Filtration Device, a Filtration System and a Method of Using the Same

[0001] The present invention relates to a filtration device, a filtration system and a method of using the same and in particular to a device, system and method for the collection of liquid filtrates by centrifugation.

[0002] It is often desirable to analyse a liquid after removal of suspended particles which might otherwise clog the flow system of an analyzer or interfere with the analysis of the liquid. For example, in solvent extraction analysis an extraction liquid is reacted with a solid sample, particularly a powdered or granular solid sample, and species of interest are extracted into the liquid for analysis. Typically a filtration device is employed by which particles are separated from the liquid in which they are suspended using a filter medium. Liquid filtrate is collected for introduction into the flow system of the analyzer. Centrifuges are also often employed to aid the filtration process. Typically, the filtration device is releasably held in a holder of a centrifuge and rotated rapidly. The centrifugal force which is generated as a consequence of this rapid rotation causes liquid and particles to move along a path in the direction of this force. The filter medium is positioned along this path to act as a barrier for the particles.

[0003] One such filtration device is disclosed in US3478889 for use in conjunction with a centrifuge and comprises a disposable filtration unit having a body configured internally with a sample chamber for receiving a liquid to be filtered. The sample chamber has an open end at the bottom that in use is closed with a cap. The cap is configured with a through passage which at one end fluidly connects to the sample chamber and at the other end with a well for liquid filtrate. A filter medium covers at least one of the ends of the through passage and forms a common boundary of the sample chamber and the well. The filtration device is intended for mounting in a holder of a centrifuge. The holder holds the filtration device with the sample chamber above the well and during centrifugation the holder and device pivot towards a direction parallel to the direction of action of the centrifugal force, that is to say, perpendicular to the rotational axis of the holder. The liquid to be filtered is moved under the centrifugal force in a direction parallel to its direction of action from the sample chamber, through the filter medium, and into the well where it is retained as liquid filtrate. Once centrifugation is complete the holder and filtration device pivot back and liquid filtrate becomes retained in the well again located at a lower end of the filtration device, below the sample chamber.

[0004] A problem with this known filtration devices is that liquid filtrate is held at the bottom of the device which makes access to it for analysis difficult. Moreover, having the filter at the bottom can lead to particles falling under gravity to clog the filter before sufficient filtrate is collected. Additionally, in the known centrifuge each sample containing filtration device needs to be counterbalanced with a diametrically opposed weight, typically another sample containing filtration device, in order to maintain the stability of the rotating centrifuge and reduce wear.

[0005] According to a first aspect of the present invention there is provided a filtration device comprising a sample chamber; a body housing the sample chamber and having an open top in communication with the sample chamber; a well; a cap for closing the open top, the cap configured with the well and with a liquid passageway for communication with the sample chamber; and a filter medium disposed to filter sample from the sample chamber before passing into the well; wherein the well is positioned in the cap, typically at an upper surface of the cap, at a location closer to its outer periphery than the liquid passageway so to receive liquid filtrate (48) therefrom. This has an advantage that since the liquid filtrate can be collected in a well in a cap above the filter medium it is more easily accessible for subsequent analysis. Furthermore, as the filter medium lies above the sample chamber and above the liquid to be filtered then any particles in the liquid cannot be moved under gravity to clog the filter medium.

[0006] In some embodiments the cap is configured with an elliptical cross-section in a plane parallel to the open top when closed by the cap and the well is positioned closer to the periphery of the cap than the liquid passageway in a direction along the Major axis (M) of the ellipse. This has an advantage that during centrifugation the hydrostatic pressure on the liquid is greater in the regions of the sample chamber along the major axis so that liquid is preferentially directed through the flow conduits and towards the well.

[0007] In some embodiments the filter medium is attached to a base of the cap to cover the liquid passageway. This facilitates assembly of the filtration device and in some embodiments permits re-use of the filtration device through replacement of the cap only.

