Fluid-handling device, syringe adaptor and method for facilitating the flow of a mobile phase through a stationary phase

Abstract

Device (10) comprising: an outer barrel (12) having: a proximal end (18) comprising an opening (20) for an inner barrel (14), and a distal end (22) comprising a fluid outlet (24), and an inner barrel (14) slidably mounted inside the outer barrel (12). The inner barrel (14) comprises a proximal end (28) for receiving a cartridge (30) containing a stationary phase (32). The device (10) comprises a seal (38) on the inner barrel (14) or an inner surface (16) of the outer barrel (12). The seal (38) creates an internal volume (40) between the barrels at the distal end (22) of the outer barrel (12). Sliding the inner barrel (14) towards the proximal end (18) of the outer barrel (12) increases this internal volume (40). A fluid channel (42) extends through the inner barrel (14) connecting the fluid exit duct (34) of said cartridge (30) to said internal volume (40). The invention further relates to a method for facilitating the flow of a mobile phase through a stationary phase and to a syringe adapter.

Description

[0001] FLUID-HANDLING DEVICE, SYRINGE ADAPTOR AND METHOD FOR FACILITATING THE FLOW OF A MOBILE PHASE THROUGH A STATIONARY PHASE

[0002] Field of Invention

[0003] The present invention relates to fluid-handling device, such as a fluid-handling device that is suitable for sample preparation, such as by solid phase extraction (SPE). The present invention also relates to a method for facilitating the flow of mobile phase through a stationary phase. The present invention further relates to a syringe adaptor that is suitable for use with the outer barrel of an off-the-shelf syringe, i.e., a syringe made according to a standardized format, so that the syringe adapter may be used with equipment that is readily available to a user, to provide such a fluid-handling device, or for use in such a method.

[0004] Background of the Invention

[0005] In analytical chemistry, modification of a sample is usually required for techniques such as chromatography and mass spectroscopy. Solid phase extraction (SPE) is a sample preparation technique that uses the affinity of solutes dissolved or suspended in a liquid (known as the mobile phase) for a sorbent material through which the sample is passed (known as the stationary phase) to separate a mixture into desired and undesired components. SPE may also be used to separate reaction mixture components for preparative purposes.

[0006] The result is that either the desired analytes of interest or the undesired impurities in the sample are retained in the stationary phase. The portion that passes through the stationary phase is collected or discarded, depending on whether it contains the desired analytes or undesired impurities. If the portion retained on the stationary phase includes the desired analytes, they can then be removed from the stationary phase for collection in an additional step, in which the stationary phase is rinsed with an appropriate eluent.

[0007] The stationary phase is most commonly contained in a cartridge, such as a sorbent material-packed syringe, which can be mounted on an extraction manifold. The manifold allows multiple samples to be batch processed by holding several SPE cartridges in place and allowing for an equal number of samples to pass through them simultaneously. Most SPE manifolds are equipped with a vacuum port that is connected to a vacuum pump. A vacuum is namely applied to control the movement of the mobile phase through the stationary phase in each cartridge, by pulling the mobile phase through the stationary phase at a desired flow rate. The analytes are collected in sample tubes inside or below the manifold after they pass through the stationary phase.

[0008] Description of the Invention

[0009] The present invention concerns a fluid-handling device, such as a fluid-handling device that is suitable for sample preparation.

[0010] In a first aspect of the invention there is provided a fluid-handling device comprising the features recited in Claim 1.

[0011] The fluid-handling device comprises an outer barrel having an inner surface, a proximal end comprising an opening adapted to accommodate an inner barrel, and a distal end comprising a fluid outlet. The inner barrel is adapted to be slidably mounted inside the outer barrel and comprises an outer surface, a proximal end for receiving a cartridge that contains a stationary phase and has a fluid exit duct, and a distal end. A seal is arranged on the inner barrel whereby the seal is adapted to slidably engage the inner surface of the outer barrel to create an internal volume between the inner barrel and the outer barrel at the distal end of the outer barrel. Alternatively, a seal is arranged on the inner surface of the outer barrel, whereby the seal is adapted to slidably engage the outer surface of the inner barrel to create an internal volume between the inner barrel and the outer barrel at the distal end of the outer barrel. A sliding movement of the inner barrel through the outer barrel in a direction towards the opening at the proximal end of the outer barrel increases said internal volume. The inner barrel further comprises a fluid channel that extends from the proximal end of the inner barrel to the distal end of the inner barrel such that the fluid channel is adapted to fluidly connect the fluid exit duct of said cartridge to said internal volume.

