JPH11230970A - Sample dispensing method and automatic analyzer - Google Patents

Abstract

(57) [Problem] To dilute and dispense a sample, it is not necessary to use a reaction vessel on a reaction line, and a dedicated dilution line is not required. A dispensing probe moved by a movable arm has a mixing chamber, a pipe section, and a diluent passage. At the same time as the sample is sucked into the mixing chamber through the pipe section, the diluent flows in through the communication hole 3 and a diluted sample is formed in the dispensing probe. The ultrasonic waves from the ultrasonic oscillator 11 promote the mixing of the two liquids in the mixing chamber.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sample dispensing method and an automatic analyzer, and more particularly to a method for diluting and dispensing a sample to be analyzed when a liquid sample is analyzed by the automatic analyzer. Method and apparatus.

[0002]

2. Description of the Related Art An automatic analyzer divides a biological fluid sample such as blood or urine into a reaction vessel on a reaction line, and reacts the sample with a reaction reagent in the reaction vessel. This is an apparatus for optically measuring a reaction solution, for example, and analyzing analysis items in a sample. In such an automatic analyzer, since various reaction reagents are used according to a large number of analysis items, it is preferable that the amount of the reaction reagent used is as small as possible so as to reduce the running cost of the inspection work. One way to reduce reaction reagent consumption is to analyze using diluted samples. That is, in the case of the same volume in the diluted sample, the absolute amount of the original sample is reduced, and accordingly, the amount of the reaction reagent to be added can be reduced accordingly.

[0003] Japanese Patent Publication No. 4-7956 discloses diluting a sample on a reaction line arranged so that a number of reaction vessels can rotate. That is, a sample requiring dilution is added to an empty reaction vessel on a reaction line by a dispensing probe, and then a diluted solution is added to obtain a diluted sample.
Then, when the reaction vessel is rotated and transported near the sample dispensing position, the diluted sample is dispensed to another reaction vessel on the reaction line by the dispensing probe. The dispensed diluted sample is reacted with a reaction reagent, and the reaction solution is measured with a photometer.

JP-A-58-85168 discloses that a dedicated sample dilution line is provided separately from a reaction line to dilute a sample. In other words, after dispensing a sample into a dedicated dilution line container using a dispensing probe, a dilution sample is discharged from the dispensing probe into the container to form a diluted sample, and the diluted sample is transferred from the dedicated dilution line to the reaction line on the reaction line. Dispense into containers.

[0005]

SUMMARY OF THE INVENTION The above-mentioned Japanese Patent Publication No. Hei 4-7
According to the dilution method on the reaction line described in Japanese Unexamined Patent Publication No. 956, a dilution cycle from dispensing a sample to a reaction container for dilution to dispensing a diluted sample to another reaction container is described. I have to wait for the reaction not to start for this time. In addition, since the reaction vessels on the reaction line are used for dilution, if there are many samples that need to be diluted, the number of reaction vessels that can be used for the reaction is reduced, and the processing capacity of the analyzer is reduced. Decrease.

On the other hand, according to the dilution method using a dedicated dilution line described in Japanese Patent Application Laid-Open No. 58-85168, there is a problem that the configuration of the apparatus for diluting the sample becomes complicated and the size of the analyzer becomes large.

An object of the present invention is to provide a sample dispensing method and an automatic analyzer which can dilute a sample without using a reaction vessel on a reaction line for diluting the sample and without providing a dedicated dilution line. Is to do.

[0008]

SUMMARY OF THE INVENTION A sample dispensing method according to the present invention has a pipe section disposed on a side contacting a sample to be inhaled and a mixing chamber communicating with the pipe section. Using a probe, while the dispensing probe is positioned on the sample container, a sample and a diluent flow into the mixing chamber, and the sample diluted in the mixing chamber is passed through the pipe section on the reaction line. Discharged into a reaction vessel.

