JP3725461B2 - Dispensing device and liquid analyzer using the same - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a dispensing apparatus and an apparatus such as an immunoassay apparatus, a blood agglutination measurement apparatus, and a biochemical analysis apparatus using the same.
[0002]
[Prior art]
As prior art related to this invention,
A PTFE tube, a nozzle tip made of a conductive material attached to the tube tip, an outer cylinder made of a conductive material that mechanically supports the PTFE tube and simultaneously transmits an electric signal for detecting the liquid level, and a nozzle as a flow path By using a nozzle composed of parts such as a joint for connecting, a data defect caused by carryover of a measurement substance or a reaction interfering substance on the inner wall of the nozzle is prevented (for example, Japanese Patent Laid-Open No. Hei 11- 271329), and
[0003]
In a liquid suction device including a nozzle portion for sucking a liquid in a container, the nozzle portion includes a double-structure nozzle main body composed of an electrically insulating inner tube and a conductive outer tube, and the nozzle main body. A conductive nozzle tip provided in a state electrically insulated from the conductive outer tube at the tip of the nozzle, and between the conductive nozzle tip and the metal part on which the container is placed Based on the change in capacitance, the liquid level of the liquid in the container is detected, and based on the change in capacitance between the tip of the conductive nozzle and the conductive outer tube, An apparatus that detects the amount (see, for example, Japanese Patent Application Laid-Open No. 10-31840) is known.
[0004]
[Problems to be solved by the invention]
7 and 8 are configuration diagrams of the dispensing device for explaining the problem to be solved by the present invention.
The dispensing apparatus shown in FIG. 7 is a pipette 203 having a double tube structure comprising a conductive outer tube 201 and an electrically insulating inner tube 202, and for sucking the liquid 205 in the container 204 through the pipette 203. Based on the change in capacitance between the syringe pump 206, the connection member 207 that connects the pipette 203 and the syringe pump 206 to conduct the liquid, and the conductive member 208 on which the pipette 203 and the container 204 are placed. A liquid level detection unit 209 that detects the liquid level in the container 204 is provided, and the inner wall of the flow path from the tip of the pipette 203 to the syringe pump 206 is formed of an electrically insulating member to prevent carryover.
[0005]
By the way, generally in such a dispensing apparatus, as shown in FIG. 7, it dispenses in the state where the liquid 210 like a washing | cleaning liquid was previously stored in the flow path from the pipette 203 to the syringe pump 206, and the syringe pump 206. (Suction / discharge) is often performed. Accordingly, in this case, the capacitance between the pipette 203 and the conductive member 208 is equal to the capacitance Ct between the outer tube 201 and the conductive member 208 and the stored liquid 210 as shown in FIG. And the stray capacitance Cs.
[0006]
That is, the liquid level detection unit 209 detects the liquid level in the container 204 based on the change in capacitance (Ct + Cs). However, in such a case, as shown in FIG. 8, if the bubble 211 existing in the stored liquid suddenly divides the liquid 210 for some reason, the capacitance (Ct + Cs) changes suddenly. However, the liquid level detection unit 209 has an inconvenience that it erroneously detects that the tip of the pipette 203 is in contact with the liquid level.
[0007]
The present invention has been made in view of such circumstances, and provides a dispensing device with a liquid level detection function that does not malfunction even if the stored liquid is divided by bubbles.
[0008]
[Means for Solving the Problems]
A pipette having a double tube structure comprising an electrically conductive outer tube and an electrically insulating inner tube, a pump for sucking the first liquid in the container through the pipette, a second pipette and a second in the pump In a state where the liquid is stored, the driving mechanism moves the pipette to bring the pipette into contact with the first liquid in the container, and the contact between the pipette in the state where the second liquid is stored and the first liquid in the container a liquid level detector for detecting the first liquid level of the liquid in the container based on a change in capacitance, and the connecting member that connects the pipette and a pump, a second conductive outer tube and the pump A dispensing apparatus including a short-circuit member that electrically short-circuits the liquid is provided.
