JP2021081387A - Autoanalyzer - Google Patents

Abstract

To prevent scattering due to bubble rupture at segmental air discharge time in an autoanalyzer that performs dispensing.SOLUTION: Provided is an autoanalyzer comprising a reagent probe 121 for drawing in and discharging a liquid, a pump unit connected to the reagent probe 121 and a movement unit for moving the position of the reagent probe 121, and performing a first motion to draw in segmental air A1 that separates mutually different liquids in the reagent probe 121. The reagent probe 121 includes in the inside of it a first area 1A where the segmental air A1 can maintain a layer due to the fact that a surface tension between the segmental air A1 and the reagent probe 121 exceeds the buoyance of the segmental air A1, and a second area 2A where the segmental air A1 can no longer maintain the layer, the first area A1 being located closer to the tip position of the reagent probe 121 than the second area 2A.SELECTED DRAWING: Figure 5

Description

The present invention relates to an automatic analyzer.

In the medical field or the biotechnology field, an automatic analyzer is used in which a sample such as blood, serum, or urine is reacted with a reagent to detect a specific biological component or chemical substance contained in the sample.

In order to discharge the amount determined by the dispensing probe of such an automatic analyzer, it is necessary to discharge the sucked sample and reagent into the reaction solution with good reproducibility. If the liquid discharged into the reaction vessel is scattered during the discharge process, the mixing ratio of the sample and the reagent may differ, and the above reaction may not be performed accurately.

In Patent Document 1, when a plurality of liquids are sucked by the suction step, the gas is sucked before the next liquid is sucked, a liquid separation layer by gas is formed in the liquid passage of the dispensing probe, and the homogenization step is performed. A device for discharging a uniformly mixed liquid is disclosed.

Japanese Unexamined Patent Publication No. 2006-349638

When the sample and the reagent are continuously sucked and then discharged, the air that separates the sample and the reagent (hereinafter referred to as segmented air) is also discharged at the same time. At this time, it is considered that the segmented air becomes bubbles at the tip of the dispensing probe and bursts and scatters in the reaction vessel, but Patent Document 1 does not specify a method for suppressing the scattering. Such scattering can cause unintended mixing of the sample with the reagent, unintended mixing of the reagent with water, or hygienic contamination.

Therefore, an object of the present invention is to provide an automatic analyzer capable of avoiding scattering due to segmented air during liquid discharge.

A brief overview of typical embodiments disclosed in the present application is as follows.

An automatic analyzer according to an embodiment includes a probe that sucks and discharges a liquid, a pump part that is connected to the probe, and a moving part that moves the position of the probe, and the probe is used before sucking the liquid. The first operation of sucking the segmented air that separates the liquids that are different from each other is performed. Here, inside the probe, the surface tension between the segmented air and the probe exceeds the buoyancy of the segmented air, so that the first region where the segmented air can maintain the layer and the buoyancy exceed the surface tension. The segmented air has a second region in which the layer cannot be maintained, and the first region is located closer to the tip of the probe than the second region.

According to the present invention, it is possible to provide an automatic analyzer capable of avoiding scattering due to segmented air during liquid discharge.

The schematic diagram of the analysis system which concerns on Embodiment 1. FIG. The schematic diagram which shows the peripheral structure of the reagent probe used in Embodiment 1. FIG. The schematic diagram which shows the reagent probe cleaning part used in Embodiment 1. FIG. FIG. 5 is a cross-sectional view showing the inside of the reagent probe used in the first embodiment after cleaning. The schematic diagram which shows the suction operation of the reagent probe used in Embodiment 1. FIG. The schematic diagram which shows the ejection operation of the reagent probe used in Embodiment 1. FIG. FIG. 5 is a cross-sectional view showing system water, segmented air and reagents inside a reagent probe used in Embodiment 1. FIG. 6 is a perspective view showing details of the shape of the segmented air shown in FIG. 7. The schematic diagram of the meniscus part of the segmental air shown in FIG. An equation showing the relationship between the radius of curvature of the meniscus portion of segmented air and the radius of the probe. An equation that indicates the height of the meniscus part of segmented air. An equation showing the volume of the meniscus part of segmented air. An equation showing the distance in the height direction of the meniscus part, which is the columnar part of segmented air. An equation showing the distance in the height direction of the meniscus part, which is the columnar part of segmented air. The cross-sectional view which shows the buoyancy acting on the segmental air in the reagent probe used in Embodiment 1 and the surface tension of the segmental air. A graph showing the relationship between the inner diameter of the probe and the contact distance between the segmented air and the probe. A graph showing the relationship between the volume of segmented air and the contact distance between the segmented air and the probe. FIG. 6 is a schematic view showing a reagent suction operation and a segmented air removal operation of the probe used in the second embodiment. The schematic diagram which shows the sample suction operation and the dispensing operation of the probe used in Embodiment 2. FIG. 5 is a cross-sectional view showing a probe used in the third embodiment. FIG. 5 is a cross-sectional view showing a probe used in the fourth embodiment. FIG. 5 is a cross-sectional view showing a probe used in the fifth embodiment. The schematic diagram which shows the segmental air removal operation in the probe used in Embodiment 6. FIG. 5 is a cross-sectional view showing a probe used in the seventh embodiment. The schematic diagram which shows the suction operation of the probe used in Embodiment 7. The schematic diagram which shows the ejection operation of the probe used in Embodiment 7.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. In all the drawings for explaining the embodiment, the members having the same function are designated by the same reference numerals, and the repeated description thereof will be omitted. Further, in the embodiment, the explanation of the same or similar parts is not repeated in principle unless it is particularly necessary.

