Patent Description:
In an automatic analyzer, there is an increasing demand for reducing an amount of a sample (specimen) in order to increase the number of analysis items and reduce a burden on patients. Therefore, in order to reduce an amount of the sample (a dead volume) that is not used for analysis and remains in a sample container, a diameter of the sample container is being reduced. In order to perform appropriate dispensing to the sample container having a smaller diameter, it is required to properly align a stop position and a dispensing position of the sample container. Here, a technique is disclosed for detecting a deviation between a lower end portion of a dispensing tip and a center position of a holder based on an image of the lower end portion of the dispensing tip (see PTL <NUM>).

<CIT> describes an amplification and array loading apparatus with the features in the pre-characterizing portion of Claim <NUM>. Further analysis device related to the one of the present invention are disclosed in <CIT> and <CIT>.

According to PTL <NUM>, since the dispensing tip is imaged from below, there is a problem that a liquid attached to the tip falls downward and contaminates an imaging mechanism.

Therefore, an object of the invention is to provide an automatic analyzer that performs accurate dispensing position control with an imaging mechanism not contaminated.

The automatic analyzer according to the invention is defined in Claim <NUM>. Further advantageous features are set out in the dependent claims.

According to the invention, it is possible to provide an automatic analyzer that performs accurate dispensing position control with an imaging mechanism not contaminated.

An embodiment will be described below with reference to the drawings.

<FIG> is an overall view illustrating an automatic analyzer. The automatic analyzer includes: a sample rack <NUM> on which a sample container <NUM> is placed; a container holding device <NUM> that holds the sample container <NUM>; a reagent holding unit <NUM> that holds a plurality of reagent containers <NUM> containing a reagent; a magazine (a storage box) <NUM> that stores a reaction container <NUM> and a disposable tip (hereinafter, referred to as the tip) <NUM> for dispensing a sample; a reaction unit (an incubator) <NUM> that houses a plurality of reaction containers <NUM> and promotes a reaction of the sample and a reagent in the reaction container <NUM>; a container wasting unit <NUM> where the reagent container <NUM> is discarded; a tip wasting unit <NUM> where the tip <NUM> is wasted; a magnetic separation mechanism <NUM>; a detector <NUM>; a reagent discharging mechanism <NUM> that discharges the reagent to the reaction container <NUM> transported to the detector <NUM>; a container lid opening and closing mechanism <NUM> that opens and closes a lid of the reagent container <NUM>; a sample dispensing unit <NUM> that collects and dispenses the sample from the transported sample rack <NUM> using a sample probe <NUM>; a reagent dispensing unit <NUM> that collects and dispenses the reagent from the reagent container <NUM> using a reagent probe; a magnetic particle stirring mechanism <NUM>; a buffer <NUM> that temporarily stores the tip <NUM> for dispensing the sample; a first transport mechanism <NUM> that transports the reaction container <NUM> to the reaction unit <NUM> or the buffer <NUM>; an imaging unit <NUM> that is disposed close to the buffer <NUM> and images the sample dispensing unit <NUM>; and a second transport mechanism <NUM> that transports the reaction container <NUM> between the reaction unit <NUM>, the magnetic separation mechanism <NUM>, the detector <NUM>, the container wasting unit <NUM>, or the like.

The magnetic separation mechanism <NUM> includes a magnetic separator <NUM>, an impurity aspirating mechanism <NUM>, and a cleaning liquid discharging mechanism <NUM>. The impurity aspirating mechanism <NUM> aspirates a liquid containing impurities in the reaction container <NUM> transported to the magnetic separator <NUM>, and the cleaning liquid discharging mechanism <NUM> discharges a cleaning liquid into the reaction container <NUM>.

As a method of transporting the sample rack <NUM>, there are a method of installing the sample rack <NUM> on a belt and performing transportation by the belt, a method of using a disk in which the sample rack <NUM> itself rotates to transport a container, a method of using a disk in which a transport device installs a sample and transports the sample by rotation, a method of moving the sample rack <NUM> by grasping or lifting, and the like.

