JP4422658B2 - Liquid dispensing device - Google Patents

Description

  The present invention relates to a liquid dispensing apparatus, and more particularly to a liquid dispensing apparatus used for dispensing a liquid containing a biological component.

  Analyzing biological samples such as blood and urine derived from patients is widely performed for diagnosing pathological conditions, and automated analyzers are used in hospitals and clinical laboratories. In this automatic analyzer, in order to measure various analysis items for a large number of samples, it is common to dispense a large number of samples and reagents one after another using a dispensing probe. In this case, it is necessary to wash the dispensing probe every time the sample or reagent to be dispensed changes.

  Here, analysis items that may affect measurement when components of the liquid to be dispensed remaining in the dispensing probe are mixed into the next liquid to be dispensed, that is, analysis items that are highly necessary to avoid carryover. When dispensing the above, it is necessary to perform washing more than normal washing.

  As a known technique dealing with this type of carry-over, for example, there is a technique described in Patent Document 1. In this patent document 1, a reagent dispensing probe after dispensing a reagent of an immunological analysis item that detects an antigen or an antibody utilizing an agglutination reaction of latex particles is washed with a washing solution over a sufficient washing time. Or after increasing the amount of cleaning liquid discharged and after dispensing reagents for biochemical analysis items, clean the reagent dispensing probe for a short time or reduce the amount of cleaning liquid discharged for cleaning. By doing so, it is described that wasteful consumption of the cleaning liquid is eliminated.

  Further, Patent Document 1 points out that wasteful consumption of the cleaning liquid can be eliminated by adjusting the flow rate of the cleaning liquid even in the case of a sample dispensing probe different from the reagent.

JP-A-4-169551

  By the way, in the analysis item having a high necessity for avoiding the carry-over described above, the analysis component is often a protein, and the protein in another liquid to be dispensed adheres to the dispensing probe, and the analysis item is analyzed. It is a problem that the liquid is mixed during dispensing.

  As a method for cleaning a dispensing probe when measuring such an analysis item, a method of extending the cleaning time or increasing the amount of the cleaning solution, or a method using a cleaning solution containing a detergent such as a surfactant is generally used. is there.

  However, as described above, it may be difficult to wash proteins even by using a method of increasing the washing time or increasing the amount of washing liquid, or using a washing liquid containing a detergent such as a surfactant.

In particular, when collecting and measuring samples for analysis of biochemical items and immunity items with a wide measurement concentration range from the same container, it is required to reduce carryover between samples as much as possible, and proteins are washed effectively. There is a need.
An object of the present invention is to realize a liquid dispensing apparatus capable of efficiently removing proteins adhering to a dispensing probe and reducing carryover between samples or between reagents.

  In the liquid dispensing apparatus, the present invention provides a voltage applied to the first electrode set on the inner wall of the dispensing probe, the second electrode installed in the cleaning tank, the first electrode, and the second electrode. Voltage application means for applying, and the inner wall of the dispensing probe and at least the tip of the outer wall and the vicinity thereof are formed of an insulating material.

  The dispensing probe sucks and discharges the electrophoresis solution into the washing tank, immerses the tip of the dispensing probe in the washing tank containing the electrophoresis solution, and the first probe in the dispensing probe. The dispensing probe is washed by applying a voltage to the first and second electrodes while the electrode and the second electrode are in contact with each other via the electrophoresis solution.

  Alternatively, an electrophoretic solution supply means for supplying the electrophoretic solution into the washing tank is provided, and at least the tip of the dispensing probe is immersed in the washing tank in which the electrophoretic solution is accommodated. The dispensing probe is washed by applying a voltage to the first and second electrodes in a state in which is drawn up to the first electrode.

  Thereby, the protein which is a component in the liquid to be dispensed adsorbed on the wall surface of the dispensing probe can be moved into the solution by electrophoresis and removed together with this solution.

  According to the present invention, since the dispensing probe is washed by the action of electrophoresis, proteins in the liquid to be dispensed adsorbed on the dispensing probe can be efficiently removed, and between samples or between reagents. Carryover can be reduced.

Embodiments of the present invention will be described below with reference to the accompanying drawings.
FIG. 1 is a schematic configuration diagram of a liquid dispensing apparatus according to an embodiment of the present invention.

