Execution information recording method, execution information recording device, program, recording medium, execution information transmission method, and execution information transmission device
The method addresses the challenge of inaccurate specimen discharge determination by photographing and treating the specimen suction and discharge tool, ensuring accurate recording of discharge amounts and preventing errors in pre-processing.
Patent Information
- Application Number
- JP2024000473
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2024-01-05
- Publication Date
- 2025-04-21
- Estimated Expiration
- 2041-04-13
AI Technical Summary
Existing methods for determining the amount of specimen discharge during pre-processing in life sciences tests are hindered by events such as membranes and air bubbles, leading to inaccurate judgments and potential delays or errors.
A method and device for recording execution information that includes photographing the specimen suction and discharge tool, treating the tool to mitigate interfering events, and recording evidence before and after treatment to ensure accurate determination of discharge amounts.
This approach allows for accurate determination of specimen discharge amounts even when events like membranes or air bubbles occur, thereby preventing errors and ensuring smooth pre-processing operations.
Smart Images

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Abstract
Description
[Technical field]
[0001] The present invention relates to a method, a recording device, a program, a recording medium, an execution information transmission method, and an execution information transmission device for recording execution information when pre-processing performed before a test using a sample is performed according to a preset protocol. [Background technology]
[0002] In the fields of life sciences, such as biology, biochemistry, bioengineering, and food science, various tests using specimens are performed. Before a test using a specimen, a pretreatment such as dispensing is performed, in which the specimen in a specimen container (e.g., a tube) is dispensed into a destination container (e.g., a plate) using a specimen suction / discharge tool (e.g., a pipette or dropper with a tip attached to the end).
[0003] The pretreatment is performed manually, but in recent years, it may also be performed using a dispensing device (Patent Document 1). The dispensing device of Patent Document 1 is configured to photograph the tip before and after dispensing with an imaging means, and to judge whether dispensing has been performed accurately based on the edges of the photographed image of the tip. [Prior art documents] [Patent documents]
[0004] [Patent Document 1] JP 2006-125855 A Summary of the Invention [Problem to be solved by the invention]
[0005] However, after dispensing, a film, air bubbles, or other phenomena that hinder the determination of the amount of dispensed liquid may occur in the tip, which may cause delays or errors in the execution of pre-processing. However, in the above-mentioned Patent Document 1, such phenomena are not taken into consideration when making a determination using an image, so there is a risk that an accurate determination of whether or not dispensing is appropriate may not be made.
[0006] The present invention has been made in view of the above circumstances, and an object of the present invention is to make it possible to accurately determine the discharge amount even when an event occurs that hinders the determination of the discharge amount. [Means for solving the problem]
[0007] [How to record execution information] The execution information recording method of the present invention is a method for recording execution information when pre-processing performed before a test using a sample is performed in accordance with a preset protocol, the pre-processing including a step of discharging the sample in the sample aspirating and discharging tool into a destination container, and the method includes a step of photographing the sample aspirating and discharging tool after the sample has been discharged, a step of processing the occurrence of an event in the sample aspirating and discharging tool that hinders the determination of the amount of sample discharged so that the event does not hinder the determination, and a step of linking 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 device for recording execution information when pre-processing performed before a test using a sample is performed in accordance with a preset protocol, the pre-processing including a step of discharging the sample in the sample aspirating and discharging tool into a destination container, and the device is equipped with an imaging means for photographing the sample aspirating and discharging tool after the sample has been discharged, a processing means for processing an event that hinders the determination of the amount of sample discharged in the sample aspirating and discharging tool so that the event does not hinder the determination, and a recording means for linking and recording the evidence obtained by imaging and the evidence after 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 in which the program is recorded. Note that the computer referred to here is not limited to a personal computer (PC) described later, but is a concept including various devices constituting the execution information recording device, such as a robot, a reading means, a photographing means, and a lighting device.
[0010] [How to send execution information] The execution information transmission method of the present invention is an execution information transmission method for transmitting execution information to an external device when pre-processing performed before a test using a sample is performed in accordance with a preset protocol, 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 the external device via a communication line.
[0011] [Execution information transmission device] The execution information transmitting device of the present invention is an execution information transmitting device that transmits execution information to an external device, which is a record of when pre-processing performed before testing using a sample is performed in accordance with a predetermined protocol, and is a device equipped with a communication unit that transmits one or more pieces of execution information selected from the execution information recorded in the recording means by the execution information recording device of the present invention to the external device via a communication line. Effect of the Invention
[0012] In the present invention, when an event occurs in the sample aspirating and discharging device that hinders the determination of the amount of sample discharged, the event is processed so as not to hinder the determination of the amount of sample discharged, making it possible to accurately determine the amount of sample discharged. [Brief description of the drawings]
[0013] [Figure 1] 11 is a flowchart showing an example of pre-processing for a test using a sample. [Diagram 2] (a) to (d) are diagrams explaining the operation when sucking up a sample. [Diagram 3] FIG. 1A shows an example of a tip image after suction, and FIG. 1B is an explanatory diagram of the air portion and the sample portion in the tip image after suction of FIG. [Figure 4] (a) to (c) are diagrams explaining the action when discharging a sample. [Diagram 5](a) shows an example of a tip image after discharging, (b) is an explanatory diagram of the air and remaining sample parts in the tip image after discharging of (a), and (c) is an explanatory diagram of the air and remaining sample parts when part of the tip image after discharging of (a) is shaded black. [Figure 6] FIG. 1 is a configuration explanatory diagram showing an example of a system for performing pretreatment for a test using a sample. [Figure 7] FIG. 1 is a functional block diagram showing an example of a system for performing pretreatment for a test using a sample. [Figure 8] FIG. 4A is a perspective view showing an example of a tube vise before clamping a tube, and FIG. 4B is a perspective view showing the example of the tube vise in a state in which the tube is clamped. [Figure 9] FIG. 2 is a perspective view showing an example of a deep well plate and a plate seat. [Figure 10] FIG. 2 is a perspective view showing an example of a tip rack and a tip rack case. [Figure 11] FIG. 2 is a functional block diagram showing an example of the configuration of a PC. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[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 device for recording execution information obtained in the process of pre-processing of a test using a sample performed by a robot 30. Before describing the execution information recording method and the execution information recording device in detail, the meanings of terms used in this application will be explained.
[0015] The "test using a sample" in this application includes a test for analyzing the base sequence of a nucleic acid and a test for analyzing an amino acid sequence. Specifically, it includes a test for analyzing the base sequence of a nucleic acid (for example, the base sequence of a gene) using a sequencer (for example, a next-generation sequencer), and a test for analyzing an amino acid sequence using a peptide sequencer (protein sequencer) that automates the Edman method, which is a type of amino acid sequence analysis method. Although the terms "analysis" and "measurement" are sometimes used instead of "analysis," the analysis in this application is a concept that includes analysis, measurement, etc.
[0016] Samples that are the subject of pretreatment in the present application include feces, urine, saliva, skin, body hair, intestinal bacterial flora (intestinal flora), etc. These samples are not limited to those collected from humans, but also include those collected from various animals (mammals, fish, birds, amphibians, reptiles, etc.), insects, shellfish, agricultural crops, plants, their seeds and seedlings, microorganisms, etc.