The present invention also includes a pipette having a double tube structure comprising a conductive outer tube and an electrically insulating inner tube, a pump for sucking the first liquid in the container through the pipette, A drive mechanism that moves the pipette to bring the pipette into contact with the first liquid in the container while the second liquid is stored in the pump, and a pipette that stores the second liquid and the first in the container A liquid level detector for detecting the level of the first liquid in the container based on a change in capacitance due to contact with the liquid, and a pipette fixedly connected to the pump, and a conductive outer tube And a connecting member that electrically short-circuits the second liquid inside.
A syringe pump is preferably used as the pump from the viewpoint of quantitative accuracy, but is not limited thereto, and a roller pump or the like can also be used.
[0009]
DETAILED DESCRIPTION OF THE INVENTION
As shown in FIG. 6, the dispensing device of the present invention is characterized by a pipette 103 having a double tube structure comprising a conductive outer tube 101 and an electrically insulating inner tube 102 and a liquid 105 in a container 104. Electrical connection between the syringe pump 106 for sucking through 103, the connecting member 107 for connecting the pipette 103 and the syringe pump 106 to conduct the liquid, the conductive outer tube 101 and the liquid in the syringe pump 106 It is in the point provided with the short circuit member 112 which short-circuits.
[0010]
That is, since the liquid in the conductive outer tube 101 and the syringe pump 106 is electrically short-circuited by the short-circuit member 112, even if the liquid stored in the connection member 107 is suddenly divided by bubbles, the liquid level detection unit The stray capacitance Cs seen from 109 hardly changes. Therefore, erroneous detection of the liquid level caused by the generation of bubbles can be prevented.
[0011]
In this case, the connection member may have conductivity and constitute the short-circuit member.
The dispensing device according to the present invention includes a liquid level detection unit that detects the liquid level in the container based on a change in capacitance between the tip of the conductive outer tube and the conductive member on which the container is placed. Can be used effectively.
Furthermore, this invention provides the liquid analyzer which used the said dispensing apparatus.
[0012]
Embodiment FIG. 1 is a front view showing a liquid analyzer using the dispensing apparatus of the present invention. In this embodiment, the liquid analyzer is an immunoassay device, but is not limited to this.
The main body 20 of the immunoassay device includes a dispensing device 22, and a vertical driving mechanism 25 and a horizontal driving mechanism 26 that hold the dispensing device 22 and move it in the directions of arrows Z and X, respectively.
The dispensing device 22 is held by the vertical drive mechanism 25 via a holding member 24.
[0013]
In the vertical drive mechanism 25, the vertical moving member 23 is slidably supported by a vertical guide shaft 21a penetrating the vertical moving member 23, and is engaged with a ball screw 21 parallel to the guide shaft 21a with a screw. It moves in the direction of arrow Z by the rotation of 28. The guide shaft 21 a, the ball screw 21, and the stepping motor 28 are installed on the frame 43.
[0014]
In the horizontal drive mechanism 26, a horizontal moving member 31 is slidably supported by a horizontal guide shaft 29a penetrating the horizontal moving member 31, and is engaged with a ball screw 29 parallel to the guide shaft 29a with a screw. It moves in the direction of arrow X by the rotation of 27. The guide shaft 29 a, the ball screw 29, and the stepping motor 27 are installed on a metal frame 44. The frame 43 of the vertical drive mechanism 25 is attached to the horizontal movement member 31. The frame 44 is electrically grounded.
[0015]
The frame 44 is provided with a cleaning chamber 38 and an aluminum rack 46 that houses a specimen container 39, a buffer container 40, a latex reagent container 41, a diluent container 42, and a reaction chamber 43. A dilution chamber 45 is installed. The cleaning chamber 38 includes a liquid supply nipple 38a and a drainage nipple 38b at the lower part and the upper part, respectively, and the dilution chamber 45 includes a drainage nipple 45a at the lower part.
