Method and apparatus for stacked multi-filter device for customized fluid sample filtration and extraction

Abstract

A method and apparatus for multi-step filtering of clinical and non-clinical fluid samples to remove contaminants, or isolate or concentrate sample components (or both), using a series of filters fitted into connectable adaptors.

Description

Aty. Docket No.: UM-43592.601METHOD AND APPARATUS FOR STACKED MULTI-FILTER DEVICE FOR CUSTOMIZED FLUID SAMPLE FILTRATION AND EXTRACTIONCROSS-REFERENCE TO RELATED APPLICATIONSThe present application claims priority to United States Provisional Patent Application Serial Number 63 / 706,398, filed October 11, 2024, the disclosure of which is herein incorporated by reference in its entiretyFIELD OF THE INVENTIONThis invention relates generally to the field of filtering clinical and non-clinical fluid samples, and extracting components of those samples, with enhanced flexibility and improved performance compared to the prior art.BACKGROUND OF THE INVENTIONLarge volume sample processing of both clinical and non-clinical fluid samples is often used to separate out specific portions ("sample components") of the fluid sample, for example to filter out contaminants or to extract a specific material for downstream assays or both. Hereafter both contaminants and samples are referred to as “sample components”. Existing devices on the market, for example MilliporeSigma Steriflip® sterile Centrifuge Tube Top Filter Units, pass fluid unidirectionally through a unidirectional filter with a single uniform pore size. This kind of prior art device allows separation of sample components larger than that single pore size (and retained above the filter) from components smaller than that single pore size (which pass through the filter).This current technology can be used iteratively to filter out multiple different sample components based on size, charge, or solvency, or to obtain sample components with sizes in a specific range of sizes (between 1 pm and 10 pm for example). The iterative process requires purchasing multiple different devices, each with a different pore size (for example) and running a fluid sample sequentially through each device.Aty. Docket No.: UM-43592.601In addition, current technology filters are generally unidirectional. To recover what remains on top of the filter (components larger than the pore size), instead of simply what flowed through (components smaller than the pore size), it is necessary to run fluid in the reverse direction through the filter, which is not possible with a unidirectional filter.One example of the limitations of current technology filters is to filter blood samples, to both remove white and red blood cells (> 5 pm in size) and also extract bacteria sample components (between 1 pm and 5 pm in size) from those blood samples, to enable downstream PCR analysis of those bacteria sample components, uncontaminated by any white or red blood cells. There is currently no filtration device on the market that can accomplish such a task without an iterative process.What is needed are improved methods and apparatus for filtering clinical and non-clinical fluid samples, and extracting components of those samples, with enhanced flexibility and improved performance compared to the prior art.SUMMARY OF THE INVENTIONA first embodiment of the invention is an apparatus for multi-step filtering of liquid samples, comprising two or more connectable (e.g., threaded) filter adaptors (e.g., cylinder filter adaptors), each containing a filter (e.g., filter disk), that are connected (e.g., threaded together) to form a multi-step filter. In some embodiments, each filter has a different selectivity than other filters. For example, in some embodiments, multiple filters are provided in series with the pore sizes of the filter disks running from bigger to smaller in the stack. After centrifuging or otherwise drawing a sample solution through the multi-step filter (via gravity, vacuum pressure, etc.), the material retained on or in at least one filter adaptor or collected in solution downstream of one or more of the filters, corresponding to material with a particular range of sizes or other desired properties, is analyzed or extracted for downstream analysis.A second embodiment of the invention is a method of multi-step filtering, comprising: providing two or more connected (e.g., threaded) filter adaptors (e.g., cylinder filter adaptors), each containing a filter (e.g., filter disk), optionally, connecting (e.g., threading) the filterAty. Docket No.: UM-43592.601 adaptors together to form a multi-step filter, centrifuging or otherwise drawing a sample solution through the multi-step filter, and extracting a material retained in or on at least one filter adaptor or collected in a solution downstream of one or more of the filters, for example to enable downstream analysis of the material. The sample fluid could be, for example, blood, and the material could be, for example, blood cells or bacteria. In some embodiments, the method comprises reversing a direction of one or more of the filter adaptors and / or filters within the multi-step filter and conducting a second separating step.For example, in some embodiments, provided herein is an apparatus for multi-step fluid sample filtration comprising: (a) a first filter adaptor having a filter disk socket; and (b) a second filter adaptor