WO2002018031A2

WO2002018031A2 - A device and method for removing particulate material from suspensions

Info

Publication number: WO2002018031A2
Application number: PCT/US2001/025571
Authority: WO
Inventors: Dariusz Wodka; Robert G. Gentles
Original assignee: Abbott Laboratories
Priority date: 2000-08-25
Filing date: 2001-08-15
Publication date: 2002-03-07
Also published as: WO2002018031A3

Abstract

A filtering device comprising a filtering element that can be attached to an adapter. The filtering element comprises a mesh surrounding a cavity. The mesh of the filtering element is constructed to have sufficient porosity so that hydrostatic and mechanical pressures force the liquid components of a suspension into the cavity of the filtering element from where they can be aspirated and collected. Preferably, at least one semi-rigid rib supports the mesh. This invention also involves a method for using the filtering device in a variety of applications. These applications include, but are not limited to, sampling of suspensions, filtration of particulate materials from suspensions, and purification or isolation of chemical or biological components contained within the a suspension.

Description

A DEVICE AND METHOD FOR REMOVING PARTICULATE MATERIAL FROM SUSPENSIONS

BACKGROUND OF THE INVENTION

1. FIELD OF THE INVENTION

This invention relates to a device and a method for removing particulate materials from suspensions containing chemical and/or biological materials, and, more particularly, a device and a method for isolating components of interest from such suspensions.

2. DISCUSSION OF THE ART

An extensive array of laboratory devices for filtering suspensions containing particles of varying size in a variety of solvents exists. The most common devices comprise a filtering element housed within an assembly, the assembly designed for connection to a simple syringe or plunger-type device. In use, the liquid component of the suspension is caused to flow through the filter by mechanical force. Commercially available examples of this type of filter include: Acrodisc® Syringe Filters and the Whatman Mini-UniPrep™ system. The salient aspects of some related devices are described in part in U. S. Patent Nos. 4,800,020; 4,832,850; and 4,897, 193. The most significant limitation of these devices is the need to transfer a suspension to an appropriate vessel prior to filtering the suspension. Transferring such suspensions presents a significant problem for common automation systems currently used in chemical and biological laboratories. Another major class of filtration devices includes those in which the filter constitutes an integral part of the vessel that contains the suspension. Although these devices eliminate the need to transfer the suspension, these systems encounter limitations in terms of flexibility in application and cost. In use, these devices involve complex assembly and disassembly of components prior to filtration. Furthermore, these devices cannot be easily incorporated onto a non-dedicated automation platform. Moreover, these devices typically cannot be employed in an unattended automated process. Examples of these systems include the Argonaut Quest™ 205 synthesizer, the Argonaut Quest™ 210 synthesizer, the Robbins FlexChem™ reaction block, described in U. S. Patent No. 6,054,100, the Eli Lilly Multiblock reactor, described in U. S. Patent No. 5,785,927, the Glaxo Wellcome combinatorial synthesizer block, described in U. S. Patent No. 6,051 ,439, the Bristol Myers Squibb Company combinatorial reaction block, described in U. S. Patent No. 5,961,925, the Oxford Asymmetry Int. PLC Tube Reaction Apparatus, described in PCT Application WO 98/36829, and the Technology Partnership PLC U-Type filters, described in PCT Application WO 97/04863. Also included in this area are the Polyfiltronics microtitre type filters typified by the MultiChem™ and UNIFILTER® systems. Another major class of laboratory filters is a straw-type device comprising a glass straw capped by a porous glass filter. These filters typically operate by applying a pressure differential between the interior portion and the exterior portion of the device. The resultant pressure imbalance forces the liquid component of the suspension through the porous filter into the straw, from where it can be aspirated or collected. Such filters are relatively expensive, and they can only be employed in an automated format as part of a highly integrated system. Typical examples of these systems include the Chemspeed ASW2000 synthesizer, the PE Biosystems Solaris™ 530 synthesizer, the Argonaut Nautilus™ synthesizer, and the Argonaut Trident™ synthesizer. U. S. Patent No. 5,945,070, and U. S. Patent No. 6,045,755 describe filters in which specially modified pipette tips must be employed to carry out the filtration process. Further, in one embodiment of U.S. Patent 6,045,755, a filtering element is attached to the terminus of the pipette. This technique has the potential to result in the loss of the particulate component of the suspension during the filtration process.

Other similar devices include those that are used to contain reactive particles during the course of a chemical reaction. One example of such a device is described in U. S. Patent No. 4,631 ,211 and PCT Application WO 99/25470, in which reactive particles are contained within a sealed, porous container. The device is introduced into a liquid reaction medium. Upon completion of the reaction, the container is removed from the reaction mixture and washed. This procedure separates the materials that have become attached to the reactive particles from the materials remaining in the reaction medium.

Given the limitations of the systems described, there exists a need for a simple, flexible, and inexpensive device that can be used in combination with a variety of laboratory-scale reaction vessels and appropriate automation equipment to separate particulate materials from suspensions.

