Dispensing device and dispensing method

Abstract

This dispensing apparatus is configured to be able to dispense liquid and comprises: a piston; a first drive device that drives the piston; a syringe that has a tip mounting unit to which a dispensing tip is mounted and that receives the piston therein; a pressure sensor that measures pressure within the syringe; a processing device that processes a detection signal of the pressure measured by the pressure sensor; a block having a hole which can be fitted to the tip mounting unit; and a second drive device that varies the relative position between the syringe and the block. The processing device is characterized by: driving the second drive device so as to cause the tip mounting unit and the hole to be fitted to each other; sealing up the interior of the syringe; applying a positive pressure or a negative pressure within the syringe; and then, calculating a correction value for a dispensing command value related to the drive amount of the first drive device on the basis of the pressure in the syringe after the application of the positive pressure or the negative pressure.

Description

Technical Field

[0001] The present disclosure relates to a dispensing device and a dispensing method.

Background Art

[0002] In inspection devices in the medical and bio fields, a dispensing device that dispenses liquids such as specimens and reagents into separate containers is used. The dispensing device includes a pipette unit for sucking and discharging the liquid, a tip for sucking the liquid inside, a transport device for transporting these, and the like.

[0003] In medical and bio field inspections, it may be necessary to handle a small amount of liquid sample. In this case, since inaccurate dispensing may have an adverse effect on the test results, it is required to accurately dispense the specified amount with good reproducibility.

[0004] However, due to the influence of disturbances such as the use environment, device characteristics, deterioration due to long-term use, or the characteristics or state of the sample, even if the pressure generating means is made to operate as designed, the intended dispensing amount may not be achieved. Therefore, it is necessary to correct the dispensing command value.

[0005] Patent Document 1 discloses a dispensing device having a configuration of "a pressure sensor that measures the pressure in the pipe during liquid suction by the dispensing probe 12c, a calculation unit 34 that calculates the average pressure during liquid suction measured by the pressure sensor, a storage unit 37 that stores the correlation between the average pressure during liquid suction and the discharge operation amount for each desired discharge amount, a correction unit 38 that corrects the discharge operation amount based on the average pressure during suction calculated by the calculation unit 34 and the correlation stored in the storage unit 37, and a control unit 31 that controls the syringe pump to discharge the desired discharge amount based on the discharge operation amount corrected by the correction unit 38." (See the summary of Patent Document 1).

[0006] Patent Document 2 discloses a dispensing device configured as follows: "Measure the pressure inside and outside the sealed liquid holding container with a pressure sensor connected to the dispensing probe, and correct the operating amount of the pump according to the measured pressure amount. The correction of the operating amount of the pump is performed by calculating the amount of deformation of the dispensing flow path due to the pressure change." (See the abstract of Patent Document 2).

[0007] Patent Document 3 discloses a technique for a dispensing device comprising: "a plurality of nozzles 3 for dispensing liquid; nozzle moving means 4 for moving the plurality of nozzles 3 in the vertical direction; suction / discharge means 3a for sucking and collecting liquid into a dispensing chip 5 attached to the tip of the plurality of nozzles 3 and discharging the sucked and collected liquid from the dispensing chip 5. The dispensing device 1 is configured to have a plurality of openings 7a on the upper surface corresponding to the plurality of nozzles 3, and a dispensing chip fitting portion 7 in which a closed space is formed inside when a plurality of dispensing chips 5 to which the plurality of nozzles 3 are attached are fitted into the plurality of openings 7a, and an internal pressure detection portion 8 for detecting a pressure change inside the dispensing chip fitting portion 7." (See the abstract of Patent Document 3).

Prior Art Documents

Patent Documents

[0008]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0009] In order to accurately aspirate and discharge liquid reproducibly, the airtightness of the dispensing device is important. However, since the seal parts that block the inside of the dispensing device from the outside air slide with the piston, wear or deterioration occurs at these contact parts, reducing the accuracy of dispensing. As wear or deterioration of the seal parts progresses, it becomes impossible to generate the intended pressure during aspiration and discharge, leading to insufficient aspiration volume and liquid remaining during discharge. In particular, when dispensing a small amount of liquid, wear or deterioration of the seal parts affects the accuracy, so a slight correction of the dispensing command value is required.

[0010] In the method using the pressure change during liquid aspiration as in Patent Document 1, since the change amount of the measured pressure average value in microdispensing is extremely small or no difference is observed compared to the value stored in the storage means, it is difficult to perform correction based on the correlation.

[0011] The dispensing device of Patent Document 2 perforates the dispensing probe inside a sealed container and corrects the discharge command value corresponding to the internal pressure value. However, since the aspiration volume decreases, it is necessary to correct not only the discharge amount but also the command value during liquid aspiration. Although it is possible to compensate for the insufficient liquid amount during aspiration by aspirating a sufficient amount in advance, it may consume consumables such as reagents more than necessary, which can increase the running cost.

[0012] Patent Document 3 aims to prevent failures during dispensing by detecting problems in the attachment of the disposable chip. In the dispensing operation, proper attachment of the chip is one of the important factors, but in order to perform correction for accurate dispensing, it is necessary to measure the performance and state of the seal parts inside the dispensing device.