(Embodiment 1)
<Structure of analysis system>
FIG. 1 is a schematic view (plan view) showing the analysis system 1 according to the first embodiment from above. As shown in FIG. 1, the analysis system 1 includes an automatic analyzer (hereinafter abbreviated as “analyzer”) 100 and a computer (processing unit) 200. The analyzer 100 includes a sample rack 151, a reagent disk 171 and a reaction disk (incubator) 191. The sample rack 151 holds the sample container V1 that holds the sample. The reagent disk 171 holds a reagent container V2 for holding a reagent. The reaction disk 191 holds the reaction vessel V3 on its circumference. The analyzer 100 further includes a sample probe 110, a reagent probe 121, a sample probe cleaning unit 131, a reagent probe cleaning unit 132, a container cleaning unit 193, a stirrer 195, a light source 197, and a spectroscopic detector 198.

The sample probe (sample dispensing probe) 110 dispenses the sample sucked from the sample container V1 into the reaction vessel V3. The probe referred to here does not only refer to the tip of the container that constitutes the flow path for sucking and discharging the liquid, but also the flow path from the pump (for example, a cylinder) to the tip of the container for sucking and discharging the liquid. Refers to the entire surrounding container. Note that FIG. 1 shows a vertical rotation operation unit (moving unit) to which the sample probe 110 is connected. The vertical rotation operation unit is an operation unit for changing the location where the liquid is sucked and discharged.

The reagent probe (reagent dispensing probe) 121 dispenses the reagent sucked from the reagent container V2 in the reagent disk 171 into the reaction vessel V3. Note that FIG. 1 shows a vertical rotation operation unit (moving unit) to which the reagent probe 121 is connected. The stirring device 195 stirs the liquid in the reaction vessel V3. The container cleaning unit 193 cleans the reaction vessel V3. The light source 197 is installed near the inner circumference of the reaction disk 191 and irradiates the reaction vessel V3 with light. The spectroscopic detector 198 is installed opposite the light source 197 with the reaction vessel V3 interposed therebetween, and detects the light emitted by the light source 197 onto the sample.

The computer 200 is connected to the analyzer 100 via the controller 300. The computer 200 is connected to the spectroscopic detector 198 and analyzes the sample using the detection result by the spectroscopic detector 198. The computer 200 includes a display device (display unit) 211. The controller 300 controls the overall operation of the analyzer 100.

In FIG. 1, a plurality of reagent containers V2 arranged in the reagent disk 171 are shown by partially breaking the reagent disk 171. In the reagent disk 171 which is circular in a plan view, the reagent containers V2 are arranged side by side in a circle so as to surround the center of the reagent disk 171. Further, two reagent containers V2 are arranged side by side in the radial direction of the reagent disk 171. That is, in the reagent disk 171 there are two concentric rows of reagent containers V2 arranged so as to surround the center of the reagent disk 171. The reagents held by each of the two reagent containers V2 arranged in the radial direction may be different types of reagents. Here, the reagents and samples are liquids.

In the analysis operation using the analysis system 1, first, the sample container V1 is set in the sample rack 151 after the sample to be inspected such as blood is put in. After that, the sample collected (sucked) from the sample container V1 by the sample probe 110 is dispensed (discharged) in a fixed amount into the reaction container V3 arranged on the reaction disk 191. Next, a certain amount of reagent is dispensed (discharged) from the reagent container V2 installed on the reagent disk 171 into the reaction container V3 by the reagent probe 121. The sample and reagent in the dispensed reaction vessel V3 are stirred by the stirrer 195.

The reaction disk 191 repeatedly stops rotating periodically. The spectroscopic detector 198 measures the intensity of the light passing through the reaction vessel V3 at the timing when the reaction vessel V3 passes in front of the light source 197. The measurement by the spectroscopic detector 198 is performed a plurality of times for the same reaction vessel V3 at intervals defined for each analysis item. After that, the container cleaning unit 193 discharges the reaction solution in the reaction vessel V3 and cleans it. During those operations, including washing, another reaction vessel V3 performs operations in parallel (such as photodetection work) with another sample and reagent. The computer 200 calculates the concentration of the component according to the type of analysis using the data measured by the spectroscopic detector 198, and displays the result on the display device 211.

The above-mentioned time interval for measuring the sample discharge amount to the reaction vessel V3, the reagent discharge amount, the stirring time, the intensity of the light emitted from the light source 197, and the calculation method of the component concentration in these series of operations are analyzed. The operation programs that are defined for each content and control them are executed by the computer 200. The content of the analysis is referred to as an analysis item here. The computer 200 inputs the necessary operation program to the controller 300 in the order of the requested analysis items, and operates each unit of the analyzer 100.

<Peripheral configuration of reagent probe>
FIG. 2 is a schematic view showing the peripheral configuration of the reagent probe 121 used in the first embodiment. Although the structure of the reagent probe 121 will be described here, the sample probe 110 also has the same configuration as the reagent probe 121. Therefore, the illustration and description of the peripheral configuration of the sample probe 110 will be omitted. In FIG. 2 and the figures used in the following description, the liquid in the reagent probe 121 is hatched.