[0016]
FIG. 2 is a cross-sectional view of an essential part showing the dispensing apparatus of the present invention. As shown in FIG. 1, the pipette 1 has a double tube structure including a conductive outer tube 2 and an electrically insulating inner tube 3. The pipette 1 is connected to a syringe pump 4 via a conductive connecting member 5. The syringe pump 4 includes a cylinder 6 and a piston 7 inserted into the hole 6a of the cylinder 6 and a linear actuator 8. The linear actuator 8 reciprocates the piston 7 inside the hole 6a of the cylinder 6 by a built-in stepping motor. It has become.
[0017]
The outer cylinder 2 of the pipette 1 is formed of a stainless steel pipe having a length of 136 mm, an outer diameter of 2.4 mm, and an inner diameter of 2.0 mm. The inner cylinder 3 is formed of a PTFE tube having a length of 136 mm, an outer diameter of 2.0 mm, and an inner diameter of 1.4 mm, and is fused to the inner surface of the outer cylinder 2. The tip of the pipette 1 is drawn so that the outer shape of the outer cylinder 2 is 1.4 mm.
[0018]
The connecting member 5 is made of stainless steel, and has a stepped through hole 5b at its axis. The base end of the pipette 1 is press-fitted and fixed to the stepped portion of the through hole 5b. The male screw portion 5 a of the connection member 5 is fixed to the female screw portion provided at the tip of the syringe pump 4, and the connection member 5 is connected to the syringe pump 4 in a watertight manner by an O-ring 9.
[0019]
The protruding portion 5c at the end of the connecting member 5 is exposed to the inside of the hole 6a of the cylinder 6, and the liquid stored in the hole 6a and the outer cylinder 2 are electrically short-circuited by the connecting member 5. . The cylinder 6 of the syringe pump 4 is made of polyacetal resin, the hole 6a has an inner diameter of 4.2 mm, an effective length of 40 mm, and the moving stroke of the piston 7 is 20 mm.
[0020]
Further, a lead wire 10 for detecting a liquid level detection signal is soldered to the outer cylinder 2 through a hole 5d formed on the side surface of the connection member 5, and the hole 6a and the pipette 1 are provided on the side surface of the cylinder 6. A cleaning liquid supply nipple 11 for cleaning the inner wall is provided.
[0021]
FIG. 3 is a system diagram showing the fluid system of the embodiment of FIG. 1, and electromagnetic valves SV1 to SV7, sheath liquid tank SC, positive pressure source PS, cleaning chamber 38, drainage chambers WC1, WC2, negative pressure source NS, Dilution chamber 45, syringe pump CP, and sheath flow cell FC are connected by a flow path (tube).
The sheath flow cell FC is provided with a light emitting element (laser diode) 51 and a light receiving element (photodiode) 52 for detecting a particle signal by irradiating the sample flow (sheath flow) with light.
[0022]
FIG. 4 is a block diagram showing an electric circuit of the embodiment of FIG.
In the figure, a control unit 53 receives signals from an input unit 50 for inputting various measurement conditions, a light receiving element 52, and a liquid level detection unit 59, and based on the signals, a built-in stepping of the linear actuator 8 (FIG. 2). A pipette syringe pump drive unit 54 that drives a motor, a pipette drive unit 55 that drives the stepping motors 27 and 28 (FIG. 1) to move the pipette 1 in the X and Z directions, and a syringe pump CP (FIG. 3) The syringe pump drive unit 56 to be driven, the valve drive unit 57 to drive the electromagnetic valves SV1 to SV7, and the light emitting element 51 are driven and controlled, and the measurement result is output to the output unit 58.
[0023]
The control unit 53 is configured by a microcomputer including a CPU, ROM, and RAM, and the output unit 58 is configured by an LCD and a printer. The input unit 50 includes a keyboard.
A known driver circuit is used for each of the drive units 54 to 57.
