Droplet module and pipetting spotting station
By using a pressure-controlled droplet module and flow channel structure, the problems of uneven droplet distribution and complex operation in existing spotting methods are solved, achieving stable droplet output and efficient spotting.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-11-03
- Publication Date
- 2026-03-03
AI Technical Summary
Existing contact and non-contact spotting methods in biochip spotting equipment suffer from problems such as uneven droplet size, complex operation, and low efficiency.
The droplet module uses air pressure to control the needle to draw in and spray liquid, and combines the flow channel structure and sealing plug to control the flow channel opening and closing, so as to achieve stable output of droplets.
This achieved stability and accuracy in droplet output, reduced the coefficient of variation, and improved sampling efficiency and sensitivity.
Smart Images

Figure CN115824735B_ABST
Abstract
Description
Technical Field
[0001] This application relates to droplet modules and pipetting workstations. Background Technology
[0002] In biochip spotting equipment, the stability of spotting (e.g., controlling the coefficient of variation within a certain range) and the micro-volume (e.g., nanoliters) are important development trends in the industry.
[0003] Sampling methods are divided into two main categories: contact and non-contact.
[0004] Existing contact-type spotting methods mainly involve direct contact between the liquid at the tip of the spotting needle and the chip, forming an array of spots through capillary action. The disadvantages of this spotting method are that the droplet size (dispensing volume) is not uniform enough; the amount of reagent that the spotting needle can carry at one time is very small, resulting in extremely low efficiency.
[0005] Existing non-contact sampling methods mainly rely on the principles of syringe pumps and solenoid valves. The sample is first drawn from the sampling head into the pipe or the entire system's liquid tank to fill with liquid sample. During spraying, the syringe pump pushes the sample, while a tiny solenoid valve opens, instantly ejecting the set sampling volume from the nozzle to form the desired array. This method results in a relatively large sampling diameter and is quite complex to operate. Summary of the Invention
[0006] This application provides a droplet module and a pipetting and spotting workstation.
[0007] This droplet module is used to draw in and eject liquid. The droplet module includes a gas source controller and a droplet module body. The droplet module body is connected to a gas source through the gas source controller.
[0008] The droplet module body includes a needle tip, which is connected to the external environment. The droplet module is configured to control the needle tip to draw in and eject liquid by controlling air pressure.
[0009] The needle includes a flow channel wall and a flow path located in the flow channel wall. In a cross-section along the axis of the needle, the waistline of the flow channel wall makes an angle α with the axis, where α satisfies: α≤30°.
[0010] In at least one embodiment, the droplet module further includes:
[0011] A housing structure, wherein a flow channel is provided in the housing structure, one end of the flow channel is connected to the air source controller, and the other end of the flow channel is controllably connected to the needle; and
[0012] A flow channel control structure includes a sealing plug, which controls the connection between the other end of the flow channel and the needle by controlling whether the sealing plug blocks or does not block the connection position between the needle and the flow channel.
[0013] In at least one embodiment, the flow channel includes:
[0014] A first flow channel, one end of which is connected to the gas source controller;
[0015] The second flow channel has a circular cross-section, and one end of the second flow channel is connected to the other end of the first flow channel;
[0016] The third flow channel has a hollow cylinder structure at its first end, which is connected to the other end of the second flow channel. The second end of the third flow channel is radially deflected inward, and its cross-section is an annular. When the sealing plug is not blocked, the liquid can flow through the second end and the needle.
[0017] In at least one embodiment, the flow channel control structure further includes a sealing plug displacement device, which includes a connector and a body. The sealing plug is disposed at the end of the connector, the connector is movably connected to the body, and the body is configured to allow axial movement of the connector.
[0018] The sealing plug displacement device and the sealing plug are disposed in the central cavity of the third flow channel. When the sealing plug is pushed against the needle by the connector, the sealing plug blocks the communication between the third flow channel and the needle.
[0019] In at least one embodiment, the housing structure includes a baffle structure comprising a first baffle having a hole through which the third flow channel and the connector pass, and the diameter of the sealing plug being larger than the diameter of the connector.
[0020] After the sealing plug moves away from the needle, the sealing plug abuts against the first baffle, and a sealing space is formed between the first baffle and the needle.
[0021] In at least one embodiment, the housing structure is provided with a baffle structure, the baffle structure including a second baffle, the second baffle being disposed at the connection between the second flow channel and the third flow channel, and the main body of the sealing plug displacement device being connected to the second baffle.
[0022] In at least one embodiment, α ≤ 10°.
[0023] In at least one embodiment, the diameter of the flow path is R1, and the diameter of the end face of the flow channel wall is R2, satisfying:
[0024] 130μm≤R1≤250μm;
[0025] 350μm≤R2≤700μm.
[0026] The pipetting and spotting workstation provided in this application includes:
[0027] The droplet module as described above; and
[0028] The cleaning module includes a cleaning area.
[0029] The cleaning area includes:
[0030] A cleaning tank, wherein the bottom of the cleaning tank is provided with a drain outlet for discharging liquid;
[0031] A cleaning column is disposed in the cleaning tank. The cleaning column has one or more cleaning holes that can spray cleaning liquid vertically upwards, and the spray height of the cleaning liquid is greater than the highest point of the cleaning column.
[0032] In at least one embodiment, the top surface of the cleaning column includes two surfaces with different degrees of inclination, and the two surfaces with different degrees of inclination are connected by a turning point, which passes through the center of the cleaning hole.
