JP2014066592A - Automatic analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an automatic analyzer capable of performing accurate optical measurement of even minute reaction liquid, by measuring the height variation of a plurality of reaction cells and correcting the positional relationship between a reaction cell and the optical axis of a photometer on the basis of the numerical value of the height variation.SOLUTION: The automatic analyzer includes: a light source for emitting light to a reaction cell in which a specimen is mixed with a reagent; a detector for detecting the light coming from the reaction cell; a reaction disk on which a plurality of reaction cells are mounted; and a control section for rotating and driving the reaction disk. In accordance with the height information of the bottom of each of the plurality of reaction cells, a storage section drives the optical axis of the light in the vertical direction.

Description

  The present invention relates to an automatic analyzer for clinical examinations, and in particular, to a plurality of reaction containers (reaction cells) held by a reaction disk, dispensing of a sample such as blood, and a reagent that reacts with a component of the sample and develops a color. The present invention relates to dispensing and an automatic analyzer for optically measuring the reaction.

  Conventionally, as an automatic analyzer, there is an automatic analyzer described in JP-A-11-316237 (Patent Document 1). This device consists of a colorimetric measurement unit for analyzing and quantifying proteins and ions in blood, components in urine, and the like, and an ion analyzer for analyzing ions in blood. Therefore, a large-scale device has a processing speed of 9000 tests or more. In order to increase the processing speed, especially in the colorimetric measurement unit, a large number of reaction vessels are installed on the circumference of the reaction disk on the upper surface of the main body of the automatic analyzer, and the sample is sequentially mixed, reacted, and measured by overlap processing. It is.

  This system consists of an automatic sample / reagent supply mechanism that dispenses specimens and reagents into a reaction vessel, an automatic stirring mechanism that stirs the sample / reagent in the reaction cell, and the physical properties of the reaction solution during or after the reaction. It consists of a photometer for measurement, an automatic cleaning mechanism for sucking and discharging the measured reaction solution and cleaning the reaction cell, and a controller for controlling these operations. In the photometer, the light beam emitted from the light source is transmitted through the solution to be measured in the reaction cell, and then guided to the spectroscopic device. The light intensity value measured for a specific wavelength is measured with the light intensity value measured in advance for the reference concentration solution. The chemical components in the solution to be measured are analyzed by comparing and calculating the absorbance.

  In the field of chemical / medical analysis, the miniaturization of liquids such as specimens and reagents has become a major issue. That is, as the number of analysis items increases, the amount of sample that can be divided into single items has become small. Furthermore, analysis using a very small amount of sample or reagent, which has been regarded as a sophisticated analysis in the past, such as DNA analysis in which the sample itself is precious and cannot be prepared in large quantities, has been routinely performed. In addition, as the analysis contents become more sophisticated, expensive reagents are generally used, and there is a demand for reducing the amount of reagents in terms of running cost.

  In order to reduce the amount of reagent, it is necessary to perform optical measurement with a small amount of reaction solution, but the challenge is how to keep the positional relationship between the reaction cell and the photometer luminous flux constant. . That is, as described above, since the automatic analyzer measures the light intensity value when the light beam from the light source in the photometer passes through the reaction cell, the light beam needs to pass only in the liquid surface of the reaction cell. As a matter of course, an accurate measurement result cannot be obtained when the light beam passes through the wall of the reaction cell or other than in the liquid. In a general automatic analyzer, the reaction cell moves to the photometer position as described in Patent Document 1, and therefore the positional relationship between the reaction cell and the photometer light beam depends on the positional relationship of each component. ing.

  Such a problem is usually dealt with by improving the accuracy of each component. In addition, as described in, for example, Japanese Patent Application Laid-Open No. 2003-107096 (Patent Document 2), an attempt has been made to solve the problem by positioning the reaction cell with high accuracy during optical measurement.