The reagent probe 121 is connected to the vertical rotation operation unit (moving unit) 112. The vertical rotation operation unit 112 includes a two-axis movement mechanism of vertical rotation and rotation. The reagent probe 121 can be moved up and down and rotated by the vertical rotation operation unit 112. As a result, the reagent probe 121 can be moved to the reagent suction position, the reagent discharge position to the reaction vessel V3, or the washing position. Further, the dispensing flow path (flow path) T1 is a flow path in the reagent probe 121 passing through the inside of the vertical rotation operation unit 112. The reagent probe 121 is moved by the vertical rotation operation unit 112 to the reagent suction position where the reagent container V2 (see FIG. 1) is installed in order to collect the reagent, and further, with respect to the reaction container V3 (see FIG. 1). Can be moved to the position where the reagent is discharged.

The metering pump (pump unit) 115 has a drive unit 113 and a plunger 114, and is connected to the pump 117 through a valve 116. The operation of the metering pump 115 is controlled by the controller 300 (see FIG. 1). The metering pump 115 is connected to the reagent probe 121. The suction operation and the discharge operation by the reagent probe 121 are executed by the plunger 114 fixed to the metering pump 115 moving up and down (reciprocating operation). The reagent probe 121 (dispensing flow path T1) and the metering pump 115 before the suction operation are filled with system water L1. The system water L1 is, for example, pure water.

During the dispensing operation, the reagent probe 121 moves between the reagent suction position, the reagent discharge position, and the washing position, and discharges the reagent into the reaction vessel V3 from which the sample is discharged. The reagent in the reagent container V2 is diluted with pure water by a specified amount and adjusted to a concentration to be mixed with the sample. When the reagent probe 121 discharges the reagent by the operation of the metering pump 115, the metering pump 115 moves more than the amount operated at the time of suction, and the system water L1 in the reagent probe 121 is also discharged to obtain a mixed solution of the sample and the reagent. Dilute properly. Details of the suction operation and the discharge operation of the reagent probe 121 will be described later.

<Washing operation>
FIG. 3 is a schematic view showing the configuration of the reagent probe cleaning unit 132. The sample probe cleaning unit 131 (see FIG. 1) and the reagent probe cleaning unit 132 have the same configuration. Hereinafter, the reagent probe cleaning unit 132 will be described as an example, but the description of the configuration of the reagent probe cleaning unit 132 will be omitted.

As shown in FIG. 3, the reagent probe cleaning unit 132 has a cleaning water discharge nozzle 133, a cleaning container 134, and a pump 135. A cleaning water discharge nozzle 133 connected to the pump 135 via a valve 136 is installed on the cleaning container 134. When the reagent probe 121 moves to the cleaning container 134, the computer 200 (see FIG. 1) opens the valve 136 and discharges the external cleaning liquid L3 into the cleaning container 134 from the cleaning water discharge nozzle 133. In this way, the outer portion of the reagent probe 121 is washed. This operation is hereinafter referred to as external cleaning. The same liquid (pure water or the like) as the system water L1 is used as the external cleaning liquid L3.

Further, at the same time as the external cleaning, the valve 116 shown in FIG. 2 is also opened, and the system water L1 is allowed to flow into the reagent probe 121 to clean the inside of the reagent probe 121 (inside the dispensing flow path T1 shown in FIG. 2). .. This operation is hereinafter referred to as internal cleaning. In the internal cleaning operation, the system water L1 is flowed in the direction indicated by the arrow W1.

FIG. 4 is a cross-sectional view showing the inside of the reagent probe 121 after the washing operation. After the above external and internal cleaning is completed, the valves 116 and 136 are closed. After the cleaning operation is completed, segmented air A1 is sucked into the tip of the reagent probe 121. The tip of the probe referred to here is an end portion on the side where the liquid is sucked and discharged, and is a portion having a suction / discharge port, not an end portion on the pump side of the probe.

The reagent probe 121 has a first region 1A in which the segmented air A1 can maintain the layer, and a second region 2A in which the segmented air A1 cannot maintain the layer. The first region 1A is located closer to the tip of the reagent probe 121 than the second region 2A. That is, when the tip of the reagent probe 121 points downward, the second region 2A is located above the first region 1A.

Here, the state in which the segmented air is in contact with all of the inner walls around the probe in the lateral direction (diameter direction) of the probe is referred to as "the segmented air maintains the layer" (see FIG. 7). On the other hand, the state in which the segmented air is separated from a part of all the inner walls around the probe is called "the segmented air does not maintain the layer" (see the two figures on the right side of FIG. 5). ). In the first region 1A, the surface tension between the segmented air and the probe exceeds the buoyancy of the segmented air itself, so that the segmented air can maintain the layer.

Here, the inner diameter of the reagent probe 121 in the second region 2A is larger than the inner diameter of the reagent probe 121 in the first region 1A. In FIG. 4, a reagent is formed between a first portion in which the inner diameter of the reagent probe 121 in the first region 1A is constant, a second portion in which the inner diameter of the reagent probe 121 in the second region 2A is constant, and the portions thereof. It shows a third portion where the inner diameter of the probe 121 expands from the first region 1A side toward the second region 2A side. In FIG. 4, the boundary between the first region 1A and the second region 2A is shown between the third portion and the second portion. However, the boundary may be located at any position in the third portion as long as it is on the second portion side of the first portion. Further, there may be no third portion, and the first portion and the second portion may be connected to each other by a steep step.

