JP3043510B2 - Sample stirring suction device - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a device for agitating and sucking a liquid sample such as urine in an automatic analyzer.
By sucking and discharging the sample at different positions, even if the sample has entered a large amount in an elongated container,
The present invention relates to a highly reliable sample stirring / suctioning apparatus capable of efficiently stirring and sucking and detecting the presence or absence of a sample by detecting bubbles.

[0002]

2. Description of the Related Art In an analyzer, when analyzing a formed component in a sample, the sample is sampled before the sample is sampled.
It is necessary to previously stir and homogenize the sample. Without agitation, the solids remain settled at the bottom, preventing correct sampling. Conventionally, as a stirring method, a method in which a container is turned over and a method in which a stirring rod is inserted into a sample and rotated are well known. However, it is necessary to seal the container and cannot be used for a container without a lid. Also,
Cannot be sufficiently stirred in the case of an elongated container. Particularly in the case of a container for urine sediment, since the bottom is narrowed (see FIGS. 4 and 5), it is difficult to uniformly disperse the sediment formed on the bottom.

[0003] Japanese Patent Application Laid-Open No. 63-66466 describes an apparatus which aspirates a mixture once dispensed and mixed into a reaction vessel into a dispensing nozzle, and then discharges and agitates the mixture into the reaction vessel. Have been. Then, in that embodiment, the reagent is discharged from the nozzle into the reaction vessel containing the sample and mixed with the sample, and then the tip of the nozzle is lowered to the bottom of the reaction vessel, and almost the entire amount of the mixed solution is filled in the nozzle. It is described that suction is performed and then the entire amount is discharged from a nozzle.
In addition, a device for detecting air bubbles in aspirating a sample is also known. In Japanese Patent Application Laid-Open No. 2-61557, a set of electrodes is provided at a distance from a portion where a liquid flows, an AC voltage is supplied between the two electrodes, electric resistance is detected, and a conductive liquid and a non-conductive liquid are detected. An apparatus for discriminating between ionic gases is disclosed.

[0004]

However, the above-mentioned device disclosed in Japanese Patent Application Laid-Open No. 63-66464 does not have a sufficient stirring effect because it is sucked at the bottom and discharged at the bottom.
To compensate for this, almost all of the liquid is sucked and discharged.
When the amount of liquid is small, suction / discharge of the entire amount is possible, but it is difficult when the amount of liquid is large. In order to realize the apparatus described in this publication, a suction means having a large capacity and a large suction force is required, and the suction and discharge steps take time.
In addition, the sample, for example, urine, contains formed components such as blood cells, epithelial cells, and casts. Of these, particularly for fragile components such as casts, damage due to excessive vigorous stirring is a problem. Become. Further, the above-mentioned Japanese Patent Application Laid-Open No. 63-66
No. 466 and Japanese Patent Application Laid-Open No. 2-61557 do not describe an apparatus for stirring a sample by changing the position of a pipette between the time of suction and the time of discharge of a sample.

[0005] In view of these points, as shown in FIG.
The sample in the sample container 11 is agitated by aspirating the sample in the sample container 11 by aspirating the sample in the sample container 11 and discharging the sample in the sample container 11. A sample stirring / suction apparatus characterized by providing a driving means 25 for changing the position of the sample has been developed and a patent application has already been filed (Japanese Patent Application No. Hei 3-22212).
No. 9). The present invention is capable of efficiently stirring even a large amount of liquid sample contained in an elongated container with a simple configuration, with little damage, sucking the sample as it is after stirring, and taking the bubble detection device one step further. It is an object of the present invention to provide a sample stirring / suctioning apparatus that can detect the presence or absence of a sample by incorporating bubbles to detect the sample and improve reliability.

[0006]

In order to achieve the above-mentioned object, a sample stirring and aspirating apparatus according to the present invention will be described with reference to the drawings. After aspirating the sample and discharging the sucked sample, the sample in the sample container 11 is agitated, and then the pipette 10 is used to sample the sample. , A sensor provided in the middle of the sample suction line L for generating a difference based on a difference between liquid and air characteristics, and a detection circuit 53 for detecting the difference generated by the sensor. 55. Specifically, as shown in FIG. 1, the sample in the sample container 11 is agitated by sucking the sample in the sample container 11 with the pipette 10 for sample suction and discharging the sucked sample. In an apparatus for sampling a sample with a pipette 10, a pipette 1 at the time of aspirating a sample and discharging the sample
0, a set of electrodes 50 and 52 provided in the middle of the sample suction line L;
And a bubble detection device 55 comprising a detection circuit 53 for detecting a difference in electrical impedance Ra between the two. In this sample stirring and suction device, when the sample suction amount during sample stirring is Q1, the sample suction amount during sample suction is Q2, and the volume from the tip (lower end) of the pipette 10 to the lower electrode 50 is Q3. In addition, Q3 <(Q1-Q
It is desirable to provide the lower electrode 50 at a position satisfying 2).