[0033] This application utilizes pneumatic control to draw in and eject liquid from the droplet module. Compared to traditional contact spotting, this method provides a more stable droplet output with a lower coefficient of variation. Furthermore, compared to traditional syringe pumps, pneumatic control allows for smaller output volumes, accommodating a wider range of applications.
[0034] The pipetting and spotting workstation provided in this application also possesses the aforementioned advantages due to having the droplet module described above. Attached Figure Description
[0035] Figure 1 A schematic diagram of the overall structure of a pipetting and spotting workstation according to an embodiment of this application is shown.
[0036] Figure 2 A schematic diagram of a portion of the structure of a pipetting workstation according to an embodiment of this application is shown.
[0037] Figure 3 A schematic diagram of the droplet module of a pipetting workstation according to an embodiment of this application is shown.
[0038] Figure 4 It shows Figure 3 A schematic diagram of the main structure of the droplet module in the image.
[0039] Figure 5 It shows Figure 4 A schematic diagram of the needle structure of the droplet module body.
[0040] Figure 6 A schematic diagram of the sampling station module and the cleaning module of the pipetting workstation according to an embodiment of this application is shown.
[0041] Figure 7 A top view of the mounting slot in the sampling station module of a pipetting workstation according to an embodiment of this application is shown.
[0042] Figure 8 An isometric view of the cleaning area of the cleaning module of a pipetting workstation according to an embodiment of this application is shown.
[0043] Figure 9 It shows Figure 8 A top view of the cleaning area.
[0044] Figure 10 A side view of the guide rails and base of the drying zone of the cleaning module of a pipetting workstation according to an embodiment of this application is shown.
[0045] Explanation of reference numerals in the attached figures
[0046] 1 frame; 11 substrates;
[0047] 2. Motion module; 21. First slider; 22. Second slider; 23. Third slider;
[0048] 3. Droplet module; 31. Gas source; 32. Gas source controller; 33. Droplet body module; 331. First flow channel; 332. Second flow channel; 333. Third flow channel; 3331. First end; 3332. Second end; 3333. End opening; 334. Needle; 3341. First end; 3342. Second end; 335. Shell structure; 336. Flow channel control structure; 3361. Sealing plug; 3362. Connector; 3363. Body; 3371. First baffle; 3372. Second baffle;
[0049] 4. Detection module; 41. Detection camera; 42. Illumination equipment;
[0050] 5. Reagent module;
[0051] 6-point sampling station module; 61 First base; 611 Mounting slot; 612 First redundancy space; 613 Second redundancy space; 614 Through hole; 62 Base column; 63 Second base;
[0052] 7. Cleaning module; 71. Cleaning area; 711. Cleaning tank; 7111. Drain outlet; 712. Cleaning column; 7121. Cleaning hole; 7122. Turning point; 7123. Horizontal plane; 7124. Inclined plane; 7125. Arc-shaped surface; 713. Connecting block; 72. Drying area; 721. Drying block; 722. Base; 723. Guide rail;
[0053] L1 waistline; L2 axis. Detailed Implementation
[0054] Exemplary embodiments of this application are described below with reference to the accompanying drawings. It should be understood that these specific descriptions are for teaching those skilled in the art how to implement this application only, and are not intended to exhaustively describe all possible methods of this application, nor to limit the scope of this application.
[0055] This application provides a pipetting and sample application workstation. See also... Figure 1 , Figure 2 The pipetting and spotting workstation may include a frame 1, a motion module 2, a droplet module 3 (not shown in the figure), a detection module 4, a reagent module 5, a spotting station module 6, and a cleaning module 7.
[0056] See Figure 1 , Figure 2 The frame 1 may include a base plate 11, a housing, and an electrical cabinet. The aforementioned motion module 2, reagent module 5, sample dispensing station module 6, and cleaning module 7 can be mounted on the base plate 11. The electrical cabinet can be installed at the bottom of the base plate 11. The housing can be made of materials such as transparent glass or plastic, which provides a certain degree of sealing while facilitating observation of the pipetting and sample dispensing process.
[0057] See Figure 2 The X, Y, and Z directions are perpendicular to each other. Motion module 2 can be mounted on substrate 11. Motion module 2 can be a three-axis motion platform, enabling components such as droplet module 3 (not shown) and detection module 4 mounted on motion module 2 to move in the X, Y, and Z directions.
[0058] For example, the motion module 2 can be composed of structures such as sliders, guide rails, and motors. For instance, two guide rails can be arranged side-by-side in the Y direction. Of course, two guide rails can also be arranged side-by-side in the X and Z directions to increase stability. The sliders can include a first slider 21 that moves in the Z direction, a second slider 22 that moves in the X direction, and a third slider 23 that moves in the Y direction. Guide rails can be provided on the sliders to provide guidance; the second slider 22 can be or include the guide rail of the first slider 21, and the third slider 23 can be or include the guide rail of the second slider 22. The droplet module 3 and the detection module 4 can be connected to the first slider 21, thereby enabling movement in the X, Y, and Z directions.
[0059] See Figure 3 The droplet module 3 may include a gas source 31, a gas source controller 32, and a droplet module body 33 connected in sequence. The droplet module 3 can realize the functions of liquid intake and liquid ejection. The gas source 31 may include a gas storage tank, etc. The gas source controller 32 may be a valve, a pressure sensor, etc., and the droplet module body 33 may be a nozzle. By controlling the air pressure of the droplet module body 33, for example by providing negative pressure or positive pressure to the droplet module body 33, the intake and ejection of liquid are realized.
