Automatic sequencing pretreatment equipment compatible with multiple types of samples to be detected

Abstract

The invention provides automatic sequencing pretreatment equipment compatible with multiple types of to-be-detected samples, and relates to the technical field of nucleic acid sequencing. The apparatus comprises: a sample receiving device comprising a liquid biological sample inlet and a solid biological sample inlet; the nucleic acid extraction device comprises a first transfer module for transferring a to-be-detected sample stored in a liquid biological sample inlet to a liquid biological sample treatment area, and a second transfer module for transferring a to-be-detected sample stored in a solid biological sample inlet to a solid biological sample treatment area, a liquid biological sample treatment area and a solid biological sample treatment area; the liquid biological sample treatment area and the solid biological sample treatment area are used for performing nucleic acid extraction treatment on a to-be-detected sample to obtain a nucleic acid extract; the nucleic acid mixing device is used for mixing nucleic acid extracts; and the library construction device is used for performing library preparation treatment on the nucleic acid extract to obtain a sequencing library. According to the equipment, compatibility processing of multiple types of to-be-tested samples is realized.

Description

Technical Field

[0001] The present application relates to the field of nucleic acid sequencing technology, and in particular to an automated sequencing pre-processing device that is compatible with multiple types of samples to be tested. Background Art

[0002] Sequencing pre-processing equipment is a highly integrated laboratory device primarily used to process, analyze, and generate sequence information for biological samples such as DNA and RNA. Its core function is to complete the entire process from sample to usable gene sequence information through a series of pre-programmed steps, encompassing key steps such as nucleic acid extraction, quality control, and library construction.

[0003] In related technologies, the processing procedures for different types of test samples (such as liquid blood samples, solid tissue samples, and mixed samples) differ significantly. Consequently, sequencing pre-processing equipment is primarily optimized for specific test sample types and lacks compatibility with a wide range of sample types. This limitation necessitates the selection of appropriate sequencing pre-processing equipment based on the sample type in practical applications, making it impossible to process multiple types of test samples in a compatible manner. Summary of the Invention

[0004] The present application provides an automated sequencing pre-processing device that is compatible with multiple types of samples to be tested, thereby achieving compatible processing of multiple types of samples to be tested.

[0005] The first aspect of the present application provides an automated sequencing pre-processing device compatible with multiple types of test samples, comprising:

[0006] Sample receiving device, nucleic acid extraction device, nucleic acid mixing device and library construction device;

[0007] The sample receiving device includes: a liquid biological sample inlet and a solid biological sample inlet that are isolated from each other;

[0008] The nucleic acid extraction device comprises: a first transfer module, a second transfer module, and a liquid biological sample processing area and a solid biological sample processing area that are isolated from each other;

[0009] A first transfer module transfers the sample to be tested stored in the liquid biological sample inlet to the liquid biological sample processing area;

[0010] The second transfer module transfers the sample to be tested stored in the solid biological sample inlet to the solid biological sample processing area;

[0011] The liquid biological sample processing area and the solid biological sample processing area perform nucleic acid extraction on the samples to be tested received by each of them to obtain nucleic acid extracts;

[0012] a nucleic acid mixing device, which is in one-way communication with the liquid biological sample processing area and the solid biological sample processing area respectively;

[0013] A nucleic acid mixing device for mixing the nucleic acid extracts outputted from the liquid biological sample processing area and the solid biological sample processing area;

[0014] a library construction device, which is in one-way communication with the nucleic acid mixing device;

[0015] The library construction device performs library preparation processing on the nucleic acid extract to obtain a sequencing library.

[0016] In one possible design, the liquid biological sample inlet includes: a test tube rack;

[0017] A test tube rack, used to store test tubes containing samples to be tested;

[0018] The first transfer module is a pipette;

[0019] The pipette absorbs the sample to be tested at the test tube rack and releases the sample to be tested at the liquid biological sample processing area.

[0020] In one possible design, a label is provided on the test tube;

[0021] The liquid biological sample inlet also includes: an identification reading module;

[0022] The identification reading module reads the sample information of the sample to be tested carried by the identification.

[0023] In one possible design, a solid-state biological sample inlet includes: a cartridge slot;

[0024] A box slot, used for mounting a sample box storing samples to be tested;

[0025] The second transfer module is a fixture;

[0026] The clamp clamps the sample to be tested at the box slot and releases the sample to be tested at the solid biological sample processing area.

[0027] In one possible design, the solid-state biological sample inlet further includes: an image recognition module;

[0028] The image recognition module collects the image of the sample to be tested and obtains the sample information of the sample to be tested based on the image of the sample to be tested.

[0029] In one possible design, the liquid biological sample inlet and the solid biological sample inlet further include: a conveyor belt;

[0030] The test tube rack is fixedly mounted on the conveyor belt at the liquid biological sample entrance; the conveyor belt at the liquid biological sample entrance drives the test tube rack to reciprocate at both ends of the liquid biological sample entrance;

[0031] The pipette is located at one end of the liquid biological sample inlet;

[0032] The cartridge slot is fixedly mounted on the conveyor belt of the solid biological sample entrance; the conveyor belt of the solid biological sample entrance drives the cartridge slot to reciprocate at both ends of the solid biological sample entrance;

[0033] The clamp is located at one end of the solid biological sample inlet.

[0034] In one possible design, the liquid biological sample processing area includes: a chemical lysis module and a nucleic acid purification module;

[0035] A first transfer module transfers the sample to be tested stored in the liquid biological sample inlet to the chemical lysis module;

[0036] A chemical lysis module is used to add a first lysis solution to the sample to be tested, and to perform a temperature-controlled oscillation treatment on the sample to be tested after adding the first lysis solution;

[0037] The nucleic acid purification module adds magnetic beads to the sample to be tested after temperature-controlled oscillation treatment, and performs binding and elution treatment on the sample to be tested after adding the magnetic beads to obtain a nucleic acid extract.

[0038] In one possible design, the solid biological sample processing area includes: a freezing and grinding module, a thawing and lysis module, and a phase separation module;

[0039] A second transfer module transfers the sample to be tested stored in the solid biological sample inlet to the freezing and grinding module;

[0040] Cryo-grinding module, for performing cryo-grinding on the sample to be tested;

[0041] a thawing and lysis module, adding a second lysis solution to the sample to be tested after the freeze-grinding treatment, and vortexing and oscillating the sample to be tested after the addition of the second lysis solution;

[0042] The phase separation module adds an organic solvent to the sample to be tested after the vortex oscillation treatment, and performs centrifugal stratification on the sample to be tested after the addition of the organic solvent to obtain a nucleic acid extract.

[0043] In one possible design, the library construction device includes: a fragmentation module, an end repair and adapter ligation module, an amplification module, and a magnetic bead purification module;

[0044] Fragmentation module, which performs ultrasonic fragmentation on nucleic acid extracts;

[0045] The end repair and adapter connection module performs end repair on the nucleic acid extract after ultrasonic fragmentation and adds sequencing adapters to the nucleic acid extract after end repair;

[0046] Amplification module, which amplifies the nucleic acid extract after adding sequencing adapters;

[0047] The magnetic bead purification module performs magnetic bead purification on the nucleic acid extract after amplification to obtain a sequencing library.

