JP3728484B2 - Pipetting method and pipetting device - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a pipetting method for detecting an insufficient discharge amount of a liquid to be transported in a pipetting operation for sucking the liquid to be transported in a container and discharging it at a desired position, and pipetting employing the pipetting method. about the equipment.
[0002]
[Prior art]
When liquids such as human or animal serum, blood, urine, or various liquids to be transported, such as drugs, cleaning liquids, and adhesives, are sucked from a container and discharged at a predetermined position, the discharge amount of the liquid to be transported is a predetermined amount It is extremely important that For example, when a pipetting device is incorporated in a clinical testing device, an insufficient discharge amount of a liquid sample as a transported liquid may cause a test result to be incorrect.
[0003]
Therefore, in the conventional pipetting device, when sucking the liquid to be transported, it is determined whether or not normal suction has been performed by monitoring the pressure change in the nozzle pipe. That is, when the suction is normally performed, the discharge amount is determined on the premise that a predetermined amount of the liquid to be transported is sucked and therefore a predetermined amount of the liquid to be transported is discharged.
[0004]
However, in the above-described conventional pipetting device, it was determined that a predetermined amount of the liquid to be transported was discharged when the transported liquid was normally sucked. It was not possible to detect a shortage of the discharge amount due to this. In addition, even if it is determined that the liquid to be transported has not been sucked normally, but it has been judged that it has been performed normally, a shortage of discharge will occur. However, such a shortage of discharge can also be detected. There wasn't. That is, the shortage of the suction amount occurs when the film or bubble position of the liquid to be transported in the container is erroneously detected as the liquid surface position or the viscosity of the liquid to be transported is very high. It is not always possible to detect these completely by monitoring the pressure change in the inside, and erroneous detection may occur for some reason.
[0005]
DISCLOSURE OF THE INVENTION
The present invention, which was conceived under the circumstances described above, pipetting method that can reliably detect the discharge amount shortage of the conveyed liquid, and provides adopted pipetting equipment the pipetting method The task is to do.
[0006]
In order to solve the above problems, the present invention takes the following technical means.
[0007]
According to the first aspect of the present invention, a pump that communicates with the nozzle and sucks and discharges the liquid to be transported from the nozzle opening, and a pressure detection that detects the pressure of the air flow path between the pump and the nozzle opening. A suction step of sucking a predetermined amount of liquid to be transported from the nozzle opening and a discharge step of discharging the liquid to be transported sucked in the suction step from the nozzle opening. A pipetting method to be executed, wherein a change in pressure in an air flow path between a pump and an opening of a nozzle is detected based on an output signal from a pressure detection means in a discharge process, and is conveyed based on the change in pressure. thereby determining the ejection amount of the liquid, this pressure of the air flow path between the opening of the pump and the nozzle is less than the predetermined value, it is determined that the discharge amount of the transported liquid does not reach the predetermined value Wherein the pipetting method is provided.
[0008]
According to this pipetting method, in the discharge process, the pressure change in the air flow path between the pump and the nozzle opening is detected based on the output signal from the pressure detection means, and the liquid to be transported based on the pressure change. Therefore, it is possible to reliably detect an insufficient discharge amount of the transported liquid. In other words, if the discharge amount of the liquid to be transported is insufficient, the time of pressure drop in the air flow path between the pump and the nozzle opening is advanced in the discharge process, so by detecting the pressure drop, Insufficient liquid discharge can be reliably detected. In addition, when the discharge amount of the liquid to be transported is insufficient, all of the liquid to be transported is spread, and this reduces the pressure of the air flow path between the pump and the nozzle opening. Thus, it is possible to detect the shortage of the discharge amount.
[0009]
Accordingly, since a predetermined amount of liquid to be transported can be supplied accurately, for example, when used in a clinical testing apparatus, it is possible to eliminate an error in test results due to insufficient sample amount at the time of spotting and trouble of retesting.
