Liquid Handling Equipment

Abstract

Embodiments described herein relate to a liquid handling apparatus comprising a capsule configured to store a liquid reagent, a liquid handling device having a first conduit in fluid communication with a first port and a second conduit in fluid communication with a second port, and a capsule interface mechanism configured to form a first hole in the capsule in fluid communication with the first port and a second hole in the capsule in fluid communication with the second port, wherein forming the first hole and the second hole allows for removal of the liquid reagent from the capsule.

Description

[Technical field]

[0001] The present disclosure relates to a liquid handling device, in particular a liquid handling device comprising a liquid handling device and a capsule configured to store a liquid reagent. [Background technology]

[0002] Reagent storage capsules, such as blister capsules, are commonly used in point-of-care diagnostic devices to store liquid reagents used in certain diagnostic tests, such as immunoassays. The capsules are typically formed of a rigid container made of a material that can be compressed to empty the capsule, and a film (e.g., foil) that is used to seal the capsule after the container is filled with reagent. The sealed capsule can then be attached to the point-of-care diagnostic device using an adhesive layer around the perimeter of the sealing film.

[0003] To release the liquid reagent from the capsule, a pressing or squeezing force is typically applied to the rigid container, thereby compressing the rigid container and bringing the sealing film into contact with a piercing structure (e.g., a spike) in the device. The piercing structure is located below the capsule (assuming the force is applied from above) and will pierce the sealing film when sufficient force is applied. After piercing the capsule, continued pressing or squeezing forces the liquid reagent out of the hole in the capsule and into the fluid layer of the device.

[0004] The reagent storage capsules used in existing devices cannot be completely filled with liquid reagent because the liquid in a completely filled capsule would be displaced by the piercing structure, which would release the liquid in the capsule in an uncontrolled manner. Furthermore, it is not possible to seal a completely filled capsule because the liquid in the capsule would wet the sealing film and spread to the sealing area, thereby preventing a proper seal from being formed. Therefore, it is inevitable that the reagent storage capsule will contain air. The action of squeezing or squeezing the capsule to expel the liquid reagent introduces air bubbles into the flow of the liquid reagent, which can interfere with the diagnostic test being performed.

[0005] To alleviate this, some existing devices include a vent chamber into which the reagent is transferred after it is released from the capsule. The vent chamber allows air in the reagent to escape. The reagent is then transferred from the vent chamber for use in the diagnostic test. A drawback of this method is that the vent chamber requires additional space within the device, thereby increasing the size of the liquid handling device.

[0006] In addition, the pressing or squashing action may be insufficient to completely expel all of the liquid reagent from the capsule. In particular, the force required to expel the liquid reagent may increase as the percentage of liquid in the capsule decreases. This means that very high pressing or squashing forces may be required to push the remaining reagent out of the capsule. The systems used to process the point-of-care diagnostic device to perform the diagnostic test may not be able to apply such large forces to completely expel the liquid reagent. Furthermore, applying larger forces may cause the adhesive used to attach the capsule to the device to break, resulting in the liquid reagent being forced out of the joint between the capsule and the device. Applying larger forces therefore has an impact on the choice of adhesive material, which means that an adhesive with high adhesive strength to both the capsule foil and the cartridge material is required, which may lead to increased costs for the point-of-care diagnostic device.

[0007] One solution might be to use larger capsules so that only a portion of the liquid reagent is needed, but such a solution would result in an increase in the footprint of the point-of-care diagnostic device, which is often constrained.

[0008] A further drawback of existing capsule manufacturing methods is that the process of heat sealing the capsules can damage reagents that are sensitive to temperature changes. This can be mitigated by filling the capsules to a lower height to allow a gap between the surface of the liquid reagent and the sealing area, reducing the effect of temperature changes on the liquid reagent. However, this method means that a larger capsule is required for a given amount of liquid reagent. Alternative methods involve adjusting the temperature or contact time used in the sealing process, but these methods can reduce the quality of the seal.

[0009] Thus, there is a need for improved liquid handling equipment that can address at least some of the problems set forth above. Summary of the Invention

[0010] This Summary introduces concepts that are described in more detail in the Detailed Description. It is not intended to identify essential features of the claimed subject matter, nor is it intended to limit the scope of the claimed subject matter.

[0011] According to a first aspect of the present disclosure, there is provided a liquid handling apparatus comprising: a capsule configured to store a liquid reagent; a liquid handling apparatus having a first conduit in fluid communication with a first port and a second conduit in fluid communication with a second port; and a capsule interface mechanism configured to form a first hole in the capsule in fluid communication with the first port and a second hole in the capsule in fluid communication with the second port, wherein forming the first hole and the second hole enables the liquid reagent to be removed from the capsule.

[0012] Forming the first and second holes in the capsule allows the liquid reagent to be removed from the capsule via the first conduit and / or the second conduit. For example, air may be supplied via the first conduit and the liquid reagent may be exhausted via the second conduit. By expelling the liquid reagent from the capsule in this manner, a large portion of the liquid reagent may be removed from the capsule, which means that a smaller capsule is required to deliver a volume of liquid reagent than those used in existing liquid handling devices.

[0013] Also, forming the first and second holes in the capsule allows the liquid reagent to be removed from the capsule without crushing the portion of the capsule containing the liquid reagent, such that the liquid reagent does not become trapped within the crushed material of the capsule.

[0014] The liquid treatment device may further comprise a gas supply port configured to receive gas supplied by a variable pressure source, the gas supply port being in fluid communication with the first conduit, the first conduit being configured to supply the received gas via the gas supply port to the first hole and to expel the liquid reagent from the second hole after the first and second holes are formed.

[0015] The capsule interface feature may be configured to form the second hole while forming the first hole, in this way the hole in the capsule can be formed in one operation.