having a filter disk socket; wherein the first filter adaptor and second filter adaptor are configured to attach to one another to form a multi-step sample filtration flow path to allow fluid flow through both the first filter adaptor and the second filter adaptor; and wherein the apparatus is reconfigurable to allow one or more of: (i) replacement or removal of a filter in the filter disk socket of the first filter adaptor or the second filter adaptor; (ii) reversal of an orientation of a filter positioned in the filter disk socket of the first filter adaptor or the second filter adaptor; (iii) reversal of an orientation of the filter disk socket of the first filter adaptor or the second filter adaptor; (iv) reversal of an orientation of the first filter adaptor relative to the second filter adaptor when connected; (v) replacement of the first filter adaptor or second filter adaptor with a third filter adaptor having a filter disk socket; and (vi) addition of a third filter adaptor having a third filter socket. In some embodiments, the first filter adaptor and the second filter adaptor are configured to attach to one another via threaded connectors, although any type of connection may be utilized.In some embodiments, the apparatus further comprises a first filter disk mounted in the filter disk socket of the first filter adaptor, and a second filter disk mounted in the filter disk socket of the second filter adaptor. The apparatus may contain any number of additional filter adapters (e.g., a third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, etc.). Each filter adapter may contain one or more filters or no filters. The filters may be the same or different than one another. In some embodiments, a first filter disk has a first pore size and a second filter disk has a second pore size. In some embodiments, the first pore size is larger than, smaller than, or theAty. Docket No.: UM-43592.601 same size as the second pore size. In some embodiments, a first filter differs from a second filter disk in one or more physical or chemical properties (e.g., hydrophobicity, flexibility, susceptibility to degradation, thermal stability, etc.). In some embodiments, any one or more (or all) of the filter adapters may comprise a vacuum adaptor.In some embodiments, the system further comprises a sample contained in one or more of the filter adaptors. In some embodiments, the sample is a fluid sample. In some embodiments, the sample is a biological sample (e.g., a biological fluid sample (e.g., blood sample)). In some embodiments, the sample is an environmental sample. In some embodiments, the sample is an industrial sample.Also provided herein are methods using the systems and apparatus to filter a sample. For example, in some embodiments, the methods comprise flowing a sample through any apparatus described herein. In some embodiments, the sample comprises a first component (e.g., a desired component) and second component (e.g., an undesired component or a second desired component) that are desired to be separated or isolated from each other. The sample may comprise any one or more additional components (e.g., desired or undesired components). In some embodiments, the first component comprises blood cells. In some embodiments, the second component comprises bacteria.In some embodiments, the method further comprises the step of replacing or removing a filter in a filter disk socket (e.g., a filter disk socket of the first filter adaptor or the second filter adaptor).In some embodiments, the method further comprises the step of reversing an orientation of a filter positioned in a filter disk socket (e.g., a filter disk of the first filter adaptor or the second filter adaptor).In some embodiments, the method further comprises the step of reversing an orientation of a filter disk socket (e.g., a filter disk socket of the first filter adaptor or the second filter adaptor).In some embodiments, the method further comprises the step of reversing an orientation of a first filter adaptor relative to a second filter adaptor when connected.Aty. Docket No.: UM-43592.601In some embodiments, the method further comprises the step of replacing the first filter adaptor or second filter adaptor with a third filter adaptor having a filter disk socket.Also provided herein are uses of any of the described apparatus (e.g., to filter a sample).Further objects, features, and advantages of the invention will be apparent from the following detailed description when taken in conjunction with the accompanying drawings.BRIEF DESCRIPTION OF THE DRAWINGSIn the drawings:Fig. 1 depicts a threaded cylinder filter adaptor according to our invention;Fig. 2 shows a top adaptor according to our invention;Fig. 3 shows a vacuum filter adaptor according to our invention;Fig. 4 shows, in general terms, how multiple threaded filter adaptors of Fig. 1 can be stacked to implement a multi-step filter;Fig. 5 shows how one threaded filter adaptor can be separated from the multi-step filter of Fig. 4 and capped with a top adaptor of Fig. 2, and inverted so that fluid can be passed in the reverse direction to initiate reverse filtration and extract material retained in the filter of Fig. 5 in a method according to our invention; andFig. 6 shows a coupling adaptor according to an embodiment of the invention.Fig. 7 shows an exemplary filter adaptor configured to place and position a filter.

