Patent Description:
Such filter apparatus can be used for instance in analysis laboratories where relatively delicate, complex and costly machines are employed which are designed to perform sophisticate chemical or composition measurements, such as liquid chromatographers, titrators, water analyzers or similar.

In particular, high-performance liquid chromatography (HPLC; formerly referred to as high-pressure liquid chromatography), or ultra performance liquid chromatography (UPLC), used to separate, identify, and quantify each component in a sample mixture, require that a fluid sample be filtered, lest the analysis machinery be harmed by residual particulates in the fluid sample.

Sample materials processed can take many forms and can be inorganic, organic or biological. In particular, the sample material can be a hard and/or dry and/or brittle material, but also a softer material containing moisture, as in a biological tissue, or a viscous flowing mass in general. Therefore, the filter apparatus according to the present invention can be advantageously employed not only in the chemical and bio-chemical industry, but for instance also in food industry, e.g., if the food sample is analysed for heavy metals and similar. The automated system according to the present invention can be adapted to specific requirements of different areas of application, such as construction materials, metallurgy, textiles, pharmaceuticals or environmental analysis.

The present invention also relates to an automated system for the preparation of a sample for a chemical or composition analysis, comprising an injection head for the injection of an amount of sample in a receptacle and a filter apparatus.

The present invention further relates to a method of automated preparation of a sample for a chemical or composition analysis by way of an automated system, wherein the automated system comprises an injection head for the injection of an amount of sample in a receptacle via a needle.

According to conventional practices of sample preparation, a sample can be collected from a storing position, wherein the sample is typically contained in a vial retained in a vial rack recess.

The vial in which the sample is contained needs then to be carefully opened in order to enable taking out the sample and its consequent introduction into an extraction device.

Separation processes aimed at making a representative sample of a given material suitable for a subsequent chemical analysis require a preliminary fine size-reduction and homogenisation. Laboratory sample preparation protocols, in fact, require that the sample be manipulated, for instance by heating, screening, grinding, mixing etc., up to a target point of dissolution.

The extraction device can be operated to bring samples into a homogenous pulverized state and to prepare them perfectly for either additional sample preparation steps, and/or for subsequent analysis steps.

Subsequent analysis steps can be separating analytical methods like high-performance liquid chromatography (HPLC), or ultra performance liquid chromatography (UPLC), used to separate, identify, and quantify each component in a sample mixture.

As already mentioned, particulates or solids should be removed from a suspension of a fluid sample preparation, prior to submission to analysis machinery because of their adverse effect on the lifetime thereof. Particulates can affect HPLC hardware (e.g. flow lines, rotary injection valves, and inlet frits) and gas chromatography (GC) inlets, columns, and detectors.

Filtration is one common method for removing particulates or solids from the suspension created by the manipulated sample. Centrifugation and sedimentation are also known.

For the purpose of filtering, syringes and syringe filters are known. These however do not allow a real automation of the sample preparation and are not compatible with high-throughput autosamplers. <CIT>, <CIT>, <CIT>, <CIT> relate to syringe filter assemblies.

Preassembled filtration devices, in the form of disposable units, are already in use which comprise a plunger moving within a vial chamber. A filtration membrane is attached to a bottom end of the plunger; a pre-attached cap closes a top end of the plunger and a reservoir is created therebetween. An unfiltered suspension containing the sample is placed in the chamber. By fitting the plunger into the suspension-filled chamber, and by consequently pressing the plunger through the suspension, a clean filtrate is forced into the reservoir of the plunger. Excess air is vented through venting means integrated in the cap. Once the filtration has been carried out but dully pushing the plunger into the vial chamber, the cap can be removed or pierced with a needle and a sample drawn off for manual injection into an analyser machine.

However, such preassembled filtration devices have several drawbacks. It is difficult to ensure a fluid-tight sliding of the plunger into the chamber, with the ensuing risk of actually letting some undesired particle pass into the plunger reservoir. Moreover, the filtration membrane attached to the bottom end of the plunger is inherently small in surface: by construction, the filtration membrane cannot extend beyond the dimension of the plunger, which, in its turn, is limited by the dimension of the chamber within which it is made slidable. This structural limitation to the extension of the surface of the filtration membrane brings about problems with clogging of the pores of the membrane, as they do not have the capacity of effectively keeping on blocking physically the particulates from the suspension while letting the fluid through.

