JP2001174469A - Analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an analyzer provided with a dispensing function to make a probe suck and discharge a liquid, able to be appropriately monitored and capable of reliably detecting the suction and discharge of the liquid. SOLUTION: This analyzer provided with a dispensing function to make a probe suck and discharge a liquid, is provided with a sensor to detect the state of the suction and discharge of the liquid by the probe through the use of an image processing means. Whether the liquid is sucked or discharged by the probe is monitored by capturing and processing image information, for example, by a CCD camera 130. It is possible to more reliably detect whether the dispensing operation is normally performed or not on a probe for which this analyzer is not adopted and also to ensure the reliability in data.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an analyzer,
More specifically, the present invention relates to an analyzer capable of monitoring a dispensing state by image processing.

[0002]

2. Description of the Related Art In an analyzer, a probe can suck and discharge a liquid by a pipetting operation. Here, for example, the following are known for detecting the suction and discharge of a liquid.

That is, (a) a method in which a pressure sensor is provided in a pipe to monitor its fluctuation, and (b) a method of monitoring by a change in capacitance of a probe (Japanese Patent Application Laid-Open No. 8-114604).
And (c) a method of irradiating a part of the probe or the discharged liquid with light or laser and monitoring the change in the received light.

[0004] As similar to the above (c), the present applicant has previously disclosed a method utilizing the blocking of light by a discharged liquid as disclosed in Japanese Patent Application Laid-Open No. 58-11859 (Reference 2).
And Japanese Unexamined Patent Publication No. Hei 5-223830 (Literature 3), there has been proposed a method of monitoring the dispensed amount based on the time during which the discharged liquid blocks light, and Japanese Patent Application Laid-Open No. 62-16805.
Japanese Patent Application Laid-Open No. 5-154765 (Document 5) discloses a method based on a change in transmission of light in a nozzle, and a method described in Japanese Patent Application Laid-Open No. 5-154765 (Document 5) measures a projected shape of a liquid. Is known.

[0005]

However, each of the above-mentioned methods has advantages over those which do not employ these methods. For example, in the case of the proposal of the above-mentioned reference 3, dispensing is performed. Although the amount can be monitored, there is still room for improvement from the viewpoint of making liquid suction and discharge detection more reliable and accurate.

(A) In the method of the above (a), it is difficult to obtain a change when the amount of suction and discharge is very small. Therefore, when more certainty and accuracy are required, it is not possible to respond to this, and if suction and discharge are not reliably detected, it is detected with sufficient certainty whether the dispensing operation has been performed normally. If not, it is difficult to guarantee the data obtained with the analyzer, and therefore
In order to guarantee the reliability of the obtained data, it is more reliable to detect whether the dispensing operation was performed normally.
It can be said that the importance of the analyzer is great.

(B) In the case of (b) above, in this case, there is a surface which is easily affected by the composition of the liquid and noise from the apparatus, and as a result, stable monitoring is always performed. Is difficult. Therefore also
The same can be said for case (a).

(C) In the case of the above (c), it is difficult to irradiate light to a target location and to secure the positional accuracy of light reception. If the amount is very small, it is difficult to ensure accuracy, and the layout is limited, so that there is still room for improvement.

(D) Therefore, it is desirable that these difficulties can be avoided, the state after suction of the liquid and after discharge can be appropriately monitored, and the suction and discharge of the liquid can be reliably detected. It is also desirable to be able to more accurately and reliably monitor the state where the probe is holding or discharging the liquid, and to confirm that the dispensing operation has been performed normally. It is possible to reliably detect the data and to guarantee the reliability of the data obtained by the analyzer.

According to the present invention, based on the above considerations and the following considerations, it is possible to improve the analyzer having a dispensing function for sucking and discharging a liquid by a probe, thereby avoiding the above disadvantages and the like. So that proper monitoring is possible,
It is intended to reliably detect whether the liquid has been sucked or discharged.

[0011]

According to the present invention, the following analyzer is provided. That is, an analyzer having a dispensing function of causing a probe to suck and discharge a liquid,
An analyzer comprising: a sensor that detects a state in which the probe sucks and / or discharges the liquid by using an image processing unit.

[0012]

According to the present invention, the analyzer has a dispensing function of causing the probe to suck and discharge the liquid, and uses the image processing means to determine the state in which the probe has suctioned and / or discharged the liquid. It has a sensor to detect.
For this reason, it is possible to provide an improved analyzer capable of monitoring whether the probe has sucked or discharged the liquid by capturing and processing image information with a sensor and processing the detected information. When more certainty and accuracy are required, this can be easily met. Therefore, according to the analyzer of the present invention, it is possible to more accurately and reliably monitor the state in which the probe is holding the liquid or the state in which the liquid is discharged, as compared with the conventional method, and more reliably, It is possible to detect whether or not the dispensing operation has been performed normally, and to ensure the reliability of the data obtained by the analyzer.

According to a preferred embodiment of the analyzer of the present invention, the state in which the probe sucks and / or discharges the liquid is determined by changing the liquid in the probe or
The present invention can be suitably implemented as a mode in which a change in the liquid in the sample container or the reaction container is detected by, for example, a CCD camera, and similarly, the above can be achieved.

