Well for processing a fluid Number:7,135,117 from the United States Patent and Trademark Office (PTO) owispatent A well (50) comprising a side wall (10), a sealing ring (40), a rib arrangement (5), and a filter (20), for use in processing a fluid, e.g., by microtitration or microfiltration, is disclosed.<H processing, fluid, Well, for, proces, 7135117.html, Patent, pto, 7135117

Title: Well for processing a fluid

Abstract: A well (50) comprising a side wall (10), a sealing ring (40), a rib arrangement (5), and a filter (20), for use in processing a fluid, e.g., by microtitration or microfiltration, is disclosed.

Patent Number: 7,135,117 Issued on 11/14/2006 to Kane

Inventors: Kane; Jeffrey (Manchester, MI)
Assignee: Pall Corporation (East Hills, NY)

Appl. No.: 10/478,050

Filed: May 29, 2002

PCT Filed: May 29, 2002

PCT No.: PCT/US02/16686

371(c)(1),(2),(4) Date: November 18, 2003

PCT Pub. No.: WO02/096563

PCT Pub. Date: December 05, 2002

Current U.S. Class: 210/650 ; 210/321.6; 210/321.75; 210/767; 422/101; 422/99

Current International Class: B01D 61/00 (20060101); B01D 63/00 (20060101); B01L 11/00 (20060101); B01D 37/00 (20060101)

Field of Search: 210/321.6,321.75,432,650,232,767 422/99,101

References Cited [Referenced By]

U.S. Patent Documents


3663374	May 1972	Moyer et al.
4014653	March 1977	Gianos et al.
4127131	November 1978	Vaillancourt
4162979	July 1979	Wahlefeld et al.
4167875	September 1979	Meakin
4170056	October 1979	Meyst et al.
4301010	November 1981	Eddleman et al.
4472276	September 1984	Taylor
4623461	November 1986	Hossom et al.
4699013	October 1987	Kroner
4734262	March 1988	Bagshawe
4787988	November 1988	Bertoncini et al.
4797259	January 1989	Matkovich et al.
4800020	January 1989	Savas et al.
4828801	May 1989	Lombardy wife Alric et al.
4832850	May 1989	Cais et al.
4895706	January 1990	Root et al.
4902481	February 1990	Clark et al.
4948422	August 1990	Yoshizawa et al.
4948442	August 1990	Manns
4948561	August 1990	Hinckley et al.
4948564	August 1990	Root et al.
5047215	September 1991	Manns
5096575	March 1992	Cosack
5108704	April 1992	Bowers et al.
5116496	May 1992	Scott
5120504	June 1992	Petro-Roy et al.
5124041	June 1992	Sheer et al.
5137804	August 1992	Greene et al.
5208161	May 1993	Saunders et al.
5264184	November 1993	Aysta et al.
5334538	August 1994	Parker et al.
5423989	June 1995	Allen et al.
5464541	November 1995	Aysta et al.
5516490	May 1996	Sanadi
5620663	April 1997	Aysta et al.
5679310	October 1997	Manns
5710049	January 1998	Noppe et al.
5733449	March 1998	Bowers et al.
5846745	December 1998	Christensen et al.
5861094	January 1999	Goehde
5918273	June 1999	Horn
6083760	July 2000	Ditlow et al.
6159368	December 2000	Moring et al.
6358730	March 2002	Kane
6419827	July 2002	Sandell et al.
6782354	August 2004	Ikegami
6805840	October 2004	Tajima
6830732	December 2004	Hoffman et al.
6896849	May 2005	Reed et al.
6913152	July 2005	Zuk, Jr.

Foreign Patent Documents


30 16 490	Nov., 1981	DE
41 14611	Nov., 1991	DE
359 249	Mar., 1990	EP
403 679	Dec., 1990	EP
1 110 611	Jun., 2001	EP
2 098 087	Nov., 1981	GB
7811021	May., 1979	NL
WO 88/06723	Sep., 1988	WO
WO 90/14161	Nov., 1990	WO

Primary Examiner: Fortuna; Ana M.
Attorney, Agent or Firm: Leydig, Voit & Mayer, Ltd.

Parent Case Text

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

This patent application claims the benefit of U.S. Provisional Patent Application No. 60/294,211, filed May 31, 2001.

Claims

What is claimed is:

1. A well for use in processing a fluid comprising: a hollow tube having an axis, the tube comprising a side wall having an inner surface; upper and lower axially spaced ends, the lower end comprising a bottom wall and a fluid flow port, and a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface spaced from the inner surface of the side wall; a sealing ring having an outer surface, and a bottom surface, the outer surface of the sealing ring pressing against the inner surface of the side wall of the tube; a filter comprising at least one filter element, the filter having an upper surface and a lower surface, the filter being compressed between the bottom surface of the sealing ring and the top surface of the rib arrangement.