[0013] Therefore, the present disclosure provides a technique for optimizing the dispensing command value when dispensing a small amount of liquid.

Means for Solving the Problems

[0014] In order to solve the above problems, the dispensing device of the present disclosure is a dispensing device configured to be able to dispense liquid, and includes: a piston; a first drive unit that drives the piston; a syringe having a tip mounting portion to which a dispensing tip is attached and that receives the piston; a pressure sensor that measures the pressure inside the syringe; a processing unit that processes a detection signal of the pressure measured by the pressure sensor; a block having a hole that can be fitted into the tip mounting portion; and a second drive unit that changes the relative position of the syringe and the block, wherein the processing unit drives the second drive unit to fit the tip mounting portion into the hole, seals the inside of the syringe, applies positive or negative pressure into the syringe, and calculates a correction value for the dispensing command value related to the drive amount of the first drive unit based on the pressure inside the syringe after the positive or negative pressure has been applied.

[0015] Further features related to the present disclosure will become apparent from the description of this specification and the accompanying drawings. Also, aspects of the present disclosure are achieved and realized by the elements and combinations of various elements and the aspects of the following detailed description and the appended claims. The description of this specification is merely exemplary and does not limit the scope or application of the claims of the present disclosure in any way. [Effects of the Invention]

[0016] According to the technology of the present disclosure, it is possible to optimize the dispensing command value when dispensing a minute amount of liquid. Problems, configurations, and effects other than those described above will become apparent from the following description of the embodiment. [Brief explanation of the drawings]

[0017]

Figure 1A

Figure 1B

Figure 2

Figure 3A

Figure 3B

Figure 4

Figure 5

Figure 6A

Figure 6B

Figure 7

Figure 8

Figure 9

Mode for Carrying Out the Invention

[0018] Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. The drawings shown below illustrate specific embodiments in accordance with the present disclosure, but these are for the purpose of understanding the present disclosure and are by no means for limiting the interpretation of the present disclosure.

[0019] [First Embodiment] [Configuration Example of Automatic Analyzer] FIG. 1A is a schematic diagram showing the configuration of a dispensing device 100 of an automatic analyzer according to a first embodiment. The automatic analyzer is a device that automatically analyzes the components of biological samples such as blood and urine. In FIG. 1, the cross-sections of some components of the dispensing device 100 are shown. The dispensing device 100 collects liquid from a sample container and a reagent container (not shown) mounted on the automatic analyzer and dispenses it into a reaction container (not shown). The dispensing device 100 is installed on an automatic stage (driving device, not shown) configured to be drivable in the horizontal direction (XY direction) and the vertical direction (Z direction).

[0020] The dispensing device 100 includes a base 101, a motor 102, a coupling 103, a screw shaft 104, a nut 105, a slider 106, a linear guide 107, a piston 108, a syringe fixing base 109, a syringe 110, a chip removal part 111, a spring member 112, an analysis part 113, a pressure sensor 114, a chip mounting part 115, a seal part 116, an inspection block 117, and a computer 118.

[0021] The base 101 has an L-shaped cross-sectional shape in the YZ plane. A motor 102 (driving device) is provided on the upper part of the base 101. A screw shaft 104 connected to the rotation shaft of the motor 102 via a coupling 103 is rotatably provided on the base 101. As the screw shaft 104, for example, a trapezoidal screw or a ball screw can be used.

[0022] The screw shaft 104 is provided with a slider 106 through which the screw shaft 104 passes and a nut 105 screwed to the screw shaft 104. One end of the slider 106 in the Y direction is connected to a linear guide 107 provided along the Z direction on the base 101, and each of the nut 105 and the slider 106 is movable up and down along the direction of the arrow Z (Z direction) shown in FIG. 1. Further, the other end of the slider 106 in the Y direction is joined to a piston 108 protruding downward and is configured to move up and down without rotating.

[0023] The syringe fixing base 109 is fixed to the lower end of the base 101. A syringe 110 is connected to the syringe fixing base 109. The syringe 110 receives the piston 108 therein. A chip mounting portion 115 is provided at the tip of the syringe 110. The chip mounting portion 115 has a shape that tapers downward. For example, at the start of the analysis operation of the automatic analyzer, an automatic stage that moves the dispensing device 100 is driven, and a chip (not shown) for liquid dispensing is mounted on the chip mounting portion 115.

[0024] Above the chip mounting portion 115, a chip removal portion 111 is provided. The chip removal portion 111 may be a U-shaped notch, or a through hole having a diameter smaller than the diameter of the opening of the chip may be provided. By a spring member 112 connected to the upper end of the chip removal portion 111 and the base 101, the chip removal portion 111 is constantly biased upward and is configured to be movable up and down along the Z direction. As the spring member 112, for example, a spring or the like can be used.

[0025] The piston 108 and the syringe 110 constitute a pipetting mechanism and serve as a pump by the above-described mechanism that moves up and down. In order to function as a pump, a seal component 116 is incorporated between the piston 108 that moves up and down and the syringe 110. The piston 108 has a shape that penetrates the seal component 116, and the piston 108 can slide smoothly, and is sealed so that air does not flow into or out of the inside of the dispensing device 100 during operation.

