Biological sample automatic extraction system and device

Abstract

A system for automatically extracting biological specimens from a set of biological samples with a small footprint and minimal movement of the set of consumables, thereby reducing potential contamination during the extraction process. The extraction system includes a set of reaction tubes, a storage unit for storing the set of consumables, a sample preparation unit, a sample extraction unit, a waste unit, a plurality of robots for moving tubes, samples and boxes, and a programmable control system, which is programmed to process samples in a serial mode, wherein a series of samples are processed sequentially in a time sequence, thereby maintaining a continuous mode. Therefore, a fixed processing turnaround time for each sample is achieved regardless of when the sample processing begins.

Description

Technical Field

[0001] The present invention generally relates to an automated sample extraction system that serves a variety of analytical processing systems and techniques. Background Art

[0002] Sample preparation and extraction for analytical processing systems involves the manipulation and processing of multiple biological samples in a largely sterile environment. It is important that samples are handled without contamination, otherwise the results will be inaccurate, will be affected and may lead to false positives in subsequent analytical processing and testing.

[0003] Various analytical processing systems are required to prepare biological samples, such as polymerase chain reaction "PCR" systems. "PCR" is a technique used in molecular biology to amplify a single or a few copies of a nucleic acid (such as deoxyribonucleic acid "DNA" or ribonucleic acid "RNA") over several orders of magnitude to produce thousands to millions of copies of a specific sequence.

[0004] "PCR" is generally considered to be the amplification of a focused segment of nucleic acid, which can be used to diagnose and monitor genetic diseases, study the function of the target segment, for forensic individual identification, and other related uses.

[0005] Another example of an analytical processing system for a sample that can be prepared using a preferred system is an enzyme-linked immunosorbent assay (ELISA), which detects antigens or antibodies for use in immunology and toxicology. The purity of biological samples is important for analytical processing systems to produce accurate results in subsequent analytical processing processes. A problem with preparing samples for analytical processing systems (such as PCR or ELISA enzyme-linked immunosorbent assays) is that when the amplification container is opened and the sample is being prepared, the preparation process is at risk of contamination. In addition, during the movement of the sample and when the lid is removed, the possibility of spillage, droplet formation and / or aerosols can lead to a risk of contamination. Since a contaminated pipette moves over an open sample container, cross contamination may also occur during the introduction and removal of the pipette from the system. This contamination can quickly lead to erroneous results or biased and incorrect test results. Such contamination must be carefully prevented.

[0006] Physical separation between sample preparation, amplification, and detection areas is often used to limit contamination between samples and from the surrounding environment. These measures are cumbersome, expensive, and require rigorous training to prevent material transfer to lab coats, gloves, pipettes, or lab equipment between these isolated areas.

[0007] The biomaterial processing system includes a mobile pipette assembly in which a plurality of individual pipettes are mounted on a movable frame that is movable in longitudinal and lateral directions relative to a sample tray that includes sample tubes preferably loaded with biological material (e.g., whole blood, serum or other biological material for nucleic acid amplification.) Multiple stops and starts of the pipette assembly on the sample tubes, typically after the pipettes come into contact with the samples in the sample tubes, cause cross contamination of the sample tubes on the robotic frame as the robotic frame moves, starts, stops and vibrates, resulting in widespread potential contamination of all samples on the sample tray and failure of expensive and precise tests.

[0008] It is worthwhile to design a sample handling system that reduces or eliminates the risk of cross-contamination by subjecting the sample tray to potential vibration loads when a contaminated pipette is moved, stopped, and started. Sample tubes also require that sample and other materials (e.g., buffers) in the sample tubes be moved in and out through a top opening, which further creates potential contamination issues.

[0009] Many methods of processing samples include shaking, heating, applying a magnetic field to the magnetic bead-target compound complex, and draining liquid waste. Typically, these steps are performed in independent and separate stations, such as using a shaking tube device, a magnetic separation device, a heater, and a waste container.

[0010] The above traditional shaking, heating, magnetic bead separation and waste liquid discharge process requires separate stations and takes up too much space on the workbench. The use of these separate stations also requires manual handling and transportation of samples from one station to another, which is time-consuming and leads to the possibility of cross-contamination between samples. Therefore, these problems need to be solved. Summary of the invention

[0011] The present invention generally relates to an automated system for separating and extracting target compounds from biological samples. In particular, the present invention is an automated sample extraction system that can be used to prepare samples for a variety of analytical processing systems and techniques (eg, PCR systems).

[0012] The system consists of units configured to process samples continuously so that it maintains a fixed processing turnaround time for each sample regardless of when the sample processing begins. The present invention processes samples in a serial mode, wherein a series of samples are processed sequentially in chronological order. The main units of the system are controlled by a computer to achieve automated extraction of nucleic acids.

[0013] The system consists of five different units: storage unit, sample preparation unit, sample extraction unit, waste disposal unit and reaction tube unit. All units are configured to minimize the amount of sample movement and reduce the risk of contamination.

