Systems and methods for collecting and transferring cells to microscope slides

Abstract

Systems and methods for collecting and applying cells to a microscope slide are disclosed and described. In one embodiment, one such system can include a cell collection assembly having a fluid reservoir and a cell collecting membrane fluidly coupled to the fluid reservoir. A vacuum source can be fluidly coupled to the fluid reservoir, the vacuum source operable to draw fluid through the cell collecting membrane to thereby collect cells contained in the fluid. The cell collection assembly can be operable to maintain liquid in the fluid reservoir when gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane. A stabilizer can be operable to minimize unwanted motion of the cell collecting membrane as the collected cells are applied to a slide.

Description

[0001] Thorpe North & Western, LLP

[0002] Docket No. 3919-001.PCT

[0003] SYSTEMS AND METHODS FOR COLLECTING AND TRANSFERRING CELLS

[0004] TO MICROSCOPE SLIDES

[0005] PRIORITY CLAIM

[0006] Priority is claimed of and to U.S. Provisional Patent Application Serial No. 63 / 728.076, filed December 4. 2024, which is hereby incorporated herein by reference in its entirety.

[0007] FIELD OF THE INVENTION

[0008] The present invention relates generally to systems for collecting cells from a liquid suspension and transferring the cells to microscope slides. Accordingly, the present invention involves the mechanical arts field and the chemical arts field.

[0009] BACKGROUND OF THE INVENTION

[0010] Liquid-based cytology involves the collection of cells from a test subject and suspending such cells in a liquid. Cells are then extracted from the liquid suspension and deposited upon a microscope slide for examination. This process is often used, for example, to test for the presence of cervical and colon cancer. Numerous conventional systems have been developed for this process. While such systems have proved effective, they are often very sophisticated and costly, and often not available in marginalized markets. Accordingly, designers continue to seek solutions that can be implemented accurately, simply and in a cost-effective manner.

[0011] SUMMARY OF THE INVENTION

[0012] In one embodiment, a system for collecting cells from a liquid to transfer the cells to a microscope slide is provided. The system can include a cell collection assembly having a fluid reservoir and a cell collecting membrane fluidly coupled to the fluid reservoir. A vacuum source can be fluidly coupled to the fluid reservoir, the vacuum source operable to draw liquid through the cell collecting membrane to thereby collect cells contained in the fluid. The cell collection assembly can be operable to maintain liquid in the fluid reservoir when gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane.

[0013] In another example, a cell collection assembly for collecting cells from a liquid to transfer the cells to a microscope slide is provided. The cell collection assembly can Thorpe North & Western, LLP

[0014] Docket No. 3919-00 LPCT include a cell collecting membrane fluidly coupled to a fluid reservoir. The fluid reservoir can be coupleable to a vacuum source to enable the vacuum source to draw fluid through the cell collecting membrane to thereby collect cells contained in the fluid. The cell collection assembly can be operable to maintain liquid in the fluid reservoir when a gravitational force applied by gravity' to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane.

[0015] In another example, a method of collecting cells and applying them to a microscope slide is provided. The method can include obtaining a cell collection assembly having a fluid reservoir with a cell collecting membrane fluidly coupled thereto. The cell collecting membrane can be introduced into a liquid carrying a plurality of cells. A vacuum can be applied to the cell collection assembly to draw liquid through the cell collecting membrane and into the fluid reservoir, thereby collecting cells contained within the liquid across a collection surface of the cell collecting membrane. The cell collection assembly can be oriented such that gravitational force applied by gravity7to contents of the fluid reservoir tends to force the contents toward the cell collecting membrane. The cell collection assembly and a microscope slide can be positioned relative to one another. Contact can be caused between the microscope slide and the collection surface of the cell collecting membrane to thereby apply the cells collected on the collection surface to the slide while restraining liquid in the fluid reservoir from passing through the cell collecting membrane.

[0016] There has thus been outlined, rather broadly, the more important features of the invention so that the detailed description thereof that follows may be better understood, and so that the present contribution to the art may be better appreciated. Other features of the present invention will become clearer from the following detailed description of the invention, taken with the accompanying drawings and claims, or may be learned by the practice of the invention.

[0017] BRIEF DESCRIPTION OF THE DRAWINGS

[0018] FIG. 1 is a front, sectioned view of a cell collection and transferring system in accordance with an example embodiment.

[0019] FIG. 2 is a front, sectioned view of the system of FIG. 1, after collection of a liquid from a liquid container.

[0020] FIG. 3 is a front, sectioned view of the system of FIG. 1, prior to application of cells to a microscope slide. Thorpe North & Western, LLP

[0021] Docket No. 3919-001.PCT

[0022] FIG. 4 is a front, sectioned view of another example of a cell collection and transferring system in accordance with the present technology.

[0023] FIG. 5 is a front, sectioned view of another example of a cell collection and transferring system in accordance with the present technology.

[0024] FIG. 6 is a front, sectioned view of another example of a cell collection and transferring system in accordance with the present technology.

[0025] FIG. 7A is a front, sectioned view of another example of a cell collection and transferring system in accordance with the technology.

[0026] FIG. 7B is a top view of an exemplary component of a fluidic check valve in accordance with the present technology.

[0027] FIG. 8 is a front, sectioned view of a cell collection and transferring assembly in accordance with the technology.

[0028] FIG. 9 is a front, sectioned view of a cell collection and transferring assembly in accordance with the technology.

[0029] FIG. 10 is a front view of an exemplary stabilizer carrying a cell collection and transferring assembly for use atop a microscope slide support surface in accordance with the technology.

[0030] FIG. 11 is a front view of an exemplary stand-alone stabilizer carry ing a cell collection and transferring assembly and a microscope slide in accordance with the technology.

[0031] FIG 12 is a perspective view an exemplary alignment block in accordance with the technology.

[0032] FIG 13A is a front, schematic view of an exemplary sample collection and transferring assembly in accordance with the technology’.

[0033] FIG. 13B is a front, schematic view of the assembly of FIG. 13 A, shown with a filling cylinder separated from a filter assembly.

[0034] These drawings are provided to illustrate various aspects of the invention and are not intended to be limiting of the scope in terms of dimensions, materials, configurations, arrangements or proportions unless otherwise limited by the claims.

[0035] DETAILED DESCRIPTION OF THE INVENTION

[0036] While these exemplary' embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, it should be understood that other embodiments may be realized and that various changes to the invention may be made Thorpe North & Western, LLP

[0037] Docket No. 3919-00 LPCT without departing from the spirit and scope of the present invention. Thus, the following more detailed description of the embodiments of the present invention is not intended to limit the scope of the invention, as claimed, but is presented for purposes of illustration only and not limitation to describe the features and characteristics of the present invention, to set forth the best mode of operation of the invention, and to sufficiently enable one skilled in the art to practice the invention. Accordingly, the scope of the present invention is to be defined solely by the appended claims.

[0038] Definitions

[0039] In describing and claiming the present invention, the following terminology will be used in accordance with the definitions set forth below.

[0040] The singular forms “a,” “an,’’ and, “the” in the written description include express support for plural referents unless the context clearly dictates otherwise.

