WO2001085299A1

WO2001085299A1 - Centrifugal filtration apparatus

Info

Publication number: WO2001085299A1
Application number: PCT/US2000/012876
Authority: WO
Inventors: Peter Zuk, Jr.
Original assignee: Schleicher & Schuell, Inc.
Priority date: 1997-08-11
Filing date: 2000-05-11
Publication date: 2001-11-15
Also published as: US6156199A

Abstract

A filtration apparatus (186) for separating filtrate (191) and concentrate (190) from a solution that contains a dead stop feature. The dead stop volume is determined by the location of an outlet port (130). The apparatus includes a filtrate tube (104) for collecting filtrate and a filter unit insertable within the filtrate tube (104). The filter unit contains a semipermeable membrane filter element (102) thereon for separating filtrate from concentrate.

Description

CENTRIFUGAL FILTRATION APPARATUS

TECHNICAL FIELD

The present invention relates to the filtration field, and more particularly, to an improved centrifugal filtration apparatus for filtering and concentrating a solution. The improvement comprises eliminating any retentate pockets below the filter and instead employing a port on the filtrate side of the filter that is above the bottom level of the filter, thereby not permitting filtering to dryness.

RELATED APPLICATION

The present application is a continuation-in-part of Serial Number 09/132,358, filed

August 11, 1998, which is incorporated by reference hereto.

BACKGROUND ART

The filtration of fluids may be accomplished through the use of filtration devices which utilize microporous filters to filter and concentrate a macro-molecular solution is well known. This technique has been used in centrifugal filtration apparatuses that rely on centrifugal forces to create pressure in the apparatus to force solutions through a filter which separates liquid solutions into filtrate and concentrate.

There are certain drawbacks, however, associated with conventional centrifugal filtration apparatus. hUe many apparatus designs can prevent filtering to dryness in certain applications, they do not in other applications, such as a swinging bucket centrifuge. Those that work in both a fixed angle centrifuge and a swinging bucket centrifuge without filtering to dryness may present the problem of either retaining a different amount of concentrate when used in a fixed angle centrifuge than they will when used in a swinging bucket centrifuge or

_ 2 _ retaining a different amount of concentrate when used in fixed angle centrifuges with different fixed angles.

Some of the conventional centrifugal filtration apparatus require a second spin to remove the retained concentrate (i.e. dead stop volume). In these apparatus it is difficult or impossible to remove the retained concentrate from the concentrate tube with a pipette.

Another problem with some of the conventional centrifugal filtration apparatus is that as the concentrate volume approaches its final retained volume, the active filter area approaches zero. Therefore, the filtration rate will slow dramatically as the concentrate volume approaches its final retained volume.

Another problem with the conventional centrifugal filtration apparatus is that they are open systems (i.e. they contain a venting means that vents to the atmosphere in the centrifuge).

Yet another problem with some of the conventional centrifugal filtration apparatus is that they are not scaleable (i.e. they are designed to be used as small volume centrifugal filters, or large volume centrifugal filters, not both).

Certain types of filtration devices, such as that disclosed in U.S. Patent No. 4,632,761 to Bowers et alia, are capable of preventing filtration to dryness and contain a dead stop feature which causes filtration to cease while there is concentrate remaining within the apparatus. This device, however, filters to dryness when spun at a 90° angle and therefore the dead stop feature will not work if the device is spun in a swinging bucket centrifuge. Also, in this type of filtration device, the amount of concentrate remaining after dead stop is dependent upon the angle of the centrifuge rotor. The filter surface area in this type of device is limited by the diameter of the device, and the surface area is relatively small when compared to the volume of liquid solution within the housing. Another problem with this type centrifugal filtration apparatus is that is an open system (i.e. it contains a venting means that vents to the atmosphere in the centrifuge). This type of filtration device is conductive to clogging because the heaviest and denser molecules within the liquid solution are forced into the membrane filter. Accordingly, this device is limited because it will filter to dryness when spun in a swinging bucket centrifuge, it will filter to different dead stop volumes when used in fixed angle rotors with different angles, it is an open system and will vent potentially harmful gases to atmosphere during filtration, and its active filter surface area is limited by the diameter of the device.

The types of filtration devices disclosed in U.S. Patent No. 4,722,792 to Miyagi et alia are capable of preventing filtration to dryness and contain a dead stop feature which causes filtration to cease while there is concentrate remaining within the apparatus. In this type of filtration device, the amount of concentrate remaining after dead stop is dependent upon the angle of the centrifuge rotor. Therefore, the dead stop volume will be different when the device is used in a swinging bucket rotor centrifuge than it will be when used in a fixed angle rotor, and will also be different when the device is used in fixed angle rotor centrifuges of different rotor angle. This means that the results obtained from this type of device when used in one type of centrifuge rotor cannot be compared to the results obtained from this type of device when used in another type of centrifuge rotor. Another problem with this type centrifugal filtration apparatus is that is an open system (i.e. it must contain a venting means that vents to the atmosphere in the centrifuge). Another problem with this type of centrifugal filtration apparatus is that the filtration rate starts out high because of its relatively large filter surface area. However, as the concentrate volume approaches its dead stop volume, the active filter area approaches zero. Therefore, the filtration rate will slow dramatically as the concentrate volume approaches its final retained volume. Accordingly, this device is limited because it will filter to different dead stop volumes when used in centrifuge rotors with different angles, it is an open system and will vent potentially harmful gases to atmosphere during filtration, and the filtration rate will slow dramatically as the concentrate volume approaches the dead stop volume.

The types of filtration devices disclosed in U.S. Patent No. 5,112,484 to Zuk are capable of preventing filtration to dryness and contain a dead stop feature which causes filtration to cease while there is concentrate remaining within the apparatus. In this type of filtration device, the amount of concentrate remaining after dead stop is dependent upon the angle of the centrifuge rotor. Therefore, the dead stop volume will be different when the device is used in a swinging bucket rotor centrifuge than it will be when used in a fixed angle rotor, and will also be different when the device is used in fixed angle rotor centrifuges of different rotor angle. This means that the results obtained from this type of device when used in one type of centrifuge rotor cannot be compared to the results obtained from this type of device when used in another type of centrifuge rotor. Another problem with this type centrifugal filtration apparatus is that is an open system (i.e. it must contain a venting means that vents to the atmosphere in the centrifuge). Another problem with this type of centrifugal filtration apparatus is that as the concentrate volume approaches its final retained volume, the active filter area approaches zero. Therefore, the filtration rate will slow dramatically as the concentrate volume approaches its final retained volume. Although the retained concentrate can be removed from this device with a pipette, the retained concentrate is best removed from this type of device using the concentrate cup with a second spin. This type of device is not well suited to filter small volumes. Accordingly, this device is limited because it will filter to different dead stop volumes when used in centrifuge rotors with different angles, it is an open system and will vent potentially harmful gases to atmosphere during filtration, the filtration rate will slow dramatically as the concentrate volume approaches the dead stop volume, it is not designed to filter small volumes, and it is not easy to remove the dead stop volume with a pipette.

The types of filtration devices disclosed in U.S. Patent No. 5,490,927 to Herczeg are capable of preventing filtration to dryness and contain a dead stop feature which causes filtration to cease while there is concentrate remaining within the apparatus. In this type of filtration device, the amount of concentrate remaining after dead stop is dependent upon the angle of the centrifuge rotor. Therefore, the dead stop volume will be different when the device is used in a swinging bucket rotor centrifuge than it will be when used in a fixed angle rotor, and will also be different when the device is used in fixed angle rotor centrifuges of different rotor angle. This means that the results obtained from this type of device when used in one type of centrifuge rotor cannot be compared to the results obtained from this type of device when used in another type of centrifuge rotor. Another problem with this type centrifugal filtration apparatus is that is an open system (i.e. it must contain a venting means that vents to the atmosphere in the centrifuge). This type of device is not well suited to filter small volumes. This type of device utilizes the entire filter surface area until the dead stop volume is reached when used in a swinging bucket centrifuge. However when this type of device is used in a fixed angle rotor centrifuge the active filter area will approach zero as the concentrate volume approaches its final retained volume. Therefore, the filtration rate will slow dramatically as the concentrate volume approaches its final retained volume when used in a fixed angle centrifuge. This type of device requires a second spin to remove the retained concentrate solution. Accordingly, this device is limited because it will filter to different dead stop volumes when used in cenfrifuge rotors with different angles, it is an open system and will vent potentially harmful gases to atmosphere during filtration, the filtration rate will slow dramatically as the concentrate volume approaches the dead stop volume when used in a fixed angle rotor centrifuge, it is not designed to filter small volumes, and it requires a second spin to remove the retained concentrate solution.

Finally, the art discloses the use of a lower retentate pocket to address the issue of filtering to dryness with centrifugal filtration devices. U. S. 5,647, 990 to Nassarotti reveals a device having a concentrate retention pocket located at the bottom of a pre-filtration chamber, below the level of the filter membrane. Fluid flows through the filter into filtrate outlet channels, exiting these channels into the filtrate reservoir. These exit channels do not collect filtrate.

It is therefore an object of the present invention to provide a filtration device that may be used in a swinging bucket centrifuge, as well as a fixed angle centrifuge, without filtering to dryness.

It is also an object of the present invention to provide a filtration device that will filter to approximately the same dead stop volume when used in either a swinging bucket rotor centrifuge, or when used in a fixed angle rotor centrifuge.

It is also an object of the present invention to provide a filtration device having a relatively high filtration membrane surface area thereby enabling filtration to occur at a higher rate. It is also an object of the present invention to provide a filtration device that continues to use a relatively high filtration membrane surface area until the dead stop volume is attained, thereby enabling filtration to occur at a higher rate throughout the entire filtration process.

It is also an object of the present invention to provide a filtration device, which minimizes the clogging of the semi-permeable membrane thereby maximizing filter efficiency.

It is also an object of the present invention to provide a filtration device from which the retained concentrate solution can be easily removed with a pipette.

It is also an object of the present invention to provide a filtration device which can be used as a closed system (i.e. does not vent to atmosphere), or that can be used as an open system (i.e. vents to atmosphere).

It is a further object of the present invention to provide a filtration device, which can be manufactured as a disposable small volume device, or as a disposable large volume device.

DISCLOSURE OF THE INVENTION

The foregoing problems of the prior art are solved, and the objects of the present invention are achieved, by use of a filtration apparatus constructed in accordance with the principles of the present invention.

In accordance with the present invention, the filtration apparatus for filtering and concentrating a solution includes a concentrate tube, which is divided into two sections. The upper cylindrical section acts primarily as a reservoir for unfiltered solution and directs unfiltered solution from the upper section into the lower section of the concentrate tube. The upper section is shaped so that all of the solution in the upper section will flow into the lower section regardless of the centrifuge rotor angle. The lower section of the concentrate tube is mainly rectangular, but may be triangular shaped at the bottom. The volume of the lower section is made as small as possible to insure that the entire filter surface area is used to filter the maximum amount of solution. The lower section may contain a pipette tip channel to facilitate the removal of the retained concentrate with a pipette. The lower section is open on one side, or two sides.