JP-A-11-316237 JP 2003-107096 A

  The method for improving the accuracy of the component parts for performing the optical measurement with the minute amount of the reaction liquid has problems such as cost increase, production management, and insufficient accuracy. In addition, since it is difficult to control the accuracy, it is often done to allow a margin in the design at the time of design. It was a hindrance. Similarly, the light flux is reduced in order to provide a margin, but this method may cause deterioration of the S / N ratio of the signal.

  Further, in the method of positioning the reaction cell with high accuracy, it is necessary to stop the reaction disk at the time of positioning, and there is a problem that cannot be used for optical measurement performed while the reaction disk is rotating.

  An object of the present invention is to provide an automatic analyzer capable of accurately positioning the positional relationship between a reaction cell and a light beam without improving the accuracy of individual parts and capable of performing an accurate analysis with a small amount of reaction liquid.

  A representative invention of the present application includes a light source that irradiates light to a reaction cell that mixes a specimen and a reagent, a detector that detects light from the reaction cell, a reaction disk on which a plurality of the reaction cells are mounted, and a reaction A control unit that rotates the disk, and the control unit is an automatic analyzer that drives the optical axis of the light in the vertical direction according to the height information of the bottom of each reaction cell of the plurality of reaction cells. is there.

  The optical axis, which is the center of the light beam, is driven in the vertical direction with high speed and high accuracy by an actuator. By driving the reaction disk according to the height of each reaction cell passing through the optical axis by rotating the reaction disk, the positional relationship between the light beam and the reaction cell is adjusted, thereby solving the above-mentioned problem.

  In addition, a target value for driving the optical axis can be determined by providing a mechanism for measuring the height of the reaction cell in advance or during measurement.

  According to the present invention, it is possible to perform optical measurement with a very small amount of reaction solution, and there is an effect of reducing the running cost of an automatic analyzer with multi-item analysis of a valuable trace sample. In addition, since it is possible to ensure a sufficient size of the light flux while minimizing the amount of the reaction solution, there is an effect of maintaining and improving the accuracy of the measurement data. In addition, since it is not necessary to improve the accuracy of the component parts and a small light source with a small amount of light can be used, an effect of reducing the manufacturing cost of the apparatus can be expected. In addition, since interference with the cell wall and the liquid surface of the light beam is reduced, stray light is reduced, and an effect of enabling highly sensitive specimen analysis by detecting a more minute signal can be expected.

It is a figure which concerns on the Example of this invention and represents the structure of an automatic analyzer. It is a figure which concerns on the Example of this invention, and represents the height variation of a reaction cell. FIG. 4 is a diagram illustrating an outline of an optical system and a mechanism for driving an optical axis in a vertical direction according to an embodiment of the present invention. FIG. 4 is a diagram illustrating an outline of an optical system and a mechanism for driving an optical axis in a vertical direction according to an embodiment of the present invention. It is a figure which concerns on the Example of this invention and represents the mechanism which measures the height of a reaction cell.

  An embodiment of the present invention will be described.

  An outline of the automatic analyzer will be described with reference to FIG.

  The automatic analyzer includes an analysis unit 110 and an interface / control unit 111. The analysis unit 110 includes a reagent disk 105, a reaction cell 101, a reagent sampling mechanism 108, a sample 107, a sample sampling mechanism 106, a water discharge mechanism 102 (cell washing water / cell blank water injection mechanism), Waste liquid discharge mechanism 104 (sampling mechanism for specimen / reagent / washing water / cell blank water after measurement), photometer 103 (optical measurement means), and a plurality of reaction cells 101 are fixed, and a plurality of reaction cells 101 are mounted. And a reaction disk 109 that is driven to rotate. As will be described later, the photometer 103 includes a light source that irradiates light to the reaction cell 101 that mixes the specimen and the reagent, and a detector that detects light from the reaction cell 101. In addition to this, a stirring mechanism (not shown) for stirring the reaction solution in the reaction cell 101 is also provided around the reaction disk 109.