[0060] See Figure 4 The droplet module body 33 may include flow channels, which may include a first flow channel 331, a second flow channel 332, a third flow channel 333, a needle 334, a shell structure 335, and a flow channel control structure 336. Among them, the first flow channel 331, the second flow channel 332, and the third flow channel 333 may be disposed inside the shell structure 335.
[0061] The first flow channel 331 can be a cylindrical flow channel, which is connected to the gas source controller 32 and the second flow channel 332.
[0062] The cross-section of the second flow channel 332 can be annular. The second flow channel 332 connects the first flow channel 331 and the third flow channel 333. Of course, the cross-section of the second flow channel 332 does not have to be annular; the cross-section at the position where the second flow channel 332 connects to the third flow channel 333 only needs to be annular.
[0063] The first end 3331 of the third flow channel 333 is connected to the second flow channel 332. The structure of the first end 3331 can be a hollow cylinder with a circular cross-section, and the cross-section of the second end 3332 of the third flow channel 333 can also be a circular cross-section. It can be understood that the third flow channel 333 and the second flow channel 332 with circular cross-sections maximize the volume of liquid that can be contained, thereby increasing the amount of liquid that can be ejected in a single flow, enabling spotting at the picoliter and nanoliter levels as well as at the microliter and milliliter levels.
[0064] The second end 3332 of the third flow channel 333 can be deflected radially inward, and the end opening 3333 of the second end 3332 is close to the needle tip 334. Further, the end opening 3333 of the second end 3332 can face radially inward.
[0065] The needle 334 can be a cylindrical flow channel, which can be disposed on the outside of the housing structure 335. The first end 3341 of the needle 334 is connected to the inside of the housing structure 335, and the second end 3342 of the needle 334 is directly connected to the external environment.
[0066] The flow control structure 336 may include a sealing plug 3361 and a sealing plug displacement device. The sealing plug displacement device can control the displacement of the sealing plug 3361 to control the connection or disconnection between the third flow channel 333 and the needle 334. For example, the sealing plug 3361 moves to block the first end 3341 of the needle 334, or the sealing plug 3361 moves away from the blocking position, so that the third flow channel 333 and the needle 334 are connected.
[0067] For example, the sealing plug displacement device may include a connector 3362 and a main body 3363. A sealing plug 3361 may be provided at the end of the connector 3362. The axial movement of the connector 3362 can be achieved by means of electromagnetic force or the like, causing the sealing plug 3361 to press against or move away from the first end 3341 of the needle 334, thereby blocking or releasing the blockage. The connector 3362 may be a push rod or a spring, etc.
[0068] This application controls the flow channel opening and closing by using a sealing plug and regulates the pressure by using an air source controller. Compared to a system that does not have physical opening and closing control and only relies on air pressure to control whether liquid is sprayed out, the implementation method of this application physically controls the flow channel opening and closing, making the spray volume more precise.
[0069] It is understood that placing the sealing plug displacement device on the axial position can save space. However, in other embodiments of this application, the sealing plug displacement device may not be placed on the axial position. For example, the structure of the flow channel can be adjusted to place the sealing plug displacement device on the side. Of course, the sealing plug displacement device can also be other structures that enable the sealing plug 3361 to block the needle 334, and this application does not limit its specific structure.
[0070] The housing structure 335 may also include a baffle structure. For example, the baffle structure may include a first baffle 3371 and a second baffle 3372.
[0071] The first baffle 3371 can be located at the second deflected end 3332 of the third flow channel 333. The diameter of the sealing plug 3361 can be larger than the diameter of the connector 3362. After the sealing plug 3361 moves away from the needle 334, the first baffle 3371 can limit the axial movement range of the sealing plug 3361.
[0072] Additionally, when the droplet module 3 draws liquid, the liquid in the needle 334 may not be drawn into the third flow channel 333 in time, but may remain in the housing structure 335. The first baffle 3371 can block these stagnant liquids, thereby allowing the liquid to enter the third flow channel 333 as much as possible, improving the sensitivity and accuracy of liquid control.
[0073] More specifically, even if the liquid does not completely enter the third flow channel 333 during aspiration, the liquid will at most overflow into the small space enclosed by the connector 3362, the sealing plug 3361, the deflected second end 3332 of the third flow channel 333, and the first baffle 3371.
[0074] Preferably, the deflected second end 3332 of the third flow channel 333 is sealed at the position where it passes through the first baffle 3371. Preferably, a seal is formed between the first baffle 3371 and the connector 3362. For example, a seal may be provided between the first baffle 3371 and the connector 3362, or the first baffle 3371 may be made of, or include, a material that readily forms a seal with the connector 3362, such as rubber, silicone, or polytetrafluoroethylene (PTFE).
[0075] The first baffle 3371 can be provided with hollow holes to achieve splicing with the third flow channel 333. The first baffle 3371 can be a split structure located on the inner and outer sides of the third channel 333; or the baffle and flow channel can be manufactured as a whole by 3D printing.
[0076] Similarly, the second baffle 3372 can be provided with perforated holes to achieve splicing with the third flow channel 333. The second baffle 3372 can be a split structure located on both the inner and outer sides of the third flow channel 333. The second baffle 3372 can be used to fix the position of the main body 3363 of the sealing plug displacement device, for example, by using adhesive or other methods to fix the main body 3363 to the second baffle 3372.
