WO2016050753A1

WO2016050753A1 - Microfluidic vent structure

Info

Publication number: WO2016050753A1
Application number: PCT/EP2015/072390
Authority: WO
Inventors: André DO ROSÁRIO MAGALHÃES; Ricardo MANUEL MARQUES CALEIRO CABEÇA; Andreia ANDRADE DOS SANTOS; Sandro MIGUEL PINTO BORDEIRA
Original assignee: Biosurfit S.A.
Priority date: 2014-09-29
Filing date: 2015-09-29
Publication date: 2016-04-07

Abstract

A liquid handling device arranged for capillary flow of a sample from a liquid receiving structure to a downstream liquid handling structure is provided. The downstream liquid handling structure is vented to the liquid receiving structure via a liquid retaining structure configured to prevent clogging of the vent path. The vent path includes an airspace between the liquid and a lid for sealing the liquid receiving structure.

Description

MICROFLUIDIC VENT STRUCTURE

The present invention relates to a liquid handling device in which liquid flows by means of capillary effect and, specifically, although not exclusively, to such a liquid handling device for handling a blood sample.

A variety of driving mechanisms for driving liquid flows in a liquid handling device, specifically a microfluidic liquid handling device, exist, for example, using electrophoretic, centrifugal forces and capillary forces. Capillary forces are advantageous as driving forces in microfluidic devices in that they do not require external driving forces to be applied, as would be the case with electrophoretically driven flow, and do not require movement of the liquid handling device to help the flow, as would be the case with centrifugally driven flow. Further, controlled flow can be achieved with lower flow rates than, for example, in most centrifugal flow applications. Microfluidic devices with centrifugally driven flow are therefore particularly suitable to applications where the sample is to be imaged during flow. However, given the relatively low magnitude of capillary forces, microfluidic devices employing capillary driven flow require careful design to ensure gas pressures within the device can equilibrate so as not to impede flow. While it is necessary to ensure efficient pressure equilibration around the device, it is also desirable for the microfluidic device to be environmentally sealed to a substantial degree from surrounding atmosphere to prevent or reduce the risk of spillage out of the device.

In some aspects of the invention, there is provided a liquid handling structure as defined in claim 1. Some other aspects of the invention provide a method as defined in claim 15. Optional features of embodiments of the invention are set out in the dependent claims.

In some embodiments, a device body defines a downstream liquid handling structure arranged to draw liquid from a liquid receiving structure by capillary effect. A liquid receiving structure defines an opening in the device body to receive a liquid sample. A vent structure enables gas displaced by liquid drawn from the liquid receiving structure to escape from the downstream liquid handling structure into the liquid receiving structure. In combination with the above, a lid is attached (for example by a flexible flap so that it can be opened and closed) or attachable to the device body to seal the liquid receiving structure. The lid may be sealed to the device body to seal the liquid receiving structure by an adhesive provided on the lid. For example, the adhesive may be covered by a thin film so that the lid can be sealed to the device body once the thin film has been removed. When the liquid receiving structure is filled with liquid and sealed by the lid, there is an air space between the lid and the liquid filling the liquid receiving structure. Displaced gas can flow from the vent structure to the air space to equilibrate pressures inside the device body. Advantageously, providing an air space between the lid and the liquid ensures efficient pressure equalisation by providing vented gas access over the entire liquid head.

In some embodiments, a liquid retaining structure is configured to provide a surface tension barrier to prevent ingress of liquid in the liquid receiving structure into the vent structure. The liquid retaining structure may be spaced away from an outer surface of the device body to retain liquid away from the lid. This ensures that a gap is maintained between the liquid retained by the liquid retaining structure and the lid. The outer surface of the device body may have a raised profile in a region surrounding the opening, to provide the airspace without requiring an increased thickness across the entire device body. A metering implement may be provided in combination with the above for metering a predefined volume of liquid into the liquid receiving chamber, so as to prevent overfilling. In some embodiments, the liquid retaining structure defines a channel having one or more sharp corners. For example, the channel may be formed by a plurality of features pointing into the channel to define the one or more sharp corners.

In some embodiments, the airspace may surround the opening when the liquid receiving structure is sealed with the lid. In this way, the provision of a well-defined airspace is facilitated. In some embodiments, this may be implemented by providing the airspace inside the lid, for example the lid may comprise a rim for sealing against the device body, which is spaced away from an opposed lid surface to define an airspace between the lid surface and the rim/device body.

