WO2012103214A2

WO2012103214A2 - Magnetic pipette tip

Info

Publication number: WO2012103214A2
Application number: PCT/US2012/022545
Authority: WO
Inventors: Gerard Albert LAWTHER; Steven Patrick MOSELEY; Lydia Wu; Chris LE
Original assignee: Molecular Bioproducts, Inc.
Priority date: 2011-01-26
Filing date: 2012-01-25
Publication date: 2012-08-02
Also published as: WO2012103214A3

Abstract

A magnetic pipette tip (32) is disclosed including a pipette tip housing (34) with proximal and distal ends (38, 36) and a lumen (40) extending between the proximal and distal ends (38, 36). At least one magnet (42) is located within the lumen (40) of the pipette tip housing (34) between the proximal and distal ends (38, 36). The magnetic pipette tip (32) is configured for use in magnetic isolation of biological molecules.

Description

MAGNETIC PIPETTE TIP

[0001] The present application claims the filing benefit of co-pending U.S. Provisional Patent Application No. 61/436,256, filed on 26 January 201 1 , the disclosure of which is hereby incorporated by reference herein in its entirety.

FIELD OF THE INVENTION

[0002] The present invention relates generally to the isolation of biological molecules and, more particularly, to the magnetic isolation of biological molecules.

BACKGROUND OF THE INVENTION

[0003] Biological molecules, such as DNA, RNA, proteins, and genomic DNA, may be conventionally isolated and purified from a sample using magnetic particles having an affinity to the biological molecules and a larger magnet that is positioned external to a vessel containing the sample. Generally, the process of isolating and purifying the biological molecule begins with the lysis of cells, which are cultured to produce a desired biological molecule. In other applications, samples may include serum, cell culture supernatant, and PCR reactions as well. Magnetic particles having a small magnetic or paramagnetic core coated with one or more coating materials are added into the lysed sample and the mixture is incubated under conditions that allow the desired biological molecule to reversibly bind to the outer coating of the magnetic particle. Various coating materials are known and may include one or more polymers, biological molecules, or functional groups to facilitate the capture of the target molecule.

[0004] During incubation, the biological molecule reversibly binds to the coating material. Then, a magnet is positioned adjacent to and external of the vessel containing the sample, thereby attracting the biological molecule bound magnetic particles to the internal surface of the vessel that is adjacent to the magnet. By exploiting the magnetic properties of the magnetic core and the binding properties of the coating, the biological sample is separated from the lysis solution (i.e., the matrix).

[0005] The binding of the biological molecule to the coating material then may be disrupted by altering one or more properties of the sample containing the biological sample, releasing the biological material from the vessel while the magnetic particles are retained at the internal surface of the vessel that is adjacent to the magnet.

[0006] While this process has greatly benefitted bioassay techniques, the conventional protocol has required external magnets, which increase the complexity of the protocol. When a high-throughput workflow is desired, the conventional process has incorporated specialized magnetic sample plates with robotic arms for handling samples and magnetic sample plates. However, these high throughput workflow solutions greatly increase the cost and complexity of the experimentation. Additionally, these techniques are typically limited to a small number of liquid handling platforms.

[0007] Accordingly, there is a need for an improved process to magnetically isolate biological material that increases efficiency, decreases the complexity over the known, conventional processes, decreases the costs associated with these complex conventional processes, and is readily adaptable to a variety of liquid handling platforms.

SUMMARY OF THE INVENTION

[0008] The present invention overcomes the foregoing problems and other shortcomings, drawbacks, and challenges of known conventional processes for isolating desired biological molecules using magnetic particles. While the invention will be described in connection with certain embodiments, it will be understood that the invention is not limited to these embodiments. To the contrary, this invention includes all alternatives, modifications, and equivalents as may be included within the spirit and scope of the present invention.

[0009] According to one illustrative embodiment of the invention, a magnetic pipette tip is described. The magnetic pipette tip includes a pipette tip housing having proximal and distal ends. A lumen within the pipette tip housing extends between the proximal and distal ends. A first magnet is located within the lumen of the pipette tip housing between the proximal and distal ends.

[0010] In accordance with another illustrative embodiment, a pipetting system is described. The pipetting system includes the magnetic pipette tip and a pipetter. The pipetter has a pipetter housing, a shaft extending from the pipetter housing configured to receive the proximal end of the pipette tip housing, and a fluid aspirator within the housing. The fluid aspirator is configured to aspirate a fluid into the lumen of the pipette tip housing after the magnetic pipette tip is received by the shaft.

[0011] According to another illustrative embodiment, the invention is directed to a magnetic pipette tip assay system that includes the magnetic pipette tip and a plurality of magnetic beads. Each of the magnetic beads has a magnetic core and a coating. The coating is configured to reversibly bind a biological molecule to the magnetic beads. Each of the magnetic beads may pass through the distal end of the pipette tip housing, into the lumen, and be located proximate the first magnet.

[0012] In another illustrative embodiment, the invention is directed to a method of isolating a desired biological molecule. The method includes introducing the plurality of magnetic beads into a sample that contains the desired biological molecule. The desired biological molecule reversibly binds to a binding portion of the plurality of magnetic beads within the sample. The sample with the desired biological molecule reversibly bound to the plurality of the magnetic beads is aspirated into a magnetic pipette tip having a pipette tip housing, a lumen extending through the pipette tip housing, and a magnet located within the lumen. The biological molecule is released from the plurality of magnetic beads and expelled from the magnetic pipette tip while the magnet and the plurality of magnetic beads remain within the lumen.

[0013] According to another illustrative embodiment of the invention, a magnetic pipette tip that includes a pipette tip housing having proximal and distal ends. A lumen within the pipette tip housing extends between the proximal and distal ends. A magnetic portion is supported by the pipette tip housing and is located between the proximal and distal ends.

[0014] The above and other objects and advantages of the present invention shall be made apparent from the accompanying drawings and the description thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with a general description of the invention given above, and the detailed description of the embodiments given below, serve to explain the principles of the present invention.

[0016] FIG. 1 is a flowchart of an exemplary method of isolating a desired biological molecule in accordance with one embodiment of the present invention.

[0017] FIGS. 2A-2C are diagrammatic views illustrating the process of the exemplary method of FIG. 1 .

[0018] FIG. 3 is a side elevational view illustrating a magnetic pipette tip in accordance with one embodiment of the present invention.

[0019] FIG. 3A is an enlarged elevational view of the magnetic pipette tip of FIG. 3.