[0077] See Figure 5 The needle 334 may include a flow channel wall 3343 and a flow path 3344 located in the flow channel wall 3343. The end of the flow channel wall 3343 (e.g.) Figure 4 The lower end of the flow path 3343 can be provided with a slope or without a slope, making its end frustum or cylinder. In the cross-sectional view along the axis of the needle 3343, the waist line L1 (or generatrix) of the flow channel wall 3343 makes an angle α with the axis L2, where α satisfies: α≤30°. The cross-section of the flow path 3344 can be circular.
[0078] The diameter of the flow path 3344 is R1, and the diameter of the end face of the flow channel wall 3343 is R2. The experimental results are shown in the table below.
[0079] Table 1:
[0080]
[0081]
[0082]
[0083] Table 2:
[0084]
[0085]
[0086] Table 3:
[0087]
[0088]
[0089]
[0090] Table 4:
[0091]
[0092]
[0093] Table 5:
[0094]
[0095] Table 6:
[0096]
[0097]
[0098] As shown in Tables 1 to 4, when other parameters remain constant, the smaller the angle α between the waistline L1 and the axis L2 of the flow channel wall 3343, the smaller the coefficient of variation of the liquid output, indicating a more stable liquid output from the needle 334. When the angle α ≤ 30°, it has the technical effect of ensuring that the coefficient of variation does not exceed 15%. Preferably, when the angle α ≤ 10°, it has the technical effect of ensuring that the coefficient of variation does not exceed 10%.
[0099] As shown in any of Tables 1 to 4, when other parameters remain constant, the lower the gas pressure, the smaller the liquid output (droplet volume) of the needle 334. This means that the gas pressure can be controlled by controlling the gas source controller 32 to achieve micro-sampling.
[0100] As shown in Table 5, when other parameters remain unchanged, the smaller the diameter R1 of the flow path 3344, the smaller the coefficient of variation of the liquid output, which means that the liquid output of the needle 334 is more stable.
[0101] As shown in Table 6, when other parameters remain unchanged, the smaller the diameter R2 of the end face of the flow channel wall 3343, the smaller the coefficient of variation of the liquid output, which means that the liquid output of the needle 334 is more stable.
[0102] The diameter R1 of the flow path 3344 in this application can satisfy: 130μm≤R1≤250μm. The diameter R2 of the end face of the flow channel wall 3343 can satisfy: 350μm≤R2≤700μm.
[0103] It is understood that the sample dispensing type in this application is non-contact dispensing. Compared to traditional contact dispensing, the droplet output is stable, the coefficient of variation is small, and the needle can hold a relatively large amount of reagent. Compared to traditional syringe pumps, air pressure control allows for a smaller output volume, meeting the needs of more application scenarios.
[0104] See Figure 2 The detection module 4 may include a detection camera 41 and a supplementary lighting device 42. The detection camera 41 can be tilted and aligned with the needle 334. The supplementary lighting device 42 can be a supplementary light, such as a supplementary lamp, to provide sufficient light source for the detection camera 41. The supplementary lighting device 42 can be positioned on the opposite side of the detection camera 41, i.e., in the horizontal direction, with the needle 334 ( Figure 2 (Not shown) is positioned between the detection camera 41 and the supplementary lighting device 42.
[0105] The detection module 4 and the droplet module 3 can be connected together to achieve synchronous movement.
[0106] In traditional solutions, the inspection camera is typically positioned at the top of the frame structure. After the droplet module has applied the sample three times, the camera detects the size and distribution of the droplets to determine if the sample application meets requirements. Since its position is fixed, for example, the camera can only take a picture after the needle application step on the chip is complete to assess the overall sample application result and determine if it meets processing requirements. This is inefficient. For instance, if there are 10 application steps, and the 5th application fails, the final result can only be determined after the 10th application, wasting time and materials and resulting in low work efficiency.
[0107] The detection camera 41 in this application can move synchronously with the droplet module 3, and its focal length can be fixed, enabling continuous sampling and detection with high efficiency. For example, if there are 10 sampling operations in total, and the 5th sampling is unqualified, the unqualified sample can be detected by the detection module 4 after the 5th sampling. With the corresponding program, the operator can be alerted or other robotic arms can be controlled to discard the unqualified chip, improving efficiency and saving materials.
[0108] The detection camera 41 can be broadly understood as a device capable of recognizing images.
[0109] See Figure 2 The reagent module 5 can be a structure for storing and holding reagents. The droplet module 3 can absorb liquid from the reagent module 5 and move it to the sample dispensing station module 6, etc., to realize subsequent processes.
[0110] See Figure 2 , Figure 6, Figure 7 The sampling station module 6 may include a first base 61, a base column 62, and a second base 63. The second base 63 is mounted on the base plate 11 of the frame 1. Furthermore, the second base 63 supports the first base 61 through the base column 62.
[0111] A mounting slot 611 is provided in the first base 61. For example, taking a rectangular chip as an example, the mounting slot 611 can be approximately rectangular. At least one corner of the mounting slot 611 can be provided with a first redundancy space 612, and at least one pair of opposite sides of the mounting slot 611 can be provided with a second redundancy space 613. For example, the first redundancy space 612 and the second redundancy space 613 can be spaces extending beyond the rectangular sides of the mounting slot 611. Figure 7 As shown, the edges of the first redundant space 612 and the second redundant space 613 can be arc-shaped. The first redundant space 612 can be a 3 / 4 circle, and the second redundant space 613 can be a semicircle.
