Micro-titer plate and method of making same

Details Micro-titer plate and method of making same Micro-titer plate and method of making same

2002-05-23

2004-02-17

Sells, James (Department: 1734)

Adhesive bonding and miscellaneous chemical manufacture

Methods

Surface bonding and/or assembly therefor

C156S308400, C156S309600, C210S321750, C422S105000

Reexamination Certificate

active

06692596

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to a method for producing a micro-titer test plate. Further, this invention relates to a particular micro-titer test plate that can be produced in connection with the method of the present invention.
BACKGROUND OF THE INVENTION
Multi-well test plates, also called micro-titer plates or micro-titer test plates, are well-known and frequently used for assays involving biological or biochemical materials. Micro-titer test plates have been described in numerous patents including U.S. Pat. Nos. 4,948,442, 3,540,856, 3,540,857, 3,540,858, 4,304,865, 4,948,564, 5,620,663, 5,464,541, 5,264,184, WO 97/41955, WO 95/22406, EP 645 187 and EP 98 534.
Selected wells in the micro-titer test plate can be used to incubate respective microcultures or to separate biological or biochemical material followed by further processing to harvest the material. Each well has filtration means so that, upon application of a vacuum to one side of the plate, fluid in each well is expressed through the filter leaving solids, such as bacteria and the like, entrapped in the well. The filtration means can also act as a membrane such that certain materials in the test specimen are selectively bonded or otherwise retained in the filter means. The retained material may thereafter be harvested by means of a further solvent. The liquid expressed from the individual wells through the filter means may be collected in a common collecting vessel in case the liquid is not needed for further processing or alternatively, the liquid from the individual wells may be collected in individual collecting containers as disclosed in U.S. Pat. No. 5,464,541 and EP 98 534.
Up until recently, micro-titer plates have been used that conform to a standardized size of 85.47 by 127.76 mm having 12 rows of 8 wells each. Many expensive automation equipment has been designed to this standard. However, there is now a desire to increase the productivity of such automatic sampling. Such should preferably be accomplished in the most cost effective way and it has been proposed to retain approximately the size of the micro-titer plates yet increasing the number of wells therein. This would require minimal changes in the automation equipment.
Various methods are known to produce a micro-titer plate. These methods are typically designed to produce the standard micro-titer plates having 96 wells. For example, such plates may be manufactured as multi-layer structures including a single sheet of filter material disposed to cover the bottom apertures of all the wells, the filtration material being bonded to the periphery of one or more of the well apertures. Such a structure may suffer from a problem called “cross-talk” by which fluid from adjacent wells mingles through for example capillary action, gravity or application of pressure.
As disclosed in U.S. Pat. No. 4,304,865, a micro-titer, multi-layer plate includes a substantially rigid culture tray provided with wells having upstanding edges or rims bondeding the wider openings to the wells, and incubation is achieved while the culture tray is held “upside-down”, i.e. the rims are disposed below the sheet. To harvest material from such wells, a sheet of filter paper is placed over the top of a substantially rigid harvester tray having a like plurality of wells, each disposed and dimensioned to provide a tight push-fit with respect to the periphery of the rim of a corresponding well in the culture tray. The latter is then pressed against the harvester tray to push the rims into the wells in the latter, thereby die-cutting filter discs from the filter tray. Such die-cutting may also be carried out by pressing an unused culture tray against the harvester tray. The harvester tray with the filter discs may then be pressed against the culture tray bearing the incubated material. A vacuum applied to the bottom surface of the harvester tray draws fluid from the culture tray wells through the respective filter discs. This technique of cutting the filter sheet while it overlays the wells has the disadvantage that dust formed during the cutting operation gets entrapped between the walls of the well and the filter medium which may cause poor separation performance. Such a micro-titer plate is also taught to be prone to “cross talk” according to U.S. Pat. No. 4,948,442.
Accordingly, the latter U.S. patent proposes a method of manufacturing in which the wells of a culture tray and harvester tray are welded together with there between a filter sheet which extends across the openings of the wells. However, this method still does not completely solve the problem of cross talk. In particular, welding of the wells may not be sufficient to avoid capillary action to cause mingling of fluids from adjacent wells. Moreover, this problem will be even more enhanced with micro-titer plates that have a high number of wells per unit area.
It could also be contemplated to produce the micro-titer plate by providing an array of wells connected to each other having opposite inlet and outlet openings, separately die cutting filter means conforming to the opening of the wells from a filter sheet and then inserting the filter means into the individual wells of the micro-titer plate. This method however would have the disadvantage of being difficult to automate as the handling of the individual filter means would be complicated and cumbersome thus requiring sophisticated and expensive equipment. Moreover, the degree of complexity and risk of failure during production would substantially increase when the amount of wells per area increases.
Accordingly, it is desirable to find a further method for producing micro-titer plates, which method is preferably convenient, cost effective, capable of producing micro-titer plates that have a high number of wells per unit area and which micro-titer plates preferably have a reduced problem of cross-talk and good separation performance.
DISCLOSURE OF THE INVENTION
In accordance with the method of the present invention, a micro-titer test plate having a plurality of sample containers connected to each other. Each sample container has one or more side walls enclosing the interior of said sample container, a bottom wall with an outlet opening and an opposite upper end that is open and defines an inlet opening. The micro-titer plate is produced from a first and a second part. The first part will have a plurality of wells connected to each other and the second part has a conforming number and arrangement of a plurality of spouts connected to each other. Each of the wells of the first part has one or more side walls enclosing the interior of the wells and each of the wells has an upper end that is open and that will define the inlet opening of the sample containers and an opposite bottom opening. At their bottom opening, each of the wells will be bonded to the second part. Typically, the wells will be tubular but they may also have a cross-section of a different shape parallel to the plane of the bottom openings. Further, the size of the cross-section in the axial direction of the wells may vary.
Each of the spouts of the second part encloses at its first end an opening that will define the outlet opening of a sample container once the two parts have been bonded together to form the micro-titer plate. The first end of the spout will also define the bottom wall of the sample container. Opposite to the first end, the second end is defined by the free end of the spout. In accordance with a particular embodiment in connection with the present invention, the spouts may be provided at their first end with one or more walls enclosing an upper opening that is adapted for receiving the filter means. These walls extend in the axial direction away from the second end of the spouts. In a preferred embodiment in connection with the present invention, the spouts taper towards their second end and they may be surrounded by a collar, co-axially extending from the first end.
The first and second part will generally be formed from a thermoplastic material and can be produced

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