[0026] When the motor 102 is driven, the slider 106 operates and the piston 108 operates. When the piston 108 operates, the pressure inside the tube of the dispensing device changes. The pressure sensor 114 is connected to the upper part of the chip mounting portion 115 and measures the pressure change inside the tube. Here, "inside the tube" means the space between the piston 108 and the syringe 110, the internal space of the chip mounting portion 115, and the connecting tube between the chip mounting portion 115 and the pressure sensor 114. The pressure sensor 114 may have an A / D converter. The pressure sensor 114 outputs the measured pressure value to the analysis unit 113 in the form of an analog signal or a digital signal.

[0027] The analysis unit 113 (processing device) has a processor and a storage device. The analysis unit 113 stores and analyzes the pressure value measured by the pressure sensor 114 by executing a program stored in the memory, and feeds back a correction command value to the motor 102.

[0028] The inspection block 117 is used when evaluating the performance and state of the sealing components inside the dispensing device 100. The inspection block 117 may be detachable from or fixed to the automatic analysis device. The inspection block 117 has a hole 1171 that fits with the chip mounting portion 115. The inspection block 117 has a mechanical strength such that plastic deformation does not occur due to the fitting of the chip mounting portion 115. In FIG. 1, the inner diameter from the entrance of the hole 1171 to just before the tip is constant, but the inner diameter may become smaller downward. The inner diameter of the tip of the hole 1171 becomes smaller downward, and the tip of the hole 1171 is closed.

[0029] The computer 118 (processing device), although not shown in the figure, is any computer terminal having a processor, a memory, a storage device, a display device, and an input / output device. By executing the program stored in the memory, the processor of the computer 118 controls the operation of the entire automatic analysis device, and particularly controls the driving of the motor 102 and the automatic stage. Note that the analysis unit 113 and the computer 118 may be configured as one computer terminal, or the computer 118 may be configured to be able to realize the functions of the analysis unit 113.

[0030] FIG. 1B is a schematic diagram showing a state in which the chip mounting portion 115 is fitted into the hole 1171 of the inspection block 117. As shown in FIG. 1B, the outer diameter above the tip of the chip mounting portion 115 is substantially equal to the inner diameter of the entrance of the hole 1171, and the inside of the hole 1171 is sealed in the fitting state between the chip mounting portion 115 and the hole 1171.

[0031] Note that instead of attaching the dispensing device 100 to the automatic stage, a driving device may be connected to the base 101 to move it in the horizontal and vertical directions. Alternatively, instead of moving the dispensing device 100, the inspection block 117 may be moved. That is, as long as the relative position between the chip mounting portion 115 and the inspection block 117 can be changed, the configuration of the driving device is not limited.

[0032] <Method for determining usability of dispensing device> FIG. 2 is a flowchart showing a method for determining the usability of the dispensing device 100 and a method for correcting the dispensing command value.

[0033] (Step S200) The dispensing device 100 is in a state of being stopped at the initial position shown in FIG. 1A. For example, when the user inputs an instruction for starting the determination of the usability of the dispensing device 100 via the input device of the computer 118, the computer 118 of the automatic analysis device starts an operation for determining the usability of the dispensing device 100.

[0034] (Step S201) Computer 118 drives the automatic stage, moves the dispensing device 100 above the inspection block 117, and then lowers it to fit the chip mounting part 115 of the dispensing device 100 into the hole 1171 of the inspection block 117. By this fitting, the inside of the tube becomes in a sealed state.

[0035] (Step S202) The analysis unit 113 starts recording the pressure value inside the tube measured by the pressure sensor 114.

[0036] (Step S203) Computer 118 drives the motor 102 and moves the piston 108 in the compression direction (downward) or the suction direction (upward). Thereby, the inside of the tube changes to a positive pressure state or a negative pressure state.

[0037] (Step S204) After moving the piston 108 by an arbitrary amount, computer 118 stops driving the motor 102 to stop the piston 108.

[0038] (Step S205) After a predetermined time has elapsed since the start of recording the pressure value inside the tube, the analysis unit 113 stops recording the pressure value inside the tube. Instead of this step, the analysis unit 113 may measure the pressure value after a predetermined time has elapsed from immediately after the chip mounting part 115 is fitted into the inspection block 117 and the pressure value after a predetermined time has elapsed from immediately after the piston 108 is moved by an arbitrary amount.

[0039] (Step S206) Based on the recorded pressure value inside the tube, the analysis unit 113 determines whether there is an abnormality in the seal component 116 of the dispensing device 100 and determines whether the dispensing device 100 can be used. Details of the determination of whether the dispensing device 100 can be used based on the pressure value will be described later. If it is determined that the dispensing device 100 cannot be used (NG), the process proceeds to step S207. If it is determined that the dispensing device 100 can be used (OK), the process proceeds to step S208.

[0040] (Step S207) The analysis unit 113 transmits a signal indicating that the dispensing device 100 is unusable to the computer 118. The computer 118 generates an error notification screen and causes it to be displayed on the display device. The error notification screen may include a message prompting the user to perform maintenance on the dispensing device 100.