[0112] The first redundant space 612 prevents the right angles of products, such as rectangular ones, from colliding with the right angles of the mounting slot 611, thus avoiding damage to the product due to the forces between the product and the mounting slot 611 during placement and removal. The second redundant space 613 provides operational space for product placement and removal. For example, tweezers or grippers can be inserted into the second redundant space 613 for clamping operations. Based on the function of the redundant space, the area of the second redundant space 613 can be larger than that of the first redundant space 612, further facilitating clamping operations.
[0113] In conventional solutions, when the mounting groove 611 is smooth or contains liquids such as water, the product becomes difficult to remove after installation. In the embodiment of this application, a through hole 614 penetrating the first base 61 in the height direction can be provided in the mounting groove 611. The through hole 614 reduces the pressure of vacuum adsorption and provides a force application point. For example, tools can be used to push the product upwards from the through hole 614 at the bottom of the first base 61, and then tweezers, grippers, or other tools can be used to grasp the product from above, thus facilitating product removal. This prevents damage to the product caused by the small contact area and high gripping force when directly removing it from above.
[0114] Of course, this application does not limit the number of mounting slots 611 provided in the sampling station module 6. For example, multiple mounting slots 611 can be provided to enable simultaneous sampling of multiple products. The base column 62 can be connected to the first base 61 and the second base 63 by, for example, threaded connection. It is understood that the detachable connection between the base and the base column in this application increases flexibility, allowing the first base 61 with the corresponding mounting slot 611 to be replaced according to the different products to be sampled.
[0115] See Figure 6 , Figure 8 , Figure 9 , Figure 10 The cleaning module 7 may include a cleaning zone 71 and a drying zone 72.
[0116] The cleaning area 71 may include a cleaning tank 711, a cleaning column 712, and a connecting block 713. The cleaning tank 711 may be connected to the connecting block 713 and mounted on the base plate 11 of the frame 1 through the connecting block 713.
[0117] The cleaning column 712 is disposed in the cleaning tank 711. The cleaning column 712 can spray liquid in a controlled manner. For example, after the needle 334 of the droplet module 3 is finished with one sample, it can be moved here for cleaning in order to carry out the next round of liquid collection, sample dispensing and cleaning operations.
[0118] For example, a cleaning hole 7121 can be provided in the cleaning column 712, through which cleaning fluid can be sprayed vertically, and the spray height of the cleaning fluid is higher than the highest point of the cleaning column 712. The number of cleaning holes 7121 can be one or more, for example... Figure 8 The device has three cleaning holes 7121, which can be used to clean three needles simultaneously. Of course, this application does not limit the number of cleaning holes 7121.
[0119] The top surface of the cleaning column 712 may be provided with a bend 7122, and the two sides of the bend 7122 include surfaces with different degrees of inclination, such as a horizontal surface 7123 and an inclined surface 7124. The horizontal surface 7123 may be parallel to the substrate 11, and the inclined surface 7124 may be inclined to the substrate 11. Furthermore, the height of the inclined surface 7124 gradually decreases as it moves away from the bend 7122. The bend 7122 may pass through the center of the cleaning hole 7121.
[0120] The inclined surface 7124 reduces the retention of cleaning fluid on the top surface of the cleaning column 712 and guides the flow of the cleaning fluid. See also Figure 9 A drain outlet 7111 can be provided at the bottom of the cleaning tank 711 on the inclined side 7124 (i.e., the bottom of the cleaning tank) to allow the cleaning solution to drain smoothly. See also Figure 6 The inclined surface 7124 can be oriented away from the spotting station module 6 to minimize the splashing of cleaning fluid onto the spotting station module 6.
[0121] The horizontal plane 7123 maintains the ejection height of the liquid in the cleaning orifice 7121. For example, under the same pressure, if the cleaning column 712 is set as a single inclined plane, the ejection height of the solution will be quite limited. To ensure that the needle 334 can be cleaned, the needle 334 needs to extend into the cleaning orifice 7121 to a certain extent, for example, the needle 334 should be below the highest point of the cleaning orifice 7121. However, after the sample is applied, the needle 334 may have residual corrosive and diffusive substances. If the needle 334 extends into the cleaning orifice 7121, these corrosive and diffusive substances can easily diffuse along the cleaning orifice 7121 to the source of the cleaning solution, causing cross-contamination. In this application, the horizontal plane 7123 maintains the ejection height of the cleaning solution, and the needle 334 can be located above the horizontal plane 7123 (or the highest point of the cleaning column 712) and cleaned by the ejected water column, thus minimizing the problem of cross-contamination.
[0122] The cleaning module 7 includes a cleaning fluid supply source connected to the cleaning port 7121. A check valve (not shown in the figure) can be installed between the cleaning fluid supply source and the cleaning port 7121 to prevent cross-contamination.
[0123] An arc-shaped surface 7125 can be provided on the side of the cleaning column 712 away from the discharge port 7111, and an inclined surface can be provided at the bottom of the cleaning tank 711, so that the discharge port 7111 is the lowest point of the bottom surface of the cleaning tank 711, so that the waste liquid can be recovered in time.