2. The well of claim 1, wherein the bottom surface of the ring presses against the upper surface of the filter while the top surface of the rib arrangement presses against the lower surface of the filter.

3. The well of claim 1, wherein the lower end includes a drainage grid.

4. The well of claim 1, wherein the lower end comprises an insert.

5. The well of claim 1, wherein the filter comprises a membrane.

6. The well of claim 5, wherein the membrane comprises a microporous membrane.

7. The well of claim 6, wherein the membrane comprises an ultrafiltration membrane.

8. The well of claim 1, wherein the filter comprises a fibrous medium.

9. The well of claim 1, wherein the filter comprises at least two filter elements.

10. The well of claim 1, wherein the side wall is not tapered where the sealing ring presses against the inner surface of the side wall.

11. A well for use in processing a fluid comprising: a hollow tube having an axis, the tube comprising a side wall having an inner surface and a lip extending inwardly from said side wall, the lip having a lower surface; upper and lower axially spaced ends; the lower end comprising a bottom wall and a fluid flow port and a sealing ring, the sealing ring comprising an outer surface and a top surface, the outer surface of the sealing ring pressing against the inner surface of the side wall of the tube, wherein the sealing ring further comprises a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface; a filter comprising at least one filter element, the filter having an upper surface and a lower surface, the filter being compressed between the top surface of the ring arrangement and the lower surface of the lip.

12. The well of claim 11, wherein the top surface of the rib arrangement is spaced from the inner surface of the side wall.

13. A method for processing a fluid comprising: passing a fluid into a device comprising the well of claim 11; and, passing at least a portion of the fluid through the filter and through the fluid flow port at the bottom end of the well.

14. The method of claim 13, wherein passing the fluid through the filter includes depleting the fluid of particulates.

15. The method of claim 13, further comprising analyzing the fluid passing through the filter.

16. A multiple well device comprising: a plurality of wells for receiving liquid samples to be processed, each well having a side wall having an inner surface, a bottom end comprising a bottom wall and a fluid flow port, and a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface spaced from the inner surface of the side wall; a filter comprising at least one filter element in each well, the filter having an upper surface and a lower surface; and a sealing ring sealing the filter against the rib arrangement, the sealing ring having an outer surface, and a bottom surface, the bottom surface having a width that is at least the width of the top surface of the rib arrangement, the sealing ring pressing against the inner surface of the side wall, and the bottom surface of the ring pressing against the upper surface of the filter while the top surface of the rib arrangement presses against the lower surface of the filter.

17. A multiple well device comprising: two or more wells according to claim 1.

18. The device of claim 17, comprising 96 wells.

19. The device of claim 17, comprising 384 wells.

20. A method for processing a fluid comprising: passing a fluid into a device comprising a well comprising a side wall having an inner surface, and a bottom end having a rib arrangement having a top surface, wherein the top surface of the rib arrangement is spaced from the inner surface of the side wall, and a fluid flow port; the well having a filter comprising at least one filter element sealed therein, the filter being compressed between a lower surface of a sealing ring, and the top surface of the rib arrangement; and, passing at least a portion of the fluid through the filter and through the fluid flow port at the bottom end of the well.

21. The method of claim 20, wherein passing the fluid through the filter includes depleting the fluid of particulates.

22. The method of claim 20, further comprising analyzing the fluid passing through the filter.

23. A well for use in processing a fluid comprising: a hollow tube having an axis, the tube comprising a side wall having an inner surface and a lip extending inwardly from said side wall, the lip having a lower surface, wherein the lip further comprises a rib arrangement projecting downwardly from the lip, the rib arrangement having a bottom surface; upper and lower axially spaced ends; the lower end comprising a bottom wall and a fluid flow port and a sealing ring, the sealing ring comprising an outer surface and a top surface, the outer surface of the sealing ring pressing against the inner surface of the side wall of the tube; a filter comprising at least one filter element, the filter having an upper surface and a lower surface, the filter being compressed between the top surface of the sealing ring and the bottom surface of the rib arrangement.

24. A method for processing a fluid comprising: passing a fluid into a device comprising the well of claim 23; and, passing at least a portion of the fluid through the filter and through the fluid flow port at the bottom end of the well.

25. The method of claim 24, wherein passing the fluid through the filter includes depleting the fluid of particulates.

26. The method of claim 24, further comprising analyzing the fluid passing through the filter.

27. The well of claim 23, wherein the bottom surface of the rib arrangement is spaced from the inner surface of the side wall.

Description

FIELD OF THE INVENTION

This invention relates to wells for use in processing fluids, e.g., by titration and/or filtration, and more preferably relates to multiwell microtitration and microfiltration devices.

BACKGROUND OF THE INVENTION

Multiple well test devices are used in a variety of microtitration and/or microfiltration protocols. Typically, the devices have a standard number of wells, e.g., 96 wells, or 384 wells (arranged in four blocks of 96 wells each), and the wells include a filter arranged such that application of a vacuum or air pressure to one side of the device causes the fluid in each well to pass through the filter.