[0017] The specimen in this application includes not only the specimen itself, but also a specimen to which a buffer solution (buffer component) having a buffering effect has been added (hereinafter referred to as "specimen solution"). For ease of explanation, in this application, the specimen itself or the specimen solution will be referred to as "specimen" unless a special distinction is required. The buffering effect here refers to the effect of mitigating the effects of the addition of a small amount of acid or base and maintaining a nearly constant pH.
[0018] Examples of the buffer solution include phosphate buffer, acetate buffer, citrate buffer, citrate phosphate buffer, borate buffer, tartrate buffer, Tris buffer, McIlvaine buffer, etc. One or more types of buffer solution may be added depending on the specimen.
[0019] The specimen liquid of the present application includes a suspension in which solid particles of the specimen such as feces are dispersed. A specimen liquid in which a buffer solution is added to the specimen has a characteristic that phenomena such as membranes and bubbles are likely to occur in the chip Z or tube X described later.
[0020] In addition, it is common to store the sample remaining in tube X after discharging the sample sucked up from tube X into a destination container (e.g., a plate such as a deep well plate) 18 described below. In this case, it is important to close the lid of tube X and ensure that it is airtight so that the nucleic acid in the cells of the sample remaining in tube X is not denatured.
[0021] The preprocessing in this application is carried out at a stage prior to a test using a sample (for example, a test that analyzes the base sequence of a gene or the amino acid sequence contained in a protein), and refers to processing executed by a preprocessing execution system including the robot 30 described below.
[0022] 1, an example includes a plate ID reading step S001-removal step S002-sample ID reading step S003-sample ID photographing step S004-lid removal step S005-tip mounting step S006-mounted tip confirmation step S007-suction step S008-suction amount confirmation step S009-discharge step S010-discharge amount confirmation step S011-tip removal step S012-lid closing step S013-lid closure confirmation step S014-storage step S015, etc. Note that the pretreatment of the present application is not limited to cases in which all of these steps are included, and may refer to only some of them.
[0023] In this embodiment, the preprocessing is performed by a preprocessing execution system including a robot 30, which will be described later, and various execution information obtained during the execution of the preprocessing is recorded. This preprocessing execution system includes the robot 30 and a computer (hereinafter referred to as a "PC") 40, and the preprocessing (all steps described above) is performed according to a protocol registered in either or both of them.
[0024] The protocol is an execution procedure manual that defines the processing procedure and processing conditions of the pre-processing, and is registered in both or either of the robot 30 and the PC 40 prior to the start of the process of the embodiment. The content of the protocol varies depending on the characteristics of the sample, the specifications of the test after the pre-processing, etc. The protocol may also include items that are set on the side performing the pre-processing. The protocol may be registered in a device other than the robot 30 or the PC 40 (for example, a device having functions equivalent to the processor, memory, etc. of the robot 30 or the PC 40). Furthermore, when a single robot 30 (pre-processing execution system) is responsible for pre-processing corresponding to multiple protocols, each of the multiple protocols may be assigned a unique protocol ID.
[0025] The protocol defines the starting point, movement path, movement posture, movement end point, stopping posture, movement speed, intermediate points, movement time, etc. of the robot 30 based on the three-dimensional (XYZ) workspace coordinates set based on the robot 30, and may also define some or all of the rotation speed and pressure of the first hand 31a and the second hand 32a.
[0026] In addition, the protocol specifies 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 standard amount of sample to be sucked up, the standard amount of sample to be discharged, the method of judging the amount to be sucked up, the method of judging the amount to be discharged, the method of removing the lid, the method of judging whether the lid has been removed, the method of closing the lid, the method of judging whether the lid has been closed, the method of processing evidence, the method of recording the execution information obtained at each step, etc. The "time" of processing and judgment of each step is also recorded as execution information.
[0027] In this embodiment, the actions of the robot 30 are registered in the robot 30, and the decisions and associated branching instructions for the robot 30 are registered in the PC 40, but the protocol can be registered in whole or in part in both or either one of the robot 30 and the PC 40. In executing a registered protocol, individual decisions and instructions can also be made on the PC 40 side.
[0028] In this embodiment, the operation record (execution information) executed based on the registered protocol is recorded in the robot 30 after the execution, and the judgment (including the evidence) and the processing condition branch are recorded on the PC 40 side. The operation record (execution information) executed based on the registered protocol, including the operation of the reading means 13, the photographing means 14, the tube vice 16, etc., can be recorded in whole or in any part in both or either of the robot 30 and the PC 40 after the execution. Also, the execution record (execution result, evidence, etc.) of the reading, judgment, and instruction based on the registered protocol can be recorded in whole or in part in both or either of the robot 30 and the PC 40. The execution information may be recorded in a device other than the robot 30 or the PC 40 (for example, a device having a function equivalent to the processor, memory, etc. of the robot 30 or the PC 40). The contents of the registration are omitted in this specification.
[0029] In light of the above, an example of the execution information recording method, execution information recording device, program, recording medium, execution information transmission method, and execution information transmission device of the present invention will be described. The execution information recording method and execution information recording device of the present invention are a method and device for recording execution information acquired in each step of pre-processing. The execution information acquired in each step of pre-processing is automatically recorded in storage 43 in association with specimen specific information and / or protocol specific information, etc., which will be described later, for each specimen. This recording is automatically performed simultaneously with (immediately after) the execution of each process.
[0030] [Outline of pre-processing flow] Fig. 1 shows an example of a flow chart of pre-processing performed before a test using a specimen. The pre-processing in Fig. 1 includes a plate ID reading step S001-removal step S002-specimen ID reading step S003-specimen ID photographing step S004-lid removal step (opening step) S005-tip mounting step S006-mounted tip confirmation step S007-suction step S008-suction amount confirmation step S009-discharge step S010-discharge amount confirmation step S011-tip removal step S012-lid closing step (capping step) S013-lid closing confirmation step S014-storage step S015. As described above, each of the steps is performed according to the protocol provided by a customer (for example, a business that performs a test after pre-processing). The protocol includes processing procedures as well as processing conditions, etc.
[0031] [Plate ID reading process] The plate ID reading step S001 is a step of reading, by the reading means 13, an identification code (hereinafter referred to as "plate ID") displayed on the plate 18 to which the sample is to be discharged. The plate ID is a unique identification code given to each plate, and is composed of a barcode, a QR code (registered trademark; the same applies below), or the like. The display referred to here includes a display in which a sticker with the plate ID printed thereon is affixed, as well as a display in which the plate ID is printed directly on the tube X.
[0032] In the plate ID reading step S001, the read plate ID (read plate ID) is recorded as execution information in the PC 40. The read plate ID is the plate ID displayed on the plate 18 that has been read, and matches the plate ID.
[0033] The plate ID reading step S001 is a step that is performed manually before the operation of the robot 30 is started. In this embodiment, after the plate ID reading step S001, the steps following the take-out step S002 in Fig. 1 are started.
[0034] [Removal process] The removal step S002 is a step of removing a tube X containing a sample by a hand (hereinafter referred to as the "first hand") 31a of a first robot arm (hereinafter referred to as the "first arm") 31. In this step, one of the tubes X contained in the tube rack 11 is gripped by the first hand 31a of the first arm 31.
[0035] [Sample ID reading process] The sample ID reading step S003 is a step of reading sample identification information (hereinafter referred to as "sample ID") that identifies the sample displayed on the tube X by the reading means 13. The sample ID is a unique ID given to each sample, and is composed of a barcode, a QR code, a code consisting of a combination of letters and numbers that represent the sample ID (hereinafter referred to as "identification code"). Specifically, there is 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. Note that the display referred to here includes a display in which a sticker with the sample ID printed thereon is affixed, as well as a display in which the sample ID is printed directly on the tube X, etc.
