Execution information recording method, execution information recording device, program, recording medium, execution information transmission method, and execution information transmission device
The method and device for recording execution information during specimen pretreatment address the inaccuracy in ejection volume determination by processing and recording evidence to overcome inhibiting events, resulting in precise and accurate ejection volume assessment.
Patent Information
- Application Number
- JP2025060911
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2025-04-02
- Publication Date
- 2025-06-19
AI Technical Summary
Existing methods for determining the ejection volume of specimens during pretreatment are inaccurate due to events such as films or bubbles forming on the chip, which can cause delays or errors in the inspection process.
A method and device for recording execution information that involves ejecting a specimen, photographing the specimen aspiration and discharge tool, processing the tool to prevent events from inhibiting ejection volume determination, and recording the evidence obtained before and after processing.
Enables accurate determination of the ejection volume even when events that inhibit determination occur, ensuring precise execution of pretreatment protocols and reducing errors in inspection processes.
Smart Images

Figure 2025092689000001_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to a method for recording execution information, a recording device, a program, a recording medium, a method for transmitting execution information, and an execution information transmission device when a pretreatment performed before an inspection using a specimen is executed according to a preset protocol.
Background Art
[0002] In the fields of life sciences such as biology, biochemistry, biotechnology, and food science, various tests using specimens are performed. Before a test using a specimen, pretreatment such as dispensing, which involves transferring the specimen in a specimen container (e.g., a tube) to a discharge destination container (e.g., a plate) using a specimen suction and discharge tool (e.g., a pipette or dropper with a chip attached to the tip), is performed.
[0003] In addition to being performed manually, the pretreatment may be performed using a dispensing device (Patent Document 1) in recent years. The dispensing device of Patent Document 1 is configured to capture images of the chip before and after dispensing using imaging means, and to determine whether the dispensing has been performed accurately based on the edges of the captured chip images.
Prior Art Documents
Patent Documents
[0004]
Patent Document 1
Summary of the Invention
Problems to be Solved by the Invention
[0005] By the way, events that inhibit the determination of the discharge amount, such as a film or bubbles, may occur in the chip after dispensing, which may cause delays or errors in the execution of the pretreatment. However, in Patent Document 1, when performing determination using an image, such events are not considered, so there is a possibility that an accurate determination cannot be made regarding the appropriateness of dispensing.
[0006] The present invention has been made in view of such circumstances, and the problem to be solved is to enable accurate determination of the ejection volume even when an event that inhibits the determination of the ejection volume occurs.
Means for Solving the Problem
[0007] [Method for Recording Execution Information] The method for recording execution information of the present invention is a method for recording execution information when performing pretreatment before an inspection using a specimen according to a preset protocol, and includes a step of ejecting the specimen in the specimen aspiration and discharge tool into a discharge destination container in the pretreatment, a step of photographing the specimen aspiration and discharge tool after the specimen is ejected, a step of processing the specimen aspiration and discharge tool so that an event that inhibits the determination of the ejection volume of the specimen does not inhibit the determination when the event occurs, and a step of associating and recording the evidence obtained by photographing and the evidence after the processing.
[0008] [Execution Information Recording Device] The execution information recording device of the present invention is a recording device for execution information when performing pretreatment before an inspection using a specimen according to a preset protocol, and includes a step of ejecting the specimen in the specimen aspiration and discharge tool into a discharge destination container in the pretreatment, a photographing means for photographing the specimen aspiration and discharge tool after the specimen is ejected, a processing means for processing the specimen aspiration and discharge tool so that an event that inhibits the determination of the ejection volume of the specimen does not inhibit the determination when the event occurs, and a recording means for associating and recording the evidence obtained by photographing and the evidence after the processing by the processing means.
[0009] [Program · Recording Medium] The program of the present invention is a program for operating a computer as the execution information recording device, and the recording medium of the present invention is a computer-readable recording medium on which the program is recorded. Here, the computer referred to herein is not limited to an electronic computer (PC) described later, but is a concept including various devices constituting an execution information recording device such as a robot, a reading means, a photographing means, and a lighting fixture.
[0010] [Method for Transmitting Execution Information] The method for transmitting execution information of the present invention is a method for transmitting execution information, which transmits the execution information when a pretreatment performed before an inspection using a specimen is executed according to a preset protocol, to an external device, and is a method for transmitting one or more pieces of execution information selected from the execution information recorded by the execution information recording method of the present invention to an external device via a communication line.
[0011] [Execution Information Transmitting Device] The execution information transmitting device of the present invention is an execution information transmitting device that transmits execution information, which is a record when a pretreatment performed before an inspection using a specimen is executed according to a preset protocol, to an external device, and is a device provided with a communication unit that transmits one or more pieces of execution information selected from the execution information recorded in a recording unit by the execution information recording device of the present invention to an external device via a communication line. [Advantages of the Invention]
[0012] In the present invention, when an event that inhibits the determination of the specimen discharge amount occurs in the specimen aspiration and discharge tool, the event is processed so as not to inhibit the determination of the specimen discharge amount, so that an accurate determination of the discharge amount becomes possible. [Brief Description of the Drawings]
[0013]
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Mode for Carrying Out the Invention
[0014] (Embodiment) An example of an embodiment of the present invention will be described with reference to the drawings. The present invention relates to a method and an apparatus for recording execution information obtained in the process of pretreatment of an inspection using a specimen executed by a robot 30. Prior to a specific description of the execution information recording method and the execution information recording apparatus, the meaning of terms used in the present application will be described.
[0015] The "inspection using a specimen" in the present application includes inspections for analyzing the nucleotide sequence of nucleic acids and inspections for analyzing the amino acid sequence. Specifically, it includes inspections for analyzing the nucleotide sequence of nucleic acids (for example, the nucleotide sequence of a gene) using a sequencer (for example, a next-generation sequencer), and inspections for analyzing the amino acid sequence using a peptide sequencer (protein sequencer) that automates the Edman method, which is a kind of amino acid sequence analysis method. Note that the expressions "analysis" or "measurement" may be used instead of "analysis", but the analysis in the present application is a concept that includes analysis, measurement, etc.
[0016] The specimens to be pre-treated in this application include feces, urine, saliva, skin, hair, gut microbiota (intestinal flora), etc. These specimens are not limited to those collected from humans, but also include those collected from various animals (such as mammals, fish, birds, amphibians, reptiles, etc.), insects, shellfish, crops, plants, their seeds and seedlings, microorganisms, etc.
[0017] The specimens referred to in this application include, in addition to the specimens themselves, those to which a buffer solution (buffer component) having a buffering action on the specimens is added (hereinafter referred to as "specimen solutions"). For the sake of convenience in description, in this application, unless otherwise particularly distinguished, the specimen itself or the specimen solution is referred to as "specimen". The buffering action referred to here means an action of alleviating the influence even when a small amount of acid or base is added and keeping the pH substantially constant.
[0018] Examples of the buffer solution include phosphate buffer solution, acetate buffer solution, citrate buffer solution, citrate phosphate buffer solution, borate buffer solution, tartrate buffer solution, Tris buffer solution, McIlvaine buffer solution, etc. One type or two or more types of buffer solutions may be added depending on the specimen.
[0019] The specimen solutions in this application also include those in a suspension state in which solid particles of specimens such as feces are dispersed. The specimen solutions obtained by adding a buffer solution to the specimens are characterized in that events such as membranes and bubbles are likely to occur in the chip Z and the tube X described later.
[0020] In addition, after sucking up the specimen from the tube X and discharging it into a discharge destination container (for example, a plate such as a deep well plate) 18 described later, it is common to store the specimen remaining in the tube X. At this time, it is also important to ensure the closing of the lid of the tube X and the airtightness so that the nucleic acid in the cells of the specimen remaining in the tube X does not denature.
[0021] The pretreatment of this application is carried out at the stage prior to the inspection using the specimen (for example, an inspection for analyzing the nucleotide sequence of a gene or the amino acid sequence contained in a protein), and means the process executed by the pretreatment execution system including the robot 30 described later.
[0022] As an example, as shown in FIG. 1, it includes a plate ID reading step S001 - a taking-out step S002 - a specimen ID reading step S003 - a specimen ID photographing step S004 - a lid-removing step S005 - a chip mounting step S006 - a mounted chip confirmation step S007 - a suction step S008 - a suction amount confirmation step S009 - a discharging step S010 - a discharging amount confirmation step S011 - a chip removing step S012 - a lid closing step S013 - a lid closing confirmation step S014 - a housing step S015, etc. Note that the pretreatment of this application does not necessarily include all of these steps, and may refer to only a part of them.
