Patent Description:
Medicine is becoming less invasive and more personalized. For example, a patient presenting with a mass in the lung or pancreas is not necessarily scheduled for surgery to characterize the lesion as neoplastic or not. Instead, a minute sample of cells from the lesion is obtained through a minimally invasive procedure (MIP) called a core biopsy and/or fine needle aspiration (FNA). Both of these MIPs involve obtaining a sample with a small caliber needle after it is localized to the site of interest with the aid of imaging, such as a CT scan and/or ultrasound. When performing MIP, either no incision is made, or the biopsy site is inconspicuous, similar to a puncture wound following a blood draw, which allows for outpatient procedures and prevents need for hospitalization. By examining the sample obtained with a MIP under a microscope, pathologists render diagnoses of benignity or malignancy. At one time, there were limited treatment options and diagnoses of malignancy made simply by morphology assessed under a microscope would suffice and treatment would ensue. Nowadays, ancillary tests afford greater information than morphology alone about the tumor and therapeutic options that are likely to be more effective and personalized. Though MIPs and personalized treatment options provide better patient care, there is inconsistency among laboratories when imparting greater levels of information on such small tissue samples. Managing these small samples can be challenging, places a greater burden on laboratories/pathologists and has consequences for patients.

Ancillary tests to answer the pertinent questions are frequently conducted on small samples, including biopsies and cell blocks (cell pellets formed from cytology samples such as FNAs sample often with the aid of centrifugation). Currently, there is no accepted laboratory standard on the preparation of cell blocks, though labs frequently employ one of several "homebrew" methods. When samples are large, cell blocks are easier to form, but with smaller samples, the "homebrew" methods may fail or result in a suboptimal cell block. Thus, there is a growing need to develop a standardized apparatus and method for preparing cell blocks in a low cost and efficient manner to provide answers to clinicians that impact therapeutic decisions.

<CIT> describes a fixed tube of a nucleic acid extraction component and a nucleic acid extraction component. The nucleic acid extraction component comprises a cylindrical membrane tube, which is fitted over the fixed tube; the fixed tube comprises a tube body, a tube opening, and a bottom; the tube body extends along a first direction; the end of the tube opening distal from the tube body is provided with a protrusion which protrudes along a second direction, the first direction being vertical to the second direction; the bottom and the tube opening are respectively connected to two opposite sides of the tube body; the bottom is provided with a shoulder; and the shoulder of the bottom is connected to the cylindrical membrane tube.

<CIT> describes a medical apparatus and method of preparing one or more cell blocks. The medical apparatus comprises at least one elongate tubular body having a proximal end and a distal end and a filter membrane disposed between the proximal end and a distal end of the elongate tubular body. The filter membrane, which can include alignment features and structural features to engage the tubular body, and/or cover, is sectionable. Additionally, in some embodiments a second elongate tubular body is provided which telescopingly receives at least a portion of the first elongate tubular body. In other embodiments, a support member is provided for engaging the filter membrane and positioning the filter membrane at a midpoint of the elongate tubular body during centrifuging.

The purpose and advantages of the disclosed subject matter will be set forth in and apparent from the description that follows, as well as will be learned by practice of the disclosed subject matter.

The invention relates to a medical apparatus as defined in claim <NUM>. Further embodiments of the invention are defined in the dependent claims.

The invention relates to a medical apparatus including an elongated body and defining a loading chamber between a proximal end and a distal end thereof for storing a liquid therein, the elongated body defining an outlet at the distal end thereof; a cell block filter assembly including a cell block body and defining a well portion matingly engageable with the distal end of the elongated body for receiving fluid from the outlet of the elongated body and defining a well opening on a bottom thereof; a filter membrane disposed across the well opening on the bottom of the well portion; and a cover member positionable over the well portion wherein the entire cell block filter assembly is sliceable into slices having a thickness suitable for mounting on a laboratory slide.

The medical apparatus further includes a base member for securing the cell block filter assembly at the distal end of the elongate portion, and wherein the outer surface of the distal end of the elongate body is configured to engage with the base member, wherein the base member prevents the passage of fluid out of the filter assembly. The base member can be secured to the elongate body with threaded engagement or a ratchet engagement.

In some embodiments, the cell block body is fabricated substantially from LLDPE. The cover can fabricated substantially from LLDPE. In some embodiments, the cover defines a cover opening, the cover further comprising a filter membrane disposed across the cover opening.