[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 specimen ID displayed on the tube X is read by the reading means 13. The specimen ID can be read while the tube X is stopped, or while the tube X is rotated in the forward or reverse direction. By rotating the tube X in the forward or reverse direction, the specimen ID can be read accurately and reliably even if it is displayed at an angle to the longitudinal axis of the tube X. When reading the specimen ID, the tube X can be rotated continuously or intermittently in multiple steps. Furthermore, when reading the specimen ID, the tube X may be moved up and down to accommodate vertical errors in the affixing position of the sticker on the tube X.
[0037] In the specimen ID reading step S003, if the reading is successful, the specimen ID read by the reading means 13 (hereinafter referred to as the "read specimen ID") is recorded as execution information in the PC 40. If the reading is unsuccessful, the fact that the tube X has been moved to the evacuation box is recorded. Since the read specimen ID is the specimen ID displayed on the tube X that has been read, it matches the specimen ID.
[0038] [Sample ID photography process] The specimen ID photographing step S004 is a step of photographing the specimen ID displayed on the tube X by the photographing means 14. In this step, the tube X is moved by the first arm 31 to a photographing position for the photographing means 14, and the specimen ID displayed on the tube X is photographed by the photographing means 14.
[0039] Since the specimen ID displayed on the tube X may be displayed at an angle to the longitudinal axis of the tube X, displayed in the reversed left-right direction, or displayed upside down, it is preferable to photograph the tube X multiple times by continuously or intermittently rotating it forward and backward. Traceability can be ensured by the image obtained by photographing (hereinafter referred to as the "specimen ID image"). The specimen ID image can also be used to verify the read specimen ID read by the reading means 13.
[0040] In the sample ID photographing step S004, the sample ID image obtained by photographing with the photographing means 14 is recorded in the PC 40 as execution information.
[0041] [Lid removal process] The lid removal step S005 is a step of removing (opening) the lid Y of the tube X. In this step, the tube X is placed at a predetermined position in the tube vice 16 by the first arm 31, and the lid Y of the tube X clamped by the clamping 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 vice 16 is gripped by the first hand 31a of the first arm 31, and the lid Y of the tube X is removed by rotating the first hand 31a.
[0043] When the lid removal operation 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) that have been set in advance based on the protocol. Whether or not the lid removal has been successful can be determined by various methods, but in this embodiment, whether or not the lid Y has been gripped is determined based on the pressure and position of the two claws of the first hand 31a.
[0044] In other words, when the lid Y is grasped by the first hand 31a, the two claws are open to a distance greater than the diameter of the lid Y, whereas when the lid Y is not grasped, the distance between the two claws is less than the diameter of the lid Y. Therefore, by measuring the positions (distance) of both claws, it is possible to determine whether the lid Y is being grasped (whether the lid Y has been opened).
[0045] Whether or not the lid removal has been 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. If the lid Y has not been removed from the tube X held by the tube vice 16, a load of a predetermined amount or more is applied to the wrist of the first hand 31a when rotating the lid Y, and by measuring this load, it can be determined whether or not the lid removal has been successful. This method can be adopted in place of or together with the method of measuring the pressure and position of the first hand 31a (two claws).
[0046] In the lid removal process S005, the result of the determination as to whether or not the lid removal was successful (lid removal determination result) is recorded in the PC 40 as execution information. In this embodiment, the robot 30 is temporarily stopped if it is determined that the lid removal has failed. In this embodiment, when the robot 30 temporarily stops, it is notified by sound, light, or the like.
[0047] [Chip mounting process] The tip mounting step S006 is a step of mounting a tip Z to the tip of a pipette P held by a hand (hereinafter referred to as the "second hand") 32a of a second robot arm (hereinafter referred to as the "second arm") 32. In this step, the pipette P moved above the tip rack 19 by the second arm 32 is lowered toward a predetermined tip Z, so that the tip Z fits and is mounted on the tip of the pipette P.
[0048] In this step, the tip Z attached to the tip of the pipette P is moved by the second arm 32 to a photographing position for the photographing means 14, and the tip Z is photographed by the photographing means 14. The photographing can be performed in a stationary state, or can be performed while the tip Z is rotated forward or backward. The photographed image taken in this step (hereinafter referred to as the "mounted tip image") ensures traceability.
[0049] In the chip mounting step S006, an image of the mounted chip obtained by photographing with the photographing means 14 is recorded in the PC 40 as execution information.
[0050] [Installed chip confirmation process] The attached tip confirmation step S007 is a step of confirming whether or not a tip Z is attached to the tip of the pipette P based on a judgment criterion (tip attachment judgment criterion) previously set based on a protocol. In this step, it is also confirmed whether or not the attached tip Z is empty. Whether or not the attachment of the tip Z has been successful can be determined by various methods, but in this embodiment, whether or not the tip Z is attached is determined based on the attached tip image.
[0051] This determination is made by processor 41 of PC 40, and if tip Z is attached to the tip of pipette P from the attached tip image, it is determined that attachment is successful, and if tip Z is not attached to the tip of pipette P, it is determined that attachment is unsuccessful.
[0052] In the chip mounting confirmation step S007, the result of the determination as to whether the chip mounting was successful or not (chip mounting determination result) is recorded in the PC 40 as execution information. In this embodiment, the robot 30 is temporarily stopped if it is determined that the chip mounting has failed. As in the other steps, when the robot 30 is temporarily stopped in this step, a sound, light, or the like is used to notify the user.
[0053] [Suction process] The suction step S008 is a step of suctioning up the sample in the tube X held by the tube vice 16 into the tip Z attached to the tip of the pipette P. This step is performed by the cooperation of the first arm 31 and the second arm 32.
[0054] 2(a) to 2(d), the push button PB of the pipette P held by the second hand 32a of the second arm 32 is pressed down by the first hand 31a of the first arm 31, and in this state, the tip Z attached to the pipette P is inserted into the tube X. Thereafter, the push button PB of the pipette P is released from being pressed down, so that the sample in the tube X is sucked up into the tip Z. When inserting the tip Z into the sample in the tube X, the tip of the tip Z should be positioned near the liquid surface of the sample and should not touch the bottom of the tube X.
[0055] In this embodiment, the speed at which the first arm 31 that presses down the push button PB of the pipette P descends is made slower than the speed at which the second arm 32 holding the pipette P descends, so that the push button PB is released and the sample is sucked up into the tip.
[0056] In this embodiment, the descent speed of the second arm 32 (in other words, the descent speed of the pipette P held by the second arm 32) is adjusted to be the same as or faster than the rate at which the sample liquid level drops (rate at which the sample decreases), so that the tip of the tip Z does not protrude above the sample liquid level in the tube X when the sample is sucked up.
[0057] When the sample is sucked up, the liquid level of the sample gradually drops as the sample is sucked up, so depending on the speed at which the second arm 32 is lowered, the tip of the tip Z may protrude above the liquid level of the sample in the tube X, which may cause air to get mixed in. As in this embodiment, by adjusting the speed at which the second arm 32 is lowered as described above, it is possible to prevent air from getting mixed in when the sample is sucked up.
