VACUUM MANIFOLD FOR LABORATORY PROCESSING OF MULTIPLE LIQUID SAMPLES

Abstract: The invention provides a vacuum manifold which can be conveniently used in semi-automated and fully-automated laboratory machines to carry out a sequence of vacuum-assisted laboratory manipulations on a large number of individual liquid samples. The invention has a base (12) which is sized and dimensioned to accept and retain a first liquid receptacle (24), such as a microtitre dish. Generally, the base (12) has a bottom wall (16) and side walls (18) and the first receptacle (24) is designed to be retained within the side walls (18). The invention also has an adapter frame which is sized and dimensioned to accept and retain a second liquid receptacle (30), such as a second microtitre dish. The adapter frame (14) is typically a rectangular frame structure having a lip (32) which supports the second receptacle (30). The base (12) generally has a port (26) which is attachable to a source of vacuum. In operation, the first liquid receptacle (24) is placed within the base (12), the adapter frame (14) is placed on top of the base (12) and the second liquid receptacle (30) is placed on the adapter frame (14) so that a second receptacle (30) is located directly above the first receptacle (24). When vacuum is applied to the base using the vacuum port (26), a uniform vacuum is drawn along the bottom of the second liquid receptacle (30) which provides a driving force which acts upon liquid within the second receptacle (30). In a typical operation, the bottom of the second receptacle (30) is a filtration membrane and the vacuum is used to draw liquid from the second receptacle (30) across the filtered membrane into the first receptacle (24). Because of its modular construction, the various elements of the vacuum frame are easily stacked in stacking frames disposed to one side of the vacuum manifold. This stacking capability allows a large number of vacuum-assisted laboratory operations to be carried out on multiple sets of liquid samples without the necessity of a large amount of horizontal lab bench area. The stacking capability also facilitates the adaption of the invention with robotic equipment to provide a fully-automated laboratory processing tool.

Description: VACUUM MANIFOLD FOR LABORATORY PROCESSING OF MULTIPLE LIQUID SAMPLES FIELD OF THE INVENTION This invention relates generally to vacuum manifold devices, and specifically, to vacuum manifold devices useful in the simultaneous laboratory processing of multiple liquid samples. BACKGROUND It has become a common practice in testing laboratories to carry out simple laboratory processing steps on multiple liquid samples at the same time, in a single apparatus. This practice has greatly increased the efficiency of testing laboratories, especially laboratories doing a large volume of routine test work. The simultaneous testing of multiple liquid samples in a single apparatus is conducted with apparatus especially designed for this purpose. The most common piece of apparatus is a disposable tray having multiple individual "wells. " These trays, commonly called "microtitre dishes," are made by a large number of manufacturers in a variety of sizes and shapes. In practice, an individual liquid sample is placed within each of the wells, where it is manipulated as part of the testing process. Recently, equipment manufacturers in the trade have begun marketing specially designed vacuum manifolds for use with microtitre dishes. Such manifolds allow the practitioner to carry out common laboratory processes in microtitre dishes using vacuum as assisting force. Examples of such practices are filtration, drying and chromatography processes. Unfortunately, the vacuum manifolds presently useful with microtitre dishes are not completely satisfactory. One problem is that such prior art vacuum manifolds are designed to work with specific microtitre dishes of a particular size and shape. If a practitioner wishes to another his microtitre dish, one with a different height or "footprint," the practitioner must invest in another vacuum manifold, one designed specifically for such other microtitre dish Another problem arises from the fact that vacuum processes generally constitute only one of several other processes which any particular liquid sample is to be subjected to. Handling the microtitre dishes from one testing operation to another frequently takes up a great deal of laboratory bench area as the various microtitre dishes are set aside between process steps A third problem is that, because of the relative inflexibility of present-day vacuum manifolds, and the excessive amount of area required by present-day multiple testing operations, present-day vacuum manifolds are not easily incorporated into fully automated machines capable of carrying out a multiplicity of laboratory procedures using a relatively small amount of work space. Accordingly, there is a need for a vacuum manifold which can simply, conveniently and inexpensively be used