<Suction / discharge operation>
After the cleaning operation, the reagent probe 121 sucks and discharges the reagent. FIG. 5 is a schematic view showing the suction operation of the reagent probe 121. FIG. 6 is a schematic view showing the discharge operation of the reagent probe 121. 5 and 6 show the operation at the tip of the reagent probe 121 in order from left to right.

After the washing operation, the reagent probe 121 rotates and moves to the sky above the reagent suction position, and descends toward the liquid surface of the reagent L2 in the reagent container V2. At this time, as described with reference to FIG. 4, the system water L1 exists in the reagent probe 121, and the segmented air A1 exists in the reagent probe 121 in the region from the system water L1 to the tip of the reagent probe 121. doing. When the reagent probe 121 comes into contact with the liquid surface of the reagent L2, the system water L1 does not come into contact with the reagent L2 because it is separated by the segmented air A1.

Next, the reagent probe 121 immersed in the liquid surface of the reagent L2 starts the reagent suction. Immediately after the start of reagent suction, the segmented air A1 rises in the first region 1A where the layer can be maintained. As the suction progresses, the segmented air A1 eventually rises to the second region 2A. When the segmented air A1 rises to the second region 2A, the layer cannot be maintained and becomes bubbles. The segmented air A1 that has become bubbles rises to the outside of the discharge region (discharge range) in the reagent probe 121 due to buoyancy. As a result, the reagent L2 and the system water L1 are in contact with each other. The discharge region (discharge range) referred to here is a region in which the reagent L2 and the system water L1 to be discharged in the discharge operation performed after the sample suction operation are held, and the reagent L2 and the system water L1 are mutual to each other. Includes the area between.

Next, as shown in FIG. 6, the reagent probe 121 that has completed the reagent suction moves to the discharge position where the reaction vessel V3 into which the sample L4 is discharged by the sample probe 110 is installed, and the reagent L2 and the system water L1 are installed. Continue to discharge. At this time, since there is no segmented air A1 between the reagent L2 and the system water L1, no bubbles are formed at the tip of the reagent probe 121 during the discharge operation. Therefore, the ejection operation can be performed without generating the scattering of the reagent or the like due to the bursting of bubbles.

The concentration of the reagent L2 before the suction operation is adjusted so as to be an ideal concentration by mixing with a certain amount of pure water or the like. Here, as shown in FIG. 6, the system is performed after the reagent L2 is discharged. A constant amount of water L1 is discharged. Therefore, as shown in FIG. 5, there is no problem even if the segmented air A1 floats and the reagent L2 and the system water L1 come into contact with each other to cause mixing.

<Method of defining the first area and the second area>
Next, a method of defining the first region 1A and the second region 2A will be described. FIG. 7 is a cross-sectional view showing system water, segmented air and reagents in the probe. When the segmented air A1 is held in the first region 1A, the segmented air A1 is a layer that separates the system water L1 and the reagent L2. At this time, Vair volume segmental air A1, the contact distance between the segmental air A1 and the reagent probe 121 t, the inner diameter of the probe in the first region 1A 2r _1, the radius of curvature of the meniscus portion of a segmented air A1 and R .. The distance t is the length in the longitudinal direction (axial direction) of the reagent probe 121 having a cylindrical shape.

FIG. 8 is a perspective view showing details of the shape of the segmented air A1 shown in FIG. 7. The volume Vir of the segmented air A1 is composed of the volume Vvm of the meniscus portions Vm at both ends in the longitudinal direction (axial direction) of the reagent probe 121 and the volume of the central cylindrical portion Vn. Here, the cross-sectional area of the cylindrical portion Vn is S, and the height of the meniscus portion Vm is h.

FIG. 9 is a schematic view of the meniscus portion Vm of the segmented air A1 shown in FIG. That is, FIG. 9 is a diagram showing the relationship between the meniscus portion Vm of the segmented air A1 in the reagent probe 121 and the probe diameter and contact angle. Here, the contact angle between the liquid (solution) and the inner wall of the probe is θ. At this time, the relationship between the radius r ₁ of the curvature radius R and the probe of the first region 1A of the meniscus portion can be represented by the formula 1 shown in FIG. 10.

The height h of the meniscus portion Vm can be expressed by Equation 2 shown in FIG.

The volume Vvm of the meniscus portion Vm can be expressed by the formula 3 shown in FIG.

The distance (height) t in the height direction of the meniscus portion Vm, which is a cylindrical portion, can be expressed by the formula 4 shown in FIG.

Equation 4 can be represented by Equation 5 shown in FIG. 14 using Equations 1 to 3. That is, in FIG. 4, the distance t in the height direction of the meniscus portion Vm, which is the cylindrical portion of the segmented air, is shown by Equation 5.

When t ≦ 0, the segmented air A1 does not come into contact with the inner wall of the probe, so that the layer cannot be maintained. However, in reality, since the buoyancy of the segmented air A1 itself acts on the segmented air A1, the segmented air A1 cannot maintain the layer even if t ≦ 0 is not satisfied. Therefore, the condition that the segmented air A1 cannot form a layer can be expressed by the following equation 6.
t ≤ threshold Th ... (6)
FIG. 15 is a cross-sectional view showing the buoyancy acting on the segmented air in the reagent probe and the surface tension of the segmented air. As shown in FIG. 15, a surface tension f acts from the segmented air A1 toward the inner wall of the reagent probe 121, and an upward buoyancy F acts on the segmented air A1. When the value of the distance t is larger than the threshold Th, the segmented air A1 can maintain the layer. This means that the surface tension f between the segmented air A1 and the reagent probe 121 exceeds the buoyancy F of the segmented air A1 itself, so that the segmented air A1 can maintain the layer.