[0058] In this step, the tip Z after suctioning the sample, which is attached to the tip of the pipette P, is moved by the second arm 32 to a photographing position for the photographing means 14, and the tip Z is photographed by the photographing means 14. The photographing can be performed in a stationary state, or while the tip Z is rotated forward or backward. The photographed image taken in this step (hereinafter referred to as the "post-suction tip image") ensures traceability.
[0059] In the siphoning step S008, the post-siphoning tip image obtained by photographing with the photographing means 14 is recorded in the PC 40 as execution information.
[0060] [Suction volume confirmation process] The suction volume confirmation step S009 is a step for confirming the amount of sample suctioned. In this step, it is determined from the tip image after suction whether a specified volume of sample has been suctioned into the tip Z attached to the tip of the pipette P. The specified volume here is an amount that is arbitrarily set according to the characteristics of the sample and the specifications of the analytical test, and is specified as part of the protocol. The manufacturer, model number, size, etc. of the tip may also be included as part of the protocol.
[0061] In this step, the image may be captured of the entire chip Z or a portion thereof. When a portion thereof is captured, for example, the image may be captured so that the sucked-up specimen portion and the air portion above it are included. The post-suck-up chip image includes the entire chip Z, the specimen sucked up into the chip Z, and the air above the sucked-up specimen.
[0062] In this embodiment, whether or not a specified volume of sample has been sucked up is determined by image processing of the tip image after suction. Specifically, as shown in Figures 3(a) and 3(b), if the size, width, configuration, target area, or a numerical representation of the figure within a plane or curved surface of the air portion S1 (area surrounded by a dashed line in Figure 3(b)) in the tip Z of the captured image data (Figure 3(a)), it is determined that a specified volume of sample has been sucked up, and if the determination criterion is not met, it is determined that a specified volume of sample has not been sucked up.
[0063] In this embodiment, the size, width, configuration, target area, or numerical values of the figure within the plane or curved surface of the air portion S1 in the chip Z are used as the judgment criteria, but the size, width, configuration, target area, or numerical values of the figure within the plane or curved surface of the specimen portion S2 in the chip Z (the area surrounded by the two-dot chain line in FIG. 3(b)) can also be used as the judgment criteria. In this case, too, if the size, width, configuration, target area, or numerical values of the figure within the plane or curved surface of the photographed specimen portion S2 in the chip Z meets the suction amount judgment criteria set in advance based on the protocol, it can be determined that the specified volume of the specimen has been suctioned, and if the judgment criteria are not met, it can be determined that the specified volume of the specimen has not been suctioned.
[0064] Whether or not a specified volume of sample has been sucked up can also be determined based on the size, width, configuration, and target area of the air portion S1 and the sample portion S2 within a plane or curved surface, or on numerical values of these, as well as the distance from the top to the bottom of the air portion S1, the distance from the top to the bottom of the sample portion, the area ratio between the air portion and the sample portion, and the ratio of the distances from the top to the bottom of both.
[0065] In the suction volume confirmation step S009, the result of the determination as to whether or not a specified volume of sample has been suctioned into the tip Z (suction volume determination result) is recorded as execution information in the PC 40. The suction volume determination result here may include a specific numerical value of the suction volume in addition to whether or not the suction volume is within the specified volume range.
[0066] In this embodiment, the robot 30 is temporarily stopped if it is determined that the specified volume of sample has not been sucked up. As in the other steps, when the robot 30 is temporarily stopped in this step, a sound, light, or other notification is given.
[0067] [Discharge process] The discharging step S010 is a step of discharging the sucked-up specimen into the plate hole 18a. As shown in Figures 4(a) to (c), this step is performed by cooperation between the first arm 31 and the second arm 32. Specifically, after the second arm 32 moves the tip Z at the end of the pipette P to a predetermined position on the plate 18, the push button PB of the pipette P is pressed down by the first hand 31a at that position, and the specimen in the tip Z is discharged into the plate hole 18a.
[0068] In the discharge step S010, the destination plate ID (hereinafter referred to as "destination plate ID") and information on the plate hole in the destination plate ID (destination plate hole) are recorded in the PC 40 as execution information.
[0069] The destination plate hole is specified by XYZ coordinates (for example, three axes of XYZ coordinates or two axes of X and Y coordinates) in the workspace coordinate system set with reference to the robot 30. The destination plate hole specified by the plate ID or the X and Y coordinates here is recorded in the PC 40 as destination specification information for specifying the destination. The destination specification information can also use a combination of information on the codes A to H assigned to the vertical columns (X axis) of the plate 18 and the numbers 1 to 12 assigned to the horizontal columns (Y axis).
[0070] [Discharge amount confirmation process] The discharge amount confirmation step S011 is a step for confirming whether or not a specified volume of sample has been discharged from tip Z. In this step, tip Z attached to the tip of pipette P is moved by second arm 32 to a photographing position for photographing means 14, tip Z is photographed by photographing means 14, and processor 41 of PC 40 determines whether or not a specified volume of sample has been discharged from tip Z from the photographed tip image (hereinafter referred to as "post-discharge tip image").
[0071] As with the suction amount confirmation step S009, the image captured in this step may be of the entire tip Z or a portion thereof. When only a portion thereof is captured, for example, the image may be made to include the sample remaining in the tip Z after it has been expelled (hereinafter referred to as the "remaining sample") and the air above the remaining sample portion. In this case, the post-extrusion tip image includes the entire tip Z, the remaining sample, and the air above the remaining sample portion.
[0072] In this embodiment, as in the suction amount confirmation step S009, whether or not a specified volume of sample has been discharged is determined by image processing of the tip Z photographed by the photographing means 14. Specifically, as shown in Fig. 5(a)(b), if the size, width, configuration, target area, or numerical representation of the figure within a plane or curved surface of the air portion S1 (area surrounded by a dashed line in Fig. 5(b)) of the photographed post-discharge tip image meets a criterion (hereinafter referred to as "discharge amount criterion") previously set based on a protocol (if it is within the range of a threshold), it is determined to be normal, and if the criterion (threshold) is not met (if it is outside the range of the threshold), it is determined to be an error. As in the suction amount confirmation step S009, this determination is made by the processor 41 of the PC 40.
[0073] Furthermore, when making the judgment, even if the amount of sample dispensed is appropriate, a film or air bubble (hereinafter referred to as "film, etc.") F that occurs in the tip Z may be mistaken for a sample, and it may be judged that the specified volume of sample has not been dispensed. The film, etc. F is an event that hinders the judgment of the amount of sample dispensed, and may occur, for example, due to the characteristics and temperature of the buffer solution, the shape and size of the tip Z, etc.
[0074] If an event such as a film or the like F that hinders the determination of the discharged amount occurs, processing is performed so that the event does not hinder the determination. One processing method is, for example, duplicating the post-discharge tip image on the PC 40 as shown in Fig. 5(c) and hiding (blacking out) part of the copied post-discharge tip image (for example, the upper part of the tip where a film or the like F is likely to occur) to narrow the region to be determined. In this case, the size, width, configuration, target region, or numerical values of the figures within a plane or curved surface of the air portion S1 or remaining specimen portion S3 in the narrowed region to be determined may be calculated, and it may be determined from the calculated value whether or not a specified volume of specimen has been discharged.
