JP3606040B2 - Automatic dispensing apparatus and dispensing method - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an automatic dispensing apparatus and a dispensing method used for dispensing specimens and reagents.
[0002]
[Prior art]
In tests and analyzes performed in the biochemical field and the like, a dispensing operation is performed in which a liquid such as a specimen or a reagent is divided into sample containers. This dispensing operation is performed using a suction tool in which a pipette-shaped dispensing tip is attached to the tip of a dispensing nozzle that can suck and discharge air by driving an internal piston. The dispensing operation is performed by inhaling the liquid and discharging the inhaled liquid. During the inhalation, the lower end of the dispensing tip is submerged in the liquid in the sample container, The liquid is sucked by the negative pressure generated by sucking the air. When discharging, the liquid in the dispensing tip is discharged by discharging air into the dispensing nozzle with the lower end of the dispensing tip positioned on the liquid level of the liquid already present in the sample container. It is dripped on the liquid level in a sample container.
[0003]
[Problems to be solved by the invention]
By the way, with the recent refinement and sophistication of test contents in the biochemical field, the accuracy required for dispensing performed in various processes of the test tends to become more sophisticated. However, in the conventional dispensing method, it has been difficult to improve the accuracy of dispensing for the following reasons. As described above, in the dispensing operation, the piston is driven to suck and discharge air, and the pressure in the space in the dispensing tip is reduced and pressurized to draw in liquid from the lower end of the dispensing tip. To be discharged. Therefore, even if the driving amount of the piston is constant, the amount of liquid sucked and discharged varies depending on whether or not the lower end portion of the dispensing tip is in a state where it is easy to suck and discharge liquid. Whether or not it is easy to suck and discharge the liquid at this time mainly depends on the relative positional relationship between the lower end portion of the dispensing tip and the liquid surface.
[0004]
That is, if the lower end portion of the dispensing tip is positioned near the liquid level at the time of inhalation, the air near the liquid level is simultaneously sucked at the time of liquid inhalation, and the amount of sucked liquid varies. In addition, when the lower end portion of the dispensing tip is located near the liquid level at the time of discharge, free drop of the discharged droplet is hindered by the liquid level, and the discharge amount is not constant. Further, when the position of the lower end portion of the dispensing tip is excessively above the appropriate position, a dispensing error due to the rebound of the droplet dropped on the liquid surface occurs.
[0005]
Thus, the dispensing accuracy greatly depends on the relative positional relationship between the dispensing tip and the liquid level, in other words, the height position of the dispensing tip and the liquid level in the sample container. However, there are various types of cross-sectional shapes of sample containers used at present, such as a simple cylindrical shape with a flat bottom surface and a bottom surface with a cone shape. Therefore, even if the amount of suction / discharge per hour is kept constant, the rising / lowering speed of the liquid level varies depending on the cross-sectional shape of the container. This is the relative relationship between the liquid level and the dispensing tip. It is more difficult to keep the positional relationship constant. As described above, in the conventional dispensing method, it is difficult to stabilize the suction / discharge amount and improve the dispensing accuracy due to the relative positional relationship between the dispensing tip and the liquid surface. There was a problem.
[0006]
SUMMARY OF THE INVENTION An object of the present invention is to provide an automatic dispensing apparatus and a dispensing method that can improve the dispensing accuracy by stabilizing the inhalation / discharge amount.
[0007]
[Means for Solving the Problems]
The automatic dispensing apparatus according to claim 1 includes a dispensing head having a suction tool for sucking and discharging the liquid in the sample container, and moves the dispensing head relative to the sample container in the horizontal direction. A moving means; a piston for sucking and discharging liquid from the suction tool; a driving means for driving the piston at a given piston driving speed; an elevating means for moving the dispensing head up and down; A plurality of data tables indicating the relationship between the amount of liquid in the sample container and the liquid level height according to the amount of injection, the shape of the bottom of each sample container , and the liquid level in the sample container at the start of dispensing A storage unit storing control data including data, and when the control unit reads out the control data from the storage unit and controls the driving unit and the lifting unit to suck the liquid in the sample container, and / or The trial When ejecting the liquid in the container, wherein the lower end of the suction device to control the lifting speed of the dispensing head on the basis of the data table and the piston driving speed corresponding to the shape of the bottom of each sample container sample Control means for keeping the relative distance from the liquid level in the container constant and updating the liquid level to the liquid level after dispensing.