In some embodiments, the filter membrane is fabricated substantially from ePTFE,.

The distal end portion of the elongate body defines a smaller aperture than the proximal portion to define a generally conical portion in some embodiments. The outlet can be offset from the longitudinal axis of the elongated body.

In some embodiments, the medical apparatus includes a lid disposed on the proximal end of the elongated body, the lid configured to engage the proximal end of the elongate body to form an airtight seal between the lid and the elongated body.

In some embodiments, the lid is threadedly engaged with the elongated body by threads formed on the outer surface of the lid and by threads formed on the inner surface of the proximal end of the elongated body.

In some embodiments, the outlet is sized to prevent fluid from flowing from the loading chamber when the elongated body is positioned such that the outlet and the fluid are disposed at a bottom portion of the elongated body.

The medical apparatus can include a cell block filter assembly for preparing a cell block formed at least in part from the condensed biological sample. The cell block filter assembly is formed from a material that is sliceable by for example, a blade such as a microtome blade, into slices having a thickness suitable for mounting on a slide for microscopy or other laboratory analyses. A cell block filter assembly is provided including a body defining a well for receiving a biological sample, the body fabricated substantially from low-density polyethylene (LLDPE); and a filter membrane disposed across an aperture in the bottom portion of the well and defining pores therethrough, the filter membrane being fabricated substantially from expandable polytetrafluoroethylene (ePTFE) wherein the entire cell block filter assembly is sliceable into slices having a thickness suitable for mounting on a laboratory slide.

Both the filter membrane and frame components of the cell block filter assembly are designed to both hold a prepared cell block and be sliceable by a blade (such as a microtome blade) to form slices containing both the cell block and the cell block assembly. In this regard, the cross section of the slice contains cell block and surrounded by the sliced cell block filter assembly because the assembly is designed so that the cell block need not be removed from the cell block assembly for laboratory processing. This advantageously concentrates and confines the sample. Also, this reduces waste and loss of cells, which can occur if the cells were transferred into a paraffin mold from the cell block filter assembly with a forceps-the tool typically used in the laboratory. The sectionable slices are suitable for mounting on a slide for microscopy or for other laboratory analyses. In some embodiments, the slicing of the cell block filter assembly containing a cell block results in a ribbon comprising a plurality of interconnected slices (of cell block and filter assembly) wherein each of the plurality of slices are separatable from each other for mounting on a microscopic slide or other laboratory analyses.

In another embodiment, a medical apparatus is provided including an elongated body and defining a loading chamber between a proximal end and a distal end thereof for storing a liquid therein, the elongated body defining an outlet at the distal end thereof; a cell block filter assembly including a cell block body and defining a well portion matingly engageable with the distal end of the elongated body for receiving fluid from the outlet of the elongated body and defining a well opening on a bottom thereof; a filter membrane disposed across the well opening on the bottom of the well portion; a cover member positionable over the well portion, and a hinge portion connecting the cover and the cell block body, wherein the entire cell block filter assembly is sliceable into slices having a thickness suitable for mounting on a laboratory slide.

In the some embodiments, the hinge portion is a "living hinge.

Additionally, the apparatus or select components thereof can be disposable, or designed for repeated use and cleansing.

It is to be understood that both the foregoing general description and the following detailed description are exemplary and are intended to provide further explanation of the disclosed subject matter claimed.

The accompanying drawings, which are incorporated in and constitute part of this specification, are included to illustrate and provide a further understanding of the method and system of the disclosed subject matter. Together with the description, the drawings serve to explain the principles of the disclosed subject matter.

A detailed description of various aspects, features, and embodiments of the subject matter described herein is provided with reference to the accompanying drawings, which are briefly described below. The drawings are illustrative and are not necessarily drawn to scale, with some components and features being exaggerated for clarity. The drawings illustrate various aspects and features of the present subject matter and may illustrate one or more embodiment(s) or example(s) of the present subject matter in whole or in part.

Reference will now be made in detail to select embodiments of the disclosed subject matter, examples of which are illustrated in the accompanying drawings. The method and corresponding steps of the disclosed subject matter will be described in conjunction with the detailed description of the system.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosed subject matter belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosed subject matter, this disclosure may specifically mention certain exemplary methods and materials.