[0075] In Figure 5(c), the area to be judged is restricted by blackening out and hiding the part of the membrane etc. F where the event occurred (hereinafter referred to as the "event occurrence part"), but the area to be judged can also be restricted by a method other than blackening. For example, it is conceivable to restrict the area to be judged by cutting out (removing) a part of the image including the event occurrence part, and to judge whether or not a specified volume of the sample was discharged based on the evidence after the cutting out.
[0076] One method of hiding the part where an event has occurred is, for example, to set the range to be hidden in advance so that the relevant range of the evidence is uniformly hidden. For example, the range to be hidden on the evidence can be set in advance, such as the range of the top 10% of the evidence or the range of 50 mm from the top, so that the relevant range on the evidence is hidden. The range to be hidden can also be set in a way such as 50 mm from the top of the evidence. Note that these numerical values are only examples, and other numerical values can also be set. Furthermore, the standard for the position to be hidden is not limited to the top of the evidence, and for example, the top end of the chip in the evidence can be used as the standard, and it can be set to a few percent or a few mm from the top end of the chip in the evidence.
[0077] It is also possible to hide the event occurrence portion by varying the hiding position and range for each evidence based on a certain criterion. For example, when a specific event is confirmed on the evidence (such as a line appearing in tip Z on the evidence), it is also possible to vary the hiding position and range for each evidence based on that event. It is also possible to vary the hiding position and range for each evidence based on the characteristics and properties of the specimen or buffer solution, mechanical wear of the pipette P or tip Z, the working environment (temperature, humidity, air pressure, etc.), etc.
[0078] For example, the part where the event occurred can be hidden by detecting the attachment angle from the image taken when the tip Z is attached, predicting the change in the discharge amount from that angle, and changing the place to be hidden (e.g., the position or range) accordingly, or by moving the hidden area downward every predetermined time (e.g., several seconds). The former can be an effective method for dealing with mechanical wear, such as when the sealing of the joint C between the pipette P and the tip Z becomes unstable, and the latter can be an effective method for dealing with cases where the amount of the remaining adhesion to the wall inside the tip Z needs to be taken into consideration due to the viscosity of the sample. Note that, although a case where part of the evidence is hidden is explained here, a similar method can also be used to cut off part of the evidence.
[0079] When limiting the area to be judged by blacking out or removing the event occurrence portion or by other methods, it is preferable to keep a record of both the evidence (discharged chip image) before the restriction (before blacking out or cutting out processing is performed) and the evidence (processed chip image) after the restriction (after blacking out or cutting out processing is performed). In addition, the evidence before the restriction and the evidence after the restriction can be displayed side by side on the monitor 21. However, the two evidences may be displayed separately instead of side by side.
[0080] By keeping both the evidence before the restriction (for example, raw image data such as still images and videos) and the evidence after the restriction as records, it is possible to confirm the state of the part where the event occurred after the fact. In this embodiment, the evidence before the restriction and the evidence after the restriction are linked and recorded in the recording means (storage 43).
[0081] In this example, a photograph (still image) taken by the photographing means 14 is used as evidence (hereinafter referred to as "photographed evidence"), but a video taken by the photographing means 14 can also be used as the photographed evidence. Photographing is also done by the photographing means 14 in other steps of the present application, but in each case the image may be either a still image or a video. The still image or video obtained by photographing can be used as the photographed evidence.
[0082] When an event occurs that impedes judgment, the method of image processing may be a method other than hiding or removing parts, and the image may be processed by methods such as image correction, image conversion, image processing, feature extraction, image recognition, three-dimensionalization, and quantification.
[0083] Image correction here includes correcting contrast, brightness, color, etc., image conversion includes converting color images to monochrome images, image processing includes noise removal, edge emphasis, enlargement, reduction, etc., image feature extraction includes measuring area and circularity, image recognition includes identifying objects, three-dimensionalization includes processing two-dimensional images into three-dimensional images, and digitization includes converting images into numerical values. All of these processes are methods of processing on digital images. For example, with image recognition, it is possible to identify the part where an event occurred for each document and hide or remove the part where the event occurred.
[0084] Whether or not a specified volume of sample has been dispensed can be determined using the size, width, configuration, target area, or numerical values of the figure within a plane or curved surface of the remaining sample portion S3 in the chip Z after dispensing as a criterion. In this case, too, if the size, width, configuration, target area, or numerical values of the figure within a plane or curved surface of the photographed remaining sample portion S3 in the chip Z meets a criterion (threshold) previously set based on a protocol (if it is within the threshold range), it can be determined to be normal, and if it does not meet the criterion (threshold) (if it is outside the threshold range), it can be determined to be an error.
[0085] Whether or not a specified volume of sample has been expelled can be determined based on the size, area, composition, target area, or numerical values of the shape of the air portion S1 within a plane or curved surface, the size, area, composition, target area, or numerical values of the shape of the remaining sample portion S3 within a plane or curved surface, as well as the distance from the top to the bottom of the air portion, the distance from the top to the bottom of the remaining sample portion, the area ratio of the air portion to the remaining sample portion, the ratio of the distance from the top to the bottom of both, etc.
[0086] In the discharge amount confirmation step S011, in addition to the post-discharge tip image obtained by photographing with the photographing means 14, the post-processing tip image and the determination result as to whether or not a specified volume of sample was discharged (hereinafter referred to as the "discharge amount determination result") are recorded as execution information in the PC 40. The discharge amount determination result here may include a specific numerical value of the discharge amount in addition to whether or not the discharge amount was within the specified volume range.
[0087] In this embodiment, the robot 30 is temporarily stopped when it is determined that the discharge amount does not satisfy a criterion (hereinafter, referred to as "discharge amount criterion") that is set in advance based on the protocol. As in the other steps, when the robot 30 is temporarily stopped in this step, a sound, light, or the like is used to notify the user.
[0088] [Chip removal process] The tip removal step S012 is a step of removing the tip Z attached to the tip of the pipette P. In this step, the second arm 32 hooks the coupling portion C of the pipette P and the tip Z onto the periphery of the locking recess 20d of the tip remover 20, and in this state, the pipette P is raised upward, whereby the tip Z is removed from the pipette P.
[0089] [Lid closing process] The capping step S013 is a step of capping (plugging) the tube X held by the tube vice 16. In this step, a new cap Y stored in the cap rack 12 is taken out by the first hand 31a of the first arm 31, and the cap Y is attached (capped) to the tube X held by the tube vice 16. In this embodiment, the tube X is capped by rotating the first hand 31a holding the cap Y.
[0090] [Lid closure check process] The capping confirmation step S014 is a step for confirming whether or not the tube X is capped (whether or not the cap Y is attached to the tube X) after the capping step S013 is completed. In this step, it is determined whether or not the capping has been successfully completed based on a criterion (capping criterion) that is preset based on a protocol. Whether or not the cap has been successfully closed can be confirmed, for example, by the following two methods.
[0091] The first method is to judge whether or not the load applied to the first hand 31a when the lid Y of the tube X is picked up by the first hand 31a of the first arm 31 satisfies the lid closing judgment criteria set in advance based on the protocol. When judging by this method, if the tube X is lifted together with the lid Y (if the lid closing judgment criteria are satisfied), it is judged that the lid closing is successful, and if the tube X is not lifted and only the lid Y is lifted (if the lid closing judgment criteria are not satisfied), it is judged that the lid closing is insufficient (insufficient airtightness) and that the lid closing has failed.