[0048] In one possible design, it also includes:

[0049] Sample separation devices and quality control devices;

[0050] The liquid biological sample inlet and the solid biological sample inlet are respectively connected to the sample separation device in a one-way manner;

[0051] A sample separation device separates the stored samples to be separated, and transfers the liquid type samples to be tested to the liquid biological sample inlet, and transfers the solid type samples to be tested to the solid biological sample inlet;

[0052] a library construction device, which is in one-way communication with the nucleic acid mixing device;

[0053] The quality control device comprises: a quality detection module and a notification trigger module;

[0054] The quality detection module performs quality detection on the nucleic acid extract stored in the nucleic acid mixing device; the detection results of the nucleic acid extract include: the concentration and purity ratio of deoxyribonucleic acid, and the integrity coefficient of RNA;

[0055] The notification trigger module outputs a sample replenishment notification when the test result indicates that the concentration of deoxyribonucleic acid is lower than a preset concentration, or the integrity coefficient of RNA is lower than a preset coefficient; the sample replenishment notification is used to instruct the sample to be replenished;

[0056] The notification trigger module outputs a protein contamination notification when the test result indicates that the purity ratio of the deoxyribonucleic acid is lower than the preset ratio, and the nucleic acid mixing device adds protease to the nucleic acid extract and digests the nucleic acid extract after the protease is added.

[0057] The present application provides an automated sequencing pre-processing device compatible with multiple types of test samples, the device comprising: a sample receiving device including a liquid biological sample inlet and a solid biological sample inlet; a nucleic acid extraction device including a first transfer module for transferring the test sample stored in the liquid biological sample inlet to a liquid biological sample processing area, a second transfer module for transferring the test sample stored in the solid biological sample inlet to the solid biological sample processing area, as well as a liquid biological sample processing area and a solid biological sample processing area; the liquid biological sample processing area and the solid biological sample processing area perform nucleic acid extraction processing on the test sample to obtain nucleic acid extracts; a nucleic acid mixing device for mixing the nucleic acid extracts; and a library construction device for performing library preparation processing on the nucleic acid extracts to obtain a sequencing library. The following technical effects are achieved: different types of test samples are processed respectively by the liquid biological sample processing area and the solid biological sample processing area, and the test samples are automatically mixed by the nucleic acid mixing device, thereby achieving compatible processing of multiple types of test samples; by the liquid biological sample inlet and the solid biological sample inlet, as well as the liquid biological sample processing area and the solid biological sample processing area, which are isolated from each other, cross contamination between different types of test samples is avoided, thereby achieving compatible processing of liquid and solid types of test samples; by the sample receiving device, the nucleic acid extraction device and the library construction device, automated pre-sequencing processing of the test samples is achieved, thereby improving the processing efficiency and quality of the test samples. BRIEF DESCRIPTION OF THE DRAWINGS

[0058] In order to more clearly illustrate the technical solutions in the present application or the prior art, a brief introduction will be given below to the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0059] Figure 1 A schematic diagram of the process of pre-sequencing treatment provided for related technologies;

[0060] Figure 2 Schematic diagram of the structure of the automated sequencing pre-processing device compatible with multiple types of test samples provided in the embodiment of the present application Figure 1 ;

[0061] Figure 3 Schematic diagram of the structure of the automated sequencing pre-processing device compatible with multiple types of test samples provided in the embodiment of the present application Figure 2 ;

[0062] Figure 4 Schematic diagram of the structure of the automated sequencing pre-processing device compatible with multiple types of test samples provided in the embodiment of the present application Figure 3 .

[0063] Reference numerals:

[0064] 200-Automated sequencing pre-processing equipment compatible with multiple types of test samples;

[0065] 210 - sample receiving device; 211 - liquid biological sample inlet; 2111 - test tube rack; 212 - solid biological sample inlet; 2121 - box slot; 213 - conveyor belt;

[0066] 220 - nucleic acid extraction device; 221 - first transfer module; 2211 - pipette; 222 - second transfer module; 2221 - fixture; 223 - liquid biological sample processing area; 224 - solid biological sample processing area;

[0067] 230 - Nucleic acid mixing device; 240 - Library construction device; 250 - Quality control device; 260 - Sample separation device. DETAILED DESCRIPTION

[0068] Exemplary embodiments will be described in detail herein, with examples illustrated in the accompanying drawings. In the following description, when referring to the drawings, identical numerals in different figures represent identical or similar elements, unless otherwise indicated. The embodiments described in the following exemplary embodiments are not intended to represent all embodiments consistent with the present application. Rather, they are merely examples of apparatus and methods consistent with certain aspects of the present application, as detailed in the appended claims.

[0069] In this application, words such as "first" and "second" are used to distinguish between identical or similar items with substantially the same functions and effects. Those skilled in the art will understand that words such as "first" and "second" do not limit the quantity and execution order, and words such as "first" and "second" do not necessarily limit differences. It should be noted that, in this application, words such as "exemplary" or "for example" are used to indicate examples, illustrations or explanations. Any embodiment or design described in this application as "exemplary" or "for example" should not be interpreted as being more preferred or advantageous than other embodiments or design. Specifically, the use of words such as "exemplary" or "for example" is intended to present related concepts in a concrete way. In this application, "at least one" refers to one or more, and "more than one" refers to two or more.

[0070] It should be noted that the "at..." in this application can be the instant when a certain situation occurs, or it can be a period of time after a certain situation occurs, and this application does not make specific limitations on this. In addition, the automated sequencing pre-processing equipment compatible with multiple types of samples to be tested provided in this application is only an example, and the automated sequencing pre-processing equipment compatible with multiple types of samples to be tested can also include more or less content. The user information (including but not limited to user nucleic acid information and user personal information, etc.) and data (including but not limited to data used for analysis, stored data and displayed data, etc.) involved in one or more embodiments of this application are all information and data authorized by the user or fully authorized by all parties, and the collection, use and processing of relevant data need to comply with relevant laws, regulations and standards, and provide corresponding operation entrances for users to choose to authorize or refuse.

[0071] To facilitate a clear description of the technical solution of this application, the following briefly introduces some of the terms and technologies involved in this application:

[0072] Deoxyribonucleic acid (DNA): A biological macromolecule that carries genetic information, composed of bases, deoxyribose, and phosphate. DNA is the genetic material foundation of most organisms and determines their genetic characteristics. In sequencing, DNA is one of the primary target molecules used to decipher an individual's genetic information.

[0073] Ribonucleic acid (RNA): A type of nucleic acid molecule transcribed from DNA. It primarily participates in protein synthesis and is composed of bases, ribose, and phosphate. RNA is also an important target molecule in certain sequencing applications, such as transcriptome sequencing.

[0074] Sample type refers to the physical state or structure of the sample, including liquid, solid, and mixed types. Different sample types require significant differences in processing procedures, which may affect the design and operation of sequencing pre-processing equipment.

[0075] Mixed samples: These are samples that contain both liquid and solid components and are primarily used for tumor heterogeneity studies and microbiome analysis. It is important to note that to ensure the validity and reliability of research results, mixed samples must be spatiotemporally consistent, meaning that the liquid and solid components must originate from the same anatomical location and be collected at the same time.

[0076] In order to clearly understand the technical solution of the present application, the solution of the prior art is first introduced in detail.