A micro-porous membrane or membranes may be sealed to the lower section in several ways. First, the membrane can cover the open side of the lower section of the concentrate tube, of the membranes can cover the open sides of the lower section of the concentrate tube. Alternately the micro-porous membrane may be sealed to the filter cover, or covers. A second alternative is to seal the micro-porous membrane or membranes between the filter cover and a filter sealing gasket or gaskets. A third alternative is to seal the micro-porous membrane between the filter cover and the concentrate tube using a compression rib that compresses a portion of the outer periphery of the micro-porous filter between the filter cover and the concentrate tube.

A filter cover is sealed to the open side of the lower portion of the concentrate tube, or two filter covers are sealed to the two open sides of the lower portion of the concentrate tube. The filter cover or covers contain a filter support means such as filter support ribs. The filter cover or covers also contains a filtrate outlet port. The position of the filtrate outlet port or ports determines the retained concentrate volume. The concentrate tube may contain a port or ports to allow displaced filtrate air to flow into the upper part of the concentrate tube to replace the filtered solution that flows from the concentrate tube into the filtrate tube.

The means for collecting the filtrate may include a filtrate tube. The concentrate tube may be sealed into the filtrate tube. The filtrate tube cap may contain a means to nest the concentrate storage tube.

BRDSF DESCRIPTION OF THE DRAWINGS

These and other objects, features and advantages of the invention will be evident from the following detailed description when read in conjunction with the accompanying drawings. Figure 1 is an exploded isometric view of an embodiment of the filtration apparatus, constructed in accordance with the principles of the present invention, usable in a centrifuge.

Figure 2 is a partial isometric view of the lower section of the concentrate tube of an embodiment of the filtration device depicted in Figure 1.

Figure 3 is an exploded isometric view of the filter and filter cover of the embodiment of the filtration device depicted in Figure 1.

Figure 4 is a cross-sectional view of the concentrate tube assembly with concentrate tube cap, and the filtrate tube of the embodiment of the filtration device depicted in Figure 1. Figure 4 shows the fluid flow when the device is used in a swinging bucket centrifuge.

Figure 5 is a cross-sectional view of the concentrate tube assembly, the filtrate tube, and a pipette tip, of the embodiment of the filtration device depicted in Figure 1.

Figure 6 is an isometric view, having portions thereof removed, of the concentrate tube assembly of the embodiment of the filtration device depicted in Figure 1.

Figure 7 is a partial top view of a transparent concentrate tube assembly of the embodiment of the filtration device depicted in Figure 1, showing the retained concentrate in a 30° fixed angle rotor.

Figure 8 is a partial top view of a transparent concentrate tube assembly of the embodiment of the filtration device depicted in Figure 1, showing the retained concentrate in a swinging bucket rotor.

Figure 9 is a cross-sectional view of the filtrate tube, filtrate cap, and concentrate storage tube, of the embodiment of the filtration device depicted in Figure 1. Figure 10a is a partial top view of a transparent concentrate tube assembly of the embodiment of the filtration device depicted in Figure 1, showing the concentrate, and active filter area in a swinging bucket rotor.

Figure 10b is a partial top view of a transparent concentrate tube assembly of the embodiment of the filtration device depicted in Figure 1, showing the concentrate, and active filter area in a 30° fixed angle rotor in.

Figure 11 is an exploded isometric view of the components of a second embodiment of a filtration apparatus, constructed in accordance with the principles of the present invention, usable within a centrifuge.

Figure 12 is an isometric view, having portions thereof removed, of the concentrate tube of the embodiment of the filtration device depicted in Figure 11.

Figure 13 is a partial isometric view of the concentrate tube of the embodiment of the filtration device depicted in Figure 11.

Figure 14 is an isometric view, having portions thereof removed, of the concentrate tube of the embodiment of the filtration device depicted in Figure 11.

Figure 15 is an isometric view, having portions thereof removed, of the concentrate tube of the embodiment of the filtration device depicted in Figure 11.

Figure 16a is a top isometric view of the filter cover of the embodiment of the filtration device depicted in Figure 11.

Figure 16b is a bottom isometric view of the filter cover of the embodiment of the filtration device depicted in Figure 11.

Figure 17 is a cross-sectional view of the embodiment of the filtration device depicted in Figure 11, depicting the filtration device in a swinging bucket rotor. Figure 18 is a partial cross-sectional view of the concentrate tube assembly of the embodiment of the filtration device depicted in Figure 11, depicting the filter portion of the concentrate tube assembly.

Figure 19 is a cross-sectional view of the concentrate tube assembly, with a pipette tip, of the embodiment of the filtration device depicted in Figure 11.

Figure 20 is a partial top view of a transparent concentrate tube assembly of the embodiment of the filtration device depicted in Figure 11, showing the retained concentrate in a swinging bucket rotor.

Figure 21 is a partial top view of a transparent concentrate tube assembly of the embodiment of the filtration device depicted in Figure 11, showing the retained concentrate in a 30° fixed angle rotor.

Figure 22 is an isometric view, having portions thereof removed, of the concentrate tube assembly of the embodiment of the filtration device depicted in Figure 11.

Figure 23a is a partial top view of a transparent concentrate tube assembly of the embodiment of the filtration device depicted in Figure 11, showing the usable filter surface area in a swinging bucket rotor.

Figure 23b is a partial top view of a transparent concentrate tube assembly of the embodiment of the filtration device depicted in Figure 11, showing the usable filter surface area in a 30° fixed angle rotor.

Figure 24 is a cross-sectional view of the concentrate tube assembly with concentrate tube cap, and the filtrate tube of a second embodiment of the filtration device depicted in Figure 1. Figure 24 shows the fluid flow when the device is used in a swinging bucket centrifuge. Figure 25 is a partial isometric view of the lower section of the concentrate tube of a second embodiment of the filtration device depicted in Figure 1.

Figure 26 is an exploded isometric view of the components that make up the concentrate tube assembly of a third embodiment of a filtration apparatus, constructed in accordance with the principles of the present invention, usable within a centrifuge.

Figure 27 is an exploded isometric view, having portions thereof removed, of the concentrate tube assembly of the embodiment of the filtration device depicted in Figure 26.

Figure 28 is a partial cross-sectional view of the concentrate tube assembly of the embodiment of the filtration device depicted in Figure 26, depicting the filter portion of the concentrate tube assembly.

Figure 29 is a partial top view of the concentrate tube of the embodiment of the filtration device depicted in Figure 26, depicting the filter portion of the concentrate tube.

Figure 30 is a bottom isometric view of the filter cover of the embodiment of the filtration device depicted in Figure 26.

Figure 31 is an exploded isometric view having portions thereof removed, of the components that make up the concentrate tube assembly of a fourth embodiment of a filtration apparatus, constructed in accordance with the principles of the present invention, usable within a centrifuge.

Figure 32 is a partial isometric view of the concentrate tube of the embodiment of the filtration device depicted in Figure 31, depicting the filter portion of the concentrate tube.

Figure 33A is a bottom isometric view of the filter cover of the embodiment of the filtration device depicted in Figure 31. Figure 33B is a partial sectional view of the filter cover shown in Figure 33A, taken through AA.

Figure 34 is a partial cross-sectional view of the concentrate tube assembly of the embodiment of the filtration device depicted in Figure 31, depicting the filter portion of the concentrate tube assembly.

Figure 35 is a magnified view of the front portion of the partial cross-sectional view of the concentrate tube assembly shown in Figure 34.

Figure 36 is a partial isometric view, having portions thereof removed, of the concentrate tube of the embodiment of the filtration device depicted in Figure 31;

BEST MODES FOR CARRYING OUT THE INVENTION

As referred to herein, the term upstream refers to a location of the flow of liquid prior to filtration through the filter element within the filtration device of the present invention. Conversely, the term downstream refers to a location of the flow of liquid after filtration through the filter element within the filtration device of the present invention. The term concentrate refers to the unfiltered liquid on the upstream side of the filter element. The term filtrate refers to the filtered liquid on the downstream side of the filter element. The terms retained volume or dead stop volume refer to the concentrate that remains on the upstream side of the filter element after filtration is complete. The term swinging bucket rotor refers to a centrifuge rotor that swings to an angle of 90° from the vertical (i.e. horizontal). The term active filter surface area refers to the filter surface area inside of the filter seal. The term usable filter surface area refers to the portion of active filter surface area actually being used at a particular time. The term axial orientation refers to the orientation relative to a central axis (i.e. the axial orientation of a cylinder is the radial orientation of the cylinder relative to an axis passing through the center of the cylinder). Although various embodiments of the filtration device constructed in accordance with the principles of the present invention are disclosed herein, each embodiment enables the filtration device to keep the ratio of usable filter surface area to concentrate volume high throughout the filtration process. This can be best understood by referring to Figure 4. The radii shown in Figure 4 are defined as follows. R0 is the radius measured from the axis of rotation of the centrifuge to the top of the liquid on the upstream side of the device. RBF is the radius measured from the axis of rotation of the centrifuge to the bottom of the active filter surface area (Le. the bottom of the wetted portion of the filter), and also the bottom of the liquid on both the upstream and downstream sides of the filter. RTF is the radius measured from the axis of rotation of the centrifuge to the top of the active filter surface area (i.e. the top of the wetted portion of the filter). Rl is the radius measured from the axis of rotation of the centrifuge to the bottom of the outlet port of the filter cover. R can have a value measured from the axis of rotation of the centrifuge that is less in value than RBF and greater in value than or equal to R0. In the pressure drop calculations that follow the variable p refers to the liquid density, and the variable ω refers to the angular velocity of the centrifuge (ω=2π * (rev/sec)) .

Using the radii definitions defined in the previous paragraph the pressure drop across the filter can be calculated as follows.

First the pressure drop across the filter below the outlet port (i.e. Rl < R < RBF) can be calculated as follows:

UPSTREAMPRESSURE = jp juωt²r rdrr = — ^-{R² - RO²}

R 2

DOWNSTREAMPRESSURE = jpω²rdr = ^~- {R² - Rl²}

Rl ² Therefore the pressure drop across the filter at any radius R below the outlet port is:

Hence the region of the filter below the outlet port remains active until RO = Rl (i.e. the dead stop volume is reached). Second the pressure drop across the filter above the outlet port (i.e. RTF < R < Rl) can be calculated as follows:

UPSTREAMPRESSURE = {R² - RO² }

For RTF < R < Rl the downstream pressure is equal to zero.

From the above equations it can be seen that filtration will stop when RO = Rl (i.e. the dead stop volume is reached).

One embodiment of the filtration device constructed in accordance with the principles of the present invention, is shown in Figure 1, Figure 2, Figure 3, Figure 4, and Figure 6. This embodiment includes the following major components: concentrate tube 101, filter element 102, filter cover 103, concentrate tube cap 178, filtrate tube 104, filtrate tube cap 105, and concentrate storage tube 170.