[0010]
According to the second aspect of the present invention, a pump that communicates with the nozzle and sucks and discharges the liquid to be transported from the opening of the nozzle, and a drive device that relatively moves the nozzle and the container containing the liquid to be transported. A pressure detection means for detecting the pressure of the air flow path between the pump and the nozzle opening, and a control device for controlling the pump and the drive device by receiving an output signal from the pressure detection means. A pipetting device that sucks a predetermined amount of the liquid to be transported in the container from the opening of the nozzle and discharges the sucked liquid to be transported from the opening of the nozzle by controlling the pump and the driving device by the control device. When the sucked liquid is discharged from the nozzle opening, the pressure change in the air flow path between the pump and the nozzle opening is detected based on the output signal from the pressure detection means. Thereby determining the ejection amount of the transported liquid on the basis of the pressure variation, if the pressure of the air flow path is less than a predetermined value between the aperture of the said pump nozzle, the discharge amount of the object to be conveyed liquid is predetermined A pipetting device is provided that is configured to determine that the value has not been reached .
[0011]
According to this pipetting device, since the pipetting method of the present invention is adopted, the effects of the method can be enjoyed.
[0012]
The nozzle and the pump may be connected directly or via a connector and may be arranged close to each other, or may be connected via a flexible tube so as to be movable relative to each other. The entire nozzle may be configured integrally or may be configured by connecting a plurality of components. The nozzle opening is generally formed at the tip of the nozzle, but may be formed at other positions. The pump may be, for example, a syringe pump including a cylinder and a pulse motor that reciprocally moves a plunger of the cylinder, or may be another type of pump.
[0013]
Examples of liquids to be transported include liquid samples such as serum, blood, and urine, but of course, the liquid is not limited to these, and any kind of liquid may be used, such as reagents, cleaning agents, and adhesives. Good.
[0014]
The drive device that relatively moves the nozzle and the container containing the liquid to be transported may be composed of, for example, a rack and pinion mechanism and an electric motor, or may be another mechanism. Moreover, when moving a nozzle, the structure which moves only a nozzle may be sufficient and the structure which moves a nozzle and a pump integrally may be sufficient.
[0015]
The pressure detecting means for detecting the pressure of the air flow path between the pump and the nozzle opening may be directly installed in the air flow path, or may be a pump, a nozzle, or a connecting tool for connecting the pump and the nozzle. You may be comprised so that it may connect to an air flow path through the conduit | pipe extended from the flexible tube. The pressure detecting means may be a combination of a diaphragm and a semiconductor strain detecting element, for example, or may be of another configuration.
[0016]
The control device can be realized by a microcomputer or a personal computer, for example.
[0017]
According to a preferred embodiment, the liquid to be transported is a liquid sample to be spotted on the reagent pad, and the control device discharges the sucked liquid sample from the nozzle opening to the reagent pad. If the pressure of the air flow path between the pump and the nozzle opening at a predetermined time after the driving is completed and before the nozzle opening is separated from the reagent pad is less than a predetermined value, the discharge amount of the liquid sample is It is determined that the predetermined value has not been reached.
[0018]
That is, when the discharge amount of the liquid sample is normal, the air flow path between the pump and the nozzle opening is maintained while the liquid sample is spread on the reagent pad after the driving of the pump for discharge is completed. The pressure of the air flow path between the pump and the nozzle opening is relieved as the nozzle rises and the nozzle opening moves away from the reagent pad. However, if the discharge amount of the liquid sample is insufficient, all of the liquid sample is spread on the reagent pad before driving the pump for discharging and raising the nozzle. Since the pressure of the air flow path between the nozzle and the nozzle opening decreases, it is possible to detect the shortage of the discharge amount by the decrease in the pressure. The timing for detecting the pressure of the air flow path between the pump and the nozzle opening and the value of the detected pressure for determining that the discharge amount is insufficient are appropriately determined based on the allowable range of the discharge amount error of the liquid sample. That's fine.
[0024]
Other features and advantages of the present invention will become more apparent from the detailed description given below with reference to the accompanying drawings.
[0025]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, preferred embodiments of the present invention will be specifically described with reference to the drawings.
