WO2005042165A1

WO2005042165A1 - Microplate with metal insert

Info

Publication number: WO2005042165A1
Application number: PCT/JP2004/014427
Authority: WO
Inventors: Masaki Shirakawa; Satoshi Teramoto; Masashi Honda
Original assignee: Olympus Corporation; Evotec Technologies Gmbh
Priority date: 2003-10-31
Filing date: 2004-09-24
Publication date: 2005-05-12
Also published as: JP2005134341A

Abstract

To present lowering of surface flatness of a resin plate caused by cure shrinkage of plastic resin. A metal plate (4) is inserted into a resin plate (5). A light transmissible plate is attached to one surface of the resin plate (5) to form a microplate. In the resin plate (5), a thick resin area (11) having a large plastic resin thickness and a thin resin area (12) having a smaller plastic resin thickness than that of the thick resin area (11) are formed in a connecting part (3) connecting a well (2). A first region (13) and a second region (14) are provided in the resin plate (5) setting a boundary along the thin resin area (12).

Description

DESCRIPTION MICROPLATE WITH METAL INSERT

Technical Field The present invention relates to a structure of a holder and a method of manufacturing the holder, and particularly to a microplate provided with a plurality of wells for holding a sample to be observed in such fields as biology, medical science and chemistry.

Background Art There has been a conventional microplate in which a metal plate is inserted into a plastic resin plate and a light transmissible plate is bonded to one surface of the plastic resin plate. The metal plate of the microplate of this type exhibits excellent thermal conductivity, and it is thus easy to heat and cool a sample held on the microplate and apply temperature gradients to each sample held on the same microplate. Thus, such amicroplate is preferably utilized for sample observation by PCR (Polymerase Chain Reaction) method and for other purposes. FIG. 6 illustrates a structure example of a microplate of this type. In FIG.6, (a) is a perspective view of a microplate 1 having the above structure, while (b) is a cross-sectional view of the microplate 1 cut along a straight line whichpasses the centers of wells 2 disposed adjacent to each other in either a lateral or a longitudinal direction. As illustrated in FIG.6, the microplate 1 includes a plurality of (10 X 10 in the figure) the cylindrical wells 2 which are provided at fixed intervals in lateral and longitudinal directions to form a square and connected by a plate-shaped connecting part 3. A metal plate 4 formed from an aluminum plate or other material is inserted into the connecting part 3. Additionally, round through holes each having a diameter larger than an inside diameter of the well 2 are provided on the metal plate 4 at intervals corresponding to the positions of the wells 2 so as to prevent exposure of the metal plate 4 to the inside surfaces of the wells 2 and direct contact between a sample and the metal plate 4. A resin plate 5 consisting of the wells 2 and the connecting part 3 is made of plastic resin. A light transmissible plate 6 such as cover glass capable of transmitting light is attached to one surface of the resin plate 5 with adhesive, and one of the openings of the cylindrical body forming the well 2 is sealed by the light transmitting plate 6. Thus, a sample as an observation obj ect can be accommodated and heldwithin the cylindrical bodies of the wells 2. There is known SBS (Society for Biomolecular Screening) Standardwhich shows the relationship between the number of wells provided on a single microplate and a well pitch (an interval between centers of two adjacent wells in lateral and longitudinal directions) . According to this standard, for example, the pitch is required to be 9mm when the number of the wells is 96 (12 X 8) , 4.5mm when the number of the wells is 384 (24 X 16), and 2.25mm when the number of the wells is 1536 (48 X 32) . Next, a use example of a microplate is explained with reference to FIG. 7. In FIG.7, sample mixed liquid 7 in which a sample is mixed is poured into the inside of the well 2 of the microplate 1. When the fluorescence of the sample is observed using an inverted fluorescence microscope, for example, an object glass 8 is provided below the light transmissible plate 6 to observe the sample through the light transmissible plate 6. Pure water 9 is poured between the object glass 8 and the light transmissible plate 6 when the object