[0016] The capsule interface feature may be configured to form the first and second holes on the same side of the capsule, for example, the capsule interface feature may be configured to form the first and second holes in a sealing layer of the capsule.

[0017] The capsule interface mechanism may be configured to form a second hole in the base of the capsule. Forming the second hole in the base of the capsule maximizes the amount of liquid reagent that can be removed from the capsule because the liquid reagent outlet (i.e., the second hole) is always below the liquid reagent level in the capsule.

[0018] The capsule may comprise a deformable material, the capsule interface feature being configured to form a second hole in the capsule when the deformable material is deformed.

[0019] One or more of the capsule and the liquid treatment device may include a compressible layer configured to bias the capsule away from the capsule interface feature, the capsule interface feature configured to form a second hole in the capsule when the compressible layer is compressed.

[0020] The compressible layer may include a passageway in fluid communication with the second conduit, the passageway configured to allow flow of the liquid reagent from the second hole through the compressible layer. Thus, the compressible layer biases the capsule away from the capsule interface feature before the hole is formed, and provides a path for liquid reagent released from the capsule to flow into the liquid treatment device.

[0021] The capsule interface feature may include a piercing element configured to pierce the capsule to form a second hole. The piercing element may be disposed within the passageway.

[0022] The liquid treatment device may comprise a capsule interface feature, or the capsule may comprise at least a part of a capsule interface feature.

[0023] The capsule may comprise a liquid storage chamber configured to store a liquid reagent, an inlet chamber and an outlet chamber, each of which is in fluid communication with the liquid storage chamber, a first restriction configured to prevent the flow of liquid between the liquid storage chamber and the outlet chamber prior to formation of a hole in the capsule, and a second restriction configured to prevent the flow of liquid between the liquid storage chamber and the inlet chamber prior to formation of a hole in the capsule.

[0024] The restriction between the chambers of the capsule means that the liquid reagent can be released from the capsule in a controlled way. In particular, the liquid reagent can be pushed from the liquid storage chamber to the exit chamber when the liquid reagent is required. This can be achieved by supplying air via a first hole (which can be in the inlet chamber) and expelling the liquid reagent via a second hole (which can be in the exit chamber). Expelling the liquid reagent in this way also avoids introducing air bubbles into the liquid reagent flow, as the liquid reagent can be expelled in one single volume.

[0025] Additionally, the restriction acts as a capillary stop to prevent liquid from filling the inlet and outlet chambers during storage and handling of the capsule.

[0026] The capsule interface feature may be configured to form a second hole in the outlet chamber.The capsule interface feature may be configured to form a first hole in the inlet chamber.

[0027] The cross-sectional area of ​​the second restriction may be equal to or greater than the cross-sectional area of ​​the second conduit. By having the cross-sectional area of ​​the second restriction equal to or greater than the cross-sectional area of ​​the second conduit, the flow rate of the liquid reagent in the liquid treatment device is not limited by the flow rate through the second restriction in the capsule. The cross-sectional area of ​​the first restriction may also be equal to or greater than the cross-sectional area of ​​the second conduit. The cross-sectional area of ​​the first restriction may be greater than the cross-sectional area of ​​the second restriction.

[0028] The exit chamber may comprise a recess in the surface of the capsule body that defines the exit chamber. The inclusion of a recess in the surface of the capsule body that defines the exit chamber reduces the displacement of the capsule body required to form the second hole. This means that the deformation of the capsule body required to form the second hole is reduced, which means that less force is required to form the second hole. The entrance chamber may also comprise a recess in the surface of the capsule body that defines the entrance chamber.

[0029] The recess may be filled with a rigid material. Filling the recess with a rigid material means that the surface of the outlet chamber can be displaced without needing an actuatable element that fits the shape of the recess (and without needing precise positioning of the actuatable element in the recess). The second hole can therefore be formed in a simpler way, without needing such precise positioning of the liquid treatment device in the liquid treatment system with the actuatable element.

[0030] The capsule may comprise a sealing layer configured to seal the opening of the capsule body, the inner surface of the recess being in contact with the sealing layer prior to the formation of the hole in the capsule. This means that any downward displacement of the recess (e.g. by an actuatable element of a liquid handling system) acts directly on the sealing layer. This minimises the force required to form the hole (and thus minimises the amount of deformation of the capsule body required to form the hole).

[0031] The inner surface of the recess may be sealed to a sealing layer, which further reduces the amount of force required to form the hole by preventing the sealing layer from sliding over the surface of the recess.

[0032] The liquid storage chamber may have a half-teardrop shape with a bulbous portion adjacent the first restriction and an apex portion providing a taper between the bulbous portion and the second restriction. Using a half-teardrop shape for the liquid storage chamber maximizes the volume of the liquid storage chamber while minimizing the free surface of the liquid reagent in the liquid storage chamber and maximizes the tendency of the liquid reagent to remain in a uniform volume that coalesces toward the second restriction during release of the liquid reagent from the capsule (i.e., minimizes the tendency of the liquid reagent to split in the liquid storage chamber during release of the reagent). The half-teardrop shape also minimizes the tendency of the liquid reagent to fragment during settling of the liquid reagent after manufacture of the capsule and during processing of the capsule.

[0033] The shape of the bulbous portion may be defined by an entrance angle, which is the minimum angle between a first line that lies on the plane of symmetry of the liquid storage chamber and is tangent to a surface of the bulbous portion and a second line that is perpendicular to the base of the capsule; the shape of the apex portion may be defined by an exit angle, which is the minimum angle between a third line that lies on the plane of symmetry of the liquid storage chamber and is tangent to a surface of the apex portion and a fourth line that is perpendicular to the base of the capsule; and the exit angle may be greater than the entrance angle.