[0077] Sequencing pre-processing equipment is a highly integrated laboratory device primarily used to process, analyze, and generate sequence information for biological samples such as DNA and RNA. Its core function is to complete the entire process from sample to usable gene sequence information through a series of pre-programmed steps, encompassing key steps such as nucleic acid extraction, quality control, and library construction.

[0078] In related technologies, the processing workflows for different types of test samples (such as liquid blood samples, solid tissue samples, and mixed samples) differ significantly. Consequently, sequencing pre-processing equipment is primarily optimized for specific test sample types, supporting only one type, either liquid or solid, and struggling to accommodate a wide range of sample types.

[0079] Figure 1 Schematic diagram of the process of pre-sequencing treatment provided by related technologies. Figure 1 As shown, in the related art, the pre-sequencing treatment method generally includes the following steps:

[0080] S101, sample classification. Specifically, the sample to be tested is classified through manual operation, semi-automatic operation or automatic operation to determine whether the type of the sample to be tested is liquid or solid.

[0081] S102. Nucleic acid extraction and processing. Specifically, appropriate pre-sequencing equipment is selected based on the type of sample to be tested. For liquid samples, a sequencing pre-sequencing equipment specifically designed for liquids is used; for solid samples, a sequencing pre-sequencing equipment specifically designed for solids is used. The sample is processed using the aforementioned pre-sequencing equipment to ultimately obtain a nucleic acid extract in the form of DNA or RNA.

[0082] S103. Quality testing. Specifically, the nucleic acid extract is subjected to quality testing through manual, semi-automatic, or automated operation. If the test result indicates that the nucleic acid extract is of qualified quality, the process proceeds to S104. If the test result indicates that the nucleic acid extract is of unqualified quality, appropriate treatment measures are taken based on the specific circumstances, such as re-extracting nucleic acid, supplementing the sample to be tested, adjusting the test protocol, or discarding the nucleic acid extract.

[0083] S104: Library preparation: Specifically, the nucleic acid extracts of qualified quality are subjected to library preparation to obtain a sequencing library that can be used for high-throughput sequencing.

[0084] It can be seen from this that the pre-sequencing treatment methods in related technologies have the following limitations:

[0085] Poor equipment compatibility: The need to select the appropriate pre-sequencing equipment based on the type of sample being tested not only increases the cost and maintenance difficulty of the pre-sequencing equipment, but also increases the operational complexity of the pre-sequencing method. This makes it impossible to achieve compatible processing of multiple types of samples.

[0086] High human error: Although the relevant technologies can be partially automated, key steps such as nucleic acid extraction, quality testing, and library preparation still require manual operation. The operator's experience and technical level directly affect the accuracy of sample processing. Incorrect sample addition, mixing, or temperature control operations can lead to data deviations and even sequencing failure.

[0087] Limited overall efficiency: Manual operations will also reduce the standardization and operational efficiency of the entire pre-sequencing process, affecting the ability to process large-scale samples.

[0088] Therefore, in response to the above technical problems, the research found that in order to solve this problem, it is necessary to provide a sequencing pre-processing device that can realize full-process automated processing in multiple steps and is compatible with various sample types such as liquid and solid types.

[0089] Based on the above creative findings, the technical solution of the present application is proposed.

[0090] The technical solution of the present application is described in detail below with specific embodiments. The following specific embodiments can be combined with each other, and the same or similar concepts or processes may not be repeated in some embodiments. The embodiments of the present application will be described below in conjunction with the accompanying drawings.

[0091] Figure 2 Schematic diagram of the structure of the automated sequencing pre-processing device compatible with multiple types of test samples provided in the embodiment of the present application Figure 1 .like Figure 2 As shown, the automated sequencing pre-processing device 200 compatible with multiple types of test samples includes:

[0092] Sample receiving device 210, nucleic acid extraction device 220, nucleic acid mixing device 230 and library construction device 240;

[0093] The sample receiving device 210 includes a liquid biological sample inlet 211 and a solid biological sample inlet 212 , which are isolated from each other.

[0094] Specifically, the sample receiving device 210 is the front-end interface of the device, used to receive and store liquid and / or solid samples to be tested. The device is designed with functional zoning, with a liquid biological sample inlet 211 and a solid biological sample inlet 212 respectively provided to achieve the classified reception and independent storage of different types of samples to be tested. Specifically, the two can be located on the same side of the automated sequencing pre-processing device 200 that is compatible with multiple types of samples to be tested and physically isolated by a partition; the two can also be located on opposite sides or adjacent sides of the automated sequencing pre-processing device 200 that is compatible with multiple types of samples to be tested.

[0095] Among them, the liquid biological sample inlet 211 adopts an anti-splashing design, which is used to receive and store liquid type samples to be tested, such as blood, saliva or urine, to prevent liquid type samples to be tested from splashing or contamination during the loading process; the solid biological sample inlet 212 is used to receive and store solid type samples to be tested, such as tissue samples or cell sediments.

[0096] For liquid type test samples, they are stored in the liquid biological sample inlet 211; for solid type test samples, they are stored in the solid biological sample inlet 212; for mixed type test samples, technicians or professional equipment can first perform preliminary separation operations on them to extract the liquid components and solid components in the test samples, and respectively introduce them into the corresponding liquid biological sample inlet 211 and solid biological sample inlet 212 for storage.

[0097] The physical structural design of the mutual isolation between the liquid biological sample inlet 211 and the solid biological sample inlet 212 effectively avoids cross contamination between different samples, while meeting the requirements of automated transmission of different types of samples in subsequent processes, thereby improving the overall compatibility and safety of the device.

[0098] The nucleic acid extraction device 220 includes a first transfer module 221, a second transfer module 222, and a liquid biological sample processing area 223 and a solid biological sample processing area 224 that are isolated from each other.

[0099] The first transfer module 221 transfers the sample to be tested stored in the liquid biological sample inlet 211 to the liquid biological sample processing area 223;

[0100] The second transfer module 222 transfers the sample to be tested stored in the solid biological sample inlet 212 to the solid biological sample processing area 224;

[0101] The liquid biological sample processing area 223 and the solid biological sample processing area 224 perform nucleic acid extraction processing on the samples to be tested respectively received to obtain nucleic acid extracts.

[0102] Specifically, the nucleic acid extraction device 220 is used to separate and purify nucleic acids from test samples, a core operation in the pre-sequencing process. This device utilizes a functionally partitioned design with separate transfer and processing components for liquid and solid samples, enabling parallel and automated processing of different sample types.

[0103] The first transfer module 221 can use high-precision liquid handling equipment such as a multi-channel pipette, which is suitable for efficient and accurate transfer of liquid-type test samples; the second transfer module 222 can use a collaborative robot arm or other mechanical operation unit, which is suitable for grasping, positioning and transferring solid-type test samples.

[0104] The liquid biological sample processing area 223 may include but is not limited to a magnetic bead nucleic acid extractor, a centrifuge, and a vortex oscillator, etc., which are suitable for performing steps such as lysis, binding, washing, and elution on liquid type test samples to complete the extraction of high-quality nucleic acids.

