Full-automatic pathogen detection device

Abstract

The embodiment of the utility model discloses a full-automatic pathogen detection device which comprises a device platform which comprises a horizontally-arranged first platform frame and a second platform frame located below the first platform frame, and the first platform frame and the second platform frame are fixedly connected through a plurality of platform supports; the automatic library building module is adaptively arranged on the first platform frame and is used for automatically building a library of the biological sample to be detected; the library automatic transfer module is adaptively arranged on the first platform framework and is used for automatically receiving and transferring the established biological sample library; the sequencing module is adaptively arranged on the first platform frame and is used for receiving the transferred biological sample library and automatically sequencing; the information processing module is used for controlling the automatic library building module, the library automatic transfer module and the sequencing module; wherein the library automatic transfer module comprises: a peristaltic pump configured to convey a biological sample library; the flow meter is used for metering the flow of the biological sample library; and the bubble remover is used for removing bubbles in the biological library sample.

Description

Technical Field

[0001] This utility model belongs to the field of gene detection technology, specifically relating to a fully automated pathogen detection device. Background Technology

[0002] Electrowetting chips for automated library construction are extremely small in size, making them suitable for building high-density microfluidic systems and portable gene diagnostic devices. Simultaneously, electrowetting chips can control multiple droplets, enabling high-throughput droplet manipulation suitable for massively parallel processing. Electrowetting chips can be integrated with other microelectronics and microelectromechanical systems (MEMS) technologies to achieve multifunctionality and automation.

[0003] Nanopore sequencers can output sequencing results in real time, eliminating the need for steps like PCR amplification, sequencing reactions, and data analysis required by second-generation sequencing (such as the Illumina platform). This allows researchers to obtain data more quickly and make real-time decisions.

[0004] However, electrowetting chip technology has some technical problems, such as the long-term stability of surface hydrophobicity, electrochemical corrosion, and compatibility with biological samples. Nanopore sequencing technology also has its limitations, such as the error rate of single-molecule sequencing is usually higher than that of second-generation sequencing technology. Nanopore sequencing technology provides a powerful tool that complements traditional second-generation sequencing technology and is suitable for specific research and application scenarios.

[0005] For the reasons mentioned above, there is currently no sequencing product that can fully automate library preparation and sequencing related to nanopore sequencing. Utility Model Content

[0006] In view of this, some embodiments disclose a fully automated pathogen detection device, comprising:

[0007] The device platform includes a horizontally arranged first platform frame and a second platform frame located below the first platform frame, and the first platform frame and the second platform frame are fixedly connected by multiple platform supports.

[0008] The automated library construction module is adapted and set on the first platform framework to automatically construct libraries for biological samples to be tested.

[0009] The automatic library transfer module is adapted and set on the first platform framework to automatically receive and transfer the established biological sample library.

[0010] The sequencing module, adapted and set on the first platform framework, is used to receive transferred biological sample libraries and automatically sequence them;

[0011] The information processing module is used to control the automated library construction module, the automated library transfer module, and the sequencing module, and to perform information processing.

[0012] The automatic document transfer module includes:

[0013] A peristaltic pump, configured to deliver biological sample libraries;

[0014] Flow meter, used to measure the flow rate of biological sample libraries;

[0015] Defoamer, used to remove air bubbles from biological library samples.

[0016] Furthermore, some embodiments of the fully automated pathogen detection device also include:

[0017] The heating module is adapted to be installed on the second platform frame, located below the automated database construction module, and is used to control the temperature of the automated database construction module;

[0018] The magnet module, which is adapted to be mounted on the second platform frame and located below the automated library construction module, is used to achieve magnetic bead separation and biological sample purification.

[0019] Some embodiments disclose a fully automated pathogen detection device, wherein the automated library construction module includes a probe plate assembly and a library construction chip configured to be placed in the probe plate assembly; wherein:

[0020] The library construction chip includes a base plate and an upper cover plate set on the base plate. The edges of the base plate and the upper cover plate are sealed to each other. The middle part of the upper cover plate protrudes outward to form a cavity with the base plate. The upper cover plate is provided with an oil injection hole, a sample addition hole and a collection hole.

[0021] The probe plate assembly includes:

[0022] The probe board body has a through-hole structure, the shape of which is adapted to the library construction chip.

[0023] The probe board base plate is adapted to be located below the probe board body and is movably connected to the probe board body to support the library construction chip.

[0024] Probe plate base, used to mount the probe plate body;

[0025] The probe plate handle is located on the probe plate body and is movably connected to the probe plate body for rotating the probe plate body.