[0012] In use, the fluid outlet of the outer barrel of the fluid-handling device is closed. The fluid outlet may be closed in any suitable way, such as by means of a valve, by a check valve, by connecting the fluid outlet of the outer barrel of the fluid-handling device to a fluid container, such as a vial, in a fluid-tight manner, or by merely temporarily blocking the fluid outlet. The sliding movement of the inner barrel through the outer barrel in a direction towards the opening at the proximal end of the outer barrel will then increase said internal volume and thereby create a negative pressure that draws a mobile phase that has been loaded into the cartridge, through the stationary phase, out of the cartridge's fluid exit duct, along the fluid channel that extends through the inner barrel and into the internal volume at the distal end of the outer barrel for subsequent controlled release, or for direct release into a fluid container, such as a vial, that is fluidly connected to the fluid outlet of the outer barrel of the fluid-handling device.

[0013] Using such a fluid-handling device eliminates the need for a vacuum pump since a user of the device can control the flow of a mobile phase through a stationary phase by moving the inner barrel of the fluid-handling device with respect to the outer barrel to achieve a desired flow rate.

[0014] The fluid-handling device according to the present invention provides several advantages over such processes in which a vacuum pump is required. It does not require a long time to reach a desired ultimate pressure. The equipment needed to provide a vacuum is much simpler and less expensive to produce, it requires less space, and is less susceptible to wear and damage than vacuum systems according to the prior art. It may be quickly and simply dismantled for cleaning, maintenance, or repair work, or between sample preparation process steps, thereby reducing the cost and complexity of the process and the time in which it can be carried out. There is no risk of cross contamination with other samples since each cartridge is isolated from other cartridges. Furthermore, a mobile phase may be made to flow through a stationary phase at any desired flow rate, and the flow rate may be quickly and easily changed while the mobile phase is flowing through the stationary phase.

[0015] According to an embodiment, the fluid-handling device comprises at least one of the following: a one-way valve, such as a duckbill valve, or a valve that is adapted to selectively open or close the fluid outlet at the distal end of the outer barrel.

[0016] According to an embodiment, the fluid-handling device comprises at least one check valve adapted to prevent a backward flow of fluid from the internal volume into the fluid channel of the inner barrel. Such a one-way valve may be used to prevent back flushing if a counter pressure is created in the internal volume. A check valve may be located at a distal end of the inner barrel and / or at a proximal end of the inner barrel.

[0017] According to an embodiment, the fluid-handling device comprises at least one filter that is adapted to filter fluid as it passes through the fluid-handling device. At least one filter may be provided as a filter cartridge that is adapted to be connected to the fluid-handling device, such as by inserting into the outer barrel of the fluid-handling device. According to an embodiment, the fluid-handling device comprises a connector at the distal end of the outer barrel which is adapted to receive a corresponding connector of a fluid container, such as a vial, for receiving fluid from the internal volume and to fluidly connect the fluid outlet at the distal end of the outer barrel with the fluid container. Preferably, the connector is adapted to connect the fluid-handling device to the fluid container in a fluid-tight manner, whereby the inner volume of the fluid container may constitute part of the internal volume in which a negative pressure is created.

[0018] According to an embodiment, the fluid-handling device comprises a connector at a proximal end of the outer barrel which is adapted to receive said cartridge or a corresponding connector of said cartridge and to fluidly connect the fluid exit duct of the cartridge with the fluid channel of the inner barrel. Preferably, the connector is adapted to releasably or non-releasably connect the cartridge to the fluid container in a fluid-tight manner.

[0019] According to an embodiment, the inner barrel comprises a luer lock connector, which is adapted to receive a corresponding luer lock connector of said cartridge to connect at the fluid exit duct of the cartridge to the inner barrel and fluidly connect the fluid exit duct with the fluid channel of the inner barrel.

[0020] According to an embodiment, the cartridge is a solid phase extraction (SPE) cartridge or disk.

[0021] According to an embodiment, at least one of the following comprises or consists essentially of polyethylene or polypropylene: the outer barrel, the inner barrel, the seal.

[0022] According to an embodiment, at least one part of the outer surface of the inner barrel comprises a material that has a higher Young's Modulus (i.e., is stiffer) than at least one part of the inner surface of the outer barrel, and at least one part of the outer surface of the inner barrel has a transverse cross-section that is slightly greater (i.e., up to 0.1 mm greater, or up to 0.2 mm greater) than the transverse cross-section of at least one part of the inner surface of the outer barrel, whereby a tight fit between at least one part of the inner barrel and at least one part of the outer barrel may be achieved. According to an embodiment, the inner barrel and the outer barrel are cylindrical although the inner barrel and the outer barrel may be of any desired uniform or non- uniform shape and have any desired uniform or non-uniform cross-section.