Further, in the automatic analyzer according to the present invention, the dispensing probe which can be moved up and down is provided with a pipe section arranged on the side in contact with a sample to be inhaled, and a mixing chamber communicated with the pipe section. A diluent passage communicated with the mixing chamber, and the diluent flows from the diluent passage into the mixing chamber as the sample from the sample container is sucked into the mixing chamber through the pipe section. It is composed of

In a preferred embodiment of the present invention, an undiluted sample is accommodated in a pipe section, and a sample diluted with a diluent is formed in a mixing chamber. After discharging to the sample receiving section for the analysis item, the diluted sample in the mixing chamber is discharged to the reaction container.
Further, the degree of dilution of the sample is changed by changing the ratio between the flow rate of the sample flowing into the mixing chamber and the flow rate of the diluent flowing into the mixing chamber. Further, by vibrating the liquid in the mixing chamber into which the sample and the diluent flow, the mixing between the sample and the diluent is promoted.

[0011]

FIG. 1 shows a schematic configuration of an automatic analyzer according to one embodiment of the present invention. In FIG. 1, on a rotatable sample disk 30, a number of sample containers 23 containing a biological fluid sample such as serum are arranged. On the rotatable reagent disk 40, a number of reagent liquid bottles 46 corresponding to various analysis items are placed.
A reaction line 60 composed of a large number of reaction vessels 18 arranged in a circle is formed on a reaction disk 61 and is intermittently rotated and transferred. The reaction vessel 18 is kept at a predetermined temperature. The luminous flux from the light source 64 is applied to the reaction line 6.
The light passes through the reaction vessel on the zero and enters the multi-wavelength photometer 65. After completion of the photometry, the reaction container 18 is washed by the container washing mechanism 67 and used for receiving a new sample.

The dispensing probe 50 is held by the movable arm 32, and moves down and up at the sample suction position on the sample disk 30 and the sample discharge position 18a on the reaction line 60 as the movable arm moves up and down. Ascent is possible. With the turning operation of the movable arm 32, the dispensing probe 50 can reciprocate in the turning range from the sample suction position to the sample discharge position 18a via the probe washing tank 19 and the electrolyte analyzer 17.

As will be described later, the dispensing probe 50 includes
The first syringe pump 27 and the second syringe pump 28 are connected. The solenoid valves 15 and 29 are opened when pure water is sent to the corresponding syringe pump. In this example,
Pure water is used as a diluent for diluting the sample and a washing water for washing the probe. Pure water is supplied by a water supply pump 16 from a pure water supply source, for example, a pure water tank (not shown).

As shown in FIG. 1, the ultrasonic oscillator 11 as a means for applying vibration to the liquid in the dispensing probe 50 is provided separately from the dispensing probe 50 and has a through hole in the center. The probe moves up and down in the through hole of the ultrasonic oscillation unit 11 to collect a sample from the sample container 23. That is, when the dispensing probe 50 moves up and down when provided separately, the ultrasonic oscillation unit does not change its position. On the other hand, as shown in FIG. 2, when the ultrasonic oscillation unit 11 is provided integrally with the dispensing probe 50, the ultrasonic oscillation unit 11 also moves together with the vertical movement and the turning movement of the dispensing probe 50.

The automatic analyzer has a control unit (usually a microcomputer) for controlling the operation of each mechanism unit. In the case of the operation control of the dispensing probe, the control unit controls the dispensing probe according to an instruction from the operation unit (which functions as a condition setting unit having a screen display unit and an operation key) of the analyzer. It is determined whether or not the sample is diluted within 50, and if an instruction is made to dilute the sample with inhalation, the suction operation of the first syringe pump 27 and the second operation are performed.
Control is performed so that the discharge operation of the syringe pump 28 proceeds simultaneously. On the other hand, if it is instructed that the dilution is not necessary with the inhalation of the sample, only the suction operation by the first syringe pump 27 is controlled. Thus, the dispensing probe 50 can selectively dispense a diluted sample or an undiluted sample into the reaction container 18 positioned at the discharge position 18a.

The reaction vessel 18 that has received the diluted sample or the undiluted sample is rotated counterclockwise by the reaction disk 61 and stops at the reaction reagent addition position, where the reaction reagent is added from the reagent nozzle 42. In this case, the reaction reagent bottle 46 corresponding to the analysis item of the reaction container
However, the reagent nozzle 42 is lowered in advance by the operation of the reagent dispensing arm 44 by the rotation operation of the reagent disk 40, and the reagent is sucked into the nozzle. The liquid in the reaction vessel 18 to which the sample and the reaction reagent have been added is stirred by the stirring device 48. When the reaction vessel in which the reaction solution is formed passes through the photometry position,
The absorbance is measured by the multi-wavelength photometer 65. After the photometry, the reaction vessel is washed by the vessel washing mechanism 67.