with a large variety of microtitre dishes. There is a further need for apparatus useful in simultaneously conducting a laboratory procedure on a multiplicity of samples which does not require an excessive amount of laboratory work space. Still further, there is a need for a fully automated machine which can simply, reliably and inexpensively conduct a series of laboratory tests on a multiplicity of liquid samples without requiring an excessive amount of work space. SUMMARY The invention satisfies these needs. The invention is a vacuum manifold useful in combination with first and second liquid receptacles, such as microtitre dishes. The invention comprises: (a) a base which is sized and dimensioned to accept and retain the first receptacle, the base having a bottom wall and side walls, the side walls having uppermost portions which cooperate to form a base wall perimeter; (b) an adapter frame which is sized and dimensioned to accept and retain the second receptacle, the adapter frame being further sized and dimensioned to attach to the base wall perimeter in substantially sealed relationship such that the first receptacle can be fully enclosed within a chamber formed by the base, the adapter frame and the second receptacle; and (c) vacuum means for drawing a vacuum on the bottom of the second receptacle when the second receptacle is disposed within the adapter frame and the first receptacle is disposed within the base. Typically, the vacuum means comprises a port defined within the base. Both the base and the adapter frame can be sized and dimensioned to handle a wide variety of liquid receptacles. In one typical embodiment, the second receptacle is adapted for filtration, its bottom comprising a filtration material. Typically, both the first and second liquid receptacles complies a plurality of separate "wells." This facilitates the simultaneous processing of a large number of individual liquid samples in a single step. The invention can also comprise stacking trays for retaining unused liquid receptacles and frames when not in use. The invention is easily adaptable in a semi-automated or fully- automated machine having a computerized mechanical manipulator. Typically, the mechanical manipulator is programmed to robotically configure and reconfigure the various elements of the vacuum manifold to serially carry out a number of laboratory manipulations of a large number of individual liquid samples. The invention can be conveniently and easily used to perform a wide variety of vacuum-assisted laboratory procedures, such as filtration, drying, column purification and column chromatography. The invention is inexpensive and simple to manufacture and operate, and its use conserves valuable laboratory work space. DESCRIPTION OF THE DRAWINGS These and other features, aspects and advantages of the present invention will become better understood with reference to the following description, appended claims and accompanying drawings where: FIGURE 1 is an exploded perspective view showing a vacuum manifold having features of the invention and adapted for use with a narrow dish microtitre tray; FIGURE 2 is an exploded cross-sectional view of the vacuum manifold shown in FIG. 1 ; FIGURE 3 is a cross-sectional side view of the fully assembled vacuum manifold shown in FIG. 1 ; FIGURE 4 is an exploded perspective view showing a vacuum manifold having features of the invention and adapted for use with a deep dish microtitre tray; FIGURE 5 is an exploded cross-sectional view of the vacuum manifold shown in FIG. 4; FIGURE 6 is a cross-sectional side view of the fully assembled vacuum manifold shown in FIG. 4; FIGURE 7 is an exploded perspective view of a stacking tray assembly having features of the invention; FIGURE 8 is an exploded cross-sectional view of the stacking tray assembly shown in FIG. 7; FIGURE 9 is a cross-sectional view of the fully assembled stacking tray assembly shown in FIG. 7; and FIGURE 10 is a perspective view of a machine and a kit having features of the invention. DETAILED DESCRIPTION The following discussion describes in detaii one embodiment of the invention and several variations of that embodiment. This discussion should not be construed, however, as limiting the invention to those particular embodiments. Practitioners skilled in the art will recognize numerous other embodiments as well. For a definition of the complete scope of the invention, the reader is directed to the appended claims. As shown in Figures 1 -6, the vacuum manifold of the invention 10 comprises a base 12, an adapter frame 14 and a means for drawing a vacuum. The base has a bottom wall 16 and side walls 18. The side walls 18 have uppermost portions 20 which cooperate to form a base wall perimeter 22. The base 12 is sized and dimensioned to accept and retain a first liquid receptacle 24. Typically, the base 12 has a foot print with an area smaller than about 200 square centimeters. As used herein, the term "footprint" is meant to indicate the horizontal area and dimensions