[0023] In a second aspect of the invention there is provided a method for facilitating the flow of a mobile phase through a cartridge containing a stationary phase, such as a solid phase extraction (SPE) cartridge. The method comprises providing a fluid-handling device according to any of the embodiments of the invention, connecting at least a fluid exit duct of the cartridge containing a stationary phase to the fluid-handling device, closing the fluid outlet at the distal end of the outer barrel, and moving the inner barrel through the outer barrel in a direction towards the opening at the proximal end of the outer barrel to increase the internal volume between the inner barrel and the outer barrel at the distal end of the outer barrel and thereby create a negative pressure that draws a mobile phase contained in or loaded into the cartridge through the stationary phase, out of the fluid exit duct of the cartridge, through the fluid channel in the inner barrel, and into the internal volume.

[0024] The method according to the present invention provides several advantages over methods according to the prior art in which vacuum pumps are used. It is simple to carry out and more environmentally friendly, it results in a quieter and cleaner work environment and constitutes less of a working environment risk to users. Additionally, it can be carried out in the field, and samples can be collected and isolated in the cartridge in which they will subsequently be processed.

[0025] Preferably, the distal end of the inner barrel is moved so that it located as closely as possible to the distal end of the outer barrel before the inner barrel is moved through the outer barrel in a direction towards the opening at the proximal end of the outer barrel so that the initial inner volume between the inner barrel and the outer barrel is as small as possible.

[0026] Preferably, the fluid-handling device comprises stopping means to prevent the inner barrel from being pulled out of the outer barrel via the opening at the proximal end of the outer barrel.

[0027] The steps of connecting at least a fluid exit duct of the cartridge containing a stationary phase to the fluid-handling device and closing the fluid outlet at the distal end of the outer barrel may be carried out in any order. According to an embodiment, once fluid has been collected in the internal volume, the method further comprises opening the fluid outlet at the distal end of the outer barrel and moving the inner barrel through the outer barrel in a direction away from the opening at the proximal end of the outer barrel to expel fluid from the internal volume via the fluid outlet at the distal end of the outer barrel of the fluid-handling device.

[0028] According to an embodiment, at least one of the following components is manufactured using injection moulding, 3D-printing, or turning: the outer barrel, the inner barrel, the seal.

[0029] In a third aspect of the invention there is provided a syringe adaptor for use as an inner barrel in a fluid-handling device or method according to any of the embodiments described herein, wherein the outer barrel of the fluid-handling device is constituted by an outer barrel of an off-the shelf syringe. This means that a custom-made outer barrel does not need to be manufactured for use with the syringe adaptor.

[0030] The syringe adapter may namely be used in place of the plunger of an off-the-shelf syringe to convert the off-the-shelf syringe into a fluid-handling device according to the present invention. The syringe adaptor is adapted to comprise all of the features of an inner barrel of a fluid-handling device according to any of the embodiments of the invention described herein. The syringe adapter is arranged to be slidably mounted inside the outer barrel of the off-the-shelf syringe and comprises a proximal end and a distal end. The syringe adaptor also comprises a seal that is adapted to slidably engage an inner surface of the outer barrel of the off-the-shelf syringe to create an internal volume between the syringe adaptor and the outer barrel of the off-the-shelf syringe, whereby a sliding movement of the syringe adaptor through the outer barrel of the off-the-shelf syringe in a direction away from a fluid outlet of the outer barrel of the off-the-shelf syringe increases said internal volume. The syringe adaptor further comprises a fluid channel that extends through the syringe adaptor from the proximal end of the syringe adaptor to the distal end of the syringe adaptor such that the fluid channel is adapted to fluidly connect a fluid exit duct of a cartridge containing a stationary phase to said internal volume. The outer barrel of the off-the-shelf syringe becomes a chamber having an internal volume in which a negative pressure is created by a user to control the flow of a mobile phase through the stationary phase of a cartridge.

[0031] All embodiments of the invention and particular features mentioned herein may be taken in isolation or in combination with any other embodiments and / or particular features mentioned herein (hence describing more particular embodiments and particular features as disclosed herein) without departing from the disclosure of the invention.

[0032] Definitions

[0033] Unless otherwise indicated, 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 invention pertains.

[0034] As used herein, the term fluid, means a liquid or a gas or a combination of both, a mixture of liquids, a mixture of gases, or a mixture of liquids and gases.

[0035] As used herein, the term "for sample preparation" means for use in any technique in which a mobile phase is required to pass through a stationary phase. The mobile phase may have a volume of up to 5 ml, from 1-5 ml, 5-10 ml, 10-15 ml, 15-20 ml, 20-25 ml, 25-30 ml, 30-35 ml, 35-40 ml, 40-45 ml, 45-50 ml, 50-60 ml, 60-70 ml, 70-80 ml, 80-90 ml, 90-100 ml, 100-150 ml, 150-200 ml, 200 ml or more.