[0041] In this disclosure, “comprises,” “comprising,” “containing” and “having” and the like can have the meaning ascribed to them in U.S. Patent law and can mean “includes.” “including,” and the like, and are generally interpreted to be open ended terms. The terms “consisting of’ or “consists of’ are closed terms, and include only the components, structures, steps, or the like specifically listed in conjunction with such terms, as well as that which is in accordance with U.S. Patent law. “Consisting essentially of' or “consists essentially of’ have the meaning generally ascribed to them by U.S. Patent law. In particular, such terms are generally closed terms, with the exception of allowing inclusion of additional items, materials, components, steps, or elements, that do not materially affect the basic and novel characteristics or function of the item(s) used in connection therewith. For example, trace elements present in a composition, but not affecting the composition’s nature or characteristics would be permissible if present under the “consisting essentially of’ language, even though not expressly recited in a list of items following such terminology. When using an open-ended term, like “comprising” or “including,” in the written description it is understood that direct support should also be afforded to “consisting essentially of’ language as well as “consisting of’ language as if stated explicitly and vice versa.

[0042] The terms “first,” “second,” “third,” “fourth,” and the like in the written description and in the claims, if any, are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances Thorpe North & Western, LLP

[0043] Docket No. 3919-001.PCT such that the embodiments described herein are, for example, capable of operation in sequences other than those illustrated or otherwise described herein. Similarly, if a method is described herein as comprising a series of steps, the order of such steps as presented herein is not necessarily the only order in which such steps may be performed, and certain of the stated steps may possibly be omitted and / or certain other steps not described herein may possibly be added to the method.

[0044] The terms “left,” “right,” “front,” “back,” “top,” “bottom,” “over,” “under,” and the like in the written description and in the claims, if any, are used for descriptive purposes and not necessarily for describing permanent relative positions. It is to be understood that the terms so used are interchangeable under appropriate circumstances such that the embodiments described herein are. for example, can be capable of operation in other orientations than those illustrated or otherwise described herein. The term “coupled,” as used herein, is defined as directly or indirectly connected in a mechanical or nonmechanical manner. Objects or structures described herein as being “adjacent to” each other may be in physical contact with each other, in close proximity to each other, or in the same general region or area as each other, as appropriate for the context in which the phrase is used. Occurrences of the phrase “in one embodiment,” or “in one aspect,” herein do not necessarily all refer to the same embodiment or aspect.

[0045] When reference is made herein to fluid flow, directional terms can be used to indicate positions of various components relative to one another as those components experience or are subject to fluid flow. Such terms do not necessarily describe such positions as they would occur in space. For example, a component that is "downstream" of another may be physically located above such component. A component that is “upstream” of another may be physically located below, or to the side, of such component.

[0046] When used herein, reference to the direction of gravity, or to the gravity vector, refers to the direction in which a body near the surface of the Earth will fall in a vacuum. Generally, this direction is that considered to be vertical or “plumb:” e.g.. that direction that is orthogonal to a surface considered horizontal or “level.”

[0047] Reference throughout the written description to “an example” means that a particular feature, structure, or characteristic described in connection with the example is included in at least one embodiment. Thus, appearances of the phrases “in an example” in various places throughout this specification are not necessarily all referring to the same embodiment. Thorpe North & Western, LLP

[0048] Docket No. 3919-00 LPCT

[0049] Reference in the written description may be made to devices, structures, systems, or methods that provide "‘improved” performance. It is to be understood that unless otherwise stated, such ‘'improvement” is a measure of a benefit obtained based on a comparison to devices, structures, systems or methods in the prior art. Furthermore, it is to be understood that the degree of improved performance may vary between disclosed embodiments and that no equality or consistency in the amount, degree, or realization of improved performance is to be assumed as universally applicable.

[0050] As used herein, the term “about” is used to provide flexibility to a numerical range endpoint by providing that a given value may be “a little above” or “a little below” the endpoint. However, it is to be understood that even when the term “about” is used in the present specification in connection with a specific numerical value, that support for the exact numerical value recited apart from the “about” terminology is also provided.

[0051] As used herein, the term “substantially” refers to the complete or nearly complete extent or degree of an action, characteristic, property, state, structure, item, or result. For example, an object that is “substantially” enclosed would mean that the object is either completely enclosed or nearly completely enclosed. The exact allowable degree of deviation from absolute completeness may in some cases depend on the specific context. However, generally speaking the nearness of completion will be so as to have the same overall result as if absolute and total completion were obtained. The use of “substantially” is equally applicable when used in a negative connotation to refer to the complete or near complete lack of an action, characteristic, property, state, structure, item, or result. For example, a composition that is “substantially free of’ particles would either completely lack particles, or so nearly completely lack particles that the effect would be the same as if it completely lacked particles. In other words, a composition that is “substantially free of’ an ingredient or element may still actually contain such item as long as there is no measurable effect thereof.

[0052] As used herein, a plurality7of items, structural elements, compositional elements, and / or materials may be presented in a common list for convenience. However, these lists should be construed as though each member of the list is individually identified as a separate and unique member. Thus, no individual member of such list should be construed as a de facto equivalent of any other member of the same list solely based on their presentation in a common group without indications to the contrary.

[0053] As used herein, comparative terms such as “increased.” “decreased.” “better,” “worse,” '‘higher,” '‘lower,” “enhanced,” and the like refer to a property of a device. Thorpe North & Western, LLP

[0054] Docket No. 3919-001.PCT component, or activity that is measurably different from other devices, components, or activities in a surrounding or adjacent area, in a single device or in multiple comparable devices, in a group or class, in multiple groups or classes, or as compared to the known state of the art. For example, composition or system that has or provides “increased” stabi 1 i ty exhibits a higher degree of stability as compared to a different, yet comparable composition or system, or as compared to a composition or system known in the art. A number of factors can cause such increased stability, including composition ingredients, system components or structures, operation, etc.

[0055] The term “coupled,” as used herein, is defined as directly or indirectly connected. “Directly coupled” objects or structures are in physical contact and are attached. “Fluidly- coupled” objects, structures, or components are in a sufficient relationship so as to allow movement or transfer of fluid from one of the objects, structures, or components to the other. Objects described herein as being “adjacent to” each other may be in physical contact with each other, in close proximity to each other, or in the same general region or area as each other, as appropriate for the context in which the phrase is used.

[0056] Numerical data may be expressed or presented herein in a range format. It is to be understood that such a range format is used merely for convenience and brevity and thus should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or subranges encompassed within that range as if each numerical value and sub-range is explicitly recited. As an illustration, a numerical range of “about 1 to about 5” should be interpreted to include not only the explicitly recited values of about 1 to about 5, but also include individual values and sub-ranges within the indicated range. Thus, included in this numerical range are individual values such as 2, 3, and 4 and sub-ranges such as from 1-3, from 2-4, and from 3-5, etc., as well as 1, 2, 3, 4, and 5, individually. This same principle applies to ranges reciting only one numerical value as a minimum or a maximum. Furthermore, such an interpretation should apply regardless of the breadth of the range or the characteristics being described.