Next, operations of the automatic analyzer will be described. First, the first transport mechanism <NUM> transports the reaction container <NUM> from the magazine <NUM> onto the reaction unit <NUM>, and transports the tip <NUM> to the buffer <NUM>. The reaction unit <NUM> rotates and moves the transported reaction container <NUM> to a reagent dispensing position. Then, the reagent dispensing unit <NUM> dispenses the reagent from the reagent holding unit <NUM> to the reaction container <NUM> on the reaction unit <NUM>.

The reaction unit <NUM> rotates again to move the reaction container <NUM> to a sample dispensing position. The tip <NUM> of the buffer <NUM> is mounted on the sample probe <NUM> by a vertical movement of the sample dispensing unit <NUM>. The sample dispensing unit <NUM> collects the sample from the sample container <NUM> on the sample rack <NUM>, and dispenses the sample into the reaction container <NUM> moved to the sample dispensing position. At the time of collection, the sample container <NUM> is held by the container holding device <NUM>. The used tip <NUM> is removed from the sample dispensing unit <NUM> by the vertical movement of the sample dispensing unit <NUM>, and is discarded to the tip wasting unit <NUM>.

The reaction container <NUM>, in which the sample and the reagent are dispensed, is heated in the reaction unit <NUM> for a certain period of time, and then moved to the reagent dispensing position by rotation of the reaction unit <NUM>. Next, the reagent dispensing unit <NUM> collects magnetic particles from the reagent holding unit <NUM>, and dispenses the magnetic particles into the reaction container <NUM> at the reagent dispensing position. Further, after the reaction container <NUM> is heated by the reaction unit <NUM> for a certain period of time, the reaction unit <NUM> rotates, and the second transport mechanism <NUM> transports the reaction container <NUM> on the reaction unit <NUM> to the magnetic separator <NUM>.

On the magnetic separator <NUM>, a magnetic component containing a reaction product and a non-magnetic component containing impurities in the reaction container <NUM> are separated. That is, aspiration by the impurity aspirating mechanism <NUM> and discharge of the cleaning liquid by the cleaning liquid discharging mechanism <NUM> are repeated several times, and finally only the magnetic component containing the reaction product is left in the reaction container <NUM>. The reaction container <NUM> is transported to the detector <NUM> by the second transport mechanism <NUM>. Thereafter, the reagent discharging mechanism <NUM> discharges the reagent for detection into the reaction container <NUM>, and the detection is performed. The reaction container <NUM> for which the detection is completed is discarded by the second transport mechanism <NUM> to the container wasting unit <NUM>. Thereafter, the above-mentioned operations are repeated for a subsequent sample.

Here, in an automatic immunological analyzer, a tip (a consumable) is used in order to prevent carryover and ensure analysis performance. In order to further improve a reliability of the analysis, it is desirable to control a dispensing position for each tip used in each analysis. Therefore, an example of an automatic immunological analyzer using a tip will be described below.

<FIG> is a diagram illustrating a flow of a dispensing position control. First, the imaging unit <NUM> images the tip held by the buffer <NUM> (S21). A measurement by the imaging unit <NUM> may be performed for each analysis, or may be performed at other timings. Here, the buffer <NUM> is a mounting base having a hole through which the tip <NUM> passes so as to hold the tip <NUM>. Next, the sample dispensing unit <NUM> moves the sample probe <NUM> to an upper side of the tip <NUM> of the buffer <NUM>, inserts the sample probe <NUM> into a hole at an upper end portion of the tip <NUM> by a lowering operation, and presses the sample probe <NUM> against an inner wall of the buffer <NUM>. As a result, the tip <NUM> fits into the sample probe <NUM> (S22). Next, an image processing unit <NUM> (the correcting unit) connected to the imaging unit <NUM> corrects a deviation amount between a center position of a lower end portion (tip portion) of the tip <NUM> and a center position of the sample container <NUM> based on an acquired image (S23). Next, a controller <NUM> connected to the image processing unit <NUM> controls, based on a correction value of the deviation amount, a stop position of the sample probe <NUM> such that the lower end portion of the tip <NUM> is at a region immediately above the center position of the sample container <NUM> (S24). A position correction between the center position of the tip <NUM> and the center position of the sample container <NUM> may be performed only by the sample probe <NUM>, or may be performed by a combination of the transport mechanism of the sample rack <NUM> and the container holding device. Then, the sample dispensing unit <NUM> collects the sample from the sample container <NUM> on the sample rack <NUM> (S25).