As described above, in the first region 1A, the segmented air A1 can maintain the layer, but in the second region 2A, t ≦ threshold Th, and the segmented air A1 cannot maintain the layer. That is, in the second region 2A, the buoyancy F exceeds the surface tension f, so that the segmented air A1 cannot maintain the layer. Therefore, the segmented air A1 separates from the inner wall of the reagent probe 121 and floats.

Next, an example of inner diameter calculation using the above formula will be described.

An experimental result was obtained that when a solution having a volume of Vair of 20 μl and a contact angle of θ of 70 ° was sucked, segmented air could not form a layer at a probe inner diameter r = 1.9. In this case, when calculated using Equation 5, t = 1.7 was obtained. That is, in this case, the threshold Th of t is 1.7. Therefore, in this dispensing system, it is t ≦ 1.7 that the segmented air cannot form a layer. Based on this result, the inner diameter of the probe to which this embodiment can be applied is determined when the segmented air is changed to 1 μl at the same solution and the same suction rate.

FIG. 16 is a graph showing the relationship between the probe inner diameter r when Vair = 1 in the dispensing system used in the above evaluation and the distance t which is the contact distance between the segmented air and the probe. When t> Th, the segmented air can maintain the layer, and when t ≦ Th, the layer cannot be maintained. In the graph, t ≦ Th at the time of _{r = th.} In other words, _th is the inner diameter of the probe when t = Th. That is, _th is a threshold value of the lower limit of the inner diameter at which the segmented air cannot maintain the layer when the buoyancy F of the segmented air exceeds the surface tension f. That is, when the inner diameter of the probe is _rth or more, the buoyancy F of the segmented air exceeds the surface tension f, so that the segmented air cannot maintain the layer.

Therefore, in order to design the probe of the present embodiment including the first region 1A in which the segmented air can maintain the layer and the second region 2A in which the segmented air cannot maintain the layer, the probe in the first region 1A The probe may be designed so that the inner diameter 2r _{1 of the above and the inner diameter 2r 2} of the probe in the second region 2A satisfy the condition of the following equation 7. Here, r ₂ is the radius of the probe in the second region 2A.
2r ₁ < _rth ≤ 2r ₂ ... (7)
Further, by carrying out the same study with other liquid solutions, more versatile design values can be obtained.

Next, a calculation example of the volume Vair of the segmented air in the dispensing system in which the probe inner diameter has already been determined will be described.

FIG. 17 shows segmented air when the inner diameter of the probe in the first region 1A is 2r ₁ = 1.0 and the inner diameter of the probe in the second region 2A is 2r _{2 = 1.5 in the same dispensing system as in the above example.} It is a graph which shows the relationship between the volume Vair of the above, and the contact distance t between the segmented air and the probe. In FIG. 17, _{the graph when 2r 1} = 1.0 is represented by a triangular plot, and the graph when 2r ₂ = 1.5 is represented by a round plot. In the first region 1A, when 2r ₁ = 1.0, _{if Vair th1} <Vair is satisfied, the segmented air can maintain the layer. Further, in the second region 2A, when 2r ₂ = 1.5, if Vair _th2 > Vair, the segmented air cannot maintain the layer. Therefore, in order to prevent the segmented air from maintaining the layer in the first region 1A of the probe and the segmented air from being unable to maintain the layer in the second region 2A of the probe, the segmented air having a volume satisfying the following equation 8 is satisfied. Should be used.
Vair _th1 <Vair <Vair _th2 ... (8)
Here, Vair _th1 is the volume of segmented air when t = Th in the first region 1A of _{the probe, and Vair th2} is the volume of segmented air when t = Th in the second region 2A of the probe. Is. At this time, in the first region 1A of the probe, the segmented air can maintain the layer when t ≦ Th, and in the second region 2A of the probe, the segmented air can maintain the layer when t ≧ Th. In other words, Th in the first region 1A here is the upper limit threshold value at which the segmented air can maintain the layer, and Th in the second region 2A is the lower threshold value at which the segmented air can maintain the layer.

That is, Vair _th1 is the upper threshold of the volume Vair when the segmented air cannot maintain the layer in the first region 1A of the probe. Further, Vair _th2 is a threshold value of the lower limit of the volume Vair when the segmented air can maintain the layer in the second region 2A of the probe.

<Effect of this embodiment>
When aspirating reagents with the dispensing probes that make up the analyzer, segmented air is applied to the tips of the dispensing probes to prevent system water that fills most of the dispensing probes from mixing with the reagents in the reagent container. With a certain amount of suction, the tip of the dispensing probe is brought into contact with the surface of the reagent, and then suction is performed. Therefore, in the dispensing probe in the state where the reagent is sucked, segmented air forms a layer between the reagent near the tip of the dispensing probe and the system water.