SUMMARY OF THE INVENTION

In one aspect, this invention provides a filtering device. The device comprises a filtering element that can be attached to an adapter. The filtering element comprises a mesh surrounding a cavity. The mesh of the filtering element is constructed to have sufficient porosity so that hydrostatic pressure forces the liquid components of a suspension into the cavity of the filtering element from where they can be aspirated and collected. Preferably, at least one semi-rigid rib supports the mesh. Both the mesh and the semi-rigid rib (or ribs) are made of chemically inert material. The preferred shape of the filtering element is cylindrical or frusto- conical. The purpose of the adapter is to correctly position the filtering element within a vessel containing a suspension. In one embodiment, a single adapter is attached to a single filtering element. In another embodiment, a multiple adapter assembly can be used to join a plurality of adapters to a plurality of filtering elements and to position the thus-joined filtering elements in a linear or matrix format, so that a plurality of suspensions can be filtered in parallel.

In another aspect, this invention provides a method for using the filtering device in a variety of applications. These applications include, but are not limited to, sampling of suspensions, filtration of particulate materials from suspensions, and purification or isolation of chemical or biological components contained within the suspension. The method for using the device requires the following steps: (a) the filtering element is attached to the adapter, (b) the filtering element is inserted into a vessel containing a suspension, and

(c) the filtering element is retained within the suspension for a period of time sufficient to ensure that at least a portion of the liquid component of the suspension flows through the mesh into the cavity of the filtering element.

In another embodiment of the invention, steps (a) through (c) of the above method are repeated; then, in an additional step (d), the contents of the cavity are removed, thereby effecting at least partial separation of the solid and liquid components of the suspension. During step (d), the liquid component of the suspension remaining in the vessel continues to flow through the mesh into the cavity of the filtering element, whereby filtration of the suspension can be completed. In another embodiment of the invention, steps (a) through (d) of the previous embodiment are repeated; upon removal of the liquid component, in an additional step (e) fresh solvent is introduced into the suspension by dispensing the solvent into the cavity of the filtering element. After a suitable period of time has elapsed, an optional step (f) may be performed, which step involves the aspiration from the cavity of the filtering element and dispensing to the cavity of the filtering element a volume of liquid at such a rate as to substantially agitate the suspension. Then, an additional step (g) can be performed, which step involves removal of the additional solvent from the cavity of the filtering element. Steps (e), (f), and (g) can be repeated in an iterative fashion, as often as required by the particular application in which method is employed.

In another embodiment, steps (a) through (g) of the method are repeated, with the exception that the solvent can be varied during each iteration, the choice of a particular solvent for a particular iteration being a function of the nature of the application.

The device of this invention can be applied in a number of applications. The applications include, but are not limited to, sampling of suspensions, filtration of particulate material from suspensions, and purification or isolation of chemical or biological components contained within the suspension. The filtering device is reusable and the same filtering element can be attached to a variety of adapters, and vice versa. Filtration can be performed on a variety of scales, from a variety of vessels, and, when required, in parallel. In addition, the method can be easily integrated onto common automation platforms, as the filtering device and the method for its use do not involve complex assembly or disassembly of components. The methods described herein have the advantage of specifying procedures that provide for either sampling or filtering of suspensions. In addition, the methods allow the selective separation of dissolved materials by means of appropriate combinations of solvents.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 A is a perspective view illustrating one embodiment of a filtering element suitable for the filtering device of this invention.

FIG. 1 B is a side view in elevation of the filtering element of FIG. 1A.

FIG. 1 C is a top plan view of the filtering element of FIG. 1A.

FIG. 1 D is a side view in elevation of the filtering element of FIG. 1 A.

FIG. 1 E is a side view in elevation of the filtering element of FIG. 1A. FIG. 1 E is identical to FIG. 1 D, with the exception that the filtering element is rotated 90° about its longitudinal axis.

FIG. 2A is a perspective view illustrating one embodiment of an adapter suitable for the filtering device of this invention.

FIG. 2B is a side view in elevation illustrating an adapter suitable for the filtering device of this invention.

FIG. 2C is a cross-sectional view in elevation of the adapter of FIG. 2B. FIG. 2D is a bottom plan view of the adapter of FIG. 2B.

FIG. 2E is a cross-sectional view, greatly enlarged, of the portion of FIG. 2B bounded by line 2E-2E.

FIG. 2F is a side view in elevation, greatly enlarged, of the portion of FIG. 2B bounded by line 2F-2F.

FIG. 3A is a schematic view of a filtering element of this invention in combination with an adapter. This view illustrates the proper location of the device within a vial.

FIG. 3B is a schematic view of a filtering element of this invention in combination with an adapter. This view illustrates the proper location of the device within a round-bottom flask.

FIG. 4 is a schematic view of an array-type adapter connected to a plurality of filtering elements. This view illustrates the proper location of the device within a plurality of vials.

FIGS. 5A, 5B, 5C, 5D, 5E, and 5F are schematic views illustrating a method for using the filtering device of this invention.