Referring to Figure 1, Figure 2, and Figure 6 the concentrate tube assembly 185 contains concentrate tube 101, filter element 102, and filter cover 103. The concentrate tube assembly 185 contains a concentrate chamber, which is divided into two parts, an upper concentrate chamber 182, and a lower concentrate chamber 183. The upper concentrate chamber 182 is formed by cylindrical wall 110, conical wall 181, cylindrical wall 180, front tapered walls 123, side tapered walls 124, and top and bottom walls 176. The lower concentrate chamber 183 is formed by side walls 128, bottom wall 112, back wall 129, and the upstream side of filter element 102. Conical wall 181, tapered walls 123, and tapered walls 124 assure that as filtration occurs all of the liquid in the upper concentrate chamber 182 will flow into lower concentrate chamber 183 when the apparatus is used at any rotor angle from 28° to 90°, regardless of the axial orientation of the apparatus in the centrifuge rotor.

Referring to Figure 3, Figure 7, and Figure 8 the outer periphery of filter element 102 is bonded to rib 113 of filter cover 103. The bond is preferably a heat seal, but could be a glue seal, a solvent bond or any other type of leak tight seal. Filter cover 103 contains filtrate chamber 138 which is formed by top inside surface 139 of filter cover 103, interior side walls support ribs 131 protrude from top inside surface 132 of filter cover 103. Filter cover 103 also contains outlet port 130. As filtrate flows through filter element 102 into filtrate chamber 138, it collects in grooves 139 between filter support ribs 131, and grooves 139 between rib 113 and the filter support ribs 131. Filtrate flow from filtrate chamber 138 into outlet port 130 will be explained below.

Referring to Figure 2, Figure 3, Figure 4, and Figure 6, surface 132 of filter cover 103 is bonded to surface 172 of concentrate tube 101. The bond is preferably an ultrasonic weld, but could be a glue bond, a solvent bond, a heat bond, or any other type of leak tight bond. Outer walls 137 of filter cover 103 retain any weld flash.

The apparatus 186 is assembled, as shown in Figure 1, Figure 4, and Figure 6 for filtration by inserting the concentrate tube assembly 185 into filtrate tube 104 so that outer surface 143 of the concentrate tube assembly 185 engages the inner surface 142 of filtrate tube 104 with an interference fit. The solution to be filtered or concentrated is then placed within the concentrate tube assembly. The solution fills the lower concentrate chamber 183 of concentrate tube assembly 185, and partially fills the upper concentrate chamber 182 of concentrate tube assembly 185. Concentrate tube cap 178 is then placed on the top of concentrate tube 101. The assembled device 186 is then inserted into an appropriate centrifuge rotor to perform the filtration. Figure 4 shows the assembled device 186 oriented 90° from the vertical centrifuge axis (i.e. in the spinning swinging bucket rotor orientation).

Referring to Figure 1, Figure 3, and Figure 4 the centrifugal force created by the spinning centrifiige rotor causes the lower molecular weight molecules of concentrate 190 on the upstream side of filter element 102 to flow through filter element 102, into filtrate chamber 138. Chamber 138 of concentrate tube assembly 185 is in fluid flow relationship with the interior of filtrate tube 104 via outlet port 130 of filter cover 103. Hence, filtrate that flows through filter element 102 into filtrate chamber 138 will accumulate in the bottom filtrate chamber 138, until the filtrate level in filtrate chamber 138 reaches outlet port 130 of filter cover 103. At this point any additional filtrate will flow from filtrate chamber 138 through outlet port 130 into the interior 149 of filtrate tube 104. Vent grooves 119 on concentrate tube 101 allow air in the interior of filtrate tube 104 to be vented into the centrifuge 1/85299

atmosphere, the air being displaced by filtrate 191 in the interior of filtrate tube 104. Vent grooves 119 on concentrate tube 101 prevent pressure buildup in filtrate tube 104 as filtrate tube 104 fills with filtrate. Vent hole 151 on concentrate tube cap 178 allows air to enter the interior of the concentrate tube assembly 185 to replace the filtered liquid, and thus prevent a vacuum buildup in the interior of concentrate tube assembly 185.

The filtration process continues until the liquid level on both the concentrate side of filter element 102, and the filtrate side of filter element 102 reach the outer most edge of outlet port 130 of filter cover 103. The outer most edge of outlet port 130 of filter cover 103 is the edge of outlet port that is the furthest from the axis of rotation of the centrifuge rotor. Figure 8 shows this level for a swinging bucket centrifuge rotor, and Figure 7 shows this level for a fixed angle rotor. Once the liquid reaches the level shown in Figure 7 for a fixed angle rotor, or in Figure 8 for a swinging bucket rotor, the pressure on the upstream side of filter element 102 will be the same as the pressure on the downstream side of filter element 102, thus liquid flow through filter element 102 will stop. The concentrate that remains on the upstream side of the filter element when filtration is complete is called the retained concentrate volume, or dead stop volume. When device 186 is used in a swinging bucket rotor the dead stop volume will be the same regardless of filter orientation. That is to say the dead stop volume will be the same if filtration device 186 is placed in the swinging bucket centrifuge rotor so that the filter element is oriented parallel to a vertical plane as shown in Figure 8, or so that the filter element is oriented parallel to a horizontal plane as shown in Figure 4, or so that the filter element is oriented at any angle relative to either the horizontal or vertical planes.

The dead stop volume will be approximately the same for any centrifuge rotor angle from 28° to 90° when the filter element is oriented parallel to the vertical plane as shown in Figure 7. For any axial orientation of the apparatus in a swinging bucket rotor the centrifugal force will force more dense molecules in the solution being filtered away from the upstream filter surface toward the dead stop region of lower concentrate chamber 183, thus keeping the filter element clean and maximizing the filter elements efficiency. When the apparatus is oriented in a fixed angle rotor as shown in Figure 7 the centrifugal force will force the more dense molecules in the solution being filtered away from the upstream filter surface toward the dead stop region of lower concentrate chamber 183, thus keeping the filter element clean and maximizing the filter elements efficiency. When the apparatus is oriented in a fixed angle rotor 90° from the orientation shown in Figure 7, so that the centrifugal force forces the more dense molecules away from the upstream side of the filter element the efficiency of the filter element will also be maximized. At all other axial orientations of the apparatus in a fixed angle rotor the filter elements efficiency will be reduced.

As long as the upstream side of the lower chamber 183 of concentrate tube assembly 185 is filled with liquid the entire active surface area of filter element 102 will be used. Referring to Figure 10a and Figure 10b, as the liquid level in lower chamber 183 of concentrate tube assembly 185 fells the portion 187 of the active surface area of filter element 102 that is wet by upstream liquid 190 becomes the usable filter surface area. A substantial portion 187 of the active filter surface continues to be usable filter surface area throughout the entire filtration process. For the embodiment shown in Figures 1 through 10b the ratio of (usable surface area)/(concentrate volume) increases throughout the filtration process. Throughout the entire filtration process none of the downstream active filter surface area is occluded.

Referring to Figure 5 and Figure 9, when the filtration process is complete the user will remove the filtration device 186 from the centrifuge, and then remove the concentrate tube cap 178, and then remove the retained concentrate with the pipette tip 195 which will be attached to a pipette mechanism not shown. The retained concentrate can then be transferred from the pipette tip 195 to the concentrate storage tube 170. The concentrate tube assembly can then be removed from the filtrate tube 104 and discarded in a safe manner. The filtrate tube cap 105 can now be placed onto the filtrate tube. Filtrate tube cap 105 contains chamber 159 that is used to nest concentrate tube storage tube 170. This allows the concentrate sample and the filtrate sample to be conveniently stored together.

A second embodiment of the filtration device constructed in accordance with the principles of the present invention, is shown in Figure 11, Figure 12, Figure 13, Figure 14, and Figure 15, Figure 16a, Figure 16b, and Figure 17. This embodiment includes the following major components: concentrate tube 1, filter element 2, filter cover 3, filtrate tube 4, and filtrate tube cap 5. Referring to Figure 11, Figure 12, and Figure 13, Figure 14, Figure 15, and Figure 22 the concentrate tube assembly 85 contains concentrate tube 1, filter element 2, and filter cover 3. The concentrate tube assembly 85 contains a concentrate chamber, which is divided into two parts, an upper concentrate chamber 82, and a lower concentrate chamber 83. The upper concentrate chamber 82 is formed by cylindrical wall 10, front tapered walls 23, side tapered walls 24, and top and bottom walls 25. The lower concentrate chamber 83 is formed by side walls 28, bottom wall 12, back wall 29, the upper side walls of the pipette channel 27, the bottom pipette channel wall 11, the end pipette wall 62, and the upstream side of filter element 2. Tapered walls 23, and tapered walls 24 assure that as filtration occurs all of the liquid in the upper concentrate chamber 82 will flow into lower concentrate chamber 83 when the apparatus is used at any rotor angle from 28° to 90°, regardless of the axial orientation of the apparatus in the centrifuge rotor.

The outer periphery of filter element 2 is preferably bonded to surface 13 of concentrate tube 1. The filter element bond is preferably a heat seal, but could be a glue seal, a solvent bond or any other type of leak tight seal. The well formed by side walls 61 of concentrate tube 1 facilitates the placement of filter element 2 prior to sealing the filter to surface 13 of concentrate tube 1.

Referring to Figure 16a, Figure 16b, Figure 20, and Figure 21 the filter cover 3 contains a well 32 formed by inside top surface 39, and side walls 37. Filter support ribs 31 protrude from top surface 39. Grooves 45 are formed in-between and around filter support ribs 31 of filter cover 3 by the top surface 39 of filter cover 3 and the side walls of filter support ribs 31 of filter cover 3, and by the side walls 37 of well 32 of filter cover 3. Filter cover 3 can also contain energy director 33. Filter cover 3 also contains alignment grooves 35 and 36. Filter cover 3 also contains outlet port 30.

Referring to Figure 13, Figure 16b, Figure 18, and Figure 22, the concentrate tube assembly 85 is assembled as follows. The outer periphery of filter element 2 is preferably bonded to surface 13 of concentrate tube 1. The filter element bond is preferably a heat seal, but could be a glue seal, a solvent bond or any other type of leak tight seal. The well formed by side walls 61 of concentrate tube 1 facilitates the placement of filter element 2 prior to sealing the filter to surface 13 of concentrate tube 1. In an alternate embodiment, not shown, filter element 2 could be bonded to surface 38 inside energy director 33 of filter cover 3. Surface 34 of filter cover 3 is bonded to surface 22 of concentrate tube 1, preferably using energy director 33 of filter cover 3 and an ultrasonic weld to create bond 48. Bond 48 could however be a glue bond, a solvent bond, a heat bond, or any other leak tight bond. Once filter element 2 and filter cover 3 are bonded to concentrate tube 1, chamber 43 will be formed by well 32 of filter cover 3 (defined above), and the downstream surface of filter element 2. Chamber 43 is in fluid flow relationship with the outside atmosphere of filter cover 3 via outlet port 30 of filter cover 3. The user would purchase the concentrate tube assembly 85, assembled. Referring to Figure 11 and Figure 17, the concentrate tube assembly may contain rim gasket 7.