[0105] The solid biological sample processing area 224 may include but is not limited to a tissue grinder, an ultrasonic lysis device, and a protease digestion module, etc., which are suitable for crushing, lysing, and releasing nucleic acids from solid samples to be tested, so as to improve the yield and integrity of the target nucleic acid.

[0106] For example, the first transfer module 221 can transfer a blood sample to the liquid biological sample processing area 223, where it uses magnetic bead adsorption to efficiently extract nucleic acids. Another example is the second transfer module 222, which can transfer a tissue sample to the solid biological sample processing area 224, where it undergoes grinding and lysis to release nucleic acids. During this process, the liquid biological sample processing area 223 and the solid biological sample processing area 224 can optimize their processing parameters, including but not limited to lysis time, temperature control, and reagent ratios, based on different sample types to improve the efficiency and quality of nucleic acid extraction.

[0107] In addition, the physical structural design of the mutual isolation between the liquid biological sample processing area 223 and the solid biological sample processing area 224 effectively avoids cross contamination between different samples, further improving the overall compatibility and safety of the device.

[0108] The nucleic acid mixing device 230 is in one-way communication with the liquid biological sample processing area 223 and the solid biological sample processing area 224 respectively;

[0109] The nucleic acid mixing device 230 mixes the nucleic acid extracts outputted from the liquid biological sample processing area 223 and the solid biological sample processing area 224 .

[0110] Specifically, one-way connectivity allows nucleic acid extracts to flow only from upstream modules to downstream modules, but not from downstream modules to upstream modules, preventing reverse contamination. One-way connectivity can be achieved through pneumatic tubing or conveyor belts, combined with one-way valves or sensors, to achieve automated transmission.

[0111] The nucleic acid extract output from the liquid biological sample processing area 223 is transported to the first inlet of the nucleic acid mixing device 230 through a pneumatic pipe; the nucleic acid extract output from the solid biological sample processing area 224 is transported to the second inlet of the nucleic acid mixing device 230 through a conveyor belt.

[0112] Specifically, for liquid type samples to be tested, the nucleic acid extract is directly transferred from the liquid biological sample processing area 223 to the nucleic acid mixing device 230; for solid type samples to be tested, the nucleic acid extract is directly transferred from the solid biological sample processing area 224 to the nucleic acid mixing device 230; for mixed type samples to be tested, the nucleic acid extract is synchronously or asynchronously transferred from the liquid biological sample processing area 223 and the solid biological sample processing area 224 to the nucleic acid mixing device 230, and the nucleic acid mixing device 230 is used to mix the nucleic acid extracts output from the liquid biological sample processing area 223 and the solid biological sample processing area 224.

[0113] The library construction device 240 is in one-way communication with the nucleic acid mixing device 230 .

[0114] The library construction device 240 performs library preparation processing on the nucleic acid extract to obtain a sequencing library.

[0115] Specifically, the library construction device 240 may include but is not limited to an automated library preparation workstation, a thermal cycler, and a magnetic bead purification magnetic stand, etc., which are used to perform library preparation processing on the nucleic acid extract and convert the extracted nucleic acid into a sequencing library that can be recognized by the sequencer.

[0116] An embodiment of the present application provides an automated sequencing pre-processing device compatible with multiple types of test samples, the device comprising: a sample receiving device including a liquid biological sample inlet and a solid biological sample inlet; a nucleic acid extraction device including a first transfer module for transferring the test sample stored in the liquid biological sample inlet to a liquid biological sample processing area, a second transfer module for transferring the test sample stored in the solid biological sample inlet to the solid biological sample processing area, as well as a liquid biological sample processing area and a solid biological sample processing area; the liquid biological sample processing area and the solid biological sample processing area perform nucleic acid extraction processing on the test sample to obtain nucleic acid extracts; a nucleic acid mixing device for mixing the nucleic acid extracts; and a library construction device for performing library preparation processing on the nucleic acid extracts to obtain a sequencing library. The following technical effects are achieved: different types of test samples are processed respectively by the liquid biological sample processing area and the solid biological sample processing area, and the test samples are automatically mixed by the nucleic acid mixing device, thereby achieving compatible processing of multiple types of test samples; by the liquid biological sample inlet and the solid biological sample inlet, as well as the liquid biological sample processing area and the solid biological sample processing area, which are isolated from each other, cross contamination between different types of test samples is avoided, thereby achieving compatible processing of liquid and solid types of test samples; by the sample receiving device, the nucleic acid extraction device and the library construction device, automated pre-sequencing processing of the test samples is achieved, thereby improving the processing efficiency and quality of the test samples.

[0117] Figure 3 Schematic diagram of the structure of the automated sequencing pre-processing device compatible with multiple types of test samples provided in the embodiment of the present application Figure 2 In one possible design, if Figure 2 and Figure 3 As shown, the liquid biological sample inlet 211 includes: a test tube rack 2111;

[0118] The test tube rack 2111 is used to store test tubes containing samples to be tested;

[0119] The first transfer module 221 is a pipette 2211;

[0120] The pipette 2211 absorbs the sample to be tested at the test tube rack 2111 and releases the sample to be tested at the liquid biological sample processing area 223 .

[0121] Specifically, the test tube rack 2111 is used to hold and securely store test tubes containing samples to be tested, ensuring their stable placement within the sample receiving device 210 and facilitating the subsequent automated transfer of the samples by the first transfer module 221. The test tube rack 2111 can be a standard microplate rack or a customized test tube rack equipped with a spring clamp 2221 or other compatible structure to accommodate test tubes of various specifications.

[0122] The pipette 2211 is used to draw liquid samples from the test tube rack 2111 and transfer them to the liquid biological sample processing area 223. The pipette 2211 can be a multi-channel electric pipette or a positive displacement pipette, which can be flexibly configured according to experimental requirements and sample throughput.

[0123] The transfer process of liquid samples to be tested includes:

[0124] Sample loading stage: The technician places the test tube containing the sample to be tested on the test tube rack 2111, ensuring that it is firmly installed;

[0125] Equipment positioning stage: When the automated sequencing pre-processing device 200 compatible with multiple types of test samples determines that the liquid biological sample inlet 211 is to receive and store the liquid type of test sample, the test tube rack 2111 moves to the bottom of the pipette 2211, or the pipette 2211 moves to the top of the test tube rack 2111, or the two move in coordination to a preset operating position;

[0126] Sample transfer stage: The tip of the pipette 2211 is lowered below the liquid surface, and a set volume of the sample to be tested is sucked up by air pressure control, and then the sample to be tested is released into the liquid biological sample processing area 223 to complete the sample transfer.

[0127] Furthermore, the test tube rack 2111 is equipped with a pressure sensor to detect whether the test tube is correctly placed. After detecting a valid pressure signal, the automated sequencing pre-processing device 200 compatible with multiple types of test samples confirms that the liquid biological sample inlet 211 is ready.

[0128] Furthermore, the pipette 2211 is equipped with a disposable tip module, which automatically replaces the new tip module after the transfer of the current batch of samples to be tested is completed, so as to avoid cross contamination between different samples to be tested and improve the safety of operation and data reliability.

[0129] The technical effect of the embodiment of the present application is that the automated transfer of liquid samples to be tested is achieved through the test tube rack and the pipette.

[0130] In one possible design, a label is provided on the test tube;

[0131] The liquid biological sample inlet 211 further includes: an identification reading module;

[0132] The identification reading module reads the sample information of the sample to be tested carried by the identification.