FIG. 6 is a graph illustrating the kinetics of sequestration of a secondary amine from a mixture containing the secondary amine and a tertiary amine. This graph illustrates the results of Example 3.

DETAILED DESCRIPTION OF THE INVENTION As used herein, the term "suspension" means a relatively coarse, noncolloidal dispersion of solid particles in a liquid. Suspensions include, but are not limited to, slurries. The term "solvent" means a liquid capable of dissolving another substance. The term "solvent" includes, but is not limited to, organic solvents, aqueous solvents, and buffers. The term "sampling" means the act or process of selecting, testing, or examining a sample, i. e., a part representative of a whole.

Referring now to FIGS. 1 A through 1 E, FIGS. 2A through 2F, and FIGS. 3A through 3B, this invention provides a filtering device 10 comprising a filtering element 12 that can be attached to an adapter 14. The filtering element 12 preferably has a substantially cylindrical, a substantially conical, or a substantially frusto-conical shape. The material of the filtering element 12 is a mesh 16 comprising a chemically inert material. It is preferred that that material from which the mesh 16 is formed be chemically inert so that it does not interact with the components of the suspension. The material from which the mesh is formed is preferably a polymeric material, such as, for example, polypropylene, polytetrafluoroethylene (e. g., "TEFLON"). The mesh 16 surrounds a cavity 18. If the filtering element is substantially cylindrical or substantially frusto-conical in shape, one end 20 of the filtering element 12 is also preferably constructed of a mesh comprising a chemically inert material. The open spaces of the mesh preferably have at least one major dimension (e. g., length, diameter) ranging from about 20 micrometers to about 150 micrometers, preferably from about 30 micrometers to about 150 micrometers, more preferably from about 50 micrometers to about 150 micrometers. This dimension is selected to ensure that the particulate material of the suspension will be excluded from the cavity 18 of the filtering element 12. However, the mesh 16 must also have sufficient porosity to allow the liquid components of the suspension to flow into the cavity 18 of the filtering element 12 under the force of the hydrostatic pressure that is created when the filtering device 10 is used.

The shape of the filtering element 12 is preferably maintained by at least one rib 22, which supports the mesh 16. The at least one rib 22 comprises a semi-rigid, chemically inert material. The material from which the ribs 22 are formed is preferably a polymeric material, such as, for example, polypropylene. The mesh 16 is preferably attached to the at least one semi-rigid rib 22 by means of thermal bonding, ultrasonic welding, or molding. Another end 24 of the filtering element 12, distal from the end 20, is capable of being attached to the adapter 14. The end 24 of the filtering element 12 has an orifice 25 into which an end of the adapter 14 can be inserted. When the filtering element 12 is not conical in shape, the end 20 of the filtering element may have sufficient area to cause the filtering element 12 to have a base at the end 20. When the filtering element 12 has such a base, it is preferred that at least one protrusion 26, and preferably a plurality of protrusions 26, projects from the periphery of the end 20. This protrusion 26 or protrusions 26 serves to prevent the end 20 from resting on the bottom of the vessel in which the filtering element 12 is used. This separation of the end 20 from the bottom of the vessel increases the efficiency of an optional agitation step of the method of this invention, which will be discussed below.

The adapter 14 is preferably constructed from a chemically inert material, such as, for example, a polymeric material, such as, for example, polypropylene. The filtering element 12 is preferably attached to the adapter 14 by releasable retaining means 27, as shown in FIG. 2E.

In a preferred embodiment, the adapter 14 has a substantially frusto-conical body having a first end 28 and a second end 30. However, the shape of the adapter 14 need not be frusto-conical. For example, the adapter 14 can be cylindrical in shape. The first end 28 of the adapter 14 communicates with the end 24 of the filtering element 12. The second end 30 of the adapter 14 comprises a flange 32. The adapter 14 comprises a wall 33 that surrounds a cavity 34. The first end 28 of the adapter 14 has an orifice 36 and the second end 30 of the adapter 14 has an orifice 38 positioned in the flange 32. The portion of the adapter 14 surrounding the orifice 38 is preferably beveled to aid in guiding any aspirating apparatus within the adapter 14 of the filtering device 10. The slope resulting from the beveling serves as a mechanical guide to aid in properly locating any aspirating apparatus within the adapter 14. When the adapter 14 is joined to the filtering element 12, the orifices 36 and

38 of the adapter 14 are aligned with the orifice 25 in the end 24 of the filtering element 12. This alignment allows the tip of a pipette to be inserted through the adapter 14 and into the cavity 18 of the filtering element 12 so that liquid in the cavity 18 of the filtering element 12 can be aspirated from the cavity 18.