[0092] When the tube X after the lid is closed is returned to the tube rack 11, it is lifted by the first hand 31a of the first arm 31. This method can be performed when the lid Y is picked up and lifted when the tube X after the lid is closed is returned to the tube rack 11. Since there is no separate process, the lid closure can be efficiently determined.
[0093] The second method is to judge from the image captured by the imaging means 14 (hereinafter referred to as the "tube image after lid closing"). When making a judgment 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 of 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 image after lid closing includes the tube X together with the lid Y, it is judged that the lid closing was successful, and if the tube image after lid closing includes only the lid Y but not the tube X, it is judged that the lid closing was unsuccessful. Whether or not the lid closing was successful can also be judged by other methods.
[0094] Checking whether or not lid Y is attached to tube X, in other words, whether or not tube X is sealed, is performed to prevent harmful effects such as contamination and denaturation of the sample caused by tube X not being sealed. If lid Y is not closed, tube X may fall over or tilt, causing the remaining sample to scatter, 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 acids in the cells to denature).
[0095] In order to prevent these inconveniences, in this embodiment, it is confirmed whether or not the lid Y is attached to the tube X, and if the lid closing fails, the robot 30 is stopped. This makes it possible to avoid in advance the above-mentioned problems caused by the lid Y not being closed.
[0096] In the lid closure confirmation step S014, the PC 40 records, as execution information, the image of the tube after lid closure obtained by photographing with the photographing means 14, as well as the determination result as to whether or not the lid closure was successful (lid closure determination result).
[0097] In this embodiment, the robot 30 is set to pause if it is determined that the lid closing has failed. As in the other steps, when the robot 30 pauses in this step, a sound, light, or the like is used to notify the user.
[0098] [Containment process] The storage step S015 is a step of removing the capped tube X from the tube vice 16 and returning it to the storage recess 11a of the tube rack 11. In this step, the capped tube X is removed from the tube vice 16 by the first hand 31a of the first arm 31, and the removed tube X is returned to the original storage recess 11a of the tube rack 11.
[0099] [Other processes] 1, in this embodiment, after reading in the sample ID reading step S003, it is determined whether the read sample ID overlaps with a sample ID that has already been read. If it is determined that the sample ID overlaps, the tube X on which the sample ID is displayed is stored in a shelter 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] In this embodiment, it is determined whether the specimen ID is missing from the specimen ID list registered in advance. If it is determined that the specimen ID is missing from the specimen ID list, the tube X on which the specimen ID is displayed is stored in a shelter box (not shown) by the operation of the robot 30. In this case, the specimen ID displayed on the tube X is also recorded in the PC 40.
[0101] The execution information obtained in each step of the pre-processing is linked to the specimen ID (read specimen ID) and recorded in the storage (recording means) 43 of the PC 40. That is, each execution information is recorded for each specimen ID. For example, for a specimen with a specimen ID "xxxxx", all execution information related to this specimen ID "xxxxx" is linked and recorded.
[0102] This makes it possible to check, for example, whether the discharge amount for a sample ID "xxxxx" satisfies the judgment criteria from the discharge amount judgment result, and to verify whether the discharge amount judgment result for the sample ID "xxxxx" is appropriate by comparing it with the post-discharge tip image linked to the sample ID "xxxxx". In this way, by recording two or more pieces of execution information for one process, it becomes possible to verify the protocol and the execution result (execution information), and to verify the execution results (execution information) with each other.
[0103] In each step of the embodiment, the processor 41 of the PC 40 judges whether the lid has been removed successfully, whether the tip has been attached successfully, whether the amount of suction is within the range of a specified volume, whether the amount of discharge is within the range of a specified volume, whether the lid has been closed successfully, etc., and each judgment criterion that is the basis for the success or failure is appropriately set according to the specifications of the test using the sample and the equipment used (pipette P, tip Z, tube X, lid Y, etc.). Each judgment criterion is set in advance according to a designation from the customer side, and the positions and pressures of the first arm 31, second arm 32, first hand 31a, second hand 32a, etc., the image processing method, etc. may also be created by the pre-processing execution system provider.
[0104] In the above embodiment, the steps from the removal step S002 to the reading step S015 are performed in a single flow, but each step can be performed individually or in multiple steps. Not all steps are essential, and unnecessary steps can be omitted as appropriate. The above embodiment is an example, and steps can be replaced, changed, added, etc. as appropriate without changing the gist of the embodiment.
[0105] [Outline of the system that performs preprocessing] Next, an example of a pre-processing execution system for carrying out each of the above steps will be described with reference to the drawings. This pre-processing 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 system shown in Figures 6 and 7 includes an installation stand 10, a tube rack 11, a lid rack 12, a reading means 13, a photographing means 14, a lighting device 15, a tube vice 16, a lid collection box 17, a plate 18, a tip rack 19, a tip remover 20, a monitor 21, an input / output port 23, a robot 30, a PC 40, etc.
[0106] The installation stand 10 is a stand on which various devices such as a tube rack 11, a lid rack 12, a reading means 13, an imaging means 14, a lighting device 15, a tube vice 16, a plate 18, a tip rack 19, a tip remover 20, a monitor 21, a robot 30, and a PC 40 are installed. A stainless steel stand or the like can be used for the installation stand 10.
[0107] In this embodiment, the various devices that make up the system are installed on a single installation stand 10, which has the advantage of taking up less installation space than conventional systems that are composed of modularized devices organized by function (process).
[0108] The tube rack 11 is a container for storing tubes X containing specimens. In this embodiment, a tube rack 11 having 96 (8 vertical × 12 horizontal) bottomed storage recesses 11a is used. The tube rack 11 is sized to a height such that at least the lids Y of the tubes X protrude above the upper surface of the tube rack 11 when the tubes X are stored in the storage recesses 11a.
[0109] The lid rack 12 is a container for accommodating new lids Y to be attached to tubes X after sample aspirating. In this embodiment, a lid rack 12 having 96 (8 vertical × 12 horizontal) bottomed lid storage sections 12a is used. The lid rack 12 is sized to a height such that at least the lids Y protrude above the upper surface of the lid rack 12 when the lids Y are stored in the lid storage sections 12a.
[0110] The lid rack 12 may be, for example, a removable type that can be placed in an irradiation type sterilizer (an ultraviolet sterilizer equipped with an ultraviolet lamp) with all or some of the lids Y still mounted thereon. When a removable type that can be placed in an irradiation type sterilizer is used, if a human (e.g., worker) gene accidentally adheres to the lid Y, the gene can be destroyed, thereby preventing contamination.
[0111] The reading means 13 is a device for reading the sample ID displayed on the tube X. Various readers such as a barcode reader and a QR code reader can be used for the reading means 13. In this embodiment, a stationary barcode reader capable of reading one-dimensional and two-dimensional codes is used as the reading means 13. Others can also be used for the reading means 13.
[0112] In this embodiment, when the sample ID displayed on the tube X arrives within the reading range of the reading means 13, the sample ID is read by the reading means 13. The read 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 and chip Z displayed on the tube X. A camera equipped with a variable focus lens or the like can be used as the photographing means 14. In this embodiment, the case where one camera is used is taken as an example, but the photographing means 14 can also be configured with a plurality of cameras. Furthermore, the photographing means 14 can be one that photographs still images, one that photographs moving images, or one that photographs both still images and moving images, etc.