glass 8 is an immersion lens. A microplate in which a metal plate is inserted into plastic resin is disclosed in this patent reference, for example. International Publication No. 01/94018 Pamphlet In the microplate 1 into which the metal plate 4 is inserted, the light transmissible plate 6 is bonded to one surface of the resin plate 5. The resin plate 5 can be formed by, for example, disposing the metal plate 4 within a mold chamber in a mold and subsequently inj ecting dissolved plastic resin into the mold chamber . A disposition example of gates 10 for injecting plastic resin into a mold chamber of a mold is herein described with reference to FIG. 8. This figure illustrates a positioning example of the gates 10 on a mold used for forming the rectangular resin plate 5 having the 16 X 10 wells 2. Two gates 10 are provided in this example, and these gates 10 are disposed at the respective centers of two identical rectangles which are formed by dividing the surface of the resin plate 5 along a line passing themiddlepoint of its longitudinal side and extending in the lateral-side direction. A plurality of gates are provided and disposed at such positions in this manner for the purpose of injecting the plastic resin into the mold chamber as evenly as possible. In the microplate 1 as described above, a material such as a glass plate is employed for the light transmissible plate 6. For the microplate 1 in typical size (for example, the resin plate 5 is approximately 110mm X 74mm) , an extremely thin glass plate having a thickness such as from approximately 0.1 to 0.2mm is used. Thus, the glass platewill be damagedwhen deformed. Accordingly, the resin plate 5 is required to have a preferable surface flatness on the side to which the light transmissible plate 6 is bonded (hereinafter abbreviated as "attachment surface") . When the resin plate 5 is formed by injection molding in the manner as described above, compression stresses caused by cure shrinkage (shrinkage caused when dissolved plastic resin hardens after injected into a mold chamber) which is produced at the time of molding of the resin plate 5 deform the entire resin plate 5 including the metal plate 4. As a result, the flatness of the attachment surface is lowered. Since the compression stresses are proportional to the volume of the resinplate 5 (plastic resin) , the entire deformation of the resin plate 5 increases as its volume increases, which further reduces the flatness of the attachment surface. Also, since the cooling speed of the plastic resin is accelerated due to the excellent thermal conductivity of the metal plate 4, it is known that the lowering of the flatness of the attachment surface due to cure shrinkage further lowers as the contact area between the resin plate 5 and the metal plate 4 increases . However, the microplate 1 as illustrated in FIG. 6 has large contact area between the resin plate 5 and the metal plate 4. Thus, large warp is produced in the resin plate 5 (that is, the flatness of the attachment surface of the resin plate 5 around the size described above is approximately from 0.2mm to 0.3mm, for example) , causing damage to the light transmissible plate 6, insufficient bonding between the light transmissible plate 6 and the resin plate 5 (lowering of the flatness of the light transmissible plate 6 after bonding) or other phenomena. As a result, an additional process may be required for improving the warp of the attachment surface by heating the attachment surface and correcting its flatness after formation of the resin plate 5 in some cases, increasing the manufacturing cost of the microplate 1. There is a solution for this problem that the thickness of the plastic resin in the entire connecting part 3 of the resin plate 5 is uniformly reduced. For reducing the thickness, it is necessary to narrow the portion on which the connecting part 3 is formed in the mold chamber of the mold. However, when this forming portion is narrowed, the flowability of the dissolved plastic resin flowing within the mold chamber during molding is lowered. As a result, insufficiency of injection of the plastic resin into the mold chamber is caused. In particular, there is a possibility of poorly molded well 2 to be produced. The present invention has been developed to solve the above-described problems. It is an object of the invention to prevent the lowering of the surface flatness of a resin plate caused by cure shrinkage of plastic resin.

