JP2009210351A - Liquid sample dispensing device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a liquid sample dispensing device can dispense accurately a necessary amount of liquid sample into each reaction container. <P>SOLUTION: This liquid sample dispensing device for dispensing the liquid sample held by a dispensing nozzle as much as each prescribed amount into a plurality of reaction containers is equipped with a discharge operation storage part for storing data related to operation during discharge operation of an actuator for dispensation; a normal discharge operation storage part for storing data related to operation during normal discharge operation of the actuator for dispensation; and a discharge operation determination part for calculating an evaluation function based on the data related to the operation during the discharge operation of the actuator for dispensation stored in the discharge operation storage part and on the data related to the operation during the normal discharge operation of the actuator for dispensation stored in the normal discharge operation storage part, and determining existence of an abnormality of the liquid sample dispensing device based on the calculation result. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a liquid sample dispensing apparatus that dispenses a required amount of a liquid sample into a reaction container with high accuracy, for example.

  In the fluid handler and method for processing the fluid of Conventional Example 1, the tip of the nozzle is moved below the surface of the fluid to be processed, the pump fluidly coupled to the nozzle is operated, and the fluid is moved into the nozzle. The combined pressure transducer is activated to monitor the pressure in the nozzle, the pressure transducer is used to continuously monitor the pressure in the nozzle during pump operation, and the fluid movement into the nozzle is expected. Fluid handler and method that can inform an automated medical analyzer operator when an incorrect amount of sample and / or fluid is used in a particular medical test (See, for example, Patent Document 1).

  FIG. 15 illustrates one embodiment of the fluid handler 110. The illustrated embodiment 110 includes a nozzle 112 having a tip 114 connected via a conduit 116 to a pump 118 driven by a prime mover 120. A pressure transducer 122 having a sensor 124 is fluidly connected to the conduit 116 between the nozzle 112 and the pump 118. The nozzle 112 can be movably supported by a gantry (not shown) so that it can move toward and away from the container 126 holding a fluid 128 having a fluid surface 130. The nozzle 112, conduit 116, and pump 118 contain a liquid 132, such as distilled water or buffer, that facilitates the suction and discharge of the fluid 128. Therefore, the pressure conversion device 122 is arranged along the liquid 132. In order to control and monitor the operation of the fluid handler 110, the pressure transducer 122 is electrically connected to the operable electronic device 134, which is electrically connected to the controller 136. The controller 136 is electrically connected to the prime mover 120 of the pump 118 so that the pump 118 and the operable electronic device 134 can operate in harmony.

  The nozzle 112 is a rigid suction probe. The probe has a tip with an inner diameter of about 0.04 inches and a length of about 7 inches, and an inner diameter of about 0.014 inches and a length of about 0.278 inches. In this configuration, conduit 116 is comprised of a low compliance polymer, such as TEFZEL tubing (commercially available from Du Pont Co., Wilmington, Del.) Having an inner diameter of about 0.063 inches. Where it is desirable to minimize the attenuation of transient pressure fluctuations, particularly the axial length of the conduit 116 between the nozzle 112 and the pressure transducer 122 should be minimized or as short as possible. The pressure transducer 122 may be TransPac IV manufactured by Abbott Laboratories, Salt Lake City, Utah. In general, the pressure transducer 122 should be able to detect a sudden transient pressure change at least in the range of about −2 psig to about 6 psig, and in particular, has an overpressure capability of up to about 100 psig so that the nozzle 112 can be effectively cleaned. Should have. The pressure transducer 122 should have a fast response time up to about 10 kHz. The pressure transducer 122 monitors the pressure in the conduit 116 substantially continuously (in one embodiment, at least about 1000 times per second), thereby monitoring the transient pressure in the conduit 116 and providing unintended suction and discharge. It can be shown immediately. Pump 118 is a syringe pump such as Cavro 3000 (Cavro Scientific Instruments Inc., Sunnyvale, Calif.).

  A desired suction and discharge profile will be described. When suctioning about 50 μl and about 40 μl of porcine serum, the analog pressure signal from the sensor 124 was sampled almost continuously at a rate of about 1000 samples / second, and the fluid 128 was aspirated and dispensed. Both were stored as numerically filtered numerical data representing the instantaneous pressure profile detected by the sensor 124. The results of repeating this experiment five times are shown in FIG. 16A (five suctions) and FIG. 16B (five discharges). These figures demonstrate the repeatability of the pressure sensing method. Pressure spikes immediately before and after suction and discharge were intentionally imposed on the data to facilitate the extraction and display of pressure during actual suction and discharge. From this it can be seen that the instantaneous pressure profile derived from the data obtained by the sensor 124 is compared with a predetermined pressure profile to conclude whether the performed fluid treatment operation is the intended operation.

  The suction and discharge contrary to the intended purpose will be described. The aspiration of porcine serum was prevented by removing the container 126 from the nozzle 112 during approximately 50 μl aspiration, allowing air to be partially aspirated. Therefore, partial discharge of air is included in the discharge portion of the suction / discharge cycle. An instantaneous pressure profile of suction and discharge contrary to the expected five times was generated. This profile is shown in FIG. 17A (five suctions) and FIG. 17B (five discharges). At the time of aspiration contrary to the intended purpose, various amounts of air were aspirated.

  The pressure profile data was filtered using a Butterworth filter. This is a 31 coefficient digital low-pass filter with a cutoff frequency of about 0.01 times the sampling frequency (ie about 10 Hz). The results of this filtering are shown in FIG. 18A (five desired aspirations and discharges contrary to the five expected times) and FIG. 18B (five desired discharges and discharges contrary to the five expected values). . The intended suction and discharge can be clearly distinguished from the intended suction and discharge profiles.