[0014] The reaction tube unit is a specially designed reaction tube, the upper part of which is used for sample extraction, and the lower part is used for receiving waste liquid from the upper part. The two parts are separated by a valve.

[0015] The storage unit stores consumable boxes that are easy to access. The storage unit also stores sample tubes and magnetic beads. The magnetic beads are stored in a cooler.

[0016] The sample preparation unit includes a rotating table with a transfer unit, the transfer unit including a sample tube rack for accommodating sample tubes and a reaction tube rack for accommodating reaction tubes adjacent to each other. The rotating table can also accommodate box-shaped consumables and reaction tubes for quick access each time. The sample preparation unit also has a sample rack to hold the sample tubes, and the sample rack is located on one side of the rotating table. The rotating table rotates to position the sample rack next to the sample tube rack on the transfer unit, and then the sample tube is transferred. This minimizes sample movement. The sample preparation unit also includes a cooler to accommodate magnetic beads.

[0017] The sample extraction unit is close to the rotating platform and includes a set of tube shaking devices for receiving and shaking the reaction tubes and a set of magnet racks with magnets, and the magnets are used to manipulate the magnetic beads in the reaction tubes.

[0018] The waste disposal unit includes separate bins for disposal of consumables, waste liquids and tubing.

[0019] The sample preparation unit is designed to minimize sample movement to reduce the risk of contamination. Samples must be moved from sample tubes to reaction tubes for the extraction process. To minimize sample movement, sample racks and reaction tube racks are placed side by side on a rotating table. The sample robot moves sample tubes from the sample tube box into the sample tube rack and simultaneously moves reaction tubes from the reaction tube box into the reaction tube rack. The sample robot then prepares the samples in the reaction tubes by adding different types of solutions, such as lysis buffer.

[0020] Once the samples in the reaction tubes are prepared, the rotating stage rotates to bring the reaction tube rack with the reaction tubes close to the sample extraction unit.

[0021] The reaction robot grabs the reaction tube and moves it from the rotating table to the shaking tube device in the sample extraction unit. The extraction unit consists of a separate shaking tube device and a separate magnetic unit. Each shaking tube device with a reaction tube can be placed at a different distance from the magnetic unit to change the strength of the magnetic field and the position of the magnetic beads in the reaction tube.

[0022] First, the reaction tube is placed in a position where the magnetic effect is small and shaken. Then the magnetic beads and binding buffer are added to the solution and the reaction tube is further shaken.

[0023] Next, the reaction tube is moved to a second position so that the reaction tube is between the vertical legs of the L-shaped magnet. The magnet attracts the magnetic beads with the sample to the wall of the tube. The waste valve is opened to discharge the waste liquid into the second compartment of the reaction tube. The valve is closed, wash buffer is added, and the test tube is shaken. The shaking tube assembly is then moved back to a position close to the magnet, the magnet is fixed to the wall of the tube, and the valve is opened to discard the waste liquid into the second compartment. This process may be repeated multiple times (two or more washes), depending on the sample requirements to wash out impurities.

[0024] After sample purification, the eluent is added to the sample in the reaction tube and the tube is shaken to separate the sample from the magnetic beads. The reaction tube is then moved to the third position, where the magnetic beads are completely attached to the top of the tube, allowing the sample to be easily removed via a pipette. The reaction robot grabs the pipette, removes the purified sample from the reaction tube, and places it in a purified sample tube with a cap for storage.

[0025] Integrating each of these units onto the frame reduces the footprint of the sample preparation system and reduces the need to transport the associated components over relatively long distances, thereby reducing potential contamination.

[0026] Therefore, an object of the present invention is to provide a biological sample extraction system and method that can reduce and eliminate the risk of contamination.

[0027] Another object of the present invention is to process samples in a serial mode, wherein a series of samples follow each other in a time series to be processed.

[0028] Another object of the present invention is to provide a fully automatic sample extraction device to automatically process a large number of biological samples every day with minimal manual operation and a shorter operating time.

[0029] Another object of the present invention is to provide a system that reduces cross contamination by reducing pipette and liquid transfer time. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The following will describe the embodiments in conjunction with the provided drawings, but it does not constitute any limitation on the scope of protection of the claims, wherein the same reference numerals represent the same components.

[0031] Figure 1 It is a front stereoscopic diagram of the biological sample extraction system of the present invention.

[0032] Figure 2 It is a front view of the biological sample extraction system of the present invention.

[0033] Figure 3 It is a left side stereogram of the biological sample extraction system of the present invention.

[0034] Figure 4 is a top view of the biological sample extraction system of the present invention.

[0035] Figure 5 It is a perspective view of the rotating table of the present invention.

[0036] Fig. 6A It is a front perspective view of the shaking tube device and the reaction tube.

[0037] Figure 6B It is a front stereoscopic view of the reaction tube of the present invention.