[0026]
FIG. 1 is an external perspective view showing an example of a sample inspection apparatus provided with a pipetting device according to the present invention. The sample inspection device 1 is a case 2 in which a pipetting device 3 described later is incorporated. An opening 5 that can be opened and closed by a lid 4 is provided on the front surface of the housing 2. The lid 4 includes a touch panel type display device 6 that also serves as an operation switch on the front surface in the opened state, and has a function as an operation panel of the sample inspection device 1. The housing 2 is provided with a slide table 7 that is slidable in the direction of arrow a so as to move from a position in front of the opening 5 of the housing 2 to the back of the housing 2. On the upper surface of the slide table 7, a holder 9 for standing up and holding a plurality of containers 8 containing a liquid sample as an example of a transported liquid to be inspected, and a plurality of reagent pads 10 for inspecting the liquid sample. And a measuring device (not shown) for measuring a change in color after the liquid sample is spotted on the reagent pad 10. The lid 4 is provided with a printer 11 that prints out test results and the like adjacent to the display device 6.
[0027]
In this sample inspection device 1, for example, serum is used as a liquid sample, and when this serum is spotted on the reagent pad 10 by the operation of the pipetting device 3, it is then monochromatic with respect to the reagent pad 10 via an optical fiber. After irradiating light, the reflected light is read by a photodiode. Then, the measurement data is analyzed using a known method, and various components in the serum are displayed on the display screen of the display device 6 or printed out on a recording paper using the printer 11.
[0028]
FIG. 2 is a schematic overall configuration diagram of the pipetting device 3, and the nozzle 21 includes a nozzle body 22 and a nozzle tip 23. That is, the nozzle tip 23 is made of resin, and is attached to the small diameter portion of the tip of the nozzle body 22 so as to be freely inserted and removed, and the tip is open. A syringe pump 25 is connected to the end of the nozzle body 22 opposite to the nozzle tip 23 side via a joint pipe 24. The syringe pump 25 includes a cylinder 26, a plunger 27 that moves in the cylinder 26, and a pulse motor 28 that reciprocates the plunger 27. Note that a mechanism for converting the rotational motion of the output shaft of the pulse motor 28 into the linear motion of the plunger 27 is well known, and the description thereof is omitted. The nozzle 21 and the syringe pump 25 are mounted on a moving table (not shown) driven by an electric motor 29 via a rack / pinion mechanism or a belt / pulley mechanism, and are orthogonal to the vertical direction and the arrow a direction in FIG. It is configured to be movable in the horizontal direction. A branch pipe 30 is branched from a joint pipe 24 connecting the nozzle 21 and the syringe pump 25, and a pressure sensor 31 is connected to the branch pipe 30.
[0029]
The movement of the nozzle 21 and the syringe pump 25, that is, the driving of the electric motor 29, and the driving of the syringe pump 25, that is, the driving of the pulse motor 28 are controlled by the control device 32. The control device 32 includes a CPU 33, a ROM 34, a RAM 35, and an input / output interface 36. The input / output interface 36 includes a pulse motor 28, an electric motor 29, a pressure sensor 31, an operation unit 37, a display unit 38, and printing. Part 39 is connected. The operation unit 37 and the display unit 38 are configured by the display device 6 of FIG. 1, and the printing unit 39 is configured by the printer 11 of FIG.
[0030]
The pulse motor 28 is controlled by the control device 32 and moves the plunger 27 of the syringe pump 25 to cause the nozzle 21 to suck and discharge the liquid sample in the container 8 or to suck and discharge air. . The electric motor 29 is controlled by the control device 32 to move the nozzle 21 and the syringe pump 25 up and down and move horizontally, so that the tip opening of the nozzle tip 23 is immersed in the liquid sample in the container 8 or the reagent pad 10 shown in FIG. Or touch it. The pressure sensor 31 includes, for example, a diaphragm and a semiconductor strain detection element, detects the pressure of the air flow path between the syringe pump 25 and the opening of the nozzle 21, and outputs an analog signal having a voltage corresponding to the pressure. The control device 32 controls the entire sample inspection device 1. The CPU 33 operates based on a program stored in the ROM 34 in advance, and controls the pulse motor 28, the electric motor 29, the display unit 38, the printing unit 39, and the like based on signals from the pressure sensor 31, the operation unit 37, and the like. Output data. The ROM 34 stores programs, predetermined data, and the like. The RAM 35 is backed up by a battery (not shown) and stores various data. The input / output interface 36 controls transmission / reception of signals between the CPU 33 and an external device, such as analog / digital conversion, serial / parallel conversion, or timing control. The operation unit 37 supplies a command signal corresponding to a touch operation on the display screen of the display device 6 (FIG. 1) by the user to the control device 32. The display unit 38 is controlled by the control device 32 to display various characters or graphics on the display screen of the display device 6 (FIG. 1). The printing unit 39 is controlled by the control device 32 to print out analysis results and the like on recording paper. This printing unit 39 is actually the printer 11 of FIG.
