Patent Grant
8361418
This invention relates generally to containers for fluids, and in particular to containers for small quantities of fluid used in chemical and biomedical research and development.
In chemical and biomedical research and development, it is common to manipulate large numbers (e.g., thousands) of fluid containers which must be readily and automatably opened and closed, and yet must also be stored for months or years. The need to open and close the containers readily tends to induce the use of relatively poorly sealed containers, whereas the desire to store the containers for months or years tends to make it desirable to achieve tight sealing, for example to avoid evaporation loss and contamination from the outside.
The fluid containers used in chemical and biomedical research are subject to substantial chemical compatibility constraints, for example that they should not be made of materials which would be attacked by the solvents which they are designed to hold. Such constraints will also apply to the closures of such fluid containers. Adhesives are generally not preferred for closure of such fluid containers because of concerns about contamination and nonuniformity arising from adhesive residue left over from one closure to the next. Adhesives are nonetheless in widespread use.
Examples of fluid containers widely used in chemical and biomedical research and development are well plates and micro tubes. Well plates are commonly used which have 96, 384, and 1536 wells, although other numbers of wells are also in use. The dimensions and other characteristics of well plates have been standardized by the Society for Biomolecular Screening. A common size of well plate is 127.76 by 85.48 by 14.35 mm. Well plates are commonly designed to be stacked on top of each other in storage. Microtubes are commonly used in racks of 96 or 384. These racks of microtubes conform to dimensions similar to the length and width of well plates so they can be handled by similar robotic and automation equipment.
For well plates, a wide variety of lids have been developed. An example of a well plate lid of the prior art is described in U.S. Patent Application Publication No. 2003/0108450. That well plate lid uses the weight of the lid to provide the force which holds the lid to the well plate. The lid is stated to weigh 400 g preferably. A compliant sealing member, preferably of silicone rubber, forms part of the lid and is pressed against the well plate.
A commercially available lid for well plates is the SealTite lid from TekCel, Inc. (Hopkinton, Mass.). The SealTite lid has a metal spring/clamp structure to form a better seal than would be possible if the weight of the lid were the only force holding the lid to the well plate. The use of force as provided, for example, by a spring/clamp may give rise to difficulties in automation of the handling of well plates with lids. See in this regard the TekCel poster at http://lab-robotics.org/Presentations/Posters/Poster2038.pdf.
There have also been efforts in the art to adapt to evaporation losses. In particular, in some cases the outer wells of a well plate are not used to hold fluids of interest but instead are filled with a volume of the solvent in which those fluids are stored. This solvent in the outer wells has been observed to reduce the rate at which the solvent in the inner wells evaporates. The outer wells are sometimes referred to as “moat wells” when so used.
An alternative means to adapt to evaporation losses is to periodically audit the fluid levels in the reservoirs of the container and to add solvent to those reservoirs as needed. United States Patent Application Publication No. 2003/0150257 describes a convenient automatable way of carrying out the auditing by means of focused acoustic energy.
Cost considerations make it preferable for the containers and their closures to be manufactured by means of molding or similarly economical processes, with limited or no machining. Typical molding processes such as injection molding result in different reservoirs within a container, such as wells in a well plate, being different from each other. For example, there may be a small overall bending or “bow” across a well plate. Such bow is expected, for example, when polymer is injected into the mold at a single point—the “gate”—which is located in or near the center of a substantially flat part such as a well plate. Such processes may also result in there being dimensional differences between different supposedly identical containers or closures manufactured from the same molds or molds intended to be identical. In addition, because containers and their closures may be manufactured separately, by different companies, there may be dimensional mismatches in both containers and closures which result in imperfections in intended mating of containers and closures.
It is often desired to maintain well plates for periods of months. In such situations, it is desired to be certain that the well plates can last for a known time without need for inspection or replenishment. If even only one well of the well plate loses solvent too quickly, this desirable certainty is not achieved.
There is therefore a need in the art to adapt to the evaporation losses caused by less than perfect seals which are used in order to facilitate the automated opening and closing of containers which hold small quantities of fluid.
In a preferred embodiment of the invention, a closure for a container comprises at least two closure members. The relative position of the closure members with respect to each other is altered upon mating of the closure and container.
The alteration of the relative position of the closure members may result in one or more of the members approaching the container more closely. The alteration may result in one or more of the members pressing against the container. The pressing may take place in such a way that exit paths for vapor from fluid in the container would require passage through the pressed surfaces.
Before describing the present invention in detail, it is to be understood that this invention is not limited to specific fluids, containers, or device structures, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.
As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include both singular and plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a reservoir” includes a plurality of reservoirs as well as a single reservoir, reference to “a droplet” includes a plurality of droplets as well as single droplet, and the like.
In describing and claiming the present invention, the following terminology will be used in accordance with the definitions set out below.