[0038] Figure 7 It is a front view of the sample extraction unit and the tube shaking device driving system of the present invention.

[0039] Figure 8 is a side view of the sample extraction unit of the present invention.

[0040] Fig. 9 1 is a top view of the sample extraction unit of the present invention.

[0041] Fig. 10A This shows the reaction tube of the present invention.

[0042] Fig. 10B This shows the reaction tube of the present invention.

[0043] Fig. 10C This shows the reaction tube of the present invention.

[0044] Fig. 10D This shows the reaction tube of the present invention.

[0045] Fig.11 It is a three-dimensional view of the L-shaped magnet frame of the present invention (the reaction tube is at position 1).

[0046] Fig.12 It is a three-dimensional view of the L-shaped magnet frame of the present invention (the reaction tube is at position 2).

[0047] Fig.13 It is a three-dimensional view of the L-shaped magnet frame of the present invention (the reaction tube is at position 3).

[0048] Fig.14 is a perspective view of a waste treatment unit of the present invention.

[0049] Fig.15A It is a side view of the propulsion system of the shaking tube device.

[0050] Fig. 15B It is a top view of the propulsion system of the shaking tube device.

[0051] Fig.16 It is a perspective view of the robot system of the present invention.

[0052] Fig.17A front view of a robot system of the present invention is schematically shown.

[0053] Fig.18 It is a front view of the robot system of the present invention.

[0054] Fig.19 is a top view of the robot system of the present invention.

[0055] Fig. 20A The process of nucleic acid extraction in the system is shown.

[0056] Fig. 20B The process of nucleic acid extraction in the system is shown.

[0057] Fig. 20C The process of nucleic acid extraction in the system is shown.

[0058] Fig.21 The reaction tube is shown in position 1 (corresponding to Fig.11 ), position 2 (corresponding to Fig.12 ), position 3 (corresponding to Fig.13 ) The reaction of magnetic beads in the reaction tube under three conditions. DETAILED DESCRIPTION

[0059] Figures 1 to 5 An automated sample extraction system 100 is described that can be used to prepare samples for a variety of analytical processing systems and techniques. The system 100 includes multiple units that are all controlled by a computer to achieve automated sample extraction. The system 100 can process samples in a serial mode, with a series of samples being processed in a chronological order following each other.

[0060] The system 100 includes a frame 10 having a horizontal platform 11, which divides the frame into a top section 12 and a bottom section 13. Preferably, the frame 10 is composed of relatively hard, strong and sterilizable materials that are assembled to provide structural support to the various units of the system 100 and enable the automatic sample extraction system to operate. For example, the frame 10 can be composed of stainless steel that is biocompatible and sterilizable for use with the system 100. The system 100 includes a plurality of units that are located in the interior space of the frame and supported by the frame 10, and the units can be moved in a manner to operate a fully automatic sample extraction system.

[0061] The storage unit: The sample automatic extraction system includes a storage unit. The storage unit includes a rotating storage device 20, which is installed on the bottom section 13 near the left side of the frame 10. The rotating storage device 20 includes a plurality of movable trays 21 (preferably eight trays 21), which are assembled in a vertical position and each tray 21 includes a plurality of receiving spaces (preferably five receiving spaces), and five receiving spaces accommodate five consumable boxes 22. The operator of the machine can remove the tray 21 and load the consumable box 22. The consumable box 22 includes samples and additional elements for the extraction process. The rotating storage device 20 stores a large number of consumable boxes for the extraction process, about forty boxes in total, and the rotating storage device 20 can rotate around the Z axis. Preferably, the rotating storage device 20 includes a variety of consumable storage spaces, including reaction tube boxes, buffer boxes, elution tube boxes and various pipette tip boxes, and the above consumables are stored in the rotating storage device 20 and transported by the box-lifting robot 30 for replacement. The rotating storage device 20 can accommodate a large number of consumables for easy access, for example, 16 reaction tube boxes, 2 buffer boxes, 2 elution tube boxes, 12 (1 ml) pipette tip boxes, 4 (175 μL) pipette tip boxes and 4 (25 μl) pipette tip boxes.

[0062] like Figure 4 As clearly shown, the storage unit also includes a sample rack 50 mounted on the top section 12 on the left side of the frame, the sample rack comprising a plate with guide rails, the sample tubes 1 being positioned in the system. The sample tubes 1 can be loaded automatically or manually onto the sample rack 50 by a machine or an operator.

[0063] The storage unit also includes a cooler 90 to store consumables that need to be stored in a low temperature (e.g., 4° C.) environment. For example, the magnetic bead solution is placed in the cooler for storage and then transferred to the reaction tube 201. The cooler 90 can be any type of usable cooler, preferably, a thermoelectric cooler. The function of the cooler 90 is to keep the solution between 4-8° C. so that they can work.