[0031]
That is, the syringe pump 25 constitutes a pump that communicates with the nozzle 21 and sucks and discharges the liquid sample from the opening of the nozzle 21. The electric motor 29 constitutes a part of a drive device that moves the nozzle 21. The pressure sensor 31 constitutes a pressure detection means for detecting the pressure of the air flow path between the syringe pump 25 and the opening of the nozzle 21. The control device 32 constitutes a control device that receives the output signal from the pressure sensor 31 and controls the pulse motor 28 and the electric motor 29. The ROM 34 performs a suction program for executing a suction process for sucking a predetermined amount of liquid sample from the opening of the nozzle 21, a discharge program for executing a discharge process for discharging the liquid sample sucked in the suction process from the opening of the nozzle 21, and a discharge In the process, discharge in which the pressure change of the air flow path between the syringe pump 25 and the opening of the nozzle 21 is detected based on an output signal from the pressure sensor 31, and the discharge amount of the liquid sample is determined based on the pressure change. A storage medium in which a program including a quantity determination program is stored is configured.
[0032]
The sample inspection apparatus 1 sucks a predetermined amount of the liquid sample in the container 8 with the nozzle 21, deposits the liquid sample on the reagent pad 10, and a serum component that is a liquid sample by changing the color of the reagent pad 10. The analysis is performed, and all of these are automatically performed under the control of the control device 32. Of such control operations by the control device 32, the procedure of the discharge process including the step of determining whether the discharge amount of the liquid sample is insufficient will be described with reference to the flowchart shown in FIG.
[0033]
Now, it is assumed that the liquid sample is sucked into the nozzle tip 23, and the tip opening of the nozzle tip 23 exists at a predetermined height just above the reagent pad 10 in FIG. First, the CPU 33 controls the pulse motor 28 to move the plunger 27 of the syringe pump 25 to the discharge side, and slightly discharges a liquid sample from the tip opening of the nozzle tip 23 to form a liquid ball (S1). Further, the CPU 33 controls the electric motor 29 to lower the nozzle 21 and the syringe pump 25 and bring the tip opening of the nozzle chip 23 into contact with the surface of the reagent pad 10 (S2). Thereby, the liquid ball of the liquid sample formed in the vicinity of the tip opening of the nozzle tip 23 is spread on the reagent pad 10. Then, the CPU 33 controls the pulse motor 28 to move the plunger 27 of the syringe pump 25 to the discharge side, and discharges a small amount of the liquid sample remaining in the nozzle tip 23 from the tip opening of the nozzle tip 23 (S3). Then, the CPU 33 sets a timer for measuring a predetermined time (S4), and determines whether or not the timer has expired (S5). That is, since a certain amount of time is required for the discharged liquid sample to be spread on the reagent pad 10, the apparatus waits for a predetermined time in a state where the tip opening of the nozzle chip 23 is in contact with the surface of the reagent pad 10.