The filtration apparatus 86 is assembled by the user, as shown in Figure 11, Figure 15, Figure 17, and Figure 22 for filtration by inserting the concentrate tube assembly 85 into filtrate tube 4. There is a gap 80 between the outer surface 26 of concentrate tube 1 and the inner surface 42 of filtrate tube 4, because the outer surface 26 of concentrate tube 1 is smaller in diameter than the inner surface 42 of filtrate tube 4. To maximize the liquid capacity of concentrate tube 1 the gap 80 should be made as small as possible. The gap should however, be a minimum of 0.002 inches. The solution to be filtered or concentrated is then placed within the concentrate tube assembly 85. The solution fills the lower chamber 83 of concentrate tube assembly 85, and partially fills the upper chamber 82 of concentrate tube assembly 85. The filtrate tube cap 5 which contains filtrate tube gasket 6 is screwed onto the filtrate tube 4 so that the threads 51 of filtrate tube cap 5 engage the threads 41 of filtrate tube 4. After the filtrate tube cap 5 is secured to filtrate tube 4 the filtrate tube cap gasket 6 will be compressed between the inside surface 52 of filtrate cap 5 and the top of flange 18 of concentrate tube 1, thus sealing the top open end of concentrate tube 1. Likewise concentrate tube rim gasket 7 will be sealed between the bottom of concentrate tube flange 18 and the top rim 89 of filtrate tube 4. Hence the interior of filtrate tube 4, and the interior and exterior of concentrate tube assembly 85 will be sealed, and neither the interior of filtrate tube 4, or the exterior of concentrate tube 1, or the interior of concentrate tube 1 will be in fluid flow relationship, or in air flow relationship with the atmosphere outside of the filtrate tube 4. The assembled device 86 is then inserted into an appropriate centrifuge rotor to perform the filtration. Figure 17 shows the assembled device 86 oriented 90° from vertical (i.e. in a spinning swinging bucket rotor orientation).

Referring to Figure 11, Figure 17, and Figure 22 the centrifugal force created by the spinning centrifuge rotor causes the lower molecular weight molecules of concentrate 90 on the upstream side of filter element 2 to flow through filter element 2, into chamber 43. Hence, filtrate that flows through filter element 2 into chamber 43 will accumulate in the bottom of chamber 43, until the filtrate level in chamber 43 reaches outlet port 30 of filter cover 3. At this point any additional filtrate will flow from chamber 43 through outlet port 30 into the interior 49 of filtrate tube 4. Chamber 43 of concentrate tube assembly 85 is in fluid flow relationship with the interior of filtrate tube 4 via outlet port 30 of filter cover 3. Hence, filtrate that flows through filter element 2 into chamber 43 will flow from chamber 43 through outlet port 30 into the interior of filtrate tube 4. The interior of filtrate tube 4 is in air flow relationship with the interior of concentrate tube assembly 85, via the gap 80 between the outer surface 26 of concentrate tube 1 and the inner surface 42 of filtrate tube 4, vent grooves 19 on concentrate tube 1, and vent channels 20 on the top of flange 18 of concentrate tube 1. Therefore as filtrate enters the interior of filtrate tube 4 via port 30 of filter cover 3, the air that is displaced by this filtrate flows through gap 80 between the outside wall of concentrate tube assembly 85 and the inside wall of filtrate tube 4, through grooves 19 of concentrate tube 1, and channels 20 of the top of flange 18 of concentrate tube 1, into the interior of concentrate tube assembly 85 to replace the filtrate that flows from lower chamber 83 of the interior of concentrate tube assembly 85, through filter element 2, into chamber 43, through outlet port 30, into the interior of filtrate tube 4 Hence the pressure in the interior of filtrate tube 4, and the pressure in the interior of concentrate tube assembly 85 remain at atmospheric pressure throughout the filtration process. An additional benefit of securing the concentrate tube assembly 85 to filtrate tube 4, with filtrate tube cap 5 is that if the user accidentally drops the assembled apparatus its contents will not spill.

Alternatively, the filtration apparatus 86 may be assembled by the user, (as shown in

Figure 11, Figure 15, Figure 17, and Figure 22 for filtration), as described above, without installing concentrate tube rim gasket 7. In this case the interior of filtrate tube 4 will be in air flow relationship with the centrifuge atmosphere via gap 80 between the outer surface 26 of concentrate tube 1 and the inner surface 42 of filtrate tube 4, and via any gap that may exist between the bottom face of the concentrate tube flange and the top edge 89 of filtrate tube 4 because of imperfect mating between these two surfaces, and via the gap between the male threads 41 of filtrate tube 4 and the female thread 51 of filtrate tube cap 5. Hence air that is displaced by filtrate entering filtrate tube 4 may be vented to the centrifuge atmosphere. The interior of the concentrate tube assembly is in air flow relationship with the centrifuge atmosphere via vent channels 20 on the top of flange 18 of concentrate tube 1 and vent grooves 19 on concentrate tube 1, and via the gap between the male threads 41 of filtrate tube 4 and the female threads 51 of filtrate tube cap 5. Hence as the filtrate that flows from lower chamber 83 of the interior of concentrate tube assembly 85, through filter element 2, into chamber 43, through outlet port 30, into the interior of filtrate tube 4, it may be replaced by air from the centrifuge atmosphere. The interior of filtrate tube 4 will also be in air flow relationship with the interior of concentrate tube assembly 85, via the gap 80 between the outer surface 26 of concentrate tube 1 and the inner surface 42 of filtrate tube 4, vent grooves 19 on concentrate tube 1, and vent channels 20 on the top of flange 18 of concentrate tube 1. Therefore as filtrate enters the interior of filtrate tube 4 via port 30 of filter cover 3, the air that is displaced by this filtrate may also flow through grooves 19 of concentrate tube 1, and channels 20 of the top of flange 18 of concentrate tube 1, into the interior of concentrate tube 82 to replace the filtrate that flows from lower chamber 83 of the interior of concentrate tube assembly 85, through filter element 2, into chamber 43, through outlet port 30, into the interior of filtrate tube 4. Hence the pressure in the interior of filtrate tube 4, and the pressure in the interior of concentrate tube assembly 85 remain at atmospheric pressure throughout the filtration process.

The filtration process continues until the liquid level on the concentrate side of filter element 2, and the liquid level on the filtrate side of filter element 2 both reach the outer most edge of outlet port 30 of filter cover 3. The outer most edge of outlet port 30 of filter cover 3 is the edge of outlet port 30 that is the furthest from the axis of rotation of the centrifuge rotor. Figure 20 shows this level for a swinging bucket centrifuge rotor, and Figure 21 shows this level for a fixed angle rotor. Once the liquid reaches the level shown in Figure 21 for a fixed angle rotor, or in Figure 20 for a swinging bucket rotor, the pressure on the upstream side of filter element 2 will be the same as the pressure on the downstream side of filter element 2, thus liquid flow through filter element 2 will stop. The concentrate that remains on the upstream side of the filter element when filtration is complete is called the retained concentrate volume, or dead stop volume. If device 86 is used in a swinging bucket rotor the dead stop volume will be the same regardless of filter orientation. The dead stop volume will be the same if filtration device 86 is placed in the swinging bucket centrifuge rotor so that the filter element is oriented parallel to a vertical plane as shown in Figure 20, or so that the filter element is oriented parallel to a horizontal plane as shown in Figure 17, or so that the filter element is oriented at any angle relative to either the horizontal or vertical planes. The dead stop volume will be approximately the same for any fixed angle centrifuge rotor angle from 30° to 90° when the filter element is oriented parallel to the vertical plane as shown in Figure 21.

As long as the upstream side of the lower chamber 83 of concentrate tube assembly 85 is filled with liquid the entire active surface area of filter element 2 will be used. Referring to Figure 23 a and Figure 23b, as the liquid level in lower chamber 83 of concentrate tube assembly 85 falls the portion 87 of the active surface area of filter element 2 that is wet by upstream liquid 90 becomes the usable filter surface area. A substantial portion 87 of the active filter surface continues to be usable filter surface area throughout the entire filtration process. For the embodiment shown in Figures 11 through 23b the ratio of (usable surface area)/(concentrate volume) increases from the start of the filtration process until upper chamber 82 of concentrate tube assembly is empty. As lower chamber 83 of concentrate tube assembly goes from full to its dead stop volume the ratio of (usable surface area)/(concentrate volume) will decrease a small amount.

Referring to Figure 11, Figure 17, Figure 19, and Figure 22 after the filtration process is complete the apparatus 86 can be removed from the centrifuge. The filtrate tube cap 5 with filtrate tube cap gasket 6 can then be removed from apparatus 86, and the remaining concentrate (i.e. the dead stop volume) in lower chamber 83 of concentrate tube assembly 85 can be removed using a pipette tip 95 attached to a pipette mechanism, not shown. The removal of the dead stop volume is facilitated by the pipette channel that is formed by the upper side walls of the pipette channel 27, the bottom pipette channel wall 11, and the end pipette wall 62. After removing the dead stop volume from the concentrate tube assembly with the pipette tip, the dead stop volume can be transferred to a concentrate storage tube such as the concentrate storage tube 170 shown in Figure 9. The concentrate tube assembly 85, and concentrate tube rim gasket 7 can now be discarded in a safe manner. The filtrate 91 remaining in filtrate tube 4, can be safely stored in filtrate tube 4 by screwing filtrate tube cap 5 with filtrate tube cap gasket 6 back onto filtrate tube 4.

A third embodiment of the filtration device constructed in accordance with the principles of the present invention, is shown in Figure 24 and Figure 25. Referring to Figure 2, Figure 4, Figure 24, and Figure 25 the third embodiment is identical to the first embodiment shown in Figure 2 and Figure 4 except for the following changes to the concentrate tube assembly. Surface 112 is removed so that well 183 goes completely through the lower portion of concentrate tube 101 (i.e. well 183 is open on its top and bottom sides). Surface 173 is removed so that outside walls 171 extend from the top to the bottom of well 183. A filter cover 103 covers the top of well 183 as in the first embodiment. A second filter cover 103 covers the bottom of well 183. One filter element 102 is bonded to each filter cover as shown in Figure 3, and described above.

The apparatus 286 shown in Figure 24 is assembled for filtration the same as apparatus 186 shown in Figure 4 is assembled for filtration. The assembly process is described above. The apparatus 286 shown in Figure 24 functions the same way that the apparatus 186 shown in Figure 4 functions, with the exception that the apparatus 286 shown in Figure 24 contains twice the filter element surface area as the apparatus 186 shown in Figure 4, and the apparatus 286 contains two chambers 138, and two outlet ports 130.

Referring to Figure 3, and Figure 24 the centrifugal force created by the spinning centrifuge rotor causes the higher molecular weight molecules of concentrate 190 on the upstream side of filter elements 102 to flow through the two filter elements 102, into filtrate chambers 138 of the two filter covers 103. Chambers 138 of concentrate tube assembly 185 are in fluid flow relationship with the interior of filtrate tube 104 via outlet ports 130 of the two filter covers 103. Hence, filtrate that flows through filter elements 102 into filtrate chambers 138 will accumulate in the bottom of filtrate chambers 138, until the filtrate level in filtrate chambers 138 reaches outlet ports 130 of filter covers 103. At this point any additional filtrate will flow from filtrate chambers 138 through outlet ports 130 into the interior 149 of filtrate tube 104. Nent grooves 119 on concentrate tube 101 allow air in the interior of filtrate tube 104 to be vented into the centrifuge atmosphere, the air being displaced by filtrate 191 in the interior of filtrate tube 104. Nent grooves 119 on concentrate tube 101 prevent pressure buildup in filtrate tube 104 as filtrate tube 104 fills with filtrate. Nent hole 151 on concentrate tube cap 178 allows air to enter the interior of the concentrate tube assembly 185 to replace the filtered liquid, and thus prevent a vacuum buildup in the interior of concentrate tube assembly 185.