The term “fluid” as used herein refers to matter that is nonsolid, or at least partially gaseous and/or liquid, but not entirely gaseous. A fluid may contain a solid that is minimally, partially, or fully solvated, dispersed, or suspended. Examples of fluids include, without limitation, aqueous liquids (including water per se and salt water) and nonaqueous liquids such as organic solvents and the like. As used herein, the term “fluid” is not synonymous with the term “ink” in that an ink must contain a colorant and may not be gaseous.
“Optional” or “optionally” means that the subsequently described circumstance may or may not occur, so that the description includes instances where the circumstance occurs and instances where it does not.
The term “reservoir” as used herein refers to a receptacle or chamber for containing a fluid. A reservoir may also be a volume of a member within which a fluid is constrained or held.
The term “closure” as used herein refers to a member used to close a container for fluids. It thus encompasses for example lids, stoppers, and caps. A container may be closed with one closure or, in some cases, with multiple closures. Closures normally meet with containers at respective surfaces on each member. The mechanical match of the closure and container at the surfaces where they meet may not be perfect, so that some exchange of vapor between the inside and outside of the container may be possible even with closures in place.
In a preferred embodiment of the invention, a closure for a container comprises at least two closure members. The relative position of the closure members with respect to each other is altered upon mating of the closure and container.
The alteration of the relative position of the closure members may result in one or more of the members approaching the container more closely. The alteration may result in one or more of the members pressing against the container. The pressing may take place in such a way that exit paths for vapor from fluid in the container would require passage through the pressed surfaces.
A motivation for having closure members press against the container is that, all else being equal, a seal formed by such pressure will be tighter than a seal formed without such pressure.
In many cases the relative motion of the members of the closure is achieved by connecting them in such a way that relative motion is enabled. This can be achieved by an elastic component, through the flexure of a connecting element, or by having the components interlocked with a loose fit.
When closure members press against the container, the force is preferably generated by interaction of the container and the closure, such as through the process of putting the closure on the container. However, the force could be generated through external means such as magnets.
The relative motion of the closure members may be designed such that two members press against the container in directions which are at an angle to each other. This angle may be 90 degrees or greater. In certain embodiments the angle may be approximately 180 degrees, so that two members press against the container in directions which are approximately opposite to each other.
Commonly, the places at which the container and closure meet when the container is closed are close to a horizontal plane. The closure in normal use commonly lies on top of the container. In that way, the force of gravity helps the closure remain affixed to the container.
The container may be designed so that it has approximately vertical projections which meet the closure. For example, a closure which is roughly flat and rectangular in form, as for example a well plate, may have two concentric vertical projections surrounding its outer edge, and the closure may be designed to meet one or both of the vertical projections.
In
It is also possible in the embodiments of
If the spring-like structures of the upper member press against a corner of the outer container projection opposite to the corner of the inner container projection against which the lower member presses, then the interior of the inner container projection is almost entirely surrounded by a superior, more sealing contact on all four sides. This may be seen in
In situations where the fluid in the container is hygroscopic and thus tends to trap water molecules which diffuse inward, the arrangement depicted in
In
It is desired in certain embodiments that the closure be easily put into contact with the container and removed from contact with the container, for example by a robot arm or similar automated piece of machinery. Commonly, when this is carried out, the container is held firmly while the robot arm also presses firmly against the closure. When the closure needs to be brought into contact with the container, the robot arm brings the closure into a suitable, calculated position atop the container and then presses down with moderate force. The position into which the closure is put may need to be determined based on the position of the container, which may for example be sensed by some type of sensor.
In U.S. patent application Ser. No. 11/077,630, closures containing reservoirs for solvent are described. Such reservoirs are conveniently employed in the closures of the present invention. While many of the techniques described in the 11/077,630 application are usable with the closures of the present invention, a particularly attractive possibility is for a reservoir for solvent to be attached to the top of the lower closure or bottom of the upper closure. The solvent reservoir could, for example, be made of a substance which absorbs and holds the solvent.
In application 11/077,630 referred to above there is also a discussion of so-called “labyrinth seals.” In general, it is desirable for the closures of the invention to be so arranged as to make a labyrinth seal which serves to prevent the outward diffusion of volatilizing solvent and the inward diffusion of water and of other undesirable vapor into the container.
The materials of which the closure could be made are dependent on the types of fluids which the reservoir contains. The two members of the closure may be made, for example, of polymers widely used for the manufacture of well plates as described in the literature. Fluids where DMSO by itself or DMSO and water are solvents are of particular interest in chemical and biomedical research. Materials for closures which are compatible with DMSO include cyclic olefin co-polymers (COC), polyethylene (PE), polypropylene (PP), ethylene-propylene rubber (EPR) and polytetrafluoroethylene (PTFE). COC is made by Ticona Engineering Polymers (Summit, N.J.), which is part of Celanese Corporation, and goes by the trade name Topas. One preferred Topas resin is 8007.