[0133] Specifically, a label refers to an information carrier attached to the surface of a test tube that carries sample information about the sample being tested, such as the patient number, sample type, and sample collection time. Labels include, but are not limited to, one-dimensional barcodes, two-dimensional codes, radio frequency identification (RFID) tags, or near-field communication (NFC).

[0134] The identifier reading module is an automated component integrated into the liquid biological sample inlet 211, used for contactless reading of the sample information carried by the identifier. When the identifier is a one-dimensional barcode or a two-dimensional code, the identifier reading module can be a barcode scanner, mounted above the liquid biological sample inlet 211. When the identifier is a radio frequency identification tag, the identifier reading module can be an RFID reader / writer, mounted to the side of the liquid biological sample inlet 211. When the identifier is a near-field communication (NFC) module, the identifier reading module can be an NFC module, mounted to the side of the liquid biological sample inlet 211.

[0135] The technical effect of the embodiment of the present application is: the sample information of the sample to be tested carried by the identifier is read by the identifier reading module, so as to optimize the processing parameters of the sample to be tested according to the sample information, thereby improving the processing efficiency and quality of the sample to be tested.

[0136] In one possible design, the solid biological sample inlet 212 includes: a cartridge slot 2121;

[0137] The box slot 2121 is used to mount a sample box storing samples to be tested;

[0138] The second transfer module 222 is a clamp 2221;

[0139] The clamp 2221 clamps the sample to be tested at the cartridge slot 2121 and releases the sample to be tested at the solid biological sample processing area 224 .

[0140] Specifically, the cartridge slot 2121 is used to hold and secure the sample cartridge containing the sample to be tested, ensuring its stable placement within the sample receiving device 210 and facilitating the subsequent automated transfer of the sample to be tested by the second transfer module 222. The cartridge slot 2121 can be a standard microplate cartridge slot, or one equipped with a spring-loaded locking mechanism or other adaptable structure to accommodate a variety of sample cartridge sizes.

[0141] The clamp 2221 is used to clamp the solid sample to be tested in the cartridge slot 2121 and release the solid sample to be tested in the solid biological sample processing area 224. The clamp 2221 can be a parallel gripper, a vacuum suction cup, or an electromagnetic adsorption module, and can be flexibly configured according to experimental requirements and the type of cartridge slot 2121.

[0142] The transfer process of solid-state samples to be tested includes:

[0143] Sample loading stage: The technician places the sample box containing the sample to be tested on the box slot 2121, ensuring that it is firmly installed;

[0144] Device positioning stage: When the automated sequencing pre-processing device 200 compatible with multiple types of test samples determines that the solid biological sample inlet 212 is to receive and store the solid type of test sample, the cartridge slot 2121 moves below the fixture 2221, or the fixture 2221 moves above the cartridge slot 2121, or both move in coordination to a preset operating position;

[0145] Sample transfer stage: The clamp 2221 adjusts the gripping mode according to the sample type, such as mechanical clamping for fresh tissue blocks and vacuum adsorption for frozen tissue blocks, and then releases the sample to be tested to the solid biological sample processing area 224 to complete the sample transfer.

[0146] Furthermore, the cartridge slot 2121 is equipped with a pressure sensor for detecting whether the sample cartridge is correctly placed. When the pressure sensor detects a valid pressure signal, the automated sequencing pre-processing device 200 compatible with multiple types of test samples determines that the solid biological sample inlet 212 is used to receive and store the solid type of test sample.

[0147] Furthermore, the fixture 2221 is equipped with a disposable chuck module, which automatically replaces the chuck module after the transfer of the current batch of samples to be tested is completed, so as to avoid cross contamination between different samples to be tested and improve the safety of operation and data reliability.

[0148] The technical effect of the embodiment of the present application is that the automated transfer of solid-state samples to be tested is achieved through the box slot and the clamp.

[0149] In one possible design, the solid biological sample inlet 212 further includes: an image recognition module;

[0150] The image recognition module collects the image of the sample to be tested and obtains the sample information of the sample to be tested based on the image of the sample to be tested.

[0151] Specifically, the image recognition module refers to an automated component integrated in the solid biological sample inlet 212 , which is used to collect images of solid biological samples to be tested and obtain sample information of the samples to be tested based on the images of the solid biological samples to be tested.

[0152] The image recognition module may include at least one of a camera, a scanner, a three-dimensional imaging device, a microscope camera, and an infrared camera, and may be installed above the solid biological sample inlet 212 .

[0153] The sample information of the sample to be tested may include the type of the sample to be tested (such as tumor tissue or normal tissue, etc.), size, morphological characteristics and contamination level, etc.

[0154] The technical effect of the embodiment of the present application is: sample information of the sample to be tested is obtained through the image recognition module, so as to optimize the processing parameters of the sample to be tested according to the sample information, thereby improving the processing efficiency and quality of the sample to be tested.

[0155] In one possible design, the liquid biological sample inlet 211 and the solid biological sample inlet 212 further include: a conveyor belt 213;

[0156] The test tube rack 2111 is fixedly mounted on the conveyor belt 213 of the liquid biological sample inlet 211 ; the conveyor belt 213 of the liquid biological sample inlet 211 drives the test tube rack 2111 to reciprocate at both ends of the liquid biological sample inlet 211 ;

[0157] The pipette 2211 is located at one end of the liquid biological sample inlet 211;

[0158] The cartridge slot 2121 is fixedly mounted on the conveyor belt 213 of the solid biological sample inlet 212 ; the conveyor belt 213 of the solid biological sample inlet 212 drives the cartridge slot 2121 to reciprocate at both ends of the solid biological sample inlet 212 ;

[0159] The clamp 2221 is located at one end of the solid biological sample inlet 212 .

[0160] Specifically, the conveyor belt 213 refers to a belt-shaped transmission device that circulates and is used to directionally move the test tube rack 2111 or the box slot 2121 inside the liquid biological sample inlet 211 or the solid biological sample inlet 212 .

[0161] The transfer process of liquid samples to be tested includes:

[0162] Sample loading stage: The technician places the test tube containing the sample to be tested on the test tube rack 2111. At this time, the conveyor belt 213 of the liquid biological sample inlet 211 stops running. The test tube rack 2111 is set at the first end of the liquid biological sample inlet 211, and the pipette 2211 is located at the second end of the liquid biological sample inlet 211.

[0163] Equipment positioning stage: The conveyor belt 213 of the liquid biological sample inlet 211 continues to operate until it drives the test tube rack 2111 to move from the first end of the liquid biological sample inlet 211 to the second end of the liquid biological sample inlet 211;

[0164] Sample transfer stage: The pipette 2211 absorbs the sample to be tested at the test tube rack 2111 and releases the sample to be tested at the liquid biological sample processing area 223. At this time, the conveyor belt 213 of the liquid biological sample inlet 211 stops running;

[0165] Secondary positioning stage of the device: the conveyor belt 213 of the liquid biological sample inlet 211 continues to run until it drives the test tube rack 2111 to move from the second end of the liquid biological sample inlet 211 to the first end of the liquid biological sample inlet 211 .

[0166] The transfer process of the solid type sample to be tested is similar to the transfer process of the liquid type sample to be tested, and will not be described in detail in the embodiment of the present application.