[0124] See Figure 6 , Figure 10 The drying zone 72 may include a drying block 721, a base 722, and a guide rail 723. The drying zone 72 may be located between the cleaning tank 711 and the sample dispensing station module 6. The drying block 721 may be made of clean cotton or similar materials.
[0125] Maintaining a certain distance between the sampling station module 6 and the cleaning tank 711 helps to minimize liquid splashing onto the sampling station module 6 during the cleaning process. A drying zone 72 is provided between the sampling station module 6 and the cleaning tank 711, which not only makes the module more compact but also absorbs some of the splashed liquid, reducing the possibility of contamination. After cleaning the needle 334, the needle 334 can be inserted into the drying block 721 to dry it as much as possible.
[0126] A guide rail 723 can be provided on the substrate 11, and a base 722 is slidably mounted on the guide rail 723. The drying block 721 is connected to the base 722. This makes the base easy to pull out, thereby making the drying block 721 easy to replace. The drying block 721 may include a shell and a core. The shell may be provided with a magnet to attract and fix it to the cleaning tank 711 or the sample dispensing station module 6, reducing shaking.
[0127] The above description is the preferred embodiment of this application. It should be noted that, for those skilled in the art, several improvements and modifications can be made without departing from the principle of this application, and these improvements and modifications should also be considered within the scope of protection of this application.
[0128] In addition, the term "liquid" in this application should be interpreted broadly. For example, liquid may include solutions, suspensions, emulsions, dispersions, melts, water, etc.
[0129] The embodiments disclosed in this application present the following solutions.
[0130] This pipetting and spotting workstation includes:
[0131] substrate;
[0132] A motion module is mounted on the base plate. The motion module includes a guide rail and a slider. The slider is capable of moving in three mutually perpendicular directions: X, Y, and Z.
[0133] A droplet module, comprising a needle connected to an external environment, wherein the droplet module is configured to control the needle's intake and ejection of liquid by controlling air pressure; and
[0134] The detection module is connected to the droplet module via the same slider in the motion module, enabling the droplet module and the detection module to move synchronously. The detection module includes a detection camera and a supplementary lighting device. The detection camera can take pictures of the liquid ejected from the needle. In the horizontal direction, the needle is located between the detection camera and the supplementary lighting device.
[0135] In at least one embodiment, the needle includes a flow channel wall and a flow path located in the flow channel wall, wherein in a cross section along the axis of the needle, the waistline of the flow channel wall makes an angle α with the axis, satisfying: α≤30°, and the cross section of the flow path is circular.
[0136] In at least one embodiment, α ≤ 10°.
[0137] In at least one embodiment, the diameter of the flow path is R1, and the diameter of the end face of the flow channel wall is R2, satisfying:
[0138] 130μm≤R1≤250μm;
[0139] 350μm≤R2≤700μm.
[0140] In at least one embodiment, the droplet module further includes:
[0141] A shell structure, wherein a flow channel is provided in the shell structure, and one end of the flow channel is controllably connected to the needle tip; and
[0142] A flow channel control structure includes a sealing plug, which controls the connection between the flow channel and the needle by controlling whether the sealing plug blocks or does not block the connection position between the needle and the flow channel.
[0143] In at least one embodiment, a cleaning module is further included, the cleaning module comprising a cleaning area.
[0144] The cleaning area includes:
[0145] A cleaning tank, wherein the bottom of the cleaning tank is provided with a drain outlet for discharging liquid;
[0146] A cleaning column is disposed in the cleaning tank. The cleaning column has one or more cleaning holes that can spray cleaning liquid vertically upwards, and the spray height of the cleaning liquid is greater than the highest point of the cleaning column.
[0147] In at least one embodiment, the top surface of the cleaning column includes two surfaces with different degrees of inclination, and the two surfaces with different degrees of inclination are connected by a turning point, which passes through the center of the cleaning hole.
[0148] In at least one embodiment, the two surfaces with different degrees of inclination include a horizontal surface and an inclined surface.
[0149] In at least one embodiment, the height of the slope gradually decreases as it moves away from the bend, and in the horizontal direction, the slope is closer to the outlet than the horizontal plane.
[0150] The needle cleaning module includes a cleaning area, which includes:
[0151] A cleaning tank, wherein the bottom of the cleaning tank is provided with a drain outlet for discharging liquid;
[0152] A cleaning column is disposed in the cleaning tank. The cleaning column has one or more cleaning holes through which cleaning liquid can be sprayed vertically upwards, and the spray height of the cleaning liquid is greater than the highest point of the cleaning column.
[0153] The top surface of the cleaning column includes two surfaces with different inclinations, and there is a turning point between the two surfaces with different inclinations. The turning point passes through the center of the cleaning hole.
[0154] In at least one embodiment, the two surfaces with different degrees of inclination include a horizontal surface and an inclined surface.
[0155] In at least one embodiment, the height of the slope gradually decreases as one moves away from the bend.
[0156] In at least one embodiment, in the horizontal direction, the inclined plane is closer to the outlet than the horizontal plane.
[0157] In at least one embodiment, the side of the cleaning column away from the outlet is provided with an arc-shaped surface.
[0158] In at least one embodiment, the bottom inner surface of the cleaning tank is an inclined surface, and the outlet is located at the lowest point of the bottom inner surface of the cleaning tank.
[0159] In at least one embodiment, the needle cleaning module includes a cleaning fluid supply source connected to the cleaning port, and a check valve is provided between the cleaning fluid supply source and the cleaning port.