  As described above, the fluid handler and method for processing the fluid of the conventional example 1 determines abnormality by monitoring the pressure profile at the time of suction / discharge by the sensor provided in the pressure conversion device fluidly coupled to the nozzle. be able to.

  The automatic continuous random access analysis system and its components of Conventional Example 2 have an apparatus and method that can simultaneously perform multiple tests on liquid samples using different test methods, and enable continuous random access. Automatic sequential random access analysis system that performs multiple different tests on the same or different samples during the same time, as well as an automatic random access system that can perform multiple tests on multiple liquid samples simultaneously A method of operation is provided (see, for example, Patent Document 2).

  19 and 20 show isometric views of the apparatus for the automatic immunoassay analysis system of Conventional Example 2. FIG. The system configuration diagram of FIG. 19 shows a system device used by a technician, and FIG. 20 shows an isometric view of the frame and cabinet with component parts removed. The system device 202 has an exposed front end carousel 204 that is operated by a first transport dispensing mechanism 206 that kits scheduled tests with the specimen into the reaction vessel. The system includes a computer screen 208 and a computer keyboard 210 along with an access panel 212 for accessing the storage and disposal compartments. The system device 202 includes a roller 214 for moving it within the laboratory premises as needed. Since the system is completely self-contained with the exception of power requirements, the system unit 202 is free to move through the rollers 214.

  Referring to FIG. 20, a system unit 202 cabinet frame 216 is shown with almost all functional components of the system unit removed. Unlike the front-end carousel 204, the controlled environment zone 218 is sealed during operation with light blocked and tightly controlled air flow and temperature. The front end carousel 204 communicates with the control environment zone 218 via the transfer port 220. The front end carousel 204 is attached to an aluminum base plate located on the support base 222 and the first transfer dispensing mechanism is attached on the means 224.

  Referring to FIG. 21, a plan view of the system apparatus 202 partially shows a part of the cabinet frame 216 and the front end carousel 204 virtually. This portion of the cabinet 216 also supports a power source 392, a supply bottle 396, a solid waste container 398, and a liquid waste container 400. Supply bottle 396 provides a buffer for the ongoing test, and containers 398 and 400 store treated waste.

  Referring to FIGS. 22A and 22B, the components of the system device are shown in more detail with relative positional relationships to illustrate the processing flow of the functional component system device. For example, the specimen cup 226 is mounted on a specimen cup carousel 228 that is concentrically fitted within the front end carousel 204 along with the reagent pack carousel 232 and the reaction vessel carousel 236. The reagent pack carousel 232 is fitted concentrically between the specimen cup carousel 228 and the reaction vessel carousel 236. The reagent pack carousel holds the reagent pack 230, and the reaction vessel carousel 236 holds the reaction vessel 234. The three front-end carousels, namely the sample cup carousel 228, the reagent cup carousel 232, and the reaction vessel carousel 236, can include, for example, the following capabilities. Specimen cup carousel 228 can hold 60 blood collection tubes, such as a Vacutainer blood collection tube, or 90 specimen cups injection molded as one piece, and can include an independent base. The independent platform is suitable for technicians to hold specimens and dispense them into specimen cups. The reagent pack carousel 232 can comprise 20 different reagent packs 230. The reaction vessel carousel 236 can include 90 reaction vessels 234.

  The front end carousel 204 has an operable bar code reader 238 that automatically identifies the reagent pack carousel 232 and the specimen carousel 228. A cleaning cup 240 is provided in the first transfer dispensing mechanism 206 to perform cleaning as needed between the transfer of various specimens and reagents. The first transfer dispensing mechanism 206 is used in kitting various reagent pack liquid materials and specimens into the reaction vessel 234. Reagents and specimens are suitably kitted via means of the first transfer dispensing mechanism 206 including pump means. The various carousels are rotated and aligned for kitting at the dispensing station. The kitted reaction vessel 234 is positioned by the reaction vessel carousel 236 in a position suitable for transfer to the transfer station 242. The reaction vessel 234 is transferred to the transfer station 242 via transfer means. The transfer station 242 then rotates and moves the reaction vessel to the process carousel 246.

  As shown in the figure, the processing carousel 246 is driven by a step motor and operated by the second transfer dispensing mechanism 250. The treatment carousel 246 is supported by two wheels to control the height and the irregularly shaped carousel 246 to control the height and the radial movement provided by the irregularly shaped carousel elements Is done. The system equipment is also used up to the processing carousel 246 in the fluorescence polarization immunoassay (FPIA) procedure. The processing carousel 246 includes an FPIA processing unit 252 and an FPIA processing lamp 254 for reading the FPIA analysis of the kitted and properly reacted reagent specimen directly from the reaction vessel 234. The treated carousel 246 holds, for example, 36 reaction vessels 234 and has a carousel diameter of about 12.5 inches (31.75 cm). The processing carousel 246 moves the reaction vessel 234 between the transfer station 242, the second transfer dispensing mechanism 250, the dispensing point, and the FPIA reading processor 252. The control environment zone 218 includes a transfer station 242 and a processing carousel 246, and performs FPIA processing by air circulation under temperature control by an in-cabinet air circulation fan 256. A cleaning cup 258 for the second transfer dispensing mechanism 250 is provided. The second transfer pipette 250 is used to add (dispense) reagents to the specimen in the FPIA test plan reaction vessel 234 for FPIA treatment according to incubation and timing conditions.