As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

In accordance with the various embodiments of the disclosed subject matter, as summarized above and as described in further detail below, there is provided an apparatus for collecting and separating a liquid component from a cellular, or solid particle component, of a biological sample. While an exemplary embodiment disclosed herein includes fine needle aspiration, the apparatus and method of the disclosed subject matter is not limited to this exemplary embodiment and will be understood by an artisan of ordinary skill to be operable for collection and separation of any bodily fluids or specimens. In an exemplary embodiment, a disposable cell block system and a method for using the system, e.g., for tumor diagnosis, benign diagnosis, and other ancillary tests including research and development analyses, is provided. As used herein, the term "cell block" refers to a concentration of cells or solid particles from a biological sample, which is embedded in a medium, such as but not limited to paraffin wax. Thin slices from the medium with embedded cells are sliceable together with the cell block assembly in sizes suitable for mounting on a glass slide for analysis on a microscope or for other analyses. For example, visualization of the cells and the extracellular environment can provide information to determine whether the tissue collected is benign or malignant. Alternatively, the slices provide cellular material (DNA, RNA, proteins) for microcellular analysis. Although particular embodiments disclosed herein may focus on collection of the tissue or solid particle component in a biological sample for further diagnostics/testing, it will be understood by one of ordinary skill in the art that the disclosed system, apparatus and method is equally applicable for applications in which the fluid component of the biological sample is to be the subject of further diagnostics/testing/research.

In one exemplary embodiment, the cell block system <NUM> is shown schematically in <FIG>. Cell block system <NUM> includes an elongate tubular body <NUM>, a cell block filter assembly <NUM>, and a base member <NUM>. The elongate tubular body <NUM> defines an interior loading chamber <NUM> (See <FIG>), and has a proximal end <NUM> and a distal end <NUM>. In some embodiments, the elongate tubular body <NUM> has a first diameter (d1) at the proximal end and a second diameter (d2) at the distal end, wherein the second diameter is smaller than the first diameter, as will be discussed in greater detail herein. A section <NUM> disposed between the proximal end <NUM> and the distal end <NUM> of the elongate tubular body <NUM>, has a decreasing diameter along a length thereof to define a generally conical configuration, and further includes structure for receiving the cell block filter assembly <NUM> as will be described below.

Various suitable volumes are available for elongate tubular body <NUM>. For purpose of illustration and not limitation, suitable volumes include between about <NUM> to about <NUM>, or any other size that fits into a centrifuge, standard or otherwise. However, it will be understood by one of ordinary skill in the art that alternative sizes are within the scope of the disclosed subject matter. The elongate tubular body is sized to fit within a conventional centrifuge. In this manner, the cell block apparatus can receive the biological sample, for example, from a needle housing the biological sample obtained by fine needle aspiration techniques, and is disposed in the centrifuge for stratification/separation of the cells in the biological sample from any liquid to isolate and consolidate the cells into a concentrated pellet by centrifugation. Using the same unit for receiving the biological sample and stratifying/separating the biological sample into component parts reduces the loss of sample size and reduces risk of contamination due to exchange between multiple components. In contrast, the most common and typical practice among technicians is to use a single pipette for multiple components, thus allowing contamination between components, the instrument most commonly and typically utilized. In some embodiments, the elongate tubular body is suitable for relative centrifugal forces of between about <NUM>,<NUM> to about <NUM>,<NUM> RCF. For example, <NUM>,<NUM> RCF, <NUM>,<NUM> RCF, <NUM>,<NUM> RCF, <NUM>,<NUM> RCF, <NUM>,<NUM> RCF, <NUM>,<NUM> RCF. For further illustration in one embodiment, the elongate tubular member has a volume of <NUM>, and is suitable for centrifugation at <NUM>,<NUM> RCF or <NUM>,<NUM> RCF. In other embodiments, for example, the elongate tubular member has a volume of <NUM> and is suitable for centrifugation at <NUM>,<NUM> RCF or <NUM>,<NUM> RCF or <NUM>,<NUM> RCF. The elongate tubular body of the device can be formed of various materials and in particular various polymers, for example, polypropylene and/or polystyrene. Further, the materials used for the elongate tubular body, filter assembly, or compressive cover or cap (the terms are used interchangeably herein), which is described below, can be biodegradable material.