[0008] According to a second aspect of the present invention there is provided a filtration system comprising a number of filtration devices according to the first aspect of the present invention and a centrifuge including a number of holders mounted for rotation about an axis of rotation substantially parallel to the vertical, each holder of the number of holders configured to releasably retain an associated filtration device of the number of filtration devices orientated with its sample chamber below its filter medium during rotation of the number of holders. The hydrostatic pressure generated by the centrifugal force created by the rotation of the holders causes the liquid to be filtered to move upwards along the inner walls of the sample chamber and through the filter medium to be retained in its well. Since the filter medium remains above liquid in the sample chamber then clogging of the filter medium due to effects of gravity is avoided.

[0009] According to a third aspect of the present invention there is provided a method of generating a liquid filtrate employing the system according to the second aspect of the present invention to provide advantages associated with the first and with the second aspects of the present invention.

[0010] Thus according to the third aspect of the present invention there is

provided a method of generating a liquid filtrate comprising the steps of: placing a filtration device according to the first aspect of the present invention into a rotatable holder of a centrifuge so as to orientate the filter medium and well above the liquid sample to be filtered when the filtration unit is placed in the holder;

centrifuging the liquid sample to be filtered whilst maintaining the filtration device in substantially the same orientation as it had when placed in the holder to cause the sample to be filtered to move upwards, through the filter medium and form the liquid filtrate and moving the liquid filtrate into the well under action of the centrifugal force on the liquid filtrate.

[001 1] According to a fourth aspect of the present invention there is provided a cap for closing an open top of a tubular filter body, the cap comprising a liquid passageway extending through the cap from one opposing surface to another; a filter medium affixed to the cap to cover at least an end of the liquid passageway; and a well for a liquid filtrate located at a position closer to an outer periphery of the cap than the liquid passageway.

[0012] These and other advantages will be appreciated from a consideration of the following description of non-limiting embodiments of the present invention made with reference to the drawings of the accompanying figures, of which:

Fig. 1 Shows a first embodiment of the filtration device

according to the present invention;

Fig. 2 Shows the cap of the filtration device illustrated in Fig.

1 ;

Fig. 3 Shows a centrifuge of a filtration system according to the present invention.

Figs. 4 Shows the filtration device illustrated in Fig. 1 in use

with the centrifuge illustrated in Fig. 3.

Fig. 5 Shows a second embodiment of a filtration device

according to the present invention.

Fig. 6 Shows a third embodiment of a filtration device

according to the present invention.

[0013] A first exemplary embodiment of a filtration device 2 according to the first aspect present invention which is shown in Fig. 1 and Fig. 2 comprises a tubular body 4 configured with an open top 6 and a closed bottom 8 so as to define a sample chamber 10 internal of the tubular body 4. A cap 12 is provided as a closure for the open top 6. In the present embodiment the cap 12 is attached to the tubular body 4 by a hinge 14 which permits movement of the cap 12 to close the open top 6 by push fit engagement with the tubular body 4 and is provided with portions 16 which extend beyond the tubular body 4 in a plane parallel to the open top 6 when the cap 12 is closed. In other embodiments the hinge 14 may be omitted; the cap 12, in other embodiments, may be fixed to permanently close the top 6, for example by forming the tubular body 4 and the cap 12 as a single piece; or the cap 12 and tubular body 4 may be configured for threaded engagement.

[0014] The cap 12 has a lower surface 18 and an opposing upper surface 19 bounded by a common outer periphery 11 . At least part 18a of the lower surface 18 acts as a carrier for a filter medium 20, here a planar filter medium such as may be provided by a filter paper or a membrane filter of known types, such that when the cap 12 is closed over the open top 6 of tubular body 4 the carrier 18a locates the filter medium 20 above a liquid to be filtered which is held in the sample chamber 10. It will be appreciated that in other embodiments at least a portion of the upper surface 19 may, alternatively or additionally, act as a carrier for the filter medium 20.