  In a microenzyme immunoassay (MEIA) process, a second transfer pipette 250 is used to add reagents to the specimen before adding the reaction mixture to the MEIA cartridge 268 mounted on an auxiliary carousel 264, also called a cartridge wheel carousel. You can also The specimen mixed with the MEIA reagent is transferred to the MEIA cartridge 268 by the second transfer pipette 250. The second transfer pipette 250 moves the pipette probe between the wells in the reaction vessel 234 on the processing carousel 246, moves to the MEIA cartridge 268 on the auxiliary carousel 264, and moves to the wash cup 258. A rack-and-pinion drive mechanism with a two-axis step motor drive performs strict drive on both the R-axis and the Z-axis. For example, travel on the Z axis is about 3 inches (7.62 cm) and about 4.5 inches or 5.0 inches (11.43 cm or 12.7 cm) on the R axis.

  The auxiliary carousel 264 holds, for example, 32 MEIA cartridges 268 and is approximately 9.5 inches (24.13 cm) in diameter. The auxiliary carousel 264 moves the MEIA cartridge 268 between various stations, including the second transfer dispenser mechanism dispensing point, the MUP discharge station 272, the MEIA cleaning station 270, the MEIA reader 274, and the MEIA cartridge discharge point 262. . The auxiliary carousel 264 is driven by a step motor and has one wheel located at the Z-axis height control mechanism at the cartridge insertion point, a second wheel at the dispensing point, and a third wheel at the MEIA reader. The auxiliary carousel 264 is thereby maintained within the desired positional relationship for these various functions.

  The MEIA cartridge 268 is loaded into a cartridge hopper 690 that feeds the MEIA cartridge 268 into the auxiliary carousel 264. Automatic feeding of the MEIA cartridge 268 is performed by adjusting the height of the cartridge 268 to the auxiliary carousel 264 as required for MEIA reading. The cartridge hopper 690 sends individual cartridges 268 to the auxiliary carousel 264 and changes the orientation axis of the cartridges 268 from horizontal to vertical by automatic means. Removal of the MEIA cartridge 268 is accomplished by using an ejector 262 that operates through a discharge rod to push the MEIA cartridge 268 out of the auxiliary carousel 264 and drop it into the solid waste container 400. The auxiliary carousel 264 is further operated by a MEIA buffer heater dispenser 270, a MUP heater dispenser probe 272, and a MEIA reader 274. The MEIA cartridge 268 is removed from the auxiliary carousel 264 by the cartridge injector 262 after the MEIA reading is complete.

  FIG. 23 presents a plan view of the isolated cuts of the drive and guide system elements of the main carousel 204 with the various carousels removed. In FIG. 23, the specimen cup carousel step motor 276 is shown as being attached by a mounting spring 278. A reagent pack carousel motor 280 is also shown with a mounting spring 282. The reaction vessel carousel motor 284 and mounting spring 286 are positioned on the outside of the two inner carousels, namely the specimen cup carousel 228 and the reagent pack carousel 232. Roller guides 288 are provided for specimen cup carousel 228 and tension spring 290. The reagent pack carousel includes a roller guide 292 and a pulling means 294. The reaction vessel roller guide 296 also includes a spring element 298, the purpose of this guide and these various spring elements is to maintain very limited tracking of the concentric carousel when moved by separate stepper motors. It is.

Operation control for the system 202 is performed by 22 step motors of various dimensions. Here, the specifications and operation of a stepper motor that identifies some of these motors are outlined below. All stepper motors are permanent magnet motors with 200 full steps per axis rotation equal to 1.8 ° per step. The single step motor control system comprises:
(1) Step motor connected to the mechanism to move the mechanism as needed (2) Apply voltage to the step motor, and the motor responds to three control signals from the control electronics, ie "indexer" (3) An indexer provided with an electronic device that controls a motor by the driving device. The indexer determines a movement profile including a rotation direction parameter, a movement step number parameter, an acceleration parameter, and a speed parameter.
(4) The home sensor is used for each step motor. The home sensor is used as a position reference by the indexer and can also be used by the indexer to check for errors.
(5) The encoder is used by the rotating device, carousel and transport mechanism to verify whether the movement is correct. At the end of the movement, the encoder count is checked to verify that the motor has moved to the correct position.

  A system macro processor (CPU) is used to determine the travel distance, speed, and acceleration of the step motor. The system microprocessor sends information to the indexer that controls the movement. At the end of the move, the indexer notifies the system microprocessor (CPU) that the move is complete. The system microprocessor (CPU) then checks the encoder to verify the movement of the rotating mechanism if it is moved, and the indexer to verify that no errors were detected.

Thus, the automatic continuous random access analysis system of Conventional Example 2 and its components are:
After the motor moves, the encoder count can be checked to verify that the motor has moved to the correct position.
JP 2002-139506 A (p. 23, 24, FIGS. 1, 4 to 6) JP 2003-156498 A (pages 73 to 75, FIGS. 1 to 5)

  However, in Conventional Example 1, dispensing abnormality is detected by monitoring the pressure profile at the time of suction / discharge by a sensor provided in a pressure conversion device fluidly coupled to the nozzle, but the pressure sensor has a response time. However, there is a problem that determination of dispensing abnormality is delayed because of a long time and variations in sensitivity. In the conventional example 2, the encoder count is inspected after the movement of the motor, and it is verified that the motor has moved to the correct position. However, the motor speed profile is not managed and the movement amount of the motor is the same. Even so, the maximum speed, acceleration, and deceleration may be different, and there is a problem that it is not known whether or not dispensing has been performed normally.

  The present invention has been made in view of such problems, and includes a discharge operation storage unit that stores operation-related data during a discharge operation of the dispensing actuator, and a normal discharge operation of the dispensing actuator. A normal discharge operation storage unit that stores operation-related data in the operation, data related to operation during the discharge operation of the dispensing actuator stored in the discharge operation storage unit, and the normal discharge operation storage unit stored in the normal discharge operation storage unit A liquid sample dispensing device that calculates an evaluation function based on operation-related data during normal discharge operation of a dispensing actuator and determines whether the liquid sample dispensing device is abnormal based on a calculation result of the evaluation function The purpose is to provide.

