranged on both sides of the first main body part 210.

[0056] In some embodiments, at least part of the side wall surface of the reagent cavity 211 is an arc-shaped structure, so as to form a streamline structure, which facilitates the introduction and discharge of the reagent 900 into and out of the reagent cavity 211. The reagent 900 enters the reagent cavity 211 from the first liquid inlet 212, and after the biochemical reaction is completed or the sequencing photographing is completed, the reagent 900 can be discharged from the first liquid outlet 213, and the reagent cavity 211 is designed to be streamline-shaped to reduce the residue of waste liquid.

[0057] In some embodiments, in order to make the reagent 900 be able to be discharged from the reagent cavity 211 completely, and avoid the reagent 900 remaining in the chip placing groove 214, an output flow channel 216 is provided on the bottom surface of the reagent cavity 211, which is communicated with the chip placing groove 214 and the first liquid outlet 213.

[0058] Optionally, the temperature control component 300 is a semiconductor cooler (TEC), which has the advantages of environmental protection, silence, energy saving and high efficiency, etc. In an embodiment, the power of the semiconductor cooler is 100W, the temperature rising and falling range is 10-60℃, and the temperature rising and falling time is within 30s. Of course, the temperature control component 300 can also adopt other structures capable of realizing temperature rising and falling, so as to realize temperature rising and falling in the range of 0-80℃.

[0059] With continued reference to Figure 1 and Figure 2 As shown, the chip sequencing device further comprises a heat dissipation component 400, the cold end of the semiconductor cooler is attached to the bottom surface of the chip flow cell 200, and the hot end of the semiconductor cooler is attached to the heat dissipation component 400. The heat dissipation component 400 can adopt liquid cooling or air cooling,

[0060] In some embodiments, the heat dissipation component 400 comprises a liquid cooling component 410 and a pump body (not shown in the figure), with continued reference to Figure 4 As shown, the liquid cooling component 410 is provided with a liquid cooling flow channel 416, the liquid cooling flow channel 416 is formed with a second liquid inlet 417 and a second liquid outlet 418 on the end surface of the liquid cooling component 410, and the pump body is used to pump the cooling liquid into the liquid cooling flow channel 416. Optionally, the cooling liquid is water. Optionally, the liquid cooling flow channel 416 is provided as a serpentine flow channel. Optionally, the second liquid inlet 417 and the second liquid outlet 418 are provided on the same side of the liquid cooling component 410, the second liquid inlet 417 and the second liquid outlet 418 are externally connected to a water source through a water pipe, the pump body is provided on the water pipe, and the pump body can be used to pump water into the liquid cooling flow channel 416. In an embodiment, the heat dissipation component 400 further comprises a heat dissipation fan (not shown in the figure), which can improve the heat exchange efficiency.

[0061] Optionally, the liquid cooling component 410 is provided with a first limiting groove 413, and the semiconductor cooler is arranged in the first limiting groove 413. Arranging the semiconductor cooler in the first limiting groove 413 can realize the plug-in connection of the semiconductor cooler and the liquid cooling component 410, so as to improve the compactness and assembly stability of the structure.

[0062] Optionally, the liquid cooling component 410 is provided with a second assembly hole 414, the number of the second assembly hole 414 is the same as that of the first assembly hole 221, and the second assembly hole 414 is arranged one by one in correspondence with the first assembly hole 221, and each set of oppositely arranged first assembly hole 221 and second assembly hole 414 is provided with a first connecting piece, which can be a screw piece. Further optionally, the number of the second assembly hole 414 and the first assembly hole 221 is four.

[0063] In one embodiment, the liquid cooling member 410 comprises a second main body part 411 and a second assembly part 412 arranged on both sides of the second main body part 411, the top surface of the second main body part 411 is arranged lower than the second assembly part 412, thereby forming the first limiting groove 413, and the lower bottom surface of the second main body part 411 is arranged protruding the second assembly part 412, thereby making part of the second main body part 411 form a protruding part of the liquid cooling member 410. Optionally, a second assembly hole 414 is arranged on the second main body part 411.

[0064] Further, a first layer of silicone grease is arranged between the cold end of the semiconductor refrigerator and the bottom surface of the chip flow cell member 200, and a second layer of silicone grease is arranged between the hot end of the semiconductor refrigerator and the heat dissipation member 400. The arrangement of the first and second layers of silicone grease is conducive to improving the heat transfer efficiency.

[0065] With continued reference to Figure 2 As shown in FIG. 4, the heat dissipation member 400 comprises a support limiting seat 420 for supporting the liquid cooling member 410. In one embodiment, the support limiting seat 420 is provided with a first accommodating space, and the protruding part of the liquid cooling member 410 is arranged in the first accommodating space, which can improve the compactness of the entire device.