[0015] With reference also to Fig. 2, in which the cap 12 is illustrated in a closed position, the cap 12 is also configured with a well 24 at its upper surface 19 for receiving a liquid filtrate. In the present embodiment two wells 24 are located in the portions 16 of the cap outside of the tubular body 4 so as to extend from the upper surface 19, along the body 4 in this closed position.

[0016] A liquid passageway, here comprised of at least one through hole 22 (here two) between the opposing surface 18,19, is provided in the cap (12) for liquid communication with the sample chamber 10 to provide a liquid filtrate for retention in the well(s) 24. At least one of the open ends of the each of the at least one through hole 22 is covered by the filter medium 20. In the present embodiment, the portion 18a of the lower surface 18 which acts as the carrier is recessed to receive the open end 6 of the body 4. [0017] More generally, the well 24 is located closer to the outer periphery 11 of the cap 12 in a direction of flow of liquid filtrate from the liquid passageway 22 than the liquid passageway (through holes) 22 itself. This relative positioning of well 24 and liquid passageway 22 facilitates flow of the liquid filtrate from the liquid passageway 22 into the well 24 during centrifugation, as will be described further below.

[0018] In the present embodiment the cap 12 is further configured with a conduit 26 providing access to the sample chamber 10 from external of the filtration device 2 and is not covered by filter medium 20. In some embodiments, such as where it is intended that liquid is to be introduced into the sample chamber 10 before the cap 12 is closed, this conduit 26 may be omitted. In some embodiments a seal (omitted from Fig.1 and Fig. 2 for sake of clarity) may be provided as an element of the cap 12 to prevent accidental ingress or egress of liquid. This seal is configured with at least the regions immediately above the wells 24 and the optional conduit 26 (when present) which are piercable or removable to provide external access to these features, for example by a hollow needle or pipette. A thin foil, film, wall or membrane may be employed in these regions for this purpose or may be provided to lie above the entire upper surface 19.

[0019] A centrifuge 30 as a component of a filtration system according to a

second aspect of the present invention is illustrated in Fig. 3 and

comprising a housing 32 in which a motor 34 is housed. The motor 34 is operable to rotate a holder 36 about a substantially vertical axis, A. The holder 36 is, in the present embodiment, coupled to the motor 34 by means of a bearing 38 and axle 40 arrangement.

[0020] The holder 36 is, in the present embodiment, open topped and internally dimensioned to receive a filtration device (2 say) according to the first aspect of the present invention so as to hold the filtration device 2 upright with the filter medium 20 and cap 12 above liquid in the sample chamber 10 before centrifugation. The holder 36 is configured to maintain the received filtration device 2 in this upright position during centrifugation and thereby keep the cap 12 in a plane substantially perpendicular to a rotational axis A. In this present embodiment, the substantially vertical rotational axis A passes along the centre of the filtration device 2 from bottom 8 to cap 12. This has an advantage that during rotation the filter device 2 does not need to be counter-balanced, allowing the centrifugation of single samples without causing undue wear on the centrifuge 30.

[0021] As is illustrated in Figs 1 and 2, the tubular body 4 may be constructed with an elliptical cross section in a plane parallel with the open end 6. The two through holes 22 are then located along the major axis M (also known as the long axis) of the ellipse, essentially equidistant from and either side of the centre C of the ellipse such that when the cap 12 is closed the through holes 22 are located adjacent a section of inner wall 46 of the sample chamber 10 which intersects the major axis M. The wells 24 are similarly located along the major axis M of the ellipse, essentially equidistant from and either side of the centre C of the ellipse at locations further from the centre C than the two through holes 22 and closer to the outer periphery 1 1 of the cap 12. Although it is not essential to provide the tubular body 4 with an elliptical cross section advantages this provides may be appreciated from a consideration of the operation of the centrifuge to rotate such a filtration device 2 as is described below with reference to Figs. 4. However, irrespective of the cross-sectional shape of the tubular body 4 it is essential that the wells 24 are located close to the outer periphery 1 1 of the cap 12, as will be apparent from the description below.