  The plurality of reaction cells 101 arranged in a circle are rotated around the reagent disk 105 by a reaction disk 109 at regular intervals for the operation of each analysis process. This rotational driving is controlled by the control unit of the interface / control unit 111. In addition, the interface / control unit 111 includes a storage unit that stores information necessary for analysis by the analysis unit, and the control unit controls various mechanisms of the analysis unit 110 using this information.

  Before the measurement of the specimen, the reaction cell 101 is cleaned by the waste liquid discharge mechanism 104 and the water discharge mechanism 102.

  Next, when the reaction cell 101 passes in front of the photometer 103, cell blank measurement is performed. The cell blank measurement is performed in order to measure the absorbance of the reaction cell 101 containing water by the water discharge mechanism 102 and correct the zero point of each reaction cell 101 at the time of sample measurement.

  After the cell blank measurement is completed, water is sucked out of the reaction cell 101 by the waste liquid discharge mechanism 104.

  Subsequently, the reaction cell 101 moves, and a part of the sample 107 is dispensed into the reaction cell 101 by the sample sampling mechanism 106.

  Subsequently, the reaction cell 101 moves, the reagent sampling mechanism 108 dispenses the reagent from the reagent disk 105 to the reaction cell 101, the reagent and the sample are mixed and reacted, and a reaction solution is generated. When the reaction cell 101 containing the reaction solution rotates at a fixed period and passes through the front of the photometer 103, or each time it passes, a spectrophotometric measurement is performed several times to measure the components of the specimen.

  The reaction cell 101 needs to stop moving when it receives water discharge / discharge by the water discharge mechanism 102 or the waste liquid discharge mechanism 104 and sample / reagent dispensing by the sample sampling mechanism 106 or the reagent sampling mechanism 108. Therefore, moving and stopping are repeated intermittently.

  The above is the outline of the automatic analyzer.

  Next, the relationship between the reaction cell 101 and the optical axis 201 will be described.

  FIG. 2 shows how the reaction cells 101 vary. Although the reaction cells 101 are fixed to each other by the reaction cell mounting portion 203, the height of each of the reaction cells 101 is 0 due to distortion of flatness of the reaction disk 109 to which the reaction cell 101 is fixed, distortion of other components, and the like. .1mm order is different. In addition, due to the tolerance of the components that determine the positional relationship between the reaction cell 101 and the photometer 103, the positional relationship is still different on the order of 0.1 mm from the design time.

  Further, since the magnitude of the signal detected by the detector of the photometer 103 is proportional to the magnitude of the luminous flux 202, the luminous flux 202 needs to be maintained at a constant magnitude in order to ensure the S / N ratio of the signal. There is.

  During the analysis operation, the reaction disk 109 is driven to rotate, so that the reaction cell 101 moves to the right side of the page. The positional relationship between the bottom of the left reaction cell and the light beam 202 (or the optical axis 201) changes due to variations in the reaction cell. Since it is necessary to store the region of the light beam 202 at least at a position lower than the liquid surface in the reaction cell, the variation in the height of the bottom of the reaction cell prevents the liquid from being minutely formed. This is because it is necessary to determine the liquid amount by taking a margin of the liquid amount in consideration of the variation in the height of the bottom of the reaction cell.

  Next, a vertical driving mechanism of the optical axis 201 will be described.

  FIG. 3 shows an outline of the photometer. Light generated from the light source 301 passes through the lens A 302 and the slit A 303 and is irradiated to the reaction cell 101. At that time, light is irradiated to a certain wide range of the reaction cell 101. A portion of the light that has passed through the reaction cell 101 is cut off by the slit B 304, passes through the lens B 305 and the slit C 306, is dispersed by the grating 307, and is converted into a signal by the detector 308. Therefore, it is understood that the slit B304 and the slit C306 determine the substantial optical axis 201. Therefore, the optical axis 201 is driven by driving the slit B304 and the slit C306 in the vertical direction. The linear motor 309 and the slits B304 and C306 are fixed and driven. These drives are performed by the control unit. The advantage of this method is that the parts to be moved are smaller and lighter than when the entire photometer is driven in the vertical direction, and high speed control is possible even with a small linear motor 309. At the time of optical measurement, since the reaction cell 101 passes through the optical axis 201 at high speed, it is necessary to drive the slit B304 and the slit C306 at high speed on the order of 0.1 mm.