[0041] (Step S208) Based on the recorded pressure value, the analysis unit 113 calculates a correction value for the dispensing command value and corrects the dispensing command value. The dispensing command value is the amount of movement of the piston 108 (the driving amount of the motor 102) for a desired liquid dispensing amount. The analysis unit 113 transmits the corrected dispensing command value to the computer 118. The corrected dispensing command value obtained in this step is used during the dispensing operation in the analysis operation of the automatic analyzer.

[0042] (Step S209) The computer 118 drives the automatic stage, moves the dispensing device 100 upward, and removes the dispensing device 100 from the inspection block 117.

[0043] (Step S210) The computer 118 ends the flow of determining the usability of the dispensing device 100 and correcting the dispensing command value, and proceeds to the analysis operation of the automatic analyzer. The analysis operation of the automatic analyzer can employ a known method.

[0044] <Method for Correcting Dispensing Command Value> FIG. 3A is an example of a dispensing command value map 300a for determining the dispensing command value. The horizontal axis of the dispensing command value map 300a indicates the pressure value Pt in the tube after a predetermined time has elapsed since the start of recording the pressure value. The vertical axis of the dispensing command value map 300a indicates an appropriate dispensing command value calculated in a dispensing amount test described later.

[0045] When a positive pressure is applied inside the dispensing device 100 and the pressure value Pt (step S205) in the tube after a lapse of a predetermined time from the start of recording of the pressure value is P1 (P1 > 0), the appropriate dispensing command value is V1. When the pressure value Pt is P2 (P2 > 0, P1 > P2), the appropriate dispensing command value is V2 (V1 < V2). When a negative pressure is applied inside the dispensing device 100 and the pressure value Pt is P3 (P3 < 0), the appropriate dispensing command value is V1. When the pressure value Pt is P4 (P4 < 0, |P3| > |P4|), the appropriate dispensing command value is V2.

[0046] As described above, when the absolute value of the pressure value Pt is large, the wear or deterioration of the seal component 116 is small, and the difference between the dispensing command value and the actual suction amount and discharge amount becomes small. Therefore, the dispensing command value may be small. On the other hand, when the absolute value of the pressure value Pt is small, the wear or deterioration of the seal component 116 has progressed, and the difference between the dispensing command value and the actual suction amount and discharge amount becomes large. Therefore, it is necessary to increase the dispensing command value.

[0047] FIG. 3B is an example of a dispensing command value map 300b for determining the dispensing command value. Instead of the dispensing command value map 300a shown in FIG. 3A, the dispensing command value may be determined using the dispensing command value map 300b shown in FIG. 3B. The horizontal axis of the dispensing command value map 300b indicates the change amount ΔP of the pressure value in the tube that has changed within a predetermined time from the start of recording of the pressure value.

[0048] When a negative pressure is applied inside the dispensing device 100 and the change amount ΔP of the pressure value in the tube within a predetermined time from the start of recording of the pressure value is P5 (P5 > 0), the appropriate dispensing command value is V3. When the change amount ΔP of the pressure value is P6 (P6 > 0, P5 < P6), the appropriate dispensing command value is V4 (V3 < V4). In this way, when the applied pressure is negative, ΔP shifts toward the atmospheric pressure side, so ΔP > 0. When a positive pressure is applied inside the dispensing device 100 and the change amount ΔP of the pressure value is P7 (P7 < 0), the appropriate dispensing command value is V3. When the change amount ΔP of the pressure value is P8 (P8 < 0, |P7| < |P8|), the appropriate dispensing command value is V4. When the applied pressure is positive, ΔP shifts toward the atmospheric pressure side, so ΔP < 0.

[0049] As described above, when the absolute value of the change amount ΔP of the pressure value is large, the wear or deterioration of the seal component 116 progresses, and the difference between the dispensing command value and the actual suction amount and discharge amount becomes large. Therefore, it is necessary to increase the dispensing command value. On the other hand, when the absolute value of the change amount ΔP of the pressure value is small, the wear or deterioration of the seal component 116 is small, and the difference between the dispensing command value and the actual suction amount and discharge amount becomes small. Therefore, the dispensing command value may be small.

[0050] The dispensing command value maps 300a and 300b may be stored in the storage device of the analysis unit 113, or may be stored in the storage device of the computer 118 and read by the analysis unit 113 communicating with the computer 118.

[0051] The dispensing command value maps 300a and 300b can be created by combining the transition of the pressure value measured under various preset conditions and the results of the dispensing test. More specifically, the dispensing command value maps 300a and 300b can be created as follows. First, the chip mounting portion 115 of the dispensing device 100 is fitted into the hole 1171 of the inspection block 117, and the piston 108 is driven to perform a pressure resistance evaluation of the seal component 116. The pressure resistance evaluation can be performed by either applying a positive pressure (compression of the piston 108) or a negative pressure (suction of the piston 108).

[0052] FIG. 4 is a graph showing the transition waveform 400 of the pressure value when a negative pressure is applied to the inside of the tube in the pressure resistance evaluation. The pressure value P11 at the time of fitting between the chip mounting portion 115 and the inspection block 117 is a positive pressure. After the piston 108 is raised by an arbitrary movement amount (expansion), the pressure value drops to P12 (P12 < 0). When the wear or deterioration of the seal component 116 has not progressed, at the time point T1 when a predetermined time has elapsed since the start of the pressure value measurement, the pressure value may slightly increase to become the pressure value P13, or may remain at the pressure value P12.