After that, when the reagent and the system water are to be discharged into the reaction vessel, the segmented air is discharged before the system water is discharged. At this time, the segmented air bursts after forming bubbles in the reaction vessel. When this rupture occurs, it is conceivable that the reagents that mainly form the bubble membrane are scattered around. For example, the scattered reagents may peel off into the reaction vessel after coagulation. In that case, the mixing ratio of the sample and the reagent varies, and the analysis performed by mixing the sample and the reagent can be performed with good reproducibility. It may not be possible to do it accurately. Further, if the bubbles composed of segmented air burst and the reagents and the like are scattered as described above, there is a risk of causing hygienic pollution.

The above problem can occur not only when the reagent is discharged but also when the sample is discharged.

Therefore, in the present embodiment, as shown in FIG. 4, a probe including a first region 1A in which the segmented air A1 can maintain the layer and a second region 2A in which the segmented air A1 cannot maintain the layer is used. There is.

In other words, the analyzer of the present embodiment has a probe for sucking and discharging the liquid, a pump part connected to the probe, and a moving part for moving the position of the probe, and before sucking the liquid. , An analyzer that performs the first operation of sucking segmented air that separates different liquids from each other in the probe. Inside the probe, the surface tension between the segmented air and the probe exceeds the buoyancy of the segmented air, so that the segmented air can maintain a layer and the buoyancy is the surface. It has a second region in which the segmented air cannot maintain the layer when the tension is exceeded, and the first region and the second region are located in order from the tip side of the probe.

As described with reference to FIG. 5, immediately after the start of suction of the reagent L2, the segmented air A1 constitutes a layer in the first region located closer to the tip of the probe than the second region 2A. When the segmented air A1 reaches the second region 2A by further suctioning, the segmented air A1 cannot form a layer and floats. Therefore, the system water L1 and the reagent L2 are in contact with each other, and in the subsequent discharge operation, the reagent L2 and the system water L1 can be continuously discharged, and the discharge operation of the reagent L2 and the discharge operation of the system water L1 The segmented air A1 is not discharged during the period.

Therefore, it is possible to prevent the bursting of air bubbles due to the discharge of segmented air, and it is possible to prevent the scattering of reagents and the like. Therefore, the analysis performed by mixing the sample and the reagent can be performed accurately with good reproducibility. In addition, it is possible to prevent hygienic contamination due to the scattering. That is, the reliability of the analyzer can be improved.

(Embodiment 2)
18 and 19 are schematic views showing a reagent suction operation and a segmented air removal operation of a dispensing probe in an analyzer that continuously sucks a sample and a reagent and discharges them in the same operation. FIG. 19 is a schematic view showing a sample suction operation and a dispensing operation of the dispensing probe. 18 and 19 show the operation at the tip of the dispensing probe 122 in order from left to right. In this embodiment, since the sample probe and the reagent probe are common, they are simply referred to as a dispensing probe. That is, in the present embodiment, unlike the first embodiment, the reagent and the sample are dispensed into the reaction vessel using only one dispensing probe.

In the present embodiment, the dispensing probe is moved from the state in which the reagent is sucked by the operation described with reference to FIG. 5 to the cleaning position, and only the external cleaning described with reference to FIG. 3 is performed. That is, the internal cleaning is not performed at this time. At this time, segmented air A2 (see FIG. 18) is sucked into the tip of the dispensing probe (the region on the tip side of the reagent L2 in the dispensing probe).

After the cleaning operation, as shown in FIG. 18, the dispensing probe 122 rotates and moves to the sky above the sample suction position, and descends toward the liquid level of the sample L4 in the sample container V1.

The dispensing probe 122 immersed in the liquid surface of the sample L4 starts sample suction. Here, when the dispensing probe 122 comes into contact with the liquid surface of the sample L4, the segmented air A2 constituting the layer is interposed between the sample L4 and the reagent L2 in the dispensing probe 122.

Immediately after the start of sample suction, the segmented air A2 rises in the first region 1A where the layer can be maintained. As the suction progresses, the segmented air A2 eventually rises to the second region 2A. When the segmented air A2 rises to the second region 2A, the layer cannot be maintained and becomes bubbles. The segmented air A2 that has become air bubbles rises to the outside of the discharge region inside the dispensing probe 122 due to buoyancy. At this time, the sample L4 and the reagent L2 are in contact with each other in the dispensing probe 122. The discharge region referred to here is a region in which the sample L4, the reagent L2, and the system water L1 to be discharged in the discharge operation performed after the sample suction operation are held, and the sample L4, the reagent L2, and the system are retained. Includes regions between the water L1s.

The dispensing probe 122 that has completed the sample suction moves to the discharge position (immediately above the reaction vessel V3), and discharges the sample L4, the reagent L2, and the system water L1 in this order. At this time, since there is no segmented air between the sample, the reagent, and the system water, the dispensing probe 122 does not discharge air bubbles. Therefore, it is possible to prevent the generation of scattering of the reagent or sample due to the bursting of bubbles.

(Embodiment 3)
Here, a dispensing probe having no step between the first region and the second region will be described.

FIG. 20 is a cross-sectional view showing a dispensing probe according to the present embodiment. As shown in FIG. 20, the probe inner diameter of the dispensing probe 123 of the present embodiment has a shape that continuously expands from the tip (lower end) of the dispensing probe 123 upward. That is, the probe inner diameter of the dispensing probe 123 continuously changes from the first region 1A to the second region 2A. Therefore, the inner wall of the dispensing probe 123 has a taper in the axial direction of the dispensing probe 123 from the first region 1A to the second region 2A.