The adapter 14 has two primary functions. The first function is to correctly orient the filtering element 12 within a vessel 40 that contains the suspension, as shown in FIGS. 3A and 3B. The filtering element 12 is preferably located centrally in the vessel 40 (i. e., equidistant from the wall 42 of the vessel 40), and the end 20 of the filtering element 12 is preferably placed near the bottom 44 of the vessel 40. Preferably, the end 20 of the filtering element 12 should not contact the bottom 44 of the vessel 40. The second function is to ensure that a partial vacuum does not develop in the space between the filtering device 10 and the wall 42 of the vessel 40. These features are important for ensuring efficient use of the filtering device 10. At least one rib 46, preferably a plurality of ribs 46, as shown in FIG. 2B, can be used to carry out the aforementioned functions. The ribs 46 are sufficiently malleable to allow the facile insertion of the filtering element 12 into the vessel 40; however, the ribs 46 are still capable of accurately positioning the filtering element 12 within the opening in the neck 48 of the vessel 40. The flange 32 of the adapter 14 controls the depth to which the filtering element 12 of the device 10 can be inserted into a suspension in the vessel 40. FIGS. 3A and 3B illustrate how the flange 32 controls the depth to which the filtering element 12 of the device 10 is inserted in the vessel 40.

In the preferred embodiment, the filtering element 12 and the adapter 14 are separable. Alternatively, the adapter 14 and the filtering element 12 can be of a unitary construction. This alternative, however, reduces the versatility of the filtering element 12. The filtering device 10 can be used in any type of vessel 40, provided that an appropriate adapter 14 is used. Because adapters 14 can be easily manufactured and are relatively inexpensive, as compared to the filtering element 12, significant cost and flexibility advantages can be realized by offering a wide variety of adapters. While the dimensions of the adapter 14, the filtering element 12, and the vessel 40 are not critical, representative examples of dimensions will be provided in order to demonstrate the scale of these components. A typical vessel suitable for use in a laboratory setting is cylindrical vessel having a length of approximately 1 3/4 inches. The base of the vessel has an outside diameter of about 9/16 of an inch. The top of the vessel has an outside diameter of about 7/16 of an inch. The diameter of the opening of the vessel, which is at the top thereof, is about 3/8 of an inch. As shown in the embodiment of FIGS. 1 A through 1 E, the filtering element 12 is substantially cylindrical in shape. The length of the mesh portion of the filtering element 12 is about 1 inch. The outside diameter of the mesh portion of the filtering element 12 is about 7/32 of an inch. The length of the portion of the filtering element 12 that connects with the adapter 14 is about 3/8 of an inch. The inside diameter of this connecting portion is sufficiently large to fit over the portion of the adapter 14 that connects with the filtering element 12. The diameter of the orifice 25 of the filtering element 12 is about 1/4 of an inch.

As shown in the embodiment of FIGS. 2A through 2E, the adapter 14 is frusto-conical in shape. One end 30 of the adapter 14 has a flange 32 that supports the filtering device 10 when that device is inserted into the vessel 40. The overall length of the adapter 12 is about 7/8 of an inch. The height of the flange is about 1/16 of an inch. The outside diameter of the first end 28 of the adapter is about 3/16 of an inch. The outside diameter of the flange 32 is about 7/16 of an inch. The diameter of the cavity 34 of the adapter 14 is about 3/16 of an inch at the first end 28. The diameter of the cavity 34 of the adapter 14 gradually increases along its length toward the second end 30, because the adapter 14 is frusto-conical in shape. It is preferred that the thickness of the wall of the adapter 14 and the thickness of the wall of the filtering element 12 be as small as possible in order to reduce the cost of materials; at the same time the thickness of the walls of these components should be sufficiently large to ensure structural integrity.

FIG. 4 shows a multiple adapter assembly 52 suitable for positioning an array of filtering elements 12 into a plurality of vessels 40. The multiple adapter assembly 52 comprises a positioning plate 54 and a plurality of adapters 56. In one preferred embodiment, the positioning plate 54 comprises a sheet, preferably made of polymeric material, having a plurality of openings 58 therein into which the plurality of adapters 56 can be inserted. The adapters 56 can be identical to the single adapter 14 previously described. The adapters 56 of the multiple adapter assembly 52 can be designed to have a height of such a length that the adapters 56, in combination with the positioning plate 54 can control the depth to which a filtering element 12 may be inserted into a vessel 40. In another embodiment, the adapter 56 does not need to have a flange as does the adapter 14. When the adapter 56. does not have a flange, it is preferred to employ some type of releasable retaining means at the end of the adapter 56 that joins with the positioning plate 54 so that the adapter 56 will be held securely during the filtering operation. A releasable retaining means suitable for such a purpose can be of a type similar to that of the releasable retaining means 27. When necessary, the areas of the positioning plate 54 of the multiple adapter assembly 52 immediately surrounding each opening 58 of the multiple adapter assembly 52 can be beveled to facilitate the insertion of liquid handling apparatus, such as tips of pipettes, into the filtering devices that are formed by the combination of the adapters 56 of the multiple adapter assembly 52 and the filtering elements 12. The slope resulting from the beveling serves as a mechanical guide to aid in properly locating any aspirating apparatus into the adapters 56 of the multiple adapter assembly 52. In an alternative embodiment, the adapters 56 of the multiple adapter assembly 52 and the positioning plate 54 of the multiple adapter assembly 52 can be of a unitary construction. In still another alternative embodiment, the adapters 56 of the multiple adapter assembly 52, the positioning plate 54 of the multiple adapter assembly 52, and the filtering elements 12 can be of a unitary construction. The multiple adapter assembly 52 is capable of holding several filtering elements 12 in a linear format or a matrix format, thereby facilitating parallel filtration of a plurality of suspensions.