Preferably, the image information of a predetermined amount of liquid suction and / or discharge is compared with image information obtained by, for example, a CCD camera, and the liquid suction and / or discharge is performed normally. The present invention can be suitably implemented as a configuration having a means for determining whether or not
Make the above possible. Here, the comparison judgment is
This is performed by comparing the image information of the preset probe with the image information of the probe obtained by, for example, a CCD camera, or the image information of a preset sample container or reaction container and the sample information obtained by, for example, a CCD camera. Alternatively, the present invention can be suitably implemented as a configuration having a means for notifying the result of the determination, or as a configuration having a mode for comparing with the image information of the reaction vessel, and in the same manner, Make it possible.

[0015]

Embodiments of the present invention will be described below with reference to the drawings. 1 to 5 show one embodiment of the present invention. 1 illustrates an example of a configuration of an analyzer according to an embodiment of the present invention, and FIG. 2 illustrates an example of monitoring of a dispensing state by image processing, which is a probe monitoring example. FIG. 3 is a diagram showing an example of the configuration of the image processing / control system. FIGS. 4 and 5 are diagrams showing an application to a sample container and an application to a reaction container, respectively. FIG. 6 shows that the present invention is applicable even if the probe used is not replaced and used, if it has transparency and can capture image information of an internal sample sample.

In FIG. 1, reference numeral 1 denotes the entire analyzer. Here, the device is an analyzer having a dispensing function of causing a probe to suck and discharge a liquid. In the illustrated example, the apparatus 1 of the present embodiment includes a reaction container transfer unit 20, a sample supply unit 30, a disposable chip (disposable probe) supply unit 40, a first and a second unit around a reaction turntable 10 (reaction table). Respective components of the reagent supply units 50 and 60 and the measurement unit 80 can be arranged as shown in the drawing.

The apparatus 1 can further include a control unit as shown in FIGS. 2 and 3. In this example, the control unit 100 has a control unit 100 as a control unit that controls the entire control of the apparatus 1. It can be. Under the control of the control unit, the components shown in FIG. 1 operate in an order corresponding to a predetermined analysis item for a sample to be inspected, including a liquid suction / discharge operation by a dispenser described later. Shall be controlled. Here, the control unit 100 can be configured to include a computer. As a basic configuration, an input circuit for various input information and an arithmetic processing circuit (CP
U) and a control program executed by the arithmetic processing circuit;
And a storage circuit (RA
M, ROM), and an output circuit for transmitting a control signal and the like to a controlled object including the above-described reaction turntable 10 and other mechanical units, and the like, can constitute the control unit 100. .

In FIG. 1, a reaction turntable 10
Is composed of a perfect circular table, and has many reaction vessels 11
Is held on the same circumference near its outer periphery and transported at a predetermined operation timing so that its rotation direction (the arrow in the figure is
A counterclockwise direction is shown), and the amount of rotation is controlled.

The reaction container transfer section 20 has a reaction container stocker 21 and a transfer device 22. The container (reaction container) 11 positioned at the take-out position of the stocker 21 is
This can be supplied to a predetermined position of the reaction turntable 10 by the transfer device 22. Here, container 1 to be used
Numeral 1 is a light-transmitting material, which can be a container in which the inside of a bottomed tubular container can be observed from outside the container wall. In this case, if the measurement unit 80 measures the light emission amount based on the light emission reaction to obtain the analysis data (measurement value) of the corresponding analysis item, the measurement can be performed from outside the container wall.

The sample supply section 30 includes a sample holding section 32 capable of holding a plurality of bottomed tubular containers (sample containers) 31 each containing a sample (sample liquid), and a dispenser having a nozzle section 33 ′ at the distal end. And a device 33. Here, when the holding unit 32 is sequentially transported under the instruction and control of the device control unit including the control unit 100 described above, the dispenser 33 moves the nozzle from the container 31 on the holding unit 31 to the nozzle. A predetermined amount is taken out by suction by the unit 33 ', and is rotated as shown in the figure, transferred to the container 11 on the reaction turntable 10, discharged, and dispensed. In the figure, the one-dot chain line indicates the tip nozzle portion 3 for sucking and discharging.
This shows the movement (rotation) locus of 3 '.

Here, in this embodiment, the nozzle portion 33 '
, A configuration using a disposable chip type that is detachable and can be replaced after each use is adopted. For this reason, the disposable chip supply unit 40 is arranged near the sample supply unit 30 as shown in the figure. The disposable chip supply unit can be configured to have a disposable chip case 42 that holds a large number of disposable chips 41 and is conveyed as shown by arrows in the drawing, and a chip disposal position (chip disposal unit) 45. The disposable chip 41 in the case can be positioned so as to face the rotation trajectory as shown in the figure.

Here, the disposable chip 41 is
A member made of a transparent resin can be used, and is detachably attached to a nozzle 33b provided at the tip of an arm portion 33a of the dispenser 33 through an attaching / detaching portion 33c as illustrated in FIG. Can be done. Thus,
When the nozzle portion as a probe for sucking and discharging is of a disposable tip type, the nozzle portion is configured to include the disposable tip 41. At the chip discarding section (chip discarding position) 45 which is set in front of.

The first reagent supply section 50 is a supply section for supplying a reagent to the container 11. This is a circular reagent turntable (reagent table) 51 and a nozzle 5 on the tip side.
A dispenser (reagent dispenser) 52 having 2 ′ may be provided. On the reagent turntable 51, a bottomed tubular container 53 containing various predetermined reagents corresponding to a plurality of desired analysis items is provided at a position on the outer circumference thereof.
(A first reagent container). Here, it is assumed that, for example, an enzyme labeling reagent is provided as an example of the first reagent.

The dispenser 52 aspirates and dispenses a predetermined amount of the reagent from the corresponding container 53 under the instruction and control of the apparatus controller including the control unit 100, and dispenses a predetermined amount of the reagent. Can be rotated in a movement (rotation) locus as shown by a one-dot chain line in the figure to perform discharge and dispensing.