[0020] FIG. 4 is a side elevational view illustrating a magnetic pipette tip in accordance with another embodiment of the present invention.

[0021] FIG. 4A is an enlarged elevational view of the magnetic pipette tip of FIG. 4.

[0022] FIG. 5 is a side elevational view illustrating a magnetic pipette tip in accordance with another embodiment of the present invention.

[0023] FIG. 5A is an enlarged elevational view of the magnetic pipette tip of FIG. 5.

[0024] FIG. 6 is a side elevational view illustrating a magnetic pipette tip in accordance with another embodiment of the present invention.

[0025] FIG. 6A is an enlarged elevational view of the magnetic pipette tip of FIG. 6.

[0026] FIG. 7 is a side elevational view illustrating a magnetic pipette tip in accordance with another embodiment of the present invention and one exemplary method of using the same. [0027] FIGS. 8A-8D are side elevational views illustrating additional embodiments of magnetic pipette tips.

[0028] FIGS. 8E-8G are side elevational views illustrating magnets having adaptors in accordance with embodiments of the present invention.

[0029] FIG. 9 illustrates one embodiment of a conventional pipetter.

[0030] FIGS. 10A, 10B, and 1 0D are photographs of electrophoretic gels exemplifying the use of a magnetic pipette tip in accordance with one embodiment of the present invention.

[0031] FIG. 10C is a graph illustrating PCR sequencing data of a base pair sequence purified by using a magnetic pipette tip in accordance with one

embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0032] FIG. 1 is a flowchart 1 0 illustrating one method of isolating and purifying a desired biological molecule ("biomolecule"), which is described in further detail with reference to FIGS. 2A-2C. A cell culture 12 is raised or cultured according to a known manner to achieve expression of the biomolecule 14. It is understood that the methods and apparatii described herein may also be employed to isolate biomolecules from samples derived from non-cultured cells, such as tissue homogenates, biological fluids, environmental samples, whole organisms, PCR reactions, and so forth. The biomolecule 14 may include DNA, RNA, genomic DNA, proteins, or other biological molecules of interest such as steroids, growth factors, hormones, cytokines, chemokines, amino acids, fatty acids, carbohydrates, biomarkers, and so forth. The cells comprising the cell culture 12 are lysed with a lysis solution 18 (block 16). This solution, in the case of an alkaline lysis, may contain a strong base (such as sodium hydroxide, "NaOH") in addition to a detergent (such as sodium dodecyl sulfate, "SDS") and usually has a pH that is greater than about 8. Other methods, such as an enzymatic digestion using lysozymes or use of other detergents (such as Triton X-1 00) and buffers with different pH values can be employed as well. In all cases, the cellular membrane is disrupted and this releases the contents of the cytoplasm into the lysis solution 18. Precipitated cellular proteins can be removed by centrifugation, if needed. Collectively, the clarified lysis solution 18 and the biomolecule 14 may be referred to as the "sample." The sample is then placed into a suitable labware 20, such as sample wells, reservoirs, tubes, vials, vessels, etc. While the labware 20 is illustrated herein as being the same container throughout the method, it would be understood that multiple types of labwares or containers may be used with this method.

[0033] A plurality of magnetic beads 24 then may be introduced into the sample (block 22). In an alternative embodiment, the sample may be centrifuged and the resultant precipitate (not shown) containing the biomolecule 14 may be washed and re-suspended in another buffer prior to introducing the plurality of magnetic beads 24. Generally, the magnetic beads 24 may comprise less than about 10% of the total bead solution, and more specifically may range from about 5% to about 1 0%; however, other concentrations may be used if necessary or desired by a particular isolation assay.

[0034] The magnetic beads 24, also known as magnetic particles, may be constructed in a known manner, which generally includes a magnetic or

paramagnetic core having a coating applied thereto. The paramagnetic cores may be comprised of any suitably magnetic material, for example, iron oxide, that is capable of being magnetically attracted to a magnetic field yet is chemically stable with the desired coating. The coating may include one or more materials having a particular chemistry to confer a generalized or specific affinity for the biomolecule 14. Exemplary coatings may include carboxyl, silica, proteins, metals, peptides, and oligonucleotides. Some examples of commercially-available magnetic beads may include those that are manufactured by Thermo Fisher Scientific (Fremont, CA), such as magnetic beads available under the SERA-MAG tradename. While the shape and dimension of the resultant magnetic bead 24 may vary, a suitable diameter may range from about 10 nm to about 100 μιη. The three-dimensional structure of the magnetic beads 24 may also vary, including shapes (such as cylinders, spheres, or cones) and irregular shapes. Any size or shape of magnetic bead may be used that has an outer dimension that is sufficiently small to be used with one or more magnetic pipette tips as described in detail below.

[0035] While wishing to not be bound by theory, it is the conventional understanding of those of ordinary skill in the art that, in some embodiments, the biomolecule 14 includes a surface charge that is dependent on several factors: the particular functional groups comprising the molecular structure of the biomolecule 14; the tertiary folding of the biomolecule 14, which positions certain functional groups at the external surface; and the matrix (i.e., the solvent, lysis solution, etc.) containing the biomolecule 14. For example, the pH of the aqueous matrix may affect the protonation of some functional groups and thereby alter the surface charge. Accordingly, the coating for the magnetic beads 24 may be selected to possess a surface charge that opposes the surface charge of the biomolecule 14 and thereby electrostatically interacts with the biomolecule 14 and form the weak reversible bond therewith. This interrelationship also can be modulated through use of different buffers, with variations in pH, ionic strength, detergents, and so on. [0036] Once the plurality of magnetic beads 24 are added to the sample (as in block 22), the biomolecules 14 reversibly bind to the coating of the magnetic beads 24 and form a "biomolecule-magnetic bead complex." The sample then may be fully aspirated into a magnetic pipette tip 32 (block 30), a first embodiment of which is shown in greater detail in FIGS. 3 and 3A. The magnetic pipette tip 32 includes an elongated housing 34 that may be constructed from a molded, inert material, generally a plastic material, such as polypropylene, or a combination of suitable materials. The housing 34 has a distal end 36 that is tapered, a proximal end 38 that is enlarged to form a hub configured to be received by a shaft 92 (FIG. 9) of a pipetter 86 (FIG. 9), and a lumen 40 extending therebetween. The distal end 36 of the illustrated embodiment of the magnetic pipette tip 32 is molded to include a sharp taper for retaining a magnet 42 that is located within the lumen 40, as described in greater detail below. The sharp taper of the distal end 36 may include an abrupt change in the diameter, i.e., from a gentle decreasing diameter to a narrow diameter fluid port 44 that extends distally away from the distal end 36. The narrow diameter fluid port 44 is configured to provide fluid movement into and out of the lumen 40 of the magnetic pipette tip 32.