Therefore, there is a need for a filter apparatus for use in an automated system for the preparation of a sample for a chemical or composition analysis or such a system allowing a highly efficient automatized handling of a substantial number of samples and, at the same time, guaranteeing that the filtering action proceeds unaffected for the whole sample amount such that the analysis machines receive safely measurable analyte.

The filter apparatus, in order to ensure high throughput of prepared samples to be fed to the analysis machines, should be able to cleanly process a relatively high amount of sample volume passing therethrough, at a compatible flow rate.

According to the invention this need is settled by a filter apparatus as it is defined by the features of independent claim <NUM>, by an automated system as it is defined by the features of independent claim <NUM> and by a method of automated preparation of a sample for a chemical analysis by way of an automated system as it is defined by the features of independent claim <NUM>. Preferred embodiments are subject of the dependent claims.

In particular, in one aspect the invention deals with a filter apparatus for use in an automated system for the preparation of a fluid sample for a chemical or composition analysis.

The sample can originally have any suitable form such as the form of a tablet or other essentially solid body, a powder, a gel, a paste, a fluid or the like, which is suitable to be then processed by a processing unit of the automated system and reduced into a fluid form substantially equivalent to a suspension which needs to be further filtered to obtain a clear, particulate-free filtrate product. The sample material can particularly involve a drug. Thereby, the term "drug" relates to a therapeutically active agent, also commonly called active pharmaceutical ingredient (API), as well as to a combination of plural such therapeutically active substances. The term also encompasses diagnostic or imaging agents, like for example contrast agents (e.g. MRI contrast agents), tracers (e.g. PET tracers) and hormones, that need to be administered in liquid form to the patient.

The chemical or compositional analysis can be or involve any suitable analysis such as, particularly, high performance liquid chromatography (HPLC) or ultra high performance liquid chromatography (UHPLC or UPLC). The automated system can comprise an autosampler, for instance consisting of a robotic device that can bring the sample to a sampling processing unit or station and/or that can dose the sample to a receptacle on a tray or a carousel or a vial rack for delivery to a machine adapted to carry out the chemical or composition analysis.

The filter apparatus comprises an inlet portion with a conduit ending in an entry port for receiving the sample in an unfiltered state typically provided by or within the automated system. A septum is held at and closing the entry port of the conduit of the inlet portion.

The filter apparatus further comprises an outlet portion with a channel for dispensing the sample in a filtered state to a receptacle; as well as an intermediate portion having a filter chamber in fluid connection with the conduit of the inlet portion and with the channel of the outlet portion and a filter layer.

The filter chamber of the intermediate portion has a diameter larger than a diameter of the conduit of the inlet portion and than a diameter of the channel of the outlet portion.

The filter layer of the intermediate portion extends through the filter chamber of the intermediate portion such that the conduit of the inlet portion is separated from the channel of the outlet portion by the filter layer. Thanks to the filter layer in the filter chamber, the sample is filtered and dispensed to the receptacle in the form of clean filtrate.

The filter apparatus can be a membrane filter or syringe membrane filter. Besides the filter layer it can be made of a plastic material such as, e.g., polypropylene (PP), polyethylene (PE) or polytetrafluoroethylene (PTFE).

The receptacle can particularly be a vial or a similar suitable container. The term "receptacle" can relate to any container suitable for receiving or holding the sample material during storage thereof. The term "vial" as used herein can relate to vials in the literal sense, i.e. a comparably small vessel or bottle, often used to store pharmaceutical products or pharmaceuticals or medications in liquid, powdered or capsuled form. The vial can be made of a sterilisable material such as glass or plastic such as, e.g., polypropylene.

The inlet portion can define a distal end of the filter apparatus and the outlet portion a proximal end thereof, wherein by distal it is meant the direction that in use if furthest away from the receptacle or vial; whereas proximal indicates the direction which in use is closest to the receptacle or vial. The inlet and outlet portions can particularly be opposed to each other. The septum can be adapted to be pierced by a needle of an injection head of the automated system for the injection of the unfiltered sample fluid. The terms "conduit" and "channel" can relate to identical or similar structures or features of the filter apparatus. They are mainly used herein for reasons of comprehensibility, in particular, in order that the structure of the inlet portion can be differentiated from the structure of the outlet portion. More specifically, the conduit and the channel can be straight or curved ducts having a constant or varying diameter.

Preferably, the inlet portion and the outlet portion substantially extend along a longitudinal axis and, transversal to the longitudinal axis, the intermediate portion is wider than the inlet portion and than the outlet portion.