[0064] The box lifting robot 30 transports the consumable box 22 from the rotating storage device 20 to the rotating table 40 on the top section 12 of the frame. The box lifting robot 30 is a vertical motion robot mounted on a rod on the bottom section 13 to allow the box lifting robot 30 to move linearly in two axes (X axis and Z axis). The box lifting robot 30 extends to the top section 12 through the opening 31, and it can move to a desired position, grab the consumable box 22 at this position, and lift it from the rotating storage device 20 to the rotating table 40 on the top section 12.

[0065] The sample preparation unit includes a rotating table 40. The rotating table 40 of the sample preparation unit includes a plurality of accommodating cavities, preferably six accommodating cavities, which are designed to accommodate the consumable boxes 22 used in the extraction process. The rotating table 40 is rotatably mounted on a horizontal platform 11 on the top section 12 of the frame. It can rotate around an axis and stop at a predetermined position in front of the box lifting robot 30 to receive the consumable box 22. Each accommodating cavity of the rotating table 40 can include various pipette tip boxes, including: long pipette tips 42, medium pipette tips 43 and short pipette tips 44. Other consumable boxes, such as nucleic acid tubes 45, various buffers 46 and reaction tubes 201 are further positioned on the rotating table 40 for the extraction process. A conveying unit 41 is provided on the rotating table 40, and the conveying unit 41 includes a sample tube rack 2, a reaction tube rack 3 and a waste discharge hole 4. In the conveying unit 41, the sample can be transferred from the sample tube 1 to the reaction tube 201, which is next to the sample tube 1 to reduce the risk of cross contamination.

[0066] For full automation of sample extraction, system 100 provides sample robot 60 and reaction robot 70 for conveying consumables of extraction process. Sample robot 60 and reaction robot 70 are Cartesian coordinate robots movable along Z axis. Sample robot 60 and reaction robot 70 are equipped with electric gripper and electric pipette assembly. Sample robot 60 and reaction robot 70 are equipped with electric gripper and electric pipette assembly to pick up consumables, place consumables in different positions, transfer liquid according to the sample extraction purpose of the system, and handle waste. The clamp is used to carry the tube. As will be understood by those of ordinary skill in the art, the pipette assembly is used to move the sample during the sample extraction process. During the operation of sample extraction system 100, the functions of the gripper and pipette are controlled by a computer program controller.

[0067] Sample extraction unit: reference Figure 1 , FIG. 6A to FIG. 13 The automatic sample extraction system also includes a sample extraction unit 80, which is installed on the top section 12 and is located on the right side of the frame 10. It includes a plurality of (preferably 32) independent shaking tube devices 200. Containing sampling materials, such as magnetic beads and buffer, for breaking cells and washing impurities, the above sampling materials flow into the reaction tube 201. Then the reaction tube 201 is placed in the shaking table 200 for the sampling process.

[0068] One embodiment of the system 100 includes a tube shaking device 200, which is mounted under four magnet racks 81 parallel to each other, wherein each magnet rack 81 receives six tube shaking devices 200. The magnet racks 81 are fixed. A magnetic gear 83 is mounted on the tube shaking device 200, and another magnetic gear 83 is mounted on a rotating shaft 84. The tube shaking device 200 can move along the X-axis on the guide rail to achieve the engagement or disengagement of a pair of magnetic gears, so as to control the opening or closing of the tube shaking device 200. The magnetic gears 83 are mounted on the rotating shaft 84, wherein each rotating shaft 84 preferably has six magnetic gears 83 mounted thereon. The rotating shaft 84 preferably runs at 1200 rpm.

[0069] Each shaking tube device 200 is configured to operate independently and provide a shaking motor to integrate orbital shaking, heating, magnetic bead separation and waste liquid discharge. Each magnetic rack 81 has a plurality of accommodating spaces, each accommodating space is configured to receive one shaking tube device 200. Each accommodating space has a pair of L-shaped magnets 95, and the L-shaped magnet has a vertical leg and a horizontal leg. The shaking tube device 200 can be located at different distances from the magnetic rack 81.

[0070] Figure 11-13 Three different positions are shown: Fig.11 As shown in FIG. 2 , when the shaking tube device 200 is in position 1, the L-shaped magnet 95 cannot attract the magnetic beads in the reaction tube 201, so the magnetic beads will not gather together. Fig.12 As shown in FIG. 2 , when the shaking tube device 200 with the reaction tube 201 is placed in position 2, the L-shaped magnet 95 can attract the magnetic beads 48 in the reaction tube 201, so that the magnetic beads 48 gather on the side close to the vertical leg of the L-shaped magnet 95 and extend along the inner wall of the reaction tube 201 at a lower position. Fig.13 In position 3 as shown, the L-shaped magnet 95 can attract the magnetic beads 48 inside the reaction tube 201, so that the magnetic beads 48 are gathered together. Compared with when the reaction tube is in position 2, the magnetic beads 48 spread wider along the inner wall, making it easy to remove the sample through a pipette. Fig.21 It further shows the reaction of the L-shaped magnet 95 and the magnetic beads 48 in the reaction tube 201 when the shaking tube device 200 is in different positions.