The filtration process will continue until the dead stop volume is reached. The dead stop volume for this device will be deteπnined as follows. If the apparatus is used in a swinging bucket rotor both outlet ports 130 will give the same dead stop volume regardless of axial orientation of the apparatus within the centrifuge rotor. If the apparatus is used in a fixed angle rotor and axially aligned so that the filter element is parallel to a vertical plane both outlet ports 130 will give the same dead stop volume. If the apparatus is used in a fixed angle rotor and the axial orientation is such that the filter element is not oriented parallel to a vertical plane, the dead stop volume will be determined by the outlet port 130 of the filter cover that gives the smallest dead stop volume.

The rest of the filtration process for the third embodiment is the same as the process for the first embodiment. In order to minimize the filtration time (i.e. the time to filter to the dead stop volume), it is necessary to keep the ratio of usable filter surface area to concentrate volume high throughout the filtration process. In addition to using the filter area below the filter cover outlet port, it is also desirable to minimize the volume of the lower part of the concentrate chamber. In the first and third embodiments of the present invention the height of the lower concentrate chamber has to be high enough to allow a pipette tip to reach to the bottom of the lower concentrate chamber to retrieve the dead stop volume. Hence the height of the lower chamber cannot be so small as to limit the insertion of a pipette tip. Referring to Figure 13 and Figure 18, if the height of side wall 28 is made to small it will not be possible to retrieve all of the dead stop volume because some of this volume will be trapped between surface 12 and the upstream side of the filter element 2 by the capillary action of the small gap between surface 12 and filter 2.

A fourth embodiment of the filtration device constructed in accordance with the principles of the present invention, is shown in Figure 26, Figure 27, Figure 28, Figure 29, and

Figure 30. This embodiment overcomes the problems described in the previous paragraph.

The fourth embodiment includes the following major components: concentrate tube 301, filter element 302, filter cover 303, filter sealing gasket 360, filtrate tube 4, and filtrate tube cap 5.

The concentrate tube assembly shown in Figure 26 fits into a filtrate tube 4, as shown in Figure 11, and is held in place with a filtrate tube cap 5, also shown in Figure 11.

Referring to Figure 26, Figure 27, Figure 28, Figure 29, and Figure 30 the concentrate tube assembly 385 contains concentrate tube 301, filter element 302, filter cover 303, and filter sealing gasket 360. The concentrate tube assembly 385 contains a concentrate chamber, which is divided into an upper chamber 382, a communication chamber 392, and a filtration chamber. The filtration chamber is further divided into the following chambers; a vent chamber 393, a pipette access chamber 394, a dead stop chamber 396, a thin channel chamber 398, and vent channels 397. In the concentrate tube shown in Figures 26 through Figure 29, the pipette access chamber 394 is formed by four sub-chambers 394a, 394b, 394c, and 394d, each chamber being narrower and shorter than the previous one. This design allows a tapered pipette tip to access the dead stop chamber 396, while keeping the volume of the pipette access chamber 394 to a minimum. The pipette access chamber 394 could also be formed as a smooth walled chamber that tapers in and up as it approaches the dead stop chamber 396. The upper concentrate chamber 382 is formed by cylindrical wall 310 and front tapered wall 323. Communication chamber 392 is formed by upper cylindrical wall 369, front tapered wall 324, side cylindrical walls 326, bottom wall 327, and by top wall 325. Nent chamber 393 is formed by front tapered wall 377, side walls 375, side round walls 374, and back wall 372. Dead stop chamber 396 is formed by front walls 366, side walls 365, back walls 363, and sloped bottom walls 364. Filter sealing gasket 360 fits into the well formed by walls 361 of concentrate tube 301 and flat surface 313 of concentrate tube 301. The filter sealing gasket 360 is rectangular in shape, and contains a cutout that is generally rectangular in shape with a N shaped front section. After the filter sealing gasket 360 is placed onto flat surface 313 of concentrate tube 301, the back edge of the gasket cutout aligns with the top edge of back wall 372, the side edges of the gasket cutout align with the top edges of surfaces 375, and the front N shaped edges of the gasket cutout align with the top edges of surfaces 366. Thin channel chamber 398 is formed by the side walls 363 of the filter sealing gasket cutout, the upstream side of filter element 302, and flat surface 313 of the concentrate tube 301. Nent channels 397 communicate between dead stop chamber 396 and vent chamber 393. Tapered wall 323, and tapered wall 324 assure that as filtration occurs all of the liquid in the upper concentrate chamber 382 will flow through communication chamber 392 into vent chamber 393 when the apparatus is used at any rotor angle from 28° to 90°, regardless of the axial orientation of the apparatus in the centrifuge rotor.

Referring to Figure 26, Figure 28, and Figure 30, the outer periphery of filter element is preferably sealed between compressed filter sealing gasket 360, and filter sealing rib 399 of filter cover 303. The compressed height of the filter sealing gasket is approximately 0.020", hence the thin channel 398 has a maximum height of 0.020". The filter element could also be sealed to filter sealing rib 399 by a heat seal, ultrasonic seal or glue seal in which case the filter sealing gasket need not be used.

Referring to Figure 26 and Figure 30 the filter cover 303 contains a filter sealing rib 399. The outer periphery of filter sealing rib 399 fits into the well formed by walls 361 of concentrate tube 301, thus providing an alignment means when assembling filter cover 303 to concentrate tube 301. After the filter cover 303 is assembled to the concentrate tube 301, filter sealing rib 399 pushes down on the outer periphery of filter element 302, which in turn compresses the filter sealing gasket 360 between the upstream side of filter element 302 and flat surface 313 of concentrate tube 301, thus creating a leak tight seal around the outer periphery of filter element 302. Filter support ribs 331 protrude from top surface 339. The space in-between and around filter support ribs 331 form channels 338. The volume formed by channels 338 and the downstream side of filter element 302, creates chamber 367. Filter cover 303 also contains outlet port 330, and may contain additional drainage ports 333.

Referring to Figure 26, Figure 27, and Figure 28, the concentrate tube assembly 385 is assembled as follows. The filter sealing gasket 360 is placed into the well formed by walls 361 of concentrate tube 301, and flat surface 313 of concentrate tube 301. The filter element 302 is placed into the same well on top of filter sealing gasket 360. Filter cover 303 is then assembled to concentrate tube 301, with walls 336 of filter sealing rib 399 of filter cover 303 fitting into the well formed by walls 361 of concentrate tube 301. Surface 332 of filter cover 303 is bonded to surface 322 of concentrate tube 301, preferably with a UN curing glue, but could also be bonded using an ultrasonic weld, a heat bond or any other type of leak tight bond.

The filtration apparatus is assembled by the user, in the same manner as the second embodiment of this invention, as described above. When the user places the solution to be filtered or concentrated into the concentrate tube assembly 385, the solution will flow from the upper chamber 382, through the communication chamber 392, into vent chamber 393, down through the pipette access chamber 394, and fill the dead stop chamber 396. The thin channel chamber 398, and vent channels 397 will then back fill from the dead stop chamber 396 up. Once the filtration chamber is filled with liquid, the liquid level will rise into the upper chamber. A small amount of air may be trapped in the top of vent chamber 393, after the concentrate tube assembly 385 has been filled with solution. This air can be dislodged by gently tapping the concentrate tube assembly 385, or this small amount of air will automatically be forced either through the filter, or into the upper chamber 382, by centrifugal force once the centrifuge begins to spin.

Referring to Figure 26, Figure 27, and Figure 28 the centrifugal force created by the spinning centrifuge rotor causes the lower molecular weight molecules of concentrate 390 on the upstream side of filter element 302 to flow through filter element 302, into chamber 367. Hence, filtrate that flows through filter element 302 into chamber 367 will accumulate in the bottom chamber 367, until the filtrate level in chamber 367 reaches outlet port 330 of filter cover 303. Chamber 367 of concentrate tube assembly 385 is in fluid flow relationship with the interior of filtrate tube 4 via outlet port 330 of filter cover 303. Additional outlet ports such as port 333 may be added to filter cover 303 above outlet port 330, to assure that there will not be any pressure buildup on the downstream side of filter element 302 above outlet port 330. Hence, filtrate that flows through filter element 302 into chamber 367 will flow from chamber 367 through outlet port 330 into the interior of filtrate tube 4. The interior of filtrate tube 4 (shown in Figure 17) is in air flow relationship with the interior of concentrate tube assembly 385, via the gap 80 between the outer surface 368 of concentrate tube 301 and the inner surface 42 of filtrate tube 4, vent grooves 319 on concentrate tube 301, and vent channels 320 on the top of flange 318 of concentrate tube 301. Therefore as filtrate enters the interior of filtrate tube 4 via port 330 of filter cover 303, the air that is displaced by this filtrate flows through gap 80 between the outside wall of concentrate tube assembly 385 and the inside wall of filtrate tube 4, through grooves 319 of concentrate tube 301, and channels 320 of the top of flange 318 of concentrate tube 301, into the interior of concentrate tube assembly 385 to replace the filtrate that flows from the filtration chamber of the interior of concentrate tube assembly 385, through filter element 302, into chamber 367, through outlet port 330, into the interior of filtrate tube 4. Hence the pressure in the interior of filtrate tube 4, and the pressure in the interior of concentrate tube assembly 385 remain at atmospheric pressure throughout the filtration process. An additional benefit of securing the concentrate tube assembly 385 to filtrate tube 4, with filtrate tube cap 5 is that if the user accidentally drops the assembled apparatus its contents will not spill.

The filtration process continues until the liquid level on the concentrate side of filter element 302, and the liquid level on the filtrate side of filter element 302 both reach the outer most edge of outlet port 330 of filter cover 303. The outer most edge of outlet port 330 of filter cover 303 is the edge of outlet port 330 that is the furthest from the axis of rotation of the centrifuge rotor. Figure 28 shows this level for a swinging bucket centrifuge rotor. The level for a fixed angle rotor is similar to that shown in Figure 7. Once the liquid reaches the level shown in Figure 7 for a fixed angle rotor, or in Figure 28 for a swinging bucket rotor, the pressure on the upstream side of filter element 302 will be the same as the pressure on the downstream side of filter element 302, thus liquid flow through filter element 302 will stop. The concentrate that remains on the upstream side of the filter element when filtration is complete is called the retained concentrate volume, or dead stop volume. After device 386 is used in a swinging bucket rotor the dead stop volume will be the same regardless of filter orientation. The dead stop volume will be the same if filtration device 386 is placed in the swinging bucket centrifuge rotor so that the filter element is oriented parallel to a vertical plane as shown in Figure 29, or so that the filter element is oriented parallel to a horizontal plane as shown in Figure 28, or so that the filter element is oriented at any angle relative to either the horizontal or vertical planes. The dead stop volume will be approximately the same for any fixed angle centrifuge rotor angle from 30° to 90° when the filter element is oriented parallel to the vertical plane the same as the orientation shown in Figure 21.