[0023] In this embodiment, it is executed by the pretreatment execution system including the robot 30 described later, and various execution information obtained during the execution of the pretreatment will be recorded. This pretreatment execution system includes the robot 30 and an electronic computer (hereinafter referred to as "PC") 40, and the pretreatment (the above-mentioned entire process) is executed according to the protocol registered in both or either of them.
[0024] The protocol is an execution procedure manual in which the processing procedure and processing conditions of the pretreatment are defined, and is registered in both or either of the robot 30 and the PC 40 prior to the start of the steps of the above-mentioned embodiment. The content of the protocol varies depending on the characteristics of the specimen, the specifications of the inspection after pretreatment, etc. The protocol may include items set by the side performing the pretreatment. The protocol may be registered in a device other than the robot 30 and the PC 40 (for example, a device having functions corresponding to the processor and memory of the robot 30 and the PC 40, etc.). Also, when a single robot 30 (pretreatment execution system) is responsible for pretreatments corresponding to a plurality of protocols, protocol IDs unique to each of the plurality of protocols may be assigned.
[0025] In the protocol, based on the three-dimensional (XYZ) working space coordinates set with respect to the robot 30, in addition to determining the starting point of the operation of the robot 30, the operation path, the operation posture, the end point of the operation, the stop posture, the moving speed, the waypoint, the operation time, etc., in some cases, part or all of the rotation speed and pressure of the first hand 31a and the second hand 32a are also determined.
[0026] In addition, the protocol defines details such as the reading method by the reading means 13, the photographing method by the photographing means 14, the gripping method by the tube vice 16, etc., the reference amount of aspiration of the specimen, the reference amount of ejection of the specimen, the determination method of the aspiration amount, the determination method of the ejection amount, the lid removal method, the determination method of lid removal, the lid closing method, the determination method of lid closing, the processing method of the evidence, the recording method of the execution information obtained in each process, etc. The "time" of the processing and determination of each process is also recorded as the execution information.
[0027] In this embodiment, among the protocol, for the operation of the robot 30, it is registered in the robot 30, and for the determination and the support for the processing branch of the robot 30 associated therewith, it is registered in the PC 40. However, the protocol can be registered in both or either one of the robot 30 side and the PC 40 side, either in whole or in part. In the execution of the registered protocol, individual determinations and instructions can also be performed on the PC 40 side.
[0028] Also, in this embodiment, the operation record (execution information) executed based on the registered protocol is recorded in the robot 30 regarding the operation of the robot 30 after its execution, and regarding the determination (including certification) and the processing condition branch, it is recorded on the PC40 side. The operation record (execution information) executed based on the registered protocol can be recorded in whole or in any part of both or either one of the robot 30 and the PC40, including the operations of the reading means 13, the photographing means 14, the tube vice 16, etc. after its execution. Also, the execution record (execution result, certification, etc.) of the reading, determination, and instruction execution based on the registered protocol can be recorded in whole or in part in both or either one of the robot 30 and the PC40. The execution information may be recorded in a device other than the robot 30 and the PC40 (for example, a device having functions corresponding to the processor and memory of the robot 30 and the PC40). Note that the content of the registration is omitted in this specification.
[0029] Based on the above, an example of the execution information recording method, the execution information recording device, the program, the recording medium, the execution information transmission method, and the execution information transmission device of the present invention will be described. The execution information recording method and the execution information recording device of the present invention are a method and a device for recording the execution information acquired in each step of the preprocessing. The execution information acquired in each step of the preprocessing is automatically recorded in the storage 43 in association with the specimen-specific information or / and the protocol-specific information, etc., which will be described later, for each specimen. This recording is automatically performed simultaneously (immediately after execution) with the execution of each process.
[0030] [Overview of the preprocessing flow] FIG. 1 shows an example of a flowchart of pretreatment performed before inspection using a specimen. The pretreatment in FIG. 1 includes a plate ID reading step S001 - a taking-out step S002 - a specimen ID reading step S003 - a specimen ID photographing step S004 - a lid removal step (unsealing step) S005 - a chip mounting step S006 - a mounted chip confirmation step S007 - a suction step S008 - a suction volume confirmation step S009 - a discharge step S010 - a discharge volume confirmation step S011 - a chip removal step S012 - a lid closing step (sealing step) S013 - a lid closing confirmation step S014 - a storage step S015. As described above, each of the above steps is performed according to the protocol provided by a customer (for example, an operator who performs inspection after pretreatment). The protocol includes processing procedures and processing conditions, etc.
[0031] [Plate ID Reading Step] The plate ID reading step S001 is a step of reading an identification code (hereinafter referred to as "plate ID") displayed on plate 18, which is the discharge destination of the specimen, by reading means 13. The plate ID is a unique identification code assigned to each plate and is composed of a barcode, a QR code (registered trademark. The same shall apply hereinafter), etc. The display here includes not only the display by attaching a sticker printed with the plate ID, but also the display by directly printing the plate ID on tube X, etc.
[0032] In the plate ID reading step S001, as execution information, the read plate ID (read plate ID) is recorded in PC40. The read plate ID is what reads the plate ID displayed on plate 18 and is the same as the plate ID.
[0033] Note that the plate ID reading step S001 is a step performed manually at a stage before the operation by robot 30 is started. In this embodiment, after the plate ID reading step S001, the steps after the taking-out step S002 in FIG. 1 are started.
[0034] [Taking-Out Step] The sample extraction step S002 is a step of extracting the tube X containing the sample with the hand 31a of the first robot arm (hereinafter referred to as the "first arm") 31. In this step, the tube X contained in the tube rack 11 is gripped by the first hand 31a of the first arm 31.
[0035] [Sample ID reading step] The sample ID reading step S003 is a step of reading, by the reading means 13, the sample identification information (hereinafter referred to as the "sample ID") for identifying the sample displayed on the tube X. The sample ID is a unique ID assigned to each sample and is composed of a barcode, a QR code, a code composed of a combination of characters and numbers representing the sample ID (hereinafter referred to as the "identification code"), etc. Specifically, there are only a barcode, only a QR code, a combination of an identification code and a barcode, a combination of an identification code and a QR code, etc. Here, the display mentioned includes not only the display by attaching a seal printed with the sample ID but also the display by directly printing the sample ID on the tube X.
[0036] In this step, the tube X is moved to the reading position of the reading means 13 by the first arm 31, and the sample ID displayed on the tube X is read by the reading means 13. The reading of the sample ID can be performed with the tube X stopped or while rotating the tube X in the forward or reverse direction. By rotating the tube X in the forward or reverse direction, it is possible to accurately and reliably read even when the sample ID is displayed obliquely with respect to the axis in the longitudinal direction of the tube X. When reading the sample ID, the tube X can be rotated continuously or intermittently in multiple times. Also, when reading the sample ID, the tube X may be moved up and down so as to cope with the vertical error at the attachment position of the seal of the tube X.
[0037] In the sample ID reading step S003, if the reading is successful, the sample ID read by the reading means 13 (hereinafter referred to as the "read sample ID") is used as the execution information. If the reading fails, the fact that the tube X has been moved to the storage box is recorded in the PC40. Since the read sample ID is the one obtained by reading the sample ID displayed on the tube X, it matches the said sample ID.
[0038] [Sample ID photographing step] The sample ID photographing step S004 is a step of photographing the sample ID displayed on the tube X by the photographing means 14. In this step, the tube X is moved to the photographing position by the photographing means 14 by the first arm 31, and the sample ID displayed on the tube X is photographed by the photographing means 14.
[0039] Since the sample ID displayed on the tube X may be displayed obliquely with respect to the longitudinal axis of the tube X, or may be displayed in the reverse left - right direction, or may be displayed upside - down, etc., it is preferable to perform the photographing a plurality of times by continuously rotating or intermittently rotating the tube X in the forward or reverse direction. Traceability can be ensured by the image obtained by photographing (hereinafter referred to as the "sample ID image"). Also, the sample ID image can be used for verification of the read sample ID read by the reading means 13.
[0040] In the sample ID photographing step S004, the sample ID image obtained by photographing by the photographing means 14 is recorded in the PC40 as the execution information.
[0041] [Cover - removing step] The cover - removing step S005 is a step of removing (unsealing) the cover Y of the tube X. In this step, the tube X is placed at a predetermined position of the tube vice 16 by the first arm 31, and the cover Y of the tube X held by the holding portion 16a of the tube vice 16 is removed by the first hand 31a of the first arm 31.
[0042] In this embodiment, the lid Y of the tube X clamped by the tube vise 16 is gripped by the first hand 31a of the first arm 31, and when the first hand 31a rotates, the lid Y of the tube X is removed.
[0043] When the operation of removing the lid by the first arm 31 is completed, it is determined whether or not the lid removal has been successful based on the determination conditions (lid removal determination conditions) set in advance based on the protocol. Whether or not the lid removal is successful can be determined by various methods. In this embodiment, it is determined whether or not the lid Y is being gripped based on the pressure and position of the two claws of the first hand 31a.