With continued reference to <FIG>, the elongate tubular body <NUM> defines an opening <NUM> having a rim <NUM> at the proximal end <NUM> of the body. The opening <NUM> is closed by a lid <NUM>, which provides a substantially airtight seal with the rim <NUM>. The lid <NUM> can be configured with a screw thread or threads on an inner surface (not shown) to engage a thread or threads <NUM> disposed on the outside surface of a proximal section <NUM> of the elongate tubular body <NUM>. Alternatively, the cover may comprise screw thread or threads disposed on an outside surface to engage thread or threads on the inner surface of the elongate tubular body at the proximal end so that the cover engages the elongate tubular body in the interior space. However, other suitable methods and features can be used to engage the lid <NUM> and elongate tubular body <NUM>, such as a snap fit, ratchet fit, interference fit, vacuum seal or other methods of engagement, as would be appreciated by one of ordinary skill in the art.

In some embodiments, the elongate tubular body <NUM> is preloaded with a fixative in the loading chamber <NUM>. A "fixative" as used herein refers to a compound, such as formalin, ethanol, methanol, RPMI, saline for preservation and/or transportation of the sample.

When the lid <NUM> is engaged with the rim <NUM>, a substantially airtight seal is provided. As will be discussed further below, the distal outlet <NUM> is sized such that any liquid, such as the fixative discussed herein, disposed within the loading chamber <NUM> will be retained therein and prevented from flowing out of the distal outlet <NUM> when the elongated body <NUM> is positioned such that the aperture <NUM> and the fluid are disposed at a bottom portion of the elongated body. This feature is particularly useful when it is desirable to reuse the liquid for further experiments. In an embodiment, the lid <NUM> includes a seal <NUM> on the inner periphery that engages with the rim <NUM> to provide the airtight seal. The distal outlet <NUM> has a diameter in the range of about <NUM> at the maximum to about <NUM> at the minimum. In some embodiments, the distal outlet <NUM> has a diameter of about <NUM>-<NUM>. Distal outlet <NUM> has a circular shape, although oval or rectangular openings are contemplated.

In an embodiment, lid <NUM> further comprises a central portion <NUM> formed from a self-sealing or resealable material that overlays the opening <NUM>. In an alternative embodiment, the cover can be a stopper formed from a self-sealing or resealable material that can be inserted into the opening <NUM> at the proximal end <NUM>. The central portion <NUM> is puncturable by a needle allowing transfer of the biological sample from the needle to the interior of the elongate tubular body. After deposit of the biological sample and removal of the needle from the lid <NUM>, the material self-seals the puncture created by the needle entry and maintains an airtight seal.

As illustrated in <FIG>, at the distal section <NUM> of the elongate tubular body <NUM> is configured to permit the engagement and secure mounting of the cell block filter assembly <NUM> thereto. The filter assembly <NUM> defines a border <NUM> circumscribing an open center well <NUM> in which a filter membrane <NUM> is disposed. The well <NUM> is configured with an opening <NUM> sized to cooperate with an inner flange <NUM> circumscribing the distal outlet <NUM> on the distal end <NUM> of the elongate tubular body <NUM>. The filter assembly <NUM> is matingly engageable with the elgonated tubular body <NUM>, e.g., to allow fluid to flow from the loading chamber <NUM> into the well <NUM>. Additionally or alternatively, the periphery of the border <NUM> of the filter assembly <NUM> is configured to receive and releasably engage the distal portion <NUM> of the elongate tubular body <NUM>, e.g., at outer flange <NUM>. In an embodiment, cells may be collected in the center well <NUM>, such as after filtration, to provide a substantially cylindrical cell block.

The base member <NUM> is configured to support the cell block filter assembly <NUM> at surface <NUM>, and to be attached to the distal section <NUM> of tubular body <NUM> to secure the assembly <NUM> thereto. In some embodiments, the outer surface of the distal section <NUM> can be configured with a thread or a plurality of threads <NUM> to engage with a thread or threads <NUM> on interior portion of the base member <NUM> to secure the base member <NUM> to the distal section <NUM> of the elongate tubular body <NUM>, thereby stabilizing the cell block filter assembly <NUM> therein during centrifuging or other similar processes. It is contemplated that other techniques, such as snap fit, ratchet fit, interference fit, vacuum seal or other methods of attachment can be used to secure the base member <NUM> to the distal section <NUM> of the tubular body <NUM>.