[0057] Description of Embodiments

[0058] The present technology relates generally to systems and related methods for preparing cells for microscopic analysis. The technology is well suited for use in cytology sample preparation and does not require costly and specialized cell preparation Thorpe North & Western, LLP

[0059] Docket No. 3919-00 LPCT equipment. In particular, examples of the present technology can be implemented using readily available, hand-held laboratory equipment.

[0060] In a typical liquid-based cytology procedure, cells are extracted from or along with tissue from a subject. For example, a cell brush or scraper can be used to extract cervical cells to test for the presence of cervical cancer. These cells are then processed into a liquid solution and centrifuged to ensure even distribution of the cells throughout the liquid. The cells are then extracted from the liquid suspension and applied as a very thin layer to a microscope slide. To ensure effective analysis of the cellular material, the material applied to the slide should present a uniform, single-cell layer across the slide. Very little of the liquid used in the suspension should be applied to the slide, as this can result in the cells being washed away from some areas and collecting in large, possibly overlapping concentration in other areas. If the cell distribution is not uniform, the slide cannot be effectively used in the test.

[0061] The present technology results in a consistent cell distribution across slides with a minimum of cost and effort required on the part of technicians preparing the slides. As shown generally in FIGs. 1-3, in one example the system 10 can include a cell collection assembly 12 that can include a fluid reservoir 14, and a cell collecting membrane 16 fluidly coupled to the fluid reservoir. A vacuum source (shown schematically at 18) can be fluidly coupled to the fluid reservoir. A liquid container 20 can be provided that includes a number of cells 22 suspended in a liquid 24. The vacuum source can be operable to draw liquid through the cell collecting membrane to thereby collect cells contained in the liquid. The cell collection assembly is advantageously operable to maintain liquid in the fluid reservoir when gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane.

[0062] In the exemplary application represented in FIGs. 1-3, the cell collection assembly 12 is first introduced into the liquid 24 to at least the extent that a cell collection surface 28 is immersed in the liquid. A vacuum force can then be applied by vacuum source 18, which results in turn in a vacuum being created in the reservoir. This vacuum, applying force shown schematically at 30. draws the liquid through the cell collecting membrane 16. As the liquid is drawn through the membrane, individual cells are collected on the collection surface 8 of the membrane, as shown by example in FIG. 2. The filtered fluid Thorpe North & Western, LLP

[0063] Docket No. 3919-00 LPCT

[0064] 25 collects in the fluid reservoir above the cell collecting membrane and is restrained in the reservoir after cell collection.

[0065] As shown in FIG. 3, the cell collection assembly 12 can then be positioned relative to a microscope slide 32, after which the cell collection surface 28 and the slide can be pressed into contact with one another. This results in the individual cells 22 being transferred from the cell collection surface to the surface of the slide, with very little of the liquid being applied to the slide. This process applies a very thin, single layer of cells with good cell distribution across the slide surface. The slide can then be evaluated as usual with a microscope according to the particular test being conducted.

[0066] It is noted that the figures provided are intended to best describe the present technology, and are not necessarily to scale, nor are components necessarily depicted to scale in relation to one another. In particular, cells 22 are depicted in the figures in a schematic representation to aid in describing the present technology: as one of ordinary' skill in the art will appreciate, they are shown much, much larger than actual scale. Also, the vacuum source is illustrated schematically at 18 in some of the figures. It is to be understood that a variety of vacuum sources can be utilized with the present technology, as discussed in more detail below: as such sources will be readily understood by one of ordinary' skill in the art, none are shown with particularity7. Various views of fluidic check valves, discussed in more detail below, are also schematically presented to best illustrate the function and purpose of such devices without necessarily showing the components therein to scale.

[0067] The examples provided are intended to represent actual clinical practice. In all such practices, the force of gravity affects all objects, including the liquid. The directionality of the force of gravity is shown in the figures, generally opposing the direction of the vacuum force shown at 30. It has not been possible, using conventional systems, to orient a sample of liquid in the manner shown in the present figures, as doing so would result in liquid being pulled by gravity from the sample container and collecting atop the slide. Such a liquid wash is undesirable, as it results in an uneven cell distribution across the slide, thus resulting in a sample that cannot be used. This aspect has driven many conventional systems to use overly' sophisticated, and often ineffective, equipment in an attempt to apply a cell layer to a slide while in an inverted position (e.g., to apply the cell layer to the surface of the slide oriented downwardly).

[0068] The present technology allows application of the cell layer to the slide in conditions that can easily be executed by technicians in standard lab conditions with little Thorpe North & Western, LLP

[0069] Docket No. 3919-00 LPCT or no specialized knowledge or equipment. As represented in FIG. 2, in one example, as the cell collection assembly 12 is removed from the liquid suspension 24. the vacuum source 18 can continue to apply the vacuum force and thus continue to retain the liquid 25 in the fluid reservoir to prevent, restrain or limit the liquid from washing back through the cell collecting membrane 16. Even positioned as shown (e.g., above the liquid container), the cells 22 can be maintained in the configuration, e.g.. the spatial arrangement, in which they were applied to the collection surface 28 of the membrane 16. This same spatial arrangement can be maintained as the cells are applied to the microscope slide 32.

[0070] The vacuum source 18 can vary, depending upon the configuration of the system as a whole. In one example, the vacuum source can be capable of providing a force of at least about 8 kilopascals ("kPa”). In one example, the vacuum source can include or comprise a hand-held syringe. In one example, the fluid reservoir 14 can comprise the barrel of a syringe, with the vacuum source provided by the plunger or piston of the syringe. In this embodiment, the cell collecting membrane 16 can be integrated within the barrel of the syringe, or can be attached to an end of the syringe, or placed in-line with the syringe using tubing or other suitable conduit. This can be advantageous in that syringes are readily available and operation of such devices is intuitively understood by technicians.

[0071] In another example, the vacuum source 18 can include or comprise a hand-held pipette. In this embodiment, the fluid reservoir 14 can be the tip or cone of a pipette, and the vacuum source can be provided by the manual or electronic pipettor typically used with pipettes. The fluid reservoir 14 can also be a tube extended from or coupled to the tip or cone of a pipette, or to the syringe discussed above. The vacuum source can be integrated within the cell collection assembly, or can be fixed to or removably coupled to the assembly.

[0072] In another example, the vacuum source 18 can be located remotely from the fluid reservoir 14. In this embodiment, a mechanical or electric pump can be fluidly coupled to the fluid reservoir to provide the vacuum desired. Such pump can be operated, for example, with a foot pedal, leaving the technician’s hands free for cell slide preparation.

[0073] In the example shown in FIG. 9, the vacuum source 18a can include or comprise an absorbent medium positioned relative to the membrane 16 such that fluid is drawn into the porous medium through the membrane 16. This example can beneficially provide a very simple and lightweight vacuum source, in addition to providing ease of handling and disposal of the collected liquid after use. Thorpe North & Western, LLP

[0074] Docket No. 3919-00 LPCT

[0075] Regardless of the type and configuration of the vacuum source 18, the system can be operable to selectively apply, discontinue or remove the vacuum force from the remaining components. For example, after the cells 22 have been collected on the cell collection surface 28, as shown for example in FIG. 2, the vacuum force 30 can be maintained while the system restrains the liquid 25 from washing downstream through the membrane 16. In another example, the vacuum force 30 can be increased while the system restrains the liquid from washing downstream. In another example, the vacuum force can be discontinued while the system restrains the liquid from washing downstream. In those cases where the cell collection assembly 12 utilizes a hand-held device, the operator can determine which degree of vacuum force to maintain or discontinue to provide the best results as the cells are moved with the membrane and applied to the slide 32, as shown for example in FIG. 3.