Next, referring to FIG.
Will be described. Dispensing probe 50 of FIG.
Is used in the analyzer of FIG. In FIG. 2, the ultrasonic oscillation unit 11 is shown as being provided integrally with the dispensing probe.

The dispensing probe 50 has an inner tube 1 and an outer tube 4 each made of stainless steel. The inner pipe 1 has a cylindrical chamber that forms the mixing chamber 13 and a pipe section 21 that communicates with the mixing chamber 13. The conduit 21 protrudes out of the outer tube 4, and is arranged on the side where the dispensing probe 50 comes into contact with the sample to be inhaled, that is, on the lower end side. The pipe section 21 functions as a sample suction nozzle, and the inside diameter thereof is smaller than the inside diameter of the mixing chamber 13. The pipe section 21 and the mixing chamber 13 communicate with each other through a throttle step taper portion, and one or two or more communication holes 3 are provided in this taper portion. This communication hole serves as a diluent inlet to the mixing chamber 13.

The lower end of the outer tube 4 is sealed, and a ring-shaped room formed between the outer tube 4 and the inner tube 1 is the diluent passage 5 in the dispensing probe 50. The upper pipe end of the outer pipe 4 is connected to a second syringe pump 28 via a bendable second flow path 26. On the other hand, the upper end of the inner pipe 1
The first syringe pump 2 through the bendable first flow path 25
7 is connected.

The first syringe pump 27 moves the dispensing probe 5 by the operation of the plunger 9 which moves forward and backward with respect to the syringe 2.
The sample suction / discharge operation at 0 is performed. The second syringe pump 28 feeds pure water 7 as a diluting liquid into the mixing chamber 13 by pushing the plunger 10 into the syringe 6.

After the dispensing operation on the preceding sample is completed, the entire passage in the dispensing probe 50 is filled with pure water. When the sample container 23 is positioned at the sample suction position on the sample disk 30, the dispensing probe 50 is lowered by the movable arm 32, and the tip of the pipe portion 21 is slightly lower than the liquid surface of the sample stock solution 8 in the sample container 23. It is inserted to the bottom and stops descending. Next, the plunger 9 of the first syringe pump 27 is withdrawn, and the sample stock solution 8 is sucked into the mixing chamber 13 through the conduit 21, and at the same time, the second syringe pump 2
The plunger 10 of 8 is pushed in, and pure water flows into the mixing chamber 13 from the communication hole 3 through the diluent passage 5. The two liquids are mixed by the simultaneous merging of the sample stock solution and the pure water, and the sample is diluted in the mixing chamber 13.

Here, assuming that the flow rate of liquid supplied by the second syringe pump 28 is D (microliter / second) and the suction flow rate of the first syringe pump 27 is F (microliter / second), the pipe section 21 Is S = FD (microliter / sec). In this case, the dilution ratio M of the sample is M = (D + S)
/ S = F / (FD). That is, the dilution ratio can be changed by controlling the flow rate of each pump.

The dilution mixing of the sample is achieved when the suction flow rate F is larger than the liquid sending flow rate D. With reference to FIG. 3, the state of the combined mixing of the sample and the diluent in the mixing chamber 13 will be described.
The sample sucked into the mixing chamber 13 from the pipe section 21 flows along the vicinity of the center of the cylindrical mixing chamber near the mixing chamber entrance where the communication hole is located. On the other hand, the pure water flowing into the mixing chamber 13 from the communication hole 3 flows near the inlet of the mixing chamber and near the pipe wall of the mixing chamber.

In order to obtain a proper mixing state from as close as possible to the merging position, it is necessary to eliminate the concentration gradient of the sample in the radial direction of the mixing chamber 13 and to make it uniform. One way to eliminate the concentration gradient is to make the flow in the mixing chamber turbulent. By setting the inner diameter and the flow rate of the mixing chamber such that the Reynolds number becomes 3000 or more, a disturbance speed in the pipe diameter direction is generated, and the stirring is promoted.