  As described above, two slits (304, 306) are provided so as to sandwich the lens B305 between the reaction cell and the detector, and the control unit vertically places the two slits relative to the light source. High speed control can be realized by driving in the direction.

  The linear motor 309 can be replaced with an actuator capable of high-speed and high-precision control, such as a pulse motor or a servo motor. These actuators have a structure that can be replaced by maintenance or the like.

  Another embodiment of the drive mechanism in the vertical direction of the optical axis 201 will be described.

  FIG. 4 shows an outline of the photometer. Light generated from the light source 401 is reflected by the mirror A 402 and passes through the reaction cell 101. The passed light is reflected by the mirror B 403, enters the grating 404, is dispersed, and is converted into a signal by the detector 405. The optical axis 201 is driven by driving the mirror A 402 and the mirror B 403 in the vertical direction by a linear motor 406. These drives are performed by the control unit. As in the above-described embodiment, the linear motor 406 can be replaced with an actuator capable of high-speed and high-precision control, such as a pulse motor or a servo motor. The mirror A 402 and the mirror B 403 can also be replaced with components that perform optical reflection, such as prisms and optical fibers.

  As described above, the mirrors (402, 403) are provided between the light source and the reaction cell and between the reaction cell and the detector, respectively, and the control unit vertically moves each mirror relative to the light source. As in the above-described embodiment, high-speed control can be realized.

  Next, a means for measuring the height of the bottom of the reaction cell 101 will be described.

  As shown in FIG. 5, the height of the reaction cell 101 is measured using a laser length measuring device 501. As the measurement point, the bottom of the reaction cell 101 is used, but the edge of the reaction cell 101 or the surface of the reaction disk 109 attached to the reaction cell 101 can be used instead. In the case of substituting with an edge or a mounting surface, the variation in the distance from the edge or the mounting surface to the bottom of the reaction cell 101 is smaller than the variation in the height of the bottom of the reaction cell, and each reaction cell is substantially constant. Based on assumptions. Even when these are substituted, it is possible to measure variations in the bottom of the reaction cell 101 without actually measuring the bottom of the reaction cell 101. The information on the height of the bottom of the reaction cell in this specification includes information substituted in this way, in addition to the information obtained by actually measuring the bottom of the reaction cell.

  The height of the bottom of the reaction cell can be measured automatically at any time during the production of the device, when the device is started, during maintenance, or when the reaction cell 101 is replaced, or at any timing of the user. . In the case of automatic execution, the timing for execution in the apparatus is set in advance. On the other hand, when executing at an arbitrary timing of the user, the user instructs the apparatus to execute by selecting the user via an interface such as an operation screen, for example.

  When the execution is instructed, the reaction disk is controlled to be driven to rotate for at least one round, and the height information is measured by the laser length measuring device 501. The control unit stores the obtained height information together with the position information of the reaction cell in the storage unit for each reaction cell.

  For this reason, when measuring the bottom of the reaction cell directly, the laser length measuring device 501 is disposed at a position where the laser can be irradiated to the bottom of the reaction cell. It is arranged at a position where a laser beam can be applied to the object. Further, when there is no need to measure the height information, the laser length measuring device 501 may be detachable from the analyzer so that the laser length measuring device 501 can be removed.

  In the above embodiment, the measurement by the laser length measuring device 501 has been described. However, any height information measuring means that can measure the height of the reaction cell 101 in principle can be substituted. For example, the height of the reaction cell 101 can be measured by applying the contact detection function of the sample sampling mechanism 108.