[0036] As used herein, the term "stationary phase" means any solid object, such as a filter or a sieve, or any solid substance, or a plurality of solid objects or solid substances, that has / have a property of collecting one or more types of molecules or particles of another substance or substances by means of any chemical reaction or physical interaction between the stationary phase and a mobile phase that passes through the stationary phase. The stationary phase may comprise sorbent material, such as a solid adsorbent and / or a solid absorbent for collecting one or more types of molecules or particles of another substance or substances by means of sorption, i.e., adsorption and / or adsorption. The stationary phase may be provided in any suitable solid form or forms, either as a single component, such as a column, disc, or layer of material of any suitable size and shape, or as a plurality of components, such as a plurality of spheres of material.

[0037] As used herein, the term "cartridge" means any case or container that holds the stationary phase or allows it to be connected to the fluid-handling device described herein, such as a tube, ring or frame, which may be inserted into, or connected to, or placed into contact with a fluid-handling device or syringe adaptor according to any embodiment described herein, or used in a method according to any embodiment described herein. A cartridge may contain a mobile phase, or a mobile phase may be loaded into the cartridge in any suitable manner which ensures that the mobile phase passes through the stationary phase.

[0038] As used herein, the term "seal" means one or more sealing components, such as O- rings, or one or more sealing substances that is / are used to join the outer surface of the inner barrel to the inner surface of the outer barrel so as to prevent fluid, i.e., to prevent liquid and gas, from passing therebetween. The seal allows an enclosed internal volume to be provided within the fluid-handling device when the fluid outlet at the distal end of the outer barrel is closed so that a negative pressure may be created in the internal volume. A seal may be integrally formed with the inner barrel or the outer barrel or may be a separate component that is mounted on the inner barrel or the outer barrel or on any other suitable part of the fluid-handling device.

[0039] As used herein, the term "connector" means any component that is adapted to link any part or parts of a first component (such as a cartridge or a fluid container, such as a vial) to a part of the fluid-handling device (such as to the inner barrel or the outer barrel) in a secure and leak-free manner. A connector may comprise a male of female luer lock fitting or a luer slip fitting, or any other connecting means that is adapted to link corresponding parts in any suitable releasable or non-releasable way, such as by means of a friction fit, threaded connection, or mechanical lock. A connector may be integrally formed with part of the fluid-handling device or may consist essentially of one or more separate components that is / are mounted on part of the fluid-handling device.

[0040] As used herein, the term "a fluid channel" means any conduit or conduits that allow a fluid to flow from the fluid exit duct of a cartridge to the internal volume in any desired manner. A fluid-handling device may comprise one or more branched or un-branched fluid channels. The cross-sectional shape and area of a fluid channel need not necessarily be uniform.

[0041] As used herein, the term "comprises" will take its usual meaning in the art, namely indicating that the component includes but is not limited to the relevant features (i.e., including, among other things). As such, the term "comprises" will include references to the component consisting essentially of the relevant feature(s). For the avoidance of doubt, the term "comprises" will also include references to the component "consisting essentially of" (and in particular "consisting of") the relevant feature(s). As used herein, unless otherwise specified the terms "consists essentially of" and "consisting essentially of" will refer to the relevant component being formed of at least 80% (e.g., at least 85%, at least 90%, or at least 95%, such as at least 99%) of the specified substance(s), according to the relevant measure (e.g., by weight thereof). The terms "consists essentially of" and "consisting essentially of" may be replaced with "consists of" and "consisting of", respectively.

[0042] The invention is illustrated by way of the following examples, which are not intended to be limiting on the general scope of the invention.

[0043] Description of the Figures

[0044] Figure 1: Schematically shows a fluid-handling device according to an embodiment of the invention, and

[0045] Figure 2: Schematically shows steps of a method according to an embodiment of the invention.

[0046] The drawings have not necessarily been drawn to scale and the dimensions of certain features may have been exaggerated for the sake of clarity.

[0047] Description of embodiments

[0048] Figure 1A shows an outer barrel 12 of a fluid-handling device 10 according to an embodiment of the invention. Figure IB shows an inner barrel 14 of the fluid-handling device 10. Figure 1C shows the fluid-handling device 10 once the inner barrel 14 has been slidably mounted inside the outer barrel 12. In the illustrated embodiment both the outer barrel 12 and the inner barrel 14 are cylindrical. However, the outer barrel 12 and the inner barrel 14 may have any suitable shape and do not necessarily have to have the same shape.

[0049] The outer barrel 12 has an inner surface 16, a proximal end 18 comprising an opening 20 adapted to accommodate the inner barrel 14, and a distal end 22 comprising a fluid outlet 24.

[0050] The inner barrel 14 comprises an outer surface 26, a proximal end 28 for receiving a cartridge 30 (shown in figure 2). The cartridge 30 contains a stationary phase 32 and has a fluid exit duct 34, and a distal end 36. In the illustrated embodiment the cartridge 30 is a solid phase extraction (SPE) cartridge containing SPE stationary phase having an affinity to certain functional groups of atoms or for facilitating a chemical or physical process such as ion exchange or sieving.