  In FIG. 1, a dispensing probe 1 is connected to a syringe 3 via a tube 2. The syringe 3 is driven by a syringe drive mechanism 4, and the syringe drive mechanism 4 is controlled by a control unit 5.

  The pump 6 sends the purified water from the tank 7 so that the inside of the syringe 3, the tube 2, and the dispensing probe 1 is filled with purified water. When the pump 6 sends purified water from the tank 7, the valve 8 is opened.

  This purified water draws the liquid to be dispensed into the dispensing probe 1 and operates the syringe 3 on the liquid to be dispensed in order to discharge the sucked liquid to be dispensed from the dispensing probe 1. The transmission medium is a transmission medium, and this transmission medium is denoted by reference numeral 9 in the figure.

  The dispensing probe 1 is made of an insulating material, but insulates a part of the dispensing probe, for example, the inner wall of the probe and the outer wall that contacts the liquid to be dispensed and the electrophoresis solution held in the probe washing tank 15. It may be composed of a body material, and the other part may be a conductor material.

  The dispensing probe 1 can be moved in the vertical direction (vertical direction) by the dispensing probe moving mechanism 11 driven by the motor 10, and the motor 10 is controlled by the control unit 5.

  In addition, the dispensing probe 1 is moved horizontally between the suction and discharge positions of the sample or reagent as the liquid to be dispensed and the dispensing probe washing tank by the dispensing probe moving mechanism 11 driven by the motor 12. This horizontal movement is also controlled by the control unit 5.

  A liquid container 14 is accommodated in the container container 13, and a sample or reagent that is a liquid to be dispensed is placed in the liquid container 14.

  Further, the dispensing probe 1 is lowered by the dispensing probe moving mechanism 11 at the suction position of the liquid to be dispensed, and the tip of the dispensing probe 1 is inserted slightly below the liquid surface of the liquid to be dispensed. After the lowering operation of the dispensing probe 1 is stopped, the required amount of liquid to be dispensed is sucked and held near the tip in the dispensing probe 1 by the operation of the syringe 3.

  Then, after the dispensing probe 1 is lifted by the dispensing probe moving mechanism 11, the dispensing probe 1 moves horizontally onto the discharge position into the reaction container.

  Next, the dispensing probe 1 is lowered to a predetermined height in the reaction container by the probe moving mechanism 11, and the liquid to be dispensed sucked and held in the dispensing probe 1 is moved by the operation of the syringe 3. Is discharged into the reaction vessel.

  The dispensing probe 1 that has finished dispensing the liquid to be dispensed is moved up by the dispensing probe moving mechanism 11 and then horizontally moved onto the probe cleaning tank 15. The dispensing probe 1 is lowered to a predetermined height in the probe washing tank 15 by the dispensing probe moving mechanism 11, opens the valve 8, and remains on the inner wall of the dispensing probe 1 with purified water as the syringe operation transmission medium 9. The liquid to be dispensed is pushed out of the dispensing probe 1.

  Further, the liquid to be dispensed remaining at the tip of the outer wall of the dispensing probe 1 is washed away by the purified water supplied from the purified water supply nozzle 17 installed in the probe washing tank 15 by opening the valve 16. At this time, the valve 18 of the probe cleaning tank 15 is opened, and the water that has cleaned the dispensing probe 1 is discharged to the waste liquid tank 19.

  Even with the washing with the purified water, the component (protein) of the liquid to be dispensed remaining adsorbed on the outer wall surface and the inner wall surface of the dispensing probe 1 is not washed and affects the analysis item to be measured in the next dispensing. If there is a possibility, a washing operation using electrophoresis is performed after washing with purified water.

  A cleaning operation using this electrophoresis will be described with reference to FIG. The electrophoresis solution supply nozzle 20 installed in the probe washing tank 15 is configured to wash a predetermined amount of electrophoresis solution (buffer solution) from the electrophoresis solution container 21 by the operation of the syringe 22 and the opening and closing of the valves 23 and 24. 15 (Step 101).

  The syringe 22 is driven by a syringe drive mechanism 25, and the syringe drive mechanism 25 is controlled by the control unit 5. The electrophoresis solution is an electrolyte solution having a pH of 8 or higher. The electrophoresis solution is filled in the washing tank so that the electrode 26 (second electrode) installed in the probe washing tank 15 is immersed.