When the device is used in for microtitration, e.g., for an immunoassay or a hybridization assay, the filter is generally used to support one or more components of the assay, such as an antigen, antibody, nucleic acid probe or nucleic acid sample. A supported component (e.g., a specific binding agent) binds to an unsupported component in a fluid sample. At least one component can be contained in, on, and/or through the filter, e.g., by physical entrapment, chemical binding and/or adsorption.

When used for microfiltration the filter is generally used to remove one or more components from solutions passed through it, e.g., on the basis of physical, biological and/or chemical interactions in or on the filter. The interactions can be, for example, between the filter and the component to be retained, or between one or more materials retained in or on the filter and the component to be retained.

Accordingly, the devices can be utilized to remove one or more undesirable and/or desirable materials from a fluid. For example, the devices can be used to remove particulates from a sample before further processing (e.g., analysis) of the sample and/or to retain a desired ligand for later recovery and further processing.

Some conventional devices are labor intensive to manufacture and/or are not adapted for use with a variety of filters. Additionally, the seal of the filter in the device can be adversely affected by handling and/or fluid processing conditions.

The present invention provides for ameliorating at least some of the disadvantages of the prior art. These and other advantages of the present invention will be apparent from the description as set forth below.

BRIEF SUMMARY OF THE INVENTION

In accordance with an embodiment of the invention, a well for processing fluid is provided, the well comprising a hollow tube comprising a side wall having an inner surface, a bottom end comprising a bottom wall and a fluid flow port, and a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface spaced away from the inner surface of the side wall; a sealing ring having an outer surface and a bottom surface, the outer surface of the sealing ring pressing against the inner surface of the side wall; and a filter comprising at least one filter element, the filter having an upper surface and a lower surface, the filter being compressed between the bottom surface of the sealing ring and the top surface of the rib arrangement. Typically, the bottom surface of the sealing ring presses against the upper surface of the filter while the top surface of the rib arrangement presses against the lower surface of the filter. In a preferred embodiment of the well, the bottom surface of the sealing ring has a width that is at least the width of the top surface of the rib arrangement.

In accordance with another embodiment, a well for processing fluid is provided, the well comprising a hollow tube comprising a side wall having an inner surface and an inwardly extending lip having a lower surface; a bottom end comprising a bottom wall and a fluid flow port, and a sealing ring comprising a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface; the sealing ring also comprising an outer surface, the outer surface of the sealing ring pressing against the inner surface of the side wall; and a filter comprising at least one filter element, the filter having an upper surface and a lower surface, the filter being compressed between the lower surface of the lip and the top surface of the rib arrangement. Typically, the top surface of the rib arrangement is spaced away from the inner surface of the side wall. Preferably, the lower surface of the lip has a width that is at least the width of the top surface of the rib arrangement.

A well for processing fluid according to another embodiment of the invention comprises a hollow tube comprising a side wall having an inner surface and an inwardly extending lip, the lip having a rib arrangement projecting downwardly from the lip, the rib arrangement having a bottom surface; a bottom end comprising a bottom wall and a fluid flow port and a sealing ring comprising an outer surface and a top surface, the outer surface of the sealing ring pressing against the inner surface of the side wall of the tube, and a filter comprising at least one filter element, the filter having an upper surface and a lower surface, the filter being compressed between the top surface of the sealing ring and the bottom surface of the rib arrangement.

In some embodiments of the well, the bottom end also includes a drainage grid comprising at least one drainage channel communicating with the fluid flow port. For example, the bottom end can include a drainage grid comprising a plurality of drainage grid spacers projecting upwardly from the bottom wall, wherein a plurality of drainage channels are provided between the drainage grid spacers, and the drainage channels communicate with the fluid flow port.

In accordance with another embodiment, a plurality of the wells are connected together to provide a multiple well device, e.g., in the form of a 96 or 384 well device, in some embodiments, a 96 or 384 well tray.

Methods are also provided for processing a fluid utilizing embodiments of the well and the multiple well devices. Suitable methods include, for example, microtitration, microfiltration, and microculture procedures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a top view of an embodiment of a base suitable for use in a multiple well device according to the present invention, showing a first well including filter and a sealing ring, a second well including a rib arrangement and fluid flow port, and a third well including a rib arrangement, a drainage grid, and a fluid flow port.

FIG. 2 shows a partial cross-sectional view of a portion of the base including the third well shown in FIG. 1, showing the inner surface of the side wall of the well, the bottom wall of the well, as well as the rib arrangement and the drainage grid projecting upwardly from the bottom wall.

FIG. 3 shows an enlarged top view of the third well shown in FIG. 1, the well including the rib arrangement, the drainage grid, and the fluid flow port.