Disclosure of Invention Amicroplate as one aspect of the present invention comprises a resin plate which includes: a plurality of wells made of plastic resin for holding a sample as an observation object; and a plate-shaped connecting part made of plastic resin into which a metal plate provided with a plurality of through holes is inserted, the connecting part connecting the wells such that the wells are positioned at the through holes / and is characterized in that: the connecting part has a thick resin area and a thin resin areahaving a smallerplastic resin thickness than that of the thick resin area; and a plurality of regions are formed in a surface of the resin plate setting a boundary along the thin resin area. The principle of the present invention is herein described with reference to FIG. 1. In the resin plate 5 employed in a conventional microplate as illustrated in FIG. 1(a), compression stresses due to cure shrinkage of plastic resin are caused as described above . As a result, warp in the resin plate

5 as well as in the metal plate 4 is produced. On the other hand, the resin plate 5 employed in a microplate according to the present invention as illustrated in FIG. 1 (b) is provided with a thick resin area 11 having a large plastic resin thickness, and a thin resin area 12 having a smaller plastic resin thickness than that of the thick resin area 11 in the connecting part 3. A first region 13 and a second region 14 are formed in the resin plate 5 setting a boundary along the thin resin area 12. This structure of the resin plate 5 reduces the compression stresses caused by the cure shrinkage without lowering the flowability of plastic resin within the mold chamber during formation of the resin plate 5 by injection molding. Thus, the lowering of the surface flatness of the resin plate 5 can be prevented. In the above-describedmicroplate according to the invention, the above-described resin plate may be formed by injecting plastic resin into a mold chamber from a plurality of gates provided on a mold in which the metal plate is disposedwithin the mold chamber, the same number of the above-described regions as the gates maybe formed in the surface of the resin plate, and the gates may be provided in forming portions of the regions in the mold such that one gate is disposed in one region. This structure allows equalized proceeding of the plastic resin injection into the mold chamber in the respective regions during injection formation of the resin plate. Additionally, in the above-described microplate according to the invention, the plastic resin thickness of the above-described thin resin area in the above-described connecting part can be 50% or lower of the plastic resin thickness of the above-described thick resin area in the connecting part. This structureprevents the loweringof the surface flatness of the resin plate in the invention considerably. Moreover, in the above-described microplate according to the invention, each of the above-described regions in the surface of the resin plate may include the same number of the above-described wells. As describe above, the wells are disposed in the microplate at fixed intervals, and thus each of the above-described regions in the surface of the resin plate has approximately the same area. Consequently, each of the regions has approximately the same contact area with the metal plate and approximately the same volume of theplastic resin forming each region, therebyequalizing the flatness of the respective regions in the resinplate . Furthermore, in the above-described microplate according to the invention, no plastic resin may be provided in the above-described thin resin area of the above-described connecting part. This structure prevents the loweringof the surface flatness of the resin plate in the invention further considerably. Also, as the metal plate is exposed at the thin resin area by eliminating plastic resin therefrom, it is possible to insert the metal plate into the mold and hold the metal plate at the position of the thin resin area during inj ection molding of the resin plate. As a result, the deformation of the metal plate due to injection pressure caused at the time of injection of the plastic resin into the mold chamber can be prevented. Additionally, in the above-described microplate according to the invention, the thin resin area of the above-described connecting part in one surface of the metal plate and the thin resin area of the above-described connecting part in the other surface of the metal plate may be disposed not oppositely to each other with the metal plate interposed between the thin resin areas. When the thin area is formed in the connectingpart, the flowability of plastic resin within the mold chamber during formation of the resin plate by inj ection molding is lowered at the position where the thin resin area is provided. However, by adopting the above-described structure, connection between adjoining areas in the resinplatebyplastic resin is alwaysmade at theposition of the thick resin area of the connecting part at least on either surface of the metal plate, thereby preventing lowering of the flowability of plastic resin within the mold chamber which may be caused when the thin resin area is provided. As described above, the present invention offers such an advantage that lowering of surface flatness of a resin plate caused by cure shrinkage of plastic resin can be prevented.

Brief Description of Drawings FIG. 1 is an explanatory view showing a principle of the present invention. FIG. 2 illustrates a structure of a resin plate employed in a microplate embodying the invention. FIG.3 illustrates a structure of amodifiedexample of a resin plate employed in the microplate embodying the invention. FIG. 4 shows dimensions of a prototype of a resin plate. FIG. 5 is a graph showing results obtained from the prototype of the resin plate. FIG. 6 illustrates a structure example of a microplate. FIG. 7 illustrates an example of a microplate in use. FIG. 8 illustrates an example of positioning of gates .