Here, when there is a problem in a forming state of the tip <NUM> (see <FIG>), it may be one of factors of variation, and thus it is necessary to detect an accurate positional relationship between the sample probe <NUM> and the tip <NUM>. On the other hand, as described above, when the tip <NUM> is imaged from below in order to grasp the positional relationship, an imaging mechanism may be contaminated. Therefore, in the present embodiment, before the sample probe <NUM> and the tip <NUM> are fitted together, the tip <NUM> is imaged from an upper side to a lower side in a gravity direction in a state where the sample probe <NUM> is not present in a region immediately above the tip <NUM> (<FIG>).

This method utilizes the matter that when the sample probe <NUM> is inserted into the hole at the upper end portion of the tip and pressed against the buffer, the center position of the sample probe <NUM> and the center position of the upper end portion of the tip match due to inertia. That is, it is not necessary to image the sample probe <NUM>, and it is only necessary to know the center position of the upper end portion of the tip and the center position of the hole at the tip portion of the tip (hereinafter, referred to as the tip hole).

<FIG> is a diagram illustrating an image in a case where the tip is imaged from above, according to the claimed invention. In the image of the sample probe <NUM> imaged from above, it is difficult to compare the center position of the sample probe <NUM> with a center position of a tip hole <NUM>. However, when an image is taken from the upper side to the lower side in the gravity direction in a state where the sample probe <NUM> is not present, respective boundary lines of an outer circumference <NUM> of the upper end portion of the tip and the tip hole <NUM> are clearly projected (a small circle is projected inside a large circle). In this way, a deviation amount between the outer circumference <NUM> and the tip hole <NUM> can be regarded as a deviation amount between the center position of the sample probe <NUM> and the center position of the tip hole <NUM>, and a correction value can be obtained.

Considering only a viewpoint of contamination prevention, since no liquid is attached to the tip at this point, in an unclaimed example, it is conceivable to image the tip <NUM> from the lower side to the upper side in the gravity direction. However, considering a viewpoint of clarity of the image described above or a viewpoint of securing a space in the automatic analyzer, it is desirable to take an image from above the tip <NUM>.

The sample probe <NUM> for collecting the sample moves to the sample dispensing position, and dispenses the sample into the reaction container <NUM>. A position correction of the sample probe <NUM> and the reaction container <NUM> at this time is the same as a position correction of the sample probe <NUM> and the sample container <NUM>. The sample dispensing unit <NUM> moves the tip <NUM>, by which dispensing to the reaction container <NUM> is completed, above the tip wasting unit <NUM>, and discards the tip <NUM> to the tip wasting unit <NUM> by removing the tip <NUM> from the sample probe <NUM> by the vertical movement.

<FIG> is a diagram illustrating a method of correcting a position deviation. Each position where the sample is aspirated and discharged by the sample dispensing unit <NUM> is corrected by the sample dispensing unit <NUM> or another mechanism based on an imaging result by the imaging unit <NUM>. This correction is performed by giving information obtained from a position measurement of the tip <NUM> by the imaging unit <NUM> as a correction value to each mechanism having one or a plurality of independent degrees of freedom.

When a mechanism to which the correction value is given has a degree of freedom only in a specific position direction, the position correction can be performed only in the direction of the degree of freedom of the mechanism. On the other hand, when the correction value has a plurality of degrees of freedom in a plane direction, a tip position of the tip can be controlled to a position on any plane by giving the correction value to each of movable directions. Further, the tip position of the tip may be controlled by dividing and giving the correction value into a plurality of mechanisms having different degrees of freedom.