[0076] In one example, the vacuum source 18 can be operable to apply a vacuum force substantially evenly across the collection surface 28 of the cell collecting membrane. This can aid in obtaining a uniform distribution of cells across the collection surface. Distributing the vacuum force across the cell collection surface can be achieved in a number of manners. In one example, an inside diameter of the fluid reservoir 14 can substantially correspond to, or match or equal, a diameter of the cell collecting membrane. In one example, the inside diameter of the fluid reservoir can differ from the diameter of the cell collecting membrane: the diameter can either be larger or smaller, to achieve a desired pressure distribution profile.

[0077] In some examples, the cell collecting membrane 16 can include a variety of components to aid in producing a desirable cell distribution. For example, the membrane can include a cell collecting film, which can be carried by or held adjacent to, or attached to a porous backing. A support plate can carry, or can be held adjacent to, or attached to, the porous backing. The support plate can include a series of perforations distributed thereacross.

[0078] In some examples, the collection surface 28 of the cell collecting membrane 16 can be formed in a substantially flat configuration, a substantially concave configuration, or a substantially convex configuration. Varying the configuration of the collection surface has been found in some cases to better aid in maintaining the desired cell distribution profile while applying the cells 22 to the microscope slide 32.

[0079] In one example, the cell collecting membrane 16 can be substantially permanently fixed to the fluid reservoir 14. For example, in the representation of FIGs. 1-3, the cell Thorpe North & Western, LLP

[0080] Docket No. 3919-00 LPCT collecting membrane can be bonded within the bore of a glass fluid reservoir 14. The membrane can also be integrally formed with the reservoir during manufacture thereof.

[0081] In one example, the cell collecting membrane 16 can be removably coupled to the fluid reservoir 14. This can be achieved in a variety of manners. In the example shown in FIG. 8, the cell collecting membrane is maintained within a membrane housing 42. The membrane housing can include a housing attachment interface 44 attachable to the fluid reservoir. In the example shown, the attachment interface includes a series of threads that can be threadably receiveable by a fluid reservoir, for example by a handheld syringe or pipette. The threads can correspond, for example, to those used in common “luer lock” assemblies. In this example, the housing attachment interface can include a fluidic diameter 45 smaller than both a diameter of the cell collecting membrane and the fluid reservoir.

[0082] The membrane 16 can be formed in a variety of sizes and shapes. The profile of the membrane that contacts the slide, e.g., the application profile, can be round, oblong, square, etc. In some examples, a membrane having a square application profile can allow multiple stamps to be more compactly applied on a single microscope slide, or adjacent slides.

[0083] FIGs. 4-8 represent various embodiments of the technology7in w hich a fluidic check valve 46a, 46b, 46c, 46d is provided. The fluidic check valve can be operable to maintain liquid in the fluid reservoir when gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane. As that term is used herein, a “fluidic check valve” is a component, or a collection of components, that functions to differently affect fluid flow in at least two distinct directions. A fluidic check valve can allow fluid flow in one direction, but restrict, prevent, limit or restrain fluid flow in an opposing direction. In the examples shown in the figures, the fluidic check valve allows substantially free fluid flow in the direction opposing the direction of gravity shown (e.g., upw ardly in the drawings), but restricts, prevents, limits, or restrains fluid flow in the direction of gravity shown (e.g., downwardly in the drawings).

[0084] In one example, the fluidic check valve comprises a static fluidic check valve. In this example, the components of the fluidic check valve do not move. In another example, the fluidic check valve can comprise a dynamic fluidic check valve. In this example, one or more components of the fluidic check valve move in one direction or another in response to, and to affect, fluid flow through the check valve. Thorpe North & Western, LLP

[0085] Docket No. 3919-00 LPCT

[0086] In the examples represented in FIGs. 4 and 5, the fluidic check valves 46a, 46b, respectively, are static check valves. In these examples, the static fluidic check valve can include a floor 52 having an upper surface oriented toward the fluid reservoir and a bottom surface oriented toward the cell collecting membrane 16. At least one column 54a, 54b, respectively, can extend through the floor to allow fluid to flow through the column from the direction of the cell collecting membrane to the fluid reservoir. Liquid drawn through the at least one column can collect on or above the upper surface of the floor adjacent the at least one column to prevent that portion of the liquid from traveling back toward the cell collecting membrane. In this manner, liquid drawn through the membrane 16 is restricted from pressing back on the membrane once drawn past the upper portion of the column 54a, 54b.

[0087] In the example represented in FIG. 4, the fluidic check valve 46a includes a single column 54a formed in a conical configuration. In the example represented in FIG. 5, the fluidic check valve 46b includes one or more columns 54b formed in a cylindrical configuration. A plurality of such columns is shown in the representation of FIG. 5, which can be arranged evenly across the floor 52.

[0088] In the examples represented in FIGs. 6-8, the fluidic check valves 46c, 46d comprise dynamic check valves. In these examples, the fluidic check valve includes at least one moveable component that allows fluid flow in one directional stream but restricts or prevents fluid flow in an opposing directional stream. In the example of FIG. 6, the fluidic check valve includes a moveable flap 56 that can freely move upwardly as fluid flows in that direction, but flaps downwardly as fluid tends to flow in that direction, thereby restricting fluid flow downwardly. In the example of FIGs. 7A, 7B and 8, the fluidic check valve 46d includes a membrane 58 having one or more slits 59 (FIG. 7B) formed therein. As fluid flows upwardly, the membrane opens around the slits and allows fluid flow in that direction. As fluid tends to flow- downwardly, however, the slits close and restrict fluid flow' in that direction.

[0089] In one example, the fluidic check valve 46a, 46b, 46c, 46d can be fluidly positioned between the fluid reservoir 14 and the cell collection assembly 16. In one example, the fluidic check valve can be disposed within the fluid reservoir. In other examples, the fluidic check valve can be removably attached to the fluid reservoir.

[0090] In the example represented in FIG. 7A, the fluidic check valve 46d is spaced from the cell collecting membrane 16 by a distance “s.” This can result in a flow equalization chamber 50 created between, or disposed between, the fluidic check valve and the cell Thorpe North & Western, LLP

[0091] Docket No. 3919-00 LPCT collecting membrane. The flow equalization chamber can equalize flow of fluid, and the distribution of pressure or vacuum in the fluid, in the distance between the fluidic check valve and the cell collecting membrane. This can aid in more evenly applying the pressure across the cell collection surface 28 of the membrane. By adjusting the distance “s,” the flow equalization chamber can be increased or decreased in size, as desirable.