[0066] In one embodiment, a third assembly hole 415 is arranged on the second assembly part 412, a fourth assembly hole 422 is arranged on the support limiting seat 420, and a second connecting member is arranged in the third assembly hole 415 and connected in the fourth assembly hole 422. Optionally, the second connecting member is a screw.

[0067] With continued reference to Figure 1 and Figure 5 As shown in FIG. 4, the chip sequencing device further comprises a connecting seat 500 and a quick release connecting member 600, the connecting seat 500 is provided with a second accommodating space 502, the support limiting seat 420 is arranged in the second accommodating space 502, and the protruding part of the liquid cooling member 410 is arranged in the second accommodating space 502 through the first accommodating space 424, which can further improve the compactness of the entire device.

[0068] Optionally, the support limiting seat 420 is provided with a first connecting hole 421 on the side, the connecting seat 500 is provided with a second connecting hole 501 on the side, and the quick release connecting member 600 is arranged in the first connecting hole 421 through the second connecting hole 501. Optionally, the quick release connecting member 600 is a quick release screw, and the first connecting hole 421 is a threaded hole.

[0069] Optionally, the support limiting seat 420 comprises two oppositely arranged airfoil sliding rails 423, the airfoil sliding rails 423 are narrow in front and wide in back, thereby forming an airfoil structure, the connecting seat 500 comprises two oppositely arranged seat plates 503, each of the seat plates 503 is formed with a sliding groove 505 which is narrow in front and wide in back, a second accommodating space 502 is formed between the two seat plates 503, and the two airfoil sliding rails 423 are correspondingly and slidably connected in the two sliding grooves 505. During the sliding and inserting process of the airfoil sliding rails 423 and the sliding grooves 505, the structure of narrow in front and wide in back makes the gap between the airfoil sliding rails 423 and the sliding grooves 505 gradually decrease until completely coupled, not only the sliding and inserting of the connecting seat 500 and the support limiting seat 420 can be realized, but also the positioning is more accurate due to the sliding cooperation of narrow in front and wide in back.

[0070] With reference to Figure 1 , Figure 2 , Figure 6 and Figure 7 continuously, the chip sequencing device further comprises an adjusting base 700 which is arranged below the connecting seat 500. The adjusting base 700 has an inclination adjusting function, and the angle of the open sequencing chip 100 can be adjusted through the adjusting base 700.

[0071] Optionally, the adjusting base 700 comprises a base body 710 and a jackscrew, the base body 710 is provided with a through hole 702 for the jackscrew to pass through, and the jackscrew passes through the through hole 702. The inclination of the base body 710 can be changed by adjusting the height of the jackscrew, thereby changing the inclination angle of the open sequencing chip 100 on the base body 710, and further ensuring that the open sequencing chip 100 is arranged vertically to the optical axis of the objective lens.

[0072] Optionally, the base body 710 is provided with a second limiting groove 701, and the connecting seat 500 is arranged in the second limiting groove 701. In order to realize accurate positioning, the second limiting groove 701 comprises two oppositely arranged positioning groove parts, and the two seat plates 503 are correspondingly clamped in the two positioning groove parts, thereby realizing accurate positioning.

[0073] In some embodiments, the base body 710 and the connecting seat 500 are detachably connected, the third connecting hole 504 is through arranged on the seat plate 503, the fourth connecting hole 703 is arranged on the base body 710, and the third connecting member passes through the third connecting hole 504 and is fixed in the fourth connecting hole 703, thereby realizing the detachable connection of the base body 710 and the connecting seat 500. Optionally, the third connecting hole 504 and the fourth connecting hole 703 are threaded holes, and the third connecting member is a screw member.

[0074] In some embodiments, as Figure 9 and Figure 10As shown, a portion of the bottom surface of the bottom plate 503 is raised to form an upper raised surface 506. After the connecting base 500 is placed on the base body 710 and relatively fixed, the upper raised surface 506 of the bottom plate 503 and a portion of the top surface of the base body 710 are surrounded to form a slide groove 505 for inserting the wing-shaped slide rail 423. It should be noted that the slide groove 505 can also be directly formed on the bottom plate 503 without relying on the base body 710.

[0075] The assembly process of the chip sequencing device is as follows:

[0076] 1. Place the temperature control component 300 in the first limiting groove 413 on the liquid cooling component 410, and place the chip flow pool component 200 on the liquid cooling component 410, and use the first connecting component to assemble the chip flow pool component 200 and the liquid cooling component 410; then, place the protruding portion of the liquid cooling component 410 in the support limiting seat 420, and use the second connecting component to assemble the liquid cooling component 410 and the support limiting seat 420 to form the first module 10.