[0034] The inlet chamber may comprise a lower portion having a truncated dome shape with a concave surface having a first curvature, and an upper portion joined to the lower portion, the upper portion having a dome shape with a concave surface having a second curvature different from the first curvature, the difference between the first curvature and the second curvature providing a gradual change in curvature at the junction between the upper portion and the lower portion. Using an inlet chamber having these portions ensures that any microscopic air bubbles in the fluid in the inlet chamber are trapped within the inlet chamber and held around the periphery of the inlet chamber after the liquid reagent is released.

[0035] The outlet chamber may comprise a lower portion having a truncated dome shape with a concave surface having a first curvature, and an upper portion joined to the lower portion, the upper portion having a dome shape with a concave surface having a second curvature different from the first curvature, the difference between the first curvature and the second curvature providing a gradual change in curvature at the junction between the upper portion and the lower portion.

[0036] The capsule may comprise a capsule body with a first opening and a second opening, a first sealing layer configured to seal the first opening, and a second sealing layer configured to seal the second opening, the area of ​​the second opening being smaller than the area of ​​the first opening. Using a second opening provides flexibility in the way the capsule is filled with liquid reagent. For example, the larger main opening (i.e. the first opening) can be heat sealed and then the liquid reagent can be filled through the smaller second opening. This avoids exposing the liquid reagent to the heat sealing process. Furthermore, using a smaller second opening means that a larger percentage of the capsule can be filled (e.g. if the smaller second opening is provided on the top surface of the capsule).

[0037] The capsule interface feature may be configured to form a first opening and a second opening in the first sealing layer.

[0038] According to a second aspect of the present disclosure, there is provided a method of extracting a liquid reagent stored in a capsule attached to a liquid treatment device, the method comprising forming a first hole and a second hole in the capsule, and supplying a gas through the first hole to expel the liquid reagent from the second hole.

[0039] Supplying gas through the first hole may comprise coupling a gas supply port of the liquid treatment device to a variable pressure source configured to supply gas, and supplying gas from the variable pressure source to the first hole via a conduit in fluid communication with the gas supply port and the first hole.

[0040] The method of the second aspect may be used to remove liquid reagents from the capsules of the liquid handling apparatus of the first aspect.

[0041] According to a third aspect of the present disclosure there is provided a computer readable medium comprising instructions which, when executed by a processor of a liquid handling system configured to receive liquid handling equipment, cause the liquid handling system to perform the method of the second aspect.

[0042] According to a fourth aspect of the present disclosure, there is provided a method for manufacturing a liquid reagent capsule, the method comprising: heat sealing a first opening of a capsule body with a first seal thereby forming a container; filling the container with a liquid reagent through a second opening of the capsule, the area of ​​the second opening being smaller than an area of ​​the first opening; and sealing the second opening with a second seal.

[0043] By constructing the capsule in this manner, the liquid reagent within the capsule is not exposed to the heat sealing process because the heat sealing of the capsule is performed before the capsule is filled with the liquid reagent, and therefore, if the liquid reagent is sensitive to temperature changes, it is not exposed to the heat sealing process in a way that could damage the liquid reagent.

[0044] The second opening may be sealed using a pressure sensitive adhesive, meaning that the second seal does not expose liquid reagents to the heat sealing process.

[0045] According to a fifth aspect of the present disclosure, there is provided a capsule comprising a liquid storage chamber configured to store a liquid reagent, an inlet chamber and an outlet chamber, each of the inlet chamber and the outlet chamber being in fluid communication with the liquid storage chamber, a first restriction configured to prevent a flow of liquid between the liquid storage chamber and the outlet chamber prior to formation of a hole in the capsule, and a second restriction configured to prevent a flow of liquid between the liquid storage chamber and the inlet chamber prior to formation of a hole in the capsule.

[0046] The restriction between the chambers of the capsule means that the liquid reagent can be released from the capsule in a controlled manner. In particular, the liquid reagent can be forced from the liquid storage chamber to the discharge chamber when the liquid reagent is required. Furthermore, since the liquid reagent can be discharged in a single volume, the liquid reagent can be discharged without introducing air bubbles into the liquid reagent flow.

[0047] Additionally, the restriction acts as a capillary stop to prevent liquid from filling the inlet and outlet chambers during storage and processing of the capsule.The cross-sectional area of ​​the first restriction may be greater than the cross-sectional area of ​​the second restriction.

[0048] The exit chamber may comprise a recess in the surface of the capsule body that defines the exit chamber. The inclusion of a recess in the surface of the capsule body that defines the exit chamber reduces the displacement of the capsule body required to form the second hole. This means that less deformation of the capsule body is required for the second hole to be formed, which means less force is required to form the second hole. The entrance chamber may also comprise a recess in the surface of the capsule body that defines the entrance chamber.

[0049] The recess may be filled with a rigid material. Filling the recess with a rigid material means that the surface of the outlet chamber can be displaced without requiring an actuatable element to fit the shape of the recess (and without requiring precise positioning of the actuatable element in the recess). The second hole can therefore be formed in a simple manner without requiring such precise positioning of the liquid treatment device in the liquid treatment system with the actuatable element.

[0050] The capsule may comprise a sealing layer configured to seal the opening in the capsule body, with the inner surface of the recess being in contact with the sealing layer prior to the formation of the hole in the capsule. This means that any downward displacement of the recess (e.g. by an actuatable element of a liquid handling system) acts directly on the sealing layer. This minimises the force required to form the hole (and thus minimises the amount of deformation of the capsule body required to form the hole).

[0051] The inner surface of the recess may be sealed against the sealing layer, which further reduces the amount of force required to form the hole by preventing the sealing layer from sliding over the surface of the recess.