[0001] Fig. 8 shows an exemplary stackable multi-filter device system.DETAILED DESCRIPTION OF THE INVENTIONProvided herein are devices, systems, and methods for filtering. The devices, systems, and methods comprise two or more (e.g., 2, 3, 4, 5, 6, 7, 8, . . .) filter adaptor sub-components, each filter adaptor comprising one or more filters. The filter adaptors are configured to attach to one another to permit serial filtration of a sample through a plurality of different filters.Aty. Docket No.: UM-43592.601Atachment of filter adaptors to one another may be through any suitable mechanism including, but not limited to, threaded attachments (a first end having internal threads and a second end having external threads), clamps (e.g., split collars or clamps), bayonet mounts, magnetic coupling, snap-fits, press-fits, pin and hole, latch or hook, quick-release couplings (e.g., employing ball detents or spring-loaded mechanisms), hook-and-loop fasteners, and the like. Attachments may be reversible or irreversible. In some embodiments, a reversible, manually actuated, locking component is included.The devices, systems, and methods find use in filtering a wide range of samples. In some embodiments, the sample is a biological sample, for example, to isolate, remove, or analyze biomolecules contained in the sample (e.g., nucleic acids (e.g., DNA, RNA), proteins, cells, exosomes, extracellular vesicles, etc.). In some embodiments, desired molecules or materials are separated or removed from undesired molecules or materials (e.g., cells, cellular debris, free proteins, etc.). In some embodiments, molecules are sorted by size or by other physical or chemical properties. Biological samples include, but are not limited to, blood or blood components (e.g., whole blood, serum, plasma), tissue (e.g., homogenized tissue), cells (e.g., lysed cells), saliva, urine, semen, cerebrospinal fluid, fecal samples, amniotic fluid, exhaled breach condensate, sweat, breast milk, lymphatic fluid, exosomes, plant extract, and the like. In some embodiments, the sample is an environmental sample (e.g., water, air, soil, etc.). In some embodiments, the sample is a chemical or solvent sample (e.g., where it is desired to remove impurities). In some embodiments, the sample comprises undesired components (e.g., microorganisms) whereby the filtering provides sterilization. In some embodiments, the sample is an industrial material (e.g., fuel, hydraulic fluid, lubricant, etc.). In some embodiments, the sample contains a component that has a property (e g., radioactivity) that is desired to be monitored. In some embodiments, the sample is derived from an analytical process or is processed by filtering prior to use in an analytical process (e.g., HPLC, mass spectroscopy, dissolution testing, ion chromatography, liquid chromatography). In some embodiments, the sample is a pharmaceutical formulation (e.g., filtration used for purification of drug delivery vehicles (liposome, micelles, exosomes, etc.). In some embodiments, the sample comprises nanoparticles or microparticle that require separation. In some embodiments, the sampleAty. Docket No.: UM-43592.601 comprises extracellular vesicles (or lysed versions thereof) and the filtering is used to purify macromolecular from the vesicles. In some embodiments, the sample comprises particulates isolated from gases, HVAC, or environmental sampling. In some embodiments, the sample is wastewater. In some embodiments, the sample comprises biodiesel fuel fouled with microorganisms. In some embodiments, filtration is performed in a redundant or repeated manner to purify or sterilize clinically relevant molecules or materials (e.g., drugs or drug components).Samples may be used directly or may undergo processing prior to filtering. Processing steps include, but are not limited to, dilution, solubilization, grinding, sonication, lysis, buffering, and the like.In some embodiments, when assembled to include two or more filter adaptors, the devices, systems, and methods comprise two or more different filters (e.g., 2, 3, 4, 5, 6, 7, 8, . . .). In some embodiments, the devices, systems, and methods comprise two or more of the same filter or same type of filter. In some embodiments, an individual filter adaptor may comprise two or more filters (e.g., stacked filters) that may be the same or different. In some embodiments, one or more modules do not contain a filter.Where the filters differ, they may differ by one or more parameters, including pore size, diameter, thickness, chemical makeup, load capacity, etc. In some embodiments, one or more of the filters may be heat resistant to allow inactivation of captured material. In some embodiments, the filters are chemically digestible to allow for recovery of captured material.In some embodiments, filter adaptors are configured to allow insertion and / or removal of a filter or filters to allow a user to modify a given filter adaptor with a specific filter or filters of choice. In some embodiments, filter adaptors have a fixed filter or filters. In some such embodiments, a kit may be provided comprising a collection of different filter adaptors to allow mix-and-match combinations of filter adaptors to yield the desired filter process.In some embodiments, filter adaptors are configured to allow