[0044] That is, when the lid Y is being gripped by the first hand 31a, the two claws are opened wider than the diameter of the lid Y, whereas when the lid Y is not being gripped, the distance between the two claws is less than the diameter of the lid Y. Therefore, by measuring the position (distance) of both claws, it is possible to determine whether or not the lid Y is being gripped (whether or not the lid Y has been opened).
[0045] Whether or not the lid removal is successful can also be determined by other methods. For example, it can be determined by measuring the load of a motor (not shown) built into the wrist. When the lid Y has not been removed from the tube X clamped by the tube vise 16, a load of a predetermined amount or more is applied to the wrist of the first hand 31a when rotating the lid Y. Therefore, by measuring the load, it is possible to determine whether or not the lid removal is successful. This method can be adopted instead of, or together with, the method of measuring the pressure and position of the first hand 31a (two claws).
[0046] In the lid removal step S005, as execution information, the determination result (lid removal determination result) as to whether or not the lid removal is successful is recorded in the PC 40. Also, in this embodiment, when it is determined that the lid removal has failed, the robot 30 is temporarily stopped. In this embodiment, when the robot 30 is temporarily stopped, it is notified by sound, light, or the like.
[0047] [Chip Mounting Process] The chip mounting process S006 is a process of mounting a chip Z on the tip of a pipette P gripped by a hand (hereinafter referred to as "second hand") 32a of a second robot arm (hereinafter referred to as "second arm") 32. In this process, the pipette P moved above the chip rack 19 by the second arm 32 is lowered toward a predetermined chip Z so that the chip Z is fitted and mounted on the tip of the pipette P.
[0048] In this process, the chip Z mounted on the tip of the pipette P by the second arm 32 is moved to the imaging position by the imaging means 14, and the chip Z is imaged by the imaging means 14. The imaging can be performed in a stationary state or while rotating the chip Z in the forward or reverse direction. Traceability can be ensured by the captured image (hereinafter referred to as "mounted chip image") captured in this process.
[0049] In the chip mounting process S006, as execution information, the mounted chip image obtained by imaging with the imaging means 14 is recorded in the PC40.
[0050] [Mounted Chip Confirmation Process] The mounted chip confirmation process S007 is a process of confirming whether or not a chip Z is mounted on the tip of the pipette P based on a determination criterion (chip mounting determination criterion) set in advance based on a protocol. In this process, it is also confirmed whether or not the inside of the mounted chip Z is empty. Whether or not the mounting of the chip Z is successful can be determined by various methods, but in this embodiment, based on the mounted chip image, it is determined whether or not the chip Z is mounted.
[0051] This determination is made by the processor 41 of the PC40. From the mounted chip image, if the chip Z is mounted on the tip of the pipette P, it is determined that the mounting is successful, and if the chip Z is not mounted on the tip of the pipette P, it is determined that the mounting has failed.
[0052] In the chip mounting confirmation step S007, as execution information, the determination result (chip mounting determination result) as to whether or not the chip has been successfully mounted is recorded in the PC 40. Also, in this embodiment, when it is determined that the chip mounting has failed, the robot 30 is configured to temporarily stop. Similar to other steps, when the robot 30 temporarily stops in this step, it is configured to be notified by sound, light, or the like.
[0053] [Suction step] The suction step S008 is a step of sucking the specimen in the tube X held by the tube vice 16 into the chip Z mounted at the tip of the pipette P. This step is performed by the cooperation of the first arm 31 and the second arm 32.
[0054] Specifically, as shown in FIGS. 2(a) to (d), the push button PB of the pipette P held by the second hand 32a of the second arm 32 is pushed down by the first hand 31a of the first arm 31, and in this state, the chip Z mounted on the pipette P is inserted into the tube X. Then, by releasing the push down of the push button PB of the pipette P, the specimen in the tube X is sucked into the chip Z. When inserting the chip Z into the specimen in the tube X, the tip of the chip Z is positioned near the liquid surface of the specimen so as not to touch the bottom of the tube X.
[0055] In this embodiment, by making the descending speed of the first arm 31 that has pushed down the push button PB of the pipette P slower than the descending speed of the second arm 32 that holds the pipette P, the push down of the push button PB is released and the specimen is sucked into the chip.
[0056] Note that in this embodiment, the descending speed of the second arm 32 (in other words, the descending speed of the pipette P held by the second arm 32) is adjusted to be the same as or faster than the speed at which the liquid surface of the specimen drops (the decreasing speed of the specimen) so that the tip of the chip Z does not rise above the liquid surface of the specimen in the tube X when sucking the specimen.
[0057] When aspirating the sample, as the liquid level of the sample gradually drops as the sample is aspirated, depending on the descending speed of the second arm 32, the tip of the chip Z may protrude above the liquid level of the sample in the tube X, and there is a risk of air mixing in. By adjusting the descending speed of the second arm 32 as in this embodiment, it is possible to avoid air mixing during sample aspiration.
[0058] In this step, the chip Z after aspirating the sample attached to the tip of the pipette P by the second arm 32 moves to the imaging position by the imaging means 14, and the chip Z is imaged by the imaging means 14. The imaging can be performed in a stationary state or while rotating the chip Z in the forward or reverse direction. Traceability can be ensured by the captured image (hereinafter referred to as the "post-aspiration chip image") captured in this step.
[0059] In the aspiration step S008, as execution information, the post-aspiration chip image obtained by imaging with the imaging means 14 is recorded in the PC40.
[0060] [Sample Aspiration Volume Confirmation Step] The sample aspiration volume confirmation step S009 is a step of confirming the aspiration volume of the sample. In this step, it is determined from the post-aspiration chip image whether a specified volume of the sample has been aspirated into the chip Z attached to the tip of the pipette P. The specified volume here is an amount arbitrarily set according to the characteristics of the sample and the specifications of the analysis test, and is specified as part of the protocol. Also, the manufacturer, model number, size, etc. of the chip may also be included as part of the protocol.
[0061] Note that in this step, the entire chip Z or a part of it may be imaged. When imaging a part, for example, it can be made to include the aspirated sample portion and the air portion above it. The post-aspiration chip image includes the entire chip Z, the sample aspirated into the chip Z, and the air above the aspirated sample.
[0062] In this embodiment, it is determined whether a sample of a specified volume has been aspirated by image processing of the chip image after aspiration. Specifically, as shown in FIGS. 3(a) and 3(b), when the size, area, configuration, target region, or the quantified values thereof of the figure within the plane or on the curved surface of the air portion S1 (the region surrounded by the dashed line in FIG. 3(b)) within the chip Z of the captured image data (FIG. 3(a)) meet the determination criteria (hereinafter referred to as the "aspiration volume determination criteria") set in advance based on the protocol, it is determined that a sample of the specified volume has been aspirated. When the determination criteria are not met, it is determined that a sample of the specified volume has not been aspirated.
[0063] In this embodiment, the size, area, configuration, target region, or the quantified values thereof of the figure within the plane or on the curved surface of the air portion S1 within the chip Z are used as the determination criteria. However, the size, area, configuration, target region, or the quantified values thereof of the figure within the plane or on the curved surface of the sample portion S2 (the region surrounded by the double-dashed line in FIG. 3(b)) within the chip Z can also be used as the determination criteria. In this case as well, when the size, area, configuration, target region, or the quantified values thereof of the figure within the plane or on the curved surface of the sample portion S2 within the captured chip Z meet the aspiration volume determination criteria set in advance based on the protocol, it can be determined that a sample of the specified volume has been aspirated. When the determination criteria are not met, it can be determined that a sample of the specified volume has not been aspirated.
[0064] Note that whether a sample of the specified volume has been aspirated can also be determined based on, in addition to the size, area, configuration, target region, or the quantified values thereof of the figure within the plane or on the curved surface of the air portion S1 or the sample portion S2, the distance from the upper end to the lower end of the air portion S1, the distance from the upper end to the lower end of the sample portion, the area ratio between the air portion and the sample portion, the distance ratio between the upper end and the lower end of both, and the like.
[0065] In the aspiration volume confirmation step S009, as execution information, a determination result (aspiration volume determination result) as to whether or not a sample of a specified volume has been aspirated into the chip Z is recorded in the PC 40. The aspiration volume determination result here may include, in addition to whether or not the aspiration volume is within the specified volume range, numerical values of the specific aspiration volume, etc.
[0066] Also, in this embodiment, when it is determined that a sample of the specified volume has not been aspirated, the robot 30 is temporarily stopped. Similar to other steps, when the robot 30 is temporarily stopped in this step, it is configured to be notified by sound, light, etc.