That is, the inner diameter of the first region 1A on the tip (lower end) side of the dispensing probe 123 is 2r ₁ , and the inner diameter of the second region 2A above the first region 1A is _{2r 2,} which is larger than 2r _1. In the cross section along the central axis of the dispensing probe 123, the inner wall of the dispensing probe 123 extending from the tip of the dispensing probe 123 to the second region 2A is linear.

When the segmented air is sucked from the tip of the dispensing probe 123, the segmented air forms a layer at the position of the _{inner diameter 2r 1 , but when the segmented air is sucked up to the position of the inner diameter 2r 2} (second region 2A), the segmented air becomes It becomes impossible to form a layer. With the shape shown in FIG. 20, mass production of the dispensing probe 123 by molding is easy, and by preparing only the probe tip shape, it can be replaced with a new probe tip each time dispensing is performed. Therefore, the washing time can be shortened (omitted), and the risk of unintentional mixing of reagents and the like with other samples can be significantly reduced.

(Embodiment 4)
FIG. 21 is a cross-sectional view showing a probe used in the present embodiment. Here, an example in which a relatively thick second region is arranged in a part of a relatively thin dispensing probe will be described.

The larger the diameter of the dispensing probe, the more system water is needed to fill the flow path. In the analyzer of the present embodiment, the suction and discharge operations are realized by the pressure fluctuation in the dispensing flow path T1 caused by the operation of the metering pump 115 shown in FIG. 2 propagating through the system water L1. The increase in the amount of system water in the dispensing flow path T1 and the decrease in the pressure propagation rate mean that the response speed between the operation of the metering pump 115 and the suction / discharge operation is decreased, resulting in a decrease in the dispensing performance. There is a possibility of connecting.

Therefore, as shown in FIG. 21, if the range of forming the second region 2A is kept to a minimum, deterioration of the dispensing performance can be avoided. Here, the dispensing probe 124 has a first region 1A at the tip, a second region 2A above the first region 1A, and a third region 3A above the second region 2A. In other words, the dispensing probe 124 includes a first region 1A, a second region 2A, and a third region 3A that are arranged in order from the tip side. The inner diameter of the second region 2A between the first region 1A and the third region 3A is larger than either the inner diameter of the first region 1A or the inner diameter of the third region 3A.

The inner diameter of the third region 3A is, for example, the same as the inner diameter of the first region 1A. That is, the third region 3A is a region in which the segmented air can maintain the layer by the surface tension between the segmented air and the dispensing probe 124 exceeding the buoyancy of the segmented air.

(Embodiment 5)
FIG. 22 is a cross-sectional view showing a probe according to the present embodiment. As shown in FIG. 22, the first region and the second region may be provided in the flow path block 10 between the tip of the dispensing probe 125 and the metering pump 115, instead of the tip of the dispensing probe. .. The flow path block 10 is a part constituting the dispensing probe 125, and includes a second region 2A and a first region 1A located closer to the tip of the dispensing probe than the second region 2A. The tip 11 of the dispensing probe 125 and the flow path block 10 are connected to each other by the flow path T2, and the flow path block 10 and the metering pump 115 are connected to each other by the flow path T3. One end of the flow path block 10 is connected to the flow path T2 by the joint portion S1, and the other end of the flow path block 10 is connected to the flow path T3 by the joint portion S2. That is, the flow path block 10 and the flow paths T2 and T3 can be separated from each other.

Here, for example, the inner diameters of the tip portion 11 of the dispensing probe 125 and the flow path T2 are smaller than the inner diameter of the second region 2A of the flow path block 10, for example, the first region 1A of the flow path block 10. It is less than or equal to the inner diameter. Further, the inner diameter of the flow path T3 is smaller than the inner diameter of the second region 2A of the flow path block 10.

In the present embodiment, the length of the tip portion 11 of the dispensing probe 125 can be designed to be short. Further, since the position of the flow path block 10 can be defined by adjusting the lengths of the flow paths T2 and T3, the layout inside the device can be easily adjusted.

(Embodiment 6)
In the present embodiment, a method of expelling the bubbled segmented air from the discharge region more reliably after sucking the solution will be described. FIG. 23 is a schematic view showing a segmented air removal operation in the probe according to the present embodiment. FIG. 23 shows the operation at the tip of the dispensing probe 126 in order from left to right.

When the suction operation described with reference to FIG. 5 is performed, as shown in the fourth figure from the left in FIG. 5, even if the segmented air A1 cannot form a layer and becomes air bubbles, the segmented air A1 is a dispensing probe. It is conceivable that it adheres to the inner wall of 126 (see FIG. 23) and does not float. Therefore, as shown in FIG. 23, after the segmented air A1 is bubbled as described above, the dispensing probe 126 is operated in the left-right direction (diameter direction, horizontal direction, lateral direction of the dispensing probe 126) to vibrate. give away. As a result, the bubbles are moved out of the discharge region 1B. The operation may be performed not only in the left-right direction but also in the vertical direction (axial direction of the dispensing probe 126).

(Embodiment 7)
In the present embodiment, a method of defining a position for expelling the bubbled segmented air will be described. The bubbled segmented air rises in the probe and adheres to the inside of the flow path and the outside of the discharge region. At this time, depending on the volume of the bubbled segmented air and the adhesion location, the pressure propagation in the flow path may be affected and the dispensing performance may be deteriorated. This effect is likely to occur especially when the volume of segmented air is large.

