Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
  • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
  • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
  • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
  • B01L3/50853—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
  • B01L2200/14—Process control and prevention of errors
  • B01L2200/142—Preventing evaporation
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2300/00—Additional constructional details
  • B01L2300/04—Closures and closing means
  • B01L2300/041—Connecting closures to device or container
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2300/00—Additional constructional details
  • B01L2300/04—Closures and closing means
  • B01L2300/041—Connecting closures to device or container
  • B01L2300/042—Caps; Plugs
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2300/00—Additional constructional details
  • B01L2300/04—Closures and closing means
  • B01L2300/046—Function or devices integrated in the closure
  • B01L2300/047—Additional chamber, reservoir
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2300/00—Additional constructional details
  • B01L2300/08—Geometry, shape and general structure
  • B01L2300/0809—Geometry, shape and general structure rectangular shaped
  • B01L2300/0829—Multi-well plates; Microtitration plates
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2300/00—Additional constructional details
  • B01L2300/10—Means to control humidity and/or other gases

Definitions

• 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.
• 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.
• 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/Poster2Q38.pdf.
• 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.
• a container has a closure.
• the container has a primary member which contains one or more reservoirs for fluids of interest.
• the primary member could be, for example, a well plate or a test tube or minitube.
• the closure also contains one or more fluid reservoirs. At least some of these reservoirs have openings which open into the interior of the container when it is closed using the closure. Preferably, these openings are near the zone at which the closure contacts the primary member, referred to as the "contact zone.”
• a container has a closure.
• the container has a primary member which contains one or more reservoirs for fluids of interest.
• the primary member could be, for example, a well plate, a test tube or a collection of minitubes in a rack.
• the closure also contains one or more fluid reservoirs. At least some of these reservoirs have openings which open into the exterior of the container when it is closed using the closure, in the vicinity of the contact zone where the closure meets the primary member.
• a closure reservoir is designed so that the portion of the primary member which contacts the closure is partially surrounded by fluid when the closure and the primary members are in contact.
• this reservoir opens both into the interior and the exterior of the container when the latter is closed.
• a fluid sample comprising a solvent is stored in a reservoir.
• the reservoir is covered using a closure which has one or more closure reservoirs.
• the closure reservoirs contain quantities of the solvent.
• the solvent in the closure reservoirs is replenished.
• 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.
• FIGs. IA- IB depict a schematic cross section and bottom view of a closure with a reservoir, the closure being designed for a well plate.
• FIG. 2A-2B depict a schematic cross section and top view of a closure for a well plate which has a facility to allow replenishment of the supply of solvent in the closure reservoirs without removing the closure.
• FIG. 3 depicts in schematic cross section a closure for a test tube which also has a facility to replenish the supply of solvent.
• FIG. 4 depicts in schematic partial cross section a closure with a reservoir for fluid which surrounds a portion of the primary member which contacts the closure.
• FIG. 5 depicts in schematic partial cross section an alternative preferred embodiment of the invention with a labyrinth seal and a single closure reservoir opening to the outside of the container close to the contact zone.
• FIG. 6 depicts in schematic partial cross section a container and a closure of the invention as the closure is brought into contact with the container.
• FIG. 7 depicts schematically a possible arrangement for the elastic component of one portion of the closure of the invention.
• FIG. 8 depicts schematically a possible arrangement for the elastic component for both the upper and lower members of the closure of the invention.
• FlG. 9 depicts schematically an arrangement of spring-like structures on one sides of one of the members of a closure of the invention.
• FIG. 10 depicts schematically an arrangement of spring-like structures on two sides of one of the members of a closure of the invention.
• FIG. 1 1 depicts schematically the positions of the upper and lower members of a closure of the invention relative to projections in the container.
• FIGS. 12A-12C depicts the results of an experiment in which four closures which press against projections on a well plate are compared to two control closures.
• a reservoir includes a plurality of reservoirs as well as a single reservoir
• a droplet includes a plurality of droplets as well as single droplet, and the like.
• fluid 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.
• fluids include, without limitation, aqueous liquids (including waterier se and salt water) and nonaqueous liquids such as organic solvents and the like.
• aqueous liquids including waterier se and salt water
• nonaqueous liquids such as organic solvents and the like.
• the term “fluid” is not synonymous with the term "ink” in that an ink must contain a colorant and may not be gaseous.