<FIG> illustrate a side view and a perspective view of cell block system <NUM>, respectively, and <FIG> illustrate cross-sectional views of the system <NUM>, in which the base member <NUM> is engaged to the distal section <NUM>, to enclose the filter assembly <NUM> in the interior space <NUM> (see <FIG>) between the base <NUM> and the distal section <NUM>. The inner flange <NUM> at the distal section <NUM> cooperates with opening <NUM> in the filter assembly <NUM> to allow the biological sample to be received in the well <NUM>. In this configuration, passage of liquid out of the filter assembly <NUM> through the filter membrane <NUM> is prevented by the solid nature of the surface <NUM> of the base member <NUM>.

In the configurations shown in <FIG>, the filter assembly <NUM> is ready to receive a biological sample through distal outlet <NUM>. After the sample has been introduced into the cell block apparatus <NUM>, lid <NUM> can be secured to the tubular body <NUM> by engaging thread(s) <NUM>. Alternatively, the sample can be delivered via a needle such as a hypodermic needle or an aspiration needle through a lid <NUM> configured with a puncturable, resealable center portion <NUM> that is already engaged with the tubular body <NUM>. In either case, the biological sample is securely sealed within the cell block system <NUM> for storage and/or transport from the locus where it is taken, such as an examination room or an operating room, to the locus where it can be analyzed, such as a pathology lab. The sealed cell block apparatus can be subjected to centrifuging process(es) without any of the sample escaping the sample loading chamber and passing through the cell block filter assembly <NUM>. Accordingly, the biological sample is separated or stratified (i.e. fluid content disposed above solid content) during the centrifuging process.

Referring to <FIG>, cell block filter assembly <NUM> is illustrated in greater detail. In an exemplary embodiment, the filter assembly <NUM> comprises a body portion <NUM> defining a well <NUM>. The body portion <NUM> is typically a non-porous member. A filter membrane <NUM> is disposed within the well <NUM> of the body portion <NUM>. In some embodiments, the body portion <NUM> includes a hub portion <NUM>, a plurality of spokes <NUM> and a border <NUM>. The configuration provides a plurality of openings <NUM> that allow the tissue sample formed within the filter assembly <NUM> to be secured in the wax or other medium during the slicing process discussed below.

In some embodiments, the body portion is made of linear low-density polyethylene (LLDPE) material. For example, the body portion can be fabricated by an injection mold process. In some embodiments, the body portion is fabricated substantially of LLDPE. In further embodiments, the body portion is fabricated from low-density polyethylene (LDPE), polyvinyl alcohol (PVA), or a blend of LLDPE, LDPE, and/or PVA or other similar materials.

In some embodiments, the filter membrane <NUM> is fabricated from a porous membrane, such as ePTFE or track etched polyethylene terephthalate (PET), for example. The membrane is specified so as to be small enough to prevent sample loss, but large enough for sufficient reagent infiltration into the sample. In some embodiments, the membrane <NUM> is attached to the base member <NUM> by heat sealing, such as thermal bonding. In some embodiments, the membrane is secured by ultrasonic welding, or by an adhesive.

In some embodiments, the filter assembly <NUM> is further provided with a cover member <NUM> defining a central aperture <NUM> in which biological sample can flow into the well <NUM>. (See <FIG>). In some embodiments, cover member <NUM> is fabricated from the same materials discussed above for the body portion <NUM>, e.g., LLDPE. In some embodiments, aperture <NUM> supports a membrane, significantly as described as above for membrane <NUM>. When installed in the aperture <NUM>, the membrane filters the material before entering the well <NUM>.

Following the tissue processing steps above, e.g., the operation of a centrifuge for stratification/separation of the cells in the biological sample from any liquid to isolate and consolidate the cells into a concentrated pellet by centrifugation, the base <NUM> and filter assembly are removed from the apparatus <NUM>, as illustrated in <FIG>. As discussed above, the airtight seal, e.g., provided by the attachment of the lid <NUM> with the body <NUM>, and by the sizing of the distal outlet <NUM>, retain a substantial portion of the liquid within the loading compartment <NUM> of the body for subsequent reuse.

The sample, as well as the filter assembly <NUM>, is then placed in mold and infiltrated with paraffin wax for subsequent sectioning on a microtome, for example. Thus, the entire filter assembly <NUM>, including filter membrane <NUM> and the body portion <NUM> and <NUM>, is sliceable by a microtome to form slices of cell block (and filter assembly) for mounting on a glass slide for analysis on a microscope or for other analyses such as microcellular analysis, e.g., DNA, RNA, and/or protein.