[0008]
The dispensing method according to claim 2, wherein the lower end portion of the suction tool provided in the dispensing head is inserted into the sample container, and the piston is driven at a piston driving speed provided by the driving means , whereby the sample is removed from the lower end portion. A dispensing method for sucking and discharging the liquid in the container, and dispensing the liquid in the sample container according to the dispensing amount of each dispensing operation and the shape of the bottom of each sample container. Control data including a plurality of data tables indicating the relationship of the length and data relating to the liquid level in the sample container at the start of the dispensing is stored in the storage unit, and the control data is read from the storage unit during dispensing. By controlling the driving means and the elevating means by the control means, when the suction tool sucks the liquid in the sample container and / or discharges the liquid into the sample container, In the shape of the bottom Flip a data table and on the basis of the piston driving speed by controlling the lifting speed of the dispensing head keeping the relative distance between the liquid level in said sample container and the lower end of the suction device constant, the after dispensing The liquid level was updated to the liquid level after dispensing.
[0009]
The dispensing method according to claim 3 is the dispensing method according to claim 2, wherein when the driving means and the lifting / lowering means are controlled, a driving speed pattern of the driving means is first set, and then the driving speed pattern is set. The speed pattern of the lifting / lowering means is set based on the above.
[0010]
According to the invention described in each claim, the piston driving means and the dispensing are performed so that the relative distance between the lower end portion of the suction tool and the liquid level when the suction tool sucks and discharges the liquid in the sample container is maintained at a predetermined value. By controlling the lifting means of the head, it is possible to stabilize the suction / discharge amount and improve the dispensing accuracy.
[0011]
DETAILED DESCRIPTION OF THE INVENTION
Next, embodiments of the present invention will be described with reference to the drawings. FIG. 1 is a perspective view of an automatic dispensing apparatus according to an embodiment of the present invention, FIG. 2 is a block diagram showing a configuration of the automatic dispensing apparatus, and FIG. 3 is a processing block showing a data flow of the automatic dispensing apparatus. 4A is a data table showing work procedure information of the automatic dispensing apparatus, FIG. 4B is a data table showing plate information of the automatic dispensing apparatus, and FIG. 4C is the automatic dispensing apparatus. Data table showing liquid level information of the pouring device, FIGS. 5 (a), (b), (c) and FIG. 6 (a) are graphs of the data table of the automatic dispensing device, and FIG. 6 (b) is the automatic FIG. 6 (c) is a graph showing a dispensing head elevation pattern of the automatic dispensing device, FIG. 7 is a flow chart of the main program of the dispensing method, and FIG. 8 is the same. FIG. 9 is a flowchart showing the discharge operation of the dispensing method. A.
[0012]
First, the structure of the automatic dispensing apparatus will be described with reference to FIG. In FIG. 1, a microplate 2 and a reservoir 3 are placed on a base 1. These microplate 2 and reservoir 3 are transported from the stocker (not shown) to the upper surface of the base 1 by the transport arm 5. The microplate 2 and the reservoir 3 are each provided with a large number of wells 2a and 3a, which are small holes of the sample container, in a lattice shape.
[0013]
An X data table 6 is disposed above the base 1, and a Y data table 7 is fixed to the X data table 6 so as to be movable in the X direction. A dispensing head 8 is fixed to the Y data table 7 so as to be movable in the Y direction. The dispensing head 8 includes a nozzle 9 on which a dispensing tip 10 is mounted at the lower end. The nozzle 9 and the dispensing tip 10 constitute a suction tool, and suck and discharge liquid from the lower end of the dispensing tip 10. Accordingly, by driving the X data table 6 and the Y data table 7 and moving the dispensing head 8, the liquid in the well 3a is sucked from the lower end of the dispensing tip 10 and discharged to the well 2a for dispensing. It can be performed.