[0071] The tube shaking device pushes the tube shaking device to different positions. Figure 7 , 15AAs shown in FIG. 15B , a two-axis (X and Y) linear motion "tube shaking device pushing" robot 82 is also provided in the sample extraction unit 80. The tube shaking device pushing robot 82 is used to push the tube shaking device 200 to different positions. A push pad 85 pushes the tube shaking device to approach or move away from the rotation axis 84. When the distance from the rotation axis 84 is about 1 mm, the tube shaking device 200 will start to shake. A metal sheet 87 is further installed at the bottom of the tube shaking device to guide the tube shaking device 200 to approach or move away from the rotation axis 84.

[0072] Reaction tube: Each reaction tube 201 includes two chambers. Figures 10A to 10D , the top chamber is the reaction chamber 202, which is a cylindrical compartment for receiving samples, buffers and magnetic beads for the extraction process. The lower compartment is the waste chamber 203, which is a cylindrical container with a diameter greater than the reaction zone 202, which is used to receive liquid waste generated during the sampling process. The reaction chamber 202 and the waste chamber 203 are connected to each other so that the reaction chamber 202 is formed separately and connected to the waste chamber 203. The reaction tube 201 is provided with a control valve 204, which is located between the reaction chamber 202 and the waste chamber 203, and the waste chamber 203 is connected to the waste liquid treatment device. When the valve 204 is opened, the waste liquid generated during the extraction process is processed in the waste chamber 203. During the extraction process, the valve 204 seals the opening between the reaction chamber 202 and the waste chamber 203. The opening and closing of the valve 204 is controlled by pushing a series of buttons 205 installed on the reaction tube 201, and the buttons press the spring element 208. Whenever the waste liquid is to be processed, applying force on these buttons can open the valve.

[0073] The opening and closing of the valve 204 is achieved by a force acting on the button 205, which is applied by the reaction robot 70. After the entire extraction process is completed, the reaction robot 70 carries the reaction tube 201, the waste liquid is retained in the waste liquid chamber 203, and discards it into the waste liquid tank. This action prevents the reaction sample from flowing into the waste chamber 203. The reaction tube 201 can be made of biocompatible, sterilizable materials.

[0074] The gripper of the reaction robot 70 has a rod holder (not shown) that can be moved in a vertical position to be inserted into the reaction area 202 to grasp and transfer the reaction tube 201. The reaction robot 70 also has a sleeve (not shown) that slides on the rod holder. The sleeve pushes a button 205 on the reaction tube 201 to open the valve 204.

[0075] Waste unit: According to Fig.14, the system provides two waste boxes 51 and 52 on the bottom section 13. During the liquid transfer, the sample robot 60 and the reaction robot 70 transfer all wastes except waste liquid, such as waste liquid sucked by the used pipette in the first waste liquid box 51 or the second waste liquid box 52. When the valve 204 is opened, the waste liquid is placed in the waste chamber 203 of the reaction tube 201. After the entire extraction process is completed, the reaction robot 70 carries the reaction tube 201, and the waste liquid remains in the waste chamber 203, and the waste liquid enters the second waste liquid box 52. The treatment of the waste liquid is carried out through a set of openings set on the horizontal platform 11 of the frame.

[0076] See again Figure 5 , the transfer unit 41 includes a sample tube rack 2 for placing the sample tube 1, a reaction tube rack 3 for placing the reaction tube 201, and a waste discharge hole 4. The sample robot 60 starts the sample processing, takes out the reaction tube 201 from the reaction tube box on the rotating table 40 and places it on the reaction tube rack 3. The sample robot 60 further takes out the sample tube 1 from the sample rack 50 and places it on the sample tube rack 2. Then, the sample robot 60 selects a pipette tip from various pipette tip boxes, such as a long pipette tip 42, a medium pipette tip 43, or a short pipette tip, depending on the extraction process of transferring the sample from the sample tube 1 to the reaction tube 201.

[0077] Each used pipette tip and pipette is discarded into the first waste liquid tank 51 through the waste hole 4 after use. The waste hole 4 is close to the transfer unit 41, so the risk of cross-contamination of samples during movement is reduced significantly when the cover is removed. This design of the system not only reduces cross-contamination, but also reduces the movement time of pipettes and liquid transfers.

[0078] The system 100 also includes a computer program for commanding and controlling the operation of the system unit. A non-transitory computer readable memory includes one or more data structures that individually or together contain a plurality of stored information related to the operation of the system, including a plurality of operating modes in which the system may operate. The controller of the system is coupled to a sample extraction application to store information related to a plurality of sample extraction types. The system 100 also includes a control application for sample extraction. At least one control application includes sample extraction instructions to cause the sample extraction unit to move and cause the sample extraction system 100 to prepare an extraction sample using one or more selected consumables corresponding to a selected sample.