The materials of the body portion <NUM> and membrane <NUM> are particularly selected for their chemical compatibility and sectionability. Regarding chemical compatibility, no significant quantity of material dissolves when exposed to typical tissue processing reagents and temperatures. For example, the materials are exposed to ethanol, xylene and formalin, up to about <NUM>. Regarding sectionability, the materials, e.g., LLDPE and ePTFE, are sliceable together with the contained cell block such that sufficiently thin slices can be achieved with a microtome for use in microscopy and other laboratory techniques. Moreover, the sectionability characteristics of the materials provide for insignificant wear on the microtome blade, and that subsequent slices are uniform, and mechanically stable, e.g., they do not break apart during slicing and subsequent handling.

Referring to <FIG>, a further embodiment of cell block filter assembly <NUM> is illustrated. Cell block filter assembly <NUM> can be used in connection with cell block system <NUM> in the same manner as cell block filter assembly <NUM>. The filter assembly <NUM> comprises a body portion <NUM> defining a well <NUM>. The body portion <NUM> is typically a non-porous member, and is fabricated of the same materials as body portion <NUM>, e.g., LLDPE, LDPE, PVA, or a combination thereof. A filter membrane <NUM> is disposed within the well <NUM> of the body portion <NUM>, and is fabricated of the same materials as membrane <NUM>, e.g., ePTFE. In some embodiments, the body portion <NUM> includes a hub portion <NUM> that defines the well <NUM>. A top wall portion <NUM> extends peripherally from the hub portion <NUM> and defines a plurality of holes <NUM>. A conical or tapered wall portion <NUM> extends from the top wall portion <NUM> and also defines a plurality of holes <NUM>. The plurality of partially cut-outs or serrations <NUM> are formed about the periphery of tapered wall portion <NUM>. The openings <NUM>, <NUM> and <NUM> allow the filter assembly <NUM> (and thus the tissue sample formed within) to be secured in the wax or other medium during the slicing process.

A further exemplary embodiment of the cell block system is shown schematically in <FIG>. Cell block system <NUM> includes an elongate tubular body <NUM>, a cell block filter assembly <NUM>, and a base member <NUM>. The elongate tubular body <NUM> defines an interior loading chamber <NUM>, and has a proximal end <NUM> and a distal end <NUM>. In some embodiments, the elongate tubular body has a first diameter d3 at the proximal end <NUM> and a second diameter d4 at the distal end <NUM>, wherein the second diameter d4 is smaller than the first diameter d3, as will be discussed in greater detail herein. A section <NUM> disposed between the proximal end <NUM> and the distal end <NUM> of the elongate tubular body <NUM>, has a decreasing diameter along a length thereof to define a generally conical configuration, and further includes structure for receiving the cell block filter assembly as will be described below. As shown in <FIG> and <FIG>, the tubular body narrows in an offset fashion, such that the distal outlet <NUM> is offset from the longitudinal axis L of the elongated body <NUM>.

With continued reference to <FIG>, the elongate tubular body <NUM> defines an opening <NUM> at the proximal end <NUM> of the body (top of the figure). The opening <NUM> is closed by a cover <NUM>, which provides a substantially airtight seal with the rim <NUM>. The lid <NUM> can be configured with external screw thread or threads <NUM> to engage a thread or threads <NUM> disposed on the inside surface of a proximal section <NUM> of the elongate tubular body <NUM>. However, other suitable methods and features can be used to engage the cover and elongate tubular body, such as a snap fit, ratchet fit, interference fit, vacuum seal or other methods of engagement, as would be appreciated by one of ordinary skill in the art.

In some embodiments, the elongate tubular body is preloaded with a fixative in the loading chamber. A "fixative" as used herein refers to a compound, such as formalin, ethanol, methanol, RPMI, saline for preservation and/or transportation of the sample.

As illustrated in <FIG>, at the distal section <NUM> of the elongate tubular body <NUM> is configured to permit the engagement and secure mounting of the cell block filter assembly <NUM> thereto. As illustrated in <FIG>, the filter assembly <NUM> defines a border <NUM> circumscribing an open off-center well <NUM> in which a filter membrane <NUM> is disposed. The well <NUM> is configured with an opening sized to cooperate with the distal outlet <NUM> on the distal section <NUM> of the elongate tubular body <NUM>. (See <FIG>). In an embodiment, cells may be collected in the center well <NUM>, such as after filtration, to provide a substantially cylindrical cell block.

