The present invention relates to multi-well platforms, lids, caddies and any combination thereof that are generally described in U.S. patent application Ser. No. 09/111,553, filed Jul. 7, 1998 (the '553 application); U.S. patent application Ser. No. 09/030,578, filed Feb. 24, 1998 (the '578 application), U.S. patent application Ser. No. 09/028,283, filed Feb. 24, 1998 (the '283 application), U.S. patent application Ser. No. 08/858,016, filed May 16, 1997 (the '016 application), U.S. patent application Ser. No. 08/867,567, filed Jun. 2, 1997 (the '567 application), U.S. patent application Ser. No. 08/868,018, filed Jun. 3, 1997 (the '018 application), U.S. patent application Ser. No. 08/867,584, filed Jun. 2, 1997 (the '584 application), and U.S. patent application Ser. No. 08/868,049, filed Jun. 3, 1997 (the '049 application); each of which is incorporated herein by reference. Designs for the multi-well platforms, lids, and caddies of the present invention have been set forth in the '578 application, the '283 application, the '567 application, the '018 application, the '584 application, and the '049 application. Designs for the multi-well platform have also been described in U.S. patent application Ser. No. 29/081,749, filed Jan. 7, 1998 (the '749 application), U.S. patent application Ser. No. 29/081,969, filed Jan. 12, 1998 (the '969 application) and U.S. patent application Ser. No. 29/081,976, filed Jan. 12, 1998 (the '976 application), each of which is incorporated herein by reference. The multi well platforms, lids, caddies and combinations described herein can be used in any of the methods or other aspects of the inventions described in the '578 application, the '283 application, the '016 application, the '567 application, the '018 application, the '584 application, or the '049 application.
Multi-Well Platforms
The multi-well platforms of the present invention are well suited for use in fluorescent based assays, but can be used for any appropriate purpose. These multi-well platforms comprise a frame, wherein said wells are disposed in said frame. The frame can be of any thickness, such as between about 0.5, 1, 2, 3, or 5 millimeters and 2, 3, 5, 10 or 20 millimeters. The frame can be made of any material, such as polymers, such as polystyrene or cycloolefins, or other materials, such as glass or quartz. The frame can be of any shape, and typically defines the footprint of the multi-well platform.
The bottom of the frame can be substantially flat, meaning in this instance that the bottom of the frame does not have additional structures, such as means to form a band of opaque material in the bottom when the frame and bottom are sealed together (see, U.S. Pat. No. 5,319,436 (Mann et al.)). Such bands of opaque material are preferred when the wall is chamfered, however, the present invention is useful with or without such bands of opaque material. The bottom of the frame can also include structures such as pins, grooves, flanges or other known structures or those developed in the future to orient the multi-well platform on another structure, such as a detector or another platform.
The multi-well platform can have a footprint of any shape or size, such as square, rectangular, circular, oblong, triangular, kidney, or other geometric or non-geometric shape. The footprint can have a shape that is substantially similar to the footprint of existing multi-well platforms, such as the standard 96-well microtiter plate, whose footprint is approximately 85.5 mm in width by 127.75 mm in length or other sizes that represent a current or future industry standard (see T. Astle, Standards in Robotics and Instrumentation, J. of Biomolecular Screening, Vol. 1 pages 163-168 (1996)). Multi-well platforms of the present invention having this footprint can be compatible with robotics and instrumentation, such as multi-well platform translocators and readers as they are known in the art.
Each well comprises a wall having less fluorescence than polystyrene wall of 100 to 70% of the wall's thickness, preferably at least 90 percent of the wall's thickness. These determinations can be made using fluorescent detection methods well known in the art, such as determining the fluorescence of appropriate sheets of the materials being compared or as described herein.