reversible filtration across one or more of the filters. For example, in some embodiments, individual filter adaptors are configured to be connectable to another filter adaptor in either orientation. In some suchAty. Docket No.: UM-43592.601 embodiments, a first filter adaptor is connected to a second filter adaptor in a top-to-bottom orientation and filtering is conducted. Next, the first filter adaptor is separated from the second filter adaptor, inverted, and attached in a bottom-to-top orientation and a second filtering is conducted. Alternatively, a filter may be inserted into a filter adaptor in a first orientation and later removed, inverted, and reinserted in an opposite orientation. Alternatively, a filter, contained in a filter adaptor, may be configured to flip orientations within the filter adaptor without requiring removal from the filter adaptor.The selection and order of filters within the two or more filter adaptors may be chosen to achieve a desired goal. For example, in some embodiments, enhanced filtration efficiency is achieved by having each filter provide a different size selection. In some embodiments, filters are selected to allow gradual filtration to reduce load on each individual filter, preventing or reducing clogging. In some embodiments, a first filter provides desired pre-filtration, followed by a second filter that collects a material of interest. In some embodiments, a series of filters provide sequential conjugation capture of different analytes of interest in a sample (e.g., multiple different protists in a water sample are collected on different filters). In some embodiments, filter adaptors are selected to allow for graded particle monitoring.The size, shape, and material composition of the filtration adaptors may be selected for optimal use, including selection based on the nature of the sample, the volume of the sample, instrumentation employed (e.g., centrifugation devices), sterility concerns, safety concerns, etc. In some embodiments, the filtrations adaptors are configured to function within another device such as a syringe (e.g., provided as a component of a barrel of a syringe).Fluid flow through the filtration devices / system may be conducted using any desired mechanism, including, but not limited to, centrifugal force, gravity, push pressure, pull pressure (e.g., vacuum force), shaking, vibration, and the like.Individual filters may be obtained from or derived from commercial sources (e.g., 3M, Millipore, Whatman) or may be custom-designed.One or more of the filters may have a defined pore size. Any suitable pore size for the application of interest may be used. Pore sizes include, but are not limited to (in microns), 0.025,Aty. Docket No.: UM-43592.6010.05, 0.1, O.2., 0.22, 0.3, 0.4, 0.45, 0.5, 0.6, 0.65, O.7., 0.8, 1.0, 1.2, 1.6, 2, 2.5, 2.7, 3, 5, 8, 10, 11, 20, 25, 30, 40, 41, 45, 60, 80, 100, 120, 140, 160, 180, or any sizes therein between.Filter dimensions (e.g., diameter, thickness, etc.) may be selected based on the desired utility. In some embodiments, the filter adaptors are configured to hold “standard” commercial filter size. For example, the filter adaptor may be selected to hold a filter having a diameter of (in millimeters) any of: 10, 13, 25, 37, 47, 50, 70, 75, 82, 90, 100, 124, 142, 150, 293 or any sizes therein between.Filters may be selected to have desired chemical properties to facilitate capture or repulsion of desired or undesired molecules in a sample. In some embodiments, filters are hydrophilic. In some embodiments, filters are hydrophobic. Filter composition may also be selected for thermostability, durability, or resistance to acidic or basic conditions. Filters may comprise one or more of various filter membrane materials, such as cellulose acetate, cellulose nitrate, polypropylene (PP), polyethersulfone (PES), nylon, polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), polycarbonate (PC), polyvinylidene chloride, alumina oxide, glass fiber, and the like. In some embodiments, each connectable filter may be comprised of a different filter membrane material. Each of these membrane materials may confer varying benefits for each stage of filtration (e.g., different filters vary in their suitability for polar versus non-polar solutes, resistance to strong acids / bases, thermal stability, resistance to degradation, flexibility, and compatibility with different flow rates). Availing of these features in the system allows for greater selectivity and optimization across a variety of parameters at each filtration step. In some embodiments, one or more filters may be uniquely coated with a reagent, or a reagent solution may be added on top of one or more filters, allowing for differential reactions as the solution flows down the modular adaptors (e.g., under controlled vacuum pressure).In some embodiments, systems and kits are provided that include two or more filter adaptors and optionally one or more additional components. Additional components include, but are not limited to, instruments (centrifuges, pressure generating devices, sample dispensers, magnets, automated robotic components, sample collectors, detection devices, analyte analysis equipment, etc.), reagents (e.g., buffers, wash solutions); beads (e.g., paramagnetic beads); sensors; computing