[0051] The fluid-handling device 10 comprises a seal 38 arranged on the outer surface 26 of the inner barrel 14 which is adapted to slidably engage the inner surface 16 of the outer barrel 12 to create an internal volume 40 between the inner barrel 14 and the outer barrel 12 at the distal end 22 of the outer barrel 12. Alternatively, a seal 38 may be arranged on the inner surface 16 of the outer barrel 12 which is adapted to slidably engage the outer surface 26 of the inner barrel 14 to create an internal volume 40 between the inner barrel 14 and the outer barrel 12 at the distal end 22 of the outer barrel 12, whereby a sliding movement of the inner barrel 14 through the outer barrel 12 in a direction towards the opening 20 at the proximal end 18 of the outer barrel 12 increases said internal volume 40.

[0052] The outer barrel 12, the inner barrel 14 and / or the seal may comprise or consist essentially of any suitable material, such as polyethylene or polypropylene and need not necessarily be made from the same material. The outer barrel 12, the inner barrel 14 and the seal may be manufactured using any suitable method, such as injection moulding, 3D-printing, or turning. At least part of the seal 38 may be manufactured from any suitable sealing material, such as any material commonly used as a plunger seal in syringes. For example, the seal 38 may comprise or consist essentially of an elastomer, a thermoplastic elastomer, ultra-high-molecular-weight (UHMW), polyethylene or Polytetrafluoroethylene (PTFE).

[0053] The seal 38 may comprise one or more sealing components, one or more of which may be integrally formed with the outer barrel 12, or with the inner barrel 14, or with both the outer barrel 12 and the inner barrel 14. In the illustrated embodiment the seal 38 is an O-ring.

[0054] The inner barrel 14 comprises a fluid channel 42 that extends from the proximal end 28 of the inner barrel 14 to the distal end 36 of the inner barrel 14 such that the fluid channel 42 is adapted to fluidly connect the fluid exit duct 34 of said cartridge 30 to said internal volume 40.

[0055] The fluid-handling device 10 may comprise a valve 44 (shown in Figure 2) that is adapted to selectively open or close the fluid outlet 24 at the distal end 22 of the outer barrel 12. The valve 44 may be a one-way valve that is adapted to allow fluid to flow out of the internal volume 40 and to prevent fluid from entering the internal volume 40 via the fluid outlet 24 at the distal end 22 of the outer barrel 12.

[0056] Optionally, the inner barrel 14 of the fluid-handling device 10 comprises an insertable or integrated connector 46, such as a female luer lock connector that is adapted to receive a cartridge 30 or a corresponding connector of said cartridge, such as a male luer lock connector to connect at least the fluid exit duct 34 of the cartridge 30 to the inner barrel 14 of the fluid-handling device 10 and fluidly connect the fluid exit duct 34 with the fluid channel 42 of the inner barrel 14.

[0057] According to an embodiment an inner barrel 14 may comprise at least one check valve (not shown) adapted to prevent the backward flow of fluid from the internal volume 40 into the fluid channel 42 of the inner barrel 14. At least one check valve may be used to prevent back flushing if a counter pressure is created in the internal volume 40. A check valve may be located at a proximal end 28 and / or at a distal end 36 of the fluid channel 42 of the inner barrel 14.

[0058] According to an embodiment a fluid-handling device 10 comprises at least one filter, which may be provided by means of a filter cartridge that is configured to be connected to the fluid-handling device 10. The, or each filter is adapted to filter fluid 48 as it passes through the fluid-handling device 10. A filter may be configured to be connected to the proximal end 18 of the outer barrel 12, inserted into the outer barrel 12, connected to the proximal end 28 and / or connected to the distal end 36 of the inner barrel 14.

[0059] The present invention also concerns a syringe adaptor for use as an inner barrel 14 in a fluid-handling device or method according to any embodiment described herein. In such a case the outer barrel 12 of the fluid-handling device is constituted by an outer barrel of an off-the shelf syringe, whereby the syringe adaptor is custom-made to fit inside the outer barrel of an existing off-the-shelf syringe. The syringe adapter thereby replaces the plunger of an off-the-shelf syringe. A fluid-handling device comprising such a syringe adaptor and an outer barrel of an off-the shelf syringe look the same as the fluid-handling device 10 shown in Figures 1 and 2 and will function in the same way.

[0060] Figure 2 schematically shows steps of a method for facilitating the flow of a mobile phase 48 through a cartridge 30, such as a solid phase extraction (SPE) cartridge, containing a stationary phase 32 in the form of SPE material according to an embodiment of the invention. A cartridge 30 may comprise one or more frits 33 to retain the stationary phase 32. A frit 33 may comprise porous plastic or metal.