The base member <NUM> is configured to support the cell block filter assembly <NUM>, and to be attached to the distal section <NUM> of tubular body <NUM> to secure the assembly <NUM> thereto. In some embodiments, the outer surface of the distal section <NUM> can be configured with a thread or a plurality of threads <NUM> to engage with a thread or threads <NUM> on interior portion of the base member <NUM> to secure the base member <NUM> to the distal section <NUM> of the elongate tubular body <NUM>, thereby stabilizing the cell block filter assembly <NUM> therein during centrifuging or other similar processes. It is contemplated that other techniques, such as snap fit, ratchet fit, interference fit, vacuum seal or other methods of attachment can be used to secure the base member <NUM> to the distal section <NUM> of the tubular body <NUM>. In this configuration, passage of liquid out of the filter assembly <NUM> through the filter membrane <NUM> is prevented by the solid nature of the surface of the base member <NUM>.

In the configurations shown in <FIG>, the filter assembly <NUM> is ready to receive a biological sample through distal opening of elongate body <NUM>. After the sample has been introduced into the cell block apparatus <NUM>, cap <NUM> can be secured to the tubular body <NUM>. Alternatively, the sample can be delivered via a needle such as a hypodermic needle or an aspiration needle through a cap <NUM> configured with a puncturable, resealable center portion that is already engaged with the tubular body <NUM>. In either case, the biological sample is securely sealed within the cell block system <NUM> for storage and/or transport from the locus where it is taken, such as an examination room or an operating room, to the locus where it can be analyzed, such as a pathology lab. The sealed cell block apparatus can be subjected to centrifuging process(es) without any of the sample escaping the sample loading chamber and passing through the cell block filter assembly <NUM>. Accordingly, the biological sample is separated or stratified (i.e. fluid content disposed above solid content) during the centrifuging process.

Referring to <FIG>, cell block filter assembly <NUM> is illustrated in greater detail. In an exemplary embodiment, the filter assembly <NUM> includes a body portion <NUM> typically fabricated from a non-porous material and defines a well <NUM> that is off-center. A filter membrane <NUM> is disposed within the well <NUM>. In some embodiments, support member(s) <NUM> extend from a border <NUM> to support the well <NUM>. The filter assembly <NUM> further includes a flexible hinge <NUM> (also referred to as a "living hinge") and a cover portion <NUM>. The hinge portion <NUM> can be fabricated from the same material as the body of the filter assembly, linear low-density polyethylene (LLDPE) material. The lid <NUM> is sized and configured to fit over the well <NUM>. In some embodiments, the cover includes an aperture that is covered with the filter membrane material. In some embodiments, the filter membrane <NUM> is fabricated from a porous membrane, such as ePTFE or track etched polyethylene terephthalate (PET), for example. The membrane is specified so as to be small enough to prevent sample loss, but large enough for sufficient reagent infiltration into the sample. In some embodiments, the membrane <NUM> is attached by heat sealing, such as thermal bonding, to the lid <NUM> and the well <NUM> and covers an opening at the bottom portion of the well <NUM>. In some embodiments, the membrane is secured by ultrasonic welding, or by an adhesive.

Claim 1:
A medical apparatus comprising:
an elongated body (<NUM>) having a proximal end (<NUM>), a distal end (<NUM>), and defining a loading chamber (<NUM>) between the proximal end and the distal end for storing a liquid therein, the elongated body defining an outlet (<NUM>) at the distal end thereof;
a cell block filter assembly (<NUM>) comprising:
a cell block body (<NUM>) defining a well portion (<NUM>) matingly engageable with the distal end of the elongated body for receiving fluid from the outlet of the elongated body and defining a well opening on a bottom thereof;
a filter membrane (<NUM>) disposed across the well opening within the well portion; and
a cover member (<NUM>) positionable over the well portion; and
a base member (<NUM>) for securing the cell block filter assembly (<NUM>) at the distal end (<NUM>) of the elongated body (<NUM>), and wherein the outer surface of the distal end of the elongated body is configured to engage with the base member;
wherein the entire cell block filter assembly is sliceable into slices having a thickness suitable for mounting on a laboratory slide; and
wherein the base member (<NUM>) prevents the passage of fluid out of the filter assembly (<NUM>).