In the example shown in FIG. 3, by disposing a vibration applying means such as the ultrasonic oscillating section 11 near the communication hole 3, further stirring and mixing of both liquids is promoted. When ultrasonic waves are focused on the focal position 20 while flowing the sample and the diluent into the mixing chamber 13, the liquid in the mixing chamber 13 vibrates slightly and the sample is mixed with the diluent, and the ultrasonic wave is generated. A diluted sample 12 having no concentration gradient in the radial direction is formed on the downstream side.
By stopping the operation of both syringe pumps 27 and 28, the steps of sample suction and merging and mixing are completed.

The largest factors that determine the concentration gradient in the length direction (flow direction of the liquid) in the mixing chamber 13 are the above-mentioned suction flow rate F and liquid transfer flow rate D. However, generation of a concentration gradient downstream of the mixing chamber 13, that is, on the upper end side cannot be ignored. During and after inhalation of the sample into the mixing chamber 13,
Although the diluted sample is present in the mixing chamber 13, the liquid end thereof comes into contact with pure water filled before the sample is sucked into the mixing chamber, so that the diluted sample 12 is diluted by diffusion.

The thinning of the diluted sample accompanying the sample inhalation will be described with reference to FIGS. FIG. 4 shows that a boundary region 14 between the diluted sample 12 and the pure water 7 is formed in the mixing chamber. The liquid in this boundary region is not used as a sample for analysis because the concentration of the sample is not constant. Therefore, reducing the non-uniform concentration region in the length direction of the mixing chamber can increase the amount of the diluted sample that can be used for analysis.

The presence of an air layer between the diluted sample and pure water can reduce the non-uniform concentration region. However, since the air layer has high elasticity, the dispensing probe 50
This is not adopted in the present embodiment because the dispensing accuracy at the time of discharging the sample from the sample decreases.

The flow rates of the first and second syringe pumps 27 and 28 can be adjusted by controlling the moving speed of the plungers 9 and 10 by the control unit. Using this function, the concentration of the sample corresponding to the boundary region in the mixing chamber is slightly increased to offset the concentration of the sample due to the diffusion, thereby reducing the size of the boundary region. That is, the suction flow rate F is set to 1 to 3 only at the start of the sample inhalation and thereafter.
%, Or the flow rate D is slightly reduced. The curve (a) in FIG. 5 shows the case where a constant suction flow rate is maintained from the start of suction to the end of suction of the sample, and the curve (b) of FIG. This shows a case where the suction flow rate is returned to a constant value. In the case of the curve (b), the uniform density region is expanded.

When the inhalation of the sample into the dispensing probe 50 is completed, a diluted sample is formed in the mixing chamber. At this time, as shown in FIG. A sample stock solution 8 is present. The undiluted sample in the pipe section 21 can be discharged to a sample receiving section for an analysis item that does not require a diluted sample, and those analysis items can be analyzed.
When such a sample receiving section is the electrolyte analyzing section 17, a non-diluted sample is dispensed there, and analysis items of each ion such as sodium, potassium, chlorine and the like are measured. When the sample receiving section is the reaction container 18 on the reaction line 60, the undiluted sample is discharged to the reaction container at the sample discharge position in order to measure, for example, an immunological analysis item (especially a low sensitivity item).

After the dispensing probe 50 has dispensed the undiluted sample in the pipe section 21, the dispensing probe is moved to the probe washing tank 19.
The sample is moved upward to discharge the remaining undiluted sample, and to make the uniformly diluted sample reach the tip of the conduit 21. In this case, there is a possibility that pure water may diffuse from the communication hole toward the pipe section 21. Therefore, while the plunger 9 of the first syringe pump 27 is being pushed, the plunger 10 of the second syringe pump 28 is pulled out little by little. , Mixing chamber 13
The diluted sample therein is slightly sucked into the diluent passage 5 to prevent the diluted sample to be dispensed from thinning.

Thereafter, the dispensing probe 50 is moved to the sample discharge position 18a, and pushes the plunger 9 of the first syringe pump 27 to discharge a predetermined amount of the diluted sample to the reaction vessel 18. The diluted sample is supplied to a plurality of reaction vessels 18.
Can also be distributed. The dispensing probe 50 which has finished dispensing the diluted sample is moved to the probe washing tank 19, opens the electromagnetic valves 15 and 29, and sets the water supply pump 16.
The inside of the probe is cleaned by discharging the pure water sent by the above through the mixing chamber 13 from the pipeline 21. The outer wall of the pipe section 21 of the probe is washed with washing water from the washing tank 19.