[0167] Furthermore, when the liquid biological sample inlet 211 and the solid biological sample inlet 212 are located on the same side or opposite sides, their conveyor belts 213 are arranged in parallel. When the liquid biological sample inlet 211 and the solid biological sample inlet 212 are located on adjacent sides, their conveyor belts 213 are arranged perpendicularly or in a V-shape. The conveyor belts 213 can be driven by the same drive device or by separate drive devices.

[0168] The technical effect of the embodiment of the present application is that the automated transfer of the sample to be tested at the liquid biological sample inlet or the solid biological sample inlet is achieved through the conveyor belt.

[0169] In one possible design, the liquid biological sample processing area 223 includes: a chemical lysis module and a nucleic acid purification module;

[0170] The first transfer module 221 transfers the sample to be tested stored in the liquid biological sample inlet 211 to the chemical lysis module;

[0171] A chemical lysis module is used to add a first lysis solution to the sample to be tested, and to perform a temperature-controlled oscillation treatment on the sample to be tested after adding the first lysis solution;

[0172] The nucleic acid purification module adds magnetic beads to the sample to be tested after temperature-controlled oscillation treatment, and performs binding and elution treatment on the sample to be tested after adding the magnetic beads to obtain a nucleic acid extract.

[0173] Specifically, the first lysis solution refers to a cell lysis reagent designed for liquid-type test samples, which may include a detergent (eg, sodium dodecyl sulfate (SDS)), proteinase K, buffer salts, and RNase inhibitors.

[0174] Magnetic beads are superparamagnetic microspheres with silicon or carboxyl functional groups on the surface, which are used to specifically bind nucleic acids. The characteristics of magnetic beads can be: particle size 1-5 , the saturation magnetization is greater than 10emu / g, and it can be quickly aggregated and separated in a magnetic field.

[0175] The processing flow of the chemical cracking module includes:

[0176] Lysis solution addition: The chemical lysis module automatically adds a certain amount of the first lysate to the sample to be tested;

[0177] Temperature-controlled oscillation treatment: The sample to be tested after adding the first lysis buffer is incubated for a certain period of time under certain temperature and oscillation conditions;

[0178] Lysis termination: After the incubation is completed, the chemical lysis module automatically adds a certain amount of stop solution, such as Tris-HCl buffer (a buffer with tris (hydroxymethyl)aminomethane (Tris) as the main component and its pH is adjusted by adding hydrochloric acid) to stop the reaction from continuing.

[0179] Furthermore, the chemical cracking module is equipped with an infrared sensor for detecting real-time temperature fluctuations during the temperature-controlled oscillation process, thereby achieving temperature control during the reaction process.

[0180] The processing flow of the nucleic acid purification module includes:

[0181] Magnetic bead binding: The nucleic acid purification module automatically adds a certain amount of magnetic bead suspension to the sample to be tested after temperature-controlled oscillation treatment, and performs oscillation binding under certain temperature and oscillation conditions;

[0182] Magnetic separation: The nucleic acid purification module automatically absorbs and discards the supernatant by adsorbing magnetic beads on a magnetic frame. The supernatant includes cell debris and proteins.

[0183] Elution treatment: The nucleic acid purification module repeatedly adds a certain amount of washing solution to the sample to be tested after magnetic separation to clean the magnetic beads, and then elutes the nucleic acid with nuclease-free water to obtain a nucleic acid extract; the washing solution can be added twice, and the washing solution can include ethanol and Tris-HCl buffer.

[0184] The technical effect of the embodiments of the present application is: through chemical lysis and magnetic bead purification, automated nucleic acid extraction of liquid-type test samples is achieved, thereby improving the processing capacity and nucleic acid quality of pre-sequencing processing.

[0185] In one possible design, the solid biological sample processing area 224 includes: a freezing and grinding module, a thawing and lysis module, and a phase separation module;

[0186] The second transfer module 222 transfers the sample to be tested stored in the solid biological sample inlet 212 to the freezing and grinding module;

[0187] Cryo-grinding module, for performing cryo-grinding on the sample to be tested;

[0188] a thawing and lysis module, adding a second lysis solution to the sample to be tested after the freeze-grinding treatment, and vortexing and oscillating the sample to be tested after the addition of the second lysis solution;

[0189] The phase separation module adds an organic solvent to the sample to be tested after the vortex oscillation treatment, and performs centrifugal stratification on the sample to be tested after the addition of the organic solvent to obtain a nucleic acid extract.

[0190] Specifically, the second lysis solution refers to a cell lysis reagent designed for solid-type test samples, which may include detergents, proteinase K, buffer salts, and RNase inhibitors.

[0191] An organic solvent refers to a phase separation agent used for nucleic acid extraction, and may be chloroform or a phenol / chloroform mixture. The characteristics of an organic solvent may include being immiscible with water and having a large density difference, effectively separating nucleic acids into the aqueous phase.

[0192] The processing flow of the cryo-grinding module includes:

[0193] Pre-cooling treatment: The grinding jar is immersed in liquid nitrogen for a certain period of time to prevent the sample to be tested from thawing;

[0194] Grinding operation: Grind the sample to be tested at a certain frequency and for a certain period of time to break the tissue into particles that meet certain requirements;

[0195] Sample collection: Transfer the ground powder to the centrifuge tube of the thawed lysis module.

[0196] The process of thawing the lysis module includes:

[0197] Lysis solution addition: The thawing and lysis module automatically adds a certain amount of second lysis solution to the sample to be tested after the frozen grinding process;

[0198] Vortex oscillation treatment: vortex and incubate the sample to be tested after adding the second lysis buffer for a certain period of time under certain temperature and vortex oscillation conditions;

[0199] Lysis termination: After the incubation is completed, the thawing lysis module automatically adds a certain amount of stop solution, such as Tris-HCl buffer, to stop the reaction from continuing.

[0200] Furthermore, the thawing and lysis module is equipped with an infrared sensor for detecting real-time temperature fluctuations during the vortex oscillation process, thereby achieving temperature control during the reaction process.

[0201] The processing flow of the phase separation module includes:

[0202] Organic solvent addition: The phase separation module automatically adds a certain amount of organic solvent to the sample to be tested after vortex oscillation, and vigorously oscillates for a certain period of time to form an emulsion;

[0203] Centrifugal stratification: The phase separation module centrifuges the emulsion at a certain centrifugal speed for a certain period of time, separating the emulsion into an upper aqueous phase, a middle protein phase, and a lower organic phase; the upper aqueous phase contains nucleic acids;

[0204] Nucleic acid collection: Transfer the upper aqueous phase to a new centrifuge tube and add an equal volume of isopropanol to precipitate the nucleic acid to obtain the nucleic acid extract.

[0205] The technical effect of the embodiments of the present application is: through freezing and grinding, thawing and lysis, and phase separation, automated nucleic acid extraction of solid-state test samples is achieved, thereby improving the processing capacity and nucleic acid quality of pre-sequencing processing.