[0092] The flow equalization chamber 50 can also be used to introduce air or another gas beneath the liquid 25 as the cells 22 are collected on the cell collection surface 28. As air or another gas can reactive differently to the pressure or vacuum applied to the fluid reservoir 14, gathering gas into the flow equalization after drawing the liquid 24 through the membrane 16 can aid in restraining the liquid from flowing back through the membrane. In one exemplary application, a technician can draw liquid from the liquid container 20 as previously described. Immediately after drawing the liquid, the cell collection assembly can be withdrawn from the liquid pool, while the vacuum is still applied, resulting in air being drawn into the flow equalization chamber. If sufficient air is drawn into the chamber, all or the majority of the liquid in the assembly is trapped above the fluidic check valve. The liquid is then restricted from passing back through the membrane, and the gas in the chamber is less likely to disturb the cell distribution on the membrane.

[0093] The cell collection assembly 12 can advantageously be compatible with a number of commercially available systems. In one non-limiting example, the cell collection assembly can be, or can include, a universal serological pipettor compatible filter or adaptor to fit within available test systems.

[0094] FIG. 10 illustrates an embodiment of the technology in which a stand, base or stabilizer is utilized to minimize unwanted motion of the cell collection surface of the membrane as the cells are applied to a slide. In this example, the stabilizer 60a can include a pair of legs 61a, 61b, between which a microscope slide 32 can be positioned. The legs can stably support the stand upon a tabletop or other surface 68 such that the membrane is positioned above the slide. The cell collection assembly 12 can be attached to the stabilizer in a variety of manners appreciable by one of ordinary skill in the art having possession of this disclosure. For example, a column 66 of the stabilizer can include a simple clamping mechanism, or bayonet securement, or threaded interface, that can receive the cell collection assembly.

[0095] In one embodiment, the column 66 can be slidably moveable relative to the stabilizer, such that it can move downw ardly relative to the stabilizer to apply the cells to Thorpe North & Western, LLP

[0096] Docket No. 3919-00 LPCT the slide. The column can be limited to movement in a single degree of freedom: e.g., upward and downward relative to the surface of the slide. In this manner, smudging or smearing of the cells as they are deposited on the membrane surface is minimized.

[0097] In addition, the stabilizer can include a movement and / or force limiter 64 that can control or limit movement of the column 66, and accordingly movement the cell collection membrane 16 relative to the slide. A control knob or similar device 62 can be provided to allow an operator to move the column upwardly and downwardly. The limiter can prevent the column from moving downwardly beyond a predetermined distance to ensure that the membrane applies the cells collected thereon in the correct amount. Alternately, or in addition, the limiter can restrict application of force by the membrane to the slide. The system can be configured, for example, such that after the membrane applies the predetermined amount force, further downward motion is prevented.

[0098] In addition to the control knob 62, a cantilever input can be utilized that allows an operator to lever the column 66 downward. In another example, a spring-loaded actuator can be provided that moves the column through a predetermined distance or to a predetermined load. The force limiter 64 or spring-loaded actuator can alternately be incorporated into a hand-held device. For example, the force limiter can prevent an operator from applying the membrane 16 to the slide 32 with too much force, or by incorporating a travel limit, from applying the membrane beyond a specified limit.

[0099] In the example shown in FIG. 11 , stabilizer 60b includes a platform or similar structure 66 upon which slide 32 can be received. In the example shown, the platform spans legs 61a and 61b to receive the slide. In addition to the simple platform shown, the system can be integrated with a slide deck or carousel to at least partially automate movement of multiple slides successively into position beneath the membrane.

[0100] The stabilizers 60a, 60b can be beneficial in removing or reducing inconsistencies in applying the cells to the slide due to operator ability. For example, not every technician will apply the cells with the same force and with the same degree of shakiness, or lack thereof. The stabilizers can ensure that each time cells are applied to a slide with the present system, a single, consistent layer can be applied, regardless of operator variability.

[0101] FIG. 12 illustrates another embodiment of a stabilizer, that includes an exemplary' alignment guide 70 that can be used as a stand-alone guide or in conjunction with the stabilizers 60a, 60b. The alignment guide can include one or more bores 72 that can Thorpe North & Western, LLP Docket No. 3919-00 LPCT guide the cell collection assembly to ensure a uniform direction of travel and alignment as the membrane 16 is advanced toward the slide 32. This device can be particularly useful when manually applying the cell collection assembly to slides. When incorporated into a stabilizer, the alignment guide can ensure that the cell collection assembly is advanced toward the slide with the proper alignment, regardless of whether or not the stabilizer is placed on a level surface, or is otherwise not well aligned relative to the slide.

[0102] FIGs. 13A and 13B illustrate a further embodiment of the technology in which a vacuum source is used to draw cells through a cell collecting membrane 16 from a fluid suspension 24, shown positioned above the membrane in a fluid or filling reservoir 82. The collecting membrane can be held by, attached to, or integrated with a passthrough reservoir 84. The passthrough reservoir can be releasably attached to, and sealed relative to, a collecting chamber 86. The collecting chamber can be fluidly coupled to a vacuum source 18.

[0103] As vacuum is applied to the system by the vacuum source 18, the fluid 24 is drawn through the cell collecting membrane 16 such that individual cells 22 are collected on the surface 28 of the membrane (see FIG. 13B). Once the fluid has passed through the membrane, and collected in the chamber 86, the fluid or fdling reservoir 82 can be removed from the passthrough chamber 84. The chambers 84, 86 can be removably or frangibly coupled one to another at 90 to allow easy separation once desired. As shown in FIG. 13B, once the cells are collected atop the membrane, the (now empty) reservoir 82 can be discarded, and a slide can be positioned against the membrane to apply the cells 22 to the slide.

[0104] In addition to the structure disclosed above, the present technology also provides various methods of configuring, assembling, manufacturing and using cell collection and application systems, as more fully delineated in the examples and claims to follow. It is noted that no specific order is required in any methods disclosed herein unless required by the claims set forth herein, though generally in some embodiments, the method steps can be carried out sequentially.

[0105] Example Embodiments

[0106] The following examples pertain to specific technology embodiments and point out specific features, elements, or steps that can be used or otherwise combined in achieving such embodiments.

[0107] In one example there is provided a system for collecting cells from a fluid to Thorpe North & Western, LLP Docket No. 3919-00 LPCT transfer the cells to a microscope slide, the system comprising a cell collection assembly having: a fluid reservoir; and a cell collecting membrane fluidly coupled to the fluid reservoir; a vacuum source fluidly coupled to the fluid reservoir, the vacuum source operable to draw fluid through the cell collecting membrane to thereby collect cells contained in the fluid; the cell collection assembly being operable to maintain liquid in the fluid reservoir when gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane.

[0108] In one example of a cell collecting and application system, the vacuum source is operable to apply a vacuum force substantially evenly across a collection surface of the cell collecting membrane.

[0109] In one example of a cell collecting and application system, an inside diameter of the fluid reservoir substantially corresponds to a diameter of the cell collecting membrane.

[0110] In one example of a cell collecting and application system, an inside diameter of the fluid reservoir differs from a diameter of the cell collecting membrane.

[0111] In one example of a cell collecting and application system, the vacuum source is located remotely from the fluid reservoir.

[0112] In one example of a cell collecting and application system, the vacuum source includes a hand-held syringe.

[0113] In one example of a cell collecting and application system, the vacuum source includes a hand-held pipettor.