[0067] [Dispensing Step] The dispensing step S010 is a step of dispensing the aspirated sample into the plate hole 18a. As shown in FIGS. 4(a) to 4(c), this step is performed by the cooperation of the first arm 31 and the second arm 32. Specifically, after the tip of the pipette P, the chip Z, is moved to a predetermined position on the plate 18 by the second arm 32, the push button PB of the pipette P is pushed down by the first hand 31a at that position, and the sample in the chip Z is dispensed into the plate hole 18a.
[0068] In the dispensing step S010, as execution information, the plate ID of the dispensing destination (hereinafter referred to as "dispensing destination plate ID") and information on the plate hole (dispensing destination plate hole) in the dispensing destination plate ID are recorded in the PC 40.
[0069] Note that the dispensing destination plate hole is specified by XYZ coordinates (for example, the three axes of the XYZ coordinates or the two axes of the X coordinates and the Y coordinates) in the work space coordinates set with the robot 30 as a reference. The plate ID and the dispensing destination plate hole specified by the X coordinates and the Y coordinates here are recorded in the PC 40 as dispensing destination specifying information for specifying the dispensing destination. As the dispensing destination specifying information, combination information of the signs A to H assigned to the vertical columns (X axis) of the plate 18 and the numbers 1 to 12 assigned to the horizontal rows (Y axis) can also be used.
[0070] [Dispensing Volume Confirmation Step] The dispensing volume confirmation step S011 is a step of confirming whether a sample of a specified volume has been dispensed from the chip Z. In this step, the chip Z mounted at the tip of the pipette P by the second arm 32 is moved to the imaging position by the imaging means 14, and the chip Z is imaged by the imaging means 14. From the captured chip image (hereinafter referred to as the "post-dispensing chip image"), it is determined by the processor 41 of the PC40 whether a sample of a specified volume has been dispensed from the chip Z.
[0071] Similar to the aspiration volume confirmation step S009, in this step, the entire chip Z or a part of it may be imaged. When imaging a part, for example, it is possible to include the sample remaining in the chip Z (hereinafter referred to as the "remaining sample") after dispensing and the air portion above the remaining sample portion. In this case, the post-dispensing chip image includes the entire chip Z, the remaining sample, and the air above the remaining sample portion.
[0072] In this embodiment, similar to the aspiration volume confirmation step S009, it is determined whether a sample of a specified volume has been dispensed by image processing of the chip Z imaged by the imaging means 14. Specifically, as shown in FIGS. 5(a) and 5(b), when the size, area, configuration, target area of the figure in the plane or curved surface of the air portion S1 (the area surrounded by the dashed-dotted line in FIG. 5(b)) of the captured post-dispensing chip image meets the determination criteria (hereinafter referred to as the "dispensing volume determination criteria") set in advance based on the protocol (when within the threshold range), it is determined to be normal, and when it does not meet the determination criteria (threshold) (when outside the threshold range), it is determined to be an error. Similar to the aspiration volume confirmation step S009, this determination is made by the processor 41 of the PC40.
[0073] In addition, when performing the determination, even though the ejection volume is appropriate, a film or bubbles (hereinafter referred to as "film etc.") F generated in chip Z may be misrecognized as the sample, and it may be determined that the sample of the specified volume has not been ejected. Film etc. F is an event that inhibits the determination of the ejection volume, and may occur, for example, due to the characteristics and temperature of the buffer solution, the shape and size of chip Z, etc.
[0074] When an event that inhibits the determination of the ejection volume, such as film etc. F, occurs, it is processed so that the determination is not inhibited by this event. As a processing method, for example, as shown in Fig. 5(c), after ejection, the chip image is replicated on PC40, and a part of the replicated chip image after ejection (for example, the upper part of the chip where film etc. F is likely to occur) is hidden (blackened) to narrow the determination target area. In this case, the size, area, configuration, target area of the figure in the plane or curved surface of the air part S1 and the remaining sample part S3 in the state where the determination target area is narrowed, or the numerical values thereof are calculated, and it may be determined whether the sample of the specified volume has been ejected from the calculated values.
[0075] In Fig. 5(c), the determination target area is restricted by blackening and hiding the part where the event of film etc. F occurs (hereinafter referred to as "event occurrence part"), but the determination target area can also be restricted by methods other than blackening. For example, it is conceivable to restrict the determination target area by cutting (removing) a part including the event occurrence part on the image, and determining whether the sample of the specified volume has been ejected based on the evidence after cutting.
[0076] As a method of hiding the event occurrence part, for example, there is a method of presetting the hiding range so that the corresponding range of the evidence is uniformly hidden. For example, the hiding range of the evidence can be preset, such as the upper 10% range of the evidence or the range of 50 mm from the top of the evidence, so that the corresponding range on the evidence is hidden. The hiding range can also be set in a way such as 50 mm from the top of the evidence. Note that these numerical values are just examples, and other numerical values can also be used for setting. Also, the reference for the hiding position is not limited to being from the top of the evidence. For example, it can be set based on the upper end of the chip in the evidence, such as a few percent or a few millimeters from the upper end of the chip in the evidence.
[0077] Based on a certain criterion, it is also possible to hide the event occurrence part by varying the hiding position and range for each piece of evidence. For example, when a specific event (such as a line appearing within chip Z on the evidence) is confirmed on the evidence, the hiding position and range can be varied for each piece of evidence based on that event. Also, for example, the hiding position and range can be varied for each piece of evidence based on the characteristics and properties of the specimen or buffer solution, the mechanical wear of pipette P and chip Z, the working environment (temperature, humidity, atmospheric pressure, etc.).
[0078] For example, it is also possible to hide the event occurrence part by detecting the mounting angle from the captured image when chip Z is mounted, predicting the change in the discharge amount from that angle, and changing the hiding location (such as position and range, etc.) accordingly, or by moving the hidden area downward every predetermined time (such as a few seconds). The former can be an effective method for dealing with cases such as when mechanical wear occurs, for example, when the sealing performance of the connection part C between pipette P and chip Z fluctuates. The latter can be an effective method for dealing with cases such as when it is necessary to consider the remaining amount adhering to the inner wall of chip Z due to the viscosity of the specimen. Here, the case of hiding a part of the evidence is described, but the case of cutting off a part of the evidence can also be carried out in a similar way.
[0079] When restricting the determination target area by blackening or removing the event occurrence part or other methods, it is preferable to keep both the evidence before the restriction (the chip image after ejection) and the evidence after the restriction (the processed chip image after the blackening or excision process) as records. Also, the evidence before the restriction and the evidence after the restriction can be displayed in parallel on the monitor 21. However, the two pieces of evidence may be displayed individually instead of in parallel.
[0080] By keeping both the evidence before the restriction (for example, raw image data such as a still image or a moving image) and the evidence after the restriction as records, it is possible to retrospectively confirm the state of the event occurrence part. In this embodiment, the evidence before the restriction and the evidence after the restriction are linked and recorded in the recording means (the storage 43).
[0081] Here, the case where the photograph (still image) taken by the photographing means 14 is used as evidence (hereinafter referred to as "photographing evidence") is taken as an example, but a moving image taken by the photographing means 14 can also be used as the photographing evidence. In other processes of this application, photographing by the photographing means 14 is performed, and in any case, it may be a still image or a moving image. The still image or moving image obtained by photographing can be used as photographing evidence.
[0082] The method of image processing when an event that inhibits determination may be a method other than partially hiding or removing, and for example, it can also be processed by methods such as image correction, image conversion, image processing, feature extraction, image recognition, three-dimensionalization, and quantification.
[0083] The image correction mentioned here includes correcting contrast, brightness, color, etc. Image conversion includes converting a color image into a monochrome image. Image processing includes noise removal, edge enhancement, enlargement, reduction, etc. Image feature extraction includes measuring area, circularity, etc. Image recognition includes identifying an object. Three-dimensional conversion includes three-dimensional conversion processing of a two-dimensional image. Numerical conversion includes converting an image into a numerical value. All of these processes are methods of processing on a digital image. For example, in the case of image recognition, the event occurrence part can be identified for each document, and the event occurrence part can be hidden or removed.
[0084] Whether or not a specimen of a specified volume has been ejected can also be determined using, as a criterion, the size, area, configuration, target area of the figure in the plane or on the curved surface of the remaining specimen portion S3 in the chip Z after ejection, or the digitized values thereof. Also in this case, when the size, area, configuration, target area of the figure in the plane or on the curved surface of the remaining specimen portion S3 in the photographed chip Z, or the digitized values thereof, satisfy the determination criterion (threshold value) set in advance based on the protocol (within the threshold value range), it can be determined as normal, and when the determination criterion (threshold value) is not satisfied (outside the threshold value range), it can be determined as an error.