• 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.
• a container has a closure.
• the container has a primary member which contains one or more reservoirs for fluids of interest.
• the primary member could be, for example, a well plate or a test tube.
• the closure also contains one or more fluid reservoirs. At least some of these reservoirs have openings which open into the interior of the container when it is closed using the closure. Preferably, these openings are near the zone at which the closure contacts the primary member, referred to as the "contact zone.”
• the fluids of interest are held within the reservoirs of the container.
• a solvent which the fluids of interest comprise is held in one or more closure reservoirs.
• the solvent evaporates from both the fluids of interest and from the closure reservoirs. If the seal between container and closure were perfect the evaporation would reach an equilibrium when the partial pressure of the solvent in the interior of the container equaled the vapor pressure of the solvent. However, the inevitable imperfections of the seal mean that there will be slow diffusion of the vapor-phase solvent into the external atmosphere. The rate of this diffusion may be expected to relate to the difference in partial pressure of the solvent immediately inside and immediately outside the seal.
• the reservoirs of solvent in the closure may be expected to reduce the rate at which solvent evaporates from the fluids of interest.
• the solvent in the closure reservoirs may be viewed as "sacrificial" solvent which is used for the purpose of sparing the solvent employed in the fluids of interest so as to prevent the premature evaporation of the solvent in the fluids.
• the fluids of interest in the invention may be any fluid which is being used in research, development, or in some cases manufacturing and education.
• the fluids of interest may contain biological samples such as living organisms or materials derived from such organisms. They may form part of libraries of compounds generated through combinatorial chemistry or otherwise. They may comprise biomolecules or they may comprise synthetic or naturally occurring organic or inorganic molecules.
• the reservoirs in the closure may be of a wide variety of shapes. They may be simple indentations, for example of hemispherical or cylindrical shape, arranged around the contact zone on the inside of the closure. A reservoir may simply be a groove arranged around the contact zone on the inside of the closure. Alternatively, it may be a compartment of substantial size spanning much of the closure.
• Figs. IA and IB show a schematic partial cross section and bottom view of a closure 10 of the invention.
• Fig. IA also depicts a portion of a primary member 20 in contact with closure 10 at a contact zone 30. Contact is achieved with a projection 22 of the primary member.
• the primary member 20 has a number of reservoirs 24, 26, 28 which can hold fluids of interest.
• the closure 10 has a reservoir 12 for a quantity of fluid.
• this reservoir is a continuous channel that goes around the entire outer edge of the closure 10.
• the outer edge of the closure 10 also has a Hp 32 which also goes around the entire edge.
• primary member 20's projection 22 would also go around the entire edge of the primaiy member.
• the closure reservoirs be of sufficiently small dimensions that the surface forces are able to hold fluids in place in them even when the earth's gravitational force tends to detach the fluids.
• the closure of this embodiment of the invention may be a substantially flat lid for a well plate, and the reservoirs may be small hemispherical indentations in the lower surface of the lid. If these indentations are sufficiently small, even the maximum amount of fluid that they hold will be able to remain in place simply through surface forces in any orientation with respect to the earth's gravitational field.
• these reservoirs will always have an adequate supply of fluid, for example of solvent.
• This periodic replenishment could take place by removing the closure from the container, potentially inverting the closure or otherwise altering its orientation, and using some sort of fluid transport system to dispense fluid into the reservoirs through the openings that open into the interior of the container.
• the fluid transport system could be, for example, an automatic pipetting system, or a tip-based transport system, or an acoustic ejection system.
• the closure could be designed in such a way that the replenishment can take place without removing the closure from the primary member of the container.
• the closure could be designed to have a removable cover or plug, or alternatively a septum plug of a type which allows replenishment without removal, for example from a manufacturer such as ABgene (Epsom, United Kingdom).
• the reservoirs would have one or more openings which open into the interior of the container and another opening which is exposed when the removable cover or plug is removed.
• the replenishment of the fluid in the reservoirs of the closure could be performed by removing the cover or plug, dispensing fluid, and then replacing the cover or plug.
• the addition of fluid would not cause any fluid to travel from the reservoirs into the interior of the container. It would be possible, for example, to dispense into reservoirs which do not have openings to the inside of the closure and then to allow the dispensed fluid to travel slowly through suitably sized channels from these reservoirs to other reservoirs which have such openings.