of various elements of the invention 10. In the embodiment of the invention shown in the drawings, the base 12 further comprises a vacuum port 26 capable of attachment to an external source of vacuum, such as a laboratory vacuum line. Typically, the vacuum port 26 is defined in the side walls 18 proximate to the bottom wall 16. In embodiments having such a vacuum port 26, a discontinuous lip 28 is provided to support the first receptacle 24 above and spaced-apart from the bottom wall 16. This allows a vacuum generated using the vacuum port 26 to be uniform across the bottom wall 16. The base 12 can be made out of a wide variety of suitable materials, such as metals and plastics. For ease and inexpense of manufacture, the base 12 is typically made from a plastic. In a typical embodiment, the base 12 has a rectangular footprint with the width between about 1 0 and about 1 3 centimeters and a length between about 1 2 and about 1 6 centimeters. The base 12 is inexpensively made with dimensions capable of accepting and retaining the footprint of any first receptacle 24 having a footprint smaller than the footprint of the base 12. The adapter frame 14 is sized and dimensioned to accept a second liquid receptacle 30. Typically, this is accomplished by providing the adapter frame 14 with an interior lip 32 capable of supporting the second receptacle 30 in a horizontal position. In the embodiments shown in the drawings, a sealing gasket 34 is disposed around the perimeter of the lip 28 to provide sufficient sealing of the second receptacle 30 to the adapter frame 14 when a vacuum is applied to the bottom side 36 of the second receptacle 30. The adapter frame 14 is further sized and dimensioned to attach to the base wall perimeter 22 of the base in a substantially sealed relationship such that, when a first receptacle 24 is disposed within the base 12 and a second receptacle 30 is disposed within the adapter frame 14, the first receptacle 24 is fully enclosed within a chamber 38 formed by the base 12, the adapter frame 14 and the second receptacle 30. Typically, the adapter frame 14 is rectangular with substantially the same footprint as that of the base 12. The adapter frame 14 defines a central opening 40 which is sized and dimensioned to accept and retain the footprint of a particular second receptacle 30. The invention allows the use of a second receptacle 30 which has a different footprint than that of the first receptacle 24. In the invention, this is easily accomplished by adapting the base 12 to accept and retain the footprint of the first receptacle 24 and adapting the adaptor frame 14 to accept and retain the different footprint of the second receptacle 30. Similarly, the invention makes it easy to use liquid receptacles 24 and 30 of differing height. The base 12 is sized and dimensioned to accept and retain the first receptacle 24 having a given height while the adapter frame 14 is sized and dimensioned to accept a second receptacle 30 having a different height. Figures 4-6 illustrate the invention using an adapter frame 14 sized and dimensioned to accept and retain a typical deep well microtitre plate. Like the base 12, the adapter frame 14 can be made from a wide variety of suitable materials. Metals and plastics are easily used. Plastics are generally the preferred material because of the ease and inexpense of its use in the manufacturing process. In the embodiment shown in the drawings, locator pins 42 are disposed within the base 12 and adapted to cooperate with matching holes 44 within the adapter frame 14 to facilitate the proper alignment and sealing of the adapter frame 14 to the base 12. In another embodiment (not shown in the drawings), the base 12 and the adapter frame 14 have matching beveled walls so that the adapter frame 14 "nests" with the base 12. The invention 10 can further comprise a first receptacle 24, such as a microtitre dish, disposed within the base 12. Similarly, the invention 10 can comprise a second receptacle 30, such as a microtitre dish, disposed within the adapter frame 14 above the first receptacle 24. In the embodiments shown in the drawings, the receptacles 24 and 30 are microtitre dishes having a plurality of separate wells 46 disposed in fixed arrays. For most applications, the fixed array of the second receptacle 30 is similar in layout to the fixed array of the first receptacle 24. This allows each well 46 in the second receptacle 30 to discharge liquid into a corresponding well 46 in the first receptacle 24. This is commonly the case, for example, in filtration processes using the invention 10. In such filtration processes, the bottoms 48 of each separate well 46 of the second receptacle 30 comprise a filter material, such as a filtering membrane. As liquid is filtered from a well 46 in the second receptacle 30 across the filter membrane in the well bottom 48, the liquid drops by gravity into the corresponding well 46 in the first receptacle 24. The vacuum means is for drawing a vacuum on the bottom side 