[0053] On the other hand, when wear or deterioration of the seal component 116 progresses, the pressure profile 401 indicated by the two-dot chain line may occur. In the pressure profile 401, the pressure value P14 (P14 < 0, P14 > P13) is obtained at the time point T1, and it is changing toward the atmospheric pressure side.

[0054] When wear or deterioration of the seal component 116 further progresses, the pressure profile 402 indicated by the one-dot chain line may occur. In the pressure profile 402, the pressure value at the time point T1 is P15 (P15 < 0, P15 > P14), and it is changing toward the atmospheric pressure side. Thus, when an arbitrary same operation (expansion) is applied to the piston 108 for seal components 116 with different progress states of wear and deterioration, it is possible to utilize the difference in the measured pressure profiles.

[0055] When the seal component 116 cannot sufficiently seal the inside of the dispensing device 100 due to wear or deterioration, when the piston 108 is raised by an arbitrary movement amount as in the pressure profile 402, instead of the pressure value P12 that should originally be obtained, it only decreases to the pressure value P16 (P16 < 0, P16 > P12) higher than the initial movement failure determination value Th1 (Th1 > P12). Also, at the time point T1, the pressure value P15 (P15 < 0) higher than the preset failure determination value Th2 (Th2 > Th1) is obtained. In this case, since the liquid cannot be sucked reproducibly, it is difficult to obtain dispensing reproducibility and it is difficult to solve the problem by correcting the dispensing command value.

[0056] On the other hand, when wear or deterioration of the seal component 116 is slight, the pressure value (P12) when the piston 108 is raised by an arbitrary movement amount is lower than the initial movement failure determination value Th1, and the pressure value (P14) at the time point T1 is lower than the failure determination value Th2, as in the pressure profile 401. In this case, it is possible to cope with it by correcting the dispensing command value. Since the liquid amount during liquid suction decreases from the specified value, and also during liquid discharge, a decrease in the discharged liquid amount and liquid remaining in the tip occur, it is necessary to correct both the suction command value and the discharge command value.

[0057] In this way, by comparing the pressure value when the piston 108 is lifted by an arbitrary amount of movement with the initial movement failure determination value Th1, or by comparing the pressure value at the time point T1 after a predetermined time has elapsed with the failure determination value Th2, it is possible to determine whether the seal component 116 has failed (worn or deteriorated). More specifically, when the initial movement failure determination value Th1 or the failure determination value Th2 is closer to atmospheric pressure than the measured pressure value, it can be determined that the dispensing device 100 can be used. On the other hand, when the measured pressure value is closer to atmospheric pressure than the initial movement failure determination value Th1 or the failure determination value Th2, it can be determined that the dispensing device 100 cannot be used.

[0058] Figure 5 is a graph showing the transition waveform 500 of the pressure value when a positive pressure is applied to the inside of the tube in the pressure resistance evaluation. The pressure value P21 at the time of fitting between the chip mounting portion 115 and the inspection block 117 is a positive pressure. After the piston 108 is lowered by an arbitrary amount of movement (compressed), the pressure value rises to the pressure value P22 (P22 > 0). When the wear or deterioration of the seal component 116 has not progressed, at the time point T1 when a predetermined time has elapsed since the start of measuring the pressure value, the pressure value may slightly decrease to become the pressure value P23, but there are also cases where it remains at the pressure value P22.

[0059] On the other hand, when the wear or deterioration of the seal component 116 is progressing, it may become the pressure profile 501 shown by the two-dot chain line. In the pressure profile 501, at the time point T1, the pressure value becomes P24 (P24 > 0, P24 < P23) and changes toward the atmospheric pressure side.

[0060] When the wear or deterioration of the seal component 116 further progresses, it may become the pressure profile 502 shown by the one-dot chain line. In the pressure profile 502, at the time point T, the pressure value becomes P25 (P25 > 0, P25 < P24) and changes toward the atmospheric pressure side. In this way, similar to when applying a negative pressure, it is possible to utilize the fact that when an arbitrary same operation (compression) is applied by the piston 108 to the seal component 116 with different progress states of wear or deterioration, there are differences in the measured pressure profiles.

[0061] When the seal component 116 cannot sufficiently seal the inside of the dispensing device 100 due to wear or deterioration, as in the pressure profile 502, when the piston 108 is lowered by an arbitrary amount of movement, instead of the pressure value P22 that should originally be obtained, the pressure only rises to a pressure value P26 lower than the initial failure determination value Th3 (Th3 < P22). Also, at time T1, the pressure value P25 (P25 > 0) is lower than the preset failure determination value Th4 (Th4 < Th3). In this case, since the liquid cannot be discharged reproducibly, it becomes difficult to obtain dispensing reproducibility and it is difficult to solve the problem by correcting the dispensing command value.