Typically, wells will be arranged in two-dimensional linear arrays on the multi-well platform. However, the wells can be provided in any type of array, such as geometric or non-geometric arrays. The number of wells can be no more than 864 wells, or greater than 864 wells, on a standard multi-well platform footprint. Larger numbers of wells or increased well density can also be easily accomplished using the methods of the claimed invention. Other commonly used number of wells include 1536, 3456, and 9600. The number of wells can be between about 50, 100, 200, 500, 700, 800 or 1000 wells and 150, 250, 600, 800, 1000, 2000, 4000 5000, or 10000 wells. Preferably, the number of wells can be between about 50 and 10000, more preferable between about 800 and 5000, and most preferably between about 900 and 4000. The number of wells can be a multiple of 96 within these ranges, preferably the square of an integer multiplied by 96.
Well volumes typically can vary depending on well depth and cross sectional area. Well volumes can range between about 0.5, 1, 5, 10, 25, 50, 75, 100 or 200 microliter and about 5, 15, 40, 80, 100, 200, 500, or 1000 microliters. Preferably, the well volume is between about 500 microliters and 500 microliters, more preferably between about 1 microliter and 200 microliter, and most preferably between about 0.5 microliters and 10 microliters.
Wells can be made in any cross sectional shape (in plan view) including, square, round, hexagonal, other geometric or non-geometric shapes, and combinations (intra-well and inter-well) thereof. Wells can be made in any cross sectional shape (in vertical view) including shear vertical or chamfered walls, wells with flat or round bottoms, conical walls with flat or round bottoms, and curved vertical walls with flat or round bottoms, and combinations thereof.
As shown in
As shown in
The wells can have a depth between about 0.5, 1, 2, 3, 4, 5, 10, 20, or 50 millimeters and about 5, 10, 20, 50, or 100 millimeters. Preferably, the well depth is between about 1 millimeter and 100 millimeters, more preferably between about 2 millimeters and 50 millimeters, and most preferably between about 3 millimeters and 20 millimeters.
The wells can have a diameter (when the wells are circular) or maximal diagonal distance (when the wells are not circular) between about 0.2, 0.5, 0.7, 1, 5, 10, or 50 millimeters and about 1, 5, 10, 20, 50, or 100 millimeters. Preferably, the well diameter is between about 0.5 and 100 millimeters, more preferably between about 1 and 50 millimeters, and most preferably, between about 2 and 20 millimeters.
The wells of the multi-well platform can comprise an optically opaque material that can interfere with the transmission of radiation, such as light, through the wall of a well or bottom of a well. Such optically opaque materials can reduce the background associated with optical detection methods. Optically opaque materials can be any known in the art or later developed, such as dyes, pigments or carbon black. The frame can be made of an optically opaque material, or the walls or bottom, or both, can be coated with an optically opaque material. The optically opaque material can prevent radiation from passing from one well to another, to prevent cross-talk between wells, so that the sensitivity and accuracy of the assay is increased. The optically opaque material can also be reflective, such as those known in the art, such as thin metal layers, mirror coatings, or mirror polish. Optically opaque materials can be coated onto any surface of the multi-well platform, or be an integral part of the frame or bottom as they are manufactured. Optically opaque material can prevent the transmittance of between about 100% to about 50% of incident light, preferably between about 80% and greater than 95%, more preferably greater than 99%.
Since most measurements will not typically require light to pass through the wall of the well, materials such as polymers can include pigments to darken well walls or absorb light. Such application of pigments will help reduce background fluorescence. Pigments can be introduced by any means known in the art, such as coating or mixing during the manufacture of the material or multi-well platform. Pigment selection can be based on a mixture of pigments to dampen all background inherent to the polymer, or a single pigment or ensemble of pigments selected to filter or absorb light at desired wavelengths. Pigments can include carbon black. Such pigmentation is generally not desired in embodiments where light is directed through the well wall as a method for illuminating the contents of the well.