36 of the second receptacle 30 when the second receptacle 30 is disposed within the adapter frame 14 and the first receptacle 24 is disposed within the base 12. The vacuum means is typically one or more ports disposed within the base 12 or adapter frame 14. As discussed above, the embodiments illustrated in the drawings define a vacuum port 26 near the bottom wall 16 of the base 12. In this embodiment, when the vacuum manifold of the invention 10 is fully assembled with first and second liquid receptacles 24 and 30 are in place, a uniform vacuum is drawn across the bottom wall 16 of the base 12. This uniform vacuum propagates around the first receptacle 24 so as to result in a uniform vacuum across the bottom side 36 of the second receptacle 30. Those skilled in the art will appreciate that, where the invention 10 is to be used with liquid receptacles 24 and 30 having small, separate wells 46, the distance between the first receptacle 24 and the second receptacle 30 must be carefully chosen in conjunction with the degree of vacuum to be used within the vacuum manifold 10 so as not to horizontally divert liquid dripping from the second receptacle 30 to the first receptacle 24. Said another way, the degree of vacuum must be sufficiently small, given the distance between the bottom side 36 of the second receptacle 30 and the uppermost portion of the first receptacle 24, so that liquid dripping from a specific well 46 in the second receptacle 30 falls precisely vertically into the corresponding well 46 within the first receptacle 24. Should the degree of vacuum be excessive, liquid falling from the second receptacle 30 towards the first receptacle 24 may be diverted horizontally into a non-corresponding well 46 within the first receptacle 24. The invention is also a kit 50 comprising the vacuum manifold 10 described above, together with one or more stacking trays 52 which are sized and dimensioned to accept at least one of the receptacles 24 and 30. In a typical embodiment, the stacking trays 52 are similar in design and construction to the base 12. The stacking trays, however, have no vacuum ports 26. The purpose of the stacking trays 52 is to allow receptacles 24 and 30 and/or adapter frames 14 to be stacked at a single location when not in use. This stacking capability maximizes the use of precious horizontal laboratory bench area. As shown in Figures 7-9, the kit can also provide additional adapter frames 14, each sized and dimensioned to accept and retain receptacles 24 and 30 having different footprints and/or differing heights. The invention 10 is conveniently used with semi-automated DNA purification equipment, such as BioMek 2000 purification equipment sold by Beckman Instruments, Inc. of Fullerton, California. The vacuum manifold of the invention 10 is also conveniently adapted to a fully automatic machine 54 capable of robotically carrying out a number of laboratory manipulations to a plurality of individual liquid samples. Such a machine 54 comprises the vacuum manifold 10 described above and a computerized mechanical manipulator 56 having a moveable gripper tool 58. The mechanical manipulator 56 is basically a computerized robotic device programmed to robotically manipulate the various elements of the vacuum manifold 10 to perform first one laboratory manipulation on a plurality of liquid samples, then reconfigure the vacuum manifold 10 to perform a second or more laboratory manipulations on those liquid samples. In such a machine 54, one or more stacking trays 52 described above can be conveniently used to stack various elements of the invention 10 in between use. For example, as shown in Figure 10, a machine of the invention 54 comprises a vacuum manifold 10 and two stacking trays 52. Such a machine 54 can conveniently perform five or more different laboratory manipulations using the vacuum manifold 10. One of skill in the art will appreciate the relative lack of space required by the machine 54 because of the stacking capabilities of the component elements. The machine of the invention 54 is relatively easy and inexpensive to construct and maintain. Because of the simplicity of its construction and operation, such a machine 54 has a very high reliability factor Any process that can use vacuum as a driving force can generally be adapted for use in the invention. Such processes include column chromatography, column-based purification methods, vacuum drawing and filtration. For example, the invention can be easily adapted to carrying out chromatography procedures. In this case, the second liquid receptacle would have a plurality of chromatography columns, each having a semi-permeable bottom to allow a vacuum below the bottom to operate on liquid within each column. Having thus described the invention, it should be apparent that numerous structural modifications and adaptations may be resorted to without departing from the scope and fair meaning of the instant invention as set forth hereinabove and as described hereinbelow by the claims.