[0077] 2. Place the connecting base 500 in the second limiting groove 701 of the base body 710 and use the third connecting member to achieve a detachable connection between the connecting base 500 and the base body 710 to form the second module 20;

[0078] 3. According to Figure 8 Move the first module 10 as a whole in the direction of the arrow shown in , and slide the two wing-shaped slide rails 423 on the support and limit seat 420 into the slide groove 505 formed by the connecting seat 500 and the base body 710 in a one-to-one correspondence, so as to achieve sliding connection and accurate positioning of the first module 10 and the second module 20;

[0079] 4. Pass the quick-release connector 600 through the second connection hole 501 and connect it to the first connection hole 421 to achieve quick disassembly and assembly of the connecting seat 500 and the support and limiting seat 420, thereby achieving quick disassembly and assembly of the first module 10 and the second module 20.

[0080] It should be noted that the quick-release connector 600 enables rapid assembly and disassembly of the first module 10 and the second module 20. When the experimenter needs to remove or place the open sequencing chip 100 from the instrument, they can loosen the quick-release connector 600 and remove the first module 10, which is composed of the chip flow cell 200, the temperature control component 300, and the heat dissipation component 400, from the second module 20. The self-positioning design between the wing-shaped slide rail 423 and the slide groove 505 also ensures accurate positioning between multiple experiments.

[0081] In the embodiment, the chip sequencing device further comprises a control mechanism, which can be a centralized or distributed controller, for example, the controller can be a single microcontroller or a plurality of microcontrollers distributed, and the microcontroller can run a control program to control all electrically controlled components in the chip sequencing device to realize their functions respectively.

[0082] The utility model discloses still disclose a sequencer, as shown in it, Figure 11 The sequencer comprises an imaging module and the chip sequencing device, and the imaging module comprises an immersion objective 800 which can be inserted into the reagent cavity 211. The specific structure of the immersion objective 800 is prior art and is not described here.

[0083] The sequencer provided in the embodiment improves sequencing throughput by inserting the immersion objective 800 into the reagent 900 in the reagent cavity 211, using the immersion objective 800 to observe and collect images of the sample to be tested on the open sequencing chip 100.

[0084] In some embodiments, the sequencer further comprises a moving platform (not shown in the figure), and the adjusting base 700 is arranged on the moving platform, and the moving platform can drive the chip sequencing device to move. The moving platform can move in the x direction and the y direction, and the position of the open sequencing chip 100 can be changed through the movement of the moving platform, so that large-scale scanning imaging of the open sequencing chip 100 is realized.

[0085] Specifically, the fourth connecting member passes through the fifth connecting hole 704 on the base body 710 to fix the base body 710 on the moving platform.

[0086] The structure of the open sequencing chip 100 is introduced as follows:

[0087] As shown in Figure 12 The open sequencing chip 100 comprises a substrate layer 1, a feature array layer 3 and a feature protection layer 2, the feature array layer 3 and the feature protection layer 2 are arranged on the substrate layer 1, the feature array layer 3 comprises a plurality of feature units arranged in rows and columns, the feature protection layer 2 is arranged outside the feature units, and the feature protection layer 2 is higher than the feature units to form a reaction groove for accommodating the sample to be tested.

[0088] In some embodiments, the substrate layer 1 is composed of silicon or silicon dioxide.

[0089] In some embodiments, the feature array layer 3 is composed of metal compounds with sample adsorption function to be tested. Optionally, the metal compound material used in the feature array layer 3 can be titanium nitride, zirconium nitride, thallium nitride, hafnium nitride, etc. The feature array layer 3 composed of metal compounds can generate surface plasmon effect, so as to enhance the local excitation energy.

[0090] Figure 13 The influence of the feature array layer 3 with different feature heights on the absorption cross section (the greater the absorption cross section, the better the local enhancement effect) is simulated. The height of the feature array layer 3 is tested in the range of 50nm-250nm, and the simulation result shows that the effect is best when the height is about 200nm.

[0091] In some embodiments, the feature units are cylindrical structures, and a plurality of feature units are arranged on the substrate layer 1 at equal intervals. Optionally, the reaction groove interval between two adjacent feature units is 100nm-500nm, and preferably, the reaction groove interval is 360nm. Optionally, the size of the reaction groove is 50nm-150nm.