devices; software; written instructions; etc.Aty. Docket No.: UM-43592.601Non-limiting illustrative embodiments are provided in more detail below.Fig. 1 depicts a threaded cylinder filter adaptor 100 according to an embodiment of the invention. The filter adaptor 100 has a first / upper end 105 and a second / lower end 110. The first end 105 bears first end threads 115 that are preferably external (i.e. positive / male) threads, and the second end 110 bears second end threads 120 that are preferably internal (i.e. negative / female) threads. In an alternate embodiment, the first end threads 115 could be internal threads and the second end threads 120 could be external threads.The first end 105 of the filter adaptor 100 includes first end cavity walls 125, preferably but not necessarily cylindrical in shape, surrounding a first end cavity 130. The second end 110 of the filter adaptor 100 includes cavity walls 135, also preferably but not necessarily cylindrical in shape, surrounding a second end cavity 140. A filter disc socket 145, adapted to receive a filter disc 150, is positioned between the first end cavity 130 and the second end cavity 140. When two filter adaptors 100 are threaded together, the upper filter adaptor 100 holds the filter disc 150 in place in the bottom filter adaptor 100.Fig. 2 shows a top adaptor 200 according to an embodiment of the invention. The top adaptor 200 includes a first / upper end 205 and a second / lower end 210. The second end 210 includes fifth end threads 215 that are preferably positive / male threads. In an alternate embodiment the fifth end threads 215 could be negative / female threads. The first end 205 includes a cap 220. The second end 210 includes top cavity walls 225, preferably but not necessarily cylindrical in shape, surrounding a top cavity 230. When a top adaptor 200 is threaded onto the top of a filter adaptor 100, it holds the filter disc 150 in place in that filter adaptor 100.Multiple filter adaptors 100 can be coupled together into a stack, placed in a tube and simply centrifuged to pass sample fluids through the stack. Alternatively, depending on the application, a vacuum filtration adaptor 300 can be used to initiate vacuum filtration instead.Fig. 3 shows a vacuum filtration adaptor 300 according to an embodiment of the invention. The vacuum filtration adaptor 300 includes a first / upper end 305 bearing sixth end threads 315 that are preferably negative / female threads, and a second / lower end 310 bearingAty. Docket No.: UM-43592.601 seventh end threads 320 that are preferably negative / female threads. The vacuum filtration adaptor 300 has vacuum cavity walls 325 surrounding a vacuum cavity 330, and a vacuum port 335 into the vacuum cavity 330.The cylinder adaptor 100, top adaptor 200, vacuum port adaptor 300, and coupling adaptor 600 can be formed using 3D printing methods, however this is not required and they could be formed with other methods, such as injection molding.Fig. 4 shows, in general terms, how multiple threaded filter adaptors of Fig. 1 can be stacked to implement a multi-step filter 400. The exemplary multi-step filter 400 includes a first cylinder adaptor 100 A and a second cylinder adaptor 100B threaded together. While the multi- step filter 400 includes 2 cylinder adaptors 100A and 100B, more than two could be used depending on the application.The multi-step filter 400 may also include a top adaptor 200 threaded onto the first end 105 A of the first cylinder adaptor 100 A, and a vacuum filtration adaptor 300 threaded onto the second end HOB of the second cylinder adaptor 100B, however this is not required and one or both could be omitted depending on the application.The first cylinder adaptor 100 A and second cylinder adaptor 100B preferably have the same shape and dimensions as the cylinder adaptor 100 of Fig. 1, however this is not required, and they could have different dimensions and / or different shapes for a particular application. The first and second cylinder adaptors 100 A, 100B each have a first end 105 A, 105B, a second end 110A, 110B, a first cavity 130A, 130B and a second cavity 140A, 140B respectively.The first and second cylinder adaptors 100A, 100B may be configured and dimensioned with a diameter small enough to fit in 50 ml conical sample tubes, however this is not required. Depending on the application, they could be configured and dimensioned to be used with Eppendorf or other common sample tube types.The first and second cylinder adaptors 100A, 100B each may include a filter disk socket 145A, 145B configured to receive a filter disk 150A, 150B. A suitable filter could be, for example, a Millipore(R) 47 mm diameter mixed cellulose esters (MCE) membrane hydrophilic white filter, however this is not required, and other filter disks could be used.Aty. Docket No.: UM-43592.601After placing the filter 150A onto the filter socket 145A, the filter 150A is retained in place by threading the top adaptor 200 onto the first, adaptor 100A. Similarly, after placing the filter 150B onto the filter socket 145B, the filter 150B is retained in place by threading the first adaptor 100 A onto the second adaptor 100B.The filter disks 150A and 150B may have different pore sizes, with the first filter disk 150A having a pore size (e.g. 5 microns) larger