The elastic component may be made of a suitable polymer having the appropriate elasticity, or alternatively for example of a metallic alloy such as steel. It may be desirable that the elastic component be made of a polymer which can conveniently be welded ultrasonically to the closure members. It may alternatively be desirable that the elastic component be made integral to the closure members and that the elastic component be fabricated in the same molding process that serves to fabricate the closure members. It is believed that an elastic component as depicted in
Instead of two members it would be possible to practice this invention with three, four, or more closure members, each pressing against a particular zone in the container. If the container included, for example, three rather than two concentric projections around its circumference, there could be value in having a third closure member lying above the upper member in an embodiment analogous to
It is generally desired that closure members be dimensioned for convenient insertion into the corresponding portions of the container with which they are intended to mate, leaving as small a gap as is compatible with successful insertion taking into account the dimensional variation encountered both in the closure members and in the containers themselves, as well as the accuracy of positioning achievable with available robots. In general, each of these tolerances may be expected to be on the order of a few tenths of a millimeter, so that it is generally desired that the gap between a closure member and the portion of the container with which it is intended to mate be less than 2 mm, preferably less than 1.5 mm or less than 1 mm, more preferably less than 0.8 mm or less than 0.4 mm or less than 0.25 mm.
In the figures of this application the projections of the closures and containers have been depicted as being vertical. While it is preferred that these projections be approximately vertical, it is advantageous that such projections be 1, 2, 3, or more degrees away from the vertical. This facilitates their extraction from the mold during manufacture if they are made by a molding process. The desired angle will vary with the material, molding conditions and other factors know to those of skill in the art. This deviation from being precisely vertical also facilitates their coming into contact as the closure is lowered, as depicted for example in
As will be appreciated by those of skill in the art, gravitational force assists in the maintenance of the seals in closures of the invention where their projections which meet corresponding projections in the container have a deviation from the vertical. While it is desirable from a simplicity and cost standpoint not to add artificial weight to the closures of the invention, it would be possible to do so if that were seen as valuable for improving the quality of the seal due to the additional force which gravity would exert in that case.
In
It is to be understood that while the invention has been described in conjunction with the preferred specific embodiments thereof, that the foregoing description and the examples that follow are intended to illustrate and not limit the scope of the invention. Other aspects, advantages, and modifications within the scope of the invention will be apparent to those skilled in the art to which the invention pertains.
All patents, patent applications, and publications mentioned herein are hereby incorporated by reference in their entireties. However, where a patent, patent application, or publication containing express definitions is incorporated by reference, those express definitions should be understood to apply to the incorporated patent, patent application, or publication in which they are found, and not to the remainder of the text of this application, in particular the claims of this application.
Well plates containing DMSO were tested over a 64-day period. Each well plate had two concentric projections around its circumference. Two well plates, 400C and 250C, had a closure which contained a reservoir for DMSO but did not have any elastic component causing the closure to press against the well plate. Four well plates were provided with a single elastic component causing the closure to press towards a corner of the projections. Two of these, 400A and 250A, were connected to an elastic component causing the closure to press towards the lower right corner; two others, 400FF and 250FF, were connected to an elastic component causing the closure to press towards the upper left corner. The well plates denoted by numbers beginning with 400 had closures designed to leave a 400 micrometer gap between a projection on the well plate and the closest projection on the closure; those denoted by numbers beginning with 250 had closures designed to leave a 250 micrometer gap between a projection on the well plate and the closest projection on the closure. No screws, clips, adhesives, or any other means besides the weight of the closure and the elastic components were used to maintain the seal between the closures and the well plates.
The results obtained are depicted in
Similar improvements in the lid performance would be expected for protecting other solvents in the container when covered by the closure containing a reservoirs of the solvent. For example, to preserve aqueous solutions in the container, the lid may be filled with water. Compared to DMSO, water is lighter and more volatile. It would be expected to both evaporate more rapidly and have a faster rate of diffusion. Hence, the time scales for the process would be much faster, measuring in days rather than months. Performance of a closure of this type with water would be expected to achieve no wells with more than 10% water loss over a period of three days.
This application is a continuation of U.S. patent application Ser. No. 11/698,004, filed Jan. 24, 2007, which claims priority to U.S. Provisional Patent Application No. 60/761,908, both of which are incorporated by reference in their entirety.
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| Number | Date | Country | |
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| 20110277425 A1 | Nov 2011 | US |
| Number | Date | Country | |
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| Number | Date | Country | |
|---|---|---|---|
| Parent | 11698004 | Jan 2007 | US |
| Child | 13105790 | US |