[0206] In one possible design, the library construction device 240 includes: a fragmentation module, an end repair and adapter ligation module, an amplification module, and a magnetic bead purification module;

[0207] Fragmentation module, which performs ultrasonic fragmentation on nucleic acid extracts;

[0208] The end repair and adapter connection module performs end repair on the nucleic acid extract after ultrasonic fragmentation and adds sequencing adapters to the nucleic acid extract after end repair;

[0209] Amplification module, which amplifies the nucleic acid extract after adding sequencing adapters;

[0210] The magnetic bead purification module performs magnetic bead purification on the nucleic acid extract after amplification to obtain a sequencing library.

[0211] Specifically, the processing flow of the fragmentation module includes:

[0212] Nucleic acid loading: a certain amount of nucleic acid extract is transferred to a microtube, and a certain amount of buffer is automatically added to the nucleic acid extract;

[0213] Ultrasonic treatment: The nucleic acid extract is treated with ultrasound at a certain peak power and duty cycle for a certain period of time to obtain nucleic acid fragments of a certain base pair length;

[0214] Fragment verification: Detection of the fragment distribution of nucleic acid fragments.

[0215] The processing flow of the end repair and adapter ligation module includes:

[0216] End repair: The end repair and adapter connection module automatically adds a certain amount of end repair enzyme mixture to the nucleic acid extract after ultrasonic fragmentation, and reacts at a certain temperature for a certain period of time;

[0217] Adapter ligation: The end repair and adapter ligation module automatically adds a certain amount of sequencing adapters and ligase to the end-repaired nucleic acid extract and reacts at a certain temperature for a certain period of time;

[0218] The processing flow of the amplification module includes:

[0219] Polymerase Chain Reaction (PCR): The amplification module automatically adds a premix to the nucleic acid extract after the addition of sequencing adapters and continues running for multiple cycles. The premix can include a buffer, a mixture of deoxynucleoside triphosphates (dNTPs), a polymerase, and primers that provide the starting point for DNA synthesis.

[0220] Real-time monitoring: Fluorescent dyes are used to monitor amplification curves in real time to avoid overcycling.

[0221] The processing flow of the magnetic bead purification module includes:

[0222] Size screening: The magnetic bead purification module automatically adds a certain amount of magnetic beads to the amplified nucleic acid extract to remove small fragments and primer dimers;

[0223] Elution: The magnetic bead purification module automatically adds a certain amount of elution buffer to the size-selected nucleic acid extract and collects the supernatant.

[0224] The technical effect of the embodiments of the present application is: through fragmentation, end repair and connector connection, amplification, and magnetic bead purification, efficient and automated construction of sequencing libraries is achieved, and the processing capacity and library quality of pre-sequencing processing are improved.

[0225] Figure 4 Schematic diagram of the structure of the automated sequencing pre-processing device compatible with multiple types of test samples provided in the embodiment of the present application Figure 3 In one possible design, if Figure 2 and Figure 3 As shown, the automated sequencing pre-processing device 200 compatible with multiple types of test samples also includes:

[0226] a sample separation device 260 and a quality control device 250;

[0227] The liquid biological sample inlet 211 and the solid biological sample inlet 212 are respectively connected to the sample separation device 260 in a one-way manner;

[0228] The sample separation device 260 performs separation operations on the mixed type of samples to be tested, transfers the liquid components of the mixed type of samples to be tested to the liquid biological sample inlet 211 , and transfers the solid components of the mixed type of samples to be tested to the solid biological sample inlet 212 .

[0229] Specifically, the sample separation device 260 can separate the sample to be tested by physical means such as centrifugation, filtration, and precipitation, and transfer the separated sample to be tested to the liquid biological sample inlet 211 and / or the solid biological sample inlet 212 .

[0230] For liquid or solid samples to be tested, they can be directly transferred to the liquid biological sample inlet 211 or the solid biological sample inlet 212 by technicians or professional equipment; they can also be first input into the sample separation device 260, and the sample separation device 260 does not perform the separation operation, but only serves as a transmission channel to transfer the sample to be tested to the liquid biological sample inlet 211 or the solid biological sample inlet 212; they can also be first input into the sample separation device 260, and the sample separation device 260 performs the separation operation to transfer the separated liquid components to the liquid biological sample inlet 211, or transfer the separated solid components to the solid biological sample inlet 212.

[0231] For a mixed type of sample to be tested, the sample separation device 260 performs a separation operation to transfer the separated liquid component to the liquid biological sample inlet 211 and transfer the separated solid component to the solid biological sample inlet 212 .

[0232] The quality control device 250 includes: a quality detection module and a notification trigger module;

[0233] The quality detection module performs quality detection on the nucleic acid extract stored in the nucleic acid mixing device 230; the detection results of the nucleic acid extract include: the concentration and purity ratio of the deoxyribonucleic acid, and the integrity coefficient of the RNA;

[0234] The notification trigger module outputs a sample replenishment notification when the test result indicates that the concentration of deoxyribonucleic acid is lower than a preset concentration, or the integrity coefficient of RNA is lower than a preset coefficient; the sample replenishment notification is used to instruct the sample to be replenished;

[0235] The notification trigger module outputs a protein contamination notification when the test result indicates that the purity ratio of the deoxyribonucleic acid is lower than the preset ratio, and the nucleic acid mixing device 230 adds protease to the nucleic acid extract and digests the nucleic acid extract after the protease is added.

[0236] Specifically, the quality inspection module can include a spectrophotometer and a capillary electrophoresis instrument. The spectrophotometer is used to detect the concentration and purity ratio of DNA in the nucleic acid extract. The DNA concentration can be expressed as the A260 value, which refers to the absorbance of DNA by ultraviolet light at a wavelength of 260 nanometers. The DNA purity ratio can be expressed as the A260 / A280 ratio, which refers to the absorbance of DNA by ultraviolet light at a wavelength of 280 nanometers. The A280 value is used to reflect protein contamination. The capillary electrophoresis instrument is used to detect the RNA integrity index (RIN) value in the nucleic acid extract.

[0237] The qualified standard of the test result can be: DNA concentration ≥ 20ng / , A260 / A280∈[1.8, 2.0]; or, RIN value ≥ 7.0.

[0238] When the test result indicates that the concentration of DNA is lower than the preset concentration, that is, the concentration of DNA is less than 20ng / Or, when the integrity coefficient of RNA is lower than the preset coefficient, that is, when the RIN value is less than 7.0, a resample notification will be output.

[0239] If the test results indicate that the DNA purity ratio is below a preset value (i.e., A260 / A280 < 1.8), a protein contamination notification is output. The nucleic acid mixing device 230 then automatically adds a dose of protease, specifically proteinase K, to the nucleic acid extract. The proteinase K-added nucleic acid extract is then oscillated and digested for a predetermined period of time under certain temperature and oscillation conditions. The enzyme residues are then removed through magnetic bead purification.

[0240] Furthermore, after the sample filling process and the protease digestion process are completed, the nucleic acid extract re-enters the quality control device 250 and undergoes a quality inspection process again. The above process is repeated until the inspection result indicates that the inspection is qualified.

[0241] Furthermore, the quality detection module includes a fluorescence quantitative PCR instrument. In the polymerase chain reaction, the fluorescence quantitative PCR instrument is used to detect the real-time fluorescence signal of the nucleic acid extract to obtain the cycle threshold value (Ct value) and melting curve.