The proper use of the filtering device 10 requires that the following steps be performed. The filtering element 12 is first attached to an appropriate adapter 14. See FIGS. 3A and 3B. The combination of the filtering element 12 and the adapter 14 is then inserted into a vessel 40 containing a suspension. See FIGS. 5A and 5B, where the combination of the filtering element 12 and the adapter 14 is designated by the reference numeral 10, the vessel is designated by the reference numeral 40, the suspension is designated by the letter "S" and the filtrate is designated by the letter "F". By inserting the filtering device 10 into the suspension, liquid is forced into the cavity of the filtering element by the hydrostatic pressure arising from the physical insertion of the filtering device 10 into the suspension. See FIGS. 5B and 5C. The liquid can then be aspirated from the cavity of the filtering element and collected. See FIGS. 5D, 5E, and 5F. During the step of removing the liquid component from the cavity of the filtering element of the filtering device 10 during a filtering operation, the liquid component of the suspension remaining in the vessel 40 continues to flow through the mesh into the cavity of the filtering element. The procedure for using a plurality of filtering elements 12 with the adapter of the type shown in FIG. 4 is substantially similar to the procedure for using the filtering element 12 with the adapter 14. The main difference between the embodiments is that a plurality of filtering elements 12 and a plurality of vessels 40 are used with the adapters 56 of the type shown in FIG. 4.

In one application of this invention, the filtering device 10 can be employed as described above to sample a suspension of interest. The filtering device 10 is inserted into a suspension, and a small volume of the filtrate is sampled and analyzed. The filtering device 10 can then be removed, and the suspension subjected to the same conditions as those prior to the sampling. The method allows periodic analysis of reaction mixtures occurring in suspensions. If reaction conditions permit, the filtering device 10 can be left within the suspension throughout the course of sampling. In another application of this invention, an appropriate volume of fresh solvent can then be dispensed into the cavity 18 of the filtering element 12, from where it passes into the surrounding suspension as a result of the aforementioned forces. After a sufficient equilibration period, the liquid in the cavity 18 is again aspirated and collected. This process is repeated a sufficient number of times to ensure that the required degree of recovery of the desired components is achieved. This process can be repeated with different solvents that are selected to optimize the efficiency of the process. The efficiency of the process can be improved by agitating the suspension after each addition of solvent, either by rapidly dispensing solvents through the mesh of the filtering element 12, or by a separate mechanical agitation. By using a different solvent from that present in the original suspension, and by employing the iterative embodiment previously described, the filtration method can be performed with solvents having gradually differing compositions. The precise composition of the solvents can be modified by varying the percentage of the solvent aspirated from the suspension in each iteration of the filtration method.

The filtering device 10 of this invention and the method for its use are designed to be applied principally on a laboratory scale, and most commonly with suspensions comprising polystyrene beads dispersed in organic or aqueous solvents.

The following non-limiting examples further illustrate the device and method of this invention. In the examples, the expression "robotic pipette" refers to a Tecan Genesis™ robotic platform comprising with eight syringes (1 mL) equipped with standard tips employing methanol as a system fluid. The vials (4 mL) used for reactions and filtrations were supplied by Kimble Glass [Art. No. 60881 A-1545]. The scintillation vials (20 mL) specified were supplied by the same company [Art. No. 60957-1]. Nuclear magnetic resonance analytical data on the product samples was acquired by means of a Varian Unity 500 MHz NMR spectrometer, and mass spectra were acquired by means of a Finnigan XSQ 7000 mass spectrometer. The prototype devices used to perform the filtrations in the examples were provided by Abbott Laboratories Development Shop and were similar to those shown in FIGS. 1 , 2, 3, and 4.

EXAMPLE 1

This example demonstrates the use of this invention to filter a reaction mixture containing a reagent supported on a polymeric particle. The chemical reaction associated with this reaction mixture has been described in Tetrahedron Letters, Vol. 37, No. 40. pp. 7193-7196, 1996. The reaction involves a procedure for the introduction of an alkyl group onto a variety of different amines, in a process referred to as Reductive Alkylation (Scheme 1).

4-Phenylbenzaldehyde [1] (0.600 g; 3.29 mmol) was dissolved in dry methanol (24 mL). Aliquots of this solution (1 mL) were distributed by means of a robotic pipette to 24 open vials (4 mL) contained in a 6 x 4 Irori block (AccuCleave®- 96 Collection Rack; Irori Product No. AC96-04-24). A different primary amine [2] was then added to each of the vials, and the resultant mixtures were agitated on a shaker for two hours. Borohydride resin (Aldrich 32,864-2, -2.5 mmol BH₄7g on Amberlite® IRA-400; 0.110 g per reaction; 0.275 mmol) was added to each vial, after which all the vials were capped and the resulting suspensions agitated for an additional 12 hours. The reactions were conducted at room temperature.