[0052] The liquid storage chamber may have a semi-teardrop shape with a bulbous portion adjacent the first restriction and an apex portion providing a taper between the bulbous portion and the second restriction. Using a semi-teardrop shape for the liquid storage chamber maximizes the volume of the liquid storage chamber while minimizing the free surface of the liquid reagent in the liquid storage chamber and maximizes the tendency of the liquid reagent to remain in a uniform volume that coalesces towards the second restriction during release of the liquid reagent from the capsule (i.e., minimizes the tendency of the liquid reagent to split within the liquid storage chamber during release of the reagent). The semi-teardrop shape also minimizes the tendency of the liquid reagent to split during settling of the liquid reagent after manufacture of the capsule and during processing of the capsule.

[0053] The shape of the bulbous portion may be defined by an entrance angle, which is the minimum angle between a first line that lies on the plane of symmetry of the liquid storage chamber and is tangent to a surface of the bulbous portion and a second line that is perpendicular to the base of the capsule; the shape of the apex portion may be defined by an exit angle, which is the minimum angle between a third line that lies on the plane of symmetry of the liquid storage chamber and is tangent to a surface of the apex portion and a fourth line that is perpendicular to the base of the capsule; and the exit angle may be greater than the entrance angle.

[0054] The inlet chamber may comprise a lower portion having a truncated dome shape with a concave surface having a first curvature, and an upper portion joined to the lower portion, the upper portion having a dome shape with a concave surface having a second curvature different from the first curvature, the difference between the first curvature and the second curvature providing a gradual change in curvature at the junction between the upper portion and the lower portion. Using an inlet chamber having these portions ensures that any microscopic air bubbles in the fluid in the inlet chamber are trapped within the inlet chamber and held around the periphery of the inlet chamber after the liquid reagent is released.

[0055] The outlet chamber may comprise a lower portion having a truncated dome shape with a concave surface having a first curvature, and an upper portion joined to the lower portion, the upper portion having a dome shape with a concave surface having a second curvature different from the first curvature, the difference between the first curvature and the second curvature providing a gradual change in curvature at the junction between the upper portion and the lower portion.

[0056] The capsule may comprise a capsule body with a first opening and a second opening, a first sealing layer configured to seal the first opening, and a second sealing layer configured to seal the second opening, wherein an area of ​​the second opening is smaller than an area of ​​the first opening.

[0057] The capsule of the fifth aspect may further comprise any of the features of a capsule for use with the liquid handling apparatus of the first aspect. [Brief description of the drawings]

[0058] Specific embodiments are now described, by way of example only, and with reference to the accompanying drawings. [Figure 1] FIG. 2 is a schematic diagram of a capsule mounted on a liquid treatment device. [Diagram 2] 2 is a schematic diagram showing a port of the liquid treatment device shown in FIG. 1. [Diagram 3] FIG. 3 is a schematic diagram of the liquid treatment device shown in FIGS. 1 and 2 coupled to a variable pressure source. [Figure 4] FIG. 2 is a schematic diagram of a deformable capsule attached to the liquid treatment device shown in FIG. 1. [Figure 5A] FIG. 13 is a schematic diagram of a deformable capsule attached to an alternative liquid treatment device. [Figure 5B] FIG. 5B is a schematic diagram showing the deformable capsule shown in FIG. 5A in a deformed state. [Figure 6A] FIG. 5B is a schematic diagram of an alternative deformable capsule attached to the liquid treatment device shown in FIG. 5A. [Figure 6B] FIG. 6B is a schematic diagram illustrating the alternative deformable capsule shown in FIG. 6A in a deformed state. [Figure 7A] FIG. 5B is a schematic diagram of a further alternative deformable capsule attached to the liquid treatment device shown in FIG. 5A. [Figure 7B] FIG. 7B is a schematic diagram illustrating a further alternative deformable capsule shown in FIG. 7A in a deformed state. [Figure 8] FIG. 1 is a schematic diagram of a capsule with a compressible layer attached to a liquid treatment device. [Figure 9] FIG. 9 is a schematic diagram showing the piercing of the capsule shown in FIG. [Figure 10A] FIG. 2 is an isometric view of a first capsule comprising a liquid storage chamber having a teardrop shape. [Figure 10B] FIG. 10B is a top view of the first capsule shown in FIG. 10A. [Figure 10C] FIG. 10B is a side view of the first capsule shown in FIG. 10A. [Figure 10D] 10B shows a simulation of the free surface of the first liquid reagent in the first capsule shown in FIG. 10A prior to release of the first liquid reagent from the first capsule. [Figure 10E] 10D shows a simulation of the free surface of the second liquid reagent in the first capsule shown in FIG. 10D during the release of the second liquid reagent from the first capsule. [Figure 10F] FIG. 10E shows an alternative capsule defined by parameters adjusted to minimize disruption of the second liquid reagent. [Figure 11A]FIG. 13 is an isometric view of a second capsule with a teardrop-shaped liquid storage chamber. [Figure 11B] FIG. 11B is a top view of the second capsule shown in FIG. [Figure 11C] FIG. 11B is a side view of the second capsule shown in FIG. [Figure 12A] FIG. 13 is an isometric view of a third capsule comprising a liquid storage chamber having a teardrop shape. [Figure 12B] FIG. 12B is a top view of the third capsule shown in FIG. 12A. [Figure 12C] FIG. 12B is a side view of the third capsule shown in FIG. 12A. [Figure 12D] 12B shows a simulation of the free surface of a liquid reagent in the third capsule shown in FIG. 12A. [Figure 13A] FIG. 13 is an isometric view of a fourth capsule having a liquid storage chamber with a teardrop shape. [Figure 13B] FIG. 13B is a top view of the fourth capsule shown in FIG. 13A. [Figure 13C] FIG. 13B is a side view of the fourth capsule shown in FIG. 13A. [Figure 14] 2 is a schematic diagram of a capsule with a teardrop-shaped liquid storage chamber when the capsule is attached to the liquid treatment device shown in FIG. 1. [Figure 15A] FIG. 1 is an isometric view of a capsule with a liquid storage chamber having a flattened dome shape. [Figure 15B] FIG. 15B is a top view of the capsule shown in FIG. 15A. [Figure 15C] FIG. 15B is a side view of the capsule shown in FIG. 15A. [Figure 16A] FIG. 2 is an isometric view of a capsule with a liquid storage chamber having an elongated shape. [Figure 16B] FIG. 16B is a top view of the capsule shown in FIG. 16A. [Figure 16C] FIG. 16B is a side view of the capsule shown in FIG. 16A. [Figure 17A] FIG. 1 is an isometric view of a capsule with a U-shaped liquid storage chamber. [Figure 17B] FIG. 17B is a top view of the capsule shown in FIG. 17A. [Figure 18] 4 is a flow chart of a method for extracting a liquid reagent stored in a capsule. [Figure 19] FIG. 1 is a schematic diagram showing the construction of a capsule. [Figure 20] 1 is a flowchart showing a method for manufacturing a liquid reagent capsule. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0059] Embodiments of the present disclosure are described below with particular reference to liquid reagent storage. However, it will be understood that the capsules disclosed herein may be used to store any type of liquid and are not limited to storing reagents. References herein to a capsule being "configured to" store a liquid reagent should not be taken to mean that the capsule is limited to storing a liquid reagent.