In some embodiments, separate openings may be provided for the liquid retaining structure and vent structure. Connection between the openings may be via the lid. The airspace may surround both openings. Where the lid has a rim to define the airspace, the rim may be configured to encompass both openings.

In some embodiments, the device may be configured to handle blood samples.

Sealing the liquid receiving structure with the lid may seal the interior of the device body from gas exterior to the device body. Alternatively, in some embodiments, the vent structure is itself connected to atmospheric air surrounding the device so that venting is at least in part via the surrounding atmosphere, so that the interior of the device body is not isolated from the surrounding atmosphere when sealed but the risk of liquid spilling is still significantly reduced.

The downstream liquid handling structure may comprise a sample conduit with a detection zone in which liquid flowing in the sample conduit can be detected from outside the device body, for example the liquid sample can be imaged through a window in the device body, as it flows.

The vent structure may include one or more vent conduits connecting the downstream liquid handling structure downstream of the detection zone to the liquid receiving structure. The one or more vent conduits may connect the downstream liquid handling structure to the liquid receiving structure through the liquid retaining structure in relevant embodiments. The sample conduit may be coated with one or more dry reagents upstream of the detection zone. This is particularly advantageous in the case of a device for handling blood samples as the dry reagents may include lysing and staining agents, so that red blood cells are lysed and white blood cells are stained before reaching the detection zone. This enables white blood cells to be imaged in the detection zone.

In some embodiments, the devices body is configured for rotation about an axis to enable centrifugally driven liquid flow from the liquid receiving structure. For example, this enables a liquid sample, such as a blood sample, to be processed centrifugally subsequent to an imaging phase involving capillary flow. For example, the white blood cells may be imaged using capillary flow as described above and, subsequently, a haematocrit may be obtained for a remaining portion of the sample using centrifugal processing.

In some embodiments, the liquid handling device is a microfluidic liquid handling device. It will be understood that a microfluidic liquid handling device is a liquid handling device that has at least one liquid handling structure, such as a channel or a conduit, with a dimension less than 1 mm.

In some further embodiments, a method is provided for preparing a liquid handling device, for example a microfluidic liquid handling device or any liquid handling device as described above, to image a liquid sample as it flows in the liquid handling device. By way of example, the liquid sample may be a blood sample. The method involves introducing a liquid sample into a liquid receiving structure of the liquid handling device. This causes capillary flow of the liquid sample in a downstream liquid handling structure of the liquid handling device. The liquid receiving structure is sealed with a lid, such that an airspace is created between the liquid sample and the lid. Gas displaced from the downstream liquid handling structure is vented to the airspace.

Some specific embodiments are now described, by way of example only and with reference to the accompanying drawings, in which: Figure 1 illustrates a capillary microfluidic liquid handling device;

Figure 2 illustrates a cross-sectional view of the device along line B (see figures 4, 5 and 6);

Figure 3 illustrates a portion of the cross-section illustrated in Figure 2 in an enlarged view;

Figures 4, 5 and 6 illustrates cross-sectional views along line A (see figures 1 and

2) in accordance with respective embodiments;

Figure 7 illustrates a perspective view of a lid illustrated in Figure 6;

Figures 8 to 13 illustrate a disc-shaped capillary microfluidic liquid handling device in accordance with some embodiments;

Figures 14 and 15 illustrate some further embodiments; and

Figure 16 illustrates a metering implement.

With reference to Figure 1 , a microfluidic device 2 comprises a liquid receiving structure 4, which can be filled with a blood sample through an opening 6. The opening 6 can be sealed with a lid 8. In some embodiments, the lid 8 may be a flap of adhesive film of appropriate stiffness or may involve a three dimensional structure. The lid 8 is secured to a body 10 of the device 2 by a flexible flap 12, which may be integrated or separate from the lid, depending on the embodiment. In some embodiments the lid is not secured to the body 10 but is provided separately for attachment to the body 10 by means of an adhesive surface. The position of the lid 8 when the opening 6 is sealed is indicated by a dashed out line 14. A window 16 in the device body defines a detection zone 18, in which a sample flowing in the device 2 can be imaged.