[0037] The magnet 42 within the lumen 40 may be constructed from any inert magnetic or paramagnetic material that may be structured to reside within the lumen 40 of the magnetic pipette tip 32. For example, the magnet 42 should have dimensions that are suitable for residing within the lumen 40 while maximizing the surface area of the magnet 42 for capturing a majority of the magnetic beads 24 from the sample. Some suitable diameters may range from about 1/16^th inch (1 .58 mm) in diameter and about 1 /16^th inch (1 .58 mm) in thickness, and may vary in three- dimensional structure, including, for example, cylinders, spheres, cones, rings, or other shape/structure as appropriate. One suitable magnet, by way of example only, is a neodymium cylinder magnet from K&J Magnetics, Inc. of Jamison, PA. The magnetic field strength generated by the magnet 42 must be sufficiently large to magnetically attract and retain the magnetic beads 24; for example, the 6619 Gauss surface magnetic field strength of the commercially-available neodymium cylinder magnet may be considered to be suitable but not limiting.

[0038] When the sample is aspirated into the pipette tip 32 (block 30), the sample passes through the fluid port 44, past the sharp taper of the distal end 36, and into the lumen 40 of the housing 34. Once within the lumen 40, the magnetic beads 24 are positioned within the magnetic field of the magnet 42 and thus magnetically attracted and bound to the magnet 42. Because the biomolecule 14 is reversibly bound to the coating of the magnetic beads 24, the magnetic attraction of the magnetic bead 24 to the magnet 42 effectively immobilizes and retains the biomolecule 14 within the magnetic pipette tip 32. Because the lysis solution 18 and the contaminants contained therein are not magnetically attracted to the magnet 42 nor reversibly bound to the coating of the magnetic beads 24, the lysis solution 1 8 may be expelled, with contaminants, out of the magnetic pipette tip 32 and into the labware 20 (FIG. 2A) (block 46).

[0039] Referring again to FIG. 1 and now with reference to FIG. 2B, the biomolecule-magnetic bead complex, the magnet 42, and lumen 40 may be washed (block 48). Washing of the magnetic beads 24 with the bound biomolecule 14 may include aspirating and dispensing a wash buffer 50, one or more times, between the magnetic pipette tip 32 and the labware 20, to further remove contaminants or lysis solution 18 (FIG. 2A) from the magnetic pipette tip 32. The use of the wash buffer 50 may be optionally excluded or repeated one or more times, as necessary or desired, and in accordance with the particular isolation procedure. Once the washing is complete, the wash buffer 50 is expelled from the magnetic pipette tip 32 and disposed in an appropriate manner. Though not specifically shown, multiple and differing wash buffers may be used in the repeated washings. One example of a suitable wash buffer may be a 70% ethanol solution (pH of about 7.4). Alternatively, a 5 M sodium chloride ("NaCI") solution followed by a solution comprised of 25 mM Tris Acetate (pH of about 7.8), 1 00 mM potassium acetate ("KOAc"), 10 mM magnesium acetate ("Mg₂OAc"), and 1 mM dithiothreitol ("DTT") may be used.

[0040] With the contaminants and/or lysis solution 18 (FIG. 2A) removed, the biomolecule 14 may be eluted from the magnetic pipette tip 32 into a clean buffer for further analysis or processing. According to the illustrative embodiment of FIG. 2C and with reference to FIG. 1 , an elution buffer 56 is aspirated into the magnetic pipette tip 32 to release the biomolecule 14 (block 54). The elution buffer 56 differs from the previous lysis solution 1 8 and wash buffer 50 in at least one chemical property that is configured to sufficiently disrupt the reversible bond between the biomolecule 14 and the coating of the magnetic bead 24. One exemplary method of disrupting the reversible bond is to use an elution buffer 56 having a pH that differs from the pH of the previous buffers 18, 50. Altering the pH, by definition, alters the concentration of protons in the solution and may resultantly affect the degree of protonation of some functional groups (i.e., acidic buffers will protonate anionic functional groups while alkaline buffers remove protons from cationic functional groups with a by-product of water). Affecting the protonation of the functional groups of at least one of the biomolecule 14 or the magnetic bead coating may alter the static surface charge of the biomolecule 14 or the coating, respectively. Sufficiently altering the static surface charge disrupts the electrostatic bond of the biomolecule- magnetic bead complex and releases the biomolecule 14 from the coating of the magnetic bead 24. Other embodiments of elution buffers 56 are known, and may alternatively include, for example, varying the salt concentration and/or including detergents.

[0041] It is readily appreciated that the elution buffer 56 does not affect the magnetic attraction between the magnet 42 and the magnetic beads 24; therefore, the magnetic beads 24 remain within the lumen 40 and magnetically attracted to the magnet 42 even after expelling the elution buffer 56 from the magnetic pipette tip 32.

[0042] With the reversible bond disrupted, the released biomolecule 14 is free to be expelled with the elution buffer 56 from the magnetic pipette tip 32 and into the labware 20. The magnet 42 and the magnetic beads 24 remain within the lumen 40 of the magnetic pipette tip 32. The isolated biomolecule 14 then may be studied in accordance with an assay or other biotechnique that is known to those of ordinary skill in the art.

[0043] FIGS. 4-7 illustrate other magnetic pipette tips in accordance with other embodiments of the present invention. One such magnetic pipette tip 60 is shown in FIG. 4A. The magnetic pipette tip 60 includes a molded housing 62 having a gentle taper from a proximal end hub 66 to a distal tip 64 and a lumen 70 therebetween. In the present embodiment, the magnetic pipette tip 60 further includes a porous member 72 within the lumen 70 and proximate the distal tip 64. The porous member 72 spans a cross-sectional dimension of the lumen 70, which as shown may have a diameter ranging from about 3 mm to about 5 mm, in order to retain a magnet 74 within the lumen 70 of the magnetic pipette tip 60 while permitting passage of the magnetic beads 24. While the magnet 74 of the particular embodiment is shown to include a spherical shape, it would be understood that the cubic magnet 42 of FIG. 3 or another shape may alternatively be used.

[0044] The porous member 72 may be a porous frit, constructed from polyethylene or ceramic materials with a porosity ranging from about 10 nm to about 100 μιη, or larger, as necessary to permit passage of the magnetic beads 24.