[0026] Some embodiments of the fully automated pathogen detection device disclose a magnet module comprising:

[0027] magnet;

[0028] A vertically movable component for setting up and vertically moving the position of the magnet;

[0029] A horizontally movable component is used to set the position of the vertically movable component and the horizontally movable magnet.

[0030] Some embodiments of the fully automated pathogen detection device disclose a heating module including:

[0031] Heating plate;

[0032] The base; the heating plate is mounted on the base via a vertically movable component; the vertically movable component includes a motor and a vertical linear guide rail component, the motor being used to drive the heating plate to move vertically under the guidance of the vertical linear guide rail component.

[0033] Some embodiments of the fully automated pathogen detection device disclose a digital microfluidic chip for library construction.

[0034] Some embodiments disclose fully automated pathogen detection devices, in which the sequencing module is a nanopore sequencer.

[0035] Some embodiments of the fully automated pathogen detection device also include a reflux condensation module adapted to be mounted on a second platform frame.

[0036] The fully automated pathogen detection device disclosed in this embodiment of the invention uses digital microfluidic chip technology to achieve rapid sample library construction. Through microfluidic technology, it realizes automated connection of library construction and nanopore sequencing without manual intervention, truly achieving unattended operation, thereby improving sequencing efficiency and accuracy. It realizes continuous automation of gene library construction, sequencing and pathogen identification, and has good application prospects in the field of pathogen detection technology. Attached Figure Description

[0037] Figure 1 Some embodiments disclose schematic diagrams of the structure of a fully automated pathogen detection device;

[0038] Figure 2 Schematic diagram of the structure of a fully automated pathogen detection device disclosed in some embodiments Figure 2 ;

[0039] Figure 3 Some embodiments disclose schematic diagrams of the library construction chip structure;

[0040] Figure 4 Some embodiments disclose schematic diagrams of probe plate assembly structures;

[0041] Figure 5 Some embodiments disclose schematic diagrams of the composition of the automatic document transfer module;

[0042] Figure 6 Some embodiments disclose schematic diagrams of the magnet module structure;

[0043] Figure 7 Some embodiments disclose schematic diagrams of the heating module structure.

[0044] Figure Labels

[0045] 1. Device platform 2. Probe plate assembly

[0046] 3. Library creation chip; 4. Automatic document transfer module

[0047] 5 Sequencing module 6 Magnet module

[0048] 7 Heating module 8 Reflux condenser module

[0049] 9 Information processing module 20 Probe board body

[0050] 21 Through-hole structure 22 Probe plate handle

[0051] 23 Probe board base plate 24 Probe board base

[0052] 31 Base plate 32 Top cover plate

[0053] 33 Oil injection hole; 34 Sample feeding hole

[0054] 35 Collection port 41 Peristaltic pump

[0055] 42 Flow meter 43 Deaerator

[0056] 44 Check valve 45 Liquid receiver

[0057] 51 sequencing chips, 60 magnets

[0058] 61 Magnet bracket 62 First cylindrical connecting column

[0059] 63 First support bracket 64 First motor

[0060] 65 Second bracket 66 Lateral linear guide rail assembly

[0061] 67 Second motor 70 Heating plate

[0062] 71 Vertical linear guide rail component 72 Heating plate base

[0063] 73 Third Motor 100 First Platform Frame

[0064] 101 Second Platform Frame 102 Platform Support Detailed Implementation

[0065] The term "embodiment" used herein, as an example, is not necessarily to be construed as superior to or better than other embodiments. Performance testing in these embodiments of the present invention, unless otherwise specified, employs conventional testing methods in the art. It should be understood that the terminology used herein is merely for describing particular implementations and is not intended to limit the scope of the disclosed embodiments of the present invention.

[0066] Unless otherwise stated, the technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this invention pertains; other test methods and technical means not specifically noted in this invention refer to test methods and technical means commonly used by one of ordinary skill in the art.

[0067] The terms “basic” and “approximately” used in this document are to describe small fluctuations. For example, they can mean less than or equal to ±5%, such as less than or equal to ±2%, such as less than or equal to ±1%, such as less than or equal to ±0.5%, such as less than or equal to ±0.2%, such as less than or equal to ±0.1%, such as less than or equal to ±0.05%. Numerical data presented or expressed in range format in this document are used for convenience and brevity only, and should therefore be flexibly interpreted to include not only the explicitly listed values ​​that define the range, but also all independent values ​​or subranges contained within that range. For example, a numerical range of “1–5%” should be interpreted to include not only the explicitly listed values ​​from 1% to 5%, but also the independent values ​​and subranges within the indicated range. Thus, this numerical range includes independent values ​​such as 2%, 3.5%, and 4%, and subranges such as 1%–3%, 2%–4%, and 3%–5%, etc. This principle also applies to ranges that list only one value. Furthermore, this interpretation applies regardless of the width of the range or the characteristics described.