In order to solve the above problem, the present invention is configured as follows.
The invention according to claim 1 is a dispensing nozzle for sucking and holding a liquid sample, a syringe composed of a cylinder and a plunger for generating suction / discharge pressure of the liquid sample, a flexible tube for flowing the liquid sample, A dispensing actuator that performs suction and discharge of a liquid sample from the dispensing nozzle via the syringe and the flexible tube, a dispensing actuator driving unit that drives the dispensing actuator, and the dispensing In the liquid sample dispensing apparatus, comprising a dispensing actuator control unit for controlling the actuator driving unit, and dispensing a predetermined amount of the liquid sample held by the dispensing nozzle into a plurality of reaction containers. A discharge operation storage unit for storing operation-related data during the discharge operation of the actuator, and the dispensing actuator A normal discharge operation storage unit for storing operation-related data at the time of normal discharge operation, an operation-related data at the time of discharge operation of the dispensing actuator stored in the discharge operation storage unit, and the normal discharge operation storage unit Discharge that calculates an evaluation function based on the stored operation-related data during the normal discharge operation of the dispensing actuator, and determines whether the liquid sample dispensing apparatus is abnormal based on the calculation result of the evaluation function An operation determination unit is provided.

  According to a second aspect of the present invention, operation-related data during the normal discharge operation is prepared in accordance with a dispensing condition, the operation-related data during the dispensing operation of the dispensing actuator and the dispensing actuator An evaluation function is calculated based on operation-related data during normal ejection, and the liquid sample dispensing device is determined to be abnormal by comparing the calculation result of the evaluation function with a predetermined threshold value. It is.

  According to a third aspect of the present invention, the operation-related data during the discharge operation of the dispensing actuator selectively uses the speed, acceleration, and thrust during a plurality of discharge operations.

  According to a fourth aspect of the present invention, when the discharge operation determination unit determines that there is an abnormality in the liquid sample dispensing device, a difference from each operation command of operation-related data during the discharge operation of the dispensing actuator Is calculated, and an operation command correction unit is provided in which each operation command and the difference are added as a new operation command.

  According to the first aspect of the present invention, a discharge operation storage unit that stores operation-related data during the discharge operation of the dispensing actuator, and operation-related data during a normal discharge operation of the dispensing actuator are stored. Normal discharge operation storage unit, operation-related data stored in the discharge operation storage unit during the discharge operation, and normal discharge of the dispensing actuator stored in the normal discharge operation storage unit An evaluation function is calculated based on operation-related data during operation, and includes a discharge operation determination unit that determines whether there is an abnormality in the dispensing actuator based on the calculation result of the evaluation function, and the calculation result of the evaluation function And the predetermined threshold value can be accurately determined whether or not the liquid sample dispensing apparatus is abnormal.

  According to the second aspect of the present invention, since the operation-related data during the normal discharge operation is prepared according to the dispensing conditions, the presence or absence of abnormality of the liquid sample dispensing apparatus can be accurately determined under any dispensing condition. Can be determined.

  According to a third aspect of the present invention, liquid-related sample dispensing is performed by selectively using speed, acceleration, and thrust during a plurality of discharge operations as operation-related data during the discharge operation of the dispensing actuator. It is possible to accurately determine whether there is an abnormality in the apparatus.

  According to the fourth aspect of the present invention, when the discharge operation determination unit determines that there is an abnormality in the liquid sample dispensing apparatus, each operation command of operation-related data during the discharge operation of the dispensing actuator By calculating the difference and adding each operation command and the difference as a new operation command, the operation when the liquid sample dispensing apparatus is abnormal can be corrected.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

  FIG. 1 is a diagram showing a configuration of a liquid sample dispensing apparatus according to a first embodiment of the present invention. 1 is a liquid sample dispensing device, 2 is a dispensing nozzle for sucking and holding a liquid sample, 3 is a flexible tube made of a material such as urethane or fluorocarbon resin, and 4 is a syringe composed of a cylinder and a plunger. , 5 is a cylinder, 6 is a plunger that discharges and sucks a liquid sample in the syringe, 7 is a dispensing actuator (for example, a linear motor), 8 is a dispensing actuator drive unit that drives the dispensing actuator, and 9 is Dispensing actuator control unit for controlling the dispensing actuator drive unit, 10 is a CPU in the dispensing actuator control unit, 11 is a discharge amount for the stroke of the plunger 6 in the syringe 4 in the dispensing actuator control unit And a discharge condition storage unit that stores the number of discharges after aspiration of a liquid sample. Discharge operation storage unit that stores data in time series, 13 is normal discharge operation storage that stores operation-related data during normal discharge operation of the dispensing actuator in time series, and 14 is in the discharge operation storage unit. An evaluation function is calculated based on the operation-related data during the discharge operation of the dispensing actuator stored in series and the operation-related data during the normal discharge operation, and the liquid sample is calculated based on the calculation result of the evaluation function A discharge operation determination unit that determines whether there is an abnormality in the dispensing apparatus, 15 is a liquid sample container that supplies a liquid sample, 16 is a reaction container that discharges the liquid sample, and 17 is a liquid sample.

  The dispensing nozzle 2 is hollow and is shaped so that the inner diameter becomes smaller toward the tip. The dispensing nozzle 2 is held in a posture perpendicular to the liquid sample 17, sucks the liquid sample 17 contained in the liquid sample container 15, and discharges the liquid sample 17 to the reaction container 16. Although not shown, the dispensing nozzle 2 sucks and discharges the cleaning water in the cleaning water container. Various general methods can be employed as a cleaning water supply method and a suction / discharge method.