Best Mode for Carrying Out the Invention Embodiments of the present invention are hereinafter described in conjunction with the drawings . FIG. 2 illustrates structures of resin plates employed in a microplate which embodies the invention.

In FIG. 2, (a) shows an example in which the surface of the resin plate 5 is divided into two regions, while (b) shows an example in which the surface of the resin plate 5 is divided into four regions. The figure of (c) is a cross-sectional view illustrating the resin plate 5 cut along a straight line A-A shown in (b) . The resin plate 5 made of plastic resin includes the plural wells 2 disposed at fixed intervals in lateral and longitudinal directions, and a plate-shaped connecting part for connecting the wells 2. The respective resinplates 5 shown in (a) and (b) are provided with the 192 wells 2 (lateral:12 X longitudinal : 16) . The resin plate 5 in (a) has two regions setting a boundary along a band of a thin resin area 12 which is positioned in the middle in the longitudinal direction and extends linearly in the lateral direction. Thus, the two regions in the surface of the resin plate 5 have approximately the same area, and each region includes the same number of the wells 2 (96 wells) . Also, a gate vestige 15 can be observed at the central formation portion in each of the two rectangular regions. More specifically, a gate for injecting plastic resin into a mold chamber of a mold used for forming the resin plate 5 by injection molding is provided at a position corresponding to the gate vestige 15 in the mold. The resin plate 5 in (b) has four regions setting boundaries along bands of thin resin areas 12 which are positioned in the middle in the longitudinal and lateral directions and extend lineally in the lateral and longitudinal directions, respectively. Thus, the four regions in the surface of the resin plate 5 have approximately the same area, and each region includes the same number of the wells 2 (48 wells) . Also, the gate vestige 15 can be observed at the central formation portion in each of the four rectangular regions. More specifically, a gate for injecting plastic resin into a mold chamber of a mold used for forming the resin plate 5 by injection molding is also provided at a position corresponding to the gate vestige 15 in the mold. As illustrated in (c) , the connecting part for connecting the plural wells 2 on the resin plate 5 shown in (b) has a thick resin area 11 and the thin resin area 12 having a smaller plastic resin thickness than that of the thick resin area 11. Ametal plate 4, which surface is provided with a plurality of through holes at fixed intervals in the lateral and longitudinal directions, is inserted into the connecting part, and connects the wells 2 such that the wells 2 are positioned at the through holes. In this figure, the respective thin resin areas 12 in contact with both surfaces of the metal plate 4 have the same plastic resin thickness. However, this thickness is not required to be the same. FIG. 2(c) is a cross-sectional view of the resin plate 5 shown in (b) . If the resin plate 5 having the two regions shown in (a) is cut along a straight line which extends in the longitudinal direction and crosses the thin resin area 12, the resultant sections will be similar to those illustrated in (c) . When the resin plate 5 is formed to have regions divided along one or a plurality of the thin resin areas 12 as boundaries as described above, compression stresses caused by cure shrinkage can be reduced without lowering the flowability of plastic resin within the mold chamber during formation of the resinplate 5 by injectionmolding. As a result, lowering of the surface flatness of the resin plate 5 can be prevented. Additionally, the same number of regions as the gates which are provided in themoldused for the injection molding of the resin plate 5, i.e., which are outlets of the plastic resin to be injected into the mold chamber are formed in the resin plate 5, and gates are provided in formation portions of the regions in the mold such that one gate is disposed in one region. Consequently, the injection proceeding of plastic resin into the mold chamber during formation of the resin plate 5 can be equalized in the respective regions. Moreover, each region in the surface of the resin plate 5 has approximately the same area since the resin plate 5 is so formed that each region is provided with the same number of the wells 2. As a result, each region has almost the same contact area with the metal plate 4 and almost the same volume of plastic resin forming each region, thereby equalizing the flatness in the respective regions of the resin plate 5. An example of a modified structure of the resin plate 5 shown in FIG. 2 is hereinafter described with reference to FIG. 3. FIG. 3(1) shows an example in which the plastic resin thickness of the thin resin area 12 in the resin plate 5 as shown in FIG. 2 is zero, that is, plastic resin is not provided in the thin resin area 12. The figure of (a) is a partial enlarged view of the resin plate 5 having this structure, where the metal plate 4 is exposed by elimination of plastic resin in the thin resin area 12. The figure of (b) is a cross-sectional view of the resin plate 5 cut along a straight line B-B shown in (a) . Whenplastic resin is not provided in the thin resin area 12 of the connecting part as described above, lowering of the surface flatness of the resin plate in the invention can be prevented further considerably. In addition, since the metal plate 4 is exposed at the position of the thin resin area 12, the metal plate 4 can be inserted into the mold at this position to be held thereat during injection molding of the resin plate 5. As a result, deformation of the metal plate 4 caused by inj ection pressure at the time of inj ection of plastic resin into the mold chamber can be prevented. In the figure of (b) , the sides of the cylindrical bodies, i.e., the outside surfaces of the wells 2 adjacent to the portion where plastic resin is not provided in the thin resin area 12 and the