[1] PI

Scheme 1. Reductive Alkylation of 4-Phenylbenzaldehyde

Filtration Step

The vials were then uncapped. A filtering device of the type shown in FIG. 4 comprising an adapter capable of accommodating a 6 x 4 array of the filtering elements was employed to insert the filtering elements into the 24 vials. The filtering elements were constructed from 74 μm polypropylene mesh (Spectrum, Product No. 148495). The resultant assembly was then transferred to the deck of the robotic pipette. The filtration process was accomplished by the following operations executed in parallel. For each vial, the process involved the following activities:

A. Initial Transfer

B. First wash

C. Second wash D. Third wash

E. Further processing A. Initial Transfer [Steps (1) through (6)]

(I) The suspension was agitated by aspirating liquid from and dispensing liquid into the cavity of the filtering element. Three aspirate-dispense cycles, each involving 0.500 mL of liquid, were employed. (2) A short pause (10 seconds) was allowed to re-establish equilibrium.

(3) Liquid (0.750 mL) was aspirated from the cavity.

(4) The aspirated liquid was dispensed into a separate vial (4 mL) placed in a destination rack.

(5) Residual liquid remaining in the cavity of the filtering element was collected by means of an additional aspiration step. The residual volume of approximately 0.300 mL was over-aspirated (0.600 mL) to ensure completeness of transfer.

(6) The aspirated liquid was dispensed into the appropriate vial in the destination rack.

B. First Wash [Steps (7) through (13)]

(7) Methanol (0.750 mL) was dispensed into the cavity of the filtering element.

(8) The resulting mixture was agitated by aspirating liquid from and dispensing liquid into the cavity of the filtering element. Three aspirate- dispense cycles, each involving 0.500 mL of liquid, were employed.

(9) A short pause (10 seconds) was allowed to re-establish equilibrium. (10) Liquid (0.750 mL) was aspirated from the cavity of the filtering element.

(I I) The aspirated liquid was dispensed into the appropriate vial in the destination rack.

(12) Residual liquid remaining in the cavity (0.400 mL) was aspirated.

(13) The aspirated liquid was dispensed into the appropriate vial in the destination rack.

C. Second Wash [Steps (14) through (20)]

(14) Methanol (0.750 mL) was dispensed into the cavity of the filtering element. (15) The resulting mixture was agitated by aspirating liquid from and dispensing liquid into the cavity of the filtering element. Three aspirate- dispense cycles, each involving 0.500 mL of liquid, were employed.

(16) A short pause (10 seconds) was allowed to re-establish equilibrium. (17) Liquid (0.750 mL) was aspirated from the cavity of the filtering element.

(18) The aspirated liquid was dispensed into the appropriate vial in the destination rack.

(19) Residual liquid remaining in the cavity (0.500 mL) was aspirated.

(20) The aspirated liquid was dispensed into the appropriate vial in the destination rack.

D. Third Wash

Steps (14) through (20) were then repeated.

Further Processing

The resulting filtrates contained in the destination rack were then evaporated to dryness, weighed, and the crude weights determined. The residues were then re- splvated in a solvent mixture (1.5 L of 1 :1 dimethyl sulfoxide/methanol) and purified by preparative HPLC (Waters Nova-Pak^® HR C18; 6 μm 6θA; 25x100 mm; 0-95%) acetonitrile/0.1% trifluoroacetic acid over 10 min at 40 mL/min). As a result, the alkyl ethers [3] were obtained as TFA salts at yields ranging from 43% to 83% (average yield = 71%). The purified products were characterized by means of Mass Spectrometric Analysis and Nuclear Magnetic Resonance Spectroscopy.

When methylamine hydrochloride (Aldrich 24,101-6, 18.5 mg, 0.274 mmol) was used as a reactant in the process described above, the crude alkyl ether [4] (33.8 mg) was isolated. After the purification, the product was obtained as a white amorphous solid of its trifluoroacetic acid salt (22.0 mg (46%)). ¹H NMR (500 MHz, methanol-d₄) δ ppm 7.72 (m, 2H), 7.64 (m, 2H), 7.55 (m, 2H), 7.46 (m, 2H), 7.37 (m, 1H), 4.22 (s, 3 H), 2.74 (s, 3 H). MS: ESI (M+1 - pos. ion) 198.

EXAMPLE 2

The purpose of this example was to examine the efficiency of the filtration method of this invention. The same type of borohydride resin as was used in Example 1 (0.065 g; 0.275 mmol) was added to three vials (4 mL) containing a solution comprising an alkyl ether of type [3] shown in Example 1 (15.6 mg, molecular weight 225.33 g/mol) in 1 mL of methanol. The vials were then capped and the resulting suspensions agitated for 12 hours. The vials were then uncapped, and filtering devices of the type shown in FIGS. 3A and 3B were inserted into the vials. The filtering elements were constructed of a 74 μm polypropylene mesh. The entire assembly was then transferred to the deck of the robotic pipette, and filtration was carried out as described in steps (1)-(20) of Example 1. The solutions in the destination vials were evaporated to give on average 14.8 mg of the reaction product. When the washing protocol was repeated in the absence of the alkyl ether (resin only), the destination vials contained on average 0.3 mg of the unidentified material originating from the resin. Thus, the efficiency of the filtration process described above was approximately 93% [(14.8-0.3)/15.6x 100%].