The intermediate portion, the inlet portion and the outlet portion may be, for instance, substantially cylindrically shaped.

Preferably, the intermediate portion is configured to remain in a fixed position relative to the outlet portion while the unfiltered sample is filtered through the filtering layer. Such a configuration overcomes any construction complication and the proneness to clogging typical of filter vials according to the prior art, wherein a plunger provided with a filtering membrane is slidably movable within the body of a vial chamber filled with unfiltered liquid.

In one possible embodiment, the filter apparatus preferably comprises a distal piece with a flange section and a proximal piece with a flange section, wherein the inlet portion is formed in the distal piece, whereas the outlet portion is formed in the proximal piece. In such case, the distal piece and the proximal piece are preferably mounted to each other at the flange sections, and the flange section of the distal piece and the flange section of the proximal piece are configured to form the intermediate portion when the distal piece is mounted to the proximal piece. Hence, a simple and effective construction of the intermediate portion incorporating a filter chamber is given, also offering the possibility of easily affixing the filter layer thereto.

Preferably, in the configuration of the embodiment above described, the filter layer is clamped in between the distal piece and the proximal piece such that it extends across the filter chamber of the intermediate portion.

Moreover, the flange section of the distal piece may be provided with a distribution structure and the flange section of the proximal piece may be additionally provided with a distribution structure, such that the distal and proximal walls of the filter chamber are equipped with the distribution structures when the distal piece is mounted to the proximal piece. The distribution structures allow for an optimal coverage and penetration of the filter layer by the fluid sample, thanks to an enhanced, uniform spreading of the fluid sample over the whole surface of the filter layer available. No limited region of the filter layer is thus overly burdened by the passing fluid sample.

Preferably, the filter chamber is substantially liquid-tight. This feature also guarantees that no portion of the fluid sample circumvents the filter layer and is left unfiltered.

A recess of the flange section of the proximal piece and/or a recess of the flange section of the distal piece may comprise a further filtering element adapted to cooperate with the filter layer. A further filtering element could for instance be conceived to preliminarily capture bigger particles upstream of the filter layer and/or refine the filtrate in a targeted way. Additional filtering elements can also be incorporated or embedded in the above described distribution structures, for instance in case the suspension of the fluid sample is particularly dense.

Preferably, the filter layer has a surface area adapted to allow a complete filtration passage of the unfiltered fluid sample received in the conduit of the inlet portion in a target time. In order to improve a throughput of the automated system, the target time within which all of the fluid sample has passed through the filter layer is advantageously minimized. The relatively large area of the filter layer configured as previously described enables a quick passage of the fluid sample.

Preferably, the surface area of the filter layer is in a range of about <NUM><NUM> to about <NUM><NUM> and/or the filter layer has a porosity in a range of about <NUM> to about <NUM>.

Preferably, the outlet portion has a dispensing nozzle, the channel ends the dispensing nozzle and the dispensing nozzle is configured to prevent the formation of drops. Thus, a clean and lossless delivery of the filtered fluid sample to an underlying receptacle, such as a vial, is guaranteed.

Preferably, the filter layer comprises a filter membrane. The filter membrane can be made of polyethersulfone (PES), regenerated cellulose (RC) or polyvinylidene fluoride.

Preferably, the filter chamber of the intermediate portion extends transversal to a direction of flow defined by the conduit of the inlet portion and the channel of the outlet portion.

In order to enable a fast, complete and unobstructed passage of the fluid sample through the filter layer therein contained, the diameter of the filter chamber of the intermediate portion is at least two times, at least three times, at least four times or at least five times larger than the diameter of the conduit of the inlet portion and than the diameter of the channel of the outlet portion.

The present invention also relates to an automated system for the preparation of a sample for a chemical or composition analysis, comprising an injection head -also designatable as dosing apparatus- for the injection -or dosage- of an amount of sample in a receptacle and a filter apparatus according to any one of the preceding claims. The injection head is equipped with a needle adapted to be affixed to the filter apparatus by piercing a septum of the filter apparatus.

The filter apparatus can be disposable and affixable to the needle of the injection head, or dosing apparatus, every time that a fluid sample needs to be newly filtered. Alternatively, the same filter apparatus affixed to one needle of the injection head may be employed for successively distributing a sample fluid into a series of different receptacles.

The present invention also relates to a method of automated preparation of a sample for a chemical analysis by way of an automated system, wherein the automated system comprises an injection head for the injection of an amount of sample in a receptacle via a needle.