[0014]
Next, the system configuration of the automatic dispensing apparatus will be described with reference to FIG. As shown in FIG. 2, a piston 11 is fitted in the nozzle 9, and the piston 11 is connected to a rack gear 13 by a rod 12. The rack gear 13 meshes with a pinion gear 14 that is rotationally driven by a motor 15. Accordingly, by driving the motor 15, the piston 11 moves up and down in the nozzle 9 and sucks and discharges air in the dispensing tip 10 attached to the nozzle 9. Therefore, the motor 15, the pinion gear 14, and the rack gear 13 are driving means for driving the piston 11.
[0015]
The nozzle 9 is provided by being fitted into a block 16, and the block 16 is connected to a rack gear 18. The rack gear 18 meshes with a pinion gear 19 that is rotationally driven by the motor 20. When the motor 20 is driven, the nozzle 9 and the dispensing tip 10 move up and down together with the block 16. Therefore, the motor 20, the pinion gear 19 and the rack gear 18 serve as raising / lowering means for raising and lowering the dispensing head 8.
[0016]
Next, the configuration of the control system will be described with reference to FIG. 2, FIG. 3 and FIG. The piston drive control unit 21 controls the piston drive motor 15 based on a piston drive speed pattern (described later). The dispensing head lifting / lowering control unit 22 controls the lifting / lowering motor 20 of the dispensing head 8 based on a dispensing head lifting speed pattern (described later). The process control unit 23 reads control data from the storage unit 30 described later, and outputs a speed pattern and the like to the piston drive control unit 21 and the dispensing head lifting control unit 22. The input means 24 is a keyboard or the like, and inputs setting data. The display unit 25 is a display and displays an image when data is input.
[0017]
The memory | storage part 30 memorize | stores the various control data for piston drive control and dispensing head raising / lowering control which are demonstrated below. The program 31 is a sequence program for the entire dispensing operation. As shown in FIG. 4A, the work procedure information 32 is obtained by ordering each element work constituting the dispensing operation in the order of operation, and each work NO. (Reference numeral 51), and each work NO. Information about work contents (reference numeral 52) necessary for each element work is shown for each.
[0018]
The plate information 33 is information relating to the microplate 2 and the reservoir 3 to be dispensed, and as shown in FIG. (Reference numeral 53), each data of the matrix number 54 of the wells included in the plate, the hole diameter 55 of the well, and the cross-sectional shape 56 of the bottom of the well are included. Examples of the shape of the bottom of the well include a flat bottom shape, a spherical shape, and a conical shape.
[0019]
As shown in FIG. 4 (c), the liquid surface position information 34 is stored in each plate NO. For each well (row, column) 57, the liquid level height (h) at that time is stored. The data table 1, data table 2, and data table 3 to which reference numerals 35, 36, and 37 are attached are prototypes of the lifting pattern of the dispensing head 8 corresponding to the shapes of the bottoms of the above-described three types of wells. . The offset data 38 indicates the relative distance d between the liquid level in the well 2 a and the lower end portion of the dispensing tip 10. Although FIG. 2 shows a state at the time of liquid ejection, the lower end portion of the dispensing tip 10 sinks below the liquid level during inhalation, so that data on the amount of settlement is designated.
[0020]
Next, a data table serving as basic data for determining the lifting pattern of the dispensing head 8 will be described. 5 (a), 5 (b), and 5 (c) show the relationship between the liquids in the wells having a flat bottom shape, a spherical shape, and a conical shape on the horizontal axis and the liquid level height on the vertical axis, respectively. It is shown in a graph. The flat bottom shape shown in FIG. 5A is a simple cylinder, and the liquid level is proportional to the amount of liquid, and therefore is represented by a linear graph.
[0021]
On the other hand, in the example shown in FIGS. 5B and 5C, the liquid surface height is within the range equal to or higher than a predetermined height (spherical radius R in the spherical shape, conical height H in the conical shape). ) Is a linear graph, but since the cross section is narrowed within the range where the liquid level is below the predetermined height, the rate of change of the liquid level with respect to the same liquid amount Is not constant, and the graphs shown in FIGS. 5B and 5C are obtained according to the respective cross-sectional shapes.
[0022]
That is, when the liquid level is in the above-described range, even if suction (or discharge) is performed with a constant amount, the amount of decrease (or increase) in the liquid level is not constant over time, and FIG. It is along the graph shown in (c). Therefore, in order to keep the relative distance d between the liquid level and the lower end of the dispensing tip 10 at a predetermined amount during suction / discharge, the ascending / descending operation of the dispensing head 8 may be synchronized with the movement of the liquid level.