FIG. 4 shows an embodiment of a sealing ring. FIG. 4a shows a top view, and FIG. 4b shows a cross-section view along lines 4b--4b in FIG. 4a.

FIG. 5 shows partial cut away views of a portion of a well according to an embodiment of the invention, showing a sealing ring, a filter, a rib arrangement, and a drainage grid. FIG. 5a shows an exploded view, and FIG. 5b shows an assembled view wherein the sealing ring is retained such that the outer surface of the sealing ring presses against the inner surface of the side wall of the well, and the bottom surface of the ring presses against the upper surface of the filter while the top surface of the rib arrangement presses against the lower surface of the filter so that the filter is sealed in the well.

FIG. 6 shows a partial cross-sectional view of another embodiment of a multiple well device according to the invention, showing a top plate including a plurality of sealing rings, and a bottom plate including the bottom ends of a plurality of wells, wherein each end includes a bottom wall, a fluid flow port, and a rib arrangement projecting upwardly from the bottom wall, herein the sealing ring is retained such that the outer surface of the sealing ring presses against the inner surface of the side wall of the well, and the bottom surface of the ring presses against the upper surface of the filter while the top surface of the rib arrangement presses against the lower surface of the filter so that the filter is sealed in the well.

FIG. 7 shows a top view of the bottom plate shown in FIG. 6, showing the bottom ends of a plurality of wells, wherein each end includes a bottom wall, a fluid flow port, and a rib arrangement projecting upwardly from the bottom wall.

FIG. 8 shows a top view of the bottom plate including the bottom end of one of the wells shown in FIG. 6, showing a bottom wall, a rib arrangement, and a fluid flow port.

FIG. 9 shows a top view of the top plate shown in FIG. 6.

FIG. 10 shows partial cross-sectional views of the plates shown in FIG. 6. FIG. 10a shows a partial cross-sectional view of the top plate, and FIG. 10b shows a partial cross-sectional view of the bottom plate.

FIG. 11 shows a partial cross-sectional view of another embodiment of a multiple well device according to the invention, showing an assembled well and an exploded view of a well. The Figure shows a top plate including inwardly extending lips, wherein each lip has a bottom surface; and individual lower chambers, each chamber including the bottom end of a well, wherein each bottom end includes a bottom wall, a fluid flow port, and a sealing ring comprising a rib arrangement projecting upwardly from the bottom wall, wherein the sealing ring is retained such that the outer surface of the sealing ring presses against the inner surface of the side wall of the well, and the bottom surface of the lip presses against the upper surface of the filter while the top surface of the rib arrangement presses against the lower surface of the filter, so that the filter is sealed in the well.

FIG. 12 shows a cut away view of the lower chamber of one of the wells shown in FIG. 11, showing the bottom end of the well, including a bottom wall, a fluid flow port, and a sealing ring comprising a rib arrangement projecting upwardly from the bottom wall.

FIG. 13 shows a top view of the bottom end of the well shown in FIG. 11, showing a bottom wall, a rib arrangement, a drainage grid, and a fluid flow port.

FIG. 14 shows a top view of the top plate shown in FIG. 11.

FIG. 15 shows a partial cross-sectional view of the top plate shown in FIG. 14.

FIG. 16 shows a partial cross-sectional view of another embodiment of a multiple well device according to the invention, showing an assembled well and an exploded view of a well. The Figure shows a top plate including inwardly extending lips, wherein each lip has a rib arrangement projecting downwardly from the lip; and individual lower chambers, each chamber including the bottom end of a well, wherein each bottom end includes a bottom wall, a fluid flow port, and a sealing ring having an outer surface and a top surface, wherein the sealing ring is retained such that the outer surface of the sealing ring presses against the inner surface of the side wall of the well, and the bottom surface of the rib arrangement presses against the upper surface of the filter while the top surface of the sealing ring presses against the lower surface of the filter, so that the filter is sealed in the well.

FIG. 17 shows a top view of the bottom end of the well shown in FIG. 16, showing a bottom wall, a drainage grid, and a fluid flow port.

FIG. 18 shows a cut away view of the lower chamber of one of the wells shown in FIG. 16, showing the bottom end of the well, including a bottom wall, a fluid flow port, and a sealing ring.

FIG. 19 shows a partial cross-sectional view of the top plate shown in FIG. 16.

DETAILED DESCRIPTION OF THE INVENTION

In one embodiment of the present invention, a well for use in processing a fluid comprises a hollow tube having an axis, the tube comprising a side wall having an inner surface; upper and lower axially spaced ends, the lower end comprising a bottom wall and a fluid flow port, and a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface spaced from the inner surface of the side wall; a sealing ring having an outer surface and a bottom surface, the outer surface of the sealing ring pressing against the inner surface of the side wall; and a filter comprising at least one filter element, the filter having a upper surface and a lower surface, the filter being compressed between the bottom surface of the sealing ring and the top surface of the rib arrangement. Preferably, the bottom surface of the sealing ring has a radial width that is at least the radial width of the top surface of the rib arrangement. Typically, the sealing ring seals the filter against the rib arrangement wherein the bottom surface of the sealing ring presses against the upper surface of the filter while the top surface of the rib arrangement presses against the lower surface of the filter. In some embodiments, the sealing ring has a hollow bore suitable for receiving fluid, wherein the bore substantially extends to the upper end of the tube.