The method of automated preparation of a sample for a chemical analysis according to the present invention comprises the steps of obtaining a filter apparatus as above described and of preventively affixing the needle by piercing a septum of the filter apparatus. The method further comprises the steps of positioning the filter apparatus adjacent to a receptacle and establishing a fluid connection between the needle of the injection head and the receptacle through the filter apparatus.

The filter apparatus is preferably designed as disposable, for instance being designed for just a single use. There can also be envisaged the possibility to design the filter apparatus such that the need for substitution thereof first arises after a programmed number of pipetting injection cycles, whether executed in one same receptacle or in a series of distinct receptacles.

The filter apparatus and the automated system for the preparation of a sample for a chemical or composition analysis adapted to employ such filter apparatus according to the invention are described in more detail herein below by way of an exemplary embodiment and with reference to the attached drawings, in which:.

In the following description certain terms are used for reasons of convenience and are not intended to limit the invention. The terms "right", "left", "up", "down", "under" and "above" refer to directions in the figures. The terminology comprises the explicitly mentioned terms as well as their derivations and terms with a similar meaning. Also, spatially relative terms, such as "beneath", "below", "lower", "above", "upper", "proximal", "distal", and the like, may be used to describe one element's or feature's relationship to another element or feature as illustrated in the figures. These spatially relative terms are intended to encompass different positions and orientations of the devices in use or operation in addition to the position and orientation shown in the figures. For example, if a device in the figures is turned over, elements described as "below" or "beneath" other elements or features would then be "above" or "over" the other elements or features. Thus, the exemplary term "below" can encompass both positions and orientations of above and below. The devices may be otherwise oriented (rotated <NUM> degrees or at other orientations), and the spatially relative descriptors used herein interpreted accordingly. Likewise, descriptions of movement along and around various axes include various special device positions and orientations.

With reference to <FIG> and <FIG>, a filter apparatus <NUM> for use in an automated system <NUM> for the preparation of a sample for a chemical or composition analysis according to the present invention comprises an inlet portion <NUM>, an outlet portion <NUM> and an intermediate portion <NUM>.

As shown represented in <FIG>, the inlet portion <NUM> comprises a conduit <NUM> ending in an entry port <NUM> for receiving an unfiltered fluid sample delivered by the automated system <NUM>. In this specific case, the conduit <NUM> comprises a funnel-shaped section to better collect and direct the dosed fluid.

The outlet portion <NUM> comprises a channel <NUM> for dispensing the filtered sample to a receptacle <NUM>, such as a vial. In the represented instance, the channel <NUM> has a substantially constant cylindrical section.

A septum <NUM> is held at, and closes, the entry port <NUM> of the conduit <NUM> of the inlet portion <NUM>.

Also in the section view of <FIG>, it is exemplified how the substantially cylindrical intermediate portion <NUM> has a filter chamber <NUM> which is in fluid connection with the conduit <NUM> of the inlet portion <NUM> and with the channel <NUM> of the outlet portion <NUM>.

The filter chamber <NUM> of the intermediate portion <NUM> extends transversal to a direction of flow F defined by the conduit <NUM> of the inlet portion <NUM> and the channel <NUM> of the outlet portion <NUM>.

The inlet portion <NUM> and the outlet portion <NUM> substantially extend along a longitudinal axis C-C. Transversal to the longitudinal axis C-C, the intermediate portion <NUM> is wider than the inlet portion <NUM> and than the outlet portion <NUM>.

A filter layer <NUM>, in the form of a membrane, extends through the filter chamber <NUM> such that the conduit <NUM> of the inlet portion <NUM> is separated from the channel <NUM> of the outlet portion <NUM> by the filter layer <NUM>.

Thus, the fluid sample, having been dosed into the entry port <NUM>, is conveyed via the conduit <NUM> to the liquid-tight filter chamber <NUM> and, once completely filtered by the filter layer <NUM>, is then fully carried through the channel <NUM> to be ultimately dispensed to a receptacle <NUM>.

For the dispensing purpose, the outlet portion <NUM> is provided with a dispensing nozzle <NUM>, the channel <NUM> ending the dispensing nozzle <NUM>. The dispensing nozzle <NUM> is aptly configured to prevent the formation of drops.

The diameter of the filter chamber <NUM> of the intermediate portion <NUM> is larger than the diameter of the widest section of the funnel-shaped conduit <NUM> of the inlet portion <NUM> and than the diameter of the channel <NUM> of the outlet portion <NUM>.