[0242] The technical effects of the embodiments of the present application are: automatic mixing of multiple types of test samples is performed through a nucleic acid mixing device, thereby achieving compatible processing of liquid and solid types of test samples; and quality control of multiple types of test samples is achieved through a quality control device, thereby improving the reliability of pre-sequencing processing.

[0243] So far, the technical solution of the present application has been described in conjunction with the preferred embodiments shown in the accompanying drawings. However, it is easy for those skilled in the art to understand that the scope of protection of the present application is obviously not limited to these specific embodiments. The above embodiments are only used to illustrate the technical solution of the present application, rather than to limit it. Although the present application has been described in detail with reference to the aforementioned embodiments, ordinary technicians in this field should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some or all of the technical features therein. However, these modifications or replacements do not cause the essence of the corresponding technical solution to deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. An automated sequencing pre-processing device compatible with multiple types of test samples, characterized in that: include: Sample receiving device, nucleic acid extraction device, nucleic acid mixing device and library construction device; The sample receiving device includes: a liquid biological sample inlet and a solid biological sample inlet that are isolated from each other; The nucleic acid extraction device includes: a first transfer module, a second transfer module, and a liquid biological sample processing area and a solid biological sample processing area that are isolated from each other; The first transfer module transfers the sample to be tested stored in the liquid biological sample inlet to the liquid biological sample processing area; The second transfer module transfers the sample to be tested stored in the solid biological sample inlet to the solid biological sample processing area; The liquid biological sample processing area and the solid biological sample processing area perform nucleic acid extraction processing on the samples to be tested received by each of them to obtain nucleic acid extracts; The nucleic acid mixing device is in one-way communication with the liquid biological sample processing area and the solid biological sample processing area respectively; The nucleic acid mixing device mixes the nucleic acid extracts outputted from the liquid biological sample processing area and the solid biological sample processing area; The library construction device is in one-way communication with the nucleic acid mixing device; The library construction device performs library preparation processing on the nucleic acid extract to obtain a sequencing library.

2. The automated sequencing pre-processing device compatible with multiple types of test samples according to claim 1, characterized in that: The liquid biological sample inlet includes: a test tube rack; The test tube rack is used to hold the test tubes storing the samples to be tested; The first transfer module is a pipette; The pipette absorbs the sample to be tested at the test tube rack and releases the sample to be tested at the liquid biological sample processing area.

3. The automated sequencing pre-processing device compatible with multiple types of test samples according to claim 2, characterized in that: The test tube is provided with a mark; The liquid biological sample inlet further includes: an identification reading module; The identification reading module reads the sample information of the sample to be tested carried by the identification.

4. The automated sequencing pre-processing device compatible with multiple types of test samples according to claim 2, characterized in that: The solid biological sample inlet includes: a cartridge slot; The box slot is used to mount the sample box storing the sample to be tested; The second transfer module is a fixture; The clamp clamps the sample to be tested at the cartridge slot and releases the sample to be tested at the solid biological sample processing area.

5. The automated sequencing pre-processing device compatible with multiple types of test samples according to claim 4, characterized in that: The solid biological sample inlet further includes: an image recognition module; The image recognition module collects the image of the sample to be tested and obtains the sample information of the sample to be tested based on the image of the sample to be tested.

6. The automated sequencing pre-processing device compatible with multiple types of test samples according to claim 4, characterized in that: The liquid biological sample inlet and the solid biological sample inlet further include: a conveyor belt; The test tube rack is fixedly mounted on the conveyor belt of the liquid biological sample inlet; the conveyor belt of the liquid biological sample inlet drives the test tube rack to reciprocate at both ends of the liquid biological sample inlet; The pipette is located at one end of the liquid biological sample inlet; The cartridge slot is fixedly mounted on the conveyor belt of the solid biological sample entrance; the conveyor belt of the solid biological sample entrance drives the cartridge slot to reciprocate at both ends of the solid biological sample entrance; The clamp is located at one end of the solid biological sample inlet.

7. The automated sequencing pre-processing device compatible with multiple types of test samples according to claim 1, characterized in that: The liquid biological sample processing area includes: a chemical lysis module and a nucleic acid purification module; The first transfer module transfers the sample to be tested stored in the liquid biological sample inlet to the chemical lysis module; The chemical lysis module adds a first lysis solution to the sample to be tested, and performs a temperature-controlled oscillation process on the sample to be tested after the addition of the first lysis solution; The nucleic acid purification module adds magnetic beads to the sample to be tested after the temperature-controlled oscillation treatment, and performs binding and elution treatment on the sample to be tested after the addition of the magnetic beads to obtain the nucleic acid extract.

8. The automated sequencing pre-processing device compatible with multiple types of test samples according to claim 1, characterized in that: The solid biological sample processing area includes: a freezing and grinding module, a thawing and lysis module, and a phase separation module; The second transfer module transfers the sample to be tested stored in the solid biological sample inlet to the freezing and grinding module; The freezing and grinding module performs freezing and grinding on the sample to be tested; The thawing and lysis module adds a second lysis solution to the sample to be tested after the freeze-grinding treatment, and performs a vortex oscillation treatment on the sample to be tested after the addition of the second lysis solution; The phase separation module adds an organic solvent to the sample to be tested after the vortex oscillation treatment, and performs centrifugal stratification on the sample to be tested after the addition of the organic solvent to obtain the nucleic acid extract.

9. The automated sequencing pre-processing device compatible with multiple types of test samples according to claim 1, characterized in that: The library construction device includes: a fragmentation module, an end repair and adapter connection module, an amplification module and a magnetic bead purification module; The fragmentation module performs ultrasonic fragmentation on the nucleic acid extract; The end repair and adapter connection module performs end repair on the nucleic acid extract after ultrasonic fragmentation and adds sequencing adapters to the nucleic acid extract after end repair; The amplification module performs amplification processing on the nucleic acid extract after the sequencing adapter is added; The magnetic bead purification module performs magnetic bead purification on the amplified nucleic acid extract to obtain the sequencing library.

10. The automated sequencing pre-processing device compatible with multiple types of test samples according to claim 1, characterized in that: Also includes: Sample separation devices and quality control devices; The liquid biological sample inlet and the solid biological sample inlet are respectively in one-way communication with the sample separation device; The sample separation device performs a separation operation on the mixed type of sample to be tested, transfers the liquid component of the mixed type of sample to be tested to the liquid biological sample inlet, and transfers the solid component of the mixed type of sample to be tested to the solid biological sample inlet; The library construction device is in one-way communication with the nucleic acid mixing device; The quality control device includes: a quality detection module and a notification trigger module; The quality detection module performs quality detection on the nucleic acid extract stored in the nucleic acid mixing device; the detection results of the nucleic acid extract include: the concentration and purity ratio of deoxyribonucleic acid, and the integrity coefficient of RNA; The notification trigger module outputs a sample replenishment notification when the test result indicates that the concentration of the deoxyribonucleic acid is lower than a preset concentration, or the integrity coefficient of the RNA is lower than a preset coefficient; the sample replenishment notification is used to instruct the sample to be replenished; The notification trigger module outputs a protein contamination notification when the test result indicates that the purity ratio of the deoxyribonucleic acid is lower than a preset ratio, and the nucleic acid mixing device then adds protease to the nucleic acid extract and digests the nucleic acid extract after the protease is added.

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