[0060] overview 1 is a schematic diagram of a liquid treatment device 100 (eg a cartridge such as a microfluidic cartridge) having attached thereto a capsule 120. The liquid treatment device 100 and capsule 120 together comprise a liquid treatment apparatus.

[0061] The capsule 120 stores a liquid reagent 122. The capsule 120 includes three parts: an inlet chamber 124, a liquid storage chamber 126, and an outlet chamber 128 (described in more detail with reference to Figures 10A to 10C). The capsule 120 also includes a first restriction 130 between the inlet chamber 124 and the liquid storage chamber 126, and a second restriction 132 between the liquid storage chamber 126 and the outlet chamber 128. Each of the first and second restrictions 130, 132 is provided in the form of a neck (or narrowed area) between the liquid storage chamber 126 and the inlet / outlet chamber. The inlet chamber 124 is in fluid communication with the liquid storage chamber 126 via the first restriction 130. The outlet chamber 128 is in fluid communication with the liquid storage chamber 126 via the second restriction 132.

[0062] The first restriction 130 is sized to minimize the flow of liquid reagent into the inlet chamber 124. Similarly, the second restriction 132 is sized to minimize the flow of liquid reagent into the outlet chamber 128. To minimize the flow of liquid reagent, the first and second restrictions 130, 132 are narrow enough that the surface tension of the liquid reagent prevents the liquid reagent from flowing through the restrictions 130, 132. This means that the first and second restrictions 130, 132 act as capillary stops that prevent the flow of liquid from the liquid storage chamber 126 into the inlet and outlet chambers 124, 128 before forming a hole in the capsule 120.

[0063] The capsule 120 comprises a capsule body 134 that defines the shape of the liquid storage chamber 126, the inlet chamber 124, the outlet chamber 128, and the first and second restrictions 130, 132. The capsule body 134 comprises one or more openings through which the capsule 120 is filled (in the example shown in FIG. 1, the capsule body 134 comprises a single opening). The capsule 120 further comprises a sealing layer 136 that seals the openings. The capsule body 134 can be formed, for example, by injection molding with a polymeric material such as polypropylene (PP), high density polyethylene (HDPE), or cyclic olefin copolymer (COC), by thermoforming with a polymeric material such as polyvinyl chloride (PVC), polyethylene terephthalate (PET), or polychlorotrifluoroethylene (PCTFE), or by cold forming with an aluminum-based laminate film, which typically comprises at least three layers: a plastic film (e.g., PVC, PP, PE), an aluminum layer, and a polyamide layer. The sealing layer 136 may be formed of a thin aluminum-based laminate film (also known as a lid foil, push-through foil, or easy pierceable foil).

[0064] The liquid treatment device 100 includes a surface 110 that contacts the capsule 120. The capsule 120 is attached to the liquid treatment device 100 using an adhesive layer (not shown) between the sealing layer 136 and the surface 110.

[0065] Liquid treatment device 100 also includes a first conduit 102 and a second conduit 104, each of which may be provided within a fluid layer of liquid treatment device 100. First conduit 102 is in fluid communication with a first port 116. Second conduit 104 is in fluid communication with a second port 118. Liquid treatment device 100 also includes a capsule interface feature in the form of a first piercing element 112 and a second piercing element 114.

[0066] The first piercing element 112 and the second piercing element 114 are each configured to form a hole in the capsule 120 by piercing (or breaking) the sealing layer 136 of the capsule 120 .

[0067] Specifically, the first piercing element 112 is configured to form a first hole in the inlet chamber 124 by piercing the sealing layer 136 located below the inlet chamber 124 (when the capsule 120 is oriented with the sealing layer 136 facing down). Similarly, the second piercing element 114 is configured to form a second hole in the outlet chamber 128 by piercing the sealing layer 136 located below the outlet chamber 128 (when the capsule 120 is oriented with the sealing layer 136 facing down).

[0068] 1, the first piercing element 112 is configured to form a first hole in fluid communication with a first port 116 (and thus in fluid communication with the first conduit 102). In the example shown in FIG. 1, the first conduit 102 extends through the first piercing element 112 to define the first port 116 at an upper portion of the first piercing element 112, meaning that the first hole, once formed by the first piercing element 112, is in fluid communication with the first port 116.