  Next, driving of the optical axis 201 based on the measured height of the reaction cell 101 will be described. The numerical value measured by the height measuring means of the reaction cell 101 is stored in a storage unit provided in the interface / control unit 111, and the numerical value is measured when the corresponding reaction cell 101 passes the photometer 103. The optical axis 201 is driven to the target value calculated based on the above. As a result, the positional relationship between the optical axis 201 and the reaction cell 101 can be accurately determined regardless of the accuracy of individual components. Further, since the optical axis 201 can be driven in accordance with the movement of the reaction cell 101, it can be applied to optical measurement during the movement of the reaction cell 101.

  Another embodiment of the timing for measuring the height of the reaction cell 101 will be described. So far, the embodiment has been described in which the data is stored in the storage unit and controlled. However, the height of the reaction cell 101 may be measured immediately before passing through the optical axis 201 during sample analysis. . Thereby, since the numerical value measured immediately before passing through the optical axis 201 can be fed back to the control unit and the optical axis can be controlled in the vertical direction, it is not necessary to store the measured numerical value in the storage unit. In this case, it is necessary to install the aforementioned height information measuring means for measuring in real time. Further, since the liquid to be analyzed is accommodated in the reaction cell, it is desirable to measure the height information of the bottom of the reaction cell indirectly at the edge of the reaction cell.

DESCRIPTION OF SYMBOLS 101 ... Reaction cell 102 ... Water discharge mechanism 103 ... Photometer 104 ... Waste liquid discharge mechanism 105 ... Reagent disk 106 ... Specimen sampling mechanism 107 ... Specimen 108 ... Reagent sampling mechanism 109 ... Reaction disk 110 ... Analysis part 111 ... Interface / control part 201 ... Optical axis 202 ... Light flux 203 ... Reaction cell mounting part 301 ... Light source 302 ... Lens A
303 ... Slit A
304 ... Slit B
305 ... Lens B
306 ... Slit C
307 ... Grating 308 ... Detector 309 ... Linear motor 401 ... Light source 402 ... Mirror A
403 ... Mirror B
404 ... Grating 405 ... Detector 406 ... Linear motor 501 ... Laser length measuring device

Claims (8)

A light source that emits light to a reaction cell that mixes a sample and a reagent, a detector that detects light from the reaction cell,
A reaction disk for mounting a plurality of the reaction cells;
A control unit that rotationally drives the reaction disk,
The automatic analyzer according to claim 1, wherein the control unit drives the optical axis of the light in the vertical direction according to the height information of the bottom of each of the plurality of reaction cells.   2. The automatic analyzer according to claim 1, wherein the control unit is driven in the vertical direction for each of the reaction cells irradiated with the light according to the rotation of the reaction disk.   3. The automatic analyzer according to claim 2, wherein the control unit drives the optical axis so as to reduce variations in bottom height of the plurality of reaction cells, and sets the optical axis and the bottom height of the reaction cell. An automatic analyzer that controls the distance so as to be kept substantially constant among the plurality of reaction cells during the rotation of the reaction disk.   The automatic analyzer according to any one of claims 1 to 3, further comprising height information measuring means for measuring the height information.   The automatic analyzer according to any one of claims 1 to 4, further comprising a storage unit that stores bottom height information of individual reaction cells of the plurality of reaction cells, and the control unit is provided in the storage unit. An automatic analyzer characterized in that the optical axis of the light is driven in the vertical direction according to the stored height information.   The automatic analyzer according to any one of claims 1 to 5, wherein the height measurement in the height information measuring means is automatically executed at any time during maintenance of the device, at initialization, or at the time of reaction cell replacement. Automatic analyzer equipped.   The automatic analyzer according to any one of claims 1 to 6, further comprising two slits provided so as to sandwich a lens between the reaction cell and the detector, An automatic analyzer that drives the optical axis in a vertical direction by driving the two slits in a vertical direction relative to a light source.   The automatic analyzer according to any one of claims 1 to 6, further comprising a mirror between the light source and the reaction cell, and between the reaction cell and the detector, and the control unit. Is an automatic analyzer that drives the optical axis in the vertical direction by driving the mirrors in the vertical direction relative to the light source.