Claims: What is Claimed is: A vacuum manifold device useful in combination with first and first liquid receptacles, wherein both receptacles have a bottom and an uppermost portion, the device comprising: (a) a base which is sized and dimensioned to accept and retain the first receptacle, the base having a bottom wall and side walls, the side walls having uppermost portions which cooperate to form a base wall perimeter; (b) an adapter frame which is sized and dimensioned to accept and retain the second receptacle, the adapter frame being further sized and dimensioned to attach to the base wall perimeter in substantially sealed relationship such that the first receptacle can be fully enclosed within a chamber formed by the base, the adapter frame and the second receptacle; and (c) vacuum means for drawing a vacuum on the bottom of the second receptacle when the second receptacle is disposed within the adapter frame and the first receptacle is disposed within the base. 2. The vacuum manifold device of claim 1 wherein the base has a footprint with an area smaller than about 200 sq.cm 3. The vacuum manifold device of claim 1 wherein the base further comprises a lip capable of supporting the first receptacle above the bottom wall. 4. The vacuum manifold device of claim 1 wherein the base further comprises a port capable of attachment to a source of vacuum. 5. The vacuum manifold device of claim 1 wherein the adapter frame further comprises a lip capable of supporting the second receptacle. 6. The vacuum manifold device of claim 1 wherein the base is sized and dimensioned to accept and retain a first receptacle having a first footprint and the adapter frame is sized and dimensioned to accept and retain a second receptacle having a different footprint. 7. The vacuum manifold device of claim 1 wherein the base is sized and dimensioned to accept and retain a first receptacle having a first height and the adapter frame is sized and dimensioned to accept and retain a second receptacle having a different height. 8. The vacuum manifold device of claim 1 further comprising a first receptacle disposed within the base and a second receptacle disposed within the adapter frame above the first receptacle. 9. The vacuum manifold device of claim 8 wherein the second receptacle has a footprint with dimensions different than those of the first receptacle. 10. The vacuum manifold device of claim 8 wherein the second receptacle has a height different than that of the first receptacle. 1 1 . The vacuum manifold device of claim 8 wherein the bottom of the second receptacle comprises a filtration material. 1 2. The vacuum manifold device of claim 8 wherein the second receptacle comprises a plurality of separate wells. 1 3. The vacuum manifold device of claim 8 wherein the second receptacle comprises a plurality of separate wells disposed in a fixed array and the first receptacle comprises a plurality of separate wells disposed in a similar fixed array. 14. The vacuum manifold device of claim 8 wherein the second receptacle comprises a plurality of separate wells disposed in a fixed array, the bottoms of each separate well comprising a filter material, and the first receptacle comprises a plurality of separate wells disposed in a similar fixed array, the first receptacle being disposed immediately below the second receptacle. 1 5. The vacuum manifold device of claim 8 wherein the second receptacle and the first receptacle are microtitre plates. 1 6. A kit useful in carrying out multiple laboratory manipulations of a plurality of liquid samples using first and first liquid receptacles, wherein both receptacles have a bottom and an uppermost portion, the kit comprising: (a) a base which is sized and dimensioned to accept and retain the second receptacle, the base having a bottom wall and side walls, the side walls having uppermost portions which cooperate to form a base wall perimeter; (b) an adapter frame which is sized and dimensioned to accept and retain the second receptacle, the adapter frame being further sized and dimensioned to attach to the base wall perimeter in substantially sealed relationship such that the first receptacle can be fully enclosed within a chamber formed by the base, the adapter frame and the second receptacle; (c) a stacking tray which is sized and dimensioned to accept and retain at least one of the receptacles; and (d) vacuum means for drawing a vacuum on the bottom of the first receptacle when the second receptacle is disposed within the adapter frame and the first receptacle is disposed within the base. 17. The kit of claim 16 further comprising a second adapter frame sized and dimensioned to accept and retain another second receptacle having a footprint different from the footprint of the other second receptacle. 