For example, at the sample dispensing position, there are a sample rack transport mechanism having a degree of freedom in an x-axis direction, a container holding device having a degree of freedom in a y-axis direction, and a sample dispensing unit having a degree of freedom in a rotation direction. When a correction amount at the tip position of the tip is sufficiently smaller than a driving amount of various mechanisms, the sample dispensing unit can be considered to have a degree of freedom in the x-axis direction at the sample dispensing position. That is, the tip position of the tip can be controlled to an appropriate dispensing position by giving a correction value in the y-axis direction to the container holding device and a correction value in the x-axis direction to the sample rack transport mechanism and the sample dispensing unit. In this way, even when the forming state of the tip <NUM> is bent (see <FIG>), the reliability of sample dispensing can be improved by giving a correction value to a mechanism.

Variations of arrangement will be shown below. <FIG> is a diagram illustrating a state where the imaging unit images the tip from immediately above through a mirror <NUM>. <FIG> is a diagram illustrating an unclaimed example where the imaging unit images the tip from immediately below through the mirror <NUM>. <FIG> is a diagram illustrating an unclaimed example where the imaging unit images a lower side surface of the tip. <FIG> is a diagram illustrating an unclaimed example where the imaging unit images the tip from oblique below. <FIG> is a diagram illustrating an unclaimed example where the imaging unit images the tip from oblique below through the mirror <NUM>. An appropriate arrangement may be selected according to a layout of the automatic analyzer. From the viewpoint of the contamination prevention, it is possible to take an image from the lower side through the mirror as well, and thus such a state is shown in <FIG>, but it is desirable to take an image from the upper side, according to the claimed invention, as described above.

In addition, in order to acquire the correction value, it is desirable to install a plurality of imaging units <NUM>, and image the sample dispensing unit <NUM> or the tip <NUM> from a plurality of directions, but only one imaging unit <NUM> may be installed to acquire only a one-dimensional correction value. Further, the sample dispensing unit <NUM> and the tip <NUM> may be directly imaged by the imaging unit <NUM>, and a mirror may be installed to capture an image reflected in the mirror to obtain the correction value. The imaging by the imaging units <NUM> may be performed while the sample dispensing unit <NUM> is moving, or may be performed while the sample dispensing unit <NUM> is stopped.

Although not shown, the lower side surface of the tip may be measured using a sensor. For example, a sensor is installed such that statuses can be switched; a position where a detection result of the sensor is present when the sample dispensing unit <NUM> is moved, and a position where the detection result is switched from present to absent when the sample dispensing unit <NUM> is further moved are stored; and a median value of the positions may be defined as the tip position, and used as the correction value. The sensor determines a presence or absence of a substance in a certain region, and a type and a detection method of the sensor are not limited. For example, the sensor may be a reflective or transmissive photoelectric sensor, a sensor that utilizes reflection of ultrasonic waves, or a sensor that performs a detection based on a presence or absence of contact.

In image analysis processing, the tip position may be derived from a tip shape of the imaged tip <NUM>, or the tip position may be derived from a color distribution or a brightness distribution of the image. For example, as shown in <FIG>, a center position of intersections <NUM> between two side surface positions and the tip portion of the tip <NUM> may be derived as the tip position.

Claim 1:
An automatic analyzer comprising:
a magazine (<NUM>) for storing a plurality of tips (<NUM>) for dispensing;
a probe (<NUM>) for dispensing;
a buffer (<NUM>) that is a mounting base for mounting the tip on a tip of the probe, and has a first hole through which the tip passes so as to hold the tip;
an imaging unit (<NUM>) for imaging the tip; and
a controller (<NUM>) for controlling the tip such that the tip is mounted on the probe by pressing the probe against the tip while the tip passing through the first hole is held by the buffer,
characterized in that
the imaging unit is disposed such as to image the tip from an upper side to a lower side in the gravity direction,
the automatic analyzer further comprises a correcting unit (<NUM>) for correcting a deviation between the tip and a sample dispensing position based on a correction value obtained from a deviation amount between a center position of the probe and a center position of the tip hole; and
a deviation amount between an outer circumference of an upper end portion of the tip and a tip hole of the tip, determined from an image obtained by the imaging unit, is taken as the deviation amount between the center position of the probe and the center position of the tip hole.