[0022] Fig. 4(a) illustrates, in part section, a filtration device 2 mounted in a

corresponding holder 36 of the centrifuge 30 of Fig. 3 before

centrifugation. As can be seen from Fig. 4(a) the cap 12 of filtration device 2 closes the open top 6 of sample chamber 10 and holds the filter medium 20 above liquid 42 to be filtered. The filter medium 20 is located to cover the through holes 22 that form the liquid passageway but avoids the conduit 26. The well 24 is shown to lie outside of the tubular body 4 in a direction along the major axis M of the elliptical cap 12. The cap 12 is sealed over its entire upper surface 19 with a foil seal 44.

[0023] Figs. 4(b) and (c) illustrate, in part section, a filtration device 2 mounted in a corresponding holder 36 during centrifugation by rotation of holder 36 about the substantially vertical axis A, as illustrated by the arrow in Fig. 4(b). The effect of centrifugation on the liquid to be filtered 42 in the sample chamber 10 is, as can be seen from Fig. 4(b), to urge it against the inner surface 46 which defines the sample chamber 10 and thereafter to move it along the surface 46 upwards towards the cap12. Due to the elliptical cross sectional shape of the tubular body 4 the hydrostatic pressure on the liquid 42 during centrifugation is higher along the portion of the inner surface 46 of the sample chamber 10 that intersects the major axis M than elsewhere (i.e. towards the foci of the ellipse). As is illustrated by the arrows in Fig. 4(c), the effect of this is that the liquid 42 is preferably transported upwards along this portion of inner surface 46, through the filter medium 20 covering the through holes 22 to form a liquid filtrate which, due to the effects of the centrifugation, is then moved towards the wells 24 which are located further away along the major axis M of the elliptical cap 12. After centrifugation (Fig. 4(d)) liquid filtrate 48 is retained in the wells 24 whilst the remainder of the liquid 42 is returned to the sample chamber 10.

[0024] The liquid filtrate 48 may then be accessed from outside the filtration

device 2 by piercing regions 50 of the foil seal 44 immediately above the wells 24, for example with a hollow needle in fluid communication with a liquid intake of an analysis device (not shown).

[0025] One illustrative use of the filtration element 2 and centrifuge 30 depicted in Fig. 4(a) is their use in a solvent extraction assay. A granular or powdered sample, say for example a sample of wheat, is first introduced into the sample chamber 10 through the open top 6 and the cap 12 closed. An extraction liquid, say for example 30% by volume ethanol in water, is introduced into the sample chamber 10 from external of the filtration device 2 through, for example, a needle of a syringe via the conduit 26 after the needle has perforated the foil 44 in a region 27 above the liquid passage 26. As will be appreciated, in the alternative, this extraction liquid may be introduced through the open top 6 before being closed by the cap 12. However, an advantage of with the former is that the solid sample can more easily be transported in the closed, sealed filtration device 2, to a location where the assay is to be performed or stored there without the risk of loss of any sample.

[0026] The species of interest for assay, say for example a mycotoxin, is

extracted over time from the granular sample into the extraction liquid which then forms the liquid 42 to be filtered. The filtration device 2 containing the mixture of solid wheat sample and liquid to be filtered 42 is then placed in holder 36 of the centrifuge 30 so that it is contained in the sample chamber 10 below the filter medium 20 carried by the cap 12. During centrifugation liquid containing the species of interest extracted from the sample is forced upwards along the inner surface 46 of the sample chamber 10 and passes through the flow conduits 22 covered by the filter medium 20 to form a liquid filtrate 48 above the sample chamber 10. The liquid filtrate moves in a plane perpendicular to the axis of rotation A away from the through holes 22 and falls into the wells 24 where it is retained. Once the centrifuge 30 is stopped the filtration device 2 is left with liquid filtrate 48 in the wells 24 separated from the extraction liquid and sample which remain in the sample chamber 10. This liquid filtrate 48 may then accessed for assay by a hollow needle or pipette being pressed through the regions 50 above the wells 24 to enter the liquid filtrate 48. A pumping system of an assay instrument, with which assay instrument the centrifuge 30 may be integrated, may be provided in fluid communication with the hollow needle or pipette in the liquid filtrate 48 and operated to move the filtrate 48 from the wells 24 and to a measurement region of the assay instrument.