A well for use in processing a fluid according to another embodiment of the invention comprises a hollow tube having an axis, the tube comprising a side wall having an inner surface; upper and lower axially spaced ends, the lower end comprising a bottom wall, a fluid flow port, a drainage grid arrangement comprising at least one drainage grid spacer projecting upwardly from the bottom wall, and a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface spaced from the inner surface of the side wall of the tube; a filter comprising at least one filter element, the filter having an upper surface and a lower surface; and a sealing ring sealing the filter against the rib arrangement, the sealing ring having an outer surface, and a bottom surface, the bottom surface having a radial width that is at least the radial width of the top surface of the rib arrangement, the outer surface of the sealing ring pressing against the inner surface of the side wall of the tube, and the bottom surface of the ring pressing against the upper surface of the filter while the top surface of the rib arrangement presses against the lower surface of the filter.

In yet another embodiment of the present invention, a well for use in processing a fluid comprises a hollow tube having an axis, the tube comprising a side wall having an inner surface and a lip extending inwardly from the side wall, the lip having a lower surface; upper and lower axially spaced ends, the lower end comprising a bottom wall and a fluid flow port, and a sealing ring comprising a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface; the sealing ring comprising an outer surface and the top surface of the rib arrangement, the outer surface of the sealing ring pressing against the inner surface of the side wall; and a filter comprising at least one filter element, the filter having a upper surface and a lower surface, the filter being compressed between the lower surface of the lip and the top surface of the rib arrangement. Typically, the top surface of the rib arrangement is spaced from the inner surface of the side wall. Preferably, the top surface of the rib arrangement has a radial width that is at least the radial width of the lower surface of the lip. Typically, the sealing ring seals the filter against the rib arrangement wherein the top surface of the sealing ring presses against the lower surface of the filter while the lower surface of the lip presses against the upper surface of the filter.

A well for use in processing a fluid according to another embodiment of the invention comprises a hollow tube having an axis, the tube comprising a side wall having an inner surface and a lip extending inwardly from said side wall, the lip having a lower surface; upper and lower axially spaced ends, the lower end comprising a bottom wall and a fluid flow port and a sealing ring comprising an outer surface and a top surface, the outer surface of the sealing ring pressing against the inner surface of the side wall of the tube; a filter comprising at least one filter element, the filter having an upper surface and a lower surface, the filter being compressed between the top surface of the sealing ring and the lower surface of the lip. In a preferred embodiment, the lip comprises a rib arrangement projecting downwardly from the lip, more preferably, wherein the rib arrangement has a bottom surface spaced from the inner surface of the side wall, and the filter is compressed between the top surface of the sealing ring and the bottom surface of the rib arrangement. In another embodiment, the sealing ring further comprises a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface, wherein the filter is compressed between the top surface of the rib arrangement and the lower surface of the lip. The top surface of the rib arrangement can be spaced from the inner surface of the side wall.

In accordance with another embodiment, a microtitration or microfiltration device is provided comprising a well comprising a hollow tube having an axis, the tube comprising a side wall having an inner surface, upper and lower axially spaced ends, the lower end comprising a bottom wall, a drainage grid comprising at least one drainage channel, and a fluid flow port, and a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface that does not contact the inner surface of the side wall of the tube, a filter comprising at least one filter element, the filter having an upper surface and a lower surface, and a sealing ring sealing the filter against the rib arrangement, the sealing ring having an outer surface, and a bottom surface, the bottom surface having a width that is at least the width of the top surface of the rib arrangement, the outer surface of the sealing ring pressing against the inner surface of the side wall of the tube, and the bottom surface of the ring pressing against the upper surface of the filter while the top surface of the rib arrangement presses against the lower surface of the filter.

In accordance with another embodiment, a device for culturing a cell suspension or tissue comprises a well for receiving a cell suspension or tissue, the well having a side wall having an inner surface, a bottom end comprising a bottom wall and a fluid flow port, and a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface that does not contact the inner surface of the side wall; a filter sealed in the well, the filter comprising at least one filter element suitable for culturing the cell suspension or tissue, the filter having a upper surface and a lower surface; and a sealing ring sealing the filter against the rib arrangement, the sealing ring having an outer surface, and a bottom surface, the bottom surface having a width that is at least the width of the top surface of the rib arrangement, the sealing ring pressing against the inner surface of the side wall, and the bottom surface of the ring pressing against the upper surface of the filter while the top surface of the rib arrangement presses against the lower surface of the filter. Typically, device further comprises a culture medium contained in the well.