[0024]
In the liquid level detection unit 59, a high frequency oscillator 300 having an oscillation frequency of 650 kHz and a band pass filter 302 are connected to the lead wire 10 connected to the pipette 1 via a resistor R of 39 kΩ. On the output side of the filter 302, a detector 304, a differentiator 306, and a comparator 308 are connected in series.
[0025]
The container A is placed on a grounded metal frame 44 (FIG. 1), and the capacitance C between the pipette 1 and the ground surface depends on whether the tip of the pipette 1 is in contact with the liquid level in the container A or not. Changes. Therefore, a high frequency signal having an amplitude corresponding to the capacitance C is obtained at the output of the RC integrating circuit formed by the resistor R and the capacitance C, that is, at the input side of the filter 302.
[0026]
The high-frequency signal is passed through the band-pass filter 302 and detected by the detector 304, thereby being converted into a DC signal. Further, this DC signal is detected by the differentiator 306 as the level change of the DC signal, and is compared with a predetermined value by the comparator 308.
[0027]
That is, when the pipette 1 comes into contact with the liquid surface, the capacitance C is short-circuited by the pipette 1 and the liquid, and the DC signal level becomes lower than a predetermined value, so that it is detected that the pipette 1 is in contact with the liquid surface. 308 outputs the detection signal.
[0028]
Here, the container A corresponds to the cleaning chamber 38, the specimen container 39, the buffer container 40, the latex reagent container 41, the diluent container 42, the reaction chamber 43, the dilution chamber 45, and the like in FIG.
[0029]
The measurement operation in such a configuration will be described with reference to the fluid system diagram shown in FIG. 3 and the flowchart shown in FIG.
In the initial state, all the valves SV1 to SV7 in FIG. 3 are closed.
First, in step S1, the pipette is washed. In this embodiment, a common liquid is used for the sheath liquid, the cleaning liquid, and the diluting liquid.
[0030]
The pipette 1 is inserted into the cleaning chamber 38 based on the driving of the vertical and horizontal driving mechanisms 25 and 26 and the liquid level detection. When the valves SV1 and SV2 are opened, the sheath liquid is discharged from the pipette 1 through the syringe pump 4 to clean the inner surface of the syringe pump 4 and the pipette 1, and the sheath liquid is supplied to the cleaning chamber 38 from the liquid supply nipple 38a. Inflow, the outer surface of the pipette 1 is washed.
[0031]
The liquid in the cleaning chamber 38 is recovered from the drain nipple 38b to the drain chamber WC1, and the liquid level of the cleaning liquid in the cleaning chamber 38 is maintained at a substantially constant height. Then, the valves SV1 and SV2 are closed.
[0032]
Next, the dispensing device 22 is driven, and 80 μL of the buffer solution is sucked into the pipette 1 from the buffer solution container 40 (step S2).
The dispensing device 22 is driven to suck 10 μL of the sample from the sample container 39 into the pipette 1 (step S3), and the dispensing device 22 is driven to discharge 80 μL of the buffer solution and 10 μL of the sample to the reaction chamber 43. (Step S4).
[0033]
The cleaning process similar to step S1 is performed (step S5), and the sample in the reaction chamber 43 is preincubated for about 1 minute at a temperature of 45 ° C. (step S6). Thereby, the factor which induces the nonspecific reaction contained in the specimen is absorbed and buffered by the buffer solution.
[0034]
Next, the dispensing device 22 is driven to add 10 μL of the latex reagent from the latex reagent container 42 to the reaction chamber 43 (step S7). Thereby, an antigen-antibody reaction (or antibody-antigen reaction) is started.
[0035]
Next, when the reaction time of 15 minutes elapses (step S8), the dispensing device 22 is driven to dispense 12.5 μL of the sample in the reaction chamber 43 into the dilution chamber 45. The dilution chamber 45 is supplied with 1000 μL of sheath liquid from the sheath liquid tank SC in advance by opening the valves SV4 and SV6 and driving the syringe pump CP, and the sample in the reaction chamber 43 is 81 by the sheath liquid. Dilution is doubled (step S9). As a result, the antigen-antibody reaction of the sample is stopped, and the particle concentration becomes suitable for measurement.