With reference to Figure 2, a waste reservoir 20 is connected to the liquid receiving structure 4 by a sample conduit 22. The liquid receiving structure 4, waste reservoir 20 and sample conduit 22 are configured so that liquid in the liquid receiving structure 4 flows through the sample conduit 22 to the waste reservoir 20 by virtue of capillary (surface tension) forces. The sample conduit 22 has a preparation portion 24 upstream of a shallower detection portion 26. All or a portion of the detection portion 26 is within the window 16 to define the detection zone. The preparation portion 24 is, in some embodiments, covered with dry reagents in patches or otherwise. Dry reagents may, for example, include agents for lysing red blood cells and staining white blood cells. The waste reservoir 20 is connected to the liquid receiving structure 4 by a vent conduit 28 through a liquid retaining structure 30, now described in further detail.

With reference to Figure 3, the liquid retaining structure 30 comprises first 32, second 34 and third 36 prismatic features projecting inwards from sidewalls 38 to define a channel 40, to which the vent conduit 28 connects. At least a portion of the channel 40 is within the region sealed by the lid 8 (indicated by dashed line 14 in Figure 1 ), to enable vented gas from the vent conduit 28 to reach an airspace between the lid 8 and the liquid receiving structure 4. The area covered by the lid 8 will include a sufficient extent of the channel 40 (a sufficient number of prismatic features 32, 34, 36) such that during normal operation at a least a portion of the liquid retaining structure 30/channel 40 that is not filled by liquid communicates with the airspace. The configuration, in various embodiments, of the lid 8 and the corresponding airspace is now described with reference to figures 4 to 7. Common to the various embodiments now described with reference to Figures 4 to 7, the microfluidic device 2 is formed by bonding together two layers. A first layer 42 defines liquid handling structures by corresponding trenches and cavities formed in the first layer 42 by methods such as lithographic edging or machining. For example the liquid receiving structure 4, sample conduit 22 and liquid retaining structure 30 are formed in the first layer in this way. Bonded to the first layer 42 is a second layer 44, which generally seals and covers the cavities and trenches formed in the first layer 42 to form the liquid handling structures. A cut out in the second layer 44 defines the opening 6 and a further cut out 46, communicating with the cut out 6 (which may in practice formed as a single, combined cut out) exposes at least a portion of the liquid retaining structure 30. It will, of course, be appreciated that other constructions are equally possible, for example a single layer construction or constructions involving a number of layers exceeding two.

With reference to Figure 4, in some embodiments, the lid 8 is formed by a film of sufficient strength and flexibility, or by a combination of a film and a reinforcing plate. Since the airspace above at least a portion of the liquid retaining structure 30 is formed by the cut out 46, the thickness of the second layer 44 is chosen so that a sufficiently deep airspace is provided to prevent clogging of a passage formed between an outward facing surface 48 of the liquid retaining structure 30 and an inward facing surface 50 of the lid 8.

With reference to Figure 5, in some embodiments, which are a variation of the embodiments described above with reference to Figure 4, the second layer 44 is not of uniform thickness. Rather, the second layer 44 has a raised profile in the region surrounding the opening 6 and cut-out 46, so that outside this region the second layer 44 is of a lesser thickness, but still sufficiently thick to provide a cover for the liquid handling structures. This embodiment provides a sufficiently deep airspace while reducing the amount of material required for the second layer 44. It will be understood that, while the profile of the second layer 44 of the device body 10 is tapered in the region surrounding the opening 6 and cut out 46, different profiles are used in some embodiments, for example a step profile. Some embodiments, now described with reference to Figures 6 and 7 employ an alternative configuration of the lid 8. In these embodiments, the second layer 44 is designed without regard to the required depth of the airspace, for example to be of a uniformly thin thickness sufficiently thick to provide the required mechanical resilience of the device. A sufficient depth of the airspace between surfaces 48 and 50 is ensured in these embodiments by providing the lid with a pot like configuration with a wall 52 surrounding a base 54 and providing a rim 56 for sealing against an outer surface of the device body 10. To ensure secure sealing, the rim 56 is provided with an adhesive layer that can be revealed by peeling back a foil in order to seal the device. In situ, the wall 54 (and hence the airspace) surrounds the opening 6 and cut out 46. In some embodiments, the cut-out 46 is arranged to follow the contour of the liquid retaining structure 30, so that the surface 48 is, in effect, level with an outer surface of the device 2.