Thus, the first reagent can be supplied to the container 11 which has been stopped by being rotated to rotate the reaction turntable 10 to the corresponding position facing the medicine supply section 50 and stopped.

The second reagent supply unit 60 for supplying the reagent to the container 11 can also be basically realized with the same configuration as the first reagent supply unit 50, and includes a round reagent turntable (reagent table) 61 , A dispenser (reagent dispenser) 62 having a nozzle portion 62 'on the tip side. Therefore, at the position on the outer circumference of the reagent turntable 61, a bottomed tubular container 63 (second
A plurality of reagent containers). Here, it is assumed that, for example, a luminescent reagent is provided as an example of the second reagent.

Similarly, the dispenser 62 aspirates and dispenses a predetermined amount of the reagent from the corresponding container 63 under the instruction and control of the device control section including the control unit 100, ′ Can rotate in a movement (rotation) trajectory as shown by a one-dot chain line in the figure to perform discharge and dispensing.

Thus, after the dispensing of the first reagent by the first reagent supply unit 50, the container 11 transferred to the corresponding position facing the reagent supply unit 60 and stopped with the rotation of the reaction turntable 10. To supply the second reagent.

Here, similarly to the probe for aspirating and discharging the sample, the nozzle portion as a probe for aspirating and discharging the reagent liquid in the dispenser 52 or the dispenser 62 may be transparent if desired. It is possible to use a disposable chip type having a property. When using the disposable chip type, the disposable chip supply unit 40 shown in FIG. 1 as described above is prepared in the vicinity and the detachable unit 33c shown in FIG.
In addition, a detachable dispensing probe configuration having a structure similar to that of the disposable tip 41 can be adopted.

The measuring section 80 is a means for measuring an object to be measured in accordance with an analysis item. For example, when utilizing a luminescence reaction by the enzyme labeling reagent and the luminescence reagent, the container 11 is moved from the reaction turntable 10 to the reaction chamber. After being transferred to the measuring unit 80 by a container transferring mechanism (not shown), the measuring unit measures the luminescence amount based on the luminescence reaction between the enzyme-labeled reagent and the luminescent reagent from outside the container 11 and obtains the measured value. be able to. Then, for the container 11 for which the inspection has been completed and the data has been acquired and measured, the measuring unit 8
Removed from zero. When the container disposal step is set as the subsequent process, the used container is transferred to the container disposal section.

As described above, the analyzer 1 basically has a dispensing function of dispensing by the sample supply unit 30, dispensing by the first reagent supply unit 50, and dispensing by the second reagent supply unit 60. Inspection can be performed by obtaining data by measurement by the measurement unit 80. In this embodiment, in addition to the dispensing function, the measurement function, and the like, the following functions are additionally provided. I will prepare it. In other words, when performing analysis with a dispensing function of causing the probe to aspirate and discharge a liquid, the dispensing state is monitored, and in monitoring, is the probe accurately and reliably aspirated the liquid? Or, it is possible to perform monitoring by detecting whether or not the liquid has been discharged, and thereby to reliably detect that the dispensing operation has been performed normally and to guarantee the reliability of the obtained data. Therefore, a function of monitoring the dispensing state by image processing is provided.

Preferably, in order to avoid the above-mentioned difficulties of the related art which do not employ the present invention, after sucking the liquid, the state of the probe after the discharge is monitored by image processing to thereby suction and discharge the liquid. In order to surely detect the state, it is configured to include a sensor for detecting a state in which the probe sucks and discharges the liquid by using the image processing means. For this reason, in the present embodiment, for example, as shown in FIGS. 2 and 3, an image processing unit connected to the CCD camera 130 and the control unit 100 as its sensor (image sensor) and image processing means. 101 is provided, and a device for monitoring a dispensing state by image processing is provided. The apparatus for monitoring the dispensing state by the image processing includes a CCD camera 130 and the C
A / D converter 111 for converting image information captured by CD camera 130 into digital data, memory 112 used for storing digital data, and a data processing unit for performing processing including image processing and other data processing 11
3 and an input unit 115 and an output unit 116
, Display unit 118, timing control unit 120
And can be configured. Here, the input unit 11
5 and the output unit 116 can be configured to use the input / output circuit of the control unit 110 as the device control unit described above. A display means such as a display or a printer may be used to notify the operator of various information such as data, and the timing control unit 120 captures and stores image information at a predetermined timing set in advance. Can be made to function as a control unit for controlling the processing of.

In this system, whether the probe holds or discharges the liquid can be monitored by capturing and processing the image information with the CCD camera 130 and detecting it, and the probe sucks and discharges the liquid. By monitoring the state, suction and discharge of the liquid are detected.

In this case, it is preferable that the state in which the probe sucks and discharges the liquid is the first mode in which the change in the liquid in the probe is detected by the CCD camera 130, or the change in the liquid in the sample container is detected. The CCD according to any one of the second mode of detecting with the CCD camera 130 or the third mode of detecting the change of the liquid in the reaction container with the CCD camera 130, or the two or more modes,
It is detected by the camera 13.