At the time of cleaning the dispensing probe 50, the integrated ultrasonic oscillation section 11 in FIG. 2 is operated to increase the cleaning efficiency by ultrasonic waves. As a means for applying vibration to the liquid in the dispensing probe, a vibrator that generates mechanical vibration may be used instead of the ultrasonic oscillation unit.

[0034]

According to the present invention, since the sample is diluted in the dispensing probe for dispensing the sample, it is not necessary to use a reaction vessel on the reaction line, and it is not necessary to provide a dedicated dilution line. Therefore, there is an effect that a large number of samples requiring dilution can be efficiently diluted and dispensed with a simple configuration.

[Brief description of the drawings]

FIG. 1 is a diagram showing a schematic configuration of an automatic analyzer according to one embodiment of the present invention.

FIG. 2 is a diagram for explaining the operation of a dispensing probe.

FIG. 3 is a diagram for explaining a state of merging and mixing in a mixing chamber.

FIG. 4 is a diagram for explaining a concentration gradient in a length direction.

FIG. 5 is a diagram for explaining diffusion of a diluted sample.

[Explanation of symbols]

1: inner tube, 2, 6: syringe, 3: communication hole, 4:
Outer tube, 5: diluent passage, 9, 10: plunger,
11: Ultrasonic oscillation part, 13: Mixing chamber, 17: Electrolyte analysis part, 18: Reaction vessel, 21: Pipe part, 23:
Sample container, 27: first syringe pump, 28: second
Syringe pump, 30: sample disk, 32:
Movable arm, 50: dispensing probe, 60: reaction line, 65: multi-wavelength photometer.

Claims (8)

[Claims] In a sample dispensing method for sucking a sample from a sample container into a vertically dispensable probe and discharging the sucked sample to a reaction container on a reaction line, the sample to be sucked is used as the dispensing probe. Using a probe having a pipe section and a mixing chamber communicated with the pipe section arranged on the side in contact with, while the dispensing probe is positioned on the sample container, Inject sample and diluent,
A sample dispensing method, wherein a sample diluted in the mixing chamber is discharged to the reaction vessel through the conduit on the reaction line. 2. The sample dispensing method according to claim 1, wherein an undiluted sample is accommodated in the pipe section, and a sample diluted with a diluent is formed in the mixing chamber. Discharging the undiluted sample to a sample receiving section for an analysis item that does not require a diluted sample, and then discharging the diluted sample in the mixing chamber to the reaction container. 3. The sample dispensing method according to claim 1, wherein the ratio of the flow rate of the sample flowing into the mixing chamber to the flow rate of the diluent flowing into the mixing chamber is changed to reduce the degree of dilution of the sample. A sample dispensing method characterized by changing. 4. A sample dispensing method according to claim 1, wherein the mixing of the sample and the diluent is promoted by vibrating the liquid in the mixing chamber into which the sample and the diluent are introduced. Sample dispensing method. 5. The sample dispensing method according to claim 4, wherein when the cleaning liquid is discharged through the mixing chamber and the conduit after dispensing the sample by the dispensing probe, vibration is applied to the cleaning liquid in the mixing chamber. A sample dispensing method characterized in that the sample is dispensed. 6. An automatic analyzer equipped with a dispensable probe capable of elevating and lowering a sample to be sucked from a sample container and dispensing the sample into a reaction container on a reaction line. A mixing section connected to the pipe section, a diluting liquid passage connected to the mixing chamber, and the sample flowing into the mixing chamber via the pipe section. An automatic analyzer, wherein a diluent is caused to flow into the mixing chamber from the diluent passage as the sample is sucked from the container. 7. The automatic analyzer according to claim 6, further comprising means for imparting vibration to the liquid in the mixing chamber. 8. The automatic analyzer according to claim 6, wherein the mixing chamber is connected to a first syringe pump via a first flow path, and the diluent passage is connected to a second syringe pump via a second flow path. An automatic analyzer connected to a syringe pump, wherein a ratio of a liquid suction flow rate of the first syringe pump to a liquid discharge flow rate of the second syringe pump is controlled by a control unit.