[0114] The lighting device 15 is a device for illuminating the tube X (specimen ID) or chip Z that is the subject of imaging by the imaging means 14. A first power source 22a is connected to the lighting device 15, and the lighting device 15 is configured to operate with the power supplied from the first power source 22a. In this embodiment, a highly directional white light is used as the lighting device 15. The lighting device 15 is in the form of a thin plate, and is attached to the installation table 10 in a vertically upright state. Other lighting devices may also be used as the lighting device 15.
[0115] In this embodiment, when the tube X is moved to an imaging position by a first arm 31 described later, or when the tip Z is moved to an imaging position by a second arm 32 described later, the tube X or tip Z is illuminated by the lighting device 15 and is photographed by the imaging means 14. The photographed images (such as a specimen ID image, an attached tip image, a tip image after suction, a tip image after discharging, and a tip image after closing the lid) are transmitted to the PC 40 and recorded in the storage 43.
[0116] The tube vice 16 is a device that clamps the tube X. As shown in Figures 8(a) and (b), the tube vice 16 of this embodiment includes a clamping portion 16a that clamps the tube X, a drive mechanism 16b that opens and closes the clamping portion 16a, and a drive source (motor) 16M that operates the drive mechanism 16b.
[0117] The clamping portion 16a of this embodiment has 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 base 16f provided on a base plate 16e, and the other clamping piece (hereinafter referred to as the "movable clamping piece") 16d is composed of a part (rising part) of a movable T-shaped plate 16n that is moved by a driving mechanism 16b. Cushioning 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). A 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, linear guides 16k are arranged in parallel to 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 a ball nut, and is configured so that the movable clamping piece 16d moves in a direction approaching or moving away from the fixed clamping piece 16c in conjunction with the movement of the ball nut. A guide block 16p with a through hole is provided on each of both ends in the longitudinal direction of the back surface of the T-shaped plate 16n, and a linear guide 16k is inserted into the through hole. This prevents the T-shaped plate 16n from shaking sideways when the T-shaped plate 16n moves.
[0120] The lid recovery box 17 is a container for recovering the lids Y removed from the tubes 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 that the first arm 31 can reach (in this embodiment, to the side of the installation stand 10).
[0121] The plate 18 is a container for transferring the sucked up sample. Although not shown in the figure, a plate ID such as a barcode or QR code is displayed on each plate 18. The display here includes a display in which a sticker with the plate ID printed thereon is affixed, as well as a display in which the plate ID is directly printed on the plate 18.
[0122] 9, in this embodiment, a plate 18 having 96 (8 vertical × 12 horizontal) rectangular wells (plate holes 18a) is used. This plate 18 is configured such that the columns (X-axis) are assigned symbols A to H and the rows (Y-axis) are assigned numbers 1 to 12, so that the plate holes 18a can be identified by a combination of the symbols and numbers.
[0123] The plate 18 has an outwardly protruding fitting portion 18b on the outer periphery thereof, which fits into a fitting groove 24c of a plate seat 24, which will be described later. The plate 18 shown here is an example, and other plates may be used instead of the plate 18. A plurality of plates 18 may also be added.
[0124] The plate 18 is mounted on a plate seat 24 fixed to the installation base 10. In this embodiment, the plate seat 24 has a mounting surface 24a that is rectangular in plan view. A flange 24b protrudes from the plate seat 24, and the flange 24b can be fixed to the installation base 10 with fasteners such as screws.
[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 side of the mounting surface 24a is open, from which the fitting portion 18b of the plate 18 can be inserted into the fitting groove 24c. The plate seats 24 can be increased in number according to the number of plates 18.
[0126] The tip rack 19 is a container for storing new tips Z to be attached to the pipette P. In this embodiment, the tip rack 19 used has 100 tip storage sections (10 vertical × 10 horizontal). Other types of tip racks can also be used.
[0127] In this embodiment, the tip rack 19 is stored in a tip rack case 25, allowing the positioning and adjustment of the tip rack 19. As an example, the tip rack case 25 shown in Figures 10(a) and (b) has a base portion 25a fixed to the installation table 10 and an erect portion 25b erected on the base portion 25a. The erect portion 25b is composed of three fixed walls 25c surrounding the four sides and one movable wall 25d, and the inner width of the erect portion 25b can be adjusted by appropriately moving the movable wall 25d.
[0128] Tip racks 19 vary in size and shape depending on the manufacturer, but by providing movable wall 25d and making it possible to adjust the inner width of standing portion 25b as in this embodiment, it is possible to flexibly accommodate tip racks 19 of different sizes and shapes. After movement, movable wall 25d is fixed to base portion 25a with screws (not shown) or the like to prevent it from moving accidentally.
[0129] By mounting the tip rack 19 in the tip rack case 25 having such a structure, the tip rack 19 is positioned at a portion where its four corners coincide with the four corners of the tip rack case 25, and the position of the origin is less likely to shift, so that the tip Z can be reliably mounted on the tip of the pipette P.
[0130] The tip remover 20 is a tool for removing a used tip Z attached to the tip of a pipette P. The tip remover 20 of this embodiment includes a fixed part 20a fixed to the installation table 10, a rising part 20b rising upward from the fixed part 20a, and a protruding part 20c protruding outward from the middle of the rising part 20b.
[0131] A locking recess 20d is provided at the tip of the protrusion 20c, into which the connecting portion C of the pipette P and the tip Z is accommodated. The tip Z can be removed from the pipette P by moving the pipette P upward with the connecting portion C of the pipette P and the tip Z hooked on the periphery of the locking recess 20d.
[0132] The monitor 21 displays the operating status of the system, images captured by the imaging means 14, and signals read by the reading means 13. In this embodiment, the monitor 21 also displays buttons for operating applications, such as starting, resuming, stopping, reading, and resampling.
[0133] The input / output port 23 is a means for inputting or outputting a signal. 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. The GPIO can receive a signal sent from the PC 40 and control the tube vice 16. A second power source 22b shared with the tube vice 16 is connected to the input / output port 23, and the input / output port 23 is configured to operate with power supplied from the second power source 22b.
[0134] Using GPIO as the input / output port 23 has the advantage that all of the various devices that make up the system can be controlled from the PC 40 side. This reduces the amount of control on the robot 30 side, and is expected to improve the processing speed of the robot 30. In addition, since it is now possible to control the various devices that make up the system from the PC 40 side, various robots 30 other than the robot 30 used in this embodiment can also use the various devices that make up the system, which has the advantage of making it easier to respond to customer requests.
[0135] The robot 30 is a robot that handles tubes X and pipettes P. In this embodiment, a double-arm articulated robot equipped with a first arm 31 and a second arm 32 is used as the robot 30. A first hand 31a is provided on the first arm 31, and a second hand 32a is provided on the second arm 32. The tubes X and pipettes P are held by the first hand 31a and the second hand 32a.
[0136] 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 arms are adapted to return to their origins at appropriate times and start new operations from there.
[0137] In this embodiment, the first arm 31 is configured to at least grasp the tube X stored in the tube rack 11, move the tube X to a reading position, move the tube X to a photographing position, move the tube X to the tube vice 16, remove the lid of the tube X held in the tube vice 16, discard the removed lid Y in the lid recovery box 17, close the lid of the tube X and store the tube X in the tube rack 11 after the lid is closed, and operate the push button PB of the pipette P.
[0138] In this embodiment, the second arm 32 is configured to perform at least various operations on the pipette P, move the pipette P to a tip attachment position, move the tip Z to a photography position, and move the tip Z to the tip remover 20.