In dispensing using a disposable tip, it is simple in terms of system configuration that the liquid level detection is pressure detection by blowing air, which is advantageous in terms of cost. On the other hand, the pressure transmission medium from the syringe to the dispensing tip had to be air, and the dispensing accuracy of suction / discharge was poor for non-disposable dispensing that could be filled with water, and the probability of dispensing failure was high. . The present invention particularly provides a method for confirming suction / discharge in dispensing using a disposable tip having such a specific problem, and has a remarkable effect. In the case of a disposable disposable tip type probe made of a transparent resin, which is inexpensive even at a low cost, the fact that the inside of the probe is visible as shown schematically in FIG. The second and third aspects can do this in such a way that, when the container used is, for example, a transparent container, it can be used more advantageously. Here, in the case of the second mode and the third mode, FIG.
As shown in FIG. 5 (application to a sample container) and FIG. 5 (application to a reaction container), when detecting from the side wall of the container,
For example, in the case of FIG. 4, a side portion of the container holding portion is formed with a cutout as shown in the drawing to expose a side wall portion of a transparent container (for example, a glass test tube or the like).
Through the cutout portion, the inside of the container can be seen from the outside of the container side wall, so that the CCD camera 130 can capture and detect the image from the lateral direction. In the case of FIG. 5, the upper portion of the transparent container is supported, but the lower portion of the container is arranged to penetrate the lower surface of the plate-shaped container holding portion so that the inside of the container can be seen from the outside of the container side wall as shown in the drawing. As a result, the image can be captured and detected by the CCD camera 130 from the lateral direction.

Preferably, the apparatus for monitoring a dispensing state by image processing includes, for example, image information of a predetermined amount of liquid suction and discharge, or image information of a probe, a sample container, and a reaction container. It has means for comparing the image information obtained by the CCD camera 130 at the time of measurement to determine whether or not the liquid has been sucked and discharged normally, and also has means for notifying the result of the determination. Here, the comparison and determination of the image information that has already been captured and captured in advance and the image information obtained by the CCD camera 130 at the relevant measurement time point in the actual dispensing operation, and the determination result Each means for notification can also be configured to be included in the image processing / control system (100, 101) of FIGS. The control program for executing the comparison judgment (measurement, judgment procedure) processing and the notification processing is also described in the turntable 10 in FIG.
Like a control program for controlling other mechanical parts, etc., it can be stored in a program storage unit (storage circuit; ROM) in advance, and the determination result is notified by the above-described display, printer, or the like. This can be performed through the display unit 118.

Hereinafter, the following items, ie, [1.
Device outline], [2. Measurement protocol], [3. In this order of [Determination], the dispensing state monitoring device according to the present image processing will be described with reference to the drawings.

[1. Device Overview]; [1.1-1]: In the analyzer 1, locus aspirate sample or reagent solution, the probe for discharge to move (e.g., in this embodiment, the disposable tip 41 of the dispenser 33 1 of the nozzle portion 33 ', the rotation locus of the nozzle portion 52' of the dispenser 52 in FIG. 1, and the nozzle portion 62 'of the dispenser 62 shown in FIG. When the probe arrives at a specific point on the middle rotation trajectory (middle rotation trajectory), image information of the probe is captured by the CCD camera 130 installed in advance (for example, see FIG. 2).

[1.1-2] : In addition to or instead of the above [1.1-1], in the present analyzer 1, image information of the sample container or the reaction container before and after dispensing is captured ( For example, see FIGS. 4 and 5 (A) and (B)).

[1.2-1] : It is desirable that the measurement point is a portion near the tip of the probe (for example, see FIG. 2).

[1.2-2] : In the case where the image information of the container is taken in the above [1.2-1], the measurement point may be any location where the sample container or the reaction container is located.

[1.3] : One or more measurement points ([1.2-1] and [1.2-2]) may be provided.

Here, in FIG. 1, reference numerals M1 to M8 are attached, and the CCD camera 13 is as follows.
It is an example of the 0 installation position.

[0044]

[Table 1] Example of CCD installation position Monitor of nozzle part; M1 or / and M2, M7, M8 Reaction vessel; M3, M5, M6 Sample vessel;

In this embodiment, any one or more of the M1 to M8 shown in the drawing can be set as the measurement points. When two or more locations are targeted, a CCD camera 130 can be separately installed for each. Here, to add a supplementary explanation, the CCD camera 130 depicted in FIG. 2 and the liquid surface (boundary surface) actually inside
The illustrated portion of the disposable chip 41 which is the imaging target in the state where is present represents the state at the point of M1 or M2 in FIG. 1 and the dispenser 52 or the dispenser at the same time. In the case where 62 is a transparent resin probe or a disposable chip type probe, it also represents the state at the points M7 and M8 in FIG. 1 (in this case, the arm (3 in FIG. 2).
3a), the nozzle (33b) attaching / detaching part (33c) means an arm part, a nozzle, and the like on the dispenser 52, 62 side, respectively. Here, the above-mentioned M1 is used during dispensing operation, particularly in the case of a disposable type probe, from the disposable tip case 42 to the disposable tip 4.
1 Mounting → rotation toward liquid suction position → liquid suction → rotation toward turntable 10 side after liquid suction → tip discard position (4
5) Pass over → pass M1 point → turntable 10
Reach the upper liquid discharge position → liquid discharge → return rotation from above the turntable 10 → pass M1 point → disposable chip 41 discard (discard unit 45) → disposable chip case 42 to next new disposable chip 4
The disposable tip 41 always passes twice in a series of repetition processes of 1 mounting →... (The first time the liquid passes while holding the liquid (the boundary surface exists) at the first time, and the liquid at the second time). As a result, the monitoring point is an advantageous monitoring point in the case of monitoring the dispensing state by image processing. M in FIG.
7 and M8 are the same points in that the probes of the dispensers 52 and 62 first pass while holding the liquid, and pass the second time while discharging the liquid. The example of FIG. 2 shows M3, M5 and M6 in FIG. 1 (however, in the case of M5 and M6, as described above, the probe used is assumed to be a transparent resin probe or a disposable chip. 2 (however, in the case of the measurement points at M3, M5, and M6, the object to be imaged by the CCD camera 130 is on the container side). In this example, the object to be imaged by the CCD camera 130 is set to the container side, and can be considered to represent the state at M4 in FIG.