[0114] In one example of a cell collecting and application system, the cell collecting membrane includes a cell collecting film, the cell collecting film carried by a porous backing carried by a support plate.

[0115] In one example of a cell collecting and application system, the support plate includes a series of perforations distributed evenly thereacross.

[0116] In one example of a cell collecting and application system, the collection surface of the cell collecting membrane is substantially flat, substantially convex or substantially concave.

[0117] In one example of a cell collecting and application system, the cell collecting membrane is operable to maintain a spatial arrangement of cells collected on the collection surface while applying the cells to the microscope slide.

[0118] In one example of a cell collecting and application system, the vacuum source is Thorpe North & Western, LLP

[0119] Docket No. 3919-00 LPCT integrated within the cell collection assembly.

[0120] In one example of a cell collecting and application system, the vacuum source is removably coupled to the cell collection assembly.

[0121] In one example of a cell collecting and application system, the cell collecting membrane is substantially permanently fixed to the fluid reservoir.

[0122] In one example of a cell collecting and application system, the cell collecting membrane is removably coupled to the fluid reservoir.

[0123] In one example of a cell collecting and application system, the cell collecting membrane is maintained within a membrane housing, the membrane housing including a housing attachment interface attachable to the fluid reservoir.

[0124] In one example of a cell collecting and application system, the housing attachment interface includes a fluidic diameter smaller than both a diameter of the cell collecting membrane and the fluid reservoir.

[0125] In one example of a cell collecting and application system, the housing attachment interface is attachable to a syringe.

[0126] In one example of a cell collecting and application system, the housing attachment interface is attachable to a pipette.

[0127] In one example of a cell collecting and application system, the vacuum source is capable of providing a vacuum force of at least about 8 kPa.

[0128] In one example of a cell collecting and application system, the cell collection assembly is operable to maintain liquid in the fluid reservoir after discontinuation of the vacuum.

[0129] In one example of a cell collecting and application system, a fluidic check valve is further provided, fluidly coupled to the cell collection assembly, the fluidic check valve operable to maintain liquid in the fluid reservoir when gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane.

[0130] In one example of a cell collecting and application system, the fluidic check valve comprises a static fluidic check valve.

[0131] In one example of a cell collecting and application system, the static fluidic check valve includes: a floor having an upper surface oriented toward the fluid reservoir and a bottom surface oriented toward the cell collecting membrane; and at least one column extending through the floor to allow fluid to flow through the column from the direction of the cell collecting membrane to the fluid reservoir, whereby fluid drawn through at Thorpe North & Western, LLP Docket No. 3919-00 LPCT least one column can collect on or above the upper surface of the floor adjacent the at least one column to prevent at least a portion of the fluid from traveling back toward the cell collecting membrane.

[0132] In one example of a cell collecting and application system, the at least one column is cylindrical.

[0133] In one example of a cell collecting and application system, the at least one column is conical.

[0134] In one example of a cell collecting and application system, a plurality of columns is arranged across the floor.

[0135] In one example of a cell collecting and application system, the fluidic check valve includes at least one moveable component that allows fluid flow in one directional stream but restricts or prevents fluid flow in an opposing directional stream.

[0136] In one example of a cell collecting and application system, the fluidic check valve is fluidly positioned between the fluid reservoir and the cell collection assembly.

[0137] In one example of a cell collecting and application system, the fluidic check valve is disposed within the fluid reservoir.

[0138] In one example of a cell collecting and application system, a flow equalization chamber is disposed between the fluidic check valve and the cell collecting membrane.

[0139] In one example there is provided a cell collection assembly for collecting cells from a fluid to transfer the cells to a microscope slide, the cell collection assembly comprising: a cell collecting membrane fluidly coupled to a fluid reservoir; the fluid reservoir coupleable to a vacuum source to enable the vacuum source to draw fluid through the cell collecting membrane to thereby collect cells contained in the fluid; the cell collection assembly being operable to maintain liquid in the fluid reservoir when a gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane.

[0140] In one example of a cell collecting and application assembly, an inside diameter of the fluid reservoir substantially corresponds to a diameter of the cell collecting membrane.

[0141] In one example of a cell collecting and application assembly, an inside diameter of the fluid reservoir differs from a diameter of the cell collecting membrane.

[0142] In one example of a cell collecting and application assembly, a vacuum source is integrated within the cell collection assembly.

[0143] In one example of a cell collecting and application assembly, the vacuum source is Thorpe North & Western, LLP

[0144] Docket No. 3919-00 LPCT capable of providing a vacuum force of at least about 8 kPa.

[0145] In one example of a cell collecting and application assembly, the assembly is removably coupleable to a vacuum source.

[0146] In one example of a cell collecting and application assembly, a vacuum source includes a hand-held syringe.

[0147] In one example of a cell collecting and application assembly, a vacuum source includes a hand-held pipettor.

[0148] In one example of a cell collecting and application assembly, the cell collecting membrane includes a cell collecting film, the cell collecting film carried by a porous backing carried by a support plate.

[0149] In one example of a cell collecting and application assembly, the support plate includes a series of perforations distributed evenly thereacross.

[0150] In one example of a cell collecting and application assembly, the collection surface of the cell collecting membrane is substantially flat, substantially convex or substantially concave.

[0151] In one example of a cell collecting and application assembly, the cell collecting membrane is operable to maintain a spatial arrangement of cells collected on the collection surface while applying the cells to the microscope slide.

[0152] In one example of a cell collecting and application assembly, the cell collecting membrane is substantially permanently fixed to the fluid reservoir.

[0153] In one example of a cell collecting and application assembly, the cell collecting membrane is removably coupled to the fluid reservoir.

[0154] In one example of a cell collecting and application assembly, the cell collecting membrane is maintained within a membrane housing, the membrane housing including a housing attachment interface attachable to the fluid reservoir.

[0155] In one example of a cell collecting and application assembly, the housing attachment interface includes a fluidic diameter smaller than both a diameter of the cell collecting membrane and the fluid reservoir.

[0156] In one example of a cell collecting and application assembly, the housing attachment interface is attachable to a syringe.

[0157] In one example of a cell collecting and application assembly, the housing attachment interface is attachable to a pipette.

[0158] In one example of a cell collecting and application assembly, the cell collection assembly is operable to maintain liquid in the fluid reservoir after discontinuation of Thorpe North & Western, LLP

[0159] Docket No. 3919-00 LPCT vacuum applied to the cell collection assembly.

[0160] In one example of a cell collecting and application assembly, a fluidic check valve is provided, fluidly coupled to the cell collection assembly, the fluidic check valve operable to maintain liquid in the fluid reservoir when gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane.

[0161] In one example of a cell collecting and application assembly, the fluidic check valve comprises a static fluidic check valve.

[0162] In one example of a cell collecting and application assembly, the static fluidic check valve includes: a floor having an upper surface oriented toward the fluid reservoir and a bottom surface oriented toward the cell collecting membrane; and at least one column extending through the floor to allow fluid to flow through the column from the direction of the cell collecting membrane to the fluid reservoir, whereby fluid drawn through at least one column can collect on or above the upper surface of the floor adjacent the at least one column to prevent at least a portion of the fluid from traveling back toward the cell collecting membrane.