In the above-described apparatus, the sample in the sample container 11 is agitated by sucking the sample in the sample container 11 by the sample suction pipette 10 and discharging the sucked sample. When sampling the sample, the suction of the sample and the discharge of the sample are performed at different positions in the sample container 11. For example, one of sample suction and sample discharge is performed at the lower part of the sample, and the other is performed at the upper part of the sample. In addition, by performing one or both of the suction of the sample and the discharge of the sample while moving the pipette 10,
Agitation can be performed more efficiently. Further, the sample liquid level is detected, and the pipette 10 is detected based on the liquid level detection information.
May be moved to aspirate the sample and discharge the sample. Further, the driving means 25 causes the pipette 1
0 can be positioned down and the pipette 10 can be positioned up during ejection. The reverse is also possible. Further, the pipette 10 may be moved at the time of suction and discharge. The bubble detector 55 can detect bubbles during sample stirring or sample suction to detect the presence or absence of a sample, thereby improving the reliability of the device.

[0008]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the present invention will be described below in detail with reference to the drawings. However, the materials, dimensions, shapes, relative arrangements and the like of the components described in this embodiment are as follows:
Unless there is a specific description, the scope of the present invention is not intended to limit the scope of the invention only to them, but is merely an illustrative example. FIG. 1 is a system explanatory diagram showing one embodiment of the sample stirring / suction device of the present invention. Reference numeral 10 denotes a pipette for aspirating a sample, and a suction means 12 is connected to the pipette 10. As an example of the suction means 12, a diaphragm type pump (hereinafter, referred to as a diaphragm pump 12) is used.
Is used. One chamber 14 divided by the diaphragm 13 of the diaphragm pump 12 is provided for the pipette 10, and the other chamber 16 is provided for switching between a positive pressure (higher than atmospheric pressure) source 18 and a negative pressure (lower atmospheric pressure) source 20. 22. The pipette 10 is moved up and down by the driving means 25. The driving means 25 is, for example,
A substantially horizontal arm 24 for holding the pipette 10 and a substantially vertical endless belt 30 to which the arm 24 is attached;
Pulleys 27 and 28 provided at the upper and lower ends of the endless belt 30, a driving source 26 for driving the pulley 27,
For example, it comprises a stepping motor. The endless belt 30 is stretched between the pulleys 27 and 28, and the arm 24 and the pipette 10 move up and down in the sample container 11, for example, the urine sediment spitz, when the pulley rotates in the forward and reverse directions.

FIG. 2 is an example of a timing chart for explaining the operation of the device of the present invention. FIG.
FIG. 5 is a diagram showing a state at the time of sample suction, and FIG. 5 is a diagram showing a state at the time of sample discharge. The sample container 11 shows, for example, urine sediment spitz for 10 ml. Hereinafter, the stirring operation will be described with reference to FIG. (1) The drive source 26 operates to lower the pipette 10 to the state shown in FIG. (2) The valve 22 is operated, and the other chamber 16 of the diaphragm pump 12 is connected to the negative pressure source 20, so that the diaphragm pump 12 is in the suction mode, and a sample, for example, 2 ml is sucked from the pipette 10. (3) The drive source 26 operates to raise the pipette 10 to the state shown in FIG. (4) The valve 22 returns to the original state, and the other chamber 16 of the diaphragm pump 12 is connected to the positive pressure source 18, so that the diaphragm pump 12 is in the discharge mode, and the pipette 1
From 0, discharge 2 ml of the sample previously sucked. (5) The drive source 26 operates to lower the pipette 10 to the state shown in FIG. (6) The above (2) to (5) are repeated. (7) Pipette 1 a uniformly stirred sample, for example, 1 ml.
Aspirate at 0 and proceed to the required processing required for analysis.