Each well also comprises a bottom 11 having a high transmittance portion and having less fluorescence than a polystyrene-bottom of at least about 90 percent of said bottom's thickness. This property can be determined by comparing the fluorescence of an appropriate control bottom material with the fluorescence of a test material. These procedures can be performed using well known methods. The thickness of the bottom can vary depending on the overall properties required of the plate bottom that may be dictated by a particular application. Preferably, the bottom is a plate or film as these terms are known in the art. Such properties include the amount of intrinsic fluorescence, rigidity, breaking strength, and manufacturing requirements relating to the material used in the plate. Well bottom layers typically have a thickness between about 10, 15, 20, 50, 100, 200, or 300 micrometers and about 20, 50, 100, 200, 300, 450, 500, or 1000 micrometers. Preferably, the well bottom has a thickness between about 10 micrometers and 450 micrometers, more preferably between about 15 micrometers and 300 micrometers, and most preferably between about 20 micrometers and 100 micrometers.
The bottom of a well can have a high transmittance portion, typically meaning that either all or a portion of the bottom of a well can transmit light. As shown in
The bottom can produce about 200 percent or less of the fluorescence compared to glass of 100 microns thickness at excitation wavelengths between about 290, 300, 310, 320, or 350 to about 300, 340, 370, 400, or 420 nm and at emission wavelengths between about 290, 300, 350, 400, or 500 and about 400, 600, 800, or 1000 nm.
Preferably, the bottom of the multi-well platform can be substantially flat, e.g. having a surface texture between about 0.001 mm and 2 mm, preferably between about 0.01 mm and 0.1 mm (see, Surface Roughness, Waviness, and Lay, Am. Soc. of Mech. Eng. #ANSI ASME B46.1-2985 (1986)). If the bottom is not substantially flat, then the optical quality of the bottom and wells can decrease because of altered optical and physical properties of one or both. Furthermore, the bottom of the frame can be substantially flat within the meaning set forth in this paragraph.
One feature of the preferred multi-well platform of the present invention is their low intrinsic fluorescence. Bottom layers comprising cycloolefin typically produces about 100 to 200 percent or less of the fluorescence compared to glass of about 130 to 170 micrometers in thickness. Glass, particularly fused silica, is typically used a “gold standard” for comparison of relative fluorescence. Fluorescence and relative fluorescence can be measured using any reliable techniques known or developed in the art, preferably the techniques described herein are used. Preferably, the glass standard used herein to show the surprisingly low fluorescence of polymers such as cycloolefin is used as a standard. Preferably, the bottom typically produces about 100 to 200 percent or less of the fluorescence compared to glass of about 0.085 to 0.13 millimeters (85 to 130 micrometers) thick (for glass slides, see Thomas Scientific, MicroCover Glasses, No. 0, product No. 6661-B40). The amount of intrinsic fluorescence can be dictated, in part, by the layer thickness. In some applications that can tolerate particularly thin bottoms, such as applications where the bottom does not require significant structural strength, layer thickness can be quite thin (e.g., 20 to 80 microns) in order to reduce fluorescence arising from the bottom. The thinness of a bottom is usually also balanced against the difficulty of uniformly welding or generating thinner layers in manufacturing processes. The low relative fluorescence of the multi-well platform is usually present at excitation wavelengths between about 300 to 400 nm and at emission wavelengths between about 350 to 800 nm.
The bottom or wells can also include at least one or a plurality of living cells. The cells can be prokaryotic, such as bacteria, or eukaryotic, such as plant cells, mammalian cells, or yeast cells. The cells can include more than one type of cell, such as a mixture of different mammalian cells, or a mixture of prokaryotic and eukaryotic cells. Such embodiments are useful for cell based assays described herein and for growing cells using culture methods. The multi-well platforms of the invention can include a coating (e.g., polylysine or fibronectin) to enhance attachment of cells. Coatings can also include at least one substrate for a cell adhesion molecule, such as integrins. Such substrates are known in the art.