Embodiments of a three layer construction for a disc-shaped cartridge are now described with reference to Figures 8 to 13. A disc-shaped cartridge 60 comprises a sandwich of two polycarbonate discs, each 0.6mm thick. A thin-film of dry-film polymer (DFP) is sandwiched between the polycarbonate disks and the resulting sandwich is bonded together, for example by application of heat and pressure (thermal bonding). The thin-film polymer is laminated to a blank polycarbonate disc and the resulting structure is bonded to the other polycarbonate disc which defines microfluidic features. Microfluidic features are created in the disc-shaped cartridge by a combination of injection moulding and through-cutting in the other one of the polycarbonate discs and cut outs in the thin-film polymer. The resulting construction will now be described, layer by layer with reference to Figures 9 to 12.

With reference to Figure 9, the liquid receiving chamber 4 and preparation portion 24 of the sample conduit 22 are formed by injection moulding, to a depth of 0.2mm in one of the polycarbonate discs. The vent channel 28 is also formed by injection moulding to the same depth. With reference to Figure 10, the opening 6 and liquid retaining structure 30 are formed in the polycarbonate disc by a suitably shaped cut-out through the depth of the polycarbonate disc. The cut-out is positioned so as to obliterate most of the moulding corresponding to the liquid receiving chamber 4 and some of the moulding of the preparation portion 24, as illustrated in Figure 10. The result is a liquid receiving structure which has a depth of 0.6mm inside the opening 6 and an under-cut portion 62 around a substantial extent of the opening 6, defined by the moulding of the liquid receiving structure 4, discussed with reference to Figure 9. Thus, when the blank polycarbonate disc and thin-film of DFP are bonded to the cut-out/moulded polycarbonate disc discussed with reference to Figures 9 to 10, the undercut 62 (as seen from the outside of the disc) provides a capillary channel around the opening 6 to facilitate guiding a blood sample placed in the opening 6 to enter the preparation portion 24 by virtue of the capillary effect due to the confined extent of the undercut 62.

All the features just described with reference to Figures 9 and 10 are defined in one of the polycarbonate discs by moulding or cutting through. Further features are defined in the thin film of DFP sandwiched between the two polycarbonate discs. This will now be described with reference to Figure 1 1. Figure 10 can be understood as a view of the disc with its outer surface facing away from the viewer and the thin-film of DFP and other polycarbonate disc removed to expose the features in the moulded/cut-through polycarbonate disc. Figure 1 1 presents a similar view with the thin-film of DFP in place with the blank polycarbonate disc removed (or seen through the blank polycarbonate disc).

Specifically, with reference to Figure 1 1 , a cut-out in the thin-film of DFP is placed in partially overlapping relation with the preparation portion 24 of the sub conduit 22 and the vent conduit 28. A portion of the cut-out adjacent the preparation portion 24 defines the detection portion 26 of the sample conduit 22 and a wider portion adjacent the vent conduit 28 defines the waste chamber 20. Consequently, the detection portion 26 and waste chamber 20 have a depth of 0.02mm, defined by the thickness of the thin-film of DFP. Due to, at least in part, the decreasing depth from the opening 6 (depth 0.6mm) via the undercut 62 and preparation portion 24 (depth 0.2mm) to the detection portion 26 and the waste chamber 20 (depth 0.02mm), flow of the sample from the opening 6 to the waste chamber 20 is driven by capillary/surface tension forces. When the sample reaches the vicinity of the vent conduit 28 in the waste chamber 20, the corresponding expansion stops flow of the sample from the waste chamber 20 into the vent conduit 28 again due to surface tension, with the result that the vent conduit 28 becomes blocked by the sample at its interface with the waste chamber 20 and flow ceases. By tuning the dimensions of the waste chamber 20, the volume of an initial sample in the sample receiving chamber 4/opening 6 that flows into the sample conduit 22 and onwards can be tuned to ensure that a sufficient volume of sample remains for processing in other (for example centrifugal) microfluidic downstream structures, not illustrated for simplicity. As Figures 9 to 1 1 schematically illustrate the disc from the inside out (with an outer face facing away from the viewer) the position of the lid 8 to provide the airspace connecting the liquid retaining structure 30 and liquid receiving chamber 4/opening 6 is illustrated in Figure 12 in dashed lines as applied to the outer face of the disc facing away from the viewer, below the microfluidic structures. With reference to Figure 13, in some specific embodiments, the lid 8 is an injection moulded polycarbonate component within which a depression has been moulded or cut to define a lid surface 50 surrounded by a wall 52 and a rim 56 to define an airspace that is shaped to encompass the opening 6 and liquid retaining structure 30. With reference to Figure 14, in some embodiments the vent conduit 28 and liquid receiving chamber 4/opening 6 are formed as separate, disconnected structures in the polycarbonate disc, rather than being joined by the liquid retaining structure 30 as described in the embodiments above. In these embodiments, a connection between the vent conduit 28 and the outside of the polycarbonate disc is made by a cut-out 64 adjacent but separate from the cut-out 6. The lid 8, of similar construction as described above with reference to Figure 13 (see Figure 15) provides an airspace 66 that links the opening 6 and the cut-out 64 to provide fluidic communication enabling venting of air displaced from the waste chamber 20 to the liquid receiving chamber 4. In use, a sample is introduced into the liquid receiving structure and the liquid receiving structure 4 is sealed with the lid 8 by way of an adhesive film as described above or any other suitable adhesive surface. The sample is drawn through the sample conduit into the waste reservoir 20, with displaced gas venting back to the liquid receiving structure 4 via the vent conduit 28 and liquid retaining structure 30 (in embodiments where this is present). The device 2 is disposed relative to image capture device 2 to capture images of the liquid sample through the window 18. In some embodiments, such as those described with reference to Figures 4 to 7, a metering implement is provided in combination with the device. The metering implement is configured to meter liquid to leave a predetermined air space in the liquid retaining structure 4 and/or prevent overflowing of the liquid receiving structure. By using the metering implement to fill the liquid receiving structure 4, correct operation of the device 2 is facilitated.