[0163] In one example of a cell collecting and application assembly, the at least one column is cylindrical.

[0164] In one example of a cell collecting and application assembly, the at least one column is conical.

[0165] In one example of a cell collecting and application assembly, a plurality of columns are arranged across the floor.

[0166] In one example of a cell collecting and application assembly, the fluidic check valve includes at least one moveable component that allows fluid flow in one directional stream but restricts or prevents fluid flow in an opposing directional stream.

[0167] In one example of a cell collecting and application assembly, the fluidic check valve is fluidly positioned between the fluid reservoir and the cell collection assembly.

[0168] In one example of a cell collecting and application assembly, the fluidic check valve is disposed within the fluid reservoir.

[0169] In one example of a cell collecting and application assembly, a flow equalization chamber is disposed between the fluidic check valve and the cell collecting membrane.

[0170] In one example there is provided a method of collecting cells and applying them to a microscope slide, comprising: obtaining a cell collection assembly having a fluid reservoir with a cell collecting membrane fluidly coupled thereto; introducing the cell Thorpe North & Western, LLP

[0171] Docket No. 3919-00 LPCT collecting membrane into a fluid carrying a plurality of cells; applying a vacuum to the cell collection assembly to draw fluid through the cell collecting membrane and into the fluid reservoir, thereby collecting cells contained within the fluid across a collection surface of the cell collecting membrane; orienting the cell collection assembly such that gravitational force applied by gravity' to contents of the fluid reservoir tends to force the contents toward the cell collecting membrane; positioning the cell collection assembly and a microscope slide relative to one another; causing contact between the microscope slide and the collection surface of the cell collecting membrane to thereby apply the cells collected on the collection surface to the slide while restraining fluid in the fluid reservoir from passing through the cell collecting membrane.

[0172] In one example of a method of collecting cells and applying them to a microscope slide, applying the vacuum includes applying a vacuum force substantially evenly across the collection surface of the cell collecting membrane.

[0173] In one example of a method of collecting cells and applying them to a microscope slide, the method further comprises applying a vacuum force with a vacuum source integrated within the cell collection assembly.

[0174] In one example of a method of collecting cells and applying them to a microscope slide, an inside diameter of the fluid rescrvoi r substantially corresponds to a diameter of the cell collecting membrane.

[0175] In one example of a method of collecting cells and applying them to a microscope slide, an inside diameter of the fluid reservoir differs from a diameter of the cell collecting membrane.

[0176] In one example of a method of collecting cells and applying them to a microscope slide, applying the vacuum includes applying a vacuum force from a vacuum source located remotely from the fluid reservoir.

[0177] In one example of a method of collecting cells and applying them to a microscope slide, applying the vacuum includes applying a vacuum force from a hand-held syringe.

[0178] In one example of a method of collecting cells and applying them to a microscope slide, applying the vacuum includes applying a vacuum force from a hand-held pipettor.

[0179] In one example of a method of collecting cells and applying them to a microscope slide, the cell collecting membrane includes a cell collecting film, the cell collecting film carried by a porous backing carried by a support plate.

[0180] In one example of a method of collecting cells and applying them to a microscope slide, the support plate includes a series of perforations distributed evenly thereacross. Thorpe North & Western, LLP Docket No. 3919-00 LPCT

[0181] In one example of a method of collecting cells and applying them to a microscope slide, the collection surface of the cell collecting membrane is substantially flat, substantially concave or substantially convex.

[0182] In one example of a method of collecting cells and applying them to a microscope slide, applying the cells to the microscope slide further comprises maintaining a spatial arrangement of cells collected on the collection surface while applying the cells to the microscope slide.

[0183] In one example of a method of collecting cells and applying them to a microscope slide, the method further comprises orienting the collection surface of the cell collecting membrane above the microscope slide while applying the cells to the microscope slide.

[0184] In one example of a method of collecting cells and applying them to a microscope slide, the method further comprises pressing the collection surface against the microscope slide in a direction substantially the same as the gravitational force while applying the cells to the microscope slide.

[0185] In one example of a method of collecting cells and applying them to a microscope slide, the method further comprises applying a vacuum force with a vacuum source removably coupled to the cell collection assembly.

[0186] In one example of a method of collecting cells and applying them to a microscope slide, the cell collection assembly is substantially permanently fixed to the fluid reservoir.

[0187] In one example of a method of collecting cells and applying them to a microscope slide, the cell collection assembly is removably coupled to the fluid reservoir.

[0188] In one example of a method of collecting cells and applying them to a microscope slide, the cell collecting membrane is maintained within a membrane housing, the membrane housing including a housing attachment interface attachable to the fluid reservoir.

[0189] In one example of a method of collecting cells and applying them to a microscope slide, the housing attachment interface includes a fluidic diameter smaller than both a diameter of the cell collecting membrane and the fluid reservoir.

[0190] In one example of a method of collecting cells and applying them to a microscope slide, the housing attachment interface is attachable to a syringe.

[0191] In one example of a method of collecting cells and applying them to a microscope slide, the housing attachment interface is attachable to a pipette.

[0192] In one example of a method of collecting cells and applying them to a microscope slide, applying the vacuum includes applying a vacuum force of at least about 8 kPa. Thorpe North & Western, LLP Docket No. 3919-00 LPCT

[0193] In one example of a method of collecting cells and applying them to a microscope slide, the method further comprises discontinuing the vacuum after collecting the cells on the collection surface and maintaining liquid in the fluid reservoir after discontinuation of the vacuum.

[0194] In one example of a method of collecting cells and applying them to a microscope slide, restraining the fluid further comprises restraining the fluid with a fluidic check valve, fluidly coupled to the cell collection assembly, the fluidic check valve operable to maintain liquid in the fluid reservoir when gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane.

[0195] In one example of a method of collecting cells and applying them to a microscope slide, the fluidic check valve comprises a static fluidic check valve.

[0196] In one example of a method of collecting cells and applying them to a microscope slide, the static fluidic check valve includes: a floor having an upper surface oriented toward the fluid reservoir and a bottom surface oriented toward the cell collecting membrane; and at least one column extending through the floor to allow fluid to flow through the column from the direction of the cell collecting membrane to the fluid reservoir, and wherein restraining the fluid further comprises collecting fluid on or above the upper surface of the floor adjacent the at least one column to prevent at least a portion of the fluid from traveling back toward the cell collecting membrane.

[0197] In one example of a method of collecting cells and applying them to a microscope slide, the at least one column is cylindrical.

[0198] In one example of a method of collecting cells and applying them to a microscope slide, the at least one column is conical.

[0199] In one example of a method of collecting cells and applying them to a microscope slide, a plurality of columns are arranged across the floor.

[0200] In one example of a method of collecting cells and applying them to a microscope slide, the fluidic check valve includes at least one moveable component that allows fluid flow in one directional stream but restricts or prevents fluid flow in an opposing directional stream.

[0201] In one example of a method of collecting cells and applying them to a microscope slide, the fluidic check valve is fluidly positioned between the fluid reservoir and the cell collection assembly.