  Subsequently, the dispensing probe 1 is lowered to a height at which the portion of the outer wall of the distal end of the dispensing probe 1 made of an insulating material that is in contact with the liquid to be dispensed is immersed in the solution held in the cleaning tank 15 (step 102). ).

  After stopping the lowering operation of the dispensing probe 1, the solution for electrophoresis in the probe washing tank 15 is sucked into the dispensing probe 1 by the operation of the syringe 3 (step 103). The amount of the solution sucked into the dispensing probe 1 is larger than the amount of the liquid to be dispensed sucked into the dispensing probe 1 for dispensing, and the electrode 27 (the first electrode installed on the inner wall of the dispensing probe 1) 1 electrode) is in contact with the aspirated solution.

  The electrodes 26 and 27 are made of a material such as platinum. As the insulator constituting the dispensing probe 1, materials such as glass, fused silica, and fluorine-containing hydrocarbon resin that are generally used for capillary electrophoresis are used. Moreover, the probe inner diameter comprised with an insulator is 1 mm or less.

  After the electrophoresis solution is aspirated into the dispensing probe 1, the electrode 27 in the dispensing probe 1 and the probe washing tank 15 are moved by the electrophoresis power supply device 28 (voltage applying means) controlled by the control unit 5. A voltage is applied between the two electrodes 26 (step 104). That is, a voltage is applied to the electrode 27 and the electrode 26 in a state where the electrode 27 in the dispensing probe 1 and the electrode 26 in the cleaning tank 15 are in contact via the electrophoresis solution.

  When a voltage is applied between the electrodes 26 and 27, the total charge of the protein becomes negative due to the alkaline solution, and electrically repels the negative charge charged on the inner wall of the dispensing probe 1 and the outer wall of the tip, and the protein is dispensed. It becomes difficult to adsorb on the surface of the probe 1.

  The negatively charged protein moves in the solution toward the anode by electrophoresis. On the other hand, the solution moves toward the cathode by electroosmotic flow. For example, when a voltage is applied using the electrode 27 on the dispensing probe 1 side as an anode and the electrode 26 on the washing tank 15 side as a cathode, the negatively charged protein moves toward the electrode 27 on the inner wall side of the dispensing probe 1. However, if the electroosmotic flow of the solution is faster, it will flow to the washing tank 15 side.

  Since the purpose is to release the protein adsorbed on the surface of the dispensing probe 1 into the solution, the time for applying the voltage may be short. After a certain time (for example, after 1 second), the application of voltage to the electrodes 26 and 27 is terminated (step 105).

  Immediately after the voltage application is finished, the dispensing probe 1 is moved up by the dispensing probe moving mechanism 11 so that the outer wall surface of the dispensing probe 1 is detached from the surface of the solution for electrophoresis held in the washing tank 15. At that time, the valve 8 is opened and the purified water which is the syringe operation transmission medium 9 is fed to push the electrophoresis solution in the dispensing probe 1 out of the probe and discharge it to the washing tank (step 106).

  Further, the valve 16 is opened, and the tip of the outer wall of the dispensing probe 1 immersed in the electrophoresis solution with the purified water supplied from the purified water supply nozzle 17 is rinsed (step 107), and the solution is washed into the washing tank 15.

  As a result, proteins released from the surface of the dispensing probe 1 into the electrophoresis solution by the application of voltage are washed away together with the solution. Further, the solution in the cleaning tank 15 is caused to flow by purified water supplied from the purified water supply nozzle 17.

  After the voltage application is completed, the electrophoresis solution held in the probe washing tank 15, the solution and purified water discharged from the dispensing probe 1, and the purified water supplied from the purified water supply nozzle 17 open the valve 18, and the waste liquid. It is discharged to the tank 19 (step 108).

  The transfer medium 9 is made into a solution by connecting the tube 2 and the solution supply nozzle 20 side of the valve 23 without providing the solution supply nozzle 20 on the cleaning tank 15 side, and this is discharged from the dispensing probe 1. The solution may be supplied to the probe cleaning tank 15. In this case, the operation of sucking the solution into the dispensing probe 1 is omitted. In this case, the syringe 3 and the syringe 22 may be provided, or a single syringe can be used.

