JP2007309737A - Microplate and insulating device therefor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To enhance the analyzing capacity of a specimen and to shorten the time required in analysis. <P>SOLUTION: A device includes a microplate 1, which is constituted so that the inner and outer wall surfaces in the vicinity of the bottom part of a well has the almost same shape and has an almost uniform wall thickness in at least one vertical section among the vertical sections passing the center axes of the respective wells, a heater 23 being a heat producing means for producing the heat transmitted to the microplate 1 and an insulating plate 25 being a heat transmitting means having the shape capable of being fitted to the surface containing the outer wall surfaces of the bottom parts of the wells of the microplate 1 and becoming the same in the contact areas of the respective wells when the surfaces including the outer wall surfaces of the bottom parts of the wells are fitted and transmitting the heat produced by the heater 23 to the microplate 1. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a microplate in which a plurality of wells, which are reaction containers for analyzing a component of a specimen, are arranged in a matrix, and a heat retaining device for a microplate that keeps the microplate at a constant temperature.

  When analyzing components of a specimen such as blood or body fluid, a microplate in which a plurality of reaction containers called wells are arranged in a matrix is used. In each well of the microplate, a sample containing a substance to be analyzed, a reaction reagent containing a substance to be analyzed and a substance that causes an antigen-antibody reaction are dispensed. The analysis of the components of the specimen is performed after a predetermined time has elapsed from this dispensing, by imaging the reaction occurring in the well with an imaging means such as a CCD (Charge Coupled Device) camera and using the image data obtained by this imaging. .

  Conventionally, in such analysis using a microplate, a technique for keeping the microplate at a constant temperature in order to promote the reaction in the well has been disclosed (see, for example, Patent Document 1). In this technique, heat is transmitted to the bottom surface of a microplate using a flat heat block, and the temperature of the microplate is kept constant.

JP 7-260648 A

  However, in the conventional microplate described above, the inner wall surface in the vicinity of the bottom of the well, which is a reservoir for a sample to be dispensed, forms a conical slope, while the microplate corresponding to the outer wall surface of the well bottom is Since the surface is flat, when heat is applied to the microplate by the heat block coming into contact with the flat surface, the heat is not necessarily transferred uniformly to the inside of the well, and the liquid temperature of the liquid mixture varies. It was easy to occur. As a result, the degree of progress of the reaction in the well is likely to vary, which hinders improvement in analysis performance.

  In addition, because the shape of the inner wall surface of the well bottom and the shape of the microplate surface corresponding to the outer wall surface are different, the temperature response of the microplate is poor, and the temperature inside the well becomes a predetermined value after heat is applied by the heat block. It took time to reach and it was difficult to perform analysis work in a short time.

  The present invention has been made in view of the above, and provides a microplate and a heat retaining device for a microplate capable of improving the performance of analyzing a sample and reducing the time required for the analysis. Objective.

  In order to solve the above-mentioned problems and achieve the object, the invention according to claim 1 comprises a plurality of substantially concave wells, which are reaction vessels for analyzing the components of the specimen, arranged in a matrix. In the microplate, the inner wall surface and the outer wall surface in the vicinity of the bottom of the well have substantially the same shape, and have a substantially uniform thickness in at least one of the longitudinal sections passing through the central axis of each well. It is characterized by that.

  The invention according to claim 2 is a microplate heat retention device that maintains a constant temperature at a microplate in which a plurality of substantially concave wells, which are reaction vessels for analyzing the components of a sample, are arranged in a matrix. A heat generating means for generating heat to be transferred to the microplate; and a heat transferring means for transferring the heat generated by the heat generating means to the microplate. And a shape that can be fitted to the surface including the outer wall surface of the well, and a shape in which the contact area with each well is the same when fitted to the surface including the outer wall surface of the well bottom.

  According to a third aspect of the invention, in the second aspect of the invention, the heat transfer means is detachable from the heat generating means.

  According to a fourth aspect of the present invention, in the microplate according to the second or third aspect, at least the inner wall surface and the outer wall surface near the bottom of the well have substantially the same shape, and the central axis of each well is It has a substantially uniform thickness in at least one of the passing longitudinal sections.

  According to the present invention, the inner wall surface and the outer wall surface in the vicinity of the well bottom portion have substantially the same shape, and have a substantially uniform thickness in at least one of the longitudinal sections passing through the central axis of each well. The microplate has a shape that can be fitted to the shape of the surface including the outer wall surface of the well bottom of the microplate, and the contact area between each well when fitted to the surface of the well bottom including the outer wall surface is the same. By providing the microplate heat retaining device having the heat transfer means having the shape as described above, it is possible to improve the performance of analyzing the specimen and reduce the time required for the analysis.