Suitable porous members 72 may include, for example, those that are commercially- available from Porex Technologies (Fairburn, GA). Other frits may include those that are described in detail in U.S. Patent No. 7,482,1 69, entitled "LOW DEAD VOLUME EXTRACTION COLUMN DEVICE," issued to Gjerde et al. on January 27, 2009, and U.S. Patent No. 6,566,145, entitled "DISPOSABLE PIPETTE EXTRACTION," issued to Brewer on May 20, 2003, the disclosures of both incorporated herein by reference, in their entireties. Briefly, these porous members 72 include sintered glass plugs, glass wool plugs, porous polymer plugs, or metal screens. Alternatively, the porous member may be a membrane or a filter, such as those that are constructed from nylon, polyester, polyamide, polycarbonate, cellulose, polyethylene, nitrocellulose, cellulose acetate, or polypropylene.

[0045] In yet other embodiments, the porous member 72 may include a functionalized structure or coating that is similar to those described in PCT

Application Publication No. WO 2010/093998, entitled "SYSTEM AND METHODS FOR PURIFYING BIOLOGICAL MATERIALS," by Diffinity Genomics, Inc, the disclosure of which is incorporated herein by reference, in its entirety. Briefly, the functionalized structures and coatings as disclosed by Diffinity Genomics include a target rejection chemistry, i.e., having a hydrophobicity, charge, and/or affinity that is specialized to absorb undesired molecules from the lysis solution 1 8 (FIG. 2A) and not the biomolecules 14 (FIG. 2A). Alternatively still, and as illustrated in FIGS. 5 and 5A, the functionalized coatings taught by Diffinity Genomics may be included as a coating on at least a portion of an inner surface of the lumen 70 of the magnetic pipette tip 80.

[0046] In use, the magnetic pipette tip 60 functions in a manner that is similar to the magnetic pipette tip 32 of FIG. 3. However, in the present embodiment, the porosity of the porous member 72 is selected such that the lysis solution 1 8 (FIG. 2) and the biomolecule-magnetic bead complex may traverse the porous member 72 while the magnet 74 does not. As a result, the biomolecule-magnetic bead complex enters the lumen 70 of the magnetic pipette tip 60 and is attracted and retained by the magnetic field. The process of releasing the biomolecule 14 from the magnetic beads 24 and expelling the biomolecule 14 then may proceed in a manner that is similar to the method described in detail above.

[0047] FIG. 4 further illustrates an optional barrier member 75 that is positioned distal to the proximal end hub 66 for the purpose of retaining the magnet 74 within the lumen 70 in the event that the magnetic pipette tip 60 is inverted. The barrier member 75 may be constructed in a manner that is similar to any porous member described herein or any membrane, plug, frit, or other structure that permits a displacement of air, and thus functioning of, the magnetic pipette tip 60. The position of the barrier member 75 may be just distal to a "nose cone" 77 of the magnetic pipette tip 60, which is the proximal portion of the tip 60 that is tapered to couple to the shaft 92 (FIG. 9) of the pipetter 86 (FIG. 9) by frictional fit. The use of the barrier member 75 is not necessary and should not be considered to be limiting.

[0048] FIGS. 5 and 5A illustrate a magnetic pipette tip 80 in accordance with another embodiment of the present invention. The magnetic pipette tip 80 is constructed substantially similar to the magnetic pipette tip 60 of FIG. 4; however, a porous member 81 replaces the barrier member 75 and is spaced farther from the distal end 64 as compared with the barrier member 75. The magnetic pipette tip 80 further includes a plurality of magnets 74n (shown with three magnets 74a, 74b, 74c) located within the lumen 70. Inclusion of the plurality of magnets 74n within the lumen 70 increases the magnetic field strength and/or the volume covered by the magnetic field, which results in the capture and retention of more magnetic beads 24. Further, the plurality of magnets 74n increases the surface area of coating material available for binding the biomolecule 14 (FIG. 2A) to the magnetic beads 24. In any event, a larger percentage of biomolecule-magnetic bead complexes may be retained by the magnetic pipette tip 80 and larger concentrations of biomolecule 14 (FIG. 2A) isolated.

[0049] FIGS. 6 and 6A illustrate a magnetic pipette tip 82 in accordance with yet another embodiment of the present invention. Again, the magnetic pipette tip 82 is generally constructed in a manner that is similar to the magnetic pipette tips 60, 80 of FIGS. 4 and 5, respectively. However, the magnetic pipette tip 82 of FIG. 6 includes a plurality of porous members 84n (shown with three porous members 84a, 84b, 84c) separating each of the plurality of magnets 74a, 74b, 74c. Again, similar to the embodiment shown in FIG. 5, this embodiment of the magnetic pipette tip 82 with the plurality of magnets 74n allows for the capture and isolation of larger amounts, or concentrations, of the biomolecules 14 (FIG. 2A).

[0050] In an alternate method of using the magnetic pipette tip 82, not necessarily shown herein, the plurality of porous members 84n may be constructed with varying degrees of porosity. As a result, various diameters of magnetic beads could be used, each having a separate coating for different biologies, for isolating more than one biologic material of interest, thereby allowing multiplex assay formats. [0051] Turning now to FIG. 7, a magnetic pipette tip 100 in accordance with still another embodiment of the present invention is shown with greater detail. The magnetic pipette tip 100 may be constructed in a manner that is similar to the magnetic pipette tip 32 of FIG. 3 that includes a housing 34 having a sharp taper of the distal end 36 that abruptly changes to a narrower diameter fluid port 44 extending distally away from the distal end 36. A cylindrical magnet 102 having a cylindrical lumen 104 extending lengthwise therethrough is located within the lumen 40 and resides on a surface created by the abrupt change between the distal end 36 and the fluid port 44. The magnetic poles of the cylindrical magnet 102 may correspond with the top and bottom surfaces of the cylindrical magnet 102. While the specific embodiment of the cylindrical magnet 1 02 shown in FIG. 7 has a conical shape that generally corresponds with the taper of the distal end 36, this is not necessary. Indeed, the cylindrical magnet 1 02 needs only have a diameter that is sufficiently small to allow the cylindrical magnet 102 to reside within the lumen 40.

[0052] The cylindrical lumen 1 04, as shown, has a diameter that is similar to the diameter of the fluid port 44; however, this dimension is not necessary.