In more preferred embodiments of the invention, a plurality of wells are connected together to provide a multiple well device. In accordance with embodiments of the invention, the potential for cross-contamination from one well to another can be eliminated.

An embodiment of a multiple well device according to the invention comprises a plurality of wells for receiving liquid samples to be processed, each well having a side wall having an inner surface, a bottom end comprising a bottom wall and a fluid flow port, and a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface spaced from the inner surface of the side wall; a sealing ring having an outer surface, and a bottom surface, the outer surface of the sealing ring pressing against the inner surface of the side wall of the tube; and a filter comprising at least one filter element, the filter having a upper surface and a lower surface, the filter being compressed between the bottom surface of the sealing ring and the top surface of the rib arrangement.

In another embodiment, a multiple well device comprises a plurality of wells for receiving liquid samples to be processed, each well comprising a side wall having an inner surface, a bottom end comprising a bottom wall and a fluid flow port, and a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface that does not contact the inner surface of the side wall; a filter comprising at least one filter element, the filter having a upper surface and a lower surface; and a sealing ring sealing the filter against the rib arrangement, the sealing ring having an outer surface and a bottom surface, the bottom surface having a width that is at least the width of the top surface of the rib arrangement, the outer surface of the sealing ring pressing against the inner surface of the side wall, and the bottom surface of the ring pressing against the upper surface of the filter while the top surface of the rib arrangement presses against the lower surface of the filter.

In some embodiments of multiple well devices according to the invention, the device comprises at least a top plate and a bottom plate, wherein the top plate comprises the sealing ring, and the bottom plate comprises the bottom wall and the rib arrangement. In one embodiment wherein the top plate comprises the sealing ring, the sealing ring has a hollow bore that substantially extends to the top surface of the plate.

In accordance with another embodiment, a multiple well device comprises a plurality of wells for receiving liquid samples to be processed, each well comprising a side wall having an inner surface and a lip extending inwardly from the side wall, the lip having a lower surface; a bottom end comprising a bottom wall and a fluid flow port and sealing ring comprising a rib arrangement projecting upwardly from the bottom wall, the rib arrangement having a top surface that does not contact the inner surface of the side wall, the sealing ring comprising an outer surface; and a filter comprising at least one filter element, the filter having a upper surface and a lower surface; the outer surface of the sealing ring pressing against the inner surface of the side wall; and the lower surface of the lip pressing against the upper surface of the filter while the top surface of the rib arrangement presses against the lower surface of the filter.

In accordance with an embodiment of the invention, a multiple well device comprises a plurality of wells for receiving liquid samples to be processed, each well comprising a side wall having an inner surface and a lip extending inwardly from the side wall, the lip having a rib arrangement projecting downwardly from the lip, the rib arrangement having a bottom surface that does not contact the inner surface of the side wall; a bottom end comprising a bottom wall and a fluid flow port and a sealing ring comprising an outer surface and a top surface, wherein the bottom wall of the bottom end comprises the top surface of the sealing ring; and a filter comprising at least one filter element, the filter having a upper surface and a lower surface; the outer surface of the sealing ring pressing against the inner surface of the side wall; and the top surface of the sealing ring pressing against the lower surface of the filter while the bottom surface of the rib arrangement presses against the upper surface of the filter.

Another embodiment of a multiple well device according to the invention comprises a top plate comprising the upper ends of a plurality of wells; a plurality of separate inserts comprising the lower ends of the plurality of wells, each insert comprising a bottom wall and a fluid flow port; and a plurality of filters, each filter comprising at least one filter element, wherein each filter is sealed between the top plate and an insert. In some embodiments, the top plate includes a plurality of sealing rings, and in some other embodiments, each insert comprises a sealing ring.

Yet another embodiment of a multiple well device according to the invention comprises a bottom plate comprising the bottom ends of a plurality of wells, each bottom end comprising a bottom wall and a fluid flow port; a plurality of separate inserts comprising the upper ends of the plurality of wells; and a plurality of filters, each filter comprising at least one filter element, wherein each filter is sealed between the top plate and an insert. In some embodiments, the bottom plate includes a plurality of sealing rings, and in some other embodiments, each insert comprises a sealing ring.

Embodiments of multiple well devices include wells connected together in the form of, for example, a strip, disc, or tray. Multiple well devices can include integrally formed wells (e.g., formed by injection or blow molding), or the wells can be formed from a plurality of components, e.g., an upper plate, tray or insert defining the upper portion of the wells and/or the sealing ring, and a bottom plate, tray or insert defining at least the bottom wall of the wells.

The wells, and more preferably, the multiple well devices, are suitable for use with a variety of other components such as a chamber, plenum, manifold, manifold cover, or the like, e.g., for applying reduced pressure or vacuum to the wells. Accordingly, some embodiments of the wells and multiple well devices further comprise, for example, a manifold cover.