[2. Measurement Protocol]; [2.1-1]: by the CCD camera 130 captures an image of the probe state after the probe has aspirated liquid.

[2.1-2] : In addition to or instead of the above [2.1-1], image information of a sample container or a reaction container before dispensing is previously captured.

[2.2] : In some cases, the CCD camera 130 may capture an image of the state of the probe again at a specific point until the probe sucks and discharges the liquid.

The above-mentioned image information allows a boundary surface between liquid and air to be taken in as image information.
As shown in FIGS. 4 and 5, the image is taken from the horizontal direction (preferably, as described later, when the boundary surface is to be obtained, an oblique direction so that the number of pixels in the boundary surface can be counted to a required degree). can do.

[2.3-1] : The CCD camera 130 captures an image of the state of the probe after the probe has discharged liquid.

[2.3-2 ] : When capturing image information of a container, in addition to or instead of the above [2.3-1], a signal notifying that the liquid has been ejected is used as a trigger to trigger the same. Capture image information of the container.

[3. Judgment] ; [3.1] : The image data corresponding to the predetermined liquid suction amount and discharge amount is stored, compared with the image data obtained by the measurement, and the dispensing operation is performed normally. Monitor what happened.

[3.2] : In addition to or instead of the above [3.1], the light amount at the boundary surface is compared to determine whether or not there is a cell (CCD cell) with a reduced light amount.

The dispensing state monitor by the image processing described above is intended to ensure the accurate detection of the suction and discharge of the liquid in an analyzer having a dispensing function of causing the probe to suck and discharge the liquid. In this embodiment, effective means can be provided, and according to the present embodiment, when more certainty and accuracy are required, it can be easily responded to, and the state can be monitored by image processing. Thus, it is possible to reliably detect the suction and discharge of the liquid. As described above, when monitoring fluctuations with a pressure sensor in the pipe, it is difficult to obtain a sufficient change if the suction and discharge amounts are very small. If there is, it is difficult to expect stable monitoring due to the composition of the liquid or the noise from the device.On the other hand, if monitoring is performed by changing the light received by applying light or laser to a part of the probe or the discharged liquid, Although it is difficult to irradiate light to the spot and secure the positional accuracy of the light reception, the present embodiment 1 which can avoid these problems has the following considerations (i) to (d) at the beginning of the specification. 2), which makes it possible to more accurately and reliably monitor the state in which the probe is holding the liquid or the state in which the liquid is discharged, as compared with the conventional method. That is, it is possible to reliably detect that the dispensing operation has been performed normally, and therefore, it is possible to guarantee the reliability of the data obtained by the analyzer 1.

The following are examples of application for monitoring with a probe and monitoring for a container.

[Application Example 1: Example of Probe Monitor] The following is an example applied to a probe monitor.
Here, the example is mainly applied to the case of the nozzle portion 33 ′ having the transparent disposable tip 41 of the dispenser 33. However, the present invention is also applicable to a transparent resin probe. Also, the dispenser 62 can be applied as an example in the case of a transparent resin nozzle or a transparent disposable tip type probe (this is the same in the following examples).

[11]: An image of the state of the probe after the probe sucks the liquid, that is, the image of the state of the disposable tip 41 after the disposable tip 41 with the dispenser 33 attached thereto sucks the liquid. 130
In the horizontal direction (preferably in an oblique direction (the same applies to other examples described below)).

[12] Utilizing the fact that the amount of transmitted light at the interface between the sucked liquid and air is small, it is found by image processing whether there is a portion with a small amount of light (therefore a portion corresponding to the interface). The details are as follows. The captured image information is converted into digital data by the A / D converter 111. At this time, the process is performed so that the value of bright data is large and the value of dark data is small. By performing a differentiation process on the digital data, a change point of the transmitted light amount, that is, a boundary surface between the liquid and the air is detected. This makes it possible to determine the presence of the boundary surface, that is, that the liquid has been sucked. Thus, when the presence of such a boundary surface is detected, it is determined that the liquid has been sucked (suction detection, suction determination). The judgment result can be notified through the display unit 118, and the operator who touches the judgment can recognize such a state (the same is true in the following examples). Furthermore, in addition to the above, according to the image processing, it is possible to measure the area of the liquid portion or the distance between the boundary surfaces or the position of the boundary surface by counting the number of pixels in the boundary surface. . Therefore, the volume of the sucked liquid can be calculated from the measured value and the volume of the probe. That is, the measured value (measured area value of the liquid surface portion where the suction was detected or the distance between the boundary surfaces or the position of the boundary surface) and the volume of the probe used (in this example, the disposable tip 41 in advance) There is also an advantage that the volume of the sucked liquid can be calculated (calculated and calculated) from the obtained storage volume value (volume value in the chip).
If the following [13] to [15] are detected for the sucked liquid, the value of the liquid volume obtained by the above calculation indicates that the dispensed amount in the dispensing operation is obtained. You can see it. As a result, the dispensed amount can be monitored, and in this case, it can be obtained through the above-described image processing. Therefore, even if the amount is very small, there is an advantage that accuracy can be easily ensured. Thus, accurate monitoring of such dispensed volumes, based on image processing, will also serve to further assure the reliability of the data obtained by the present analyzer 1.

