The present invention relates to a multiwell filtration plate. More particularly, it relates to a multiple well filtration plate using inserts to provide various features and functions to the plate.
The use of multiwell filtration plates is well established in the life sciences. They have been used among things as microtiter plates, cell growth plates, drug candidate screening tools and high throughput systems for the recovery of DNA, RNA, SEQ products, proteins, peptides and the like.
They all encompass the same basic design features. There is a plate having a series of two or more wells, each well having an open top and a open bottom that is essentially closed in some manner, except for an outlet and a filter positioned at or above the outlet and sealed in a manner such that all fluid to filtered must pass through the filter before reaching the outlet. Typically a collection plate is positioned below the filtration plate to collect the filtrate.
These devices are of a few basic designs.
The first being where the well bottom is open and a filter is sealed across the bottom of the well to make a semipermeable outlet. Often an underdrain is attached below the filter and contains a series of spouts that direct the filtrate into the collection plate. See U.S. Pat. No. 4,902,481.
A second version takes a bottom insert or short plate having a series of two or more wells an open top and an essentially closed bottom except for an outlet and a top plate having a corresponding series of wells having an open top and an open bottom and a filter piece positioned between the two. The two plates are formed together into one integral unit be it by thermal bonding or by injection molding one of the plates to the other. See U.S. Pat. No. 4,948,442 or U.S. Pat. No. 6,391,241.
The third version is to form a single piece multiwell device having a series of two or more wells having an open top and an at least partially to substantially closed bottom and inserting a filter piece into each well and securing it at or near the bottom by a separate ring such as a gasket (See U.S. Pat. No. 5,116,496) or by heat sealing the filter to the bottom of the well (See U.S. Pat. No. 6,309,605).
All of these devices use some type of external pressure to cause the filtration, be it a positive pressure, generated by centrifugation or a positive pressure (higher than atmospheric) applied to the top of the wells or a vacuum applied to the bottom of the wells below the outlet.
These plates have typically been arranged in rows and columns where each row and each column is parallel to the all the other rows or columns respectively and perpendicular to the intervening columns and rows respectively.
The present invention relates to a multiwell plate having a series of wells, each well having an inner bore, an open top and a bottom, the bottom being sealed with a liquid permeable filter, and an insert contained within the inner bore of each well, each insert having an outer dimension the same or larger than that of the inner bore and a through bore of a dimension less than that of the outer dimension of the insert. The use of inserts allows one to take a standard one piece plate design with a heat sealed or otherwise bonded membrane and arrange for a universal plate format. The insert may act as a base for an extension plate that can be adhered, heat sealed or overmolded over the plate top and insert top to form deeper well plates that can provide appropriate capacities for certain applications. The plate conforms to the Society of Biological Standards Microplate Standards currently in application as an ANSI standard. Additionally, the inserts may be configured to give one a different well diameter (smaller, tapered, etc), to include various media such as chromatography resins, to include multiple layers of membrane, to control the sample volume to membrane and/or plastic surface area ratio, to control the liquid column height to volume ratio, and the like. A variety of inserts may be used in the same plate to create a minilab or diagnostic tool on a plate that is capable of sequentially or non-sequentially conducting several steps of a process on the same plate (e.g. filter, wash, bind, elute, label, etc). The insert itself may act as an active component or surface that plays a principal or secondary role in the process (i.e. be coated, have material mixed or molded directly into it) or on the contrary be particularly inert to reduce non-specific effects such as non-specific binding of proteins to the device surfaces.
It is an object of the present invention to provide a filtration device formed of a filtration plate containing two or more wells, each well having an open top and an essentially closed bottom forming an outlet to the well, each well having an inner bore formed of one or more sidewalls and a bottom surface and a filter permanently sealed to the bottom surface of each well and an insert fit into the inner bore of each well, said insert having an outer dimension substantially the same or in some cases slightly larger than that of the inner bore dimension, a height substantially the same as the inner bore depth above the filter and having a through bore of a dimension less than that of the inner bore of the well, the through bore having an open top and open bottom.
It is another object of the present invention to provide a filtration device having a plurality of wells and an insert contained within each of the wells and an extension plate formed above the filtration plate, the extension plate containing a series of wells equal in number and corresponding in position to the plurality of wells of the filtration plate.