  FIG. 3 is a diagram showing an example of an automatic analyzer to which the liquid dispensing apparatus according to the present invention is applied.

  In FIG. 3, an analysis unit 200 for analyzing biochemical analysis items has a reaction disk 203 in which translucent reaction vessels 205 are arranged concentrically. Water maintained at a predetermined temperature (for example, 37 ° C.) is supplied from the constant temperature water supply device 230 to the constant temperature bath of the reaction disk 203.

  A liquid dispensing apparatus 202 for collecting a sample includes a dispensing probe 1 capable of sucking and discharging a liquid, and the dispensing probe 1 is separated into a sample suction position on the line 62 and a sample discharge position 204 on the reaction disk 203. And the probe cleaning tank 15.

  A sample rack which is a container container 13 holds a liquid container 14 containing a biological sample such as serum, plasma or urine. The dispensing device 202 inserts the tip of the dispensing probe 1 slightly below the liquid level of the sample in the liquid container 14 held by the sample rack 13 and positioned at the sample suction position. Then, a predetermined amount of sample is sucked and held near the tip of the dispensing probe 1, and the dispensing probe 1 is moved to the sample discharge position 204 in the container row on the reaction disk 203. Then, the sample held in the probe 1 is discharged into the cleaned reaction container 205 at the discharge position.

  The reaction container 205 that has received the sample is moved to the addition position of the first reagent by the reaction disk 203. There are two systems of reagent supply systems, and the first reagent selected according to the analysis item from among the reagent bottles 217 arranged in large numbers on the first reagent disk 215 is displayed on the reaction disk 203 by the reagent dispensing device 210. It is dispensed into the reaction vessel 205.

  Next, the mixture of the sample and the reagent in the reaction vessel 205 is stirred by the stirring mechanism 219, and the chemical reaction between the sample and the reagent proceeds.

  In the case of an analysis item that requires the second reagent, the second reagent selected according to the analysis item from among the reagent bottles 218 arranged in large numbers on the second reagent disk 216 is the addition position of the second reagent. The reagent is added to the reaction container 205 by the reagent dispensing device 211.

  The reaction liquid of the sample and the reagent formed in the reaction container 205 is irradiated with the light beam from the multi-wavelength light source 235 at the photometric position 241 while being accommodated in the reaction container 205. The light transmitted through the reaction vessel 205 is spectrally separated by the multi-wavelength photometer 240, and the photometric signal is digitized by the analog-digital converter 245 and input to the control unit 5 for arithmetic processing, and the concentration of the measurement object in the sample or Enzyme activity values are calculated.

  The photometric reaction container 205 is cleaned by a container cleaning unit (not shown) and moved to a sample discharge position to receive a new sample.

  The dispensing probe 1 in which one sample on the sample rack 13 is dispensed is washed in the probe washing tank 15 before another sample is collected, and is repeatedly used for many samples.

  If there is a request for an analysis item that is highly necessary to avoid carry-over with respect to another sample, the electrophoresis described with reference to FIG. 1 is used in the probe washing tank 15 before collecting another sample. The outer wall surface and inner wall surface of the dispensing probe 1 are cleaned by the cleaning method thus performed, and carry over to the next sample can be reduced.

  The washing using electrophoresis can be applied to the reagent dispensing probe of the reagent dispensing apparatus 210 or 211.

It is a schematic block diagram of the liquid dispensing apparatus which is one Embodiment of this invention. It is a flowchart of the washing | cleaning operation | movement using electrophoresis in the liquid dispensing apparatus which is one Embodiment of this invention. It is a schematic diagram of an example of an automatic analyzer to which a liquid dispensing apparatus according to the present invention is applied.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Dispensing probe 2 Tube 3, 22 Syringe 4 Syringe drive mechanism 5 Control part 6 Pump 11 Dispensing probe moving mechanism 15 Probe washing tank 20 Electrophoresis solution supply nozzle 21 Electrophoresis solution container 26 Probe washing tank electrode 27 minutes Note Probe electrode 28 Electrophoresis power supply

Claims (5)