[13]: The state of the disposable chip 41 after the liquid is discharged from the disposable chip 41 is captured as an image by the CCD camera 130.

[14]: A boundary surface is searched according to the same principle as in the above [12]. Here, regarding the detection that the disposable chip 41 has discharged the liquid (the detection of the discharge of the liquid and the direct monitoring of the state of discharging the liquid), it is confirmed that “there is no boundary surface” within the searched range. Can be done by

[15]: When it is confirmed that there is no boundary surface in the searched range, it can be determined that the liquid has been discharged (discharge detection, discharge determination). The judgment result can be notified through the display unit 118, and the operator who touches the judgment can recognize such a state (the same is true in the following examples).

As described above, in the dispensing state monitor,
These detections can be reliably performed by distinguishing between sucking and discharging. By analyzing the state of the disposable tip 41 (probe) after the liquid is sucked and discharged by image processing, the analyzer 1 that can surely detect the suction and discharge of the liquid can be more accurately measured. It is possible to monitor the state in which the disposable tip 41 holds the liquid and the state in which the liquid is discharged, and thus can reliably detect that the dispensing operation has been performed normally, The present analyzer 1
Can also guarantee the reliability of the data obtained.

In addition, in the case of the analyzer 1 in which the probe can be attached and detached by the disposable tip 41, the following operation and effect unique to the disposable probe are exhibited. In dispensing using a disposable tip, it is simple in terms of system configuration that the liquid level detection is pressure detection by blowing air, which is advantageous in cost.
On the other hand, the pressure transmission medium from the syringe to the dispensing tip must be air, and the dispensing accuracy of suction / discharge is poor for non-disposable dispensing that can be filled with water, and the probability of dispensing failure increases. However, in the analyzer 1 according to the present invention, in which the dispensing state is monitored by image processing, in the dispensing method using a disposable tip, which has such a specific problem, a method for confirming suction / discharge (amount) is particularly preferable. And has such a specific effect. Such an effect is the same in the following examples. Also,
The monitoring method based on the capacitance change discussed at the beginning of the specification cannot be used in the case of a resin probe due to its properties, and there are restrictions in this respect. In the case of a state monitor, there is no such restriction, and this point is also useful for a disposable probe employing a disposable resin tip 41.

[Application Example 2: Example of Monitoring of Probe] The following is another example applied to monitoring of a probe, and can be regarded as a modification of Application Example 1 described above.

[21]: An image of the state of the disposable chip 41 before liquid suction is captured in the horizontal direction by the CCD camera 130.

[22]: Image processing is performed on the entire disposable chip 41 to generate data (similar to [Application Example 1]).

[23]: An image of the state of the disposable chip 41 after the liquid has been sucked is taken in the horizontal direction by the CCD camera 130.

[24]: Image processing is performed on the entire disposable chip 41 to generate data (similar to [Application Example 1]).

[25]: The data (image information) in the case of [22] is compared with the data (image information) in the case of [24], and it is determined that the liquid has been sucked. The details are as follows. For each image information, the number of pixels showing a bright (large) value and the number of pixels showing a dark (small) value with respect to a certain threshold are counted. The above threshold value is obtained by digitally processing an image of the disposable chip 41 in a state in which the liquid has been sucked in advance (similar to [Application Example 1]), and differentiating this numerical value to obtain a change rate of the transmitted light amount at the boundary surface. Thus, the threshold can be set from the numerical value. Further, each image information may be differentiated each time to determine a boundary surface, and the number of pixels (the number of pixels having a dark value or a small value) covered by the boundary surface may be counted. Each disposable chip 4
It is detected that the liquid has been sucked by comparing the number of pixels of a bright (large) value and the number of pixels of a dark (small) value in the situation 1 (each image before the suction operation and after the suction operation). Yes (suction detection, suction judgment). Further, the volume of the sucked liquid can be calculated from the number of pixels having the dark (small) value and the volume of the disposable tip 41. Here, the volume of the sucked liquid can be calculated by the same method as described in [12] of [Application Example 1], but in this case, compared to the case of [Application Example 1], As a result, the volume can be obtained more accurately, and accordingly, the accuracy of monitoring the dispensed amount can be further improved.

[26]: The state of the disposable chip 41 after the discharge of the liquid by the disposable chip 41 is captured as an image by the CCD camera 130.

[27]: Image processing is performed on the entire disposable chip 41 to generate data (similar to [Application Example 1]).

[28]: The data (image information after the ejection operation) in the case of [27] is compared with the data (image information before the suction operation) in the case of [22] to confirm that they are equal (in this case) This can be performed by the processing as described in [25] above). Alternatively, the data in the case of [27] (image information after the ejection operation) is compared with the data in the case of [24] (image information after the suction operation), and it is confirmed that the difference in light amount is larger than a certain threshold value. I do.

[29]: In the comparison of the above [28],
In the case of the former method, when it is confirmed that the liquids are equal as a result of the comparison, it can be determined that the liquid has been discharged. In the case of the latter method, the light amount difference is determined to be a predetermined threshold value. If it is confirmed that the liquid is larger than the above, it can be determined that the liquid has been discharged (discharge detection, discharge determination). In this case, using both together,
Reliability and certainty can be further improved.

As a method of image processing, such a method may be used, and the present invention can be implemented in this way.