  The cylinder 5 changes its volume in the syringe 4 as the plunger 6 moves. The cylinder 4 is connected to the dispensing nozzle 2 via the flexible tube 3. The plunger 6 moves upward on the surface of the syringe 4 so that the liquid sample 17 is sucked and the volume in the syringe 4 is increased, and the plunger 6 is discharged from the syringe 4 so that the volume in the syringe 4 is reduced by discharging the liquid sample 14. Move down the page. The plunger 6 is driven by a dispensing actuator 7 and is controlled by a dispensing actuator drive unit 8. The dispensing actuator drive unit 8 is connected to the dispensing actuator control unit 9 and drives the dispensing actuator 7 based on the operation command. The dispensing actuator control unit 9 includes a CPU 10 and a discharge condition storage unit 11, and commands an operation command to the dispensing actuator drive unit 8 to discharge a predetermined liquid sample 17. The CPU 10 inputs the required dispensing amount and dispensing order based on the number of samples and a desired analysis item that are input in advance by an operator or read from the identification mark displayed on the liquid sample container 15 or the like. The dispensing actuator drive unit 8 is commanded to correspond to the above. In addition, the discharge condition storage unit 11 includes a stroke, pressure, nozzle diameter, discharge speed, liquid sample inhalation amount, air inhalation amount, discharge amount, the number of discharges after the liquid sample is sucked, and a suction-discharge operation pattern at the time of discharge. The relationship between the maximum suction speed, the suction acceleration / deceleration time, the maximum discharge speed, and the discharge acceleration / deceleration time is stored.

  Next, the operation of this embodiment will be described with reference to FIGS. FIG. 2 is a diagram illustrating a flow of the actuator control unit, and FIG. 3 is a diagram illustrating a suction state of the nozzle.

According to the procedure shown below, the liquid sample inhalation amount with respect to the discharge amount with good discharge accuracy is confirmed in advance by experiments. When the internal pressure is in a normal state where it does not decrease due to bubbles or the like, the fluid mass conservation law (inflow mass flow rate (density x flow velocity x cross-sectional area) and outflow flow rate (density x flow velocity x cross-sectional area) are equal) If it is established and the flow velocity at the tip of the nozzle is equal to or higher than the liquid running speed, the liquid can be discharged without causing a liquid pool. Therefore, if the internal pressure is kept in a normal state, for example, the maximum speed, acceleration, and deceleration, which are plunger operation patterns (trapezoid pattern), are fixed, and the air intake amount is a constant value, the plunger stroke in the syringe, liquid The relationship between the sample inhalation amount, the ejection amount, and the number of ejections after the liquid sample is aspirated is confirmed and summarized as shown in the table of FIG.
(1) First, the liquid sample inhalation amount is stored (F0).
The liquid sample suction amount with respect to the discharge amount measured in advance is stored in the discharge amount storage unit.
(2) Aspirate the washing water (F1).
When the plunger 6 in the syringe 4 is sucked and driven by the actuator 7, the cleaning water 18 in a cleaning water container (not shown) is sucked from the nozzle 2. Alternatively, cleaning water may be supplied to the flexible tube and the nozzle 2 from a pump (not shown) via a valve (not shown) and another flexible tube (not shown).
(3) Suction air (F2).
The actuator 6 sucks and drives the plunger 6 in the syringe 4 and sucks a certain amount of air 19 from the nozzle 2 into the syringe 4.
(4) Aspirate the liquid sample (F3).
The plunger 6 in the syringe 4 is sucked and driven by the actuator 7, and the liquid sample 17 in the liquid sample container 15 is sucked from the nozzle 2 based on the liquid sample suction amount stored in advance.
(5) Discharge the liquid sample (F4)
In order to eliminate the influence of the initial meniscus at the nozzle tip, the actuator 7 is driven to discharge from the plunger 6 in the syringe 4 by the thrust command to the actuator 7 based on the discharge operation pattern stored in advance, and the discharge not shown from the nozzle 2 is performed. The liquid sample 17 is discharged into the container or the liquid sample container 15 for the number of times stored in advance.
(6) Discharge the liquid sample (F5).
The actuator 7 is driven to discharge from the plunger 6 in the syringe 4 by the thrust command to the actuator 7 based on the discharge operation pattern, and the liquid sample 17 is discharged from the nozzle 2 to the reaction container 16.
(7) Repeat (2) to (6) for each discharge.

As described above, since the liquid sample inhalation amount with respect to the ejection amount and the number of ejections after the liquid sample aspiration are stored in advance and the liquid sample is ejected, both the CV value and the accuracy can be ejected with high accuracy.
When the average value of the discharge amount when discharging a predetermined number of times is σ, the standard deviation of the discharge amount when discharging a predetermined number of times is μ, and the target value of the discharge amount is α, the CV value and accuracy are They can be calculated by the equations (1) and (2), respectively.

In addition, it is assumed that the operator prepares the liquid sample container 15 and the reaction container 16 under the nozzle 2, but the control unit 9 is synchronized with the actuator 7 and the nozzle 2 or the liquid sample container 15 and the reaction container (not shown). The table or the like on which 16 is mounted may be controlled to automatically suck and discharge the liquid sample.
In this embodiment, the discharge condition storage unit 11 is provided in the dispensing actuator control unit 9, but the discharge condition storage unit 11 may be provided in the dispensing actuator drive unit 8, or the dispensing actuator drive unit 8 The dispensing actuator driving unit 9 and the discharge condition storage unit 11 may be integrated.

  Next, a method for determining abnormal operation of the dispensing actuator will be described.