  Embodiments of the present invention will be described below with reference to the accompanying drawings. FIG. 1 is a perspective view showing a schematic configuration of a microplate according to an embodiment of the present invention. FIG. 2 is a front view of the microplate as seen from the direction of arrow X in FIG. The microplate 1 shown in these drawings has a circular opening, and a plurality of wells 3 that are reaction containers having a substantially concave shape for dispensing a sample or a reagent to cause a reaction are arranged in a matrix. It is set up. The microplate 1 is formed by injection molding a synthetic resin such as acrylic, and is mainly used for automatically analyzing components of a specimen such as blood and body fluid.

  The well 3 has an arbitrary cross section (cross section) in a direction parallel to the opening surface, and the diameter of the circle formed by each cross section decreases from the opening surface to the bottom. In particular, the bottom 31 serving as a liquid storage tank at the time of dispensing has a substantially conical shape, and the inclined portion of the bottom 31 enlarges the surface area to cause an antigen-antibody reaction and easily precipitate the aggregated reaction product. It has a shape whose diameter changes minutely in a staircase pattern. FIG. 3 is an explanatory view schematically showing the shape of the bottom 31 of the well 3 in which the diameter of the cross section changes in a stepped manner.

  4 shows one of the regions passing through the lowest point of the well 3 in the cross section (vertical cross section) taken along the line AA of FIG. 2 passing through the center point of the opening of the adjacent well 3 on the surface of the microplate 1. It is an expanded partial sectional view which shows a part. In the longitudinal cross section shown in FIG. 4, the microplate 1 periodically has an upper protrusion 11 that protrudes toward the opening of the well 3. In addition, the bottom surface portion 13 of the microplate 1 in this cross section has substantially the same shape as the shape of the bottom portion 31 of the well 3 (substantially conical slope), and the thickness of the portion is substantially uniform. The bottom surface of the upper protrusion 11 is located in a boundary region between adjacent wells 3 and is substantially parallel to the front surface of the microplate 1 including the opening surface.

  Note that the longitudinal section parallel to the AA line section and passing through the lowest point of the well 3 has the same shape as FIG. Further, the shape of the vicinity of the well 3 in the cross section taken along the line D-D in FIG. 2 and the vertical cross section parallel to the cross section taken along the line D-D and passing through the lowest point of the well 3 is the same as the partially enlarged cross-sectional view shown in FIG. is there.

  5 is parallel to the AA line cross section described above, but is adjacent on the surface of the microplate 1 in the cross section along the BB line in FIG. 2 which is a vertical cross section of the microplate 1 that does not pass through the well 3. 3 is an enlarged partial cross-sectional view passing through an intermediate region of an opening of a well 3. FIG. In the vertical cross section shown in FIG. 5, the microplate 1 periodically has downward protrusions 15 that protrude toward the bottom of the well 3. The end surface of the lower protrusion 15 corresponds to the bottom surface of the upper protrusion 11.

  In addition, all the longitudinal cross sections which pass through the intermediate | middle area | region of the adjacent well 3 parallel to this BB line cross section make the same shape as FIG. Further, the vicinity of the intermediate region of the well 3 having a cross section taken along the line EE in FIG. 2 and a vertical cross section parallel to the cross section taken along the line EE has the same shape as the partially enlarged cross sectional view shown in FIG.

  FIG. 6 is an enlarged partial cross-sectional view showing a part of a region including the well 3 in the cross section taken along the line C-C where the opening passes through the bottom of the well 3 adjacent in the oblique direction on the surface of the microplate 1. In the longitudinal section shown in FIG. 6, the microplate 1 has an outer wall surface 17 having substantially the same shape along the inner wall surface of the well 3, and the thickness of the microplate 1 in the longitudinal section is substantially uniform. Note that the cross section including the well 3 having a vertical cross section parallel to the CC cross section and passing through the lowest point of the well 3 has the same shape as FIG. 6 in the vicinity of the well 3 in the cross section.