As described above, by sucking the sample in the lower part of the container and discharging the sample in the upper part of the container, the material precipitated at the lower part of the elongated container even if the suction amount is small, is reduced to the area where the material is small. , The concentration can be efficiently made uniform. Conversely, the same effect can be obtained by sucking the sample in the upper part of the container and discharging the sample in the lower part of the container. At this time, the sample portion that does not contain the material components is moved to the portion that contains a large amount of the material components, whereby the sample can be efficiently homogenized. further,
As shown in FIG. 3, if the sample is aspirated and agitated while moving the pipette up and down, the liquid in the container is more strongly disturbed, and the time required for agitation can be reduced. When the sample stirring / suctioning step is completed, the washing step is started.
The pipette 10 moves to a cleaning tank (not shown). A positive pressure source 18 is connected to one chamber 14 of the diaphragm pump 12 via a valve 32 and a cleaning liquid tank 36 via a valve 32. The valve 32 is opened to supply the cleaning liquid from the cleaning liquid tank 36, and the sample suction line including the pump 12 and the pipette 10 is washed away. Then, when the valve 32 is closed and the valve 34 is opened, the cleaning liquid is removed by air, and the cleaning process is completed.

Further, as shown in FIGS. 6 and 7, by adding a liquid level detecting function, more effective stirring can be performed. That is, a liquid level detecting means 38 for detecting the liquid level of the sample, a control circuit 40 for inputting a signal from the liquid level detecting means 38 to control the movement of the pipette 10, and a driving means 25 based on the signal of the control circuit 40. And a driving circuit 42 for driving. Hereinafter, the control of the stirring operation by the liquid level detection will be described. In the analyzer, the amount of the sample in the sample container 11 is not always constant (the liquid level is not always constant). If the sample is small and the sample is sucked / discharged and agitated with the moving amount of the pipette kept constant, foaming of the sample, suction of air bubbles at the time of sampling, scattering of the sample and the like may occur.

In order to solve the above problems, the liquid level may be detected and the moving distance of the pipette during stirring may be determined based on the information. A well-known liquid level detecting means may be used. A specific method for obtaining the moving distance of the pipette from the liquid level information obtained by the liquid level detecting means will be described with reference to FIG. First, the origin O (the pipette lowering position) is taken. This is determined by the limit switch. The height from the origin O to the pipette 10 corresponds to the number of pulses of the stepping motor. The number of pulses Pb corresponding to the pipette movement distance during stirring is obtained from the liquid level information as follows. Assuming that the number of movement pulses from the detection of the liquid level a to the origin O is Pa, Pb = K1 * Pa or Pb = Pa−K2. Note that K1 and K2 are constants, and may be set to desired values. As described above, the above problem can be solved by changing the moving distance of the pipette 10 in accordance with the difference in the amount of the sample (the height of the liquid level). In the case where the amount of the sample in the sample container 11 is large, In addition, even when the amount is small, good stirring can be achieved. In FIG. 6, b is the raised position of the pipette 10b during stirring, 10a
Denotes a pipette detecting the liquid level a, 10c denotes a pipette located at the origin O, and 10d denotes a pipette at a standby position. More specifically, as shown in FIG. 7, the liquid level of the sample is detected by the liquid level detecting means 38, and the detection signal is transmitted to the control circuit 4.
Enter 0. Then, the signal of the control circuit 40 is introduced into the drive circuit 42 to drive the drive means 25 to move the pipette 10.

In addition to the device described above, the device of the present invention is provided with a bubble detecting device 55 as shown in FIG. The bubble detecting device 55 includes, for example, an electrode 50,
52, wiring codes 76 and 78, and a detection circuit 53. Suction means 1 from the tip of suction pipette 10
2, a pair of electrodes 50 and 52 made of a corrosion-resistant conductive material, for example, stainless steel, are provided at a predetermined distance in the flow direction of the liquid. Electrode 5
Reference numerals 0 and 52 are provided so as to directly contact a sample (urine in this example) flowing through the sample suction line L. Electrodes 50, 5
2 is a detection circuit 53 by wiring codes 76 and 78, respectively.
It is connected to the. In the detection circuit 53, the electrodes 50,
Based on the difference in electric resistance Ra between the electrodes 50, 52,
It is detected whether a urine sample is present during the period (resistance value Ra is small) or air is present (Ra is large). Urine is a conductive liquid. Although the conductivity varies considerably from sample to sample, discrimination from air is sufficiently possible. Further, even if the sample suction line L is made of an opaque material, it can be discriminated.

The detection circuit 53 is connected to an oscillator 54 that continuously emits a pulse signal, an impedance (resistance) Rc connected to an output of the oscillator 54, a detection circuit 56 connected to the resistance Rc, and a detection circuit 56. Comparison circuit 58
The electrodes 50, 5 are detected by dividing the output of the oscillator 54 by the resistance Rc and the resistance Ra between the electrodes.
2 is ground via wiring cords 76 and 78, respectively.
It is connected to the resistor Rc. A voltage source 59 supplies a reference voltage for comparison. TP1 is a resistance Ra between the electrodes.
Is a test point for observing the pulse signal V1 whose peak value changes due to the difference between the above, and TP2 is a test point for observing the DC voltage V2 whose level changes due to the difference between the interelectrode resistances Ra.