[0034]
If the timer expires (S5: YES), the CPU 33 monitors the output signal from the pressure sensor 31 to determine whether or not the pressure detected by the pressure sensor 31 is equal to or greater than a predetermined value ( S6). That is, when the discharge amount of the liquid sample is normal, after the driving of the syringe pump 25 for discharge is completed, the syringe pump 25 and the nozzle chip 23 are not fully loaded until the liquid sample is sufficiently spread on the reagent pad 10. The pressure does not escape from the air flow path between the tip opening and the pressure remains elevated, and the nozzle 21 is raised and the tip opening of the nozzle tip 23 is separated from the surface of the reagent pad 10 to release the pressure. Thus, the pressure of the air flow path between the syringe pump 25 and the tip opening of the nozzle tip 23 decreases. However, when the discharge amount of the liquid sample is insufficient, almost no liquid sample remains in the nozzle tip 23 at the stage of liquid ball formation, and the drive of the syringe pump 25 for discharge is completed and the nozzle 21 is raised. All of the liquid sample is spread on the reagent pad 10 until it is discharged, and this reduces the pressure of the air flow path between the syringe pump 25 and the tip opening of the nozzle tip 23. We are trying to detect the lack of quantity.
[0035]
If the pressure detected by the pressure sensor 31 is equal to or higher than the predetermined value (S6: YES), the discharge amount of the liquid sample is normal, and the CPU 33 sets the flag F to 1 (S7). The flag F is stored in the RAM 35. And CPU33 controls the electric motor 29 and raises the nozzle 21 and the syringe pump 25 to a predetermined position (S8). Then, the CPU 33 determines whether or not the flag F is 1 (S9). If the flag F is 1 (S9: YES), it means that the liquid sample has been ejected normally, and thus this routine ends. .
[0036]
In S9, if the flag F is not 1 (S9: NO), it means that the flag F is 0 and the discharge amount of the liquid sample is insufficient. Therefore, the CPU 33 has insufficient discharge amount on the display screen of the display device 6. The occurrence is displayed (S10), and this routine is terminated. Of course, in this case, the reflectance of the reagent pad 10 is not measured, and the fact that the liquid sample is insufficiently discharged is recorded in the inspection result printed out by the printer 11.
[0037]
In S6, if the pressure detected by the pressure sensor 31 is not equal to or greater than a predetermined value (S6: NO), it means that the discharge amount is insufficient, so the CPU 33 sets the flag F to 0 (S11), Proceed to S8. That is, whether or not the discharge amount is insufficient is stored according to the contents of the flag F.
[0038]
In S5, if the timer has not expired (S5: NO), the process returns to S5 and waits until the timer expires.
[0039]
4 and 5 are explanatory diagrams of the output waveform of the pressure sensor 31 and its differential waveform in the detected pressure determination step of S6. In FIG. 4, a solid line 41 represents an output waveform of the pressure sensor 31 when the discharge amount of the liquid sample is a predetermined amount, and a solid line 42 represents a differential waveform of an output of the pressure sensor 31 when the discharge amount of the liquid sample is a predetermined amount. Yes. In FIG. 5, the solid line 43 indicates the output waveform of the pressure sensor 31 when the discharge amount of the liquid sample is less than a predetermined amount, and the solid line 44 indicates the derivative of the output of the pressure sensor 31 when the discharge amount of the liquid sample is less than the predetermined amount. Represents a waveform.
[0040]
In FIG. 4, the timing at which the nozzle 21 starts to rise after the liquid sample is discharged is indicated by 41a and 42a. The detected pressure is clearly higher before the timing 41a and 42a. This is because when the liquid sample discharged from the tip opening of the nozzle tip 23 has a predetermined amount, it takes time for the liquid sample to be spread on the reagent pad 10, and the tip opening of the nozzle tip 23 is blocked. This is because the pressure detected by the pressure sensor 31 does not decrease until the nozzle 21 starts to rise and the tip opening of the nozzle tip 23 is separated from the surface of the reagent pad 10. On the other hand, in FIG. 5, the timing at which the nozzle 21 starts to rise after the liquid sample is discharged is indicated by 43a and 44a, but the detected pressure rises almost before the timings 43a and 44a. I can't. This is because when the liquid sample discharged from the tip opening of the nozzle tip 23 is less than a predetermined amount, there is almost no liquid sample remaining in the nozzle tip 23 at the time of formation of the liquid ball, and the liquid sample is applied to the reagent pad 10. This is because the extended time becomes extremely short, so that even if the plunger 27 of the syringe pump 25 is moved to the discharge side, the tip opening of the nozzle tip 23 is not closed, and the pressure detected by the pressure sensor 31 does not increase. Therefore, at any point in time from when the liquid sample remaining in the nozzle tip 23 is discharged by bringing the tip opening of the nozzle tip 23 into contact with the surface of the reagent pad 10 and when the nozzle 21 is raised, the pressure sensor By determining whether or not the detected pressure by 31 is equal to or greater than a predetermined value, it is possible to accurately detect the shortage of the discharge amount. 4 and 5, 41 b, 42 b, 43 b, and 44 b indicate the time points when the liquid sample remaining in the nozzle chip 23 is discharged by bringing the tip opening of the nozzle chip 23 into contact with the surface of the reagent pad 10. The reference numerals 41c, 42c, 43c, and 44c respectively indicate the time points at which the liquid sample is formed.