Generally, the diameter of the cylindrical lumen 1 04 should meet or exceed the diameter of the fluid port 44 so as to not hinder fluid motion into the lumen 40 when the sample is aspirated. In some embodiments, the lumen 104 may have a diameter of about 1/16^th inch (about 1 .59 mm).

[0053] Use of the magnetic pipette tip 100 may proceed in a manner that is similar to the previous embodiments. Briefly, the magnetic beads 24 are introduced into the lysis solution 1 8. The lysis solution 18 may be incubated to permit binding of the biomolecules 14 to the magnetic beads 24. The lysis solution 1 8 then may be aspirated from the labware 20 into the magnetic pipette tip 1 00, where the lysis solution 18 passes through the fluid port 44, the cylindrical lumen 104, and into the lumen 40 of the magnetic pipette tip 100. The biomolecule-magnetic bead complexes are retained at the cylindrical magnet 102 while the lysis solution 18 may be dispensed back into the labware 20. Release of the biomolecules 14 from the magnetic beads 24 then may proceed as described previously.

[0054] FIGS. 8A-8D illustrate additional embodiments of magnetic pipette tips in accordance with the present invention. The magnetic pipette tips 1 10, 1 12, 1 14, 1 15 of FIGS. 8A, 8B, 8C, and 8D respectively, may be constructed in a manner that is similar to the magnetic pipette tip 60 of FIG. 4; however, in FIG. 8A the magnetic pipette tip 1 10 includes a ring-shaped magnet 1 16 that is molded into the housing 62, and the magnetic pipette tip 1 1 2 of FIG. 8B includes a plurality of rectangular magnetic strips 1 18 that is molded into the housing 62. By including the magnets 1 16, 1 18 in the housing 62 during the molding process, the use of a porous member 72 (FIG. 4) is not necessary but, may still be included if desired. It would be readily appreciated that various magnet shapes, sizes, and numbers may be used and are not limited to the specifically-illustrated embodiments. Further, it would be readily appreciated that the locations of the magnets 1 16, 1 1 8 need to be limited to the positions that are schematically shown. Instead, the magnets 1 16, 1 18 may be positioned, as appropriate, at any position along the length of the housing 62 so as to not interfere with the magnetic pipette tip's ability to be coupled to the shaft 92 (FIG. 9) of the pipetter 86 (FIG. 9). Also, the thickness of the molded housing 62 at the position of the magnets 1 1 6, 1 18 may be optimized to reduce interference of the magnetic field strength experienced by the magnetic beads 24 within the lumen 70 of the housing 62. [0055] The magnetic pipette tip of FIG. 8C includes a magnetic coating 120 applied to an inner wall surface 1 19 of the housing 62 and within the lumen 70. The magnetic coating 120 may be unitary, as shown, or may be partitioned within the lumen 70 and having any shape, including both regular and irregular shapes. Again, the coating 120 may be located at any position along the length of the housing 62. Indeed, the coating 1 20 need not be limited to the inner wall surface 1 19 of the housing 62 but may be a material that is included within the moldable material during the molding process or may be applied to an outer wall surface 1 17 of the housing 62 after the molding process.

[0056] The thickness of the applied coating 120 may vary and depends on a thickness necessary to provide sufficient magnetic field strength to capture the magnetic beads 24 once the magnetic beads 24 are within the lumen 70 of the magnetic pipette tip 1 14.

[0057] In still other embodiments, a small magnet may be inserted the lumen into a non-magnetic, conventional pipette tip. However, if a width dimension of the magnet (which may be, for example, a diameter of approximately 2 mm) is less than a cross-sectional dimension of the lumen, then the magnet may move freely within the lumen. According to some uses, there may be a preferred orientation of the magnet, e.g., the magnetic poles, with respect to a lengthwise central axis 121 (FIG. 8D) of the magnetic pipette tip 1 15. Therefore, securing the magnet in a particular orientation may be beneficial. While the magnet may be constructed with an outer surface matching a shape of an inner wall of the lumen of the magnetic pipette tip (for example, as described with reference to FIG. 7), the manufacture of particularly- shaped magnets increases manufacturing costs. Therefore, it may be beneficial to support a standard magnet within the lumen of the magnetic pipette tip so as to reduce tumbling of the magnetic and maintain the desired orientation of the magnet.

[0058] In that regard, and with reference now to FIG. 8D, the magnetic pipette tip 1 15 includes a magnet 1 22 (shown as cylindrical in shape and having a lumen 123 extending therethrough) supported within the lumen 70 of the magnetic pipette tip 1 15. The magnet 122 is supported by an adaptor 124, which may be constructed from any non-magnetic, semi-compliant, and moldable material, including, for example, generally plastics and specifically polypropylene, polystyrene, and polyethylene. Because the inner surface 126 lumen 70 of the magnetic pipette tip 1 15 is generally circular in cross-section, the adaptor 124 may be molded to include a generally cylindrical outer surface 1 28.

[0059] As shown in greater detail in FIG. 8E, the outer surface 128 may have a dimension ("D1 ") that approximates the cross-sectional dimension ("D2") of the lumen 70. In other configurations, for example, as shown in FIG. 8F, an adaptor 130 may be molded to correspond to the particular shape of the lumen 70. Specifically, the magnetic pipette tip 1 15 may taper from the proximal end hub 66 to the distal tip 64 such that the inner surface 126 of the lumen forms an angle, a, with a vertical plane 132. Therefore, an outer surface 134 of the adaptor 130 may be similarly angled, β, with the vertical plane 132, wherein β is substantially similar to a. As a result, the adaptor 130 may better conform to the lumen 70 of the magnetic pipette tip 1 15 while maintaining a friction fit with the same.

[0060] Referring still to FIGS. 8E and 8F, each adaptor 124, 130 may further include an inner lumen 136, 138 sized and shaped to receive the magnet 122. In the referenced and illustrated examples, the inner lumen 136, 138 is generally cylindrical to match the generally cylindrical outer surface of the magnet 1 22; however, the shape is not so limited. In fact, in FIG. 8G, a cubic-shaped magnet 140, having a lumen 141 extending therethrough, is positioned within a square lumen 142 of an adaptor 144. The square lumen 142 is molded to have a size and shape similar to the cubic-shaped magnet 140 while an outer surface 146 of the adaptor 144 retains a cylindrical shaped similar to the adaptor 1 24 of FIG. 8E.