[0160] In at least one embodiment, the needle cleaning module further includes a drying zone, which comprises a drying block, a base, and a guide rail.
[0161] The base is slidably mounted on the guide rail, the drying block is connected to the base, and the drying block abuts against the cleaning tank.
[0162] The pipetting workstation provided in this application includes the cleaning module described above; and
[0163] A droplet module, capable of drawing in and ejecting liquid, includes a needle.
[0164] When the needle moves to the cleaning hole and is being cleaned, the needle is located above the highest point of the cleaning column.
[0165] In at least one embodiment, the pipetting and spotting workstation includes the cleaning module described above; and
[0166] The sample dispensing station module has a drying zone located between the sample dispensing station module and the cleaning zone.
[0167] This droplet module is used to draw in and eject liquid. The droplet module includes a gas source controller and a droplet module body. The droplet module body is connected to a gas source through the gas source controller.
[0168] The droplet module body includes a needle tip, which is connected to the external environment. The droplet module is configured to control the needle tip to draw in and eject liquid by controlling air pressure.
[0169] The needle includes a flow channel wall and a flow path located in the flow channel wall. In a cross-section along the axis of the needle, the waistline of the flow channel wall makes an angle α with the axis, where α satisfies: α≤30°.
[0170] In at least one embodiment, the droplet module further includes:
[0171] A housing structure, wherein a flow channel is provided in the housing structure, one end of the flow channel is connected to the air source controller, and the other end of the flow channel is controllably connected to the needle; and
[0172] A flow channel control structure includes a sealing plug, which controls the connection between the other end of the flow channel and the needle by controlling whether the sealing plug blocks or does not block the connection position between the needle and the flow channel.
[0173] In at least one embodiment, the flow channel includes:
[0174] A first flow channel, one end of which is connected to the gas source controller;
[0175] The second flow channel has a circular cross-section, and one end of the second flow channel is connected to the other end of the first flow channel;
[0176] The third flow channel has a hollow cylinder structure at its first end, which is connected to the other end of the second flow channel. The second end of the third flow channel is radially deflected inward, and its cross-section is an annular. When the sealing plug is not blocked, the liquid can flow through the second end and the needle.
[0177] In at least one embodiment, the flow channel control structure further includes a sealing plug displacement device, which includes a connector and a body. The sealing plug is disposed at the end of the connector, the connector is movably connected to the body, and the body is configured to allow axial movement of the connector.
[0178] The sealing plug displacement device and the sealing plug are disposed in the central cavity of the third flow channel. When the sealing plug is pushed against the needle by the connector, the sealing plug blocks the communication between the third flow channel and the needle.
[0179] In at least one embodiment, the housing structure includes a baffle structure comprising a first baffle having a hole through which the third flow channel and the connector pass, and the diameter of the sealing plug being larger than the diameter of the connector.
[0180] After the sealing plug moves away from the needle, the sealing plug abuts against the first baffle, and a sealing space is formed between the first baffle and the needle.
[0181] In at least one embodiment, the housing structure is provided with a baffle structure, the baffle structure including a second baffle, the second baffle being disposed at the connection between the second flow channel and the third flow channel, and the main body of the sealing plug displacement device being connected to the second baffle.
[0182] In at least one embodiment, α ≤ 10°.
[0183] In at least one embodiment, the diameter of the flow path is R1, and the diameter of the end face of the flow channel wall is R2, satisfying:
[0184] 130μm≤R1≤250μm;
[0185] 350μm≤R2≤700μm.
[0186] The pipetting and spotting workstation provided in this application includes:
[0187] The droplet module as described above; and
[0188] The cleaning module includes a cleaning area.
[0189] The cleaning area includes:
[0190] A cleaning tank, wherein the bottom of the cleaning tank is provided with a drain outlet for discharging liquid;
[0191] A cleaning column is disposed in the cleaning tank. The cleaning column has one or more cleaning holes that can spray cleaning liquid vertically upwards, and the spray height of the cleaning liquid is greater than the highest point of the cleaning column.
[0192] In at least one embodiment, the top surface of the cleaning column includes two surfaces with different degrees of inclination, and the two surfaces with different degrees of inclination are connected by a turning point, which passes through the center of the cleaning hole.
[0193] The sampling station module includes a first base, in which a mounting groove is provided. The mounting groove has a through hole extending through the first base in the thickness direction. The mounting groove is rectangular, and at least one of the four corners of the mounting groove has a first redundant space.
[0194] In at least one embodiment, at least one set of opposite sides of the two sets of mounting slots is provided with a second redundant space.
[0195] In at least one embodiment, the sampling station module further includes a base column and a second base, wherein the first base is detachably connected to the second base via the base column.
[0196] The pipetting and spotting workstation provided in this application includes: the spotting station module as described above;
[0197] A droplet module, comprising a needle capable of controlled suction and ejection of liquid; and
[0198] A cleaning module, which is capable of cleaning the needle of the droplet module.
[0199] In at least one embodiment, the cleaning module includes a cleaning area, the cleaning area comprising:
[0200] A cleaning tank, wherein the cleaning tank is provided with a drain outlet for discharging liquid;
[0201] A cleaning column is disposed in the cleaning tank. The cleaning column has one or more cleaning holes that can spray cleaning liquid vertically upwards, and the spray height of the cleaning liquid is greater than the highest point of the cleaning column.