The multi-well platform of the present invention can include coatings or surface modifications to facilitate various applications of the plate as described herein and known or developed in the relevant art. Coatings can be introduced using any suitable method known in the art, including printing, spraying, radiant energy, ionization techniques or dipping. Surface modifications can also be introduced by appropriately derivatizing a polymer or other material, such as glass or quartz, before, during, or after the multi-well platform is manufactured and by including an appropriate derivatized polymer or other material in the bottom layer or frame. The derivatized polymer or other material can then be reacted with a chemical moiety that is used in an application of the plate. Prior to reaction with a chemical moiety, such polymer or other material can then provide either covalent or non-covalent attachment sites on the polymer or other material. Such sites in or on the polymer or other material surface can be used to attach moieties, such as assay components (e.g., one member of a binding pair), chemical reaction components (e.g., solid synthesis components for amino acid or nucleic acid synthesis), and cell culture components (e.g., proteins that facilitate growth or adhesion). Examples of derivatized polymers or other materials include those described by U.S. Pat. No. 5,583,211 (Coassin et al.) and others known in the art or later developed. Particularly preferred embodiments are based on polyethylene and polypropylene derivatives that can be included as cycloolefin copolymers.
The materials for manufacturing the multi-well platform will typically be polymeric, since these materials lend themselves to mass manufacturing techniques. However, other materials can be used to make the frame or bottom of the multi-well platform, such as glass or quartz. The frame and bottom can be made of the same or different materials and the bottom can comprise polystyrene, or another material. Preferably, polymers are selected that have low fluorescence or other properties using the methods described herein. The methods herein can be used to confirm that selected polymers possess the desire properties. Polymeric materials can particularly facilitate plate manufacture by molding methods known in the art and developed in the future, such as insert or injection molding.
Generally, the multi-well platforms of the present invention comprise two regions, a well field and a border. The well field can have any structure (or lack of structure), preferably having any number of wells, more preferably about 3,456 wells (see, FIG. 7). The wells can be of any shape and can be arranged in any ornamental pattern, including patterns such as hexagonal arrays. In
The border can be any dimension, shape, or thickness, but preferably forms a multi-well platform with outer dimensions that are similar to those of a standard 96-well microtiter plate. As shown in FIG. 14 and
Preferred multi-well platforms are set forth in FIG. 49 and
The multi-well platform of the present invention can optionally be fitted with an ornamental lid. The lid comprises an area corresponding to the well field and a border (see, FIG. 63). The area corresponding to the well field can be any structure (or lack thereof) that is preferably substantially flat (see,
The multi-well platform of the present invention can optionally be fitted with an ornamental caddy (see, FIG. 107). The caddy has a footprint approximately that of a standard 96-well microtiter plate. When the multi-well platform is engaged with the caddy, the wells of the well-field of the multi-well platform are preferably not obscured by the caddy when viewed from the bottom of the combination (see, FIG. 120). The caddy can optionally have additional ornamentation on at least one of its four sides (see, FIG. 103). Additional ornamentation, such as for example, pins, grooves, flanges, indentations, can be optionally present on any surface of the caddy (see,
Any multi-well platform of the present invention can be engaged with any caddy of the present invention (see,
Other aspects of the present invention are provided in the figures, all of which are drawn approximately to scale. Generally, any multi-well platform, caddy, lid or combination thereof can have any feature or combination of features described herein.
The following provides drawings and descriptions of the multi well platforms, lids, caddies and combinations of the present invention.
FIG. 1: is a top plan view of a multi-well platform,
FIG. 2: is a bottom plan view thereof,
FIG. 3: is a left elevation view thereof,
FIG. 4: is a right elevation view thereof,
FIG. 5: is a front elevation view thereof,
FIG. 6: is a back elevation view thereof, and
FIG. 7: is a top, front, and right perspective view thereof.
FIG. 8: is a top plan view of a platform for a multi-well field,
FIG. 9: is a bottom plan view thereof,
FIG. 10: is a left elevation view thereof,
FIG. 11: is a right elevation view thereof,
FIG. 12: is a front elevation view thereof,
FIG. 13: is a back elevation view thereof, and
FIG. 14: is a top, front, and right perspective view thereof.