[0027] A second embodiment of a filtration device 52 is illustrated in Fig. 5 and comprises a tubular body 54, here of circular cross-section, configured with an open top 55 and closed bottom 58 to form a sample chamber 60 for a liquid to be filtered. An upper annular surface 62 of the open top 55 is configured to act as a carrier to support a planar filter medium 64, such as a filter paper or a membrane filter, in plane parallel to the closed bottom 58. The filter medium 64 is, as in the present embodiment, optionally fixed, such as by gluing, to the upper surface 62 and may be constructed with a central opening (dashed construction 66) to provide access to the sample chamber 60 from external the tubular body 54. The filter medium 64 may alternatively be continuous across the open top 55, as is illustrated in the present embodiment. In order to gain access to the sample chamber 60 from external of the tubular body 54 the filter medium 64 is pierced, for example with a syringe needle or pipette. In the present embodiment the tubular body 54 has a circular cross-section but may be elliptical as with the embodiment shown in Fig. 1.

[0028] In an alternative embodiment (also illustrated in Fig. 5) the carrier 68 is configured as an open rigid frame 70 having an annular base 72 over which a planar filter medium 74 extends and is fixed to the base 72 about its periphery. It will be appreciated that this filter medium 74 may alternatively extend over an annular top, opposing the base 72, without departing from the invention as claimed. The carrier 68 of this alternative embodiment is formed for push fit engagement with internal walls 76 of the tubular body 54 and may be inserted into the filter body 54 after the introduction of a sample for assay, for example a powdered or granular sample to which a liquid, such as a liquid solvent, will be introduced to form a liquid to be filtered after its interaction with the sample for assay. In a further embodiment the frame 70 forms a hollow carrier into which a known depth filter medium may be placed.

[0029] The filtration device 52 further comprises a removable cap 78 (shown in cross-section in Fig. 5) configured for engagement with the tubular body

54, for example push-fit or threaded engagement, to close the open top

55. In the present embodiment the cap 78 has an internal surface 80 for push-fit engagement with an outer surface 82 of the tubular body 54.

Thus, the internal surface 80 is able to slide over the outer surface 82 until the upper surface 62 of the tubular body 54 abuts a stop, shoulder or other protrusion, here an annular stop 84, of the cap 78 which then closes the open top 55 of the tubular body 54. A well 86 for liquid filtrate is formed internal the cap 78, here by way of example formed as a single annular well, in a portion 94 of the cap 78 which lies proximal an outer periphery 83 of the cap 78 and outside of the outer surface 82 of the tubular body 54 when the open top 55 is closed by the cap 78. A liquid passageway 81 is delimited by internal surface 80 and lies further away from an outer periphery 83 of the cap 78 than the well 86. Closing the open top 55 with the cap 78, places the well 86 in liquid communication with the sample chamber 60 via the filter medium 64;74 and the liquid passageway 81.

[0030] In a modification of this embodiment, the planar filter medium 64;74 may be fixed to the annular stop 84 of the cap 78 which then also acts as the carrier for the filter medium. Thus, when the open end 55 is closed by the cap 78 the planar filter medium 64;74 covers the open end 55.

[0031] In another modification a lower wall section 92 of the cap 78 which delimits the well 86 of the presently described embodiment may be removed to allow filtrate to exit for collection outside of the filter device 52. Indeed, the embodiment of the filtration device 2 described with reference to Fig. 1 may be similarly modified.

[0032] In use, the second embodiment of the filtration device 52 is held upright for centrifugation, for example in a holder 36 of a centrifuge according to Fig. 3, so that the filter medium 64:74 lies in a plane substantially perpendicular to a vertical rotational axis about which the filtration device 52 will be rotated during centrifugation and above a particle containing liquid for filtration in the sample chamber 60. During centrifugation, the liquid in the sample chamber 60 is urged against the internal wall 76 and

consequentially moves upwards along this wall 76 towards the filter medium 64;74 under the effect of centrifugal force exerted on it.