[0085] Whether or not a specimen of a specified volume has been ejected can also be determined based on, in addition to the size, area, configuration, target area of the figure in the plane or on the curved surface of the air portion S1, or the digitized values thereof, and the size, area, configuration, target area of the figure in the plane or on the curved surface of the remaining specimen portion S3, or the digitized values thereof, the distance from the upper end to the lower end of the air portion, the distance from the upper end to the lower end of the remaining specimen portion, the area ratio of the air portion to the remaining specimen portion, the ratio of the distances from the upper end to the lower end of both, etc.
[0086] In the ejection amount confirmation step S011, as execution information, in addition to the post-ejection chip image obtained by photographing with the photographing means 14, the processed chip image, and the determination result as to whether or not a specimen of a specified volume has been ejected (hereinafter referred to as the "ejection amount determination result") are recorded in the PC40. The ejection amount determination result here may include, in addition to whether or not the ejection amount is within the range of the specified volume, numerical values of the specific ejection amount, etc.
[0087] Also, in this embodiment, when it is determined that the ejection amount does not satisfy the determination criteria (hereinafter referred to as the "ejection amount determination criteria") set in advance based on the protocol, the robot 30 is temporarily stopped. Similar to other steps, when the robot 30 is temporarily stopped in this step, it is configured to be notified by sound, light, etc.
[0088] [Chip removal step] The chip removal step S012 is a step of removing the chip Z attached to the tip of the pipette P. In this step, the second arm 32 hooks the connection portion C between the pipette P and the chip Z on the periphery of the locking recess 20d of the chip remover 20, and in this state, by raising the pipette P upward, the chip Z is removed from the pipette P.
[0089] [Lid closing step] The lid closing step S013 is a step of closing (sealing) the tube X clamped by the tube vice 16. In this step, a new lid Y housed in the lid rack 12 is taken out by the first hand 31a of the first arm 31, and the lid Y is attached (lid closed) to the tube X clamped by the tube vice 16. In this embodiment, the tube X is closed by rotating the first hand 31a holding the lid Y.
[0090] [Lid closing confirmation step] The lid closing confirmation step S014 is a step of confirming whether the tube X after the completion of the lid closing step S013 is lid-closed (whether the lid Y is attached to the tube X). In this step, it is determined whether the lid closing is successful based on a determination criterion (lid closing determination criterion) set in advance based on a protocol. The confirmation of whether the lid is closed can be performed, for example, by the following two methods.
[0091] The first method is a method of determining whether the load applied to the first hand 31a of the first arm 31 satisfies the lid closing determination criterion set in advance based on a protocol when the lid Y of the tube X is lifted by the first hand 31a of the first arm 31. When determining by this method, if the tube X is also lifted together with the lid Y (when the lid closing determination criterion is satisfied), it is determined that the lid closing is successful, and if the tube X is not lifted and only the lid Y is lifted (when the lid closing determination criterion is not satisfied), it is determined that the lid closing fails due to insufficient lid closing (insufficient sealing).
[0092] When the tube X after lid closing is returned to the tube rack 11, it is lifted by the first hand 31a of the first arm 31. Since the determination by this method can be performed during the operation of lifting the lid Y when returning the tube X after lid closing to the tube rack 11, the lid closing determination can be performed efficiently because there is no separate process.
[0093] The second method is a method of determining from the captured image by the imaging means 14 (hereinafter referred to as "tube image after lid closing"). When determining by this method, the lid Y of the tube X is picked up by the first hand 31a of the first arm 31 and moved to the imaging position by the imaging means 14. When the tube X is moved to the imaging position by the first arm 31, the tube X is imaged by the imaging means 14. If the tube X is included in the tube image after lid closing together with the lid Y, it is determined that the lid closing is successful, and if only the lid Y is included in the lid closing tube image and the tube X is not included, it is determined that the lid closing fails. Whether the lid closing is successful can also be determined by other methods.
[0094] Whether the lid Y is attached to the tube X, in other words, whether the tube X is sealed, is checked to prevent the disadvantages of contamination and sample degradation caused by the unsealed tube X. If the lid Y is not closed, the remaining sample may scatter due to the tube X falling or tilting, which may cause contamination. In addition, carbon dioxide in the air may dissolve and change the pH, causing the remaining sample to denature (the nucleic acid in the cell may denature).
[0095] To prevent these inconveniences, in this embodiment, it is checked whether the lid Y is attached to the tube X, and if the lid closing fails, the robot 30 is stopped. Thereby, the above-mentioned disadvantages caused by the lid Y not being closed can be avoided in advance.
[0096] In the lid closing confirmation step S014, as execution information, in addition to the tube image after lid closing obtained by photographing with the photographing means 14, the determination result (lid closing determination result) as to whether the lid closing was successful is recorded in the PC40.
[0097] Also, in this embodiment, the robot 30 is temporarily stopped when it is determined that the lid closing has failed. Similar to other steps, when the robot 30 is temporarily stopped in this step, it is notified by sound, light, etc.
[0098] [Containment step] The containment step S015 is a step of taking out the lid-closed tube X from the tube vise 16 and returning it to the containment recess 11a of the tube black 11. In this step, the lid-closed tube X is taken out from the tube vise 16 by the first hand 31a of the first arm 31, and the taken-out tube X is returned to the original containment recess 11a of the tube black 11.
[0099] [Other steps] Although omitted in the flowchart of FIG. 1, in this embodiment, after reading in the sample ID reading step S003, it is determined whether the read sample ID duplicates an already read sample ID. As a result of the determination, if it is determined that the sample ID duplicates, the tube X on which the sample ID is displayed is accommodated in a storage box (not shown) by the operation of the robot 30. In this case, the sample ID displayed on the tube X is recorded in the PC 40.
[0100] Also, in this embodiment, it is determined whether the sample ID is missing from a pre-registered sample ID list. As a result of the determination, if it is determined that the sample ID is missing from the sample ID list, the tube X on which the sample ID is displayed is accommodated in a storage box (not shown) by the operation of the robot 30. Also in this case, the sample ID displayed on the tube X is recorded in the PC 40.
[0101] All of the execution information obtained in each step of the preprocessing is recorded in the storage (recording means) 43 of the PC 40 linked to the sample ID (read sample ID). That is, each execution information is recorded for each sample ID. For example, for a sample to which the sample ID "xxxxx" is assigned, all the execution information related to this sample ID "xxxxx" is linked and recorded.
[0102] Thereby, for example, for the sample ID "xxxxx", it is confirmed whether the ejection amount satisfies the determination criterion from the ejection amount determination result, and by comparing the post-ejection chip image linked to the sample ID "xxxxx", it is possible to collate whether the ejection amount determination result of the sample ID "xxxxx" is appropriate. In this way, by recording two or more pieces of execution information for one process, it becomes possible to collate the protocol with the execution result (execution information) and to collate the execution results (execution information) with each other.
[0103] In each step of the above-described embodiment, whether or not the lid is removed successfully, whether or not the chip is mounted successfully, whether or not the suction amount is within the specified capacity range, whether or not the discharge amount is within the specified capacity range, whether or not the lid is closed successfully, etc. are determined by the processor 41 of the PC 40. Each determination criterion serving as the basis for success or failure is appropriately set according to the specifications of the inspection using the specimen and the instruments (pipette P, chip Z, tube X, lid Y, etc.) to be used. Each determination criterion is preset according to the specifications from the customer side. In addition, the positions and pressures of the first arm 31, the second arm 32, the first hand 31a, the second hand 32a, etc., and the image processing method may be created by the preprocessing execution system provider side.
[0104] In the above-described embodiment, the case where the steps from the taking-out step S002 to the reading step S015 are performed in a series of processes is taken as an example. However, each of the above steps can also be implemented in each individual step unit or a plurality of step units. In addition, not all of the above steps are essential steps, and unnecessary steps can be omitted as appropriate. The above-described embodiment is an example, and within the range of not changing the gist thereof, the steps can be appropriately interchanged, changed, added, etc.
[0105] [Outline of the System for Executing Pretreatment] Next, an example of the preprocessing execution system that performs each of the above steps will be described with reference to the drawings. This preprocessing execution system has a function of automatically recording execution information when each step is executed, and a part or all of it functions as the execution information recording device of the present invention. As an example, the systems shown in FIGS. 6 and 7 include an installation table 10, a tube rack 11, a lid rack 12, a reading means 13, a photographing means 14, a lighting fixture 15, a tube vise 16, a lid collection box 17, a plate 18, a chip rack 19, a chip remover 20, a monitor 21, an input / output port 23, a robot 30, a PC 40, etc.