[0061] Returning again to FIG. 8D, in use the magnet 122 may be placed within the adaptor 124 and retained by friction fit or an adhesive. The adaptor 1 24, with the magnet 1 22 positioned therein, may then be inserted into the lumen 70 of the magnetic pipette tip 1 15 to a desired, final position, and retained by friction fit or adhesive. The lysis solution 1 8 (FIG. 2A), wash buffer 50 (FIG. 2B), and elution buffer 56 (FIG. 2C) may be aspirated into and expelled from the magnetic pipette tip 1 15 via the lumen 123 extending through the magnet 121 .

[0062] It would be readily appreciated that while the magnetic pipette tips 1 10, 1 12,1 14, 1 15 are illustrated with the barrier member 75, inclusion of the barrier member 75 is not necessary or required.

[0063] FIG. 9 illustrates one embodiment of a conventional pipetter 86 suitable for use with a magnetic pipette tip in accordance with any one embodiment of the present invention; however, the present invention should not be limited to use with the particular pipetter 86 shown. The pipetter 86 is described in detail in U.S. Patent No. 7,690,274, entitled "PIPETTE WITH A TIP REMOVING MECHANISM," issued to Thermo Fisher Scientific (Vantaa, Finland) on April 6, 2010, the disclosure of which is incorporated herein by reference in its entirety. Generally, the pipetter 86 includes a housing 88 having a finger rest 90 and a shaft 92 extending from the housing 88. An activator, shown here as a plunger 94, is operably associated with the aspirating mechanism (not shown) located within the housing 88. The particular embodiment also includes a tip removal mechanism 96. Further details of the aspirating mechanism and the tip removal mechanism 96 are provided in the incorporated disclosure.

[0064] The following non-limiting examples, provided in FIGS. 10A-10D, illustrate results of the use of the invention for particular applications.

EXAMPLE 1

[0065] Example 1 , illustrated in FIG. 10A, demonstrates the results of a plasmid DNA purification using a magnetic pipette tip was constructed in a manner that is similar to the magnetic pipette tip 60 of FIG. 4.

[0066] E. coli XL10 Gold (Strategene, San Diego, CA) pBluescript (pBSK) (Strategene, San Diego, CA) plasmid transformants were cultured overnight in a suspension culture under antibiotic selection. The cells were divided into 2 ml_ aliquots and pelleted by centrifugation at 13,000 rpm for 10 minutes. All cell pellets were stored at 20 °C until use. The cells were lysed using alkaline lysis conditions. Briefly, this method involves resuspension of the cells in a solution comprised of 50 mM glucose, 25 mM Tris-HCI (pH of about 8), 10 mM ethylenediaminetetraacetic acid ("EDTA"), and 1 00 μg/mL RNAse. This was followed by the actual lysis of the cells in a solution of 0.2 N NaOH with 1 % SDS. Finally, the entire lysis is neutralized by the addition of 3 M KOAc. Precipitated cellular proteins were pelleted by centrifugation, and clarified lysis solution samples containing plasmid DNA were processed.

[0067] The plasmid DNA isolated using embodiments of the invention was analyzed using a 0.8% agarose gel prepared with Tris-acetate-EDTA ("TAE") buffer and 0.5 μg/mL ethidium bromide. After loading the samples, the gel was run at 100 V for about 1 hour. The results were visualized using a UV light box and are displayed in FIG. 10A.

[0068] Lane "L" shows a DNA marker, Fisher BioReagents exACTGene™ DNA Ladder (Thermo Fisher Scientific, Fair Lawn, NJ). Lanes "1 " and "2" show plasmid DNA that was eluted after processing and using 1 μιη functionalized magnetic particles. Lanes "3" and "4" show plasmid DNA that was eluted after processing and using 3 μιη functionalized magnetic particles; and Lanes "5" and "6" show plasmid DNA that was eluted after processing and using 5 μιη functionalized magnetic particles. All samples were eluted in Tris-EDTA ("TE") buffer by aspiration/dispensing for five cycles.

[0069] Based on the agarose gel results, all samples demonstrate a high yield of purified plasmid DNA product. Smaller diameter magnetic beads appear to have the highest yield in this case presumably due to increased surface area.

EXAMPLE 2

[0070] Example 2, illustrated in FIG. 10B, compares the results of a plasmid DNA purification using a conventional spin column protocol with the use of a magnetic pipette tip constructed in a manner that is similar to the magnetic pipette tip 60 of FIG. 4.

[0071] E. coli XL10 Gold (Strategene, San Diego, CA) pBluescript (pBSK) (Strategene, San Diego, CA) plasmid transformants were cultured overnight in a suspension culture under antibiotic selection. The cells were divided into 2 mL aliquots and pelleted by centrifugation at 13,000 rpm for 10 minutes. All cell pellets were stored at -20 °C until use. The cells were thawed to room temperature and lysed using alkaline lysis conditions. Briefly, this method involves resuspension of the cells in a solution comprised of 50 mM glucose, 25 mM Tris-HCI (pH of about 8), 10 mM EDTA, and 100 μg/mL RNAse. This was followed by the actual lysis of the cells in a solution of 0.2 N NaOH with 1 % SDS. Finally, the entire lysis is neutralized by the addition of 3 M KOAc. Precipitated cellular proteins were pelleted by centrifugation, and clarified lysis solution samples containing plasmid DNA were processed.

[0072] The plasmid DNA isolated using embodiments of the invention was analyzed using a 0.8% agarose gel prepared with TAE buffer and 0.5 μg/mL ethidium bromide. After loading the samples, the gel was run at 100 V for about

1 hour. The results were visualized using a UV light box and are displayed in FIG. 10B.

[0073] Lane "L" shows a DNA marker, Fisher BioReagents exACTGene™ DNA Ladder (Thermo Fisher Scientific, Fair Lawn, NJ). Lane "C" shows plasmid DNA that was isolated using a conventional spin column purification protocol. Lanes "1 " and "2" show plasmid DNA that was purified using a ring-shaped magnet (4 mm x

2 mm x 1 mm) (outer diameter x inner diameter x thickness) that was magnetized through the thickness of the magnet. Lanes "3" and "4" show plasmid DNA that was purified using a ring-shaped magnet (4 mm x 2 mm x 1 mm) that was magnetized across the diameter of the magnet. Lanes "5" and "6" show plasmid DNA that was purified using a ring-shaped magnet (2 mm x 1 mm x 1 mm) that was magnetized across the diameter of the magnet. Lanes "7" and "8" show plasmid DNA that was isolated using a ring-shaped magnet (3 mm x 1 mm x 1 mm) that was magnetized across the diameter of the magnet.