[0092] Figure 14 The influence of the reaction groove with different sizes on the absorption cross section (the greater the absorption cross section value, the better the signal enhancement effect) is simulated. The size of the reaction groove is tested in the range of 100nm-150nm, and the simulation result shows that the effect is best when the size is about 140nm.

[0093] Obviously, the above embodiments of the present application are only examples for clearly illustrating the present application, and are not intended to limit the implementation modes of the present application. For those skilled in the art, various obvious changes, re-adjustments and substitutions can be made without departing from the protection scope of the present application. Here, it is not necessary and impossible to enumerate all the implementation modes. Any modification, equivalent substitution and improvement made within the spirit and principle of the present application shall be included in the protection scope of the present application claim.

Claims

1. A chip sequencing device, characterized in that: include: A chip flow cell component (200), wherein the chip flow cell component (200) is provided with a reagent chamber (211) and a first liquid inlet (212) and a first liquid outlet (213) communicated with the reagent chamber (211); the top of the reagent chamber (211) is open, and a chip placement groove (214) is provided on the bottom surface of the reagent chamber (211); the chip placement groove (214) is used to place an open sequencing chip (100); a temperature control component (300), the temperature control component (300) being disposed below the chip flow pool component (200), and the temperature control component (300) being used to heat or cool the chip flow pool component (200); The reagent chamber (211) is used to accommodate a reagent (900), and the reagent (900) can be injected into the reagent chamber (211) through the first liquid inlet (212), and the reagent (900) in the reagent chamber (211) can be discharged through the first liquid outlet (213).

2. The chip sequencing device according to claim 1, characterized in that The open sequencing chip (100) comprises a base layer (1), a feature array layer (3) and a feature protection layer (2); the feature array layer (3) and the feature protection layer (2) are both arranged on the base layer (1); the feature array layer (3) comprises a plurality of feature units arranged in rows and columns; the feature protection layer (2) is arranged outside the feature units; the feature protection layer (2) is arranged higher than the feature units to form a reaction groove for accommodating a sample to be tested.

3. The chip sequencing device according to claim 1, characterized in that The chip flow pool (200) is also provided with a vacuum adsorption flow channel, one end of which is in communication with the chip placement groove (214), and the other end of which is used for connecting to an external vacuum generator.

4. The chip sequencing device according to claim 1, characterized in that At least part of the side wall surface of the reagent chamber (211) is an arc-shaped structure.

5. The chip sequencing device according to claim 1, characterized in that An output flow channel (216) communicating with the chip placement groove (214) and the first liquid outlet (213) is provided on the bottom surface of the reagent chamber (211).

6. The chip sequencing device according to claim 1, characterized in that The chip sequencing device further includes a heat dissipation component (400) disposed below the temperature control component (300), the heat dissipation component (400) including a liquid cooling component (410) and a pump body, a liquid cooling channel (416) being provided in the liquid cooling component (410), the liquid cooling channel (416) being formed with a second liquid inlet (417) and a second liquid outlet (418) on an end surface of the liquid cooling component (410), and the pump body being used to pump cooling liquid into the liquid cooling channel (416).

7. The chip sequencing device according to claim 6, characterized in that The heat dissipation component (400) further comprises a support and limiting seat (420), and a first connection hole (421) is provided on the side of the support and limiting seat (420); The chip sequencing device further comprises a connection seat (500) and a quick-release connection piece (600), wherein a second connection hole (501) is provided on the side of the connection seat (500), and the quick-release connection piece (600) passes through the second connection hole (501) and is connected to the first connection hole (421).

8. The chip sequencing device according to claim 7, characterized in that A first accommodating space (424) is provided on the support and limiting seat (420), a second accommodating space (502) is provided on the connecting seat (500), and a part of the structure of the liquid cooling element (410) passes through the first accommodating space (424) and is placed in the second accommodating space (502); And / or, the support and limit seat (420) includes two wing-shaped slide rails (423) arranged oppositely, the connecting seat (500) includes two seat plates (503) arranged oppositely, and a slide groove (505) which is narrow in front and wide in the back is formed on the seat plate (503), and the two wing-shaped slide rails (423) arranged oppositely are slidably connected in the two slide grooves (505) in a one-to-one manner.

9. The chip sequencing device according to claim 7, characterized in that: The chip sequencing device further comprises an adjustment base (700), wherein the adjustment base (700) is arranged below the connection base (500), and the tilt angle of the open sequencing chip (100) can be adjusted through the adjustment base (700).

10. A sequencer, characterized in that: A chip sequencing device comprising an imaging module and any one of claims 1 to 9, wherein the imaging module comprises an immersion objective lens (800), and the immersion objective lens (800) can extend into the reagent chamber (211).

Images