• the fluid transport system used could again be, for example, an automatic pipetting system, or a tip- based transport system, or an acoustic ejection system.
• FIG. 2A-2B depict a schematic cross section and top view of a closure for a well plate which has a facility to allow replenishment of the supply of solvent in the closure reservoirs without removing the closure.
• Fig. 2A also depicts a cover 40 for the closure and projections 60, 62 from the primary member of the container which contact the closure.
• the closure 64 has a number of reservoirs 42, 44, 46 which can hold fluid. Between these reservoirs there run channels such as 56 and 58. Each reservoir has an opening such as 48, 50, 52 which allows evaporation of fluid to proceed downwards but is sufficiently small that gross movement of fluid downwards will not occur under conditions of use.
• the closure 64 also has a reservoir 54 which, as may be seen in the top view in Fig. 2B, runs all around the edge of the closure 64.
• FIG. 3 depicts in schematic cross section a closure for a test tube 80 which also has a facility to replenish the supply of solvent.
• the closure 72 has a plug 70. It provides a reservoir 74 for fluids.
• the reservoir 74 has an opening 76 which allows evaporation of fluid to proceed downwards but is sufficiently small that gross movement of fluid downwards will not occur under conditions of use.
• closures be capable of easy opening and closing.
• the closures of the invention will be adapted to being opened and closed by means of robot arms of the type which are commonly used for the manipulation of containers in chemical and biomedical research.
• the closure can be put in place by lowering it into position, and then opened simply by lifting it out of position.
• the force of the earth's gravity suffice to hold the close in place.
• the force of the earth's gravity suffice to form the seal between closure and primary member.
• the total volume of the container be reduced to something close to the minimum volume which is necessary to contain the fluids of interest.
• these surface forces be sufficient to retain the fluid in its position when the closure is subject to the inevitable forces which accompany the process of closure insertion and removal.
• the process of insertion and removal does not subject the closure to significant forces, but in practice, to the extent this process is carried out by a human or by a general purpose robot arm, there will be some degree of impact of the closure on the primary member, resulting in a more or less sharp deceleration of the closure. It is preferred in particular that certain free surfaces of the fluid retained in the closure reservoirs lie approximately parallel to the direction of the impact force. Furthermore, it is possible to use mechanical design elements or foams in the closure reservoirs in order to improve the ability of the closure reservoir to retain fluid. Foams may include, for example, open-cell foams which have connected voids so they have the ability to hold substantial quantities of liquid and to allow the liquid to move throughout the extent of the foam.
• a foam that could withstand long-term exposure to DMSO like a polyethylene foams would be preferred.
• An open-cell polyethylene is OPCELL (described at http://www.chimeng.com.tw/e-opcell.htm) from Chi Meng Industry (Tainan, Taiwan).
• plugs and/or covers for the closure reservoirs are indicated as being desirable, it is also desirable to allow some ability for gases to enter and leave the closure reservoir as for example with a small vent. This ability prevents for example the formation of vacuums in any air space within the closure reservoir.
• the use of a commercially available septum plug may provide an adequate degree of venting for this purpose.
• the portion of the closure which contacts the primary member be made of a compliant material. Compliance allows the closure to deform elastically to match the contour of the primary member when the closure is put into place, giving a tighter seal.
• the openings from closure reservoirs to the interior of the container may need to have a relatively large surface area for the exchange of vapor. This may occur, for example, if the volume of the fluids of interest is very small. In that case, even with a very good seal to the outside, an undesirable amount of evaporation may occur simply in order to fill the interior of the container with vapor. In order to prevent this, the closure reservoirs would need to be able to raise the partial pressure in the interior of the container fairly rapidly, which can be accomplished through a large surface area.
• a large surface area is required are openings with foams, gels, and similar materials which will allow gas diffusion but will not allow bulk movement of fluid, as well as a large number of small openings. It may be desirable, for example, for the surface area of the openings from the closure reservoirs to the interior to be 10%, 20%, or 100% of the surface area of the fluids of interest which are being held in the reservoirs of the primary member.
• the surface area of the fluids of interest when the container is in use may not be known, but it will often be possible to put an approximate or exact upper bound on that surface area based on the geometry of the container.
• the surface area of the openings from the closure reservoirs to the interior may then conveniently be chosen to be 10%, 20%, 100%, or some other suitable percentage of that upper bound.