[0069] Similarly, the second piercing element 114 is configured to form a second hole in fluid communication with the second port 118 (and thus in fluid communication with the second conduit 104). In the example shown in Figure 1, the second conduit 104 extends through the second piercing element 114 to define the second port 118 at an upper portion of the second piercing element 114, meaning that the second hole, once formed by the second piercing element 114, is in fluid communication with the second port 118.

[0070] The use of first and second conduits 102,104 extending through piercing elements 112,114 prevents ports 116,118 from becoming blocked by loose portions of sealing layer 136 after holes are formed in sealing layer 136.

[0071] The first piercing element 112 and the second piercing element 114 are configured to form holes in the capsule 120 by relative movement of the piercing elements 112, 114 towards the capsule 120. The relative movement of the piercing elements 112, 114 towards the capsule 120 may be provided by applying a force to the deformable capsule (e.g., as described with reference to Figures 5 to 7). For example, the force may be applied by an actuatable element 50 (described below) of a liquid treatment system in which the liquid treatment apparatus (i.e., the liquid treatment device 100 and the capsule 120) is received. Alternatively or additionally, the relative movement of the piercing elements 112, 114 towards the capsule 120 may be provided by compression of a compressible layer of the capsule (e.g., as described with reference to Figures 8 and 9) or a compressible layer within the liquid treatment device.

[0072] In the example shown in Figure 1, a first piercing element 112 is provided in a first recess 106 and a second piercing element 114 is provided in a second recess 108. Each of the recesses 106, 108 is formed in a surface 110 of the liquid treatment device 100 that contacts the capsule 120. Each of the recesses 106, 108 may include a hole (not shown) in fluid communication with the respective conduit 102, 104. The hole is provided at the base of the piercing element 112, 114 in the recess 106, 108 to allow any liquid reagent in the recess 106, 108 to drain into the respective conduit 102, 104.

[0073] In the case of a deformable capsule (e.g. as described with reference to Figures 5 to 7), the recesses 106, 108 allow the sealing layer of the capsule to deform when a compressive force is applied to the capsule, which means that the sealing layer is brought into contact with the piercing elements 112, 114. To allow the sealing layer to deform into the recesses 106, 108, the layer of adhesive does not extend over the areas where the recesses 106, 108 are located.

[0074] However, in the case of capsules with a compressible layer (e.g. as described with reference to Figures 8 and 9), deformation of the sealing layer prior to piercing is not required, which means that the recesses 106, 108 may not be provided. Instead, as described with reference to Figures 8 and 9, each piercing element may be provided in a passage in the compressible layer that allows the liquid reagent to flow through the compressible layer. Alternatively, if the compressible layer is, for example, arranged only below the liquid storage chamber, the piercing elements may be provided in the respective cavities located below the inlet and outlet chambers.

[0075] Forming the first and second holes in the capsule 120 allows the liquid reagent 122 to be removed from the capsule 120 via the first conduit 102 and / or the second conduit 104. As an example, a gas (e.g., air) may be supplied to the capsule 120 via the first conduit 102 and the first hole. Supplying the gas to the capsule 120 displaces the liquid reagent 122 within the capsule 120 and forces the liquid reagent 122 out of the second hole and into the second conduit 104. The liquid reagent 122 may then be transported to one or more components of the liquid treatment device 100 as required by the diagnostic test or assay being performed.

[0076] 1 illustrates two actuatable elements 50 of a liquid treatment system (not shown) in which the liquid treatment device 100 is received. As explained above, the actuatable elements 50 can apply a force that deforms the capsule 120 to provide relative movement of the piercing elements 112, 114 towards the capsule 120, or, in the case of a rigid (i.e. non-deformable) capsule, can apply a force that compresses a compressible layer of the capsule 120 to provide relative movement of the piercing elements 112, 114 towards the capsule 120. Specifically, one of the actuatable elements 50 applies a force to an inlet chamber 124 of the capsule 120, and another of the actuatable elements 50 applies a force to an outlet chamber 128 of the capsule 120.

[0077] The actuatable elements 50 may be configured to simultaneously apply a force to the capsule 120. For example, one of the actuatable elements 50 may be configured to apply a force to the capsule 120 while a force is being applied to the capsule 120 by another one of the actuatable elements 50. By simultaneously applying a force to the capsule 120, a hole in the capsule 120 may be formed with a single motion (e.g., a single downward movement of the actuatable element 50).

[0078] As shown in Figure 1, the relative movement of the piercing elements 112, 114 towards the capsule 120 forms holes in the capsule 120 on the same side of the capsule 120 (specifically, in the sealing layer 136 of the capsule). In the example shown in Figure 1, the piercing elements 112, 114 are configured to form first and second holes in the base of the capsule 120. Forming the second hole in the base of the capsule 120 maximizes the amount of liquid reagent 122 that can be removed from the capsule 120 because the liquid reagent outlet (i.e., the second hole) is always below the liquid reagent level in the capsule 120.

[0079] The first and second restrictions 130, 132 have a cross-sectional area larger than the cross-sectional area of ​​the second conduit 102. This ensures that the flow rate of the liquid reagent within the liquid treatment device 100 is not limited by the size of the restrictions 130, 132 in the capsule 120.

[0080] Gas supply for discharging liquid reagents FIG. 2 is a schematic diagram illustrating the liquid treatment device 100 of FIG. 1 further comprising a gas supply port in the form of an air supply port 150 in fluid communication with the first conduit 102 .

[0081] In use, gas (e.g., air) is supplied into the first conduit 102 via the air supply port 150 after a first hole is formed in the capsule 120. Fluid communication between the first conduit 102 and the first hole allows air to be supplied to the capsule 120. After a second hole is formed in the capsule 120, the pressurized air forces the liquid reagent out the second hole and into the second conduit 104.