[0062] On the other hand, when the wear or deterioration of the seal component 116 is slight, as in the pressure profile 501, the pressure value (P22) when the piston 108 is lowered by an arbitrary amount of movement is higher than the initial failure determination value Th3, and the pressure value (P24) at time T1 is higher than the failure determination value Th4. In this case, it is possible to cope with it by correcting the dispensing command value. Since the liquid volume during liquid suction decreases compared to the specified value, and during liquid discharge, a decrease in the discharged liquid volume and liquid remaining in the chip occur, it is necessary to correct the command values for both the suction command value and the discharge command value.

[0063] In this way, by comparing the pressure value when the piston 108 is lowered by an arbitrary amount of movement with the initial failure determination value Th3, or by comparing the pressure value at time T1 after a predetermined time has elapsed with the failure determination value Th4, it is possible to determine whether the seal component 116 has failed (worn or deteriorated). More specifically, when the initial failure determination value Th3 or the failure determination value Th4 is closer to atmospheric pressure than the measured pressure value, it can be determined that the dispensing device 100 can be used. On the other hand, when the measured pressure value is closer to atmospheric pressure than the initial failure determination value Th3 or the failure determination value Th4, it can be determined that the dispensing device 100 cannot be used.

[0064] Next, after the pressure test, a dispensing amount test is performed on the dispensing device 100 equipped with the seal part 116 under wear conditions or deterioration conditions, and the actual dispensing amount with respect to the dispensing command value is tested. As methods for the dispensing amount test, for example, the gravimetric method and the fluorescence amount analysis method can be selected. The gravimetric method is a method of weighing the weight of the liquid before and after dispensing using an analytical balance. The fluorescence amount analysis method is a method of evaluating the liquid volume of the dispensed liquid by measuring the intensity of light using a photometer.

[0065] Hereinafter, a method for calculating a correction value from the results of the dispensing amount test will be described by taking the pressure evaluation shown in FIG. 4 as an example. At time point T1 after a predetermined time has elapsed, the dispensing liquid volume of the dispensing device 100 with the pressure value of P14 is insufficient with respect to the dispensing command value. Based on the shortage amount of the dispensing liquid volume calculated from the dispensing amount test with respect to the dispensing command value, a necessary correction value can be calculated. The sum of the dispensing liquid volume calculated from the dispensing amount test and the correction value becomes an appropriate dispensing command value. By performing the above test on the dispensing device 100 in various wear states and deterioration states and creating an approximate curve from these accumulated data, a dispensing command value map can be obtained.

[0066] <Summary of the First Embodiment> As described above, the dispensing device 100 according to the first embodiment includes a piston 108, a motor 102 (first driving device) that drives the piston 108, a tip mounting portion 115 to which a dispensing tip is attached, a syringe 110 that receives the piston 108, a pressure sensor 114 that measures the pressure inside the syringe 110, an analysis unit 113 and a computer 118 (processing device) that process the detection signal of the pressure measured by the pressure sensor 114, an inspection block 117 having a hole 1171 that can be fitted to the tip mounting portion 115, and an automatic stage (second driving device) that changes the relative position between the syringe 110 and the inspection block 117. The computer 118 drives the automatic stage to fit the tip mounting portion 115 and the hole 1171, seals the inside of the syringe, applies a positive pressure or a negative pressure to the inside of the syringe, and calculates a correction value of the dispensing command value related to the driving amount of the motor 102 based on the pressure inside the syringe.

[0067] In this way, by using the inspection block 117 to seal the inside of the tube and applying pressure, and then measuring the pressure after the pressure application, the sealing state inside the dispensing device 100 can be determined. Also, even when dispensing a small amount of liquid, a small change in pressure can be detected, and the dispensing command value can be optimized. Further, even when the sealing component 116 is worn or deteriorated, when the pressure value has not reached the failure determination values Th2 or Th4 (the failure determination values Th2 or Th4 are closer to the atmospheric pressure), the dispensing device 100 can be determined to be usable, so the maintenance frequency can be reduced, and as a result, the cost can be reduced.

[0068] [Second Embodiment] <Configuration Example of Automatic Analyzer> FIG. 6A is a schematic diagram showing the configuration of an automatic analyzer according to the second embodiment. In the second embodiment, it is different from the first embodiment in that the inspection block 117 is not provided, and instead of the hole 1171 of the inspection block 117, a piercing chip 601 having a shape with a closed inside is used. The configuration of the dispensing device 100 is the same as that of the first embodiment. The piercing chip 601 is held by a piercing chip holding portion 600. The piercing chip 601 is used for the purpose of opening a storage container in which a reagent or the like is sealed with a film or the like. Regarding the dispensing device 100 that does not perform the piercing process, the operation in the first embodiment is effective, and for the dispensing device 100 that performs the piercing process, this embodiment is effective.

[0069] FIG. 6B is a schematic diagram showing a state where the chip mounting portion 115 is fitted to the piercing chip 601. As shown in FIG. 6B, the outer diameter of the tip portion of the chip mounting portion 115 is substantially equal to the inner diameter of the opening of the piercing chip 601, and the inside of the piercing chip 601 is sealed in the fitting state of the chip mounting portion 115 and the piercing chip 601.

[0070] <Method for Determining Usability of Dispensing Device> FIG. 7 is a flowchart showing a method for determining the usability of the dispensing device 100 and a method for correcting the dispensing command value according to the second embodiment.