[0074] All magnetic tips tested in this example performed well with good recovery of plasmid DNA. EXAMPLE 3

[0075] Example 3, illustrated in FIG. 10C, demonstrates the results of a polymerase chain reaction ("PCR") product purification using a magnetic pipette tip that was constructed in a manner that is similar to the magnetic pipette tip 60 of FIG. 4.

[0076] A 526-base pair sequence was amplified using pBluescript (pBSK) (Stratagene, San Diego, CA) plasmid as a template, purified using the

aforementioned magnetic tip, and the results were assessed by analysis of the PCR sequencing data.

[0077] The PCR reaction mixture included 1 μΙ_ of both forward and reverse primers (25 μΜ), 1 μΙ_ of pBSK template (1 0 ng/mL), 5 mL of 10X PCR buffer, 1 μΐ of MgCI₂ (100 mM), 1 μΐ of dNTP mixture (10 mM), 0.25 μΐ Taq Polymerase (5 ϋ/μΐ), and 39.75 μΐ of HPLC water. The 50 μΐ samples were placed in a thermal cycler and cycled for 30 repetitions (95 °C for 30 seconds followed by 52 °C for 30 seconds and finally 72 °C for 30 seconds).

[0078] Reactions were processed using the magnetic tip and then sequenced using the Sanger dideoxy-sequencing method. The results for both non-processed and magnetic tip processed samples were compared for signal-to-noise ratio as well as overall accuracy in base pair calls.

[0079] The results demonstrate the processing of PCR product samples with the magnetic tip result in great improvement in signal-to-noise ratio and correct base pair calls.

EXAMPLE 4

[0080] Example 4, illustrated in FIG. 10D, demonstrates the results of

Glutathione S-Transferase ("GST") tagged protein purification using a magnetic pipette tip that was constructed in a manner similar to the magnetic pipette tip 60 of FIG. 4.

[0081] E. coli BL21 (DE3) (Novagen, Darmstadt, Germany) plasmid

transformants expressing the recombinant GST-tagged Green Fluorescent Protein ("GFP") were cultured and induced in a suspension culture under antibiotic selection. The cells were divided into 2 ml_ aliquots and pelleted by centrifugation at

13,000 rpm for 10 minutes. Prior to use, all cell pellets were stored at 20 °C. The cells were thawed to room temperature and lysed by mixing with 100 μΙ_ bacterial protein extraction reagent ("BPER") (Thermo Fisher Scientific, Rockford, IL) and subsequently centrifuged for 1 0 minutes at 1 3,000 rpm. The soluble portion of the cell lysate was isolated and then processed using the aforementioned magnetic pipette tip with Pierce Glutathione Magnetic Beads (Thermo Fisher Scientific, Rockford, IL) and using manufacturer's recommended reagents.

[0082] The proteins isolated by the magnetic pipette tip were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis ("SDS PAGE") gel. A 15 μΙ_ aliquot of each sample was mixed with 5 μΙ_ reducing sample buffer and heated at 95 °C for 5 minutes. Samples then were loaded onto an 8-20%

polyacrylamide gel and run at 100 V for approximately 1 hour. The gel then was stained using a Coomassie Blue based stain and photographed on a light box.

[0083] Lane "L" shows a protein ladder (Fisher BioReagents EZ-Run™

Prestained Rec Protein Ladder, Thermo Fisher Scientific, Fair Lawn, NJ). Lane "U" shows unprocessed cell lysate that was diluted 1 :1 in HPLC water. Lanes "1 " and "2" show the first and second elutions containing purified GST-tagged GFP proteins purified from the whole cell lysate. [0084] Results demonstrate that GST-tagged proteins can be effectively purified from whole cell lysate using the magnetic pipette tip. All samples showed acceptable yield of the target protein and good overall purity.

[0085] While the present invention has been illustrated by a description of various embodiments, and while these embodiments have been described in some detail, they are not intended to restrict or in any way limit the scope of the appended claims to such detail. Additional advantages and modifications will readily appear to those skilled in the art. The various features of the invention may be used alone or in any combination depending on the needs and preferences of the user. This has been a description of the present invention, along with methods of practicing the present invention as currently known. However, the invention itself should only be defined by the appended claims.

[0086] What is claimed is:

Claims

1 . A magnetic pipette tip, comprising:

a pipette tip housing having a proximal end, a distal end, and a lumen extending therebetween; and

a first magnet located within the lumen of the pipette tip housing between the proximal and distal ends.

2. The magnetic pipette tip of claim 1 , further comprising:

a first porous member positioned between the first magnet and the distal end and configured to maintain the first magnet within the lumen of the pipette tip housing, the first porous member being permeable to fluids.

3. The magnetic pipette tip of claim 2, wherein the first porous member is a frit, a membrane, or a filter.

4. The magnetic pipette tip of claim 2, wherein the first porous member is a frit selected from the group consisting of a sintered glass plug, a glass wool plug, a porous polymer plug, and a metal screen.

5. The magnetic pipette tip of claim 2, wherein the first porous member is a semi-permeable membrane.

6. The magnetic pipette tip of claim 2, wherein the first porous member is comprised of nylon, polyester, polyamide, polycarbonate, cellulose, polyethylene, nitrocellulose, cellulose acetate, or polypropylene.

7. The magnetic pipette tip of claim 2, wherein the first porous member has a pore volume that is less than about 1 μΙ_.

8. The magnetic pipette tip of claim 2, wherein the first porous member is comprised of a functionalized material configured to absorb at least one undesired molecule.

9. The magnetic pipette tip of claim 1 , wherein the distal end is tapered to maintain the first magnet within the lumen of the pipette tip housing.

10. The magnetic pipette tip of claim 9, further comprising:

a fluid port operably coupled to and extending distally from the tapered distal end.

1 1 . The magnetic pipette tip of claim 1 , further comprising:

a second magnet located within the lumen of the pipette tip housing between the proximal and distal ends.

12. The magnetic pipette tip of claim 1 1 , further comprising:

at least one porous member positioned within the lumen of the pipette tip housing between the proximal and distal ends, the at least one porous member being permeable to fluids.

13. The magnetic pipette tip of claim 12, wherein the at least one porous member is positioned between the first and second magnets.

14. The magnetic pipette tip of claim 13, wherein at least another porous member is positioned between the first and second magnets and the distal end and configured to maintain the first and second magnets within the lumen of the pipette tip housing.

15. The magnetic pipette tip of claim 1 , wherein the first magnet includes a lumen extending therethrough.

16. The magnetic pipette tip of claim 15, wherein the first magnet is supported within the lumen of the pipette tip housing at a selected position.