  FIG. 5 is a processing flow diagram of abnormality detection of the dispensing actuator according to the embodiment of the present invention.

The operation-related data during the dispensing operation of the dispensing actuator is obtained from a storage unit inside the servo amplifier provided in the dispensing actuator drive unit 8 (not shown).
First, operation-related data at the time of the discharge operation of the dispensing actuator that changes for each discharge operation is read one by one, and these operation-related data are acquired (G1). The discharge operation storage unit 12 stores operation-related data during the discharge operation of the dispensing actuator that changes for each discharge operation. Further, the normal discharge operation storage unit 13 stores operation-related data during the normal discharge operation of the dispensing actuator.
As an example, FIG. 6 shows a response speed waveform during normal discharge operation and a response speed waveform when clogging occurs in a tube or the like. FIG. 7 shows the thrust command waveform during normal discharge operation and the thrust command waveform when clogging occurs in the tube or the like. From the figure, it can be seen that the profiles are different for both the response speed waveform and the thrust command waveform.

Next, the discharge operation determination unit 14 calculates an evaluation function based on the acquired data (G2). The evaluation function J represents the area of the difference between the profile of the response speed V _dn during the discharge operation and the profile of the response speed V _rn during the normal discharge operation as δS, and the area of the profile of the response speed V _rn during the normal discharge operation as S. , the maximum response speed V _rmax and δV the difference between the maximum response speed V _dmax during discharge operation, V _rmax maximum response speed in the case of normal ejection operation in the normal discharge operation, and the maximum thrust command F _r in the normal discharge operation When the difference from the maximum thrust command F _d during the discharge operation is δF, the maximum thrust command during the normal discharge operation is F _r , the data sampling time is δT, and the number of data is N, the following formulas (3) to ( Calculate in step 8).

Here, a, b, and c are weighted,

It is. The weights a, b, and c may be changed according to items that place emphasis on monitoring, and can be set by the manufacturer using input means inside a discharge operation determination unit (not shown). Moreover, you may make a user set from the input means of the liquid sample dispensing apparatus which is not shown in figure.

  The evaluation function J when the liquid sample dispensing device operates normally is a value near 0, but if it is abnormal, the evaluation function is a value larger than 0. Using this, the discharge operation determination unit 14 determines normality / abnormality of the liquid sample dispensing device by threshold determination (G3). For example, it is determined that the evaluation function J is less than 0.1 is normal and 0.1 or more is abnormal. The threshold value is not necessarily limited to 0.1. Based on an operation test in advance, the area of deviation between the response speed profile during multiple discharge operations and the response speed profile during normal discharge operations, and the maximum response during multiple discharge operations It is necessary to check the difference between the speed and the maximum response speed during normal discharge operation, and the difference between the maximum thrust command during multiple discharge operations and the maximum thrust command during normal discharge operations, and determine the threshold. .

  A method for acquiring operation-related data of the liquid sample dispensing apparatus will be described.

  FIG. 8 shows a data acquisition method related to the operation of the liquid sample dispensing apparatus, and is a diagram showing a response speed acquisition method as an example. Data of k points are taken from the data waveform related to the operation changing every moment as shown in FIG.

  The acquisition location of the data related to the operation of the liquid sample dispensing device may be the sample suction section, the sample discharge section, and all sections of the sample suction section and the sample discharge section.

  The interval at which data related to the operation of the liquid sample dispensing device is taken may be constant or variable. It may be possible to narrow the capture interval at a location where an abnormality of the liquid sample dispensing apparatus is likely to occur, or to capture data roughly at a location where there is almost no abnormality.

  As a method for acquiring k-point time-series data groups, the method of obtaining only k-point data by preliminarily specifying the capture time of each point is initially acquired as finely as possible and thinned out to obtain k-point data. Either method of leaving data is acceptable.

  Data related to the operation of the liquid sample dispensing apparatus acquired as described above is summarized as shown in FIG.

  If the operation-related data at the time of the normal ejection operation of the liquid sample dispensing device is acquired in the above operation, the operation-related data of the liquid sample dispensing device serving as a reference can be acquired. FIG. 10 summarizes data related to operation of the liquid sample dispensing apparatus obtained when normal dispensing is performed n times.

  The evaluation function J is calculated based on these data, and the presence / absence of an operation abnormality such as occurrence of clogging in the tube of the liquid sample dispensing device is determined based on the magnitude relationship between the calculation result and a predetermined threshold value.

  As described above, in this embodiment, the evaluation function is calculated based on the data of the liquid sample dispensing device, and it is possible to determine whether there is an abnormal operation of the liquid sample dispensing device.

  The present invention is different from Patent Document 1 and Patent Document 2 in that a discharge operation storage unit that stores operation-related data during the discharge operation of the dispensing actuator, and an operation-related data during the normal discharge operation of the dispensing actuator. Normal discharge operation storage unit for storing data, operation-related data during the discharge operation of the dispensing actuator stored in the discharge operation storage unit, and normal discharge operation of the dispensing actuator stored in the normal discharge operation storage unit It is to provide a liquid sample dispensing device that calculates an evaluation function based on motion-related data at the time and determines whether or not there is an abnormality in the liquid sample dispensing device based on the calculation result of the evaluation function.

Since the configuration of the present embodiment is the same as that of the first embodiment, description thereof is omitted.
In the present embodiment, the number and method of fetching operation-related data during the dispensing operation of the dispensing actuator is changed for each dispensing amount, and each of the dispensing amounts is provided. Since the minimum, maximum dispensing volume, and dispensing resolution are determined according to the specifications of the liquid sample dispensing device, it is necessary to have operation-related data and evaluation functions during the dispensing operation of that number of dispensing actuators. Good.