[0023]
Usually, the suction / discharge amount per unit time, that is, the suction / discharge speed, is set to an optimum value determined by properties such as the viscosity of the liquid to be dispensed, and is given as known information at each dispensing operation. Here, during the suction / discharge operation, the suction / discharge speed, that is, the driving speed of the piston 11 is kept constant except for a very short time when the motor 15 is started / stopped. It can be regarded as proportional (see FIG. 6B). In this case, what changed the horizontal axis (liquid amount) of FIG. 5 (a), (b), (c) with time shows the temporal change of the liquid level height at the time of dispensing. . Therefore, in order to synchronize the ascending / descending operation of the lower end portion of the dispensing tip 10 with the movement of the liquid level, the ascending / descending speed of the dispensing head 8 is shown in the graphs of FIGS. What is necessary is just to change with the speed pattern obtained by differentiating in time.
[0024]
As a specific example, the speed pattern setting procedure for the spherical bottom surface example shown in FIG. 5B will be described with reference to FIG. When the dispensing target is specified, a data table shown in a graph as shown in FIG. 6A is given, and at the same time, the liquid level height (h1) and the amount of liquid to be sucked and discharged The dispensed amount (Q) is also given as known information. Further, as described above, since the optimum piston drive speed v for sucking and discharging the liquid to be dispensed is given, as shown in FIG. 6B, the time required for suction and discharge, that is, the dispensing time t1. Is required.
[0025]
Next, on the graph of FIG. 6A, a point P1 corresponding to the liquid level height h1 at the time is obtained, and the above-mentioned dispensing amount Q is set to the liquid amount (suction / discharge amount) corresponding to the point P1. to add. Then, a point P2 on the graph corresponding to the added liquid amount is obtained. The liquid level height h2 on the vertical axis corresponding to this point P2 indicates the target liquid level height after dispensing. That is, the height of the liquid level during the dispensing operation changes from the points P1 to P2 on this graph as the amount of liquid in the well changes.
[0026]
The upper graph in FIG. 6C is obtained by cutting out the range from the point P1 to the point P2 (the range of the liquid level height h2-h1) in the graph of FIG. 6A and replacing the horizontal axis with time. . This replacement is performed according to the relationship between the liquid amount (intake / discharge amount) and time shown in FIG. Thereby, the dispensing time t1 corresponding to the dispensing amount Q is obtained on the horizontal axis of the graph. Therefore, in order to keep the distance between the lower end of the dispensing tip 10 and the liquid level constant, the dispensing head lifting speed pattern obtained by differentiating the liquid level height graph shown in the upper part of FIG. What is necessary is just to drive the motor 20 for raising / lowering a dispensing head by (graph of FIG.6 (c) lower stage). By setting the position of the dispensing tip 10 at the start of dispensing to a predetermined distance d from the liquid level, the predetermined distance d can be maintained for any range of liquid level height. In the speed pattern of FIG. 6C, a predetermined rise time is required when the motor 20 is started, but this is omitted on the graph.
[0027]
In the present embodiment, the suction / discharge amount does not change with time and is constant, but the piston drive speed may be changed with time. In this case, when the upper graph of FIG. 6C is obtained from the graph of FIG. 6A, the relationship between the liquid amount and time does not become a simple proportional relationship, but is determined by the piston drive speed pattern. According to the relationship between the suction / discharge amount and time, an operation of replacing the liquid amount with time may be performed. In any case, first, the drive speed pattern of the piston drive means is set, and then the speed pattern of the lifting means of the dispensing head 8 is set based on this drive speed pattern. Accordingly, the relative positional relationship between the dispensing tip 10 and the liquid surface can be kept good while maintaining the suction / discharge speed according to the properties of the liquid to be dispensed, so that high-precision dispensing is possible. It can be performed.
[0028]
Next, various data flows and data processing contents of the automatic dispensing device will be described with reference to FIG. First, prior to the start of the dispensing operation, data is read by the data reading unit 44. From the work procedure information 32, the target plate No. The well position and the dispensing amount are read from the plate information 33 as the hole diameter and bottom shape of the target well, and the liquid level position information 34 is read from the liquid level height data of the target well at that time.