A dispensing probe in which the inner wall and at least the tip of the outer wall are formed of an insulating material, and sucks and dispenses the liquid to be dispensed;
A first electrode set on an inner wall formed of an insulating material of the dispensing probe;
A washing tank containing an electrophoresis solution for washing the dispensing probe;
A second electrode installed in the cleaning tank;
Voltage applying means for applying a voltage to the first and second electrodes;
Bei give a upper Symbol dispensing probe to suck the solution for electrophoresis discharged into the cleaning tank, at least the distal end of the dispensing probe was immersed in an electrophoretic solution contained in the cleaning tank The voltage is applied to the first and second electrodes while the first electrode and the second electrode in the dispensing probe are in contact with each other through the electrophoresis solution. A liquid dispensing apparatus characterized by cleaning the inner wall of a probe. A dispensing probe in which the inner wall and at least the tip of the outer wall are formed of an insulating material, and sucks and dispenses the liquid to be dispensed;
A first electrode set on an inner wall formed of an insulating material of the dispensing probe;
A washing tank for washing the dispensing probe;
A second electrode installed in the cleaning tank;
Voltage applying means for applying a voltage to the first and second electrodes;
An electrophoretic solution supply means for supplying an electrophoretic solution into the washing tank;
The Bei example, the least distal end of the upper Symbol dispensing probe immersed in the cleaning bath solution for the electrophoresis is accommodated, first and electrophoresis solution while sucking up to the first electrode A liquid dispensing apparatus, wherein the inner wall of the dispensing probe is washed by applying a voltage to the second electrode.   3. The liquid dispensing apparatus according to claim 1, wherein the dispensing probe discharges purified water to the washing tank, and the dispensing probe is washed prior to washing with the electrophoresis solution or the electric probe. A liquid dispensing apparatus, which is performed after washing with a solution for electrophoresis. A reaction disk in which a plurality of reaction containers are arranged; a reagent disk in which a plurality of reagent containers are arranged; a sample dispensing probe that sucks a liquid sample and discharges it to the reaction container on the reaction disk; and In an automatic analyzer having a reagent dispensing probe that sucks a reagent from the reagent container and discharges the reagent into the reaction container on the reaction disk, and an analysis means for analyzing the liquid components in the reaction container on the reaction disk ,
The sample dispensing probe has an inner wall and at least a tip portion of the outer wall formed of an insulating material, and a washing tank for washing the inner wall of the sample dispensing probe;
A first electrode set on an inner wall formed of an insulating material of the sample dispensing probe;
A second electrode installed in the cleaning tank;
Voltage applying means for applying a voltage to the first and second electrodes;
An electrophoretic solution supply means for supplying an electrophoretic solution into the washing tank;
The Bei example, immersed in the upper Symbol cleaning tank in which the sample dispensing less solution for electrophoresis the tip of the probe is accommodated, the first electrophoretic solution in the state of being sucked down to the first electrode An automatic analyzer characterized in that an inner wall of the sample dispensing probe is washed by applying a voltage to the first and second electrodes. A reaction disk in which a plurality of reaction containers are arranged; a reagent disk in which a plurality of reagent containers are arranged; a sample dispensing probe that sucks a liquid sample and discharges it to the reaction container on the reaction disk; and In an automatic analyzer having a reagent dispensing probe that sucks a reagent from the reagent container and discharges the reagent into the reaction container on the reaction disk, and an analysis means for analyzing the liquid components in the reaction container on the reaction disk ,
The sample dispensing probe has an inner wall and at least a tip portion of the outer wall formed of an insulating material, and a washing tank for washing the inner wall of the sample dispensing probe;
A first electrode set on an inner wall formed of an insulating material of the sample dispensing probe;
A second electrode installed in the cleaning tank;
Voltage applying means for applying a voltage to the first and second electrodes;
Bei give a upper Symbol sample dispensing probe sucks the electrophoresis solution discharged into the cleaning tank, the washing tank of the sample dispensing less solution for electrophoresis the tip of the probe is accommodated And applying a voltage to the first and second electrodes while the first electrode and the second electrode in the sample dispensing probe are in contact with each other through the electrophoresis solution An automatic analyzer characterized by cleaning the inner wall of the sample dispensing probe.

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