[0079] Figure 3 , Figures 16 to 19The robot system of the present invention is disclosed. The sample robot 60 and the reaction robot 70 have the same mechanism to provide an automatic and continuous sample extraction procedure. Both the sample robot 60 and the reaction robot 70 provide grippers mounted on movable arms. The sample robot 60 is movably mounted on a robot rail 61, which is fixed to a vertical support of the frame 10 for movement relative to the frame 10 in the storage unit and the sample preparation unit. The sample robot 60 provides a gripper on a gripper arm 62, which extends movably downward and can release and grip various pipette tips and tubes so that the pipette tips and tubes can be moved between different areas.

[0080] The reaction robot 70 is movably mounted on a robot rail 71, which is fixed to the vertical support of the frame 10 for moving between the sample preparation unit and the sample extraction unit 80 to continue the automated sample processing system. The reaction robot 70 is provided with a gripper 73 mounted on a gripper arm 72, the gripper 73 being movable downward, the gripper 73 being able to releasably grip various pipette tips and move between areas and place them in preprogrammed positions. The reaction robot 70 selects pipette tips, such as long pipette tips 42, from various pipette tip boxes to add various components to the extraction tube 201.

[0081] according to Figure 1 , Figure 5 , FIG. 20A to FIG. 21 , the above figure discloses the sample extraction process of the reaction tube 201 of the system. In operation, the rotating storage device 20 rotates to a position where the box-lifting robot 30 can grab the required consumables. At the same time, the rotating table 40 rotates to a position where the box-lifting robot 30 can place the consumables on the accommodation space of the rotating table 40. Then, the box-lifting robot 30 selects a consumable and lifts it, placing the consumable on the rotating table 40. In this way, the box-lifting robot 30 can pick up and place six boxes of different consumables on the rotating table 40.

[0082] The sample robot 60 takes out the reaction tube 201 from the reaction tube box and places it on the reaction tube rack 3. The sample robot 60 further takes out the sample tube 1 from the sample rack 50 and places it on the sample tube rack 2 next to the reaction tube 201. Then, the sample robot 60 picks up the pipette tip to transfer some samples (nucleic acids) from the sample tube 1 to the reaction tube 201. The rotating table 40 rotates to move the reaction tube 201 filled with the sample in the direction of the right side of the frame close to the extraction unit 80. Therefore, the risk of cross contamination, spillage, droplet formation and / or aerosol that may occur during the sample movement is significantly reduced.

[0083] FIG. 20A to FIG. 20CThe detailed procedure of extracting samples (nucleic acids) is shown. The reaction robot 70 picks up the pipette tip, adds lysis buffer to the reaction tube 201 for breaking nucleic acid cells and transfers it to the sample extraction unit 80, and places each reaction tube 201 on the shaking tube device 200 for extraction. The shaking tube device 200 shakes the reaction tube 201 for 10 minutes.

[0084] After shaking for 10 minutes, the shaking tube device pushing system 82 pushes the shaking tube device 200 away from the rotating axis to stop the shaking tube device 200. The reaction robot 70 then moves to the rotating table 40, picks up and adds some magnetic beads 48 and binding buffer to the reaction tube 201. Combined with the movement of the shaking tube device 200, the attachment and separation efficiency of the magnetic beads 48 in the sample is improved. At this stage, the sample (nucleic acid) is bound to the magnetic beads 48. Then, the shaking tube device pushing system 82 will push the shaking tube device 200 to shake on the L-shaped magnet rack 95 for 5 minutes. The most useful properties of the magnetic beads 48 and buffer are that they can reversibly bind to nucleic acids and can be safely fixed during multiple washing and operation steps when a strong magnet is present. At each stage, the reaction robot 70 disposes the used pipette tips into a waste bin.

[0085] The process of extracting the sample is achieved in multiple stages by pushing the reaction tube 201 onto the magnet rack, shaking the tube shaking device 200 to separate the magnetic beads 48, and washing impurities from the sample. The tube shaking device pushing system 82 pushes the reaction tube 201 on the magnet rack 81 to apply magnetic force to separate the magnetic beads 48 from the sample. The magnetic beads will stick to the inner wall of the reaction chamber 202.

[0086] At this stage, the valve 204 between the reaction chamber 202 and the waste chamber 203 of the reaction tube 201 is opened by the force exerted by the reaction robot on the button 205, and the waste generated during the extraction process flows from the reaction chamber 202 to the waste chamber 203. Then the reaction robot 70 adds some washing buffer ( Fig. 20B ) is added to the sample. The shaking tube device pushing system 82 pushes the shaking tube device 200 to shake for 1 minute. The shaking tube device pushing system 82 pushes the reaction tube 201 on the magnet rack 81 to separate the magnetic beads 48 by applying magnetism. The waste generated during the extraction process is then discarded from the reaction chamber (extraction area) 202 into the waste chamber 203. These steps can be repeated several times by adding additional buffer to the reaction tube, magnetizing, rotating, and draining the waste liquid required by the system.