  FIG. 11 summarizes the data related to the operation of the actuator for dispensing obtained when normal dispensing is performed n times. The dispensing amount is 1, the dispensing amount is 2, the dispensing amount is 3, and so on. -Prepared for each dispensing amount X.

  When dispensing a certain dispensed amount, an evaluation function of the dispensed amount is calculated, and by comparing the magnitude relationship between the calculation result of the evaluation function and a predetermined threshold, the liquid sample dispensing device It is possible to determine an abnormal operation such as a tube clogging.

  As described above, in this embodiment, for each dispensing amount, an evaluation function is calculated based on operation-related data during the dispensing operation of the dispensing actuator, and the calculation result of the evaluation function is compared with a predetermined threshold value. By doing so, it is possible to determine the presence or absence of abnormal operation of the liquid sample dispensing apparatus.

Since the configuration of the present embodiment is the same as that of the first embodiment, description thereof is omitted.
FIG. 12 summarizes each data of the speed, acceleration, and thrust command of the actuator for dispensing obtained when normal dispensing is performed n times. This is prepared for each of the dispensing amounts 3,...
Expression (7) of the evaluation function J is a relational expression between the response speed and the thrust command, but the evaluation function is a relational expression between the acceleration and the thrust command, a relational expression between the response speed and the acceleration, and a relation between the response speed, the acceleration, and the thrust command. It may be an expression. Further, position deviation, speed deviation, and the like, which are data related to the operation of the dispensing actuator, may be included in the evaluation function.

  Then, when dispensing a certain dispensed amount, an evaluation function of the dispensed amount is calculated, and a liquid sample dispensing is performed by comparing the magnitude relationship between the calculation result of the evaluation function and a predetermined threshold value. It is possible to determine whether there is an abnormal operation of the apparatus.

  Thus, in this embodiment, the operation-related data during the dispensing operation of the dispensing actuator selectively uses the speed, acceleration, and thrust during the multiple dispensing operations, so that the liquid sample dispensing device It is possible to determine whether there is an abnormal operation.

  FIG. 13 is a diagram showing a configuration of a liquid sample dispensing apparatus according to the fourth embodiment of the present invention. In the configuration of the first embodiment, when it is determined that the dispensing actuator is abnormal, the difference between each operation command of the operation-related data during the discharge operation of the dispensing actuator is calculated, and each operation command and the difference are calculated. An operation command correction unit 20 is added in which a new operation command is added.

  FIG. 14 is a diagram illustrating a flow of the operation command correction unit. A discharge operation storage unit that stores operation-related data during the discharge operation of the dispensing actuator, an operation-related data during the discharge operation of the dispensing actuator, and the normal discharge stored in the discharge operation storage unit An evaluation function is calculated from operation-related data during normal discharge operation of the dispensing actuator stored in the operation storage unit, the calculation result of the evaluation function is compared with a predetermined threshold value, Note: In addition to determining whether the device is abnormal, for example, if it is determined that the speed is abnormal, a new maximum speed command = current maximum speed command + (current maximum speed command−current maximum response speed) is set. If the operation of the dispensing actuator is not improved even with this setting, it is determined as abnormal, and the abnormality is presented to the user by a presentation means such as visual, auditory, or tactile sensation (not shown).

  As described above, in this embodiment, when the discharge condition determination unit determines that there is an abnormality in the liquid sample dispensing apparatus, the difference between each operation command of the operation-related data during the discharge operation of the dispensing actuator is calculated. By adding each operation command and the difference as a new operation command, the operation when the dispensing actuator is abnormal can be corrected.

In addition, a discharge operation storage unit that stores operation-related data during the discharge operation of the dispensing actuator, a normal discharge operation storage unit that stores operation-related data during the normal discharge operation of the dispensing actuator, and a discharge operation The evaluation function is calculated based on the operation-related data during the dispensing operation stored in the storage unit and the operation-related data during the dispensing operation stored in the normal dispensing operation storage unit. And since the presence or absence of abnormality of the said liquid sample dispensing apparatus can be determined based on the calculation result of the said evaluation function, it can apply not only to a liquid sample dispensing apparatus but to other apparatuses.

The figure which shows the structure of the liquid sample dispensing apparatus of the 1st Embodiment of this invention. The flowchart which shows operation | movement of the control part in the 1st Embodiment of this invention. Sectional drawing which shows the suction state of the nozzle of FIG. The table | surface which shows the relationship of the stroke of the plunger in the syringe of the 1st Embodiment of this invention, the liquid sample suction | inhalation amount, discharge amount, and the frequency | count of discharge after liquid sample suction. Processing flow chart of abnormality detection of the dispensing actuator of the first embodiment of the present invention The figure which shows the waveform of the response speed at the time of normal discharge operation | movement of the 1st Embodiment of this invention, and the waveform of the response speed when clogging occurs in a tube The figure which shows the waveform of the thrust command at the time of normal discharge operation of the 1st Embodiment of this invention, and the waveform of the thrust command when clogging arises in a tube etc. This shows how to acquire time-series data groups related to the operation of dispensing actuators, and shows an example of response speed acquisition method. Table showing time-series data related to dispensing actuator operation The figure which summarizes each time series data group related to operation of the actuator for dispensing obtained when normal dispensing is performed n times, and shows a reference space of n events and k items The data related to the operation of the actuator for dispensing obtained when the normal dispensing of the second embodiment of the present invention is performed n times is summarized. The dispensing amount is 1, the dispensing amount is 2, Table prepared for each dispensing volume 3 ..., dispensing volume X The data of the speed and acceleration of the actuator for dispensing obtained when normal dispensing of the third embodiment of the present invention is performed n times is summarized. Dispensing amount 3, ..., table prepared for each dispensing amount X The figure which shows the structure of the liquid sample dispensing apparatus of the 4th Embodiment of this invention. The figure which shows the flow of the operation command correction | amendment part of the 4th Embodiment of this invention. The figure which shows the schematic of the fluid handler of embodiment of the prior art example 1 The figure which shows the data obtained at the time of the expected operation | movement of the fluid handler of embodiment of the prior art example 1 The figure which shows the data obtained at the time of operation | movement contrary to the expectation of the fluid handler of embodiment of the prior art example 1 The figure which shows the data after filtering obtained at the time of operation | movement of the fluid handler of embodiment of the prior art example 1 The figure which shows the isometric view of the automatic analysis system which shows the system cabinet of the embodiment of the prior art example 2, the exposed front end carousel, the computer screen, and a keyboard The figure which shows the isometric view of the flame | frame and cabinet of the automatic analysis system apparatus of Embodiment of the prior art example 2 19 and 20 showing a cross-sectional plan view of the lower cabinet of FIG. 19 and FIG. 20 showing the water and / or buffer supply system of the automatic analysis system of the embodiment of the prior art 2 and the container for liquid and solid waste. The figure of the automatic analysis system from which the component cover was removed in order to show the automatic analysis system apparatus of Embodiment of the prior art example 2 in detail by relative position Separation sectional plan view of drive element and guide element of front-end carousel of detached automatic analysis system of embodiment of conventional example 2