As it can be appreciated from <FIG>, <FIG> and <FIG>, in the present embodiment the inlet portion <NUM> is formed in a distal piece <NUM>, whereas the outlet portion <NUM> is formed in a proximal piece <NUM>. The distal piece <NUM> is formed with a flange section <NUM> and the proximal piece <NUM> with a flange section <NUM>. The distal piece <NUM> and the proximal piece <NUM> are mounted to each other at the flange sections <NUM>, <NUM>, such that the intermediate portion <NUM> is formed in the mounted configuration. In the embodiment of <FIG>, the filter chamber <NUM> is created by two matching recesses respectively in the flange section <NUM> and in the flange section <NUM>.

In such mounted configuration, the filter layer <NUM> is clamped in between the distal piece <NUM> and the proximal piece <NUM> such that it extends across the filter chamber <NUM> of the intermediate portion <NUM>.

As represented in <FIG>, <FIG> and <FIG>, the flange section <NUM> of the distal piece <NUM> has a distribution structure <NUM> and the flange section <NUM> of the proximal piece <NUM> has a distribution structure <NUM>. Thus, the distal and proximal walls of the filter chamber <NUM> are equipped with the distribution structures <NUM>, <NUM>, when the distal piece <NUM> is mounted to the proximal piece <NUM>. In the specific embodiment portrayed, the distribution structures <NUM>, <NUM> take the form of wedge-shaped circular sectors integrating concentric distribution grooves <NUM>. Each circular sector is separated from adjacent circular sectors by radial grooves <NUM> opening into each of the concentric distribution grooves <NUM>. Thus, grooves <NUM> and <NUM> form a network of distribution sulci which guarantee a uniform spreading of the fluid sample to be filtered over the whole surface of the filter layer <NUM>.

The intermediate portion <NUM> is configured to remain in a fixed position relative to the outlet portion <NUM> while the unfiltered sample is filtered through the filter layer <NUM>.

The present invention also relates to an automated system <NUM> for the preparation of a sample for a chemical or composition analysis, comprising an injection head <NUM> for the injection of an amount of sample in a receptacle <NUM> and a filter apparatus <NUM> as above described. A possible embodiment for such an automated system is represented in <FIG> and <FIG>.

The automated system <NUM> comprises a handling robot <NUM>; a ball mill apparatus <NUM>; an injection head <NUM>, also designatable as dosing apparatus <NUM>; a filter dispenser <NUM> and a sample processing unit <NUM>.

The automated system <NUM> is equipped with a platform <NUM> on which several components are positioned. The platform <NUM> has height adjustable feet which allow for aligning the platform <NUM> such that it lies in an essentially horizontal plane.

The handling robot <NUM> has a vertical stand <NUM> which is equipped with vertically extending parallel rails <NUM>. On the rails <NUM> an arm unit <NUM> is slidably mounted such that the arm unit <NUM> can vertically move along the rails <NUM>. The arm unit <NUM> has a cylinder portion, which is pivotable about a vertical axis and an arm <NUM> with joints ending in gripping fingers <NUM>.

The ball mill apparatus <NUM> has an agitating station <NUM> which is positioned at a left hand side of the platform <NUM>. It further has an extraction tube rack <NUM> which extends along the complete front side of the platform <NUM>. The dosing apparatus <NUM> and the sample processing unit <NUM> are positioned between the agitating station <NUM> of the ball mill apparatus <NUM> and the stand <NUM> of the handling robot <NUM>. The dosing apparatus <NUM> has two needles <NUM> and two sucking pumps <NUM>, wherein each pump <NUM> is coupled to one of the needles <NUM> by a flexible tube.

In <FIG> the automated system <NUM> is shown top down. Thereby, it can be seen that the filter dispenser <NUM> has a filter storage <NUM> positioned left hand aside the platform <NUM> and a filter disposer <NUM> positioned left hand aside the dosing apparatus <NUM>. The extraction tube rack <NUM> forms the front of the automated system <NUM> and the other components, i.e. the agitating station <NUM>, the dosing apparatus <NUM>, the sample processing unit <NUM>, the handling robot <NUM> are arranged behind the extraction tube rack <NUM>.

A vial rack <NUM> is also arranged behind the extraction tube rack <NUM>, on platform <NUM>. The vial rack <NUM> has recesses in which glass vials <NUM> are received as receptacles. The vials <NUM> are meant to house the fluid sample once filtered, that is ready for analysis, e.g. by HPLC.