[0061] Figure 2 shows how a fluid-handling device 10 or syringe adapter (inner barrel 14) according to the present invention may be used to facilitate the flow of a mobile phase 48 through a cartridge 30.

[0062] Figure 2a shows an SPE cartridge 30. A sample containing an analyte (represented by smaller circles within the stationary phase 32) and some sample matrix compounds (represented by the largest circles within the stationary phase 32) has been loaded into the cartridge 30 via an opening 35 in the cartridge 30 and has permeated at least part of the stationary phase 32 inside the cartridge 30.

[0063] The method comprises providing a fluid-handling device 10 comprising the features recited in Claim 1, such as the fluid-handling device 10 illustrated in Figure 1C or Figure 2b.

[0064] Preferably, the fluid-handling device 10 comprises a valve 44. The valve 44 may be a manual valve or a check valve. The method also comprises releasably or non-releasably connecting at least a fluid exit duct 34 of a cartridge 30 containing a stationary phase 32 to the fluid-handling device 10.

[0065] The fluid channel 42 that extends through the inner barrel 14 of the fluid-handling device does not necessarily need to extend in a co-linear manner with respect to the fluid exit duct 34 of the cartridge and / or the fluid outlet 44 of the outer barrel of the fluid-handling device 10 but can have any desired extension through the inner barrel 14 as long as the ends of the fluid channel 42 are adapted to fluidly connect the fluid exit duct 34 of the cartridge 30 to the internal volume 40.

[0066] Figure 2c shows the fluid-handling device 10 with the distal end 36 of the inner barrel 14 located at the distal end 22 of the outer barrel 12 whereby the initial internal volume 40 created between the inner barrel 14 and the outer barrel 12 by means of the seal 38 is as small as possible. The inner barrel 14 does not necessarily have to be located in this position at the start of the method.

[0067] The method comprises the step of loading a mobile phase 48 into the cartridge 30, as shown in Figure 2d at any suitable time. The mobile phase 48 may be a wash solvent to remove interferents from the cartridge 30, or a solvent for eluting an analyte from the cartridge 30.

[0068] The method comprises closing the fluid outlet 24 at the distal end 22 of the outer barrel 12, by means of a valve 44 for example, as shown in Figure 2e. The fluid outlet 24 may be closed at any suitable time before the inner barrel 14 of the fluid-handling device 10 is moved through the outer barrel 12 of the fluid-handling device 10 in a direction towards the opening 20 at the proximal end 18 of the outer barrel 12. For example, the fluid outlet 24 may be closed before or after a cartridge 30 has been connected to the inner barrel 14 of the fluid-handling device 10, or before or after a mobile phase 48 has been added to the cartridge 30.

[0069] Once the fluid outlet 24 at the distal end 22 of the outer barrel 12 has been closed and a mobile phase 48 has been added to the cartridge 30, the inner barrel 14 of the fluidhandling device 10 is moved through the outer barrel 12 of the fluid-handling device 10 in a direction towards the opening 20 at the proximal end 18 of the outer barrel 12 (i.e., vertically upwards in Figure 2d) to increase said internal volume 40. This movement of the inner barrel 14 creates a negative pressure within the internal volume 40, the fluid channel 42 and the fluid exit duct 34 of the cartridge 30, which draws the mobile phase 48 contained in the cartridge 30 through the stationary phase 32, out of the fluid exit duct 34 of the cartridge, through the fluid channel 42 in the inner barrel 42, and into the internal volume 40, as shown in Figure 2e.

[0070] Figure 2f shows the fluid-handling device 10 with the distal end 36 of the inner barrel 14 located at the proximal end 18 of the outer barrel 12 whereby the internal volume 40 created between the inner barrel 14 and the outer barrel 12 by means of the seal 38 has reached a maximum. However, the inner barrel 14 of the fluid-handling device 10 need not necessarily be moved until the inner barrel 14 reaches such a position but only needs to be moved until a desired flow rate has fluid through the fluid-handling device 10 has been achieved or until a desired volume of liquid 48 has been drawn into the internal volume 40 at the distal end 22 of the outer barrel 12.

[0071] Preferably, the outer barrel 12 is dimensioned so as to allow a user to create a maximum internal volume 40 that is equal to or greater than the volume of mobile phase 48 that is loaded into the cartridge 40.

[0072] The outer barrel 12 may be dimensioned to allow a user to create a maximum internal volume 40 that is equal to, or at least twice, or at least three times, or at least four times, or at least five times, or at least six times, or at least seven times, or at least eight times, or at least nine times, or at least ten times, the volume of the mobile phase 48 that is loaded into the cartridge 40.

[0073] The outer barrel 12 may be dimensioned so as to allow a user to create a maximum internal volume 40 of up to 5 ml, from 1-5 ml, 5-10 ml, 10-15 ml, 15-20 ml, 20-25 ml, 25-30 ml, 30-35 ml, 35-40 ml, 40-45 ml, 45-50 ml, 50-60 ml, 60-70 ml, 70-80 ml, 80-90 ml, 90-100 ml, 100-150 ml, 150-200 ml, 200 ml or more.