Explanation of symbols

1 Liquid sample dispenser
2 Dispensing nozzle
3 Flexible tube
4 syringe
5 cylinders
6 Plunger
7 Dispensing actuator
8 Actuator actuator for dispensing
9 Dispensing actuator controller
10 CPU
11 Discharge condition storage
12 Discharge operation memory
13 Normal discharge operation memory
14 Discharge operation judgment unit
15 Liquid sample container
16 reaction vessel
17 Liquid sample
18 Wash water
19 Air
20 Operation command correction unit
110 Liquid handler
112 nozzles
114 Nozzle tip
116 conduit
118 pump
120 prime mover
122 Pressure transducer
124 sensors
126 containers
128 fluids
130 Fluid surface
132 liquid
134 Electronics
136 Controller
202 System unit
204 Front-end carousel
206 First transfer dispensing mechanism
208 computer screen
210 Computer keyboard
212 Access panel
214 Laura
216 cabinet frame
218 Control environment zone
220 Transfer port
222 Support stand
224 First transfer dispensing mechanism means
226 specimen cup
228 Specimen Cup Carousel
230 Reagent pack
232 Reagent Pack Carousel
234 reaction vessel
236 reaction vessel carousel
238 Bar code reader
240 wash cups
242 Transfer station
246 Processing carousel
250 Second transfer dispensing mechanism
252 FPIA processing unit
254 FPIA treatment lamp
258 Wash cup for second transfer dispensing mechanism
262 MEIA cartridge discharge point
264 Auxiliary carousel
268 MEIA cartridge
270 MEIA cleaning station
272 MUP Dispensing Station
273 MEIA reader
276 Specimen Cup Carousel Step Motor
278 Mounting spring
280 Reagent Pack Carousel Motor
282 Mounting spring
284 Reaction vessel carousel motor
286 Mounting spring
288 Roller guide
290 Tension spring
292 Roller Guide
294 Tensioning means
296 Reaction Container Roller Guide
298 Spring element
392 power supply
396 supply bottle
398 Solid waste container
400 Liquid waste container
690 cartridge hopper

Claims (4)

A dispensing nozzle for sucking and holding a liquid sample, a syringe composed of a cylinder and a plunger for generating a suction and discharge pressure for the liquid sample, a flexible tube for flowing the liquid sample, and the syringe for sucking and discharging the liquid sample And a dispensing actuator to be implemented from the dispensing nozzle through the flexible tube, a dispensing actuator driving unit for driving the dispensing actuator, and a dispensing actuator for controlling the dispensing actuator driving unit In a liquid sample dispensing apparatus that includes an actuator control unit, and dispenses the liquid sample held by the dispensing nozzle into a plurality of reaction containers by a predetermined amount,
A discharge operation storage unit for storing operation-related data during the discharge operation of the dispensing actuator;
A normal discharge operation storage unit for storing operation-related data at the time of normal discharge operation of the dispensing actuator;
Operation-related data at the time of discharge operation of the dispensing actuator stored in the discharge operation storage unit and operation-related data at the time of normal discharge operation of the dispensing actuator stored in the normal discharge operation storage unit A liquid sample dispensing apparatus comprising: an ejection operation determination unit that calculates an evaluation function based on the evaluation function and determines whether or not the liquid sample dispensing apparatus is abnormal based on a calculation result of the evaluation function.   Operation-related data at the time of the normal discharge operation is prepared according to a dispensing condition, operation-related data at the time of the discharge operation of the dispensing actuator, and operation-related data at the time of normal discharge of the dispensing actuator, An evaluation function is calculated based on the evaluation function, and the presence or absence of abnormality of the liquid sample dispensing device is determined by comparing a calculation result of the evaluation function with a predetermined threshold value. 1. A liquid sample dispensing apparatus according to 1.   2. The liquid sample dispensing apparatus according to claim 1, wherein the operation-related data during the discharge operation of the dispensing actuator selectively uses speed, acceleration, and thrust during a plurality of discharge operations.   When the discharge operation determination unit determines that there is an abnormality in the liquid sample dispensing device, it calculates a difference between each operation command of operation-related data during the discharge operation of the dispensing actuator, The liquid sample dispensing apparatus according to claim 1, further comprising an operation command correction unit that uses a sum of the differences as a new operation command.