[0068] In this document, including in the claims, conjunctions such as "comprising," "including," "with," "having," "containing," "involving," and "accommodating" are understood to be open-ended, meaning "including but not limited to." Only the conjunctions "consisting of" and "composed of" are closed conjunctions.

[0069] To better illustrate the content of this utility model, numerous specific details are provided in the following detailed embodiments. Those skilled in the art should understand that this utility model can be implemented even without certain specific details. In the embodiments, some methods, means, instruments, and equipment well known to those skilled in the art are not described in detail, in order to highlight the main points of this utility model.

[0070] Without conflict, the technical features disclosed in the embodiments of this utility model can be combined arbitrarily, and the resulting technical solution belongs to the content disclosed in the embodiments of this utility model.

[0071] The following combination Figure 1 , Figure 2 , Figure 3 , Figure 4 Figure 5 , Figure 6 , Figure 7 The technical details are further illustrated by specific embodiments.

[0072] Some embodiments disclose a fully automated pathogen detection device, comprising:

[0073] Device platform 1; Device platform 1 includes a horizontally arranged first platform frame 100 and a second platform frame 101 located below the first platform frame 100, the first platform frame 100 and the second platform frame 101 being fixedly connected by multiple platform supports 102; as Figure 1 , Figure 2 As shown;

[0074] An automated library construction module, adapted and installed on the first platform frame 100, is used for automated library construction of biological samples to be tested. The automated library construction module includes a probe plate assembly 2 and a library construction chip 3 placed in the probe plate assembly 2; wherein:

[0075] The library construction chip 3 includes a base plate 31 and an upper cover plate 32 disposed on the base plate 31. The edges of the base plate 31 and the upper cover plate 32 are sealed together. The middle part of the upper cover plate 32 protrudes outward to form a cavity with the base plate 31. The protruding part of the upper cover plate is provided with an oil injection hole 33, a sample application hole 34, and a collection hole 35. Usually, multiple collection holes 35 are provided and distributed in different positions to collect samples from different locations. The edge of the base plate 31 extends outward by an appropriate distance to form the base plate edge. The library construction chip 3 can usually be made of a transparent material to facilitate observation of the phenomena occurring in the biological samples inside. Figure 3 As shown;

[0076] Typically, sampling wells on library construction chips are specifically used to retrieve the library, while other circular wells are for adding samples. Oil filling wells are for selective use, used to add filling oil. All circular wells on the chip, except for the sampling wells, are for adding samples / reagents. The function of each well can be flexibly adjusted according to different experiments. The base plate of the library construction chip not only supports the top cover plate, but its surrounding probe contacts allow the probes on the probe plate to connect to the circuitry on the chip, transmitting control signals to the corresponding control electrodes to drive the droplets. The chip processing unit consists of a top cover and a bottom plate. The top cover is designed with an oil injection hole, a sample loading hole, and a droplet collection hole. The bottom plate is also engraved with circuits and electrodes. When using the library construction chip, oil needs to be filled between the top cover and the bottom plate. Changing the voltage of the electrodes can drive the sample or reagent droplets to realize the entire experimental process. Biological sample droplets are added to the library construction chip through the sample loading hole and move to different positions on the chip under the control of the control system for operations such as merging, splitting, and incubation. The biological sample or reagent droplets are protected from the influence of the laboratory environment and contamination during operation by being wrapped in oil.

[0077] like Figure 4 As shown, the probe plate assembly 2 includes:

[0078] The probe plate body 20 has a through hole structure 21, the shape of which is adapted to the library construction chip 3.

[0079] The probe plate base plate 23 is adapted to be disposed below the probe plate body 20 and is movably connected to the probe plate body to support the library construction chip 3. Typically, the probe plate body has a structure for placing the library construction chip 3. After the library construction chip 3 is placed in this structure, it is fixed in a fixed position on the probe plate base plate 23. After the probe plate base plate 23 is pushed into the position adapted to the probe plate body 20, the library construction chip 3 is located below the through hole structure 21. The lower edge of the through hole structure 21 presses against the edge of the base plate of the library construction chip, thus fixing the library construction chip 3. The interior of the library construction chip 3 can be observed through the through hole structure 21.