[Application Example 3: Example of Monitoring of Probe] The following is still another example applied to monitoring of a probe, in which a preset liquid suction amount (storage amount) and discharge amount are set. Using the image information, and comparing it with the image information obtained by the CCD camera 130,
This is an example of a case where an attempt is made to determine whether or not ejection has been performed normally. This can be regarded as a modification of the above-mentioned [Application Example 1] or [Application Example 2]. In addition, in the case of the above [Application Example 2], every time the dispensing operation is performed, for example, data obtained by capturing the image information immediately before the suction operation ([Application Example 2]). [21]
, [22]) are compared with each other, but in this example [application example 3], the data to be compared is not fetched each time, but is set in advance by setting data (a predetermined required value). (Fixed data) and stored as such, and this point can also be considered as a modified example of the above [Application Example 2].

[31]: An image of the state of the disposable chip 41 after liquid suction is captured by the CCD camera 130 in the horizontal direction.

[32]: Performs image processing of the entire disposable chip 41 and converts it into data (this is the same as [22] in [Application Example 2: Another Example of Probe Monitor], and [Application Example 1: Example of monitoring a probe]).

[33]: Image data corresponding to a predetermined liquid suction amount and discharge amount is stored in the memory 112,
The image data obtained by the measurements [31] and [32] is compared with and determined to monitor that the dispensing operation has been performed normally. The details are as follows.

In advance, a certain threshold value is bright (large)
The number of pixels indicating the value and the number of pixels indicating the dark (small) value are determined and stored. This numerical value may be determined within a range having a certain width. The following is an outline of numerical examples.

[0080]

(1a) Number of pixels with a bright value 10000 ± 200 (1a) Number of pixels with a dark value 200 ± 10 (at the time of liquid suction) (1b) 10 ± 10 (at the time of liquid discharge) (1c) )

Alternatively, the number of pixels having a darker (smaller) value in the boundary surface than the data subjected to the differential processing may be determined.

The threshold value is obtained by digitally processing a probe (an image of the disposable tip 41) in which a liquid has been sucked in advance (similar to [Application Example 1: Example of monitoring a probe]) and differentiating this numerical value. By determining the rate of change of the amount of transmitted light at the boundary surface, the threshold value can be set from the numerical value.

The above-mentioned predetermined numerical value is compared with the numerical value obtained by the dispensing operation. Specifically, at the time of liquid suction,
Further, at the time of liquid ejection, the number of pixels having the dark value is compared (the number of pixels having the bright value may also be compared at the same time). If the numbers match, it is determined that the liquid has been normally sucked or ejected. (Suction / discharge determination).

As a method of image processing, such a method may be used, and the present invention can be implemented in this way.
Further, in this case, as an application example of the determination result, the numerical data obtained in the above-described image processing process can be used as advantageous information when the following feedback control is added. That is, for example, in the suction of the dispensing operation, the liquid can be suctioned by controlling the operation of the syringe. However, due to the aging of the operation system and other factors and the operation command given to the syringe, the actual suction is performed. It is conceivable that excess or deficiency occurs in the liquid amount (actual liquid amount). Such a deviation also affects the reliability of data obtained by the analyzer. So, in such a case, for example, if you can get information about how much more you need to aspirate (and therefore how much the syringe should be operated in the suction direction) if it is insufficient, By using such information, the target value (aspiration amount required as necessary for dispensing) can always be stably secured without being affected by the factors as described above. Operation can be performed normally. Here, when looking at the above-mentioned predetermined numerical value and the numerical value (accordingly, the actual value) obtained by the dispensing operation, the difference between the two indicates the deviation between the target value and the actual value. Therefore, feedback control of the operation of the syringe based on the deviation is performed so that the deviation becomes zero, that is, the numerical value obtained by the dispensing operation matches the predetermined numerical value. Then, by such feedback correction, the actual suction liquid amount can be adjusted to the correct normal required suction amount. Therefore, when such a process is taken into consideration, it is possible to determine, with a high degree of accuracy, that the liquid has been sucked or discharged normally with high accuracy when both values match. The use of such a determination result is not limited to this application example, and can be similarly applied to the other application examples already described and the application examples described below. Further, in FIG. 2, the case of the detachable disposable tip 41 has been described. However, it is needless to say that the present invention can be implemented without using a detachable probe as shown in FIG. Absent.

[Application Example 4: Example in Case of Container Monitoring] The following is an example in which the invention is applied to container monitoring, and is based on image processing according to the method of [Application Example 3] described above.

[41] The image information of the sample container or the reaction container before dispensing is previously captured by the CCD camera 130 as described above (for example, see FIG. 5A). The image information captures a boundary surface between liquid and air from a horizontal direction.

[42]: The image information of the container is similarly captured by the CCD camera 130 using a signal notifying that the liquid has been discharged (discharge operation on the probe side) as a trigger (for example, see FIG. 5B).

[43] The image information obtained in [42] is converted into data by image processing.

[44]: Comparing the light amount at the boundary surface, it is determined whether or not there is a cell (CCD cell) with a reduced light amount (a dark (small) value exists, or a changing point of a differentiated numerical value exists). Or not). Thus, it is determined that the boundary surface exists, that is, the liquid has been discharged into the container.

In other words, it is possible to monitor (indirectly monitor) the state in which the probe has discharged liquid from the probe side during the suction and discharge operations of the probe. Can be reliably detected that the dispensing operation has been performed normally, and similarly, the reliability of the data obtained by the analyzer 1 can be guaranteed.

The present invention can be implemented in this way.