FIG. 8 is a side sectional view of the suction pipette 10. Numerals 72 and 74 are, for example, fluororesin tubes (Teflon tubes) having an inner diameter of 2 mm and an outer diameter of 3 mm. The tip (lower end) of the tube 72 is cut diagonally. The tube 74 has a spiral shape so as not to hinder the movement of the pipette 10. Tubes 72, 74
Are connected by stainless steel electrodes 50 and 52 screwed to both ends of a relay 75 and stoppers 68 and 70 screwed to the electrodes 50 and 52. Tube 72,
The connecting portion of 74 has a flange shape, and the tube is connected while maintaining airtightness by sandwiching the flange between the electrode and the stopper. The relay 75 and the electrodes 50 and 52 have internal passages.
Direct contact with the sample. The distance from the tip (lower end) of the tube 72 to the electrodes 50 and 52 is, for example, 1
They are 10 mm and 120 mm. Therefore, the volume from the tip of the tube 72 to the electrodes 50 and 52 is 0.35 ml, respectively.
0.38 ml. Wiring codes 76 and 78 are connected to the electrodes 50 and 52, respectively.

FIG. 9 is a specific circuit diagram of the detection circuit 53. A capacitor C3 is connected in series with the resistor Rc to provide a resistance R between the electrodes.
A resistor Rb is connected in parallel with a. This is for better air bubble detection. The values of these elements may be set to optimal values so that the difference between the pulse signals V1 appearing at the test point TP1 can be made large with and without the sample at the electrode portion. As an example, the resistors Rc and Rb and the capacitor C3 are, for example, 33 kΩ, 220 kΩ, and 0.047 μm, respectively.
F. The resistance R1 and the capacitor C2 are, for example, 100 kΩ and 0.015 μF, respectively. M1 is CMO
S Schmitt trigger NAND gate.

FIGS. 10 and 11 show test points TP.
1, the waveforms of the signals V1 and V2 appearing at TP2 are shown. The oscillation frequency of the pulse signal is, for example, 2.0 kHz. Reference numeral 60 denotes a signal V1 when there is a sample, and 62 denotes a signal V1 when there is no sample (in the case of air). Numeral 64 indicates the waveform of the signal V2 when there is a sample, and numeral 66 indicates the waveform of the signal V2 when there is no sample (in the case of air). The signal V1 detected by the detection circuit 56 is compared with a constant voltage V3 by a comparison circuit 58, and is binarized according to the presence or absence of a sample.

Next, the function of the bubble detecting device 55 in the sample stirring and suction device will be described with reference to a specific example. FIGS. 12A to 12D show the sample suction line L.
FIG. 6 is a diagram showing the movement of the sample in FIG. It is assumed that the sample stirring and suction device has the following specifications. Suction volume during sample stirring Q1 (2 ml) Suction volume during sample suction (sampling volume) Q2 (1 ml) Volume from tip (lower end) of pipette 10 to lower electrode 50 Q3 (0.35 ml) immediately before stirring starts FIG. 12 shows the inside of the sample suction line L.
Must be empty as shown in (a). This is first detected by the bubble detecting device 55. If the sample is not empty, the liquid will enter the sample container when the sample is stirred. When the sample is aspirated by Q1 during sample agitation, the state becomes as shown by the oblique lines in FIG. Therefore, at this time, the electrode 5
The presence of the sample between 0 and 52 can be detected, and it can be confirmed that the sample for stirring has been correctly sucked. If the amount of the sample in the sample container is small, the sample once enters the state of the sample and then enters the state of bubbles as shown in FIG. 12C (short sample). The fact that the sample is in a bubble state during stirring means that the volume of the air portion is equal to or more than Q3, which means that the sample amount Q that can be sucked is smaller than (Q1-Q3). That is, Q <(Q1-Q
3). For correct sampling to take place,
This sample amount Q needs to be larger than the sample suction amount Q2. That, Q2 <Q ₀ Therefore, it is necessary that Q2 <(Q1-Q3). If Q3 <(Q1-Q2), the condition can be satisfied. When the sample suction line L is clogged, the sample does not reach the electrode 50 and remains in a bubble state as shown in FIG. Electrode 5
The position where 0 and 52 are provided is not particularly limited, and may be provided at a position where the suction of the sample can be monitored. However, setting as described above has a useful aspect. The above embodiment shows the case where the sensor that generates the difference based on the difference between the characteristics of the liquid and the air is composed of two electrodes, but the bubble detection is not limited to the electric impedance, (Transmitted light, reflected light).