• a convenient rough upper bound is simply the area of the projection onto the plane of the contact zone of the surface of the closure or primary member which opens to the interior.
• a convenient rough upper bound is the total cross sectional area of all wells.
• a further figure of merit which may be useful in the design of closure reservoirs is the percentage of the partial pressure of a solvent or other fluid inside the container which comes from the closure reservoirs when the closure is in place. Thus, for example, it could be specified that at least 10%, 20%, or 100% of the partial pressure should come from the closure reservoirs under particular conditions of fluid loading in the primary member.
• closure reservoirs Another figure of merit for closure reservoirs is the volume ratio of the closure reservoirs to the fluid of interest in the primary member. If this ratio were low, then as evaporation occurs the closure reservoirs would need fairly frequent replenishment. For this reason, it is preferable that the volume of the closure reservoirs be greater than 10% of the volume of the fluid of interest, preferably greater than 20%, or greater than 50% of the volume of the fluid of interest. When designing a closure or container, the volume of the fluids of interest that will be placed in the container when it is in use may not be known.
• volume of the closure reservoirs may be convenient to design the volume of the closure reservoirs relative to the maximum volume which the primary member can hold or which fluids of interest can have, so that one has for example a closure reservoir volume greater than 1 %, or greater than 5%, or greater than 10%, or greater than 20%, or greater than 50% of the maximum volume which the primary member reservoirs can hold.
• Solvents used commonly in chemical and biomedical research may be hygroscopic.
• DMSO is quite hygroscopic and that DMSO solutions will commonly draw humidity from the ambient air.
• this phenomenon whereby a fluid of interest comprising a hygroscopic solvent draws humidity from the ambient air is undesirable.
• a tight seal can thus help not only to keep evaporation from occurring but also to keep the fluids of interest from drawing undesirable humidity from the ambient air.
• a further aspect of the invention is the use of humectants to draw moisture from the air.
• one or more reservoirs on the closure of the invention may be designed to contain a humectant.
• Such reservoirs are preferably arranged with openings on the outside of the container in the vicinity of the contact zone between closure and primary member.
• a closure reservoir which has been replenished with fresh hygroscopic solvent may have the advantage that it acts in effect as a humectant by attracting moisture preferentially in comparison to the fluids of interest.
• a container has a closure.
• the container has a primary member which contains one or more reservoirs for fluids of interest.
• the primary member could be, for example, a well plate or a test tube.
• the closure also contains one or more fluid reservoirs. At least some of these reservoirs have openings which open into the exterior of the container when it is closed using the closure, in the vicinity of the contact zone where the closure meets the primary member.
• the fluids of interest are held within the reservoirs of the container.
• a solvent which the fluids of interest comprise is held in one or more closure reservoirs.
• the solvent evaporates from both the fluids of interest and from the closure reservoirs.
• the evaporation from the closure reservoirs causes the partial pressure of the solvent on the exterior of the container in the vicinity of the contact zone to rise. Since the rate at which the solvent diffuses from the interior of the container to the exterior is related to the difference of partial pressures of solvent immediately inside and outside the contact zone, it may be expected that evaporation from the closure reservoirs will tend to reduce the loss of solvent from the interior of the container.
• a way of evaluating the effectiveness of the use of closure reservoirs with openings to the exterior of the container is to determine the partial pressure of the solvent of interest in the vicinity of the closure zone which is due to evaporation from the closure rather than from escape of the solvent through the seal. In that respect, it would be desirable if that pressure were 10%, preferably 20%, more preferably 50%, and more preferably 80% of the vapor pressure of the solvent of interest, so that diffusion of the solvent of interest through the seal is inhibited.
• An alternative figure of merit which may be considered in relation to this is what percentage of the partial pressure immediately outside the contact zone comes from the closure reservoirs rather than from the reservoirs containing the fluids of interest. A percentage of at least 10% or 20% of partial pressure from the closure reservoirs is preferred.
• Another figure of merit which may be considered in this regard is the ratio of fluid surface exposed by the closure reservoirs to the fluid surface exposed by the fluids of interest inside the container. If these surfaces are comparable, as for example where the ratio is close to 1, then because the vapors from the fluids of interest inside the container must pass through a seal and those from the closure reservoir do not, it may be expected that the bulk of the partial pressure of the solvent of interest in the vicinity of the contact zone will derive from the closure reservoirs.