[0071] (Step S700) The dispensing device 100 is in a stopped state at the initial position shown in FIG. 6A. For example, when the user inputs an instruction for starting the determination of the usability of the dispensing device 100 via the input device of the computer 118, the computer 118 of the automatic analyzer starts an operation for determining the usability of the dispensing device 100.

[0072] (Step S701) The computer 118 drives the automatic stage, moves the dispensing device 100 above the piercing chip holding unit 600, and then lowers it to fit the chip mounting unit 115 of the dispensing device 100 to the piercing chip 601. By the fitting, the inside of the tube becomes airtight.

[0073] (Steps S702 to S708) Steps S702 to S708 are the same as steps S202 to S208 described with reference to FIG. 2 in the first embodiment, and thus the description is omitted.

[0074] (Step S709) The computer 118 ends the flow of determining the usability of the dispensing device 100 and correcting the dispensing command value, and shifts to the analysis operation of the automatic analyzer (the piercing process for the sealed container). The analysis operation of the automatic analyzer can adopt a known method.

[0075] <Summary of the Second Embodiment> As described above, the dispensing device 100 according to the second embodiment does not require the inspection block 117, and it is possible to determine whether the dispensing device 100 can be used at the timing of acquiring the piercing chip 601. In this way, by performing the usability determination before the piercing process and displaying a notification requesting an error or maintenance on the display device in the case of a non-usable state, it is possible to prevent the sealed reagent from being unnecessarily opened. As a result, unnecessary reagent costs can be reduced.

[0076] [Third Embodiment] <Configuration Example of Automatic Analyzer> FIG. 8 is a schematic diagram showing the configuration of the automatic analyzer according to the third embodiment. In the third embodiment, instead of the inspection block 117, an inspection block 800 having a hole 801 with an L-shaped YZ cross section is provided, and a valve 802, a regulator 803, and a pump 804 are connected in this order to an air flow path leading from the hole 801. Other points are the same as those in the first embodiment. The hole 801 has a shape that penetrates the inside of the inspection block 800 in an L-shape. The hole 801 has a shape that fits with the chip mounting portion 115 and has mechanical strength that does not cause plastic deformation due to the fitting. Note that the shape of the hole 801 is not limited to an L-shape, and any shape can be adopted as long as it penetrates the inspection block 800.

[0077] The valve 802 can communicate or block the air circuit between the inspection block 800 and the regulator 803. The pump 804 can generate a positive pressure or a negative pressure and apply it to the inside of the tube. By using the pump 804 in combination with an ejector system or the like, it is also possible to selectively apply a positive pressure or a negative pressure. If the pressure generated by the pump 804 can be controlled, the regulator 803 may not be necessary.

[0078] The operations of the valve 802, the regulator 803, and the pump 804 are controlled by the computer 118.

[0079] In the first and second embodiments, the piston 108 of the dispensing device 100 was operated to be used as a pump. However, in the third embodiment, the pump 804 plays that role. The pump 804 has a performance capable of generating a change amount larger than the change amount of the pressure generated by operating the piston 108. By making the compression state and the expansion state due to the positive pressure or the negative pressure applied in the dispensing device 100 have a large differential pressure with respect to the atmospheric pressure, in addition to being able to shorten the measurement time, the change amount of the pressure can be significantly captured.

[0080] On the other hand, in order to create a large differential pressure with the dispensing device 100 alone, the pump performance is related to the nominal capacity of the dispensing device 100. For example, in order to achieve a high positive pressure application state, it is necessary to push the piston 108 against the repulsive force of the compressed air, and it is necessary to select a high-torque motor 102. Also, in the case of the dispensing device 100 with a small nominal capacity, it may not be possible to create the intended compressed or expanded state of the pressure without ensuring a sufficient stroke of the piston 108. The same can be said for the state where a negative pressure is applied.

[0081] Therefore, it is possible to cope by selecting a high-output torque motor or increasing the nominal capacity. However, the selection of a high-output motor and the increase in the nominal capacity lead to an increase in the device size and also lead to an increase in the air capacity inside the dispensing device 100, resulting in a decrease in the dispensing accuracy. However, although the device size and the dispensing accuracy are in a trade-off relationship with each other, as shown in FIG. 8, by providing the pump 804 in the circuit, it is possible to realize a dispensing device with high dispensing accuracy while maintaining the miniaturization of the dispensing device 100.

[0082] <Method for determining the usability of the dispensing device> FIG. 9 is a flowchart showing a method for determining the usability of the dispensing device 100 and a method for correcting the dispensing command value according to the third embodiment.

[0083] (Step S900) The dispensing device 100 is in a stopped state at its initial position (not shown). For example, when a user inputs an instruction to start the determination of whether the dispensing device 100 can be used via the input device of the computer 118, the computer 118 of the automatic analysis device starts an operation for determining whether the dispensing device 100 can be used.

[0084] (Step S901) The computer 118 drives the automatic stage, moves the dispensing device 100 above the inspection block 800, and then lowers it to fit the tip mounting portion 115 of the dispensing device 100 into the hole 801 (the state shown in FIG. 8). Due to the fitting, the inside of the tube becomes airtight. In the present embodiment, "inside the tube" means the space between the piston 108 and the syringe 110, the internal space of the tip mounting portion 115, the connecting tube between the tip mounting portion 115 and the pressure sensor 114, and the connecting tube from the hole 801 to the pump 804.