[0029]
These data are sent to the dispensing head lifting / lowering pattern setting unit 40 together with a predetermined distance d given as the offset data 38. Of these data, data relating to the dispensing amount and the properties of the liquid to be dispensed is sent to the piston drive pattern setting unit 45 in order to set the piston drive speed. Here, a piston drive speed pattern for obtaining an optimal suction / discharge amount corresponding to the dispensed liquid is set. The set piston drive speed pattern is sent to the piston controller 21 (see FIG. 2).
[0030]
The dispensing head raising / lowering pattern setting unit 40 corresponds to each of the data table 1, the data table 2, and the data table 3 prepared according to the shape of the bottom of the well. And a third elevating pattern setting unit 43. By these lifting / lowering pattern setting units, a speed pattern (dispensing head lifting / lowering speed pattern) of the motor 20 that lifts and lowers the dispensing head 8 is set. In addition to the setting of the speed pattern, the liquid level data of the well after dispensing is sent to the liquid level position information 34, and the data is updated. The set dispensing head lifting speed pattern is sent to the dispensing head lifting control unit 22 (see FIG. 2).
[0031]
This automatic dispensing apparatus is configured as described above. Hereinafter, the operation will be described with reference to the flowcharts of FIGS. First, the main program of the dispensing operation will be described with reference to FIG. In FIG. 7, the number N indicating the work procedure is reset to 1 (ST1). Next, the work procedure information is sequentially read (ST2), and it is first determined whether or not the work content is plate conveyance (ST3). If it is plate conveyance, a predetermined plate conveyance processing operation is performed, and the microplate 2 and reservoir 3 is carried in and out (ST4).
[0032]
If the plate is not transported, it is next determined whether or not it is a suction operation (ST5), and if it is a suction operation, a predetermined suction operation process is performed (ST6). Similarly, it is determined whether or not the operation is a discharge operation (ST7), and a discharge operation process (ST8) is performed. Thereafter, the operation number N is compared with the final number to determine whether or not the operation is completed (ST9). If the incomplete operation is not completed, 1 is added to the number N (ST10), and the same step is continued by returning to ST2.
[0033]
Next, the suction operation process will be described with reference to FIG. If it is determined in ST5 that the suction operation is performed in ST5, the suction amount Q is read from the work procedure information 32 (ST11). Next, the current liquid level h1 is read from the liquid level position information 34 (ST12), and the bottom shape information of the well is read from the plate information 33 (ST13).
[0034]
Here, it is determined whether the bottom shape of the well is a flat bottom, a spherical shape, or a conical shape (ST14). Based on the determination result, the piston drive pattern and the data table 1, data table 2, or data table 3, respectively. The raising / lowering pattern of the dispensing head is set (ST15, ST16, ST17). Then, the piston 11 and the dispensing head 8 are operated based on the drive pattern and the lifting pattern set in this way, and the suction operation is executed. The liquid level after dispensing is sent to the liquid level position information 34, the data is updated, and the suction operation is terminated.
[0035]
Similarly, FIG. 9 shows a flow of the discharge operation process. In this flow, the reading of the suction amount (ST11) in the flow of FIG. 8 is replaced with the reading of the discharge amount (ST21), and the execution of the suction operation (ST18) is replaced with the discharge operation execution (ST28). Is similar to the inhalation operation process.
[0036]
In this embodiment, an example is shown in which a piston that sucks and discharges liquid from the suction tool is built in the dispensing head. However, the piston is sucked and discharged separately from the dispensing head. It may be in the form of being built in the pump.
[0037]
As described above, the present embodiment always maintains the liquid level even when dispensing is performed using a well having a bottom surface shape in which the vertical movement of the liquid level varies depending on the range of the liquid level. For the purpose of keeping the relative distance to the lower end of the dispensing tip at a predetermined value, a data table is created that represents the relationship between the liquid level height and the suction / discharge amount taking into account the shape of the bottom surface in advance. Based on the above, the driving of the piston and the lifting and lowering operation of the dispensing head are controlled.