  Next, a microplate heat retention device (hereinafter simply referred to as a heat retention device) that maintains the above-described microplate 1 at a constant temperature will be described. FIG. 7 is an explanatory diagram showing a schematic configuration of a heat retention device according to an embodiment of the present invention. A heat retaining device 2 shown in FIG. 1 includes a temperature sensor 21 that measures the temperature of the microplate 1, a heater 23 that is a heat generation unit that generates heat to be transmitted to the microplate 1, and the heat generated by the heater 23 is transmitted to the microplate 1. The input / output unit 27 for inputting and setting the temperature of the heat retaining plate 25 and the microplate 1 which are heat transfer means for transmitting to the temperature, and outputting and displaying the temperature measurement result of the microplate 1 by the temperature sensor 21, and the heat retaining device 2 A control unit 29 that performs operation control is provided.

  FIG. 8 is a front view showing the configuration of the surface (upper surface) of the heat retaining plate 25 on the side on which the microplate 1 is placed. The heat retaining plate 25 is realized by a material having thermal conductivity, for example, aluminum, and a concave portion 251 into which the bottom 31 of the well 3 is fitted when the microplate 1 is placed, and an oblique direction on the surface of the heat retaining plate 25. And a columnar convex portion 253 projecting between the concave portions 251 adjacent to each other.

  FIG. 9 is a partially enlarged view of a cross section taken along the line F-F in FIG. 8. The enlarged partial sectional view shown in FIG. 9 is a vertical cross section of the heat insulating plate 25 on which the portion having the cross section shown in FIG. 4 (shown by a one-dot chain line in FIG. 9) is placed when the microplate 1 is placed. is there. Therefore, in this longitudinal section, the concave portion 251 having the same conical shape as the surface of the bottom surface portion 13 of the microplate 1 and the horizontal portion 255 having the same width as the bottom surface of the upper protruding portion 11 alternately form a periodic pattern. .

  In addition, all the longitudinal cross sections which pass through the lowest point of the recessed part 251 parallel to this FF line cross section have the same shape as FIG. Further, the cross section taken along the line II of FIG. 8 and the vertical cross section parallel to the cross section taken along the line II and passing through the lowest point of the recess 251 are the same as those in FIG. Make a shape.

  FIG. 10 is a partially enlarged view of a cross section taken along the line GG of FIG. The enlarged partial cross-sectional view shown in FIG. 10 is a vertical cross-section of the heat retaining plate 25 on which the portion having the cross-section shown in FIG. 5 (shown by a one-dot chain line in FIG. 10) is placed when the microplate 1 is placed. is there. Accordingly, the vertical cross section is provided with a convex portion 253 projecting upward so as to be able to be fitted with the downward projecting portion 15 of the microplate 1, and the height at which the convex portion 253 projects is the downward projecting portion. It is the same as the height which 15 protrudes below.

  In addition, all the longitudinal cross sections which are parallel to this GG line cross section and pass the convex part 253 make the same shape as FIG. Further, the cross section taken along the line JJ in FIG. 9 and the vertical cross section passing through the convex portion 253 in parallel to the cross section along the line JJ have the same shape as that in FIG.

  11 is a partially enlarged view of the HH line cross section of FIG. 8 that passes through the lowest point of the concave portion 251 that is adjacent in the oblique direction on the surface of the heat retaining plate 25. 11 is a vertical cross-sectional view of the heat retaining plate 25 on which the portion having the cross section shown in FIG. 6 (shown by a one-dot chain line in FIG. 11) is placed when the microplate 1 is placed. is there. Therefore, the upper surface of the longitudinal section has a shape that can be fitted to the outer wall surface 17. In addition, all the longitudinal cross sections which are parallel to this HH line cross section and which pass the convex part 253 make the same shape as FIG.

  By using the heat retaining plate 25 having such a shape, when the microplate 1 is accurately placed on the heat retaining plate 25, the contact area between each well 3 of the microplate 1 and the surface of the heat retaining plate 25 is the same. Become. Therefore, heat can be uniformly transferred to each well 3, temperature variations among the wells 3 can be reduced, and heat transfer efficiency from the heater 23 can be improved.

  The analysis of the sample performed using the microplate 1 and the heat retaining device 2 having the configuration described in detail above will be described. If an appropriate amount of a reagent containing a specimen such as blood or body fluid and a substance that causes a specific reaction in the specimen is dispensed into the well 3 of the microplate 1, both of them undergo antigen-antibody reaction inside the well 3. Wake up. For example, when blood type determination is performed using red blood cells in blood, if the red blood cells cause an antigen-antibody reaction with a predetermined antigen contained in the reagent and the red blood cells aggregate with each other, the aggregated red blood cells It settles on 31 step-like inclined parts. Since the aggregation pattern produced by this precipitation varies depending on the blood type, the blood type of the specimen is determined by analyzing image data obtained by imaging the aggregation pattern with an appropriate imaging means.