exposed metal plate 4 cross each other perpendicularly. However, these outside surfaces may be inclined as illustrated in (c) . This structure requires inclined configuration of a corresponding transfer portion in a convex transfer surface of the mold. Thus, the possibility of deformation of the resin plate 5 which may be caused when the resin plate 5 is separated from the mold (deformation at mold separation) is lowered. FIG. 3 (2) shows an example in which the width of the band-shaped thin resin area 12 is enlarged. The figure of (a) is a partial enlarged view of the resin plate 5 having this structure, while (b) is a cross-sectional view of the resin plate 5 cut along a straight line C-C shown in (a) . In the respective resin plates illustrated in both figures, the metal plate 4 is exposed by elimination of plastic resin in the thin resin area 12 similarly to the resin plate 5 in FIG.3 (1). The width of the exposed portion of the band-shaped metal plate 4 is enlarged to be larger than the distance between the outside surfaces of the adjacent wells 2, making the width to correspond to apitchof the respective centers of the adjacent wells 2 (well pitch) . When the width of the band-shaped thin resin area 12 is enlargedinthismanner, thewidthof a corresponding band-shapedtransferportion in a convex transfer surface of the mold becomes large accordingly. Thus, the strength of the mold is increased. FIG.3(3) shows an example in which the thin resin area 12 on one surface of the metal plate 4 is not opposed to the thin resin area 12 on the other surface of the metal plate 4 with the metal plate 4 interposed therebetween. The figure of (a) is a partial enlarged view of the resin plate 5 having this structure, while the figure of (b) is a cross-sectional view of the resin plate 5 cut along a straight line D-D shown in (a) . In the resin plates illustrated in these figures, the metal plate 4 is also exposed by elimination of plastic resin in the thin resin area 12 similarly to the resin plate 5 in FIG.3(1). The exposed portion of one surface of the metal plate 4 is not opposed to the exposed portion of the other surface of the metal plate 4 with the metal plate 4 interposed therebetween. When the thin resin area 12 is provided in the connecting part at the time of formation of the resin plate 5 by injection molding, the narrowed flow passage of plastic resin at the position of the thin resin area 12 decreases the flowability of plastic resin within the mold chamber. However, when the thin resin area 12 on one surface of the metal plate 4 is not opposed to the thin resin area 12 on the other surface of the metal plate 4 with the metal plate 4 interposed therebetween, the connection between adjoining areas in the resinplate 5 by plastic resin is made at the thick resin area 11 provided on at least either surface of the metal plate 4. As a result, the flow passage of plastic resin is secured at the portion of the thick resin area 11, thereby preventing lowering of flowability of plastic resin within the mold chamber which may be caused when the thin resin area 12 is provided. Next, results obtained from a prototype of a resin plate used in a microplate embodying the present invention are described. The dimensions of the resinplate 5 as the prototype were llOmmX 74mm, and 384 (24 X 16) wells 2 were provided on the resin plate 5. The well pitch was 4.5mm, and the height of the well was 4.8mm. An aluminum plate having a thickness of 1.0mm was employed as the metal plate 4. The plastic resin thickness of the thick resin area in the connecting part for connecting the wells 2 was 0.7mm. Other typical dimensions are shown in FIG. 4. FIG. 5 is a graph showing results obtained from the prototype varying the thickness of plastic resin in the thin resin area in the connecting part of the resinplate. In this graph, the lateral axis indicates the thickness of plastic resin in the thin resin area when the thickness of the thick resin area (=0.7mm) is 100%, and the longitudinal axis indicates the flatness of the resin plate corresponding to the thickness of the plastic resin in the thin area. FIG. 5(a) shows the case when two regions having approximately the same area are formed in the surface of the resin plate as in FIG.2 (a) , while FIG.5 (b) shows the case when four regions having approximately the same area are formed in the surface of the resin plate as in FIG. 2 (b) . Gates provided on the mold for injection molding were disposed in central formation portions of the regions in the mold such that one gate is positioned in one region. The results shown in FIG. 5 are now explained. In both of FIGS.5 (a) and 5 (b) , the thickness of plastic resin in the thin resin area is the same as that in the thick resin area at 100% on the lateral axis, and the flatness of the resin plate for this thickness corresponds to the flatness of a conventional resinplate . As the thickness of plastic resin in the thin resin area decreases from this value, the flatness of the resin plate improves, exhibiting a monotonous change with respect to the decrease in the thickness of the thin resin area. Plastic resin is not provided in the thin resin area at 0% on the lateral axis, in which case the most desirable flatness of the resin plate can be obtained. When the results in FIGS .5 (a) and 5(b) are compared, it is understood that the flatness of the resin plate is better in the case in (b) where a larger number of the regions are formed in the resin plate. Since the attachment surface of the light transmissible plate requires at least 0.2mm or a smaller value for its flatness in the current condition, it was found from the result in FIG. 5(a) that the thickness of the plastic resin in the thin resin area needs to be 50% or lower of the thickness of the thick resin area for attaining the above range of flatness. It is more preferable to set this value at 30% or lower. The present invention is not limited to the embodiments as described herein, but various improvements and modifications may be made without departing from the scope of the invention.