than the pore size of the second filter (e.g. 1 micron), with the specific pore sizes chosen depending on the particular application. The filter disks 1 0A, 150B each have a first surface 152A, 152B in fluid communication with the first cavity 130A, 13 OB, and a second surface 154 A, 154B in fluid communication with the second cavity 140 A, 140B.One aspect of our invention is a method of recovering bacteria from blood for downstream PCR analysis of the bacteria using the multi-step filter 400 to process a large volume of blood (e.g. from a 50 ml conical tube) to first remove red and white blood cells in the first cylinder adaptor 100 A and then retain any bacteria in the second cylinder adaptor 100BIn a method according to our invention, first the blood is passed through a filter disk 150A having a pore size of about 5 microns so the red and white blood cells larger than 5 microns do not pass through the filter disk 150A, but instead are retained in the first cavity 130A. The fluid without components larger than 5 microns (e.g. red and white blood cells) may pass through the filter disk 150A into the second cavity 140A. The transfer of fluid can be accomplished by centrifuging or vacuum, however this is not required and other mechanisms can be used.The first and second cylinder adaptors 100A, 100B are mated together so the second cavity 140A of the first cylinder adaptor 100A is in fluid communication with the first cavity 130B of the second cylinder adaptor 100B. The filter disk 150B may have a pore size of about 1 micron, smaller than the size of the bacteria of interest, so fluid with bacteria removed may pass through the filter disk 150B into the second cavity 140B. Any bacteria larger than 1 micron is retained in the first cavity 130B on the first surface 152B of the filter disk 150B.Aty. Docket No.: UM-43592.601A second aspect of our invention is, after an initial filtration is run, to uncouple the first cylinder adaptor 100 A from the first end 105B of the second cylinder adaptor 100B. If present, the vacuum adaptor 300 is also removed from the second end HOB. of the second cylinder adaptor 100B. Then, a top adaptor 200 may be coupled to the first end 105B of the second cylinder adaptor.Fig. 5 shows the resulting structure inverted to form a reversed flow filter 500 with the retained bacteria 510 on the first side 152B of the filter disk 150B. Water or other fluid can then be passed in a reverse flow (e.g. by centrifuging or by vacuum filtration) to displace the retained bacteria from the first side 152B of the filter disk 150B into a solution contained in the second cavity BOB for subsequent processing (e.g. downstream PCR).Fig. 6 shows a coupling adaptor 600. The coupling adaptor 600 has a first / upper end 605 and a second / lower end 610 each containing positive / male threads 615. The coupling adaptor has central cavity walls 625 surrounding a central cavity 630. The exemplary coupling adaptor 600 could be used, for example, to connect two cylinder filter adaptors together in series with one filter adaptor inverted relative to the other filter adaptor. The exemplary coupling adaptor 600 has a symmetric construction with positive / male threads 615 at both ends, but this is not required and depending on the application a coupling adaptor 600 could have negative / female threads at both ends or positive / male threads at one end and negative / female threads at the other end.Fig. 7 shows an exemplary filter adapter 700 having a filter adapter cap 710, a filter 720, and a filter adapter base 725. The filter adapter base 725 has a pair of opposing slots 730 sized and shaped to receive a pair of corresponding tabs 740 on opposing sides of the filter 720. The filter adapter base 725 comprises internal threading 750 configured to allow secure attachment of the filter adapter cap 710, having external threading 715. Attachment of the filter adapter cap 710 to the filter adapter base 725 sandwiches the filter 720 between the two when assembled. In use, either the assembled filter adapter 700 or just the filter 720 may be inverted to allow alternative capture and release of desired molecules. In some embodiments, the filter 720 has markings (not shown) that indicate top and bottom sides for easy tracking of the filter inversion position.Atty. Docket No.: UM-43592.601Fig. 8 shows an example of a stacked multi-filter device 800. This design is particularly suitable for use with a smaller (e.g., 25mm) diameter filter and is readily disposable and allows for the filter(s) to be flipped over easily for reverse filtration. The multi-filter device is assembled by connecting threading between a top adapter 810, a first cylinder adapter 820, a second cylinder adapter 830, and a vacuum filter adapter 840. Filter adapters, for example of the type shown in Fig. 7, are positioned within the first and / or second cylinder adapters at, for example, the positions 850 shown by the rectangular boxes. The design is configured for easy collection of materials in a collection tube (not shown) positioned around the lower end of the vacuum attachment sub-component. It is understood that the invention is not confined to the embodiments set forth herein as illustrative but embraces all such forms thereof that come within the scope of the following claims.