[0019]

Since the present invention is configured as described above, it has the following effects. (1) The sample is agitated by changing the position of the pipette by the driving means and sucking and discharging the sample at different positions, so that even if the sample is contained in a large amount in a long and thin container, it does not foam and the efficiency is reduced. Good and good stirring. In this case, when performing the suction and discharge operations while moving the pipette, more efficient stirring can be performed. (2) Since the sample is sampled with the same pipette after suction and discharge with the pipette and stirring, the configuration is simple. Further, it is possible to easily cope with a sample container having a different length (height) or a small amount of a sample by changing the moving distance of the pipette. (3) Since a bubble detector is provided in addition to the driving means, the presence / absence detection (bubble detection) of the sample can be performed at the time of sample stirring or sample suction, and a more reliable sample stirring and suction device is realized. it can.

[Brief description of the drawings]

FIG. 1 is a system explanatory diagram showing one embodiment of a sample stirring / suction device of the present invention.

FIG. 2 is a time chart for explaining an example of an operation in the device of the present invention.

FIG. 3 is a time chart for explaining another example of the operation of the device of the present invention.

FIG. 4 is an explanatory diagram showing a position of a pipette in a sample container at the time of aspirating a sample.

FIG. 5 is an explanatory diagram showing a position of a pipette in a sample container at the time of discharging a sample.

FIG. 6 is an explanatory view showing a state around a pipette in another embodiment of the apparatus of the present invention.

FIG. 7 is a block diagram of another embodiment of the device of the present invention.

FIG. 8 is a partially cutaway side sectional view of a suction pipette in the apparatus of the present invention.

FIG. 9 is a circuit diagram showing an example of a detection circuit in the device of the present invention.

FIG. 10 shows a test point TP1 in the apparatus of the present invention.
5 is a waveform diagram of a signal V1 appearing in FIG.

FIG. 11 shows a test point TP2 in the apparatus of the present invention.
5 is a waveform diagram of a signal V2 appearing in FIG.

FIG. 12 is an explanatory diagram showing the movement of a sample on a sample suction line L in the apparatus of the present invention.

FIG. 13: The applicant has already filed a patent application (Japanese Patent Application No. 3-222).
129) is a system explanatory diagram showing the sample stirring / suction device that performs (129).

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 10 Pipette 11 Sample container 12 Suction means (diaphragm pump) 22 Valve 18 Positive pressure source 20 Negative pressure source 24 Arm 25 Drive means 26 Drive source 27 Pulley 28 Pulley 30 Endless belt 36 Cleaning liquid tank 38 Liquid level detection means 40 Control circuit 42 Drive Circuit 50 Electrode 52 Electrode 53 Detection circuit 54 Oscillator 55 Bubble detector 56 Detection circuit 58 Comparison circuit 59 Voltage source 72 Tube 74 Tube 76 Wiring code 78 Wiring code L Sample suction line Ra Electric impedance Q1 Sample suction amount during sample stirring Q2 Sample Sample suction volume during suction Q3 Volume from tip of pipette to lower electrode

Claims (3)

(57) [Claims] 1. A sample in a sample container (11) is agitated by sucking a sample in a sample container (11) with a sample suction pipette (10) and discharging the sucked sample.
In the apparatus for sampling a sample with the pipette (10), a driving means (25) for changing the position of the pipette (10) at the time of sucking the sample and at the time of discharging the sample, and provided in the middle of the sample suction line (L). Sample agitation characterized by comprising a sensor for generating a difference based on a difference between characteristics of liquid and air, and a bubble detection device (55) including a detection circuit (53) for detecting the difference generated by the sensor. apparatus. 2. A sample in the sample container (11) is agitated by sucking the sample in the sample container (11) with a sample suction pipette (10) and discharging the sucked sample.
In the apparatus for sampling a sample with the pipette (10), a driving means (25) for changing the position of the pipette (10) at the time of sucking the sample and at the time of discharging the sample, and provided in the middle of the sample suction line (L). An air bubble detection device (55) including a set of electrodes (50) and (52) and a detection circuit (53) for detecting a difference in electric impedance (Ra) between the electrodes (50) and (52). A sample stirring and suction device, characterized in that: 3. The amount of sample suction during sample agitation is (Q1), the amount of sample suction during sample aspiration is (Q2), and the volume from the tip of the pipette (10) to the lower electrode (50) is (Q3). The sample stirring and suction device according to claim 2, wherein the lower electrode (50) is provided at a position satisfying Q3 <(Q1-Q2).