[0038]
【The invention's effect】
According to the present invention, while maintaining the suction and discharge speed always commensurate with the nature of the dispensing liquid of interest even in the case of using a specimen container that different shapes of the bottom portion, and to stabilize the suction-discharge rate dispensing Accuracy can be improved.
[Brief description of the drawings]
FIG. 1 is a perspective view of an automatic dispensing apparatus according to an embodiment of the present invention. FIG. 2 is a block diagram showing a configuration of an automatic dispensing apparatus according to an embodiment of the present invention. FIG. 4 is a processing block diagram showing the flow of data in the automatic dispensing device in the form of FIG. 4A. FIG. 4B is a diagram showing a data table showing work procedure information in the automatic dispensing device in one embodiment of the present invention. The figure which shows the data table which shows the plate information of the automatic dispensing apparatus of one Embodiment of this invention (c) The figure which shows the data table which shows the liquid level information of the automatic dispensing apparatus of one Embodiment of this invention (A) Graph of data table of automatic dispensing apparatus of one embodiment of the present invention (b) Graph of data table of automatic dispensing apparatus of one embodiment of the present invention (c) One embodiment of the present invention Fig. 6 is a graph of the data table of the automatic dispensing device of the embodiment. (B) Graph showing the piston drive pattern of the automatic dispensing device according to one embodiment of the present invention (c) Graph of the automatic dispensing device according to one embodiment of the present invention FIG. 7 is a flow chart of the main program of the dispensing method according to the embodiment of the present invention. FIG. 8 is a flow showing the suction operation of the dispensing method according to the embodiment of the present invention. FIG. 9 is a flowchart showing the discharge operation of the dispensing method according to the embodiment of the present invention.
2 Microplate 3 Reservoir 6 X data table 7 Y data table 8 Dispensing head 9 Nozzle 10 Dispensing tip 15 Motor 20 Motor 21 Piston drive controller 22 Dispensing head lifting controller 23 Processing controller 30 Storage unit 32 Work procedure information 33 Plate information 34 Liquid surface position information

Claims (3)

A dispensing head having a suction tool for sucking and discharging the liquid in the sample container, a moving means for moving the dispensing head relative to the sample container in the horizontal direction, and sucking the liquid from the suction tool A piston to be discharged, a driving means for driving the piston at a given piston driving speed, an elevating means for raising and lowering the dispensing head, a dispensing amount of each dispensing operation, and a shape of the bottom of each sample container And a storage unit storing control data including a plurality of data tables indicating the relationship between the amount of liquid in the sample container and the liquid level and data relating to the liquid level in the sample container at the start of dispensing. When reading the control data from the storage unit and controlling the driving means and the elevating means to suck the liquid in the sample container and / or to discharge the liquid into the sample container , Previous To control the lifting speed of the dispensing head on the basis of the data table and the piston driving speed corresponding to the shape of the bottom of each sample container relative distance between the liquid level in the sample container and the lower end portion of the suction attachment An automatic dispensing apparatus comprising: a control unit that keeps the liquid level constant and updates the liquid level to a liquid level after dispensing. The lower end of the suction tool provided in the dispensing head is inserted into the sample container, and the piston is driven at a piston drive speed provided by the driving means to suck and discharge the liquid in the sample container from the lower end. A dispensing method for dispensing , a plurality of data tables showing a relationship between a dispensing amount of each dispensing operation and a shape of the bottom of each sample container and a liquid amount in the sample container and a liquid surface height; Control data including data relating to the liquid level in the sample container at the start of dispensing is stored in the storage unit, and at the time of dispensing, the control data is read from the storage unit to control the driving unit and the lifting unit. by controlling the unit, when the suction attachment is inhaled liquid in the sample vessel, and or when ejecting the liquid to the sample container, the and data tables corresponding to the shape of the bottom of each sample container Serial based on the piston driving speed by controlling the lifting speed of the dispensing head keeping the relative distance between the liquid level in the sample container and the lower end of the suction device constant, the liquid level height after dispensing A dispensing method characterized by renewing the liquid level after dispensing. 3. The control device according to claim 2, wherein when controlling the driving means and the lifting / lowering means, first, a driving speed pattern of the driving means is set, and then a speed pattern of the lifting / lowering means is set based on the driving speed pattern. Dispensing method.

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