As long as the upstream side of the filtration chamber of concentrate tube assembly

385 is filled with liquid the entire active surface area of filter element 302 will be used. If the pipette access chamber 394 is made just large enough to accommodate a small pipette tip (i.e. a gel loading tip for example), and if the volume of the vent chamber 393 is made just large enough to give the proper venting, and if the dead stop chamber 396 is made just high enough to allow easy and complete removal of the dead stop volume, and if the vent channels 397 are made just large enough to allow easy and complete removal of the dead stop volume, then the volume of the filtration chamber will be minimized. For example, a concentrate tube assembly 385 with a maximum volume capacity of 4 ml, and an active filter surface area of approximately 2 cm², will have a filtration chamber with a total volume of approximately 250 μl.

After the filtration process is complete the apparatus can be removed from the centrifuge. The filtrate tube cap 5 with filtrate tube cap gasket 6 can then be removed from the filtrate tube 4, and the remaining concentrate (i.e. the dead stop volume) in dead stop chamber 396 of concentrate tube assembly 385 can be removed using a pipette tip attached to a pipette mechanism. After filtration is complete the filter element 302 will be wetted. The wetted filter will swell, and may droop down to flat surface 313 of concentrate tube 301, because the height of the thin channel chamber is 0.020" or less. After the gel loading pipette tip is inserted into the device to remove the dead stop volume it will pass through communication chamber 392, and then go through pipette access chamber 394, and then into dead stop chamber 396. The communication chamber 392 is below the filter element 302, and the pipette access chamber 394 tapers inward, and upward as it approaches the dead stop chamber 396. This geometry prevents the pipette tip from scratching against the filter element 302, and causes the end of the gel loading tip to bend up to access the end of the dead stop chamber 396. Although the pipette access chamber 394 can be a snug fit for the pipette tip, the communication chamber 392 is the full width of vent chamber 393. The volume of the dead stop chamber 396 should be larger than the dead stop volume, so that there will be an air space above the dead stop volume when the filtration is complete.

After filtration is complete, dead stop chamber 396 is in air flow relationship with upper chamber 382 through, vent channels 397, vent chamber 393, and through communication chamber 392. The height of the dead stop chamber 396 is greater than the height of the thin channel chamber 398, hence as the pipette tip removes liquid from the dead stop chamber 396 an equal volume of air can enter the dead stop chamber 396, through vent channels 397, vent chamber 393, and communication chamber 392. This venting allows easy and complete removal of the dead stop volume by the pipette tip. After removing the dead stop volume from the concentrate tube assembly with the pipette tip, the dead stop volume can be transferred to a concentrate storage tube such as the concentrate storage tube 170 shown in Figure 9. The concentrate tube assembly 385, and concentrate tube rim gasket 7 can now be discarded in a safe manner. The filtrate 91 remaining in filtrate tube 4, can be safely stored in filtrate tube 4 by screwing filtrate tube cap 5 with filtrate tube cap gasket 6 back onto filtrate tube 4.

A fifth embodiment of the filtration device constructed in accordance with the principles of the present invention, is shown in Figure 31, Figure 32, Figure 33N Figure 33B, Figure 34, Figure 35 and Figure 36. The fifth embodiment includes the following major components: concentrate tube 401, filter element 402, filter cover 403, filtrate tube 4, and filtrate tube cap 5. The concentrate tube assembly shown in Figure 31 fits into a filtrate tube 4, as shown in Figure 11, and is held in place with a filtrate tube cap 5, also shown in Figure 11.

Referring to Figure 31, Figure 32, Figure 33A, Figure 33B, Figure 34, Figure 35 and Figure 36 the concentrate tube assembly 485 contains concentrate tube 401, filter element 402, and filter cover 403. The concentrate tube assembly 485 contains a concentrate chamber that is divided into an upper chamber 482, and a filtration chamber. The filtration chamber is further divided into the following chambers; a vent chamber 493, a pipette access chamber 494, a dead stop chamber 496, a thin channel chamber 498, and vent channels 497. The pipette access chamber 494 is formed as a smooth walled chamber that tapers in and up as it approaches the dead stop chamber 496. The upper concentrate chamber 482 is formed by cylindrical wall 410, front tapered wall 423, side tapered walls 426 and wall 425. Nent chamber 493 is formed by front walls 477a, 477b, and 477c, side walls 475, bottom wall 427, and back wall 472. Dead stop chamber 496 is formed by front walls 466, side walls 465, back walls 463, and sloped bottom walls 464. Thin channel chamber 498 is formed by the side walls 463, the upstream side of filter element 402, and flat surface 489 of the concentrate tube 401. Pipette access chamber 494 is formed by the bottom wall 442 and side walls 446. Nent channels 497 communicate between dead stop chamber 496 and vent chamber 493. The top end of vent channels 497, labeled 497a increases in depth, so that the deepest level of the vent channels is approximately at the same level of wall 425. This enhances venting as the filtration chamber is initially filled from the dead stop chamber up. Tapered wall 423, and tapered walls 426 assure that as filtration occurs all of the liquid in the upper concentrate chamber 482 will flow through into vent chamber 493 when the apparatus is used at any rotor angle from 28° to 90°, regardless of the axial orientation of the apparatus in the centrifuge rotor.

Referring to Figure 32, Figure 33A, Figure 33B, Figure 34 and Figure 35, surface 432 of filter cover 403 is bonded to surface 422 of concentrate tube 401. This bond is preferably an ultrasonic bond, but could be a glue bond, a heat bond, a solvent bond or any other type of leak tight bond. When filter cover 403 is bonded to concentrate tube 401 pressure is applied to the outside surface 441 of filter cover 403, thereby squeezing the outer periphery of filter element 402 between surface 499 of filter cover 403 and surface 413 of concentrate tube 401, thereby compressing the outer periphery of filter element 402 between surface 499 of filter cover 403 and surface 413 of concentrate tube 401, creating a compression seal. To enhance the integrity of this filter compression seal filter cover 403 contains filter pinch rib 487. Referring to Figure 35 filter pinch rib 487, because of its narrow width is able to compress filter element 402 to the point where the pores of filter element 402 collapses thereby creating a leak tight seal. The height of filter pinch rib 487 will depend on the type and thickness of filter element 402. Filter element 402 could also be sealed to surface 413 of concentrate tube 401 using a heat seal, ultrasonic seal or glue seal. In this case filter pinch rib 487 would not be needed. Filter cover 403 contains filter support ribs 431 and channels 438. Filter cover 403 also contains outlet port 430 and upper vent port 433. During the filtration process filtrate will pass through the filter element 402 and collect in channels 438. Channels 438 direct the filtrate to outlet port 430, and vent port 433 prevents airlocking, thereby allowing filtrate to flow freely through channels 438, and out through outlet port 430.

Referring to Figure 31, through Figure 35, the concentrate tube assembly 485 is assembled as follows. Filter element 402 is placed into the well formed by walls 461 of concentrate tube 401, and flat surface 413 of concentrate tube 401. Filter cover 403 is then assembled to concentrate tube 401, with walls 436 of filter sealing rib 499 of filter cover 403 fitting into the well formed by walls 461 of concentrate tube 401. Surface 432 of filter cover 403 is bonded to surface 422 of concentrate tube 401, preferably with an ultrasonic weld, but could also be bonded using a glue seal, a heat bond, a solvent bond or any other type of leak tight bond. As noted above if a compression seal is used to seal the filter element 402 between surface 499 of filter cover 403 and surface 413 of concentrate tube 401, pressure must be applied to surface 441 of filter cover 403 while bonding surface 432 of filter cover 403 to surface 422 of concentrate tube 401. If a heat seal is used to bond filter element 402 to surface 413 of concentrate tube 401, this seal would be made before bonding the filter cover to the concentrate tube.

The filtration apparatus is assembled by the user, in the same manner as the second embodiment of this invention, as described above. If the user places the solution to be filtered or concentrated into the concentrate tube assembly 485, the solution will flow from the upper chamber 482, into vent chamber 493, down through the pipette access chamber 494, and fill the dead stop chamber 496. The thin channel chamber 498, and vent channels 497 will then back fill from the dead stop chamber 496 up. Once the filtration chamber is filled with liquid, the liquid level will rise into the upper chamber. A small amount of air may be trapped in the top of vent chamber 493, after the concentrate tube assembly 485 has been filled with solution. This air can be dislodged by gently tapping the concentrate tube assembly 485, or this small amount of air will automatically be forced either through the filter, or into the upper chamber 482, by centrifugal force once the centrifuge begins to spin. Referring to Figure 31, Figure 32, Figure 33A, Figure 33B, Figure 34 and Figure 35 the centrifugal force created by the spinning centrifuge rotor causes the lower molecular weight molecules of the concentrate on the upstream side of filter element 402 to flow through filter element 402, into channels 438 of filter cover 403. Hence, filtrate that flows through filter element 402 into channels 438 will accumulate in the bottom of channels 438, until the filtrate level in channels 438 reaches outlet port 430 of filter cover 403. Channels 438 of filter cover 403 are in fluid flow relationship with the interior of filtrate tube 4 (shown in Figure 17) via outlet port 430 of filter cover 403. Nent port 433 of filter cover 403 assures that there will not be any pressure buildup on the downstream side of filter element 402 above outlet port 430. Hence, filtrate that flows through filter element 402 into channels 438 will flow from channels 438 through outlet port 430 into the interior of filtrate tube 4. The interior of filtrate tube 4 is in air flow relationship with the interior of concentrate tube assembly 485, via the gap 80 between the outer surface 468 of concentrate tube 401 and the inner surface 42 of filtrate tube 4, vent grooves 419 on concentrate tube 401, and vent channels 420 on the top of flange 418 of concentrate tube 401. Therefore as filtrate enters the interior of filtrate tube 4 via port 430 of filter cover 403, the air that is displaced by this filtrate flows through gap 80 between the outside wall of concentrate tube assembly 485 and the inside wall of filtrate tube 4, through grooves 419 of concentrate tube 401, and channels 420 of the top of flange 418 of concentrate tube 401, into the interior of concentrate tube assembly 485 to replace the filtrate that flows from the filtration chamber of the interior of concentrate tube assembly 485, through filter element 402, into channels 438, through outlet port 430, into the interior of filtrate tube 4. Hence the pressure in the interior of filtrate tube 4, and the pressure in the interior of concentrate tube assembly 485 remain at atmospheric pressure throughout the filtration process. An additional benefit of securing the concentrate tube assembly 485 to filtrate tube 4, with filtrate tube cap 5 is that if the user accidentally drops the assembled apparatus its contents will not spill.