  In order to promote such antigen-antibody reaction, the inside of the well 3 is preferably about 37 degrees Celsius. Therefore, the temperature of the heat retaining plate 25 is set to 37 degrees Celsius, for example, from the input / output unit 27, and the microplate 1 is placed so as to be fitted to the heat retaining plate 25. Thereafter, the temperature sensor 21 measures the temperature of the microplate 1. When the microplate 1 has not reached the set temperature, the heater 23 generates heat under the control of the control unit 29, and the generated heat is retained. It transmits to the microplate 1 through the plate 25. Thereafter, the temperature sensor 21 continues to measure the temperature of the microplate 1, and after the microplate 1 reaches the set temperature, the control unit 29 performs control to keep the microplate 1 in a constant temperature state.

  According to the embodiment of the present invention described above, both shapes are configured so that the shape of the bottom surface of the microplate can be fitted to the shape of the microplate mounting surface of the heat retaining plate of the heat retaining device. As a result, heat can be evenly transferred to each well in the microplate, heat transfer efficiency can be improved, and temperature variations from well to well can be reduced. As a result, it is possible to accurately perform temperature management, which is important for promoting the reaction inside the well, improving the performance of analyzing the specimen and reducing the time required for the analysis.

  Further, since the microplate according to this embodiment is thinner than a conventional microplate having a flat bottom surface, less material is required for molding. Therefore, it is also suitable when the microplate is to be discarded when the sample is analyzed only once.

  The preferred embodiment of the present invention has been described in detail so far, but the present invention is not limited only to this embodiment. For example, the shape of the protrusion of the heat retaining plate may be any shape as long as the contact area with the four wells located around it is the same, and the cross section of the protrusion forms a circle or a polygon. Also good.

  Thus, the present invention can include various embodiments and the like not described herein, and various design changes and the like can be made without departing from the technical matters specified by the claims. It is possible to apply.

It is a perspective view which shows the structure of the microplate which concerns on one embodiment of this invention. It is a front view which shows the structure of the microplate which concerns on one embodiment of this invention. It is explanatory drawing which shows the structure of a well bottom part. It is an AA line expanded partial sectional view of FIG. FIG. 3 is an enlarged partial sectional view taken along line B-B in FIG. 2. FIG. 3 is an enlarged partial cross-sectional view taken along the line CC of FIG. 2. It is explanatory drawing which shows the structure of the heat insulating apparatus for microplates which concerns on one embodiment of this invention. It is a front view which shows the structure of the heat retention plate surface. It is the FF line enlarged partial sectional view of FIG. It is the GG line expanded partial sectional view of FIG. It is the HH line expanded partial sectional view of FIG.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Microplate 2 Thermal insulation apparatus 3 Well 11 Upper protrusion part 13 Bottom part 15 Lower protrusion part 17 Outer wall surface 21 Temperature sensor 23 Heater 25 Thermal insulation plate 27 Input / output part 29 Control part 31 Bottom part 251 Concave part 253 Convex part 255 Horizontal part

Claims (4)

In a microplate comprising a plurality of substantially concave wells arranged in a matrix, which is a reaction container for analyzing a component of a specimen.
The inner wall surface and the outer wall surface in the vicinity of the bottom of the well have substantially the same shape, and have a substantially uniform thickness in at least one of the longitudinal sections passing through the central axis of each well. A microplate. A microplate heat retention device that maintains a constant temperature at a microplate in which a plurality of wells having a substantially concave shape, which is a reaction container for analyzing a component of a specimen, are arranged in a matrix,
Heat generating means for generating heat transmitted to the microplate;
Heat transfer means for transferring heat generated by the heat generation means to the microplate;
With
The heat transfer means has a shape that can be fitted to the surface including the outer wall surface of the well bottom, and has the same contact area with each well when fitted to the surface including the outer wall surface of the well bottom. A heat insulating device for a microplate characterized by having a shape. The heat transfer means is
The microplate heat retaining device according to claim 2, wherein the heat generating device is detachable from the heat generating means. The microplate is
At least the inner wall surface and the outer wall surface in the vicinity of the bottom of the well have substantially the same shape, and have a substantially uniform thickness in at least one of the longitudinal sections passing through the central axis of each well. The heat retaining device for a microplate according to claim 2 or 3.

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