The handling robot <NUM> takes a container of fluid sample, possibly already partially processed by the sample processing unit <NUM>, with its gripping fingers <NUM> and places it into one of the extraction tubes pre-positioned in the extraction tube rack <NUM>. The handling robot <NUM> then relocates the extraction tube into the agitating station <NUM> of the ball mill apparatus <NUM>. There the sample material is grinded thanks to the movement imparted by a drive agitating the extraction tube and in particular by grinding balls.

After the sample has been grinded, the extraction tube is relocated into the extraction tube rack <NUM> where it is ready for further preparation by the sample processing unit <NUM>.

The fluid sample, thus broken-down and reduced by the agitating station <NUM> and processed by the sample processing unit <NUM>, is ready to be sucked by the injection head, or dosing apparatus, <NUM> via needles <NUM> under the sucking action of pumps <NUM>.

At least one of the needles <NUM> is adapted to be affixed to a filter apparatus <NUM> which is summoned from the filter storage <NUM> of the filter dispenser <NUM> and pre-arranged by the filter disposer <NUM> for the needle <NUM> to pierce its septum <NUM>.

The affixing of the needle <NUM> to the filter apparatus <NUM> is obtained by the needle <NUM> piercing a septum <NUM> of the filter apparatus <NUM>.

The injection head <NUM> positions then the filter apparatus <NUM> adjacent to a receptacle <NUM>, such as a vial, and a fluid connection is established between the needle <NUM> of the injection head <NUM> and the vial <NUM> through the filter apparatus <NUM>.

The prepared fluid sample material is thus transferred from the injection head <NUM> to the vial <NUM> through the filter apparatus <NUM> provided by the filter dispenser <NUM>, so that it can be then analysed in an appropriate HPLC equipment.

As mentioned, the filter apparatus <NUM> is preferably disposable. However, the same filter apparatus <NUM> can be employed for establishing a fluid connection between the needle <NUM> of the injection head <NUM> and a series of different receptacles <NUM>, distributing one filtrate into multiple receptacles. The filter apparatus <NUM> can be designed to be substituted only after a programmed number of injection cycles, whether the injection or dosing happens in just one receptacle <NUM> or is distributed into several distinct receptacles <NUM>.

This description and the accompanying drawings that illustrate aspects and embodiments of the present invention should not be taken as limiting the claims defining the protected invention. In other words, while the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive. Various mechanical, compositional, structural, electrical, and operational changes may be made without departing from the spirit and scope of this description and the claims. In some instances, well-known circuits, structures and techniques have not been shown in detail in order not to obscure the invention. Thus, it will be understood that changes and modifications may be made by those of ordinary skill within the scope and spirit of the following claims. In particular, the present invention covers further embodiments with any combination of features from different embodiments described above and below.

The disclosure also covers all further features shown in the Figs. individually although they may not have been described in the afore or following description. Also, single alternatives of the embodiments described in the figures and the description and single alternatives of features thereof can be disclaimed from the subject matter of the invention or from disclosed subject matter. The disclosure comprises subject matter consisting of the features defined in the claims or the exemplary embodiments as well as subject matter comprising said features.

Claim 1:
A filter apparatus (<NUM>) for use in an automated system (<NUM>) for the preparation of a fluid sample for a chemical or composition analysis, comprising:
an inlet portion (<NUM>) with a conduit (<NUM>) ending in an entry port (<NUM>) for receiving the sample in an unfiltered state;
a septum (<NUM>) held at and closing the entry port (<NUM>) of the conduit (<NUM>) of the inlet portion (<NUM>);
an outlet portion (<NUM>) with a channel (<NUM>) for dispensing the sample in a filtered state to a receptacle (<NUM>); and
an intermediate portion (<NUM>) having a filter chamber (<NUM>) in fluid connection with the conduit (<NUM>) of the inlet portion (<NUM>) and with the channel (<NUM>) of the outlet portion (<NUM>), and a filter layer (<NUM>); wherein
the filter chamber (<NUM>) of the intermediate portion (<NUM>) has a diameter larger than a diameter of the conduit (<NUM>) of the inlet portion (<NUM>) and than a diameter of the channel (<NUM>) of the outlet portion (<NUM>), and
the filter layer (<NUM>) extends through the filter chamber (<NUM>) such that the conduit (<NUM>) of the inlet portion (<NUM>) is separated from the channel (<NUM>) of the outlet portion (<NUM>) by the filter layer (<NUM>).