[Brief description of the drawings]
FIG. 1 is an external perspective view showing an example of a sample inspection apparatus provided with a pipetting device according to the present invention.
FIG. 2 is a schematic overall configuration diagram of a pipetting device according to the present invention.
FIG. 3 is a flowchart for explaining a procedure of ejection processing by the pipetting device according to the present invention.
FIG. 4 is an explanatory diagram of an output waveform and a differential waveform thereof when a discharge amount of a liquid sample is a predetermined amount by a pressure sensor provided in the pipetting device according to the present invention.
FIG. 5 is an explanatory diagram of an output waveform and a differential waveform thereof when a discharge amount of a liquid sample is smaller than a predetermined amount by a pressure sensor provided in the pipetting device according to the present invention.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Sample inspection apparatus 3 Pipetting apparatus 6 Display apparatus 8 Container 10 Reagent pad 11 Printer 21 Nozzle 22 Nozzle main body 23 Nozzle chip 25 Syringe pump 28 Pulse motor 29 Electric motor 31 Pressure sensor 32 Control apparatus

Claims (3)

A pipetting device having a pump communicating with a nozzle and sucking and discharging a liquid to be conveyed from the opening of the nozzle; and a pressure detecting means for detecting a pressure of an air flow path between the pump and the opening of the nozzle. make use of,
A suction step of sucking a predetermined amount of the transported liquid from the opening of the nozzle;
A pipetting method for performing a step including a discharge step of discharging the transported liquid sucked in the suction step from an opening of the nozzle,
In the discharge step, a change in pressure of the air flow path between the pump and the nozzle opening is detected based on an output signal from the pressure detection means, and a discharge amount of the transported liquid based on the pressure change And if the pressure of the air flow path between the pump and the nozzle opening is less than a predetermined value, it is determined that the discharge amount of the transported liquid has not reached the predetermined value. Pipetting method. A pump that communicates with the nozzle and sucks and discharges the liquid to be transported from the opening of the nozzle; a drive device that relatively moves the nozzle and the container that stores the liquid to be transported; and the opening of the pump and the nozzle A pressure detection means for detecting the pressure of the air flow path between and a control device that receives the output signal from the pressure detection means and controls the pump and the drive device,
By controlling the pump and the driving device by the control device, a predetermined amount of the transported liquid in the container is sucked from the opening of the nozzle, and the sucked transported liquid is discharged from the opening of the nozzle. A pipetting device,
The controller, when discharging the sucked liquid to be transported from the opening of the nozzle, changes the pressure in the air flow path between the pump and the opening of the nozzle based on an output signal from the pressure detecting means. And detecting the discharge amount of the transported liquid based on the pressure change, and if the pressure of the air flow path between the pump and the nozzle opening is less than a predetermined value, A pipetting device characterized in that it is determined that the discharge amount has not reached a predetermined value . The liquid to be transported is a liquid sample spotted on a reagent pad, and when the controller discharges the sucked liquid sample from the nozzle opening to the reagent pad, the pump for discharging is driven. If the pressure of the air flow path between the pump and the nozzle opening at a predetermined time after completion and before separating the nozzle opening from the reagent pad is less than a predetermined value, The pipetting device according to claim 2, wherein it is determined that the discharge amount has not reached a predetermined value .

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