FIG. 15: is a top plan view of a platform for a multi-well field,
FIG. 16: is a bottom plan view thereof,
FIG. 17: is a left elevation view thereof,
FIG. 18: is a right elevation view thereof,
FIG. 19: is a front elevation view thereof,
FIG. 20: is a back elevation view thereof, and
FIG. 21: is a top, front, and right perspective view thereof.
FIG. 22: is a top plan view of a platform for a multi-well field,
FIG. 23: is a bottom plan view thereof,
FIG. 24: is a left elevation view thereof,
FIG. 25: is a right elevation view thereof,
FIG. 26: is a front elevation view thereof,
FIG. 27: is a back elevation view thereof, and
FIG. 28: is a top, front, and right perspective view thereof.
FIG. 29: is a top plan view of a platform for a multi-well field,
FIG. 30: is a bottom plan view thereof,
FIG. 31: is a left elevation view thereof,
FIG. 32: is a right elevation view thereof,
FIG. 33: is a front elevation view thereof,
FIG. 34: is a back elevation view thereof, and
FIG. 35: is a top, front, and right perspective view thereof.
FIG. 36: is a top plan view of a platform for a multi-well field,
FIG. 37: is a bottom plan view thereof,
FIG. 38: is a left elevation view thereof,
FIG. 39: is a right elevation view thereof,
FIG. 40: is a front elevation view thereof,
FIG. 41: is a back elevation view thereof, and
FIG. 42: is a top, front, and right perspective view thereof.
FIG. 43: is a top plan view of a multi-well platform having 3,456 wells,
FIG. 44: is a bottom plan view thereof,
FIG. 45: is a left elevation view thereof,
FIG. 46: is a right elevation view thereof,
FIG. 47: is a front elevation view thereof,
FIG. 48: is a back elevation view thereof, and
FIG. 49: is a top, front, and right perspective view thereof.
FIG. 50: is a top plan view of a multi-well platform having 3,456 wells,
FIG. 51: is a bottom plan view thereof,
FIG. 52: is a left elevation view thereof,
FIG. 53: is a right elevation view thereof,
FIG. 54: is a front elevation view thereof,
FIG. 55: is a back elevation view thereof, and
FIG. 56: is a top, front, and right perspective view thereof.
FIG. 57: is a top plan view of a lid for a multi-well platform,
FIG. 58: is a bottom plan view thereof,
FIG. 59: is a left elevation view thereof,
FIG. 60: is a right elevation view thereof,
FIG. 61: is a front elevation view thereof,
FIG. 62: is a back elevation view thereof, and
FIG. 63: is a top, front, and right perspective view thereof.
FIG. 64: is a top plan view of a lid for a multi-well platform,
FIG. 65: is a bottom plan view thereof,
FIG. 66: is a left elevation view thereof,
FIG. 67: is a right elevation view thereof,
FIG. 68: is a front elevation view thereof,
FIG. 69: is a back elevation view thereof, and
FIG. 70: is a top, front, and right perspective view thereof.
FIG. 71: is a top plan view of a lid for a multi-well platform,
FIG. 72: is a bottom plan view thereof,
FIG. 73: is a left elevation view thereof,
FIG. 74: is a right elevation view thereof,
FIG. 75: is a front elevation view thereof,
FIG. 76: is a back elevation view thereof, and
FIG. 77: is a top, front, and right perspective view thereof.
FIG. 78: is a top plan view of a lid for a multi-well platform,
FIG. 79: is a bottom plan view thereof,
FIG. 80: is a left elevation view thereof,
FIG. 81: is a right elevation view thereof,
FIG. 82: is a front elevation view thereof,
FIG. 83: is a back elevation view thereof,
FIG. 84: is a top, front, and right perspective view thereof, and
FIG. 85: is a cross-sectional view along lines 8—8 of FIG. 79.
FIG. 86: is a top plan view of a lid for a multi-well platform,
FIG. 87: is a bottom plan view thereof,
FIG. 88: is a left elevation view thereof,
FIG. 89: is a right elevation view thereof,
FIG. 90: is a front elevation view thereof,
FIG. 91: is a back elevation view thereof,
FIG. 92: is a top, front, and right perspective view thereof, and
FIG. 93: is a cross-sectional view along lines 8—8 of FIG. 87.