FIG. 24 is a cross-sectional view showing a dispensing probe after the cleaning operation. FIG. 25 is a schematic view showing a suction operation of the probe according to the present embodiment. FIG. 26 is a schematic view showing the ejection operation of the probe according to the present embodiment. In FIGS. 25 and 26, the operation at the tip of the reagent probe 121 is shown in order from left to right.

After completion of the external and internal cleaning described with reference to FIG. 3, valve 116 (see FIG. 2) and valve 136 (see FIG. 3) are closed. After that, the controller 300 (see FIG. 1) sends a command to the metering pump 115 (see FIG. 2) to suck the segmented air A3. After sucking the segmented air A3, the valve 136 opens again, and the external cleaning liquid L3 is discharged from the cleaning water discharge nozzle 133 (see FIG. 3). In this state, the controller 300 sends a command to the metering pump 115 again, and the reagent probe 121 sucks the external cleaning liquid L3 as the system water L5. Next, the valve 136 is closed again, and the discharge of the external cleaning liquid L3 is stopped. At this point, the controller 300 sends a suction command again, and the segmented air A1 is sucked into the tip of the reagent probe 121. The segmented air A3 has a volume capable of maintaining the layer even in the second region 2A, and has a volume larger than that of the segmented air A1. As a result, the configuration shown in FIG. 24 is obtained.

Next, as shown in FIG. 25, the reagent L2 is sucked into the reagent probe 121 by performing the same operation as that described with reference to FIG. The segmented air A1 that has moved to the second region 2A due to the suction of the reagent cannot maintain the layer and becomes air bubbles. The bubble-shaped segmented air A1 rises in the reagent probe 121 and is taken into the segmented air A3. By performing such an operation, the destination of the bubbled segmented air A1 can be controlled to the position of the segmented air A3.

In other words, it is possible to prevent the segmented air A1 from moving to the back side (opposite the tip side, the pump side) of the reagent probe 121 from the position of the segmented air A3. As a result, it is possible to prevent the segmented air that has become bubbles from affecting the pressure propagation in the flow path and deteriorating the dispensing performance.

Further, if the segmented air A3 that has taken in the segmented air A1 is discharged, air bubbles in the flow path can be expelled, so that the amount of cleaning water consumed during cleaning can be reduced.

As described above, in the present embodiment, before the first operation of sucking the segmented air A1, the second operation of sucking the segmented air A3 that separates different liquids from each other in the probe is performed, and the suction in the first operation is performed. The segmented air A3 captures the rising segmented air A1. Thereby, the reliability of the analyzer can be improved.

Although the invention made by the present inventors has been specifically described above based on the embodiment thereof, the present invention is not limited to the embodiment and can be variously modified without departing from the gist thereof. is there.

For example, although the description has been made assuming that the analyzer is used for a biochemical test, the analyzer of the present application can be used as an immunoassay device for an immunological test or a raw device that can be used for both a biochemical test and an immunological test. It may be a chemical / immunointegrated analyzer.

1 Analysis system 1A 1st area 2A 2nd area 100 Automatic analysis device (analyzer)
110 Sample probe 115 Metering pump 121 Reagent probe 122-126 Dispensing probe A1 to A3 Segmented air L1 System water L2 Reagent L3 External cleaning solution L4 Sample V1 Sample container V2 Reagent container V3 Reaction container

Claims (6)

A probe that sucks and discharges liquid,
The pump unit connected to the probe and
A moving part that moves the position of the probe and
Have,
An automatic analyzer that performs the first operation of sucking the first segmented air that separates different liquids from each other in the probe before sucking the liquid.
The probe is inside it
When the surface tension between the first segmented air and the probe exceeds the buoyancy of the first segmented air, the first segmented air can maintain the layer, and the first region.
When the buoyancy exceeds the surface tension, the first segmented air cannot maintain the layer, and the second region.
Have,
The first region is an automatic analyzer located closer to the tip of the probe than the second region. In the automatic analyzer according to claim 1,
An automatic analyzer in which the inner diameter of the probe continuously changes from the first region to the second region. In the automatic analyzer according to claim 1,
The probe further has a third region within it that allows the first segmented air to maintain a layer when the surface tension exceeds the buoyancy.
The second region is an automatic analyzer located closer to the tip of the probe than the third region. In the automatic analyzer according to claim 1,
An automatic analyzer that moves the first segmented air in the second region out of the discharge region by operating the probe in the vertical or horizontal direction. In the automatic analyzer according to claim 1,
Prior to the first operation, a second segmented air that separates different liquids from each other in the probe is provided, and the second segmented air captures the first segmented air that has risen due to suction in the first operation. Automatic analyzer. A probe that sucks and discharges liquid,
The pump unit connected to the probe and
A moving part that moves the position of the probe and
Have,
An automatic analyzer that performs the first operation of sucking the first segmented air that separates different liquids from each other in the probe before sucking the liquid.
The probe includes a first region and a second region, which are located in order from the tip side of the probe, inside the probe.
The inner diameter of the probe in the first region is 2r ₁ , the inner diameter of the probe in the second region is 2r _2, and the buoyancy of the first segmented air is the surface between the first segmented air and the probe. when the lower limit value of the inner diameter of the probe in which the first segment air by exceeding the tension can not be maintained layers was r _th, satisfy _{2r 1 <r th ≦ 2r 2} , an automatic analyzer.

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