[0087] according to Fig. 20CIn the final stage of the extraction process to elute the nucleic acid from the magnetic beads 48, the magnetic beads must be dissolved with a small volume of eluent, the eluent is added to the sample and the shaker pusher 82 pushes the shake tube device 200 to shake for 30 seconds. The shake tube device pusher 82 pushes the shake tube device 200 on the magnetic rack to apply magnetism and the waste generated is discarded. Since contaminated pipettes are moved over the open sample container, cross contamination can also occur during the introduction and removal of pipettes from the system. This contamination will quickly lead to false results or erroneous and incorrect test results. Care must be taken to prevent such contamination.

[0088] The nucleic acid solution containing purified viral RNA / DNA is transferred to the elution tube. The reaction tube 201 is designed to allow the magnetic beads to gather together near the bottom of the tube so that the eluent can effectively and completely contact the magnetic beads. Then the reaction robot 70 transports the reaction tube 201 to the sewage outlet 4 and discharges the waste.

[0089] When the magnetic beads 48 are placed in the reaction tube 201 in the shaking tube device 200, the substances in the sample are attached to the magnetic beads by the collision of the magnetic beads 48 with the biological material. The magnetic beads 48 are added to the reaction tube 201 to allow, for example, DNA molecules to bind to the magnetic beads 48. The reaction tube 201 is then placed on the shaking tube device 200. The shaking tube device 200 is used for sample mixing to obtain a uniform mixture of the magnetic beads 48 and the sample, thereby increasing the yield of DNA bound to the magnetic beads 48. The magnetic beads 48 used in the process may be at least one of stainless steel beads, zirconium oxide beads, ceramic beads, or glass beads.

[0090] The system and method according to the embodiment of the present invention can prepare different biological samples for various analytical procedures. Examples of such biological samples include, but are not limited to, blood, serum, plasma, urine, saliva, feces, organ tissues, etc., preferably biological samples from patients. According to the precautions, the processed sample can contain one or more isolated or enriched biological molecules, which can be analyzed, detected or quantified in subsequent procedures. For example, a biological sample (e.g., a biological sample from a subject) can be processed in the system of the present invention to obtain a processed sample containing isolated or enriched nucleic acids, and the processed sample can be used to amplify, detect or quantify one or more nucleic acids of interest, for example, as a template in a PCR reaction, or one or more chemiluminescent labeled nucleic acids used in a hybridization process.

[0091] In a preferred embodiment, a method further comprises detecting or quantifying nucleic acids of a treated sample using PCR or chemiluminescent assays. In another example, a biological sample (e.g., a biological sample from a subject) can be processed in the system of the present invention to obtain a processed sample containing a polypeptide or protein, and the processed sample can be used for an immunoassay, such as a radioimmunoassay, ELISA, immunofluorescence assay, or chemiluminescent immunoassay, for detecting or quantifying one or more polypeptides or proteins of interest.

[0092] In another embodiment, the method includes detecting or quantifying peptides or polypeptides in a treated sample using ELISA, immunofluorescence assay, or chemiluminescent immunoassay (CLIA). CLIA is a more sensitive alternative to ELISA that involves generating electromagnetic radiation (in the form of light) by releasing energy through a chemical reaction and measuring the light intensity. For example, a photomultiplier tube or photodiode and associated electronic equipment are used to convert and record the signal. Known methods and reagents for detecting or quantifying biomolecules, such as PCR, ELISA, immunofluorescence, assays, or CLIA. Through the disclosure of the present invention, the above procedures can all be used in the present invention.

Claims

1. A biological sample automatic extraction system for extracting a biological sample from a set of biological samples, the extraction system comprising: a) a vertical frame divided into a top section and a bottom section by a horizontal platform, the horizontal platform having a right side and a left side; b) a rotating storage system installed in the bottom section, which is used to store a plurality of storage boxes for placing consumables, wherein the storage boxes contain a group of consumables, and the rotating storage system can rotate around a vertical axis; c) a set of reaction tubes, as part of the consumables set, for sample preparation and extraction; d) a rotating table, installed in the top section and arranged above the rotating storage system, having: i) a sample tube rack for placing sample tubes; ii) a reaction tube rack, located at a first position adjacent to the sample tube rack to reduce sample movement, the reaction tube rack being used to place reaction tubes; iii) Waste discharge holes for waste disposal iv) a plurality of housings sized to receive and hold a plurality of storage boxes containing a set of consumables; e) a box lift robot capable of vertical movement to transfer each storage box from the rotary storage system to the rotary table, wherein the rotary storage system rotates so that each storage box can be picked up by the box lift robot, and the rotary table rotates so that the rotary table can receive the storage box delivered from the box lift robot; f) a sample robot, which is used to transfer the sample tube from the sample rack to the transfer unit on the rotating table, and transfer the reaction tube to the transfer unit adjacent to the sample tube placement position, and mix the sample and consumables in the reaction tube, thereby reducing the amount of sample movement and the risk of contamination; g) a sample extraction unit, installed in the top section, having an independent tube shaking device and a plurality of magnet racks, each tube shaking device is used to accommodate each reaction tube, and each vibrator can work independently through a vibrating mechanism; h) A reaction robot, which is used to transfer the reaction tube from the rotating table to the sample extraction unit. The rotating table moves the reaction tube from a first position to a second position, wherein the second position is the shortest distance between the reaction tube and the sample extraction unit. The reaction tube and the sample extraction unit minimize sample movement and reduce the risk of contamination. The reaction robot is also used to transfer the consumables group. Since the extraction system occupies a small area and the movement of the consumables group is minimal, potential contamination during the extraction process is reduced.