EXAMPLE 3

This example demonstrates the filtration of a reaction mixture employing a sequestration agent supported on a polystyrene support. This procedure results in the removal of one of the components of the mixture and the isolation of the desired material. The method for removing secondary and primary amines by means of isocyanate supported on polystyrene was described in "Polymer Reagents and Scavengers for Parallel Solution Phase Synthesis & Purification" Argonaut Technologies application Note DS-018, 1999, Rev. 3.

A mixture of Dansylamide [5] (Aldrich; Catalog No. 21,889-8; 25.1 mg) and bis-(2,4- Dimethoxybenzyl)amine [6] (Merck-Schuchardt; Art. 810208; 31.7 mg) was dissolved in dry tetrahydrofuran (3 mL). The resulting solution was transferred to a scintillation vial (20 mL) containing a resin (PS-lsocyanate, Argonaut Technologies; Lot No 081-93, 0.200 g; 1.50 mmol/g). A filtering device of the type shown in FIGS. 3A and 3B was then inserted into the vial. The vial was then capped and the contents were vigorously shaken by means of a shaker. The cap was removed periodically, and an aliquot (10 μL) of the solution was removed from the cavity of the filtration element by means of a manual pipette. The aliquot was diluted with methanol (0.5 mL) in an HPLC vial. The sample thus prepared was analyzed by analytical HPLC (YMC ODS AQ; 5 μm; 4x50 mm, 0-95% MeCN/0.1% TFA over 10 min at 1.5 mL/min; retention time (R_τ) for the tertiary amine [5] 3.0 min, retention time (R_τ) for the secondary amine [6] 4.8 min). The kinetics of sequestration of the secondary amine were monitored by measuring disappearance of the peak at 4.8 minutes. Areas under peaks of the trace produced by an evaporative light scattering (ELS) detector were integrated and the area % of the 4.8 min peak was used as a measure of the amount of the secondary amine present in the mixture. It was assumed that the concentration of the tertiary amine that could not be sequestered by the resin would be constant. The results of the measurements are shown in Table 1 , and a plot of the data is shown in FIG. 6. TABLE 1

A rapid disappearance of the secondary amine was observed over the first five minutes of the experiment. After this time, the concentration of the secondary amine leveled off. The sampling of the reaction mixture was repeated after 12 hours. The HPLC analysis revealed that a small amount of the secondary amine was still present in the reaction mixture. At this point the solution was aspirated from the cavity of the filtering element by means of a Pasteur pipette and collected in a separate scintillation vial (20 mL). The aspiration was repeated a sufficient number of times to completely drain liquid from the vial. Then, additional tetrahydrofuran (4 mL) was then dispensed into the cavity of the filtering element, the contents of the vial were shaken for five minutes, and the liquid was removed from the cavity in the manner described previously. The filtrates were combined. Washings were repeated two more time with tetrahydrofuran (4 mL). The combined filtrates were evaporated to dryness to give 25.3 mg of a material that was shown by ¹H NMR to be the tertiary amine [5] contaminated with approximately 4.5 mol % of the secondary amine [6]. Amine [5]: ¹H NMR (500 MHz, DMSO-d₆) δ ppm 8.43 (m, 1 H), 8.29 (m, 1 H), 8.13 (m, 1 H), 7.59 (m, 4 H), 7.25 (m, 1 H), 2.83 (s, 6 H). Amine [6]: ¹H NMR (500 MHz, DMSO-d₆) δ ppm 7.19 (m, 2 H), 6.52 (m, 2 H), 6.46 (m, 2 H), 3.76 (s, 6 H), 3.74 (s, 6 H), 3.56 (s, 4 H). The amount of the residual [6] in the mixture was calculated from the ratio of areas of resonances: 2.83 ppm of [5] (integration value 100.0) and 3.76 ppm of [6] (integration value 4.65). Thus, mol % of [6] in the mixture was found to be 4.65/(100.0+4.65)*100% = 4.5 mol %. Various modifications and alterations of this invention will become apparent to those skilled in the art without departing from the scope and spirit of this invention, and it should be understood that this invention is not to be unduly limited to the illustrative embodiments set forth herein.

Claims

What is claimed is:

1. A device for filtering particulate material from a suspension, said device comprising a filtering element comprising a mesh surrounding a cavity, said mesh capable of allowing transfer of liquids through said filtering element by means of application of hydrostatic pressure, said mesh further comprising a chemically inert material.

2. The device of claim 1 , wherein said filtering element is substantially conical in shape.

3. The device of claim 1 , wherein said filtering element is substantially frusto-conical in shape.

4. The device of claim 1 , wherein said filtering element is substantially cylindrical in shape.

5. The device of claim 1 , wherein said mesh is supported by means of at least one semi-rigid rib, said at least one rib comprising a chemically inert material.