FIG. 94: is a top plan view of a lid for a multi-well platform,
FIG. 95: is a bottom plan view thereof,
FIG. 96: is a left elevation view thereof,
FIG. 97: is a right elevation view thereof,
FIG. 98: is a front elevation view thereof,
FIG. 99: is a back elevation view thereof, and
FIG. 100: is a top, front, and right perspective view thereof.
FIG. 101: is a top plan view of a caddy for a multi-well platform,
FIG. 102: is a bottom plan view thereof,
FIG. 103: is a left elevation view thereof,
FIG. 104: is a right elevation view thereof,
FIG. 105: is a front elevation view thereof,
FIG. 106: is a back elevation view thereof,
FIG. 107: is a top, front, and right perspective view thereof, and
FIG. 108: is a top, front, and left perspective view thereof.
FIG. 109: is a top plan view of a caddy for a multi-well platform,
FIG. 110: is a bottom plan view thereof,
FIG. 111: is a top plan view thereof with additional surface ornamentation,
FIG. 112: is a left elevation view thereof,
FIG. 113: is a right elevation view thereof,
FIG. 114: is a front elevation view thereof,
FIG. 115: is a back elevation view thereof,
FIG. 116: is a top, front, and right perspective view thereof,
FIG. 117: is a top, front, and left perspective view thereof, and
FIG. 118: is a bottom, front, and right perspective view thereof.
FIG. 119: is a top plan view of a combination of a multi-well platform and caddy,
FIG. 120: is a bottom plan view thereof,
FIG. 121: is a left elevation view thereof,
FIG. 122: is a right elevation view thereof,
FIG. 123: is a front elevation view thereof,
FIG. 124: is a back elevation view thereof,
FIG. 125: is a top, front, and right perspective view thereof, and
FIG. 126: is an exploded view thereof.
FIG. 127: is a top plan view of a combination of a multi-well platform, caddy and lid,
FIG. 128: is a bottom plan view thereof,
FIG. 129: is a left elevation view thereof,
FIG. 130: is a right elevation view thereof,
FIG. 131: is a front elevation view thereof,
FIG. 132: is a back elevation view thereof,
FIG. 133: is a top, front, and right perspective view thereof,
FIG. 134: is an exploded view thereof, and
FIGS. 135A and 135B: depict a cross-section of two embodiments of a multi-well platform.
This application is a continuation of and claims the benefit of the filing date of U.S. patent application Ser. No. 09/111,553, filed Jul. 7, 1998, now U.S. Pat. No. 6,426,050; which is a continuation-in-part of U.S. patent application Ser. No. 09/030,578, filed Feb. 24, 1998, now U.S. Pat. No. 6,171,780.