It is a further object of the present invention to provide a filtration device comprising a filtration plate containing two or more wells, each well having an open top and an essentially closed bottom forming an outlet to the well, each well having an inner bore formed of one or more sidewalls and a bottom surface and an insert fit into the inner bore of each well, said insert having an outer dimension substantially the same or bigger than that of the inner bore dimension, a height substantially the same as the inner bore depth above the filter and having a through bore of a dimension less than that of the inner bore of the well, the through bore having an open top and open bottom and a filter permanently sealed to a surface of each insert.
It is an additional object of the present invention to provide a filtration device comprising a filtration plate containing two or more wells, each well having an open top and an essentially closed bottom forming an outlet to the well, each well having an inner bore formed of one or more sidewalls and a bottom surface and an insert fit into the inner bore of each well, said insert having an outer dimension substantially the same or bigger than that of the inner bore dimension, a height substantially the same as the inner bore depth above the filter and having a through bore of a dimension less than that of the inner bore of the well, the through bore having an open top and open bottom and a filter permanently sealed to the bottom surface of each insert.
It is another object of the present invention to provide a process of forming a multiwell filtration device comprising forming a filtration plate containing two or more wells, each well having an open top and an essentially closed bottom forming an outlet to each well, each well having an inner bore formed of one or more sidewalls and the bottom surface, inserting a filter into each well and sealing the filter to the bottom of each well with a process selected from the group consisting of heat bonding, vibration welding and adhesives, inserting an insert into the inner bore of each well, said insert having an outer dimension substantially the same as that of the inner bore dimension, a height substantially the same as the inner bore depth above the filter and having a through bore of a dimension less than that of the inner bore of the well and the through bore having an open top and open bottom.
It is another object of the present invention to provide a process of forming a multiwell filtration device comprising forming a filtration plate containing two or more wells, each well having an open top and an essentially closed bottom forming an outlet to each well, each well having an inner bore formed of one or more sidewalls and the bottom surface, inserting a filter into each well and sealing the filter to the bottom of each well with a process selected from the group consisting of heat bonding, vibration welding and adhesives, inserting an insert into the inner bore of each well, said insert having an outer dimension substantially the same or larger than that of the inner bore dimension, a height substantially the same as the inner bore depth above the filter and having a through bore of a dimension less than that of the inner bore of the well, the through bore having an open top and open bottom and forming an extension plate on top of the filtration plate, the extension plate containing a series of two or more wells equal in number and corresponding in position to the two or more wells of the filtration plate.
It is another object of the present invention to provide a process of forming a multiwell filtration device comprising forming a filtration plate containing two or more wells, each well having an open top and an essentially closed bottom forming an outlet to each well, each well having an inner bore formed of one or more sidewalls and the bottom surface, selecting an insert, sealing a filter to the bottom of the insert with a process selected from the group consisting of heat bonding, vibration welding and adhesives, inserting an insert into the inner bore of each well, said insert having an outer dimension substantially the same or larger than that of the inner bore dimension, a height substantially the same as the inner bore depth above the filter and having a through bore of a dimension less than that of the inner bore of the well, the through bore having an open top and open bottom and forming an extension plate on top of the filtration plate, the extension plate containing a series of two or more wells equal in number and corresponding in position to the two or more wells of the filtration plate.
It is a further object to provide the process of forming a filtration plate having a plurality of wells, fitting inserts within those wells and forming an extension plate containing a plurality of wells equal in number and corresponding in position to the plurality of wells of the filtration plate and thermally bonding the extension plate to the filtration plate.
It is an additional object to provide the process of forming a filtration plate having a plurality of wells, fitting inserts within those wells and forming an extension plate containing a plurality of wells equal in number and corresponding in position to the plurality of wells of the filtration plate by overmolding the extension plate to the filtration plate.
The present invention relates to a multiwell plate that has universal application. It may be formed of two or more wells, typically 24, 48, 96, 384 or 1536. The wells are typically arranged in uniform rows and columns (such as 8 by 12 for a 96 well plate design) although this is not a requirement of the invention.