Claims

Atty. Docket No.: UM-43592.601CLAIMSWHAT IS CLAIMED IS:

1. An apparatus for multi-step fluid sample filtration comprising:(a) a first filter adaptor having a filter disk socket; and(b) a second filter adaptor having a filter disk socket; wherein the first filter adaptor and second filter adaptor are configured to attach to one another to form a multi-step sample filtration flow path to allow fluid flow through both the first filter adaptor and the second filter adaptor; and wherein the apparatus is reconfigurable to allow one or more of: (i) replacement or removal of a filter in the filter disk socket of the first filter adaptor or the second filter adaptor; (ii) reversal of an orientation of a filter positioned in the filter disk socket of the first filter adaptor or the second filter adaptor; (iii) reversal of an orientation of the filter disk socket of the first filter adaptor or the second filter adaptor; (iv) reversal of an orientation of the first filter adaptor relative to the second filter adaptor when connected; (v) replacement of the first filter adaptor or second filter adaptor with a third filter adaptor having a filter disk socket; and (vi) addition of a third filter adaptor having a third filter socket.

2. The apparatus of claim 1, further comprising a first filter disk mounted in the filter disk socket of the first filter adaptor, and a second filter disk mounted in the filter disk socket of the second filter adaptor.

3. The apparatus of claim 2, wherein the first filter disk has a first pore size and the second filter disk has a second pore size.

4. The apparatus of claim 3, wherein the first pore size is larger than the second pore size.Atty. Docket No.: UM-43592.6015. The apparatus of claim 3, wherein the first pore size is the same as the second pore size.

6. The apparatus of claim 3, wherein the first filter disk and second filter disk differ in one or more of hydrophobicity, flexibility, susceptibility to degradation, or thermal stability.

7. The apparatus of claim 1, wherein the first filter adaptor and the second filter adaptor are configured to attach to one another via threaded connectors.

8. The apparatus of claim 1, further comprising a third filter adaptor having a filter disk socket.

9. The apparatus of claim 8, further comprising one or more additional filter adaptor having a filter disk socket.

10. The apparatus of claim 1, further comprising at least one vacuum adaptor attached in series to the first filter adaptor and / or to the second filter adaptor.

11. The apparatus of claim 10, wherein two or more filter adaptors comprise a vacuum adapter.

12. A system comprising the apparatus of claim 1 and a fluid sample.

13. The system of claim 12, wherein the fluid sample is a biological fluid sample.

14. The system of claim 12, wherein the fluid sample is an environmental sample.

15. The system of claim 12, wherein the fluid sample is an industrial sample.Atty. Docket No.: UM-43592.60116. The system of claim 12, wherein the fluid sample is a blood sample.

17. A method for filtering a sample comprising: flowing a sample through an apparatus of claim 1.

18. The method of claim 17, wherein the sample comprises a first component and a second component.

19. The method of claim 18, wherein the first component comprises blood cells.

20. The method of claim 18, wherein the second component comprises bacteria.

21. The method of claim 17, further comprising the step of replacing or removing a filter in the filter disk socket of the first filter adaptor or the second filter adaptor.

22. The method of claim 17, further comprising the step of reversing an orientation of a filter positioned in the filter disk socket of the first filter adaptor or the second filter adaptor.

23. The method of claim 17, further comprising the step of reversing an orientation of the filter disk socket of the first filter adaptor or the second filter adaptor.

24. The method of claim 17, further comprising the step of reversing an orientation of the first filter adaptor relative to the second filter adaptor when connected.

25. The method of claim 17, further comprising the step of replacing the first filter adaptor or second filter adaptor with a third filter adaptor having a filter disk socket.

26. Use of an apparatus of any of claims 1 to 11.

27. Use of an apparatus of any of claims 1 to 11 to filter a sample.

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