[0082] 3, air may be supplied to the port by an air supply conduit 70 coupled to a variable pressure source (e.g., a pump). The air supply conduit 70 may be a component of a liquid handling system in which the liquid handling device is received. For example, the air supply conduit 70 may be a component of the same liquid handling system that includes the actuatable element 50.

[0083] Transformable capsule 4 is a schematic diagram showing a deformable capsule 220 mounted on the liquid treatment device 100. The capsule 220 comprises a deformable capsule body 234. The capsule 220 comprises an inlet chamber 224, a liquid storage chamber 226, an outlet chamber 228, a first restriction 230 and a second restriction 232, which respectively have the same functions as the inlet chamber 124, the liquid storage chamber 126, the outlet chamber 128, the first restriction 130 and the second restriction 132 described with reference to FIG. 1. Similar to the capsule 120 shown in FIG. 1, the capsule 220 contains a liquid reagent 222 and is sealed using a sealing layer 236.

[0084] 4 illustrates the capsule body 234 shown in a deformed state. In particular, FIG. 4 illustrates the capsule 220 after a force has been applied to the inlet chamber 224 and the outlet chamber 228 by the actuatable element 50.

[0085] Taking the inlet chamber 224 as an example, the force applied to the inlet chamber 224 by the actuatable element 50 compresses the inlet chamber 224, thereby decreasing its volume. The decrease in the volume of the inlet chamber 224 compresses the air in the inlet chamber 224, which forces the sealing layer 236 to bulge outward from the first recess 106 in which the first piercing element 112 is located. This causes the sealing layer 236 to come into contact with the first piercing element 112, which means that the first piercing element 112 pierces the sealing layer 236 below the inlet chamber 224. The sealing layer 236 below the outlet chamber 228 is similarly pierced by the second piercing element 114.

[0086] Alternative Capsule Interface Mechanisms Figures 5A and 5B are schematic diagrams of an alternative liquid treatment device 300 (e.g., a cartridge) fitted with a capsule 320 that stores a liquid reagent 322. Similar to the liquid treatment device 100 shown in Figure 1, the liquid treatment device 300 of Figures 5A and 5B includes a first conduit 302 and a second conduit 304, each of which may be provided within a fluidic layer of the liquid treatment device 300.

[0087] The liquid treatment device 300 includes a first recess 306 and a second recess 308, each of which is provided in a surface 310 of the liquid treatment device 300 that contacts the capsule 320. The first recess 306 is in fluid communication with the first conduit 302 through a first port 316 in the surface of the first recess 306. Similarly, the second recess 308 is in fluid communication with the second conduit 304 through a second port 318 in the surface of the second recess 308.

[0088] Similar to the capsule 120 shown in Figure 1, the capsule 320 shown in Figures 5A and 5B includes an inlet chamber 324, a liquid storage chamber 326, an outlet chamber 328, a first restriction 330, a second restriction 332, a capsule body 334 and a sealing layer 336. Each of these components has the same function as described above for the capsule 120 shown in Figure 1.

[0089] Additionally, the capsule 320 includes a first recess 338 in the portion of the capsule body 334 that defines the upper surface of the inlet chamber 324. The capsule 320 also includes a second recess 340 in the portion of the capsule body 334 that defines the upper surface of the outlet chamber 328.

[0090] The depressions 306 , 308 in the surface 310 of the liquid treatment device 300 and the recesses 338 , 340 in the capsule body 334 together form a capsule interface feature that allows for the formation of holes in the sealing layer 336 of the capsule 320 .

[0091] 5A and 5B show two actuatable elements 52 of a liquid treatment system (not shown) in which the liquid treatment apparatus (i.e., liquid treatment device 300 and capsule 320) is received. One end of the actuatable elements 52 is configured to fit within a first recess 338 and another end of the actuatable elements 52 is configured to fit within a second recess 340. The recesses 338, 340 and / or the actuatable elements 52 may be sized to allow the ends of the actuatable elements 52 to fit within the recesses 338, 340.

[0092] Similar to the capsule 220 shown in Figure 4, the capsule body 334 of the capsule 320 is deformable. Figure 5A shows the capsule body 334 in an undeformed state, and Figure 5B shows the capsule body 334 in a deformed state.

[0093] One of the actuatable elements 52 is configured to apply a force to the inlet chamber 324 by applying a downward force to the recess 338. Another of the actuatable elements 52 is configured to apply a force to the outlet chamber 328 by applying a downward force to the recess 340.

[0094] Taking the inlet chamber 324 as an example, the force applied by the actuatable element 52 to the recess 338 compresses the inlet chamber 324, thereby decreasing its volume. The decrease in the volume of the inlet chamber 324 compresses the air within the inlet chamber 324, which forces the sealing layer 336 to stretch outwardly of the first recess 306. The stretching of the sealing layer 336 causes the sealing layer 336 to rupture, thereby forming a hole in the sealing layer 336. The sealing layer 336 below the outlet chamber 328 is similarly pierced by the second piercing element 114.

[0095] The capsule interface features in the form of the depressions 306, 308 and the recesses 338, 340 allow the sealing layer 336 of the capsule 320 to deform into the depressions 306, 308 when a force is applied to the recesses 338, 340. This causes a hole to form in the sealing layer 336. As shown in Figures 5A and 5B, the first conduit 302 is in fluid communication with the first depression 306 via the first port 316, and the second conduit 304 is in fluid communication with the second depression 308 via the second port 318. As a result, the first depression 306 allows a hole to form in the sealing layer 336 to be in fluid communication with the first port 316. Similarly, the second depression 308 allows a hole to form in the sealing layer 336 to be in fluid communication with the second port 318.