• a further advantage of having a closure reservoir exposed to the exterior of the container in the vicinity of the closure zone is the ability for a hygroscopic solvent in the closure reservoir, particularly fresh hygroscopic solvent resulting from replenishment, to act in effect as a humectant, attracting water vapor and reducing the concentration of water vapor in the vicinity of the closure zone and thus preventing the water vapor from entering the container.
• the container comprises some sort of structures which serve to slow the diffusion of gas outward from the contact zone.
• These structures in general will be structures which lengthen and narrow the diffusion path which gas takes when moving from the immediate exterior of the contact zone into the general atmosphere.
• a wide variety of such structures sometimes referred to as "labyrinth seals," will occur to the person of skill in the art.
• a labyrinth seal seeks to increase the length of the path that a molecule in gas must travel from any of the fluids of interest to the outside of the container, or to open unobstructed ambient if the labyrinth is in whole or in part on the outside of the container.
• a measure of the effectiveness of a labyrinth seal is the increase in path length which it provides. Such increase for containers of the invention is preferably at least 1 mm, and more preferably at least 2 mm, and more preferably 1 cm. Compared to the gas exchange path length in the absence of the labyrinth seal, the gas exchange path length with the seal in place is preferably 25% more, and more preferably 100% more, than the length without the labyrinth seal.
• An alternative measure of labyrinth seal effectiveness looks at the number of changes of direction a molecule must undergo in order to trace a path from the surface of the fluid of interest closest to the outside in order to reach the outside.
• a closure reservoir may be designed so that the portion of the primary member which contacts the closure is partially surrounded by fluid when the closure and the primary members are in contact.
• this reservoir opens both into the interior and the exterior of the container when the latter is closed.
• This design creates a type of seal which bears some similarity to the water trap in household plumbing. Vapor from the interior of the container must pass through the fluid surrounding the contact zone in order to escape to the exterior of the container. As long as an adequate level of fluid is maintained surrounding the contact zone, such a seal can be quite effective in preventing evaporation as well as in limiting the inflow of water vapor. With this embodiment, it may be of particular interest to be able readily to replenish the level of fluid in the closure reservoir in which the contact between closure and primary member takes place.
• This reservoir must conform to the shape of the primary member, so that for example if the primary member is a test tube the closure reservoir must be able to receive the annular open end of the test tube.
• a reservoir on the primary member could be designed to provide fluid to immerse a portion of the closure which contacts the primary member.
• the fluid might desirably be replenished periodically.
• the closure could be provided with gaps or channels guiding replenishing fluid towards the contact zone to maintain fluid levels in a reservoir of the primary member encompassing or located near that zone.
• Figs. 2A depicts an opening 54 which is in the vicinity of the contact zone and can serve to immerse in fluid the portion of the primary member, part of projection 60, which contacts the closure 64.
• FIG. 3 also depicts an opening 78 which is in the vicinity of the contact zone and can serve to immerse in fluid the portion of the primary member 80 which contacts the closure 72.
• a class of polymers referred to as "sliding gels" has been studied, as shown for example by United States Patent No. 6,828,378 and by the Ph.D. Thesis of M.
• FIG. 4 depicts in schematic partial cross section a closure 90 with a reservoir for fluid 92 which surrounds a portion of the primary member, part of projection 96, which contacts the closure.
• the closure is also depicted as having an additional reservoir 94.
• a volume 98 which is composed of a compliant material which absorbs fluid, for example a suitable sliding gel.
• the volume 98 can serve as a further reservoir of fluid to lessen the frequency with which the fluid in reservoir 92 is replenished.
• FIG. 5 depicts in schematic partial cross section an alternative preferred embodiment of the invention with a labyrinth seal and a single closure reservoir 108 with an opening 110 to the outside of the container, close to the contact zone 118.
• the closure 100 consists of an upper part 102 and a lower part 104, the lower part contacting the primary member 106 at the contact zone 118.
• the primary member 106 has a number of reservoirs 120, 122, 124 for fluids of interest.
• the lower part 104 of the closure approaches the tops of these reservoirs closely in order to lessen the container headspace.
• the upper part 102 of the closure is provided with a pluggable hole 112 for replenishing the fluid reservoir 108 without detaching the closure from the primary member 106.