[0036]
Next, the valves SV4 and SV5 are opened to store the sample in the flow path between the valves, and then the valves SV4 and SV5 are closed.
Next, the valve SV7 is opened to drive the syringe pump CP, and the stored sample is pumped to the sheath flow cell FC. At the same time, the valve SV3 is opened to supply the sheath liquid to the sheath flow cell FC to form a sheath flow. Light is emitted from the light emitting element 51 to the formed sheath flow, and the scattered light intensity of the particles in the sheath flow is measured by the light receiving element 52 (step S10).
[0037]
The control unit 53 discriminates the agglomerated latex particles from the agglomerated latex particles based on the intensity of the scattered light, and the ratio of the number of latex particles agglomerated at least two to the total number of latex particles is the aggregation rate P / T (%). Calculate as And the value which converted the obtained aggregation rate (P / T) with the calibration curve for normal inspection created beforehand is output from the output 58 (step S11). Thus, an immunoassay is performed.
[0038]
【The invention's effect】
According to the present invention, since the conductive outer cylinder of the pipette and the liquid in the syringe pump are electrically short-circuited, even if air bubbles are generated between the pipette and the syringe pump, The change in capacity is suppressed, and erroneous detection when liquid level detection is performed is prevented.
[Brief description of the drawings]
FIG. 1 is a front view of an immunoassay device using a dispensing device of the present invention.
FIG. 2 is a cross-sectional view of a main part of the dispensing device of the present invention.
3 is a system diagram of a fluid system of the immunoassay apparatus shown in FIG. 1. FIG.
FIG. 4 is a block diagram of an electric circuit of the immunoassay device shown in FIG.
FIG. 5 is a flowchart showing the operation of the immunoassay apparatus shown in FIG.
FIG. 6 is an explanatory diagram showing the principle of the present invention.
FIG. 7 is an explanatory diagram for explaining the problem of the present invention.
FIG. 8 is an explanatory diagram for explaining the problem of the present invention.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Pipette 2 Outer cylinder 3 Inner cylinder 4 Syringe pump 5 Connection member 5a Male thread part 5b Through-hole 5c Projection part 5d Hole 6 Cylinder 6a Hole 7 Piston 8 Linear actuator 9 O-ring 10 Lead wire 11 Nipple 22 Dispensing device

Claims (5)

A pipette with a double pipe structure consisting of a conductive outer tube and an electrically insulating inner tube;
A pump for aspirating the first liquid in the container through a pipette;
A drive mechanism for moving the pipette and bringing the pipette into contact with the first liquid in the container in a state where the second liquid is stored in the pipette and the pump;
A liquid level detector that detects the liquid level of the first liquid in the container based on a change in capacitance due to contact between the pipette in a state in which the second liquid is stored and the first liquid in the container;
A connecting member that connects the pipette and a pump,
A dispensing apparatus comprising a short-circuit member that electrically short-circuits the conductive outer tube and the second liquid in the pump.  The dispensing device according to claim 1, wherein the connecting member has conductivity and forms the short-circuit member. Liquid level detection unit, according to claim to test knowledge the first surface of the liquid in the container based on a change in capacitance between the conductive member to which the container and the outer tube of the conductivity is placed The dispensing apparatus according to 1 or 2. A liquid analyzer using the dispensing apparatus according to claim 1 . A pipette with a double pipe structure consisting of a conductive outer tube and an electrically insulating inner tube;
A pump for aspirating the first liquid in the container through a pipette;
A drive mechanism for moving the pipette and bringing the pipette into contact with the first liquid in the container in a state where the second liquid is stored in the pipette and the pump;
A liquid level detector that detects the liquid level of the first liquid in the container based on a change in capacitance due to contact between the pipette in a state in which the second liquid is stored and the first liquid in the container;
A dispensing device comprising: a connecting member that fixes and connects a pipette to a pump and electrically short-circuits the conductive outer tube and the second liquid inside.

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