The present invention is not limited to the above embodiment. For example, the case where the detachable disposable tip 41 is mainly described as the probe has been described. However, it is needless to say that the present invention can be implemented with a probe that is not a detachable probe or a detachable probe. Absent.

Further, for example, in both the case where it is detachable and the case where it is not possible, not only the case where it is transparent, but also a transparency such as a semi-transparent state that image data capable of image processing can be obtained. I suffice. Similarly,
In any case, besides resin, it may be made of glass, for example, and can be advantageously implemented in such a case.

Further, for example, the image processing method is not limited to the method described above, and various methods can be adopted. Here, in the case of a transparent container, the direction in which the image information is taken in may not be the direction shown in FIGS. 4 and 5 depending on the liquid, but the boundary surface between air and liquid is detected by light amount information (for example, a dark image). It is possible in some cases, and therefore, it is not limited to taking in not only from the lateral direction but also, for example, from the vertical (or almost vertical) direction.

Further, for example, the methods of [Application Example 1] and [Application Example 2] for a probe are extended,
The present invention is applicable to a case in which the dispensing state is monitored by image processing on a container as a modification.

Further, for example, in the above-mentioned [Application Example 4] for a container, the discharge is determined. However, in the case of detecting the suction of the liquid, it is applied to the detection of the state of sucking the liquid according to the method. It is possible.

The above [Application Example 1] to [Application Example 4]
Does not preclude implementation in combinations of two or more thereof, if desired.

The contents described above can be considered as the following inventions.

[Supplementary Item 1] An analyzer having a dispensing function of causing a probe to suck and discharge a liquid is provided with a sensor for detecting a state in which the probe sucks and discharges the liquid by using image processing means. An analyzer, characterized in that:

[Appendix 2] The analyzer according to Appendix 1, wherein the probe is detachable.

[Appendix 3] The state in which the probe sucks and discharges the liquid is defined as the change in the liquid in the probe and / or the change in the liquid in the sample container and / or the change in the liquid in the reaction container. 3. The analyzer according to claim 1, wherein the detection is performed by a sensor.

[Appendix 4] The analyzer according to any one of Appendices 1 to 3, wherein the sensor comprises a CCD camera.

[Appendix 5] The image information of the probe, the sample container, and the reaction container, which is set in advance, is compared with the image information obtained by the sensor. The analyzer according to any one of additional items 1 to 4, further comprising means for judging whether or not the liquid has been sucked and discharged normally, and preferably means for notifying the result of the judgment. .

[Brief description of the drawings]

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

FIG. 2 is a diagram provided for describing an example of a monitor in a dispensing state by image processing, applicable to the example.

FIG. 3 is a diagram showing an example of the configuration of an image processing / control system.

FIG. 4 is also a diagram for explaining an example of monitoring of a dispensing state by image processing, and is a diagram showing an application to a sample container.

FIG. 5 is also a diagram for explaining an example of monitoring of a dispensing state by image processing, and is a diagram showing an application to a reaction container.

FIG. 6 is a diagram showing another example of a probe monitor.

[Explanation of symbols]

 Reference Signs List 1 analyzer 10 reaction turntable 11 container 20 reaction container transfer unit 21 reaction container stocker 22 transfer unit 30 sample supply unit 31 container 32 sample holding unit 33 dispenser 33 'nozzle unit 33a arm unit 33b nozzle 33c detachable unit 40 disposable tip Supply unit 41 Disposable tip 42 Disposable tip case 45 Tip disposal position (tip disposal unit) 50 Reagent supply unit 51 Reagent turntable 52 Dispenser 52 'Nozzle unit 53 Container 60 Reagent supply unit 61 Reagent turntable 62 Dispenser 62' Nozzle unit 63 Container 80 Measurement unit 100 Control unit 101 Image processing unit 111 A / D converter 112 Memory 113 Data processing unit 115 Input unit 116 Output unit 118 Display unit 120 Timing control unit 130 CCD camera

 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Yasuhiko Fujita 2-43-2 Hatagaya, Shibuya-ku, Tokyo F-term in Olympus Optical Industrial Co., Ltd. 2G058 CB15 CD04 CE08 EA02 EA04 EC03 ED36 GB06 GE03

Claims (8)

[Claims] 1. An analyzer having a dispensing function of causing a probe to suck and discharge a liquid, wherein the sensor detects, by using an image processing means, a state in which the probe sucks and / or discharges the liquid. An analyzer comprising: 2. The analyzer according to claim 1, wherein a state in which the probe sucks and / or discharges the liquid is detected by the sensor based on a change in the liquid in the probe. 3. The analyzer according to claim 1, wherein a state in which the probe sucks and / or discharges the liquid is detected by the sensor based on a change in the liquid in the container. 4. A method for comparing a predetermined amount of image information of a liquid suction amount and / or a discharge amount with image information obtained by the sensor to determine whether the liquid suction and / or discharge is normally performed. The analyzer according to any one of claims 1 to 3, further comprising means for determining. 5. A means for comparing image information of a probe set in advance with image information of a probe obtained by the sensor to determine whether suction and / or discharge of the liquid has been performed normally. 5. The analyzer according to claim 1, further comprising means for notifying a result of the determination. 6. A means for comparing the image information of the container set in advance with the image information of the container obtained by the sensor to determine whether or not the suction and / or discharge of the liquid has been performed normally. And means for notifying a result of the judgment.
The analyzer according to any one of the above. 7. The analyzer according to claim 3, wherein the container is a sample container or a reaction container. 8. The analyzer according to claim 1, wherein said sensor comprises a CCD camera.