2. The system according to claim 1, wherein the rotating stage is disposed on the left side of the horizontal platform; and the sample extraction unit is placed on the right side of the rotating stage; The reaction tube rack is initially placed on the left side of the rotating table. After the sample preparation process is completed, the rotating table is rotated so that the reaction tube rack is located on the right side of the rotating table, so that the reaction tube rack is located close to the sample extraction unit.

3. The system according to claim 1 further comprises a cooler installed in the top section, which is used to store a variety of consumables that need to be stored in a low temperature environment.

4. The system according to claim 1, further comprising a waste unit installed in the bottom section, wherein the sample extraction unit and the waste unit are separated by a horizontal platform to prevent contamination.

5. The system of claim 1 further comprising a programmable control system programmed to synchronize and process samples in a serial mode, wherein a series of samples follow one another to be processed sequentially in time order, thereby maintaining a fixed processing turnaround time for each sample regardless of when the sample begins processing.

6. The system according to claim 1, wherein the consumables set comprises: A set of samples, buffer, long pipette tips, medium pipette tips, short pipette tips and a set of reaction tubes.

7. The system according to claim 1, wherein: The sample extraction unit comprises a plurality of independent tube shaking devices mounted on a plurality of magnet racks, wherein each tube shaking device can accommodate the reaction tube and can function independently through a vibration mechanism.

8. The system of claim 7, wherein each tube shaking device has 1 shaking motor to integrate orbital shaking.

9. The system according to claim 7, wherein: The magnet frame is movable along the X-axis and the Y-axis and has a set of magnetic gears to control the movement of the cradle device.

10. The system of claim 9, wherein the magnetic gears are mounted on a set of rotating shafts.

11. The system according to claim 7, characterized in that Each shaking tube device comprises a substantially cylindrical containing space, and the size of each containing space is slightly larger than the bottom of the reaction tube.

12. The system according to claim 7, wherein each magnet rack has an L-shaped magnet, and the L-shaped magnet can accommodate the reaction tube placed in the tube shaking device, and the magnetic strength acting on each reaction tube is changed by setting the distance of the reaction tube relative to the L-shaped magnet.

13. The system according to claim 12, wherein: The sample extraction unit has a linear motion tube shaking device pushing robot to push the tube shaking device to a predetermined position, the reaction tube can be located at a first distance from the L-shaped magnet, and the L-shaped magnet has a small effect on the magnetic beads; The reaction tube can be located at a second distance from the L-shaped magnet, and the L-shaped magnet has a medium effect on the magnetic beads; The reaction tube can be located at a third distance from the L-shaped magnet, and the L-shaped magnet has a greater influence on the magnetic beads.

14. The system according to claim 7, wherein: The plurality of magnet frames are installed parallel to each other and can move in a horizontal plane.

15. The system of claim 7, wherein each magnet rack can accommodate six shaking tube devices.

16. The system according to claim 1, wherein the sample robot is equipped with an electric gripper for picking up and transferring sample tubes; and the reaction robot is equipped with an electric gripper for picking up and transferring reaction tubes.

17. The system of claim 1, wherein the sample robot and the reaction robot have electric pipettes for transferring consumables.

18. The system according to claim 16, wherein the gripper of the reaction robot has a rod-shaped gripper movable in a vertical position, and the rod-shaped gripper can be moved in the vertical position to be inserted into the reaction tube to grip and transfer the reaction tube.

19. The system of claim 16, wherein the electric gripper of the sample robot is mounted on a first gripper arm, the first gripper arm being movable on a sample robot track, the sample robot track being fixed to an upright frame for movement relative to the rotary storage system and the rotary stage.

20. The system of claim 16, wherein the motorized gripper of the reaction robot is mounted on a second gripper arm, the second gripper arm being movable on a reaction robot track secured to an upright frame for movement relative to the sample extraction unit and the rotating stage, the motorized gripper of the reaction robot being capable of automatically selecting and grabbing pipette tips from various pipette tip boxes to add various components to extraction tubes.

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