The invention is comprised of three basic elements, a well plate having a plurality of wells, a filter element and an insert.
The wells 4 contain an insert 20. The insert has an outer dimension substantially the same or larger than that of the inner diameter of the well and a height substantially the same as the inner height of the well from the inner bottom surface to the top plate surface. The insert has a through bore 22 of a dimension less than that of the inner bore of the well, the through bore 22 having an open top 24 and open bottom 26 as shown in
The inside diameter of each well may be either the same as that of a conventional plate, typically 7 mm in diameter or it may be made slightly larger, such as 8.2 mm in diameter so that the inner diameter of the bore corresponds to that of the conventional plate. Additionally, the well inner diameter may be greater than that normally used but the inner bore of the insert may deliberately be made smaller than the normal diameter of a well. One advantage of using this design is that one may precisely control of the volume to surface area ratios of the resultant test well. This allows one to minimize the use of a precious or scarce chemical, such as a drug candidate by limiting the amount of volume in the well. Likewise, one can limit the amount of chromatography media in the well by selecting a smaller inner bore configuration. Due to the small sample volume normally processed through such a device, most of the media is not used in the process. The present invention provides a means for providing more than enough media capacity for the application at hand without undue waste of the media or creating excess hold up volume of the sample in the column.
The insert 20 may contact the filter 14 and may if desired slightly compress the outer the edge of the filter, but the filter has already been sealed to the well structure to form a liquid impermeable seal. The contact of the insert 20 to the filter 14 does not enhance the seal but merely eliminates any dead area in the device by covering over the portion 28 of the filter 14 that is sealed to the device.
The insert of
In a further alternative to any of the embodiments of
In
In
The present invention allows one to use one platform and make devices of infinite design by simply selecting the correct insert. The cost involved in designing and manufacturing multiple molds for each plate configuration is eliminated.
The type of membrane suitable for use in this invention is not particularly limited, and may be either an ultrafilter, a microporous filter, or other specialty membranes, such as absorptive particle filled membranes and the like.
Preferred UF filters include regenerated cellulose or polysulfone filters such as YMT™ or Biomax™ filters available from Millipore Corporation of Billerica, Mass.
Representative suitable microporous filters include nitrocellulose, cellulose acetate, regenerated cellulose, polysulphones including polyethersulphone and polyarylsulphones, polyvinylidene fluoride, polyolefins such as ultrahigh molecular weight polyethylene, low density polyethylene and polypropylene, nylon and other polyamides, PTFE, thermoplastic fluorinated polymers such as poly (TFE-co-PFAVE), polycarbonates. Such filters are well known in the art and available from a variety of sources, such as DURAPORE® filters, IMMOBILON® filters, ISOPORE™ polycarbonate filters and EXPRESS® filters available from Millipore Corporation of Billerica, Mass.
Specialty or particle filled filters such as EMPORE® filters available from 3M of Minneapolis, Minn., filters that have antibodies, antigens or other interactive materials contained on their surfaces or in their structures may also be used.
The type of prefilter, if used is also not limited in any particular way by the invention and can be any prefilter commonly used in such devices such as glass mats, paper, nonwoven plastics, woven glass or plastic fabrics, paper, plastic or other felts and the like.
Likewise, the plates, inserts and extension plates (if used) may be made from any plastic material used to form such devices. Polyolefins, particularly polypropylene and polyethylene, glass filled polypropylene, polycarbonates, polystyrenes, acrylics, BAREX® resin and the like, with or without fillers such as titanium dioxide to render them opaque are suitable materials for most applications. The selected materials should be capable of allowing a filter to seal to either the plate well surface or the insert surface as discussed above. If a heat seal is used to seal the insert into the well or if an overmold is used to form the extension, then the selected materials for each piece should be compatible with each other to form a good bond between them.
This application is a Divisional patent application of U.S. patent application Ser. No. 10/838,588 filed May 4, 2004, projected U.S. Pat. No. 7,658,886, Issue Date of Feb. 9, 2010, which is incorporated herein in it's entirety.
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Number | Date | Country | |
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Number | Date | Country | |
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Parent | 10838588 | May 2004 | US |
Child | 12658569 | US |