• vent hole 114 to facilitate the refilling process
• structural support 116 to facilitate the process of plugging the hole 112.
• the reservoir 108 tapers towards the opening 110, becoming narrower as the opening is approached. The tapering draws the fluid towards the opening by capillary action.
• baffles 130 which provide further surface to hold fluid in reservoir 108. Additional features could be included in reservoir 108 to hold the fluid in place, for example additional baffles positioned elsewhere, spiral walls, or foam.
• the opening 110 allows fluid to evaporate into the volume 126 creating there a high partial pressure of the fluid, which as indicated above helps to reduce the rate at which the fluid exits through the imperfect seal at the contact zone 118.
• a fluid sample comprising a solvent is stored in a reservoir.
• the reservoir is covered using a closure which has one or more closure reservoirs.
• the closure reservoirs contain quantities of the solvent.
• the solvent in the closure reservoir is replenished.
• the step of replenishment of the solvent preferably takes place in the methods of the invention without removing the closure from the container.
• covers and plugs may be provided as already described.
• the fluids may be stored in well plates.
• a well plate or other primary member which has multiple separated reservoirs for fluid
• the methods apply to storing a number of fluids of interest, preferably having a common solvent.
• the methods of the invention are practiced with well plates, it is common for the well plates to be stored by means of stacking.
• the closures of the invention are thus preferably designed in such a way that multiple containers of the invention stack comfortably and safely atop each other.
• the methods of the invention are preferably carried out automatically.
• An overall laboratory automation system may include, for example, a carousel for holding well plates, a robot arm for moving well plates from one instrument to another, a variety of analytical instruments and reaction chambers, a pin based fluid transfer system, and/or an acoustic ejection system.
• the overall purposes of the system may include taking quantities of fluids and subjecting them to analyses (including for example the ascertainment of their composition and physical properties), reactions designed to produce particular moieties, and purification steps, all the while potentially keeping track, by computerized or other means, of the origin and destination of each fluid in the system and of the processes and results for each fluid.
• the system may also be employed to generate for further use objects which contain or are coated with fluids moved by the system.
• the tracking of the origin, destination, processes, and results for each fluid may be performed, for example, by having controllers such as the fluid transport system controller communicate that information to a general purpose computer which stores the information as flat files or in a database. Fluids are conveniently identified by assigning an identifier to each well plate in the system and by tracking what is done to each well in each plate at particular times in a way that allows one to produce an overall history for the contents of each well of each plate.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• FIG. 6 depicts an exemplary embodiment of the invention in which the container is a well plate and the closure is a lid for the well plate.
• the top portion of the figure depicts a vertical cross section through part of the container and closure.
• the bottom portion depicts a horizontal cross section through the container and closure.
• the container has two vertical projections 210 and 212 around its circumference.
• the closure has an upper and a lower member 214 and 216. In between the upper and lower members there is a reservoir for liquid.
• the upper member has two vertical projections 218 and 220 around its circumference.
• the lower member is designed to be on the inside of both vertical projections.
• An elastic component causes the lower member to press against the inner projection on the plate. In FIG. 6, this elastic component is show as being composed of four parts 222 attached to two sides of the lower closure member.
• FIG. 7 depicts schematically an exemplary construction for the elastic component in the context of the embodiment of FIG. 6. Like the upper part of FIG. 6, this figure is a vertical cross section through the container and closure. For simplicity, this figure depicts only the lower closure member 216 and a portion of the elastic component which acts upon that lower member. In the upper part of the figure, we see the lower closure member 216 prior to contact between closure and container 226.
• the elastic component which comprises one or more flexible members 228 attached at one end to the lower closure member as in FIG. 6, is depicted here to the right of the closure in the figure.
• the elastic component 228 responds to the presence of the container and bends, generating a force that sends the lower closure member 216 leftwards. The pressure forces the lower closure member against the left wall of the inner projection of the container.
• FIG. 8 we see a schematic cross-section of a closure of the invention depicting both the upper and lower members of the closure 214 and 216.
• the upper and lower closure members both have portions 232 and 234 of an elastic component attached.
• the elastic component is of a somewhat different design than that shown in FIGS. 6 and 7, being attached towards the bottom of the closure member wall and extending upward.
• the corresponding poition 234 of the elastic component is shown attached at the left hand side, while the lower member 216 has its portion 232 of the elastic component depicted as being attached on the right hand side.