[0074] For example, a mobile phase 48 may have a volume of 5-10 ml and the outer barrel 12 may be dimensioned to allow a user to create an internal volume 40 of 20 ml.

[0075] The method may further comprise opening the fluid outlet 24 at the distal end 22 of the outer barrel 12, by means of the valve 44 for example, and moving the inner barrel 14 through the outer barrel 12 in a direction away from the opening 20 at the proximal end 18 of the outer barrel 12 towards the fluid outlet 24 of the outer barrel 12 (vertically downwards in Figure 2g) to expel fluid 48 from the internal volume 40 via the fluid outlet 24 at the distal end 22 of the fluid-handling device 10 into a fluid container, such as a vial. The fluid container may be connected to the distal end of the fluid-handling device 10, in a fluid tight manner for example.

[0076] Alternatively, a fluid container may be connected to the fluid outlet 24 of the outer barrel of the fluid-handling device in a fluid-tight manner before the inner barrel 14 is moved through the outer barrel 12 in a direction towards the opening 20 in the outer barrel, whereby the internal volume of the fluid container constitutes part of the internal volume 40 in which a negative pressure is created.

[0077] The entire method, or the method steps shown in figures 2d to 2g may be repeated, either using the same mobile phase 48 or one or more different mobile phases 48, if necessary.

[0078] A fluid-handling device 10, syringe adaptor (inner barrel 14) or a method described herein may be used to simplify complex sample matrices, to purify compounds of interest, to reduce ion suppression in mass spectrometry applications, to fractionate complex mixtures for analysis by classification, to concentrate analytes present at low levels, or to filter or sieve a fluid. The fluid-handling device 10 or syringe adaptor (inner barrel 14) according to the present invention may be re-used depending on whether cleaning of the fluid-handling device 10 or syringe adaptor (inner barrel 14) is desirable and possible. Preferences and options for a given aspect, feature or parameter of the invention should, unless the context indicates otherwise, be regarded as having been disclosed in combination with any and all preferences and options for all other aspects, features and parameters of the invention. For example, preferences and options disclosed in relation to an inner barrel 14 of a fluid-handling device 10 according to the present invention should be regarded as having been disclosed in combination with the syringe adaptor according to the present invention, and vice versa.

Claims

CLAIMS1. Fluid-handling device (10) comprising: an outer barrel (12) having: o an inner surface (16), o a proximal end (18) comprising an opening (20) adapted to accommodate an inner barrel (14), and o a distal end (22) comprising a fluid outlet (24), and- an inner barrel (14) that is adapted to be slidably mounted inside the outer barrel (12), wherein the inner barrel (14) comprises:- an outer surface (26),- a proximal end (28) for receiving a cartridge (30) containing a stationary phase (32) and having a fluid exit duct (34), and- a distal end (36),- a seal (38) arranged on the inner barrel (14) which is adapted to slidably engage the inner surface (16) of the outer barrel (12) to create an internal volume (40) between the inner barrel (14) and the outer barrel (12) at the distal end (22) of the outer barrel (12), or a seal (38) arranged on the inner surface (16) of the outer barrel (12) which is adapted to slidably engage the outer surface (26) of the inner barrel (14) to create an internal volume (40) between the inner barrel (14) and the outer barrel (12) at the distal end (22) of the outer barrel (12), whereby a sliding movement of the inner barrel (14) through the outer barrel (12) in a direction towards the opening (20) at the proximal end (18) of the outer barrel (12) increases said internal volume (40), wherein the inner barrel (14) comprises:- a fluid channel (42) that extends from the proximal end (28) of the inner barrel (14) to the distal end (36) of the inner barrel (14) such that the fluid channel (42) is adapted to fluidly connect the fluid exit duct (34) of said cartridge (30) to said internal volume (40).

2. The fluid-handling device (10) according to Claim 1, wherein it comprises a oneway valve (44) or a valve (44) that is adapted to selectively open or close the fluid outlet (24) at the distal end (22) of the outer barrel (12), and / or at least one check valve adapted to prevent a backward flow of fluid from the internal volume (40) into the fluid channel (42), and / or at least one filter adapted to filter fluid (48) as it passes through the fluid-handling device (10).

3. The fluid-handling device (10) according to Claim 1 or 2, wherein it comprises a connector that is adapted to receive a corresponding connector of a fluid container for receiving fluid (48) from the internal volume (40) and to fluidly connect the fluid outlet (24) at the distal end (36) of the outer barrel (12) with the fluid container.