Claims

1. A microplate comprising a resin plate which includes : a plurality of wells made of plastic resin for holding a sample as an observation object; and a plate-shaped connecting part made of plastic resin into which a metal plate provided with a plurality of through holes is inserted, said connecting part connecting saidwells such that saidwells are positioned at said through holes; characterized in that: said connecting part has a thick resin area and a thin resin area having a smallerplastic resin thickness than that of said thick resin area; and a plurality of regions are formed in a surface of said resin plate setting a boundary along said thin resin area.

2. Amicroplate as set forth in claim 1, characterized in that: said resin plate is formed by injecting plastic resin into mold chamber from a plurality of gates provided on a mold in which said metal plate is disposed within said mold chamber; the same number of said regions as said gates are formed in the surface of said resin plate; and said gates are provided in formation portions of said regions such that one gate is disposed in one region.

3. Amicroplate as set forth in claim 1, characterized in that the plastic resin thickness of said thin resin area in said connectingpart is 50% or lower of the plastic resin thickness of said thick resin area in said connecting part.

4. Amicroplate as set forth in claim 1, characterized in that each of said regions in the surface of said resin plate includes the same number of said wells.

5. Amicroplate as set forth in claim 1, characterized in that plastic resin is not provided in said thin resin area of said connecting part.

6. Amicroplate as set forth in claim 1, characterized in that said thin resin area of said connecting part on one surface of said metal plate is not opposed to said thin resin area of said connecting part on the other surface of said metal plate with said metal plate interposed between said thin resin areas.