• the elastic component acts upon them to the right and to the left respectively.
• FIG. 9 provides further detail on an elastic component of the kind depicted in FIGS. 6 and 7.
• the elastic component has two spring-like parts 238 and 240 which project outwards from a side of a closure member.
• Each of the spring-like pieces that make up the elastic component is tapered and also has a tapered cross-section.
• the form of the pieces is thus somewhat like that of a wing.
• FIG. 9 shows the spring-like pieces 238 and 240 as having a sharp bottom edge, the bottom edge may also be rounded or blunt, and the tapering of both the overall shape and of the cross-section may be more or less gradual.
• the downward force of placing the closure on the container will First apply force between the finger and shoulder of the spring-like pieces 238 and 240 to press them closer into the body.
• the exact point at which the spring-like pieces will make contact with the container depends on design details as well as deviations from nominal dimensions and misalignment of closure and container in the insertion process. The intent, however, is that as contact is made the spring-like pieces 238 and 240 are forced towards the main portion of the closure member, exerting a force on it.
• FIGS. 7 and 8 It is also possible in the embodiments of FIGS. 7 and 8 to use more than one spring-like structure on each side of the inner and outer members. For example, we could have three or five or ten spring-like structures attached to one side of the lower member. In addition, we could have spring-like structures attached to two adjacent (non-opposite) sides of the lower member. This is shown in FIG. 10, which depicts schematically a member of a closure of the invention with a number of spring-like structures such as 244 on each of two adjacent sides. That would result in the lower member pressing against a corner of the container projection and thus making a better, more sealing contact against two of the walls of the container projection. The same multiplicity of spring-like structures is possible for the upper member.
• FIG. 8 for simplicity the upper and lower members of the closure are not depicted as being connected. It would be possible for the two members of the closure to be separate, although that would have the disadvantage that they would have to be removed in two operations. Alternatively, it is possible to have the two members of the closure be connected provided the connection between them has sufficient elasticity to allow them to be pushed apart as required for them to press against the closure as discussed above.
• 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.
• the container is held firmly while the robot a ⁇ n also presses firmly against the closure.
• 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.
• Closures containing reservoirs for solvent are described above. Such reservoirs are conveniently employed in many closures which press against the container. While many of the techniques described above are usable with two-member closures as described above, a particularly attractive possibility is for a reservoir for solvent to be attached to the top of the lower closure member or bottom of the upper closure member.
• the solvent reservoir could, for example, be made of a substance which absorbs and holds the solvent.
• labyrinth seals there is also a discussion of so-called "labyrinth seals" above.
• 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, New Jersey), which is part of Celanese Corporation, and goes by the trade name Topas.
• 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 FIG. 9 can be fabricated in the same molding process as the closure member to which it is attached. [000101] Instead of two members it would be possible to practice the invention with three, four, or more closure members, each pressing against a particular zone in the container.
• 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.
• 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.
• 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 FIG. 8, lower part.
• the projections in the closure which will press against projections on the container be designed to have an angle of deviation from the vertical which matches the angle of deviation of the projections in the container.
• FIGS. 7-10 for simplicity the elastic component of the closures has been depicted as lying on the outside walls of rectangular members. It will be appreciated that if a robot or other such machine, or a human hand, were to pick up closure members so designed (e.g., as depicted in FIG. 10) it would press against the elastic component. For this reason it may be better in some cases to have at least the outer closure member have an overhang or projection at the top at which it can be gripped. [000106] 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.
• 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 comer 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.
• FIGS. 12A-12C The results obtained are depicted in FIGS. 12A-12C.
• the black color denotes wells within the well plate where the fluid content fell to less than 90% of the original fluid content during the 64-day test period. It is desired that there be no wells of this type in the well plate.
• closures which press against a corner achieved generally a smaller number of wells of this type and in general no wells of this type in the quadrant towards which they pressed. This suggests that a closure of the type described above in connection with FIG. 8 will achieve no wells with more than 10% DMSO loss over two months.
• lid performance would be expected for protecting other solvents in the container when covered by the closure containing a reservoir of the solvent.
• 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.

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• Chemical Kinetics & Catalysis (AREA)
• Closures For Containers (AREA)
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• 2006
  • 2006-03-10 WO PCT/US2006/008572 patent/WO2006099122A1/en active Application Filing
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