[0139] In addition, in the robot 30, operation information such as the operation start position, operation end position, operation path, temporary stop position, operation speed, operation angle, branching method, etc. are registered, and the first arm 31, second arm 32, first hand 31a, second hand 32a, etc. of the robot 30 are made to operate according to the operation information and branching method, etc. These numerical values, etc. can be arbitrarily set or changed according to the characteristics, etc. of the sample to be processed.
[0140] Various existing liquid crystal displays, such as touch panel compatible displays, can be used for the monitor 21. The information displayed on the monitor 21 can be appropriately selected and displayed according to the customer's needs.
[0141] The PC 40 not only issues commands to the control means 33 of the robot 30, but also receives and records data (execution information) sent from the reading means 13, the photographing means 14, etc., performs various processes such as judgment, controls various means such as the reading means 13, the photographing means 14, the lighting equipment 15, the monitor 21, the power source 22, etc., and responds to questions from the robot 30 with the judgment results.
[0142] 11, a 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 via a bus 47.
[0143] The processor 41 functions as a determination means for determining whether the lid was removed successfully, whether the tip was attached successfully, the amount of liquid sucked up, the amount of liquid discharged, and whether the lid was closed successfully; the storage 43 functions as a recording means for recording various execution information; and the communication unit 44 functions as a communication means for sending and receiving information to and from a customer system (external device) 50 described later.
[0144] The processor 41 of this embodiment also functions as a processing means for processing the occurrence of an event that hinders the determination of the discharge amount, such as a film or the like F, so that the determination is not hindered by this event. The process executed by the processing means is as described above.
[0145] As shown in FIG. 7, the system of this embodiment is communicatively connected to a customer-side system 50 via a communication line L, and is configured to be able to transmit and receive information used in the system and information obtained during dispensing work in the system to and from the customer-side system 50. The communication line L can also be used wirelessly. wired The communication between the system of this embodiment and the customer-side system 50 may be performed via a record tamper-proof device (not shown).
[0146] For example, a registered sample ID registered in the customer DB is obtained from the customer DB 51 of the customer system 50. In addition, when multiple plates 18 are used, a designated plate ID and designated plate hole information are also obtained from the customer DB 51.
[0147] Data can be exchanged with the client system 50 according to the specifications specified by the client, such as CSV linkage, API linkage, etc. Since the required information differs for each client, any execution information selected and set from the execution information recorded on the system side can be passed to the client system 50.
[0148] This preprocessing execution system operates by software (programs) for executing each of the above processes. This software can be provided as a program separate from the preprocessing execution system, specifically, as a program that causes a computer to operate as this preprocessing execution system or the execution information recording device of the present invention. The computer referred to here is sufficient if it has functional units equivalent to a processor and memory, and is a concept that includes not only the PC 40 constituting this system, but also the robot 30, this system as a whole, and each device constituting this system.
[0149] The program does not have to be stored in one computer (for example, PC 40), but may be stored in both PC 40 and robot 30, or in one or more of the devices constituting this system. In short, the program here means a program that enables each of the above processes to be executed.
[0150] The software can be provided by downloading, or as a recording medium recorded in a computer-readable form. Recording media here include optical disks, magneto-optical disks, semiconductor memories, and more specifically, hard disks (HDs), CD-ROMs, CD-Rs, CD-RWs, DVD-ROMs, DVD-Rs, DVD-RWs, DVD-RAMs, MOs, DVDs, flash memories, memory cards, etc.
[0151] In the pre-processing flow and the system that executes the pre-processing of the above-described embodiment, the execution information is automatically recorded in association with the sample ID (read sample ID) and the plate ID (read plate ID), thereby enabling double matching of samples to be performed reliably.
[0152] In the preprocessing flow and the system that executes the preprocessing in the above embodiment, not only execution information is recorded when the system operates normally, but also execution information when the system is executed under procedures or conditions other than the processing procedures or processing conditions defined as normal operation in the protocol, such as when the robot 30 stops. Therefore, during execution of the preprocessing or after completion of the preprocessing, it is possible to verify whether the preprocessing by the robot 30 was performed according to the protocol.
[0153] The pretreatment flow and the system for performing the pretreatment according to the above embodiment have the advantage that human errors such as forgetting to record, recording errors, and recording omissions do not occur. Since the specimen contained 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 regarding which specimen has been dispensed into which hole of which plate.
[0154] Conventionally, this recording was often done manually by workers, but it was difficult to work and record at the same time because both hands were occupied during the work. In such cases, recording was done after the work was completed, but human errors such as forgetting to record, recording mistakes, and omissions in recording occurred.
[0155] In contrast, in the preprocessing flow and the system that executes the preprocessing in the above-described embodiment, the execution information obtained during the preprocessing process is automatically recorded, so there is almost no need for the worker to perform the recording work manually, and there is no human error that occurs when the worker performs the recording work manually, which also helps to reduce the burden on the worker.
[0156] Note that the preprocessing flow and the system that executes the preprocessing in the above-described embodiment are merely examples and are not limited to the configurations of the above-described embodiment. The preprocessing flow and the system that executes the preprocessing can be modified, such as by replacing or omitting, as appropriate, as long as the gist of the preprocessing flow and the system that executes the preprocessing are not changed. [Industrial Applicability]
[0157] The present invention is particularly suitable for use in pretreatment carried out prior to testing using a specimen, for example, pretreatment carried out prior to testing using various specimens collected from humans and various animals (mammals, fish, birds, amphibians, reptiles, etc.), insects, shellfish, agricultural crops, plants, their seeds and seedlings, microorganisms, etc. [Explanation of symbols]
[0158] 10 Installation stand 11 Tube Rack 11a Recessed portion 12 Lid Rack 12a Lid storage section 13 Reading means 14. Shooting Method 15 Lighting equipment 16 Tube vice 16a Clamping part 16b Drive mechanism 16c Clamping piece (Fixed clamping piece) 16d Clamping piece (movable clamping piece) 16e Base plate 16f Clamping single pedestal 16g (fixed clamp side) cushioning material 16h Cushioning material (on one side of movable clamp) 16i Coupling 16j Ball screw 16k linear guide 16m guide support 16n T-shaped plate 16p guide block 16M Drive source (motor) 17 Lid collection box 18 Discharge container (deep well plate (plate)) 18a Plate hole 18b Mating part 19 Tip Rack 20 Chip Remover 20a Fixed part 20b Rising part 20c protrusion 20d Locking recess 21 Monitor 22 Power supply 22a First power supply 22b Second power supply 23 Input / Output Ports 24 Plate seat 24a Placement surface 24b flange 24c Fitting groove 25 Tip Rack Case 25a Base 25b Standing section 25c fixed wall 25d movable wall 30. Robot 31 First Robot Arm (First Arm) 31a First arm hand (first hand) 32 Second Robot Arm (Second Arm) 32a Second arm hand (second hand) 33 Control Means 40 Electronic computer (PC) 41 Processors 42 Memory (main storage device) 43 Storage (auxiliary storage device) 44 Communications Department 44a Transmitter 44b Receiver 45 Input section 46 Output section 47 Bus 50 Customer system (external device) 51 Customer database (customer DB) C joint part F membrane etc. L Communication Line P Pipette PB Push Button S1 Air section S2 Sample part S3 Remaining specimen portion X Sample 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:
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