Embodiments of methods for using the wells and multiple well devices are also provided.

For example, one embodiment of a method for processing a fluid comprises passing a fluid into a well comprising a side wall having an inner surface, and a bottom end having a rib arrangement having a top surface, wherein the top surface of the rib arrangement is spaced from the inner surface of the side wall, and a fluid flow port; the well having a filter comprising at least one filter element sealed therein, the filter being compressed between a lower surface of a sealing ring, and the top surface of the rib arrangement, and, passing at least a portion of the fluid through the filter and through the fluid flow port at the bottom end of the well.

In another embodiment, a method for processing a fluid comprises passing a fluid into a device comprising a well comprising a side wall having an inner surface, and a lip extending inwardly from said side wall, the lip having a lower surface; and lower end comprising a bottom wall and a fluid flow port and a sealing ring, the sealing ring comprising a top surface; the well having a filter comprising at least one filter element sealed therein, the filter being compressed between a lower surface of the lip, and the top surface of the sealing ring, and, passing at least a portion of the fluid through the filter and through the fluid flow port at the bottom end of the well.

Preferably, the method comprises processing fluid in a multiple well device, wherein fluid is passed into a plurality of wells as described above.

Embodiments of the method can include binding at least one component in the fluid to be processed to at least one binding agent in the well, in some embodiments, binding at least one component in the fluid to be processed to at least one binding agent in or on the filter. For example, embodiments of the method can include antigen-antibody binding, binding a nucleic acid in a sample to a complementary nucleic acid probe, binding ligands, and binding proteins. In some embodiments, at least one binding agent is a specific binding agent such as a monoclonal antibody or a nucleic acid probe that specifically binds to a component in the fluid to be processed. Other embodiments of the method include, for example, removing particulates from the fluid to be processed, and synthesizing desired materials in the wells. If desired, embodiments of the method also include analyzing the filtrate passing through the filter and/or analyzing the bound component (in some embodiments, after cleaving the bound component from the well).

Each of the components of the invention will now be described in more detail below, wherein like components have like reference numbers.

FIG. 1 shows a top view of a multiple well device 100 according to an embodiment of the invention, comprising a base or bottom plate 101 suitable for providing the bottom ends for a plurality of wells. FIG. 1 also shows an assembled well 50 according to an embodiment of the invention, as well as two non-assembled wells 51 and 52. Assembled well 50 comprises a side wall 10, a sealing ring 40, and a filter 20. While not shown in assembled well 50, the two non-assembled wells 51 and 52 show a bottom end 3, comprising a rib arrangement 5 and a fluid flow port 7 (all covered by filter 20 in the assembled well 50), and a side wall 10. Non-assembled well 52 also shows a drainage grid 80, as well as the rib arrangement 5.

FIG. 2 shows a partial cross-sectional view of a portion of the bottom plate 101 including the non-assembled well 52 shown in FIG. 1, showing the side wall 10 having an inner surface 2, and the bottom end 3, comprising a bottom wall 4, a rib arrangement 5 projecting upwardly from the bottom wall, the rib arrangement having a top surface 6, a drainage grid 80, and a fluid flow port 7.

FIG. 3 shows a top view of the non-assembled well 52 shown in FIG. 2, showing the side wall 10 having an inner surface 2, and the bottom end 3, comprising a bottom wall 4, a rib arrangement 5 having a top surface 6, a drainage grid 80, and a fluid flow port 7.

FIG. 4 shows an embodiment of a sealing ring 40. FIG. 4a shows a top view of sealing ring 40 having an outer surface 43, and FIG. 4b shows a cross-section view along lines 4b--4b in FIG. 4a, showing the top surface 42, the bottom surface 41, and the outer surface 43 of sealing ring 40.

The separate and/or partially assembled components shown in FIGS. 1 4 are shown arranged in FIGS. 5a (exploded view) and 5b (assembled view), that illustrate a partial cut away view of a device comprising a well according to an embodiment of the invention. Using FIGS. 5a and 5b for reference, the illustrated device 100 comprises a well 50 comprising a hollow tube, and a filter 20 having an upper surface 21 and a lower surface 22 (the filter comprising a filter element 25), interposed between a sealing ring 40 having a bottom surface 41, and a rib arrangement 5 having an top surface 6, wherein the lower surface 22 of the filter contacts the top surface 6 of the rib arrangement, and the upper surface 21 of the filter contacts the bottom surface 41 of the sealing ring. The hollow tube comprises a side wall 10 having an axis, the side wall 10 having an inner surface 2, the well having a top (or upper) end 1, and a bottom (or lower) end 3, wherein the ends are axially spaced, the bottom end 3 comprising a bottom wall 4 and a fluid flow port 7, and a rib arrangement 5 projecting upwardly from the bottom wall.