An embodiment of the metering implement is illustrated in Figure 16. The metering implement 58 comprises a capillary tube 68 e.g. a glass tube of suitable dimensions. The tube comprises a restricting feature 70 in its middle, representing a surface tension barrier to flow. When one end is placed in contact with a liquid sample, the tube 68 will fill up to the restricting feature 70 by virtue of a capillary force. When the filled end is brought into contact with the liquid receiving structure 4, the sample is dispensed from the tube 68 by virtue of surface wetting forces. Alternatively, the liquid can be dispelled using an applied pressure, e.g. by attaching a flexible tube and blowing through it.

It will be appreciated that the features of the embodiments described above may be combined as appropriate. Specifically, the described embodiments are not limited to the shape of the respective substrate/cartridge and any of the described microfluidic handling structures might be provided in a cartridge of any shape, be it rectangular, disc-shaped or otherwise. It will further be appreciated that the function of the microfluidic structures is not intimately linked to the construction of how the features of varying depths and configurations are achieved, be it by bonding together several substrate layers of the same or different thickness or bonding together polycarbonate or other polymer material substrates with or without intervening thin films and irrespective of the relative material thicknesses. In one particular example, in the embodiments described above with reference to Figures 8 to 15, the blank polycarbonate disc can be of any desired thickness as long as sufficient structural rigidity for the overall cartridge is achieved. Accordingly, the embodiments described above extend to various ways of implementing them, and are not limited to specific dimensions or constructional details.

The above description of embodiments is made by way of example only and various modifications, alterations and juxtapositions of the described features will occur to the person skilled in the art. It will therefore be apparent that the above description is made for the purpose of illustration of embodiments of the invention and not limitation of the invention, which is defined in the appendant claims.

Claims

1. A liquid handling device comprising a device body defining:

a liquid receiving structure defining a liquid receiving opening in the device body to receive a liquid sample;

a downstream liquid handling structure arranged to draw liquid from the liquid receiving structure by capillary effect; and

a vent structure enabling gas displaced by liquid drawn from the liquid receiving structure into the downstream liquid handling structure to escape into the liquid receiving structure; in combination with

a lid attached or attachable to the device body to seal the liquid receiving structure such that, when the liquid receiving chamber is filled with liquid and sealed by the lid, displaced gas can flow from the vent structure to an air space between the lid and liquid filling the liquid receiving chamber.

2. A device as claimed in claim 1 , wherein the air space surrounds the liquid retaining opening and at least a portion of the vent structure when the liquid receiving structure is sealed with the lid.

3. A device as claimed in claim 1 or claim 2, wherein the lid comprises a rim for sealing against the device body to seal the liquid receiving structure and the lid defines an air space between a lid surface opposite the rim and the rim to provide at least a portion of the air space between the lid and liquid filling the liquid receiving chamber.