Number | Name | Date | Kind |
---|---|---|---|
4004150 | Natelson | Jan 1977 | A |
4154795 | Thorne | May 1979 | A |
4251159 | White | Feb 1981 | A |
4276259 | Eibl et al. | Jun 1981 | A |
D265124 | Terk | Jun 1982 | S |
D266589 | Gilford et al. | Oct 1982 | S |
D269702 | Suovaniemi et al. | Jul 1983 | S |
4431307 | Suovaniemi | Feb 1984 | A |
4468974 | Malinoff | Sep 1984 | A |
4545958 | Dopatka | Oct 1985 | A |
4626684 | Landa | Dec 1986 | A |
D288604 | Winston et al. | Mar 1987 | S |
4652553 | Hagmann et al. | Mar 1987 | A |
4657867 | Guhl et al. | Apr 1987 | A |
4689380 | Nahm | Aug 1987 | A |
4735778 | Maruyama et al. | Apr 1988 | A |
4741619 | Humphries et al. | May 1988 | A |
4770856 | Uthemann et al. | Sep 1988 | A |
4797259 | Matkovich et al. | Jan 1989 | A |
4828386 | Matkovich et al. | May 1989 | A |
4874808 | Minami et al. | Oct 1989 | A |
4892409 | Smith | Jan 1990 | A |
4899005 | Lane et al. | Feb 1990 | A |
4918133 | Moriya et al. | Apr 1990 | A |
4935475 | Kishimura et al. | Jun 1990 | A |
4948442 | Manns | Aug 1990 | A |
4948856 | Minchak et al. | Aug 1990 | A |
4956150 | Henry | Sep 1990 | A |
4968625 | Smith et al. | Nov 1990 | A |
4994354 | Toibana et al. | Feb 1991 | A |
D317360 | Gabrige | Jun 1991 | S |
5041266 | Fox | Aug 1991 | A |
5047215 | Manns | Sep 1991 | A |
5084246 | Lyman et al. | Jan 1992 | A |
5110556 | Lyman et al. | May 1992 | A |
5115052 | Wamura et al. | May 1992 | A |
5147780 | Pouletty et al. | Sep 1992 | A |
5149654 | Gross et al. | Sep 1992 | A |
5206306 | Shen | Apr 1993 | A |
5241012 | Clark | Aug 1993 | A |
5270393 | Sagane et al. | Dec 1993 | A |
5319436 | Manns et al. | Jun 1994 | A |
5395869 | Kawamoto et al. | Mar 1995 | A |
5428098 | Brekner et al. | Jun 1995 | A |
5456360 | Griffin | Oct 1995 | A |
5470757 | Gagnon et al. | Nov 1995 | A |
5487872 | Hafeman et al. | Jan 1996 | A |
5496502 | Thomson | Mar 1996 | A |
5516490 | Sanadi | May 1996 | A |
5532030 | Hirose et al. | Jul 1996 | A |
5534606 | Bennett et al. | Jul 1996 | A |
5540891 | Portmann et al. | Jul 1996 | A |
5545528 | Mitsuhashi et al. | Aug 1996 | A |
5583211 | Coassin et al. | Dec 1996 | A |
5604130 | Warner et al. | Feb 1997 | A |
5609826 | Cargill et al. | Mar 1997 | A |
5616461 | Schaffer et al. | Apr 1997 | A |
5670113 | Akong et al. | Sep 1997 | A |
5728541 | Kornblith | Mar 1998 | A |
5736400 | Moses et al. | Apr 1998 | A |
5738825 | Rudigier et al. | Apr 1998 | A |
5770860 | Franzen | Jun 1998 | A |
5789251 | Astle | Aug 1998 | A |
5792426 | Portmann et al. | Aug 1998 | A |
5858309 | Mathus et al. | Jan 1999 | A |
5876946 | Burbaum et al. | Mar 1999 | A |
5910287 | Cassin et al. | Jun 1999 | A |
6020444 | Riedel et al. | Feb 2000 | A |
6027695 | Oldenburg et al. | Feb 2000 | A |
6074614 | Hafeman et al. | Jun 2000 | A |
6083761 | Kedar et al. | Jul 2000 | A |
6232114 | Coassin et al. | May 2001 | B1 |
6258326 | Modlin | Jul 2001 | B1 |
Number | Date | Country |
---|---|---|
0 542 422 | Aug 1992 | EP |
08040914 | Feb 1996 | JP |
WO8607606 | Dec 1986 | WO |
WO9201513 | Feb 1992 | WO |
WO9201553 | Feb 1992 | WO |
WO9423839 | Oct 1994 | WO |
WO9522406 | Aug 1995 | WO |
WO9639481 | Dec 1996 | WO |
WO9705492 | Feb 1997 | WO |
Number | Date | Country | |
---|---|---|---|
20030039591 A1 | Feb 2003 | US |
Number | Date | Country | |
---|---|---|---|
Parent | 09111553 | Jul 1998 | US |
Child | 10209315 | US |
Number | Date | Country | |
---|---|---|---|
Parent | 09030578 | Feb 1998 | US |
Child | 09111553 | US |