6. The device of claim 1 , wherein said filtering element has an orifice at one end thereof.

7. The device of claim 1 , wherein said filtering element has a base, said base comprising a mesh, said mesh capable of allowing transfer of liquids through said filtering element by means of application of hydrostatic pressure, said mesh further comprising a chemically inert material.

8. The device of claim 7, wherein said base further comprises at least one protrusion projecting from the periphery of said base.

9. An adapter capable of being attached to said filtering element of claim 6.

10. The adapter of claim 9, wherein said adapter comprises an orifice that is capable of communicating with said orifice of said filtering element.

11. The adapter of claim 9, wherein said adapter has a first end and a second end.

12. The adapter of claim 11 , wherein said first end of said adapter communicates with said orifice of said filtering element.

13. The adapter of claim 11 , wherein said second end of said adapter comprises a flange.

14. The adapter of claim 10, wherein said second end of said adapter has an orifice, the portion of said adapter surrounding said orifice of said second end being beveled.

15. The adapter of claim 11 , wherein said adapter comprises a wall that surrounds a cavity.

16. The adapter of claim 15, wherein said adapter is substantially cylindrical in shape.

17. The adapter of claim 15, wherein said adapter is substantially frusto- conical in shape.

18. The adapter of claim 9, said adapter having means on the exterior thereof for allowing air or gas to enter a vessel into which said adapter has been inserted

19. The adapter of claim 18, wherein said means comprises at least one rib, said at least one rib being of sufficient malleability to allow insertion of said adapter into a vessel.

20. The device of claim 1 , further including an adapter joined to said filtering element.

21. The device of claim 20, wherein said adapter and said filtering element are of a unitary construction.

22. The device of claim 20, wherein said adapter is separable from said filtering element.

23. A multiple adapter assembly capable of being attached to a plurality of filtering elements.

24. The multiple adapter assembly of claim 23, wherein said assembly comprises a positioning plate having a plurality of openings therein arranged in a linear array, each of said openings being capable of retaining a filtering element.

25. The multiple adapter assembly of adapter of claim 23, wherein said assembly comprises a positioning plate having a plurality of openings therein arranged in a matrix array, each of said openings being capable of retaining a filtering element.

26. The multiple adapter assembly of claim 23, wherein said assembly and said filtering elements are of a unitary construction.

27. An assembly comprising (1) a device for filtering particulate material from a suspension, said device comprising a filtering element comprising a mesh surrounding a cavity, said mesh capable of allowing transfer of liquids through said filtering element by means of application of hydrostatic pressure, said mesh further comprising a chemically inert material and (2) a vessel into which said filtering device can be inserted.

28. The assembly of claim 27, wherein said device further includes an adapter joined to said filtering element.

29. The assembly of claim 27, wherein an adapter causes one end of said filtering element to be positioned at or near the bottom of said vessel.

30. The assembly of claim 27, wherein an adapter causes said filtering element to be maintained in a vertical orientation.

31. The assembly of claim 27, further comprising an adapter that fits into an orifice in said vessel.

32. An assembly comprising (1) an adapter, (2) a plurality of devices for filtering particulate material from a suspension, each of said devices comprising a filtering element comprising a mesh surrounding a cavity, said mesh capable of allowing transfer of liquids through said filtering element by means of application of hydrostatic pressure, said mesh further comprising a chemically inert material, and (3) a plurality of vessels into which said filtering elements can be inserted, said adapter being attached to each of said filtering elements.

33. A device for filtering particulate material from a suspension, said device comprising a filtering element comprising a mesh surrounding a cavity, said mesh capable of allowing transfer of liquids through said filtering element by means of application of hydrostatic pressure, said mesh further comprising a chemically inert material, said device further comprising an adapter joined to said filtering element.

34. The device of claim 33, wherein said filtering element has an orifice and said adapter has an orifice, said orifice of said filtering element communicating with said orifice of said adapter.

35. A method for separating particulate materials from a suspension comprising a liquid and particulate materials, said method comprising the steps of:

(a) providing at least one filtering device of claim 1 ;

(b) inserting said at least one filtering device into a vessel containing said suspension; and

(c) allowing said liquid to flow into said cavity of said filtering element.

36. The method of claim 35, further including the step of removing said liquid from said cavity of said filtering device.

37. The method of claim 35, further including the step of adding at least one solvent to said suspension by dispensing said solvent into said cavity of said filtering element.

38. The method claim 37, wherein said at least one solvent is dispensed sufficiently rapidly to agitate said suspension.

39. The method of claim 37, further including the step of removing said solvent from said suspension by aspirating said solvent through said cavity of said filtering element.

40. The method of claim 39, further including the steps of adding an additional solvent to said suspension by dispensing said solvent into said cavity of said filtering element and removing said additional solvent from said suspension by aspirating said solvent through said cavity of said filtering element.

41. The method of claim 40, wherein said additional solvent is different from said solvent that was used initially.