4 A device as claimed in claim 3, wherein the rim is configured to encompass at least a portion of the vent structure.

5. A device as claimed in any one of claims 1 to 4, wherein the vent structure comprises a liquid retaining structure configured to provide a surface tension barrier to limit ingress of liquid in the liquid receiving structure into the vent structure, and the airspace surrounds the opening and at least a portion of the liquid retaining structure.

6. A device as claimed in claim 3 or claim 4, wherein the vent structure comprises a liquid retaining structure configured to provide a surface tension barrier to limit ingress of liquid in the liquid receiving structure into the vent structure, and the rim is configured to surround the liquid receiving opening and at least a portion of the liquid retaining structure.

7. A device as claimed in any one of claims 1 to 4, wherein the vent structure defines a vent opening in the device body, separate from the liquid receiving opening, the airspace connecting the liquid receiving and vent openings.

8. A device as claimed in claim 3 or 4, wherein the vent structure defines a vent opening in the device body, separate from the liquid receiving opening, the rim being configured to encompass the liquid receiving opening and the vent opening.

9. A device as claimed in any preceding claim, the device being configured for the liquid sample being a blood sample.

10. A device as claimed in claim 5 or 6, wherein the liquid retaining structure defines a liquid channel having one or more sharp corners.

1 1 . A device as claimed in claim 10, wherein the liquid retaining structure comprises a plurality of features pointing into the channel to define the one or more sharp corners.

12. A device as claimed in any preceding claim, wherein sealing the liquid receiving structure with the lid seals the interior of the device body from gas exterior to the device body.

13. A device as claimed in any preceding claim, wherein the downstream liquid handling structure comprises a sample conduit having a detection zone in which liquid flowing in the sample conduit can be detected.

14. A device as claimed in claim 13, the vent structure including one or more vent conduits connecting the downstream liquid handling structure downstream of the detection zone to the liquid receiving structure.

15. A device as claimed in claim 14, wherein the vent structure comprises a liquid retaining structure configured to provide a surface tension barrier to limit ingress of liquid in the liquid receiving structure into the vent structure, and the one or more vent conduits connect the downstream liquid handling structure to the liquid receiving structure through the liquid retaining structure.

16. A device as claimed in any one of claims 13 to 15, wherein the sample conduit is coated with one or more dry reagents upstream of the detection zone.

17. A device as claimed in any preceding claim, wherein the device body is configured for rotation about an axis to enable centrifugally driving liquid flow from the liquid receiving structure in a centrifugal liquid handling structure defined by the device body.

18. A device as claimed in claim 1 , wherein the vent structure comprises a liquid retaining structure configured to provide a surface tension barrier to limit ingress of liquid in the liquid receiving structure into the vent structure, and the liquid retaining structure is spaced away from an outer surface of the device body to retain liquid away from the lid when the liquid receiving structure is sealed with the lid, thereby maintaining a gap between the liquid retained by the liquid retaining structure and the lid.

19. A device as claimed in claim 18, wherein the outer surface has a raised profile in a region surrounding the opening to space the liquid retaining structure from the outer surface by a distance greater than a normal distance from the outer surface outside the region to the liquid retaining structure.

20. A device as claimed in claim 18 or claim 19 in combination with a metering implement for metering a predefined volume of liquid into the liquid receiving chamber, wherein the predefined volume corresponds to a fill level of the liquid receiving structure that does not exceed a fill level corresponding to the gap.

21 . A liquid handling device as claimed in any preceding claim, wherein the liquid receiving structure extends outward of the liquid receiving opening to define an under cut at least partially surrounding the liquid receiving opening and extending to at least one side of a connection between the downstream liquid handling structure and the liquid receiving structure, thereby facilitating spreading of a sample introduced into the liquid receiving structure to the downstream liquid handling structure.

22. A method of preparing a liquid handling device for flow of a liquid sample in the liquid handling device, the method comprising

introducing a liquid sample into a liquid receiving structure of the liquid handling device to cause capillary flow of the liquid sample in a downstream liquid handling structure of the liquid handling device;

sealing the liquid receiving structure with a lid, thereby creating an air space between the liquid and the lid; and venting gas displaced from the downstream liquid handling structure to the airspace.

23. A device or method as claimed in any preceding claim, wherein the liquid handling device is a microfluidic liquid handling device.