[0106] The installation table 10 is a table for installing various devices such as a tube rack 11, a lid rack 12, a reading means 13, a photographing means 14, a lighting fixture 15, a tube vise 16, a plate 18, a chip rack 19, a chip remover 20, a monitor 21, a robot 30, a PC 40, etc. For the installation table 10, a stainless steel table or the like can be used.
[0107] In this embodiment, by installing various devices constituting the system on a single installation table 10, there is an advantage that it does not occupy installation space compared to a conventional system configured by combining devices modularized by function (process).
[0108] The tube rack 11 is a container for accommodating a tube X in which a specimen is accommodated. In this embodiment, a tube rack 11 having 96 (8 vertical × 12 horizontal) bottomed accommodation recesses 11a is used. The tube rack 11 is sized such that when the tube X is accommodated in the accommodation recess 11a, at least the lid Y of the tube X protrudes above the upper surface of the tube rack 11.
[0109] The lid rack 12 is a container for accommodating a new lid Y to be attached to the tube X after the specimen has been sucked up. In this embodiment, a lid rack 12 having 96 (8 vertical × 12 horizontal) bottomed lid accommodation portions 12a is used. The lid rack 12 is sized such that when the lid Y is accommodated in the lid accommodation portion 12a, at least the lid Y protrudes above the upper surface of the lid rack 12.
[0110] For the lid rack 12, for example, a detachable type that can be placed in an irradiation type sterilization device (an ultraviolet sterilization device equipped with an ultraviolet lamp) with all or some of the lids Y placed thereon can be used. When using a detachable type that can be placed in an irradiation type sterilization device, when a human (for example, an operator) gene accidentally adheres to the lid Y, this gene can be destroyed, and contamination can be prevented.
[0111] The reading means 13 is a device for reading the specimen ID displayed on the tube X. Various readers such as a barcode reader or a QR code reader can be used for the reading means 13. In this embodiment, as the reading means 13, a stationary barcode reader capable of reading one-dimensional codes and two-dimensional codes is used. Other devices can also be used for the reading means 13.
[0112] In this embodiment, when the specimen ID displayed on the tube X reaches within the reading range of the reading means 13, the specimen ID is read by the reading means 13. The read reading plate ID is transmitted to the PC 40 and recorded in the storage 43.
[0113] The photographing means 14 is a device for photographing the specimen ID or the chip Z displayed on the tube X. A camera equipped with a variable focal length lens or the like can be used for the photographing means 14. In this embodiment, the case of using one camera is taken as an example, but the photographing means 14 can also be composed of a plurality of cameras. In addition to photographing still images, the photographing means 14 can also use devices that photograph moving images or devices that photograph both still images and moving images.
[0114] The lighting fixture 15 is a device for illuminating the tube X (specimen ID) or the chip Z that is the object to be photographed by the photographing means 14. The first power supply 22a is connected to the lighting fixture 15, and it is operated by the power supply supplied from the first power supply 22a. In this embodiment, highly directional white lighting is used as the lighting fixture 15. This lighting fixture 15 is in a thin plate shape and is attached to the installation base 10 in a vertically standing state. Other devices can also be used for the lighting fixture 15.
[0115] In this embodiment, when the tube X is moved to the imaging position by the first arm 31 described later, or when the chip Z is moved to the imaging position by the second arm 32 described later, the tube X and the chip Z are illuminated by the lighting fixture 15 and imaged by the imaging means 14. The captured images (such as the specimen ID image, the mounted chip image, the chip image after suction, the chip image after ejection, the chip image after lid closing, etc.) are transmitted to the PC 40 and recorded in the storage 43.
[0116] The tube vise 16 is a device for clamping the tube X. As shown in FIGS. 8(a) and 8(b), the tube vise 16 of this embodiment includes a clamping portion 16a for clamping the tube X, a drive mechanism 16b for opening and closing the clamping portion 16a, and a drive source (motor) 16M for operating the drive mechanism 16b.
[0117] The clamping portion 16a of this embodiment includes two clamping pieces 16c and 16d arranged opposite to each other. One clamping piece (hereinafter referred to as the "fixed clamping piece") 16c is an L-shaped plate arranged on a clamping piece pedestal 16f provided on the base plate 16e, and the other clamping piece (hereinafter referred to as the "movable clamping piece") 16d is a part (rising portion) of a movable T-shaped plate 16n that moves by the drive mechanism 16b. Cushion materials 16g and 16h are provided on the opposing surfaces of both clamping pieces 16c and 16d.
[0118] The drive mechanism 16b includes a coupling 16i, a ball screw 16j, and a ball nut (not shown). The motor 16M is connected to the ball screw 16j via the coupling 16i, and a ball nut (not shown) is provided on the ball screw 16j. On both outer sides of the ball screw 16j, one linear guide 16k is arranged in parallel with the ball screw 16j. Both longitudinal ends of each linear guide 16k are supported by guide supports 16m.
[0119] The T-shaped plate 16n is fixed to the ball nut, and is configured such that the movable clamping piece 16d moves in a direction approaching or separating from the fixed clamping piece 16c in conjunction with the movement of the ball nut. Guide blocks 16p each having a through hole are provided at both longitudinal ends on the back surface of the T-shaped plate 16n, and a linear guide 16k is inserted through the through hole. Thereby, lateral movement of the T-shaped plate 16n is prevented during the movement operation.
[0120] The lid recovery box 17 is a container for recovering the lid Y removed from the tube X. An existing resin container or the like can be used for the lid recovery box 17. The lid recovery box 17 can be installed at any position reachable by the first arm 31 (in this embodiment, on the side of the installation base 10).
[0121] The plate 18 is a container for transferring the aspirated specimen. Although not shown, each plate 18 is provided with a plate ID such as a barcode or a QR code. The display here includes not only the display by attaching a sticker printed with the plate ID, but also the display by directly printing the plate ID on the plate 18.
[0122] As shown in FIG. 9, in this embodiment, 96 (8 vertical × 12 horizontal) square wells (plate holes 18a) are used as the plates 18. The plates 18 are configured such that symbols A to H are assigned to the vertical columns (X-axis) and numbers 1 to 12 are assigned to the horizontal rows (Y-axis), and the plate holes 18a can be specified by the combination of the symbols and numbers.
[0123] An engaging portion 18b that engages with a fitting groove 24c of a plate seat 24 described later protrudes outward on the outer periphery of the plate 18. The plate 18 shown here is an example, and other plates can also be used for the plate 18. A plurality of plates 18 can also be added.
[0124] The plate 18 is installed on a plate seat 24 fixed to the installation base 10. The plate seat 24 in this embodiment has a mounting surface 24a that is rectangular in plan view. A flange 24b protrudes from the plate seat 24 so that the flange 24b can be fixed to the installation base 10 with a fastener such as a screw.
[0125] Fitting grooves 24c are provided on three sides of the mounting surface 24a of the plate seat 24, and the plate 18 is fixed to the plate seat 24 simply by fitting the fitting portion 18b of the plate 18 into the fitting grooves 24c. The remaining one side of the mounting surface 24a is open, and the fitting portion 18b of the plate 18 can be inserted into the fitting groove 24c from here. The plate seat 24 can be added according to the number of plates 18.
[0126] The chip rack 19 is a container for accommodating a new chip Z to be mounted on the pipette P. In this embodiment, a chip rack 19 having 100 (10 vertical × 10 horizontal) chip accommodating portions is used. Other types can also be used for the chip rack 19.
[0127] In this embodiment, the chip rack 19 is accommodated in a chip rack case 25 so that the positioning and position adjustment of the chip rack 19 can be performed. As an example, the chip rack case 25 shown in FIGS. 10(a) and 10(b) includes a base portion 25a fixed to the installation base 10 and a standing portion 25b erected on the base portion 25a. The standing portion 25b is composed of three fixed walls 25c surrounding four sides and one movable wall 25d, and the width inside the standing portion 25b can be adjusted by appropriately moving the movable wall 25d.
[0128] Although the sizes and shapes of the chip racks 19 vary depending on the manufacturer, by providing a movable wall 25d that can move as in this embodiment so that the width inside the standing portion 25b can be adjusted, it is possible to flexibly accommodate chip racks 19 with different sizes and shapes. Note that the movable wall 25d after movement is fixed to the base portion 25a with screws or the like (not shown) so that it does not move accidentally.
[0129] By mounting the chip rack 19 on the chip rack case 25 having such a structure, the chip rack 19 is positioned at a portion where its four corners coincide with the four corners of the chip rack case 25, and the position of the origin is less likely to shift. Therefore, the chip Z can be reliably mounted on the tip of the pipette P.
[0130] The chip remover 20 is a jig for removing the used chip Z mounted on the tip of the pipette P. The chip remover 20 of this embodiment includes a fixing portion 20a fixed to the installation base 10, a rising portion 20b rising upward from the fixing portion 20a, and a protruding portion 20c protruding outward in the middle of the rising portion 20b.