17. The magnetic pipette tip of claim 16, further comprising:

an adaptor operably coupled to the first magnet and supporting the first magnet at the selected position.

18. The magnetic pipette tip of claim 17, wherein the adaptor is comprised of at least one of polypropylene, polystyrene, and polyethylene.

19. The magnetic pipette tip of claim 17, wherein the adaptor includes an outer surface shape corresponding to a shape of the lumen of the pipette tip housing.

20. The magnetic pipette tip of claim 19, wherein the lumen of the pipette tip housing is tapered from the proximal end to the distal end and the outer surface shape of the adaptor is conical.

21 . The magnetic pipette tip of claim 17, wherein the adaptor includes a lumen having a shape that corresponds to an outer shape of the first magnet.

22. The magnetic pipette tip of claim 1 , further comprising:

a functionalized coating on at least a portion of the lumen of the pipette tip housing configured to isolate a biomarker or a disease agent in a diagnostic assay.

23. The magnetic pipette tip of claim 1 , further comprising:

a functionalized coating on at least a portion of the lumen of the pipette tip housing configured to absorb at least one undesired molecule.

24. A pipetting system, comprising:

the magnetic pipette tip of claim 1 ; and

a pipetter comprising a pipetter housing, a shaft extending from the pipetter housing and configured to receive the proximal end of the pipette tip housing, and a fluid aspirator within the pipetter housing configured to aspirate a fluid into the lumen of the pipette tip housing when the magnetic pipette tip is received by the shaft.

25. The pipetting system of claim 24, wherein the magnetic pipette tip further comprises:

a first porous member positioned between the first magnet and the distal end of the pipette tip housing and configured to maintain the first magnet within the lumen of the pipette tip housing, the first porous member being permeable to fluids.

26. The pipetting system of claim 24, wherein the distal end of the pipette tip housing is tapered to maintain the first magnet within the lumen.

27. The pipetting system of claim 26, further comprising:

a fluid port on the distal end and extending from the tapered distal end.

28. The pipetting system of claim 24, further comprising:

a second magnet located within the lumen of the pipette tip housing; and a second porous member permeable to fluids and positioned within the lumen of the pipette tip housing to separate the first and second magnets.

29. A magnetic pipette tip assay system, comprising:

the magnetic pipette tip of claim 1 ; and

a plurality of magnetic beads, each of the plurality of magnetic beads comprising a magnetic core and a coating thereon, the coating configured to reversibly bind a biological molecule thereto, wherein each of the plurality of magnetic beads is configured to pass through the distal end of the pipette tip housing, into the lumen, and proximate the first magnet.

30. The magnetic pipette tip assay system of claim 29, further comprising:

31 . The magnetic pipette tip assay system of claim 29, wherein the magnetic pipette tip further comprises:

a first porous member positioned between the first magnet and the distal end of the pipette tip and configured to maintain the first magnet within the lumen of the pipette tip housing, the first porous member being permeable to fluids and the plurality of magnetic beads.

32. The magnetic pipette tip assay system of claim 29, wherein the distal end of the pipette tip housing is tapered to maintain the first magnet within the lumen.

33. A method of isolating a desired biological molecule, comprising:

introducing a plurality of magnetic beads into a sample containing the desired biological molecule, each of the plurality of magnetic beads having a magnetic portion and a binding portion, the binding portion configured to reversibly bind the desired biological molecule;

aspirating the sample having the desired biological molecule reversibly bound to the plurality of magnetic beads into a magnetic pipette tip having a pipette tip housing, a lumen extending through the pipette tip housing, and a magnet located within the lumen of the pipette tip housing between the proximal and distal ends; releasing the desired biological molecule from the plurality of magnetic beads; and

expelling the desired biological molecule from the lumen of pipette tip housing while retaining the plurality of magnetic beads with the magnet within the lumen of the pipette tip housing.

34. The method of claim 33, further comprising:

expelling the sample, with the desired biological molecule, while retaining the plurality of magnetic beads having the desired biological molecule reversibly bound thereto with the magnet within the lumen of the pipette tip housing before releasing the desired biological molecule from the plurality of magnetic beads.

35. The method of claim 33, wherein releasing the desired biological molecule from the plurality of magnetic beads further comprises:

aspirating an elution buffer into the lumen of the pipette tip housing, the elution buffer configured to chemically alter the binding portion of the plurality of magnetic beads, the desired biological molecule, or both so as to release the desired biological molecule from the plurality of magnetic beads.

36. The method of claim 33, wherein the chemically alter the binding portion of the plurality of magnetic beads or the desired biological molecule includes a change in pH, a change in salt concentration, or addition of a detergent.

37. The method of claim 33, wherein the binding portion comprises a

functionalized coating and the desired biological molecule comprises a biomarker or a disease agent.

38. The method of claim 33, wherein the plurality of magnetic beads is a first plurality of magnetic beads and the desired biological molecule is a first biological molecule, the method further comprising:

introducing a second plurality of magnetic beads into the sample, the sample containing a second biological molecule that is chemically distinguishable from the first biological molecule, each of the second plurality of magnetic beads having a magnetic portion and a binding portion, the binding portion of the second plurality of magnetic beads configured to reversibly bind the second biological molecule without binding the first biological molecule and the binding portion of the first plurality of magnetic beads configured to reversibly bind the first biological molecule without binding the second biological molecule.

39. The method of claim 38, further comprising:

isolating the first and second biological molecules in a multiplex format.

40. The method of claim 33, further comprising:

simultaneously isolating a desired biological molecule from a plurality of samples with a plurality of magnetic pipette tips during a single assay.

41 . The method of claim 40, wherein the number comprising the plurality of magnetic pipette tips equals a number comprising the plurality of samples, the number being one of 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 96, 384, and 1536.

42. A magnetic pipette tip, comprising:

a magnetic portion supported by the pipette tip housing and being located between the proximal and distal ends.

43. The magnetic pipette tip of claim 42, wherein the magnetic portion comprises a magnet provided in a wall of the pipette tip housing.

44. The magnetic pipette tip of claim 42, wherein the magnetic portion comprises a plurality of magnets provided in a wall of the pipette tip housing.

45. The magnetic pipette tip of claim 42, wherein the magnetic portion comprises a magnetic coating provided on an inner surface and within the lumen of the pipette tip housing.

46. The magnetic pipette tip of claim 42, wherein the magnetic portion comprises a magnetic coating provided on an outer surface of the pipette tip housing.