[0202] In at least one embodiment, the top surface of the cleaning column includes two surfaces with different degrees of inclination, and the two surfaces with different degrees of inclination are connected by a turning point, which passes through the center of the cleaning hole.
[0203] In at least one embodiment, the two surfaces with different degrees of inclination include a horizontal surface and an inclined surface.
[0204] In at least one embodiment, the height of the slope gradually decreases as one moves away from the bend.
[0205] In at least one embodiment, the inclined plane is further away from the sampling station module than the horizontal plane.
[0206] In at least one embodiment, the needle includes a flow channel wall and a flow path located in the flow channel wall. In a cross-section along the axis of the needle, the waistline of the flow channel wall makes an angle α with the axis, where α satisfies: α≤30°, and the cross-section of the flow path is circular.
[0207] In at least one embodiment, the cleaning module includes a drying zone, which includes a drying block, a base, and a guide rail. The base is slidably mounted on the guide rail, the drying block is connected to the base, and the drying block abuts against the cleaning tank.
Claims
1. A pipetting and spotting workstation, characterized in that, include: Droplet module (3); as well as The cleaning module (7) includes a cleaning area (71). The cleaning zone (71) includes: A cleaning tank (711) is provided at the bottom of which a drain outlet (7111) is provided for discharging liquid; A cleaning column (712) is disposed in the cleaning tank (711). The cleaning column (712) has one or more cleaning holes (7121) that can spray cleaning liquid vertically upwards, and the spray height of the cleaning liquid is greater than the highest point of the cleaning column (712). The top surface of the cleaning column (712) includes two surfaces with different inclinations, and a turning point (7122) is located between the two surfaces with different inclinations. The turning point (7122) passes through the center of the cleaning hole (7121). The two surfaces with different degrees of inclination include a horizontal surface (7123) and an inclined surface (7124), the height of which gradually decreases as one moves away from the turning point (7122). The droplet module is used to draw in and eject liquid. The droplet module includes a gas source controller (32) and a droplet module body (33). The droplet module body (33) is connected to a gas source through the gas source controller (32). The droplet module body (33) includes a needle (334) connected to the external environment. The droplet module (3) is configured to control the needle (334) to draw in and eject liquid by controlling the air pressure. The needle (334) includes a flow channel wall (3343) and a flow path (3344) located in the flow channel wall (3343). In a cross section along the axis (L2) of the needle (334), the waistline (L1) of the flow channel wall (3343) and the axis (L2) make an angle α, where α satisfies: α≤30°.
2. The pipetting and spotting workstation according to claim 1, characterized in that, The droplet module also includes: A housing structure (335) having a flow channel therein, one end of which is connected to the air source controller (32), and the other end of which is controllably connected to the needle (334); and A flow channel control structure (336) includes a sealing plug (3361), which controls the connection between the other end of the flow channel and the needle (334) by controlling whether the sealing plug (3361) blocks or does not block the connection position between the needle (334) and the flow channel.
3. The pipetting and spotting workstation according to claim 2, characterized in that, The flow channel includes: A first flow channel (331) is connected at one end to the gas source controller (32); The second flow channel (332) has a circular cross-section, and one end of the second flow channel (332) is connected to the other end of the first flow channel (331). The third flow channel (333) has a hollow cylinder structure at its first end (3331). The first end (3331) of the third flow channel (333) is connected to the other end of the second flow channel (332). The second end (3332) of the third flow channel (333) is bent inward along its radial direction. The cross-section of the second end (3332) of the third flow channel (333) is an annular ring. When the sealing plug (3361) is not blocked, the liquid can flow through the second end (3332) and the needle (334).
4. The pipetting and spotting workstation according to claim 3, characterized in that, The flow channel control structure (336) further includes a sealing plug displacement device, which includes a connector (3362) and a body (3363). The sealing plug (3361) is disposed at the end of the connector (3362), the connector (3362) is movably connected to the body (3363), and the body (3363) is configured to enable the connector (3362) to move axially. The sealing plug displacement device and the sealing plug (3361) are disposed in the central cavity of the third flow channel (333). When the sealing plug (3361) is pushed against the needle (334) by the connector (3362), the sealing plug (3361) blocks the communication between the third flow channel (333) and the needle (334).
5. The pipetting and spotting workstation according to claim 4, characterized in that, The housing structure (335) is provided with a baffle structure, the baffle structure including a first baffle (3371), the first baffle (3371) having a hole for the third flow channel (333) and the connector (3362) to pass through, the diameter of the sealing plug (3361) being larger than the diameter of the connector (3362). After the sealing plug (3361) moves away from the needle (334), the sealing plug (3361) abuts against the first baffle (3371), and a sealing space is formed between the first baffle (3371) and the needle (334).
6. The pipetting and spotting workstation according to claim 4, characterized in that, The shell structure (335) is provided with a baffle structure, the baffle structure includes a second baffle (3372), the second baffle (3372) is disposed at the connection between the second flow channel (332) and the third flow channel (333), and the main body (3363) of the sealing plug displacement device is connected to the second baffle (3372).
7. The pipetting and spotting workstation according to claim 1, characterized in that, α≤10°。 8. The pipetting and spotting workstation according to claim 1, characterized in that, The diameter of the flow path (3344) is R1, and the diameter of the end face of the flow channel wall (3343) is R2, satisfying: 130μm≤R1≤250μm; 350μm≤R2≤700μm.
Citation Information
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