[0131] A locking recess 20d for accommodating the coupling portion C between the pipette P and the chip Z is provided at the tip of the protruding portion 20c. By moving the pipette P upward with the coupling portion C between the pipette P and the chip Z hooked on the peripheral edge of the locking recess 20d, the chip Z can be removed from the pipette P.
[0132] The monitor 21 displays the operating status of the system, the captured image by the imaging means 14, the read signal by the reading means 13, etc. In this embodiment, buttons for operating the application, such as start, restart, stop, load, resampling, etc., are also displayed on the monitor 21.
[0133] The input / output port 23 is a means for inputting or outputting signals. In this embodiment, a general-purpose input / output (GPIO) that can be used for both input and output is used as the input / output port 23. With GPIO, the signal transmitted from the PC 40 can be received to control the tube vice 16. The input / output port 23 is connected to a second power supply 22b common to the tube vice 16 and is operated by the power supply supplied from the second power supply 22b.
[0134] By using the GPIO as the input / output port 23, there is an advantage that all of the various devices constituting the system can be controlled on the PC40 side. As a result, the control on the robot 30 side is reduced, and an improvement in the processing speed of the robot 30 can be expected. In addition, since the control of the various devices constituting the system has become possible from the PC40 side, various robots 30 other than the robot 30 used in this embodiment can also use the various devices constituting the system, which has the advantage of making it easier to meet customer requirements.
[0135] The robot 30 is a robot that handles the tube X and the pipette P. In this embodiment, as the robot 30, a dual-arm type articulated robot including a first arm 31 and a second arm 32 is used. A first hand 31a is provided on the first arm 31, and a second hand 32a is provided on the second arm 32. The tube X and the pipette P are held by the first hand 31a and the second hand 32a.
[0136] As shown in FIG. 7, the robot 30 is equipped (built-in) with a control means 33, and the first arm 31 and the second arm 32 are controlled by the control means 33. The robot arm returns to the origin in a timely manner and starts a new operation from there.
[0137] In this embodiment, the first arm 31 is configured to perform at least the gripping of the tube X housed in the tube black 11, the movement of the tube X to the reading position, the movement of the tube X to the imaging position, the movement of the tube X to the tube vice 16, the removal of the lid of the tube X clamped by the tube vice 16, the disposal of the removed lid Y to the lid collection box 17, the closing of the lid of the tube X, the accommodation of the tube X after lid closing to the tube black 11, and the operation of the push button PB of the pipette P.
[0138] In addition, in this embodiment, the second arm 32 is configured to perform at least various operations of the pipette P, the movement of the pipette P to the chip mounting position, the movement of the chip Z to the imaging position, and the movement of the chip Z to the chip remover 20.
[0139] Note that operation information such as the starting position, ending position, operation path, temporary stop position, operation speed, and operation angle, as well as the branching method, etc. are registered in the robot 30, and according to these operation information and branching methods, etc., the first arm 31, second arm 32, first hand 31a, second hand 32a, etc. of the robot 30 operate. These numerical values, etc. can be arbitrarily set and changed according to the characteristics of the specimen to be processed.
[0140] For the monitor 21, various existing liquid crystal displays such as those corresponding to touch panels can be used. Note that the information displayed on the monitor 21 can be appropriately selected and displayed according to the customer's requests and the information required by the customer.
[0141] In addition to sending commands to the control means 33 of the robot 30, the PC 40 performs various processes such as receiving, recording, and determining data (execution information) transmitted from the reading means 13, photographing means 14, etc., and controls various means such as the reading means 13, photographing means 14, lighting fixture 15, monitor 21, power supply 22, etc., and answers the determination results to questions from the robot 30.
[0142] As shown in FIG. 11, the PC 40 of this embodiment includes a processor 41, a memory (main storage device) 42, a storage (auxiliary storage device) 43, a communication unit 44, an input unit 45, and an output unit 46. The communication unit 44 includes a transmission unit 44a and a reception unit 44b. These elements are electrically connected by a bus 47.
[0143] The processor 41 functions as a determination means for determining the success or failure of lid removal, the success or failure of chip mounting, the suction amount, the discharge amount, and the success or failure of lid closing. The storage 43 functions as a recording means for recording various execution information. The communication unit 44 functions as a communication means for transmitting and receiving information to and from a customer-side system (external device) 50 described later.
[0144] Further, when an event that inhibits the determination of the discharge amount such as the film F occurs, the processor 41 of this embodiment also functions as processing means for performing processing so that the determination is not inhibited by this event. The processing executed by the processing means is as described above.
[0145] As shown in FIG. 7, the system of this embodiment is communicably connected to the customer-side system 50 via the communication line L, and is configured to be able to exchange information used in the system and information obtained in the dispensing operation in the system with the customer-side system 50. The communication line L may be wireless or wired. The communication between the system of this embodiment and the customer-side system 50 can also be performed via a recording forgery prevention device (not shown).
[0146] From the customer-side DB 51 of the customer-side system 50, for example, the registered specimen ID registered on the customer DB side is acquired. Also, when a plurality of plates 18 are used, the designated plate ID and the designated plate hole information are also acquired from the customer-side DB 51.
[0147] The exchange of data with the customer-side system 50 can be performed according to the specifications designated by the customer, such as CSV cooperation or API cooperation. Also, since the necessary information varies for each customer, any execution information selected and set from the execution information recorded on the system side can be passed to the customer-side system 50.
[0148] This preprocessing execution system operates by software (program) for executing each of the above processes. This software can also be provided as a program separated from the preprocessing execution system, specifically, a program that operates a computer as the preprocessing execution system or the execution information recording device of the present invention. The computer referred to here may be any device equipped with functional parts corresponding to a processor and a memory. In addition to the PC 40 constituting this system, it is a concept including the robot 30, the entire system, and each device constituting this system.
[0149] The program does not necessarily have to be stored in one computer (for example, PC40), and may be stored in both the PC40 and the robot 30, or in one or more of each device constituting the present system. In short, the program referred to here means a program that enables execution of each of the above processes.
[0150] In addition to providing the software in a downloadable manner, it can also be provided as a recording medium recorded in a computer-readable form. Examples of the recording medium here include optical disks, magneto-optical disks, semiconductor memories, etc. Specifically, they include HD (hard disk), CD-ROM, CD-R, CD-RW, DVD-ROM, DVD-R, DVD-RW, DVD-RAM, MO, DVD, flash memory, memory card, etc.
[0151] In the preprocessing flow and the system for executing the preprocessing of the above embodiment, since the execution information is automatically recorded in association with the specimen ID (read specimen ID) and the plate ID (read plate ID), it is possible to surely perform double-checking of specimens.
[0152] In the preprocessing flow and the system for executing the preprocessing of the above embodiment, not only the execution information when the system operates normally, but also the execution information when executed under procedures and conditions other than the processing procedures and processing conditions defined as normal operations in the protocol, such as when the robot 30 stops, is recorded. Therefore, it is possible to verify whether the preprocessing by the robot 30 has been performed according to the protocol during or after the execution of the preprocessing.
[0153] In the preprocessing flow and the system for executing the preprocessing of the above embodiment, there is an advantage that human errors such as forgetting to record, recording mistakes, and recording omissions do not occur. Since the specimen accommodated in the tube X cannot be identified by the specimen ID once it is sucked up from the tube X, it is necessary to record information on which specimen has been dispensed into which hole of which plate.
[0154] Conventionally, this record was often made manually by the operator. However, during the operation, both hands might be occupied, making it difficult to perform the operation and record simultaneously. In this case, the record was made after the operation was completed, but human errors such as forgetting to record, recording mistakes, and omitting to record might occur.
[0155] On the other hand, in the preprocessing flow and the system for executing the preprocessing of the above embodiment, since the execution information obtained in the process of preprocessing is automatically recorded, there is almost no need for the operator to perform the recording work manually, and human errors that occur when the operator performs the recording work manually do not occur, which also contributes to reducing the burden on the operator.
[0156] Note that the preprocessing flow and the system for executing the preprocessing of the above embodiment are merely examples and are not limited to the configuration of the above embodiment. The preprocessing flow and the system for executing the preprocessing can be appropriately changed, such as being replaced or omitted, without changing the gist thereof.
Industrial Applicability
[0157] The present invention can be particularly preferably used in preprocessing performed prior to inspection using a specimen, for example, preprocessing performed prior to inspection using various specimens collected from humans, various animals (such as mammals, fish, birds, amphibians, reptiles, etc.), insects, shellfish, agricultural crops, plants, their seeds and seedlings, microorganisms, etc.