18. The kit of claim 16 further comprising a second adapter frame sized and dimensioned to accept and retain another second receptacle having a height different from the height of the other second receptacle. 1 9. A machine useful in carrying out multiple laboratory manipulations of a plurality of liquid samples using first and first liquid receptacles, wherein both receptacles have a bottom and an uppermost portion, the machine comprising: (a) a base which is sized and dimensioned to accept and retain the first receptacle, the base having a bottom wall and side walls, the side walls having uppermost portions which cooperate to form a base wall perimeter; (b) an adapter frame which is sized and dimensioned to accept and retain the second receptacle, the adapter frame being further sized and dimensioned to attach to the base wall perimeter in substantially sealed relationship such that the first receptacle is fully enclosed within a chamber formed by the base, the adapter frame and the second receptacle; (c) vacuum means for drawing a vacuum on the bottom of the second receptacle when the second receptacle is disposed within the adapter frame and the first receptacle is disposed within the base; and (d) a computerized mechanical manipulator having a moveable gripper tool, the mechanical manipulator being programmed to robotically configure the base, the adapter frame, the stacking frame and the receptacles using the moveable gripper tool to perform at least one laboratory manipulation on at least one liquid sample. 20. The machine of claim 1 9 wherein the computerized mechanical manipulator is programmed to robotically configure the base, the adapter frame, the stacking frame and the receptacles using the moveable gripper tool to perform a plurality of laboratory manipulations on at least one liquid sample. 21 . The machine of claim 1 9 wherein the computerized mechanical manipulator is programmed to robotically configure the base, the adapter frame, the stacking frame and the receptacles using the moveable gripper tool to simultaneously perform a plurality of laboratory manipulations on a plurality of liquid samples. 22. The machine of claim 1 9 wherein at least one of the manipulations comprises the simultaneous filtration of a plurality of liquid samples. 23. A combination useful in carrying out multiple laboratory manipulations of a plurality of liquid samples using first and first liquid receptacles, wherein both receptacles have a bottom and an uppermost portion, the combination comprising: (a) a machine comprising: (2) a base which is sized and dimensioned to accept and retain the first receptacle, the base having a bottom wall and side walls, the side walls having uppermost portions which cooperate to form a base wall perimeter; (3) an adapter frame which is sized and dimensioned to accept and retain the second receptacle, the adapter frame being further sized and dimensioned to attach to the base wall perimeter in substantially sealed relationship such that the first receptacle is fully enclosed within a chamber formed by the base, the adapter frame and the second receptacle; (4) a stacking tray which is sized and dimensioned to accept and retain one of the receptacles; (5) vacuum means for drawing a vacuum on the bottom of the second receptacle when the second receptacle is disposed within the adapter frame and the first receptacle is disposed within the base; and (6) a computerized mechanical manipulator having a moveable gripper tool, the mechanical manipulator being programmed to robotically configure the base, the adapter frame, the stacking frame and the receptacles using the moveable gripper tool to perform at least one laboratory manipulation on at least one liquid sample; and (b) a stacking tray which is sized and dimensioned to accept and retain at least one of the receptacles. 24. The combination of claim 23 further comprising a second stacking tray which is sized and dimensioned to accept and retain one of the receptacles. 25. The combination of claim 23 further comprising a second adapter frame sized and dimensioned to accept and retain another second receptacle having a footprint different than the footprint of the other second receptacle. 26. The combination of claim 23 further comprising a second adapter frame sized and dimensioned to accept and retain another second receptacle having a height different than the height of the other second receptacle.

Inventors: HANAMOTO BARRY K, SASAKI GLENN C, HANAMOTO, BARRY, K., SASAKI, GLENN, C.
Applicants: BECKMAN INSTRUMENTS INC, BECKMAN INSTRUMENTS, INC.
Application year: 1996
Main classification: B01L3
IPC codes: B01D61, B01L3, B01L9, B25J15, B65D25, G01N30, G01N35