[0202] In one example of a method of collecting cells and applying them to a microscope slide, the fluidic check valve is disposed within the fluid reservoir. Thorpe North & Western, LLP

[0203] Docket No. 3919-00 LPCT

[0204] In one example of a method of collecting cells and applying them to a microscope slide, drawing the fluid through the cell collecting membrane further comprises drawing the fluid into a flow equalization chamber disposed between the fluidic check valve and the cell collecting membrane.

[0205] In one example of a method of collecting cells and applying them to a microscope slide, applying the vacuum further comprises maintaining the vacuum static after collection of the cells before application of the cells to the slide.

[0206] In one example of a method of collecting cells and applying them to a microscope slide, applying the vacuum further comprises applying the vacuum continually after collection of the cells before application of the cells to the slide.

[0207] In one example of a method of collecting cells and applying them to a microscope slide, applying the vacuum further comprises discontinuing the vacuum after collection of the cells before application of the cells to the slide, the cell collection assembly maintaining liquid in the fluid reservoir after discontinuation of the vacuum.

[0208] In one example of a method of collecting cells and applying them to a microscope slide, the cell collecting assembly can be rotated or spun by hand to agitate the cells and / or media in which the cells are suspended.

[0209] In one example there is provided a kit for collecting cells from a fluid to transfer the cells to a microscope slide, the kit comprising a cell collection assembly having: a fluid reservoir; and a cell collecting membrane fluidly coupled to the fluid reservoir; a vacuum source fluidly coupled to the fluid reservoir, the vacuum source operable to draw fluid through the cell collecting membrane to thereby collect cells contained in the fluid; the cell collection assembly being operable to maintain liquid in the fluid reservoir when gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane. A stabilizer can receive the cell collection assembly. The cell collection assembly can be moveable relative to the stabilizer in a single degree of freedom, toward and away from a slide. A limiter can be associated with the stabilizer to limit one of i) a magnitude of directional movement of the cell collection assembly and ii) an amount of force applied by the cell collecting membrane to a surface of the slide.

[0210] In one example of a kit for collecting cells from a fluid to transfer the cells to a microscope slide, a slide cassette or carousel carrying a plurality of slides is associated with the stabilizer. Thorpe North & Western, LLP

[0211] Docket No. 3919-001.PCT

[0212] In one example of a kit for collecting cells from a fluid to transfer the cells to a microscope slide, instructions are provided for operating the cell collection assembly and the stabilizer.

[0213] It is to be understood that the above-described arrangements are only illustrative of the application of the principles of the present invention. Numerous modifications and alternative arrangements may be devised by those skilled in the art without departing from the spirit and scope of the present invention and the appended claims are intended to cover such modifications and arrangements. Thus, while the present invention has been described above with particularity and detail in connection with what is presently deemed to be the most practical and preferred embodiments of the invention, it will be apparent to those of ordinary skill in the art that numerous modifications, including, but not limited to, variations in size, materials, shape, form, function and manner of operation, assembly and use may be made without departing from the principles and concepts set forth herein.

Claims

Thorpe North & Western, LLPDocket No. 3919-00 LPCTCLAIMSWhat is claimed is:

1. A system for collecting cells from a fluid to transfer the cells to a microscope slide, the system comprising: a cell collection assembly having: a fluid reservoir; a cell collecting membrane fluidly coupled to the fluid reservoir; a vacuum source fluidly coupled to the fluid reservoir, the vacuum source operable to draw fluid through the cell collecting membrane to thereby collect cells contained in the fluid; the cell collection assembly being operable to maintain liquid in the fluid reservoir when gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane; and a stabilizer being operable to minimize unwanted motion of the cell collecting membrane as the collected cells are applied to a slide.

2. The system of claim 1, wherein the vacuum source is integrated within the cell collection assembly.

3. The system of claim 2, wherein the vacuum source includes a hand-held syringe.

4. The system of claim 2, wherein the vacuum source includes a hand-held pipettor.

5. The system of claim 1, wherein the cell collecting membrane is removably- coupled to the fluid reservoir.

6. The system of claim 1, wherein the cell collection assembly is operable to maintain liquid in the fluid reservoir after discontinuation of the vacuum.

7. The system of claim 1, further comprising a fluidic check valve, fluidly coupled to the cell collection assembly, the fluidic check valve operable to maintainThorpe North & Western, LLPDocket No. 3919-00 LPCT liquid in the fluid reservoir when gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane.

8. The system of claim 7, wherein the fluidic check valve comprises a static fluidic check valve.

9. The system of claim 7, wherein the fluidic check valve includes at least one moveable component that allows fluid flow in one directional stream but restricts or prevents fluid flow in an opposing directional stream.

10. A cell collection assembly for collecting cells from a fluid to transfer the cells to a microscope slide, the cell collection assembly comprising: a cell collecting membrane fluidly coupled to a fluid reservoir; the fluid reservoir coupleable to a vacuum source to enable the vacuum source to draw fluid through the cell collecting membrane to thereby collect cells contained in the fluid; the cell collection assembly being operable to maintain liquid in the fluid reservoir when a gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane.11 . The assembly of claim 10, further comprising a vacuum source integrated within the cell collection assembly.

12. The assembly of claim 11. wherein the vacuum source includes a hand-held syringe.

13. The assembly of claim 11, wherein the vacuum source includes a hand-held pipettor.

14. The assembly of claim 10, wherein the cell collection assembly is operable to maintain liquid in the fluid reservoir after discontinuation of vacuum applied to the cell collection assembly.Thorpe North & Western, LLP Docket No. 3919-00 LPCT15. The assembly of claim 10, further comprising a fluidic check valve, fluidly coupled to the cell collection assembly, the fluidic check valve operable to maintain liquid in the fluid reservoir when gravitational force applied by gravity to the liquid in the fluid reservoir tends to force the liquid toward the cell collecting membrane.

16. A method of collecting cells and applying them to a microscope slide, comprising: obtaining a cell collection assembly having a fluid reservoir with a cell collecting membrane fluidly coupled thereto; introducing the cell collecting membrane into a fluid carrying a plurality' of cells; applying a vacuum to the cell collection assembly to draw fluid through the cell collecting membrane and into the fluid reservoir, thereby collecting cells contained within the fluid across a collection surface of the cell collecting membrane; orienting the cell collection assembly such that gravitational force applied bygravity to contents of the fluid reservoir tends to force the contents toward the cell collecting membrane; positioning the cell collection assembly and a microscope slide relative to one another; causing contact between the microscope slide and the collection surface of the cell collecting membrane to thereby apply the cells collected on the collection surface to the slide while restraining fluid in the fluid reservoir from passing through the cell collecting membrane.

17. The method of claim 16. wherein applying the vacuum includes applying a vacuum force from a hand-held syringe.

18. The method of claim 16, wherein applying the vacuum includes applying a vacuum force from a hand-held pipettor.

19. The method of claim 16, wherein applying the cells to the microscope slide further comprises orienting the collection surface of the cell collecting membrane above the microscope slide while applying the cells to the microscope slide.Thorpe North & Western, LLPDocket No. 3919-001.PCT20. The method of claim one 16, wherein applying the cells further comprises pressing the collection surface against the microscope slide in a direction substantially the same as the gravitational force while applying the cells to the microscope slide.

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