[0085] At this time, the hole 801, the valve 802, the regulator 803, and the pump 804 of the inspection block 800 are in communication, and the valve 802 is in an open state. The regulator 803 is set to an arbitrary pressure value, and the pressure value applied to the inside of the tube is preset.

[0086] (Step S902) Step S902 is the same as step S202 described with reference to FIG. 2 in the first embodiment.

[0087] (Step S903) The computer 118 drives the pump 804 to apply either positive pressure or negative pressure to the inside of the tube.

[0088] (Step S904) The computer 118 drives the valve 802 to change it from the open state to the closed state.

[0089] (Steps S905 to S910) Steps S905 to S910 are the same as steps S205 to S210 described with reference to FIG. 2 in the first embodiment, and thus the description thereof is omitted.

[0090] <Summary of the Third Embodiment> As described above, when determining whether the dispensing device 100 according to the third embodiment can be used, the inspection block 800 connected to the pump 804 is used to increase or decrease the pressure in the pipe by the pump 804. As a result, compared with the case where the pressure in the pipe is increased or decreased by the operation of the piston 108, the differential pressure with respect to the atmospheric pressure can be increased. As a result, in addition to being able to shorten the measurement time, the amount of change in pressure can be significantly captured.

[0091] [Modification Example] The present disclosure is not limited to the above-described embodiments and includes various modification examples. For example, the above-described embodiments have been described in detail for easy understanding of the present disclosure, and it is not necessary to include all the configurations described. Also, a part of one embodiment can be replaced with the configuration of another embodiment. Also, the configuration of another embodiment can be added to the configuration of one embodiment. Also, a part of the configuration of each embodiment can be added, deleted, or replaced with a part of the configuration of another embodiment.

Description of Reference Numerals

[0092] 100: Dispensing device 101: Base 102: Motor 103: Coupling 104: Screw shaft 105: Nut 106: Slider 107: Linear guide 108: Piston 109: Syringe fixing base 110: Syringe 111: Chip removal part 112: Spring material 113: Analysis unit 114: Pressure sensor 115: Chip mounting part 116: Sealing part 117: Inspection block 118: Computer 601: Piercing chip 800: Inspection block 801: Hole 802: Valve 803: Regulator 804: Pump

Claims

1. A dispensing device configured to be able to dispense a liquid, comprising: a piston; a first driving device for driving the piston; a syringe having a tip mounting portion to which a dispensing tip is attached and for receiving the piston; a pressure sensor for measuring the pressure inside the syringe; a processing device for processing a detection signal of the pressure measured by the pressure sensor; a block having a hole that can be fitted to the tip mounting portion; a second driving device for changing the relative position between the syringe and the block, wherein the processing device: drives the second driving device to fit the tip mounting portion and the hole, and seals the inside of the syringe; applies a positive pressure or a negative pressure inside the syringe; calculates a correction value for a dispensing command value related to the driving amount of the first driving device based on the pressure inside the syringe after a predetermined time has elapsed since the application of the positive pressure or the negative pressure; and calculates the correction value using a dispensing command value map showing the relationship between the pressure and the dispensing command value for obtaining a desired dispensing amount.

2. In claim 1, wherein the processing device: determines whether the dispensing device can be used based on the pressure after a predetermined time has elapsed since the application of the positive pressure or the negative pressure; when it can be used, calculates the correction value, and when it cannot be used, outputs an error to an output device.

3. In claim 2, wherein the processing device: determines that the dispensing device cannot be used when the pressure after a predetermined time has elapsed since the application of the positive pressure or the negative pressure is a value closer to atmospheric pressure than a predetermined threshold value.

4. In claim 1, wherein the processing device applies a positive pressure or a negative pressure inside the syringe by driving the first driving device to drive the piston.

5. In claim 1, wherein one end of the hole is open and the other end is closed.

6. In claim 1, wherein the block is a piercing tip holding portion for holding a piercing tip with a closed bottom, and the hole is the piercing tip.

7. In claim 1, further comprising a pump connected to the hole, wherein the processing device: applies a positive pressure or a negative pressure inside the syringe by driving the pump.

8. A dispensing method executed by a processing device of a dispensing device, The dispensing device is a first driving device that drives a piston, a syringe that receives the piston, and a second driving device that changes the relative position between a block having a hole that can be fitted to the tip mounting portion of the syringe, The method is by the processing device, driving the second driving device to fit the tip mounting portion and the hole to seal the inside of the syringe, applying a positive pressure or a negative pressure inside the syringe, calculating a correction value of a dispensing command value related to the driving amount of the first driving device based on the pressure inside the syringe after a predetermined time has elapsed from the application of the positive pressure or the negative pressure, measured by a pressure sensor of the dispensing device, including In calculating the correction value, the correction value is calculated by the processing device using a dispensing command value map showing the relationship between the pressure and the dispensing command value for obtaining a desired dispensing amount. A dispensing method characterized by this.

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