Explanation of Reference Numerals
[0158] 10 Installation table 11 Tube black 11a Receiving recess 12 Lid rack 12a Lid receiving portion 13 Reading means 14 Photographing means 15 Lighting fixture 16 Tube vice 16a Clamping portion 16b Driving mechanism 16c Clamping piece (fixed clamping piece) 16d Holding piece (movable holding piece) 16e Base plate 16f Holding piece pedestal 16g Cushion material (on the fixed holding piece side) 16h Cushion material (on the movable holding piece side) 16i Coupling 16j Ball screw 16k Linear guide 16m Guide support 16n T-shaped plate 16p Guide block 16M Drive source (motor) 17 Lid recovery box 18 Discharge destination container (deep well plate (plate)) 18a Plate hole 18b Fitting part 19 Chip rack 20 Chip remover 20a Fixed part 20b Upright part 20c Protruding part 20d Locking recess 21 Monitor 22 Power supply 22a First power supply 22b Second power supply 23 Input / output port 24 Plate seat 24a Mounting surface 24b Flange 24c Fitting groove 25 Chip rack case 25a Base part 25b Upright part 25c Fixed wall 25d Movable wall 30 Robot 31 First robot arm (first arm) 31a Hand of the first arm (first hand) 32 Second robot arm (second arm) 32a Hand of the second arm (second hand) 33 Control means 40 Electronic computer (PC) 41 Processor 42 Memory (main storage device) 43 Storage (auxiliary storage device) 44 Communication unit 44a Transmission unit 44b Reception unit 45 Input unit 46 Output unit 47 Bus 50 Customer-side system (external device) 51 Customer-side database (customer-side DB) C Coupling part F Film, etc. L Communication line P Pipette PB Push button S1 Air part S2 Specimen part S3 Residual specimen part X Specimen container (tube) Y Lid Z Chip
Claims
1. A method for recording execution information when a pretreatment performed before a test using a sample is performed according to a preset protocol, comprising: a step of photographing the specimen aspirating and discharging tool after the specimen has been aspirated and recording an image of the specimen aspirating and discharging tool; and a step of performing image processing on a duplicate image of the image obtained by the photographing when a film or air bubbles are present in the sample aspirating and discharging tool.
23. An execution information recording method comprising:
2. 2. The execution information recording method according to claim 1, The image processing procedure and / or image processing conditions are set as a protocol; 23. An execution information recording method comprising:
3. 3. The execution information recording method according to claim 1, further comprising: The images obtained by shooting The time of taking the image; and an image obtained by subjecting a duplicate image of the image to image processing; A result of absorbing and / or expelling the sample determined based on an image obtained by performing image processing on a duplicate image of the image; and The working environment at the time the image was taken; Record the information in relation to one or more of the following:
23. An execution information recording method comprising:
4. 4. The execution information recording method according to claim 1, further comprising: The specimen identification information registered in advance and / or read in the step of reading the specimen identification information, The time the image was taken, an image obtained by subjecting a duplicate image of the image to image processing; A result of absorbing and / or expelling the sample determined based on an image obtained by performing image processing on a duplicate image of the image; and The working environment at the time the image was taken; Record the information in relation to one or more of the following:
23. An execution information recording method comprising:
5. 5. The execution information recording method according to claim 1, Either or both of the following (1) and (2): (1) A plate ID that has been registered in advance and / or that has been read in the step of reading the plate ID (2) Discharge destination specific information specified by workspace coordinates set based on the robot or / and discharge destination specific information specified by a combination of codes assigned to the vertical columns and numbers assigned to the horizontal columns of the plate The time the image was taken, an image obtained by subjecting a duplicate image of the image to image processing; A result of absorbing and / or expelling the sample determined based on an image obtained by performing image processing on a duplicate image of the image; and The working environment at the time the image was taken; and Specimen identification information that has been registered in advance and / or that has been read in the step of reading the specimen identification information; Record the information in relation to one or more of the following:
23. An execution information recording method comprising:
6. 6. The execution information recording method according to claim 1, Set and / or register one or more of the robot's motion start point, motion path, motion posture, motion end point, stop posture, movement speed, waypoint, motion time, rotation speed, and pressure from the tip mounting operation to the tip removal operation; 23. An execution information recording method comprising:
7. 7. The execution information recording method according to claim 1, The test using the specimen is a test using a specimen liquid in which a buffer solution is added to the specimen, 23. An execution information recording method comprising:
8. 8. The execution information recording method according to claim 1, Displaying on a display device one or more of the image obtained by shooting, a duplicate image of the image, and an image obtained by subjecting the duplicate image to image processing; 23. An execution information recording method comprising:
9. A recording device for recording execution information when a pretreatment performed before a test using a sample is performed according to a preset protocol, an imaging means for imaging the sample aspirating and discharging tool after the sample has been aspirated; a recording means for recording an image of the sample aspirating and discharging tool obtained by the photographing; A processing means is provided for performing image processing on a duplicate image of an image obtained by photographing with the photographing means when a film or air bubbles are present in the sample aspirating and discharging tool.
23. An execution information recording device comprising:
10. 10. The execution information recording device according to claim 9, The image processing procedure and / or image processing conditions are set as a protocol; 23. An execution information recording device comprising:
11. 11. The execution information recording device according to claim 9, The images obtained by shooting The time of taking the image; and an image obtained by subjecting a duplicate image of the image to image processing; A result of absorbing and / or expelling the sample determined based on an image obtained by performing image processing on a duplicate image of the image; and The working environment at the time the image was taken; The above is recorded in the recording means in association with one or more of the above.
23. An execution information recording device comprising:
12. 12. The execution information recording device according to claim 9, The specimen identification information registered in advance and / or read in the step of reading the specimen identification information, The time the image was taken, an image obtained by subjecting a duplicate image of the image to image processing; A result of absorbing and / or expelling the sample determined based on an image obtained by performing image processing on a duplicate image of the image; and The working environment at the time the image was taken; The above is recorded in the recording means in association with one or more of the above.
23. An execution information recording device comprising:
13. 13. The execution information recording device according to claim 9, Either or both of the following (1) and (2): (1) A plate ID that has been registered in advance and / or that has been read in the step of reading the plate ID (2) Discharge destination specific information specified by workspace coordinates set based on the robot or / and discharge destination specific information specified by a combination of codes assigned to the vertical columns and numbers assigned to the horizontal columns of the plate The time the image was taken, an image obtained by subjecting a duplicate image of the image to image processing; A result of absorbing and / or expelling the sample determined based on an image obtained by performing image processing on a duplicate image of the image; and The working environment at the time the image was taken; and Specimen identification information that has been registered in advance and / or that has been read in the step of reading the specimen identification information; The above is recorded in the recording means in association with one or more of the above.
23. An execution information recording device comprising:
14. 14. The execution information recording device according to claim 9, Set and / or register one or more of the robot's motion start point, motion path, motion posture, motion end point, stop posture, movement speed, waypoint, motion time, rotation speed, and pressure from the tip mounting operation to the tip removal operation; 23. An execution information recording device comprising:
15. 15. The execution information recording device according to claim 9, The test using the specimen is a test using a specimen liquid in which a buffer solution is added to the specimen, 23. An execution information recording device comprising:
16. 16. The execution information recording device according to claim 9, A display device is provided for displaying one or more of an image obtained by photographing, a duplicate image of the image, and an image obtained by subjecting the duplicate image to image processing.
23. An execution information recording device comprising:
17. A program for causing a computer to execute the execution information recording method according to any one of claims 1 to 8.
18. A program for causing a computer to operate as the execution information recording device according to any one of claims 9 to 16.
19. A computer-readable recording medium on which the program according to claim 17 or 18 is recorded.
20. 1. An execution information transmission method for transmitting execution information when a pretreatment performed before a test using a sample is performed according to a preset protocol to an external device, comprising: transmitting one or more pieces of execution information selected from the execution information recorded by the execution information recording method according to any one of claims 1 to 8 to an external device via a communication line; 23. An execution information transmission method comprising:
21. An execution information transmitting device that transmits execution information, which is a record of a pretreatment performed before a test using a sample, performed according to a preset protocol, to an external device, a communication unit configured to transmit one or more pieces of execution information selected from the execution information recorded in the recording means by the execution information recording device according to any one of claims 9 to 16 to an external device via a communication line; 23. An execution information transmitting device comprising:
Citation Information
Patent Citations
Method and apparatus for detecting foreign matter in liquid within container
JP2004354100A
Automatic system, automatic processing method, and automatic nucleic acid extraction method
JP2005525816A
Dispensing device
JP2008209271A
Apparatus and method for programmable operation of pipettes
JP2013543984A
Experiment data recording device, computer program, experiment data, experiment data recording method, data display device, and experiment data display method
JP2019194619A