The filtration process continues until the liquid level on the concentrate side of filter element 402, and the liquid level on the filtrate side of filter element 402 both reach the outer most edge of outlet port 430 of filter cover 403. The outer most edge of outlet port 430 of filter cover 403 is the edge of outlet port 430 that is the furthest from the axis of rotation of the centrifuge rotor. The level for a swinging bucket centrifuge rotor is similar to that shown in Figure 28. The level for a fixed angle rotor is similar to that shown in Figure 7. Once the liquid reaches the level shown in Figure 7 for a fixed angle rotor, or in Figure 28 for a swinging bucket rotor, the pressure on the upstream side of filter element 402 will be the same as the pressure on the downstream side of filter element 402, thus liquid flow through filter element 402 will stop. The concentrate that remains on the upstream side of the filter element when filtration is complete is called the retained concentrate volume, or dead stop volume. If device 486 is used in a swinging bucket rotor the dead stop volume will be the same regardless of filter orientation. The dead stop volume will be the same if filtration device 486 is placed in the swinging bucket centrifuge rotor so that the filter element is oriented parallel to a vertical plane as shown in Figure 29, or so that the filter element is oriented parallel to a horizontal plane as shown in Figure 34, or so that the filter element is oriented at any angle relative to either the horizontal or vertical planes. The dead stop volume will be approximately the same for any fixed angle centrifuge rotor angle from 30° to 90° when the filter element is oriented parallel to the vertical plane the same as the orientation shown in Figure 21.

As long as the upstream side of the filtration chamber of concentrate tube assembly 485 is filled with liquid the entire active surface area of filter element 402 will be used. If the pipette access chamber 494 is made just large enough to accommodate a small pipette tip (i.e. a gel loading tip for example), and if the volume of the vent chamber 493 is made just large enough to give the proper venting, and if the dead stop chamber 496 is made just high enough to allow easy and complete removal of the dead stop volume, and if the vent channels 497 are made just large enough to allow easy and complete removal of the dead stop volume and to allow complete initial filling of the filtration chamber, then the volume of the filtration chamber will be mmimized. For example, a concentrate tube assembly 485 with a maximum volume capacity of 4 ml, and an active filter surface area of approximately 2 cm², will have a filtration chamber with a total volume of approximately 250 μl.

After the filtration process is complete the apparatus can be removed from the centrifuge. The filtrate tube cap 5 with filtrate tube cap gasket 6 can then be removed from the filtrate tube 4, and the remaining concentrate (i.e. the dead stop volume) in dead stop chamber 496 of concentrate tube assembly 485 can be removed using a pipette tip attached to a pipette mechanism. After filtration is complete the filter element 402 will be wetted. The wetted filter will swell, and may droop down to flat surface 489 of concentrate tube 401, because the height of the thin channel chamber is 0.020" or less. When the gel loading pipette tip is inserted into the device to remove the dead stop volume it will pass through, the pipette access chamber 494, and then into dead stop chamber 496. The pipette access chamber 494 tapers inward, and upward as it approaches the dead stop chamber 496. This geometry prevents the pipette tip from scratching against the filter element 402, and causes the end of the gel loading tip to bend up to access the end of the dead stop chamber 496. The volume of the dead stop chamber 496 should be larger than the dead stop volume, so that there will be an air space above the dead stop volume when the filtration is complete. After filtration is complete, dead stop chamber 496 is in air flow relationship with upper chamber 482 through, vent channels 497, and vent chamber 493. The height of the dead stop chamber 496 is greater than the height of the thin channel chamber 498, hence as the pipette tip removes liquid from the dead stop chamber 496 an equal volume of air can enter the dead stop chamber 496, through vent channels 497, and vent chamber 493. This venting allows easy and complete removal of the dead stop volume by the pipette tip. After removing the dead stop volume from the concentrate tube assembly with the pipette tip, the dead stop volume can be transferred to a concentrate storage tube such as the concentrate storage tube 170 shown in Figure 9. The concentrate tube assembly 485, and concentrate tube rim gasket 7 can now be discarded in a safe manner. The filtrate 91 remaining in filtrate tube 4, can be safely stored in filtrate tube 4 by screwing filtrate tube cap 5 with filtrate tube cap gasket 6 back onto filtrate tube 4.

Comparative Testing

To test the improved concentrating abilities of the present invention over the prior art, two preferred embodiments were constructed.

The first embodiment (#1) was made through the use of conventional stereolithography methods. The concentrate tube had a base diameter of 0.563 inches. The filter cap had seven drain channels, each 0.020" wide by 0.040" deep. The outlet port was 0.125" from the arrow tip, having a 0.025" diameter. The filter cap also contained a vent hole in the top cross channel and a vent hole in the next to top cross channel. The filtration membrane had a surface area of about 0.305 sq in and was made from 10KMW Biomax membrane for filtration (Millipore Corporation of Bedford, Massachusetts).

The second embodiment (#2) was made through the use of conventional machining methods. The concentrate tube had a base diameter of 0.563 inches. The filter cap had five drain channels 0.032" wide by 0.050" deep. The outlet port was 0.101" from the arrow tip, having a 0.045" diameter. The filter cap also contained a vent hole in the top cross channel and a vent hole in the next to top cross channel. The filtration membrane had a surface area of about 0.276 sq in and was made from 10KMW Biomax membrane for filtration (Millipore Corporation of Bedford, Massachusetts).

The above present embodiments were compared against off the shelf embodiments of the Nassarotti device made by Millipore Corporation of Bedford, Massachusetts - 4 ml Ultrafree filtration devices. These devices (#3 and #4 below) used 10KMW Biomax membrane for filtration and had a surface area of about 0.293 sq in.

Each of the devices was loaded with about 3 ml of a lmg/ml BSA solution in deionized water. The devices were put into an IEC tabletop centrifuge and spun at 1950 rpm. The results of these tests are incorporated in the following table. The end of volume listings in each column indicates that the filtration endpoint was reached.

Clearly the advantages of the present invention can be seen from these tests. Not only does the present design concentrate to a greater degree, but it does so in a significantly reduced time frame.

The ordinarily skilled artisan can appreciate that the present invention can incorporate any number of the preferred features above

Other embodiments of the present invention are not presented which are obvious to those of ordinary skill in the art, now or during the term of any patent issuing from this patent specification, and thus, are within the spirit and scope of the present invention.

Claims

I CLAIM:

1. A centrifugal liquid filtration apparatus for separating filtrate and concentrate from a solution, capable of being used in a fixed angle or swinging bucket centrifuge rotor comprising:

(a) a concentrate tube assembly capable of containing a solution therein, comprising; (i) a concentrate tube, (ϋ) a filter cover, (iii) a concentrate tube cap; and (b) a filtrate tube for collecting filtrate;

(c) the concentrate tube assembly containing a first chamber capable of containing unfiltered liquid therein;

(d) the first chamber being divided into an upper part and a lower part;

(e) a second chamber capable of collecting filtered liquid therein, the second chamber being in fluid flow relationship with the lower part of the first chamber;

(f) means for filtering liquid within the first chamber prior to flowing into the second chamber; and

(g) a port leading from the second chamber into the interior of the filtrate tube, the port being disposed a sufficient distance above the bottom of the second chamber whereby the lower part of the first chamber is prevented from filtering to dryness.

2. The filtration apparatus of claim 1 wherein the bottom portion of the upper part of the first chamber is shaped so that all liquid in the upper part of the first chamber will flow into the the lower part of the first chamber, for any centrifuge rotor angle from 28° to 90°, and for any axial orientation of the filtration apparatus within the centrifuge rotor.

3. The filtration apparatus of claim 2 wherein a lower portion of the concentrate tube assembly is inserted into the filtrate tube.

4. The filtration apparatus of claim 3 wherein the filtrate tube engages the concentrate tube assembly with an interference fit.

5. The filtration apparatus of claim 1 wherein the volume of concentrate remaining in the lower part of the first chamber after filtration is complete, is independent of the axial orientation of the filtration apparatus in the centrifuge rotor when used within a swinging bucket rotor.

6. The filtration apparatus of claim 1 wherein the volume of concentrate remaining in the lower part of the first chamber after filtration is complete, will not vary more than 10% when the apparatus is used at any rotor angle from 28° to 90°, and when the apparatus is oriented axially within the rotor so that the filter element is oriented parallel to a vertical plane.

7. The filtration apparatus of claim 1 further comprising a vented cap for covering the upper portion of the concentrate tube assembly and allowing the apparatus to be spun in a centrifuge.

8. The filtration apparatus of claim 1 further comprising a venting means for venting the filtrate tube.

9. The filtration apparatus of claim 8 wherein the venting means for venting the filtrate tube is one or more grooves in the concentrate tube.

10. The filtration apparatus of claim 1 wherein the liquid filtering means comprises a micro- porous filter element.

11. The filtration apparatus of claim 10 wherein the micro-porous filter element is sealed to the filter cover.

12. A centrifugal liquid filtration apparatus for separating filtrate and concentrate from a solution, capable of being used in a fixed angle or swinging bucket centrifuge rotor comprising:

(a) a concentrate tube assembly capable of containing a solution therein, comprising; (i) a concentrate tube, and

(ϋ) a filter cover,

(b) a filtrate tube for collecting filtrate; (c) a filtrate tube cap;

(d) a filtrate tube cap gasket;

(e) the concentrate tube assembly containing a first chamber capable of containing unfiltered liquid therein; (f) the first chamber being divided into an upper part and a lower part;

(g) a second chamber capable of collecting filtered liquid therein, the second chamber being in fluid flow relationship with the lower part of the first chamber; (h) means for filtering liquid within the first chamber prior to flowing into the second chamber; and (i) a port leading from the second chamber into the interior of the filtrate tube, the port being disposed a sufficient distance above the bottom of the second chamber whereby the lower part of the first chamber is prevented from filtering to dryness.

13. The filtration apparatus of claim 12 wherein the bottom portion of the upper part of the first chamber is shaped so that all liquid in the upper part of the first chamber will flow into the the lower part of the first chamber, for any centrifuge rotor angle from 28° to 90°, and for any axial orientation of the filtration apparatus within the centrifuge rotor.

14. The filtration apparatus of claim 13 wherein the concentrate tube assembly is inserted into the filtrate tube.

15. The filtration apparatus of claim 14 wherein a flange on the upper portion of the concentrate tube positions the concentrate tube assembly within the filtrate tube.

16. The filtration apparatus of claim 15 wherein the concentrate tube flange contains one or more ports that communicate between the top and bottom faces of the flange.

17. The filtration apparatus of claim 16 wherein the top face of the concentrate tube flange contains one or more grooves that communicate between the flange ports and the interior of the concentrate tube assembly, the number of grooves being equal to the number of flange ports.

18. A filtration apparatus of claim 17 wherein there is a gap between the outer wall of the concentrate tube assembly, and the inner wall of the filtrate tube.

19. The filtration apparatus of claim 18 wherein the filtrate tube cap is threadedly engagable to the filtrate tube.

20. The filtration apparatus of claim 19 wherein the filtrate tube cap gasket seals the opening at the top of the concentrate tube when the filtrate tube cap is threadably engaged to the filtrate tube.

21. The filtration apparatus of claim 20 wherein there is a concentrate tube gasket between the bottom face of the flange on the upper portion of the concentrate tube, and the top edge of the filtrate tube.

22. The filtration apparatus of claim 21 wherein the concentrate tube gasket seals any gap that may exist between the bottom face of the concentrate tube flange and the top edge of the filtrate tube when the concentrate tube cap is threadably engaged to the filtrate tube.