[0080] The probe plate base 24 is used to mount the probe plate body 20; furthermore, the probe plate base 24 is fixed at an appropriate position on the first platform frame 100 so that the probe plate assembly 2 is mounted and fixed.

[0081] The probe plate handle 22 is disposed on the probe plate body 20 and is movably connected to the probe plate body 20. Generally, the probe plate handle 22 includes a handle and handle brackets located at both ends thereon. One end of the handle bracket is fixedly connected to the handle, and the other end of the handle bracket is rotatably connected to the front side of the probe plate body 20. When the handle bracket is pulled up, it drives the front end of the probe plate body 20 to rotate upward, thereby pulling out the probe plate bottom plate 23 and taking out the library construction chip 3 from it.

[0082] An automatic library transfer module 4, adapted and installed on the first platform frame 100, is used to automatically receive and transfer the established biological sample library. The automatic library transfer module 4 includes: a peristaltic pump 41, configured to transport the biological sample library; one end of the peristaltic pump 41 is sequentially connected to a reservoir 45, a one-way valve 44, and a library construction chip 3; the other end of the peristaltic pump 41 is sequentially connected to a flow meter 42 and a defoamer 43, with the defoamer 43 further connected to the detection chip 51 of the sequencing module 5. Figure 5 As shown; generally, a defoamer can be a vacuum pump;

[0083] Typically, peristaltic pumps are used to move biological sample liquids and can be set with speed and positive / negative direction; the flow meters are non-contact flow meters, allowing you to control the library transfer flow rate; and defoamers can remove air from the biological sample liquids.

[0084] The library transfer module is responsible for purging air from the tubing of the automated library transfer module, injecting the sequencing chip conduction buffer, and performing subsequent fluid operations such as library injection into the chip. The workflow includes: turning on the vacuum pump connected to the defoamer to remove air from the sequencing chip through the defoamer, and waiting for the air bubbles to be removed; starting the peristaltic pump and running it for a set time, which can be adjusted according to the final test; introducing a set amount of conduction buffer (approximately 500 μL) into the sequencing chip through the defoamer; letting it stand for 15 minutes (adjustable); starting the peristaltic pump and running it for a set time (e.g., 3 minutes, adjustable according to the final test), introducing the library (e.g., approximately 400 μL) into the sequencing chip through the defoamer; and starting sequencing.

[0085] The sequencing module 5 is adapted and set on the first platform frame 100 for receiving transferred biological sample libraries and automatically sequencing them;

[0086] Heating module 7, adapted and mounted on the second platform frame 101, located below the automated database construction module, is used to control the temperature of the automated database construction module; for example... Figure 7 As shown, the heating module 7 includes a heating plate 70, which is mounted on a heating plate base 72 via a vertically movable component. The vertically movable component includes a third motor 73 and a vertical linear guide rail component 71. The motor is used to drive the heating plate to move vertically under the guidance of the vertical linear guide rail component. The magnet module 6 is adapted to be mounted on the second platform frame 101 and located below the automated library construction module. It is used to realize magnetic bead separation and biological sample purification.

[0087] like Figure 6As shown, the magnet module 6 includes: a magnet 60; a vertically movable component for setting the magnet and moving its position vertically; the vertically movable component includes a magnet bracket 61 for setting the magnet 60, the magnet being disposed at one end of the magnet bracket 61, and the other end of the magnet bracket 61 being movably connected to a linear guide rail on a vertically positioned first bracket 63; a first motor 64 drives the magnet bracket 61 to move vertically along the linear guide rail via a first cylindrical connecting post 62, thereby moving the vertical position of the magnet.

[0088] The lateral movable component includes a lateral linear guide rail assembly 66, a second support 65 fixedly mounted on the lateral linear guide rail assembly 66, and a second motor 67 connected to the second support 65. The vertical movable component is mounted on the lateral linear guide rail assembly 66. The second motor 67 drives the second support 65, thereby driving the vertical movable component to move laterally along the lateral linear guide rail assembly 66. During this process, the horizontal position of the magnet is simultaneously moved. By precisely and stably controlling the position and movement of the magnet, the requirements for magnetic bead separation and purification during library construction can be met.

[0089] Information processing module 9 controls the automated library construction module, the automatic library transfer module, and the sequencing module, and performs information processing. Typically, the sequencing module detects the gene sequence of pathogens in biological samples from the library, and further determines the type of pathogen based on the gene sequence.

[0090] Some embodiments of the fully automated pathogen detection device disclose a digital microfluidic chip for library construction.