4. The fluid-handling device (10) according to any preceding claim, wherein the inner barrel (14) comprises a connector, such as a luer lock connector, which is adapted to receive said cartridge (30) or a corresponding connector of said cartridge (30) to connect at least the fluid exit duct (34) of the cartridge (30) to the inner barrel (14) and to fluidly connect the fluid exit duct (34) to the fluid channel (42) of the inner barrel (14).

5. The fluid-handling device (10) according to any preceding claim, wherein at least one of the following comprises polyethylene or polypropylene: the outer barrel (12), the inner barrel (14), the seal (38).

6. The fluid-handling device (10) according to any preceding claim, wherein at least one part of the outer surface (26) of the inner barrel (14) comprises a material that has a higher Young's Modulus than at one least part of the inner surface )16 of the outer barrel (12), and the at least one part of the outer surface (26) of the inner barrel (14) has a transverse cross-section that is up to 0.2 mm greater than the transverse cross-section of the at least one part of the inner surface (16) of the outer barrel (12).

7. A method for facilitating the flow of mobile phase (48) through a cartridge (30) containing a stationary phase (32) and having a fluid exit duct (34), such as a solid phase extraction (SPE) cartridge (30), wherein the method comprises: providing a fluid-handling device (10) that comprises: o an outer barrel (12) having:■ an inner surface (16),■ a proximal end (18) comprising an opening (20) adapted to accommodate an inner barrel (14), and■ a distal end (22) having a fluid outlet (24),- an inner barrel (14) that is adapted to be slidably mounted inside the outer barrel (12) and that comprises:- an outer surface (26),- a proximal end (28) for receiving the cartridge (30), and- a distal end (36),- a seal (38) arranged on the inner barrel (14) which is adapted to slidably engage the inner surface (16) of the outer barrel (12) to create an internal volume (40) between the inner barrel (14) and the outer barrel (12) at the distal end (22) of the outer barrel (12), or a seal (38) arranged on the inner surface (16) of the outer barrel (12) which is adapted to slidably engage the outer surface (26) of the inner barrel (14) to create an internal volume (40) between the inner barrel (14) and the outer barrel (12) at the distal end (22) of the outer barrel (12), whereby a sliding movement of the inner barrel (14) through the outer barrel (12) in a direction towards the opening (20) at the proximal end (18) of the outer barrel (12) increases said internal volume (40), wherein the inner barrel (14) comprises:- a fluid channel (42) that extends from the proximal end (28) of the inner barrel (14) to the distal end (36) of the inner barrel (14) such that the fluid channel (42) is adapted to fluidly connect the fluid exit duct (34) of said cartridge (30) to said internal volume (40),- connecting at least a fluid exit duct (34) of the cartridge (30) containing a stationary phase (32) to the fluid-handling device (10):- closing the fluid outlet (24) at the distal end (22) of the outer barrel (12),- moving the inner barrel (14) through the outer barrel (12) in a direction towards the opening (20) at the proximal end (18) of the outer barrel (12) to increase said internal volume (40) and to thereby create a negative pressure that draws mobile phase (48) contained in the cartridge (30) through the stationary phase (32), out of the fluid exit duct (34) of the cartridge (30), through the fluid channel (42) in the inner barrel (14), and into the internal volume (40).

8. The method according to Claim 7, wherein the method further comprises:- opening (20) the fluid outlet (24) at the distal end (22) of the outer barrel (12), and moving the inner barrel (14) through the outer barrel (12) in a direction away from the opening (20) at the proximal end (18) of the outer barrel (12) to expel mobile phase from the internal volume (40) via the fluid outlet (24) at the distal end (22) of outer barrel (12) of the fluid-handling device (10).

9. The method according to Claim 7 or 8, wherein at least one of the following is manufactured using injection moulding, 3D-printing, or turning : the outer barrel (12), the inner barrel (14), the seal (38).

10. A syringe adaptor for use as an inner barrel (14) in a fluid-handling device (10) or method according to any preceding claim, wherein the outer barrel (12) of the fluid-handling device (10) is constituted by an outer barrel (12) of a syringe, wherein the syringe adaptor is adapted to be slidably mounted inside the outer barrel (12) of the syringe and comprises:- a proximal end (18) and- a distal end (22),- a seal (38) that is adapted to slidably engage an inner surface (16) of the outer barrel (12) of the syringe to create an internal volume (40) between the syringe adaptor and the outer barrel (12) of the syringe, whereby a sliding movement of the syringe adaptor through the outer barrel (12) of the syringe in a direction away from a fluid outlet (24) of the outer barrel (12) of the syringe increases said internal volume (40), and- a fluid channel (42) that extends through the syringe adaptor from the proximal end (28) of the syringe adaptor to the distal end (36) of the syringe adaptor such that the fluid channel (42) is adapted to fluidly connect a fluid exit duct (34) of a cartridge (30) containing a stationary phase (32) to said internal volume (40).

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