In the embodiment shown in FIG. 5b, the rib arrangement 5 has a raised portion such as a rib, ridge, or boss, and has a top surface 6 (that is preferably a non-planar surface, e.g., a rounded surface) disposed to contact the lower surface 22 of a filter 20 comprising at least one filter element 25. As will be described in more detail below (e.g., with reference to FIG. 16), in other embodiments of the rib arrangement, the arrangement has a surface disposed to contact the upper surface of a filter.

The top surface 6 of the rib arrangement illustrated in FIGS. 5a and 5b does not contact the inner surface 2 of the side wall of the well (the Figures show a depression between the top surface of the rib arrangement and the inner surface of the side wall), and the rib arrangement can be located a predetermined distance from the inner surface of the side wall. In this illustrated embodiment, a sealing ring 40 having a bottom surface 41, a top surface 42, and an outer surface 43, is retained against the inner surface of the hollow tubular wall, the outer surface 43 of the ring pressing against the inner surface 2 of the side wall (e.g., at location 30, that can be a predetermined position along the inner surface of the wall), and the lower surface 41 of the ring pressing against the upper surface 21 of the filter 20 while the top surface 6 of the rib arrangement 5 presses against the lower surface 22 of the filter. The sealing ring 40 efficiently seals the filter 20 in the well, typically by compressing the portion of the filter surface contacting the sealing ring lower surface 41 as the portion of the filter surface contacting top surface 6 is also compressed. Thus, fluid is prevented from bypassing the filter (i.e., passing around the edges of the filter rather than through the filter). Accordingly, fluid passes from the upper surface of the filter through the lower surface of the filter, and passes from the well through flow port 7.

Typically, the device, and more typically, the well, includes one or more additional components for more efficient fluid processing, e.g., to prevent masking or blocking of the filter. For example, using the illustrative embodiments shown in FIGS. 3, 8, 13, and 17 (described below) for reference, the bottom end can include a drainage grid comprising one or more spacers and/or channels arranged such that fluid passing through the filter passes along the drainage channels between the grid spacers and then through the fluid flow port.

In a preferred embodiment, the bottom end comprises a drainage grid comprising at least one, more preferably, at least two, and even more preferably, at least three, drainage grid spacers projecting upwardly from the bottom wall. Illustratively, as shown in FIG. 5a (cut away view), and shown in more detail in FIG. 3 (top view), the bottom end 3 comprises a drainage grid 80 comprising a drainage grid wall 85 (a portion of bottom wall 4), drainage grid spacers 81a d, 83a d and 84a d projecting upwardly from bottom wall 4, and drainage channels between the grid spacers (the drainage grid wall 85 forming the bottom of the drainage channels), wherein the drainage channels communicate with fluid flow port 7. Drainage grid spacers 81a d, 83a d, and 84a d, have top surfaces 82a d, 86a d, and 87a d, respectively.

The drainage grid can have a variety of configurations so long as the filter can be supported and sufficient space is allowed for the passage of filtrate. For example, in one embodiment (not shown), the spacers and/or channels can have a radial and/or circular configuration. Additionally, or alternatively, the drainage grid wall, the drainage channels and/or the drainage grid spacers can have, for example, a configuration sloping toward the fluid flow port 7. Fluid flow port 7 can have a tapered configuration if desired.

In some embodiments, e.g., using the embodiment illustrated in FIG. 2 for reference, the top surfaces of the drainage grid spacers (e.g., top surfaces 82a and 82c, that can be planar or non-planar) are substantially coplanar with the bottom wall 4 between the rib arrangement 5 and the inner surface 2 of the tube. If desired, this portion of the bottom wall (between the rib arrangement and the inner surface of the tube) can be substantially coplanar with the surface of the drainage grid wall 85, and other configurations can also be suitable.

The tubular wall is preferably cylindrical, but in some embodiments includes multiple sides, e.g., multiple flat sides in order to provide a pentagonal, hexagonal, heptagonal, or octagonal shape, or a combination of flat and rounded portions.

While the tubular wall of the well can include a tapered section, e.g., a reduction in the inner diameter of the well along a portion of the length of the wall, the wall is preferably not tapered at the location where the sealing ring is retained against the inner surface of the side wall.

The sealing ring is preferably arranged to be frictionally engaged against the inner surface of the side wall. Since the tubular wall is preferably cylindrical, the sealing ring 40 preferably comprises a generally annular ring, the sealing ring having an axis, and an outer surface 43.

In the embodiment illustrated in FIGS. 4b, 5a and 5b, the sealing ring also comprises a bottom surface 41. More preferably, the bottom surface 41 has a width dimension radially of the ring that is generally the same as the radial width of the top surface 6 of the circumferential rib arrangement 5. Since the sealing ring 40 is preferably frictionally engaged against the inner wall of the well at position 30, the outer surface 43 of the sealing ring before insertion in the well has a diameter that is larger than the inner diameter of the