23. The filtration apparatus of claim 22 wherein air in the filtrate tube that is displaced by filtrate entering the filtrate tube is vented through the gap between the outer wall of the concentrate tube assembly, and the inner wall of the filtrate tube, and through the one or more ports that communicate between the top and bottom faces of the flange, and through the one or more grooves that communicate between the flange ports and the interior of the concentrate tube assembly, into the interior of the concentrate tube assembly.

24. The filtration apparatus of claim 20 wherein air in the filtrate tube that is displaced by filtrate entering the filtrate tube is vented through the gap between the outer wall of the concentrate tube assembly, and the inner wall of the filtrate tube, and through any gap that may exist between the bottom face of the concentrate tube flange and the top edge of the filtrate tube when the concentrate tube cap is threadably engaged to the filtrate tube, and through the gap between the threads of the filtrate tube and the threads of the filtrate tube cap, to atmosphere; and wherein atmospheric air can enter the interior of the concentrate tube assembly to replace filtrate that passes through the filter element into the second chamber, through the gap between the threads of the filtrate tube and the threads of the filtrate tube cap, and through the one or more ports that communicate between the top and bottom faces of the flange, and through the one or more grooves that communicate between the flange ports and the interior of the concentrate tube assembly.

25. The filtration apparatus of claim 12 wherein the liquid filtering means is a micro-porous filter element that is sealed to an open face of the bottom portion of the concentrate tube.

26. The filtration apparatus of claim 12 wherein the liquid filtering means is a micro-porous filter element that is sealed to the filter cover.

27. A centrifugal liquid filtration apparatus for separating filtrate and concentrate from a solution, capable of being used in a fixed angle or swinging bucket centrifuge rotor comprising:

(a) a concentrate tube assembly capable of containing a solution therein, comprising; (i) a concentrate tube, and (ϋi) two filter covers, (iv) a concentrate tube cap, (b) a filtrate tube for collecting filtrate;

(d) the first chamber being divided into an upper part and a lower part;

(f) a third chamber capable of collecting filtered liquid therein, the third chamber being in fluid flow relationship with the lower part of the first chamber;

(g) means for filtering liquid within the first chamber prior to flowing into the second and third chambers; (h) a first port leading from the second chamber into the interior of the filtrate tube; and (i) a second port leading from the third chamber into the interior of the filtrate tube, the first and second ports being disposed a sufficient distance above the bottom of the second chamber whereby the lower part of the first chamber is prevented from filtering to dryness.

28. The filtration apparatus of claim 27 wherein the bottom portion of the upper part of the first chamber is shaped so that all liquid in the upper part of the first chamber will flow into the lower part of the first chamber, for any centrifuge rotor angle from 28° to 90°, and for any axial orientation of the filtration apparatus within the centrifuge rotor,

29. The filtration apparatus of claim 28 wherein a lower portion of the concentrate tube assembly is inserted into the filtrate tube.

30. The filtration apparatus of claim 29 wherein the filtrate tube engages the concentrate tube assembly with an interference fit.

31. The filtration apparatus of claim 27 wherein the volume of concentrate remaining in the lower part of the first chamber after filtration is complete, is independent of the axial orientation of the filtration apparatus in the centrifuge rotor when used within a swinging bucket rotor.

32. The filtration apparatus of claim 27 wherein the volume of concentrate remaining in the lower part of the first chamber after filtration is complete, will not vary more than 10% when the apparatus is used at any rotor angle from 28° to 90°, and when the apparatus is oriented axially within the rotor so that the filter element is oriented parallel to a vertical plane.

33. The filtration apparatus of claim 27 further comprising a vented cap for covering the upper portion of the concentrate tube assembly and allowing the apparatus to be spun in a centrifuge.

34. The filtration apparatus of claim 30 further comprising a venting means for venting the filtrate tube.

35. The filtration apparatus of claim 34 wherein the venting means for venting the filtrate tube is one or more grooves in the concentrate tube.

36. The filtration apparatus of claim 27 wherein the means for filtering liquid within the first chamber prior to flowing into the second chamber and third chamber, comprise two micro- porous filter elements.

37. The filtration apparatus of claim 36 wherein two micro-porous filter elements are respectively sealed to the filter covers.

38. A centrifugal liquid filtration apparatus for separating filtrate and concentrate from a solution, capable of being used in a fixed angle or swinging bucket centrifuge rotor comprising: (a) a concentrate tube assembly capable of containing a solution therein, comprising;

(i) a concentrate tube,

(ii) a filter cover, and

(ϋi) a filter sealing gasket, (b) a filtrate tube for collecting filtrate; (c) a filtrate tube cap;

(d) a filtrate tube cap gasket;

(e) the concentrate tube assembly containing a first chamber capable of containing unfiltered liquid therein;

(f) the first chamber being divided into an upper part a central part and a lower part; (g) the upper part and the lower part being connected by the central part;

(h) the lower part comprising; (i) a vent chamber; (ϋ) a pipette access chamber; (ϋi) at least one vent channel; (iv) a dead stop chamber; and

(v) a thin channel chamber; (i) a second chamber capable of collecting filtered liquid therein, the second chamber being in fluid flow relationship with the lower part of the first chamber; (j) means for filtering liquid within the first chamber prior to flowing into the second chamber; and (k) a port leading from the second chamber into the interior of the filtrate tube, the port being disposed a sufficient distance above the bottom of the second chamber whereby the lower part of the first chamber is prevented from filtering to dryness.

39. The filtration apparatus of claim 38 wherein the bottom portion of the upper part of the first chamber is shaped so that all liquid in the upper part of the first chamber will flow into the the central part, and then into the lower part of the first chamber, for any centrifuge rotor angle from 28° to 90°, and for any axial orientation of the filtration apparatus within the centrifuge rotor.

40. The filtration apparatus of claim 39 wherein the concentrate tube assembly is inserted into the filtrate tube.

41. The filtration apparatus of claim 40 wherein a flange on the upper portion of the concentrate tube positions the concentrate tube assembly within the filtrate tube.

42. The filtration apparatus of claim 41 wherein the concentrate tube flange contains one or more ports that communicate between the top and bottom faces of the flange.

43. The filtration apparatus of claim 42 wherein the top face of the concentrate tube flange contains one or more grooves that communicate between the flange ports and the interior of the concentrate tube assembly, the number of grooves being equal to the number of flange ports.

44. The filtration apparatus of claim 43 wherein there is a gap between the outer wall of the concentrate tube assembly, and the inner wall of the filtrate tube.

45. The filtration apparatus of claim 44 wherein the filtrate tube cap is threadedly engagable to the filtrate tube.

46. The filtration apparatus of claim 45 wherein the filtrate tube cap gasket seals the opening at the top of the concentrate tube when the concentrate tube cap is threadably engaged to the filtrate tube.

47. The filtration apparatus of claim 46 wherein there is a concentrate tube gasket between the bottom face of the flange on the upper portion of the concentrate tube, and the top edge of the filtrate tube.

48. The filtration apparatus of claim 47 wherein the concentrate tube gasket seals any gap that may exist between the bottom face of the concentrate tube flange and the top edge of the filtrate tube when the concentrate tube cap is threadably engaged to the filtrate tube.

49. The filtration apparatus of claim 48 wherein air in the filtrate tube that is displaced by filtrate entering the filtrate tube is vented through the gap between the outer wall of the concentrate tube assembly, and the inner wall of the filtrate tube, and through the one or more ports that communicate between the top and bottom faces of the flange, and through the one or more grooves that communicate between the flange ports and the interior of the concentrate tube assembly, into the interior of the concentrate tube assembly.

50. The filtration apparatus of claim 46 wherein air in the filtrate tube that is displaced by filtrate entering the filtrate tube is vented through the gap between the outer wall of the concentrate tube assembly, and the inner wall of the filtrate tube, and through any gap that may exist between the bottom face of the concentrate tube flange and the top edge of the filtrate tube when the concentrate tube cap is threadably engaged to the filtrate tube, and through the gap between the threads of the filtrate tube and the threads of the filtrate tube cap, to atmosphere; and wherein atmospheric air can enter the interior of the concentrate tube assembly to replace filtrate that passes through the filter element into the second chamber, through the gap between the threads of the filtrate tube and the threads of the filtrate tube cap, and through the one or more ports that communicate between the top and bottom faces of the flange, and through the one or more grooves that communicate between the flange ports and the interior of the concentrate tube assembly.

51. The filtration apparatus of claim 38 wherein the liquid filtering means comprises a micro- porous filter element is sealed between a peripheral rib of the filter cover and the filter sealing gasket, the seal forming a leak tight seal on the gasket side of the seal.

52. The filtration apparatus of claim 51 wherein the filter sealing gasket seals the lower chamber of the concentrate tube assembly, thus preventing leakage from the first chamber to the second chamber.

53. The filtration apparatus of claim 38 wherein the liquid filtering means comprises a micro- porous filter element that is sealed to the filter cover.

54. The filtration apparatus of claim 38 wherein the height of the thin channel chamber is less than 0.050 inches.

55. The filtration apparatus of claim 38 wherein the height of the dead stop chamber is greater than the height of the thin channel chamber.

56. The filtration apparatus of claim 38 wherein the pipette access channel is made small enough so that only a gel loading pipette tip can slide through the pipette access chamber to the bottom of the dead stop chamber.

57. The filtration apparatus of claim 56 wherein the pipette access channel is positioned so that the gel loading pipette tip can not scratch the surface of the filter element.

58. The filtration apparatus of claim 38 wherein the volume of the filtration chamber is less than 300 μl.

59. The filtration apparatus of claim 38 wherein the filter cover contains more than one outlet port.

60. The filtration apparatus of Claim 1 wherein the liquid filtering means is retained by a compression seal.

61. The filtration apparatus of Claim 60 wherein the liquid filtering means comprises a microporous filter element compressed between the filter cover periphery and the outer periphery of the lower chamber.

62. The filtration apparatus of Claim 61 wherein a pinch rib extends about the area where the filter cover periphery and the outer lower chamber periphery compress the microporous filter element.

63. The filtration apparatus of Claim 12 wherein the liquid filtering means is retained by a compression seal.

64. The filtration apparatus of Claim 63 wherein the liquid filtering means comprises a microporous filter element compressed between the filter cover periphery and the outer periphery of the lower chamber.

65. The filtration apparatus of Claim 64 wherein a pinch rib extends about the area where the filter cover periphery and the outer lower chamber periphery compress the microporous filter element.

66. The filtration apparatus of Claim 27 wherein the liquid filtering means is retained by a compression seal.

67. The filtration apparatus of Claim 66 wherein the liquid filtering means comprises a microporous filter element compressed between the filter cover periphery and the outer periphery of the lower chamber.

68. The filtration apparatus of Claim 67 wherein a pinch rib extends about the area where the filter cover periphery and the outer lower chamber periphery compress the microporous filter element.

69. The filtration apparatus of Claim 38 wherein the liquid filtering means is retained by a compression seal.

70. The filtration apparatus of Claim 69 wherein the liquid filtering means comprises a microporous filter element compressed between the filter cover periphery and the outer periphery of the lower chamber.

71. The filtration apparatus of Claim 70 wherein a pinch rib extends about the area where the filter cover periphery and the outer lower chamber periphery compress the microporous filter element.