Centrifugation thus causes this liquid to be transported through the filter medium 64;74 and to travel as liquid filtrate towards the well 86 (see arrows in Fig. 5) where it is retained. After centrifugation liquid filtrate in the well 86 may be removed for assay, for example by using a hollow needle or pipette pressed through suitably formed regions 88 of the cap 78 above the well 86. Alternatively, the cap 78 may be removed from the tubular body 54 and upturned so that liquid filtrate from the well 86 flows to the region 90 of the cap 78 for access via the opening formed by internal surface 80.

[0033] A third embodiment of a filtration device 96 according to the present

invention is illustrated in Fig. 6 and comprises a tubular body 98 of circular cross section configured with an open top 100 and a closed bottom 104 so as to define a sample chamber 108 internal of the tubular body 98.

Optionally, a lip 102 is provided on the tubular body 98 which projects into the sample chamber 108, for example and as illustrated in the present embodiment projecting into the open top 100.

[0034] The filtration device 96 further comprises a cap 112 for closing the open top 100. In the present embodiment the cap 112 is formed as an off-centre ellipsoid having a portion 116 in which a well 118 is formed for receiving a liquid filtrate. When the cap 112 closes the open top 100, the portion 116 extends beyond the tubular body 98 along the major axis M of the ellipsoidal cap 122 in a plane containing the open top 100 and the well 118 extends downwards from an upper surface 117 in a direction along the body 98. The cap 112 is also provided with a number of through holes 120 between a lower surface 115 and the opposing upper surface 117. These through holes 120 are located in the cap 112 further away from an outer periphery 111 than the well 118 and are positioned to overlay the open top 100 proximal the lip 102 when the open top 100 is closed by the cap 112. A filter medium 114 (broken lines in Fig. 6) is affixed to the lower surface 115 to cover the through holes 120 in order to prevent flow of liquid from the sample chamber 108 into the well 118 without first passing through the filter medium 114. A cover 122, such as a metal or plastic foil overlays an upper surface 117 of the cap 112 which opposes the lower surface 115 and prevents egress of sample or of liquid filtrate during centrifugation.

[0035] In a further embodiment of the filtration device according to the present invention (not shown) the cap and tubular body may both be formed with a circular cross section. The cap is then preferably configured with an inclined floor to lead liquid filtrate from the liquid passageway preferentially to a well which is located at the bottom of the incline towards an outer periphery of the cap beyond the tubular body portion.

[0036] In use, the third embodiment of the filtration device 96 according to Fig. 6 is held upright for centrifugation, for example in a holder 36 of a centrifuge according to Fig. 3, so that the filter medium 114 lies in a plane

substantially perpendicular to a vertical rotational axis about which the filtration device 96 will be rotated during centrifugation and above a particle containing liquid for filtration retained in the sample chamber 108. During centrifugation liquid and particles in the sample chamber 108 move towards an inner surface 106 of the tubular body 98 and are moved upwards along this inner surface 106 towards the filter medium 114.

Particles, being relatively more massive, tend to lie outside the liquid and closer to the inner surface 106. As they are moved upwards the lip 102 of the body 98 acts as a barrier to reduce their contact with the filter medium 114. The liquid is left to be moved through the filter medium 114 and via the number of through holes 120 into the cap 112. The so formed liquid filtrate, due to the shape of the cap 112 and the location of the well 118, is preferentially flowed towards the well 118 in which it is retained after centrifugation. Access to this liquid filtrate is achieved through penetration of or removal of at least a section of the cover 122 above the well 118. It will be appreciated that after use the entire filtration device 2, 52, 96 may be disposed of or just the cap 12,78,112 replaced, particularly where the cap 12,112 is configured with the filter medium 20,114 affixed to a surface 18a, 115 to cover the liquid passageway 22,120.