[0091] Some embodiments disclose fully automated pathogen detection devices, in which the sequencing module is a nanopore sequencer.

[0092] Some embodiments of the fully automated pathogen detection device also include a reflux condensation module 8, which is adapted to be mounted on the second platform frame 101.

[0093] The fully automated pathogen detection device disclosed in this embodiment integrates various technologies. During the library construction process before sequencing, it utilizes an electrowetting chip to introduce nucleic acid samples, automatically constructing and producing the library. Simultaneously, a library transfer module adds the library clips to a nanopore sequencer for sequencing. The entire process is executed with a single click, requiring no additional steps. This automated gene sequencing device is a highly integrated device that combines library construction and nanopore sequencing processes, achieving a fully automated process for standard nucleic acid library construction, sequencing, and data analysis.

[0094] The fully automated pathogen detection device disclosed in this embodiment of the invention employs digital microfluidic chip technology to achieve rapid sample library construction. Through microfluidic technology, it automates library construction and nanopore sequencing without manual intervention, truly achieving unattended operation and thus improving sequencing efficiency and accuracy. It realizes continuous automation of gene library construction, sequencing, and pathogen identification, and has promising application prospects in the field of pathogen detection technology.

[0095] The technical solutions and technical details disclosed in the embodiments of this utility model are merely illustrative of the inventive concept of this utility model and do not constitute a limitation on the technical solutions of the embodiments of this utility model. Any conventional changes, substitutions or combinations made to the technical details disclosed in the embodiments of this utility model have the same inventive concept as this utility model and are within the protection scope of the claims of this utility model.

Claims

1. A fully automated pathogen detection device, characterized in that, include: Device platform; The device platform includes a horizontally arranged first platform frame and a second platform frame located below the first platform frame. The first platform frame and the second platform frame are fixedly connected by multiple platform supports. An automated library construction module is adapted and set on the first platform framework to automatically construct libraries for biological samples to be tested. An automatic library transfer module is adapted and installed on the first platform framework to automatically receive and transfer the established biological sample library. The sequencing module, adapted and installed on the first platform framework, is used to receive the transferred biological sample library and automatically sequence it; An information processing module is used to control the automated library construction module, the automated library transfer module, and the sequencing module, and to perform information processing. The automatic document transfer module includes: A peristaltic pump, configured to deliver biological sample libraries; Flow meter, used to measure the flow rate of biological sample libraries; Defoamer, used to remove air bubbles from biological library samples.

2. The fully automated pathogen detection device of claim 1, wherein, Also includes: A heating module is adapted and installed on the second platform frame, located below the automated database construction module, and is used to control the temperature of the automated database construction module; The magnet module is adapted and installed on the second platform frame, located below the automated library construction module, and is used to realize magnetic bead separation and biological sample purification.

3. The fully automated pathogen detection device of claim 1, wherein, The automated database construction module includes a probe board assembly and a database construction chip configured to be placed within the probe board assembly; wherein: The library construction chip includes a base plate and an upper cover plate disposed on the base plate. The edges of the base plate and the upper cover plate are sealed to each other. The middle part of the upper cover plate protrudes outward to form a cavity with the base plate. The upper cover plate is provided with an oil injection hole, a sample addition hole and a collection hole. The probe plate assembly includes: The probe plate body has a through-hole structure, the shape of which is adapted to the library construction chip. The probe board base plate is adapted to be disposed below the probe board body and is movably connected to the probe board body for supporting the library construction chip. Probe plate base, used to mount the probe plate body; A probe plate handle is disposed on the probe plate body and is movably connected to the probe plate body.

4. The fully automated pathogen detection device of claim 2, wherein, The magnet module includes: magnet; A vertically movable component is used to position the magnet and move its position vertically. A laterally movable component is used to set the vertically movable component and to position the magnet laterally.

5. The fully automated pathogen detection device according to claim 2, characterized in that, The heating module includes: Heating plate; The base; the heating plate is mounted on the base via a vertically movable component; the vertically movable component includes a motor and a vertical linear guide rail component, the motor being used to drive the heating plate to move vertically under the guidance of the vertical linear guide rail component.

6. The fully automated pathogen detection device of claim 3, wherein, The library construction chip is a digital microfluidic chip.

7. The fully automated pathogen detection device of claim 1, wherein, The sequencing module is a nanopore sequencer.

8. The fully automated pathogen detection device of claim 1, wherein, It also includes a reflux condensation module, which is adapted and installed on the second platform frame.

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