[0096] In some embodiments, the sealing layer 336 is sufficiently inelastic such that compressed air in the inlet chamber 324 acting on the sealing layer 336 causes the sealing layer 336 to rupture. In other embodiments, a compressive force from the actuatable element 52 may be exerted on the sealing layer 336 to deform the sealing layer 336 into the recesses 306, 308, thereby deforming the sealing layer 336 into the recesses 306, 308 and subsequently rupturing it.

[0097] In instances where the actuatable element 52 exerts a compressive force on the sealing layer 336, each recess 338, 340 may be formed to minimize the distance between the base of the recess 338, 340 and the sealing layer 336. By minimizing the distance between the base of the recess 338, 340 and the sealing layer 336, the displacement of the actuatable element 52 required for it to contact the sealing layer 336 is minimized. This means that the amount of force required to deform the capsule body 334 is in turn minimized.

[0098] For example, as shown in FIG. 6A (undeformed capsule) and FIG. 6B (deformed capsule), each recess 338, 340 may be formed such that the inner surface of each recess 338, 340 contacts the sealing layer 336. This means that once the actuatable element 52 is fully inserted into the recess 338, 340, any further downward displacement of the actuatable element 52 acts directly on the sealing layer 336. This minimizes the force required to break the sealing layer 336 (and thus minimizes the amount of deformation of the capsule body 334 required to break the sealing layer 336). As best shown in FIG. 6B, the sealing layer 336 may be sealed against the inner surface of each recess 338, 340, which prevents the sealing layer 336 from sliding on the inner surface of each recess 338, 340. This further reduces the amount of force required to break the sealing layer 336.

[0099] 5A-6B show that the recesses 338, 340 have a profile that matches the end of the actuatable element 52. In an alternative example shown in FIGS. 7A and 7B, a capsule 420 is shown having filled recesses 438, 440. Similar to the embodiment shown in FIGS. 5A-6B, the recesses 438, 440 are formed in the capsule body 434 of the capsule 420. However, in the embodiment shown in FIGS. 7A and 7B, the first recess 438 and the second recess 440 are filled with a rigid material, such as a resin, respectively, which provides a substantially flat surface for engagement by the first and second actuatable elements 54. In this example, the end of the actuatable element 54 does not match the shape of the recesses 438, 440.

[0100] Holes are formed in the sealing layer 436 in the same manner as the embodiment described with reference to Figures 5A-6B, except that the actuatable element 54 applies a force to the rigid material in the recesses 438, 440. The force applied by the actuatable element 54 compresses the capsule body 434. Holes in the sealing layer 436 may be formed by tearing of the inelastic sealing layer material or by deformation of the sealing layer 436 due to the force applied to the filled recesses 438, 440 by the actuatable element 54 (both as described above with respect to Figures 5A-6B).

[0101] Filling the recesses 438, 440 to provide a surface for engagement by the actuatable element 54 means that the ends of the actuatable element 54 do not have to conform to the shape of the recesses 438, 440. As a result, an actuatable element 54 having a blunt end (e.g., as shown in Figures 7A and 7B) may be used to apply a compressive force to the capsule 420. Similar to the example shown in Figures 6A and 6B, the filled recesses 438, 440 may be provided in contact with, and if so, sealed to, the sealing layer 436.

[0102] Compressible Layer 8 shows an alternative liquid treatment device 500 (e.g., a cartridge) to which is attached a capsule 520 comprising a liquid reagent (not shown). Similar to the liquid treatment devices described above, the liquid treatment device 500 includes a first conduit 502 and a second conduit 504, each of which may be provided within a fluidic layer of the liquid treatment device 500.

[0103] Similar to the capsules described above, the capsule 520 shown in Fig. 8 includes an inlet chamber 524, a liquid storage chamber 526, an outlet chamber 528, a first restriction 530, a second restriction 532, a capsule body 534, and a sealing layer. Each of these components has the same function as the corresponding components of the capsules described above. In this example, the sealing layer is a first sealing layer 536.

[0104] The capsule 520 also includes a compressible layer 506 that includes a first passageway 508 and a second passageway 510. The compressible layer 506 is shown in an uncompressed state in Figure 8. The compressible layer 506 is disposed between a first sealing layer 536 and a rigid layer 516 of the liquid treatment device 500. The compressible layer 506 is attached to the first sealing layer 536 with an adhesive layer 518 between the first sealing layer 536 and the compressible layer 506.

[0105] The capsule body 534 comprises a first opening 538 at the base of the capsule 520. The first opening 538 is sealed by a first sealing layer 536. Additionally, the capsule body 534 comprises one or more second openings 540 (in the example shown in FIG. 8, two second openings 540 are shown). Each of the one or more second openings 540 is sealed by a corresponding second sealing layer 542. The openings 538, 540 allow for filling of the capsule 520, as described below with reference to FIG. 18.

[0106] Although the capsule body 534 is shown in FIG. 8 as having a first opening 538 and one or more second openings 540, the capsule attached to the liquid treatment device 500 may alternatively take the form of the capsule 120 shown in FIG. 1 or the capsule described below with reference to FIGS. 10A to 17B.

[0107] The liquid treatment device includes a capsule interface feature in the form of a first piercing element 512 and a second piercing element 514. The piercing elements 512, 514 may be integrally formed with the rigid layer 516. The piercing elements 512, 514 and / or the passages 508, 510 of the compressible layer 506 are configured such that when the capsule 520 is attached to the liquid treatment device 500, the first piercing element 512 is located in the first passage 508 and the second piercing element 514 is located in the second passage 510.

[0108] The first piercing element 512 and the second piercing element 514 are each configured to form a hole in the capsule 520 by piercing a first sealing layer 536 of the capsule 520. Specifically, the first piercing element 512 is configured to form a first hole in the inlet chamber 524 by piercing a first sealing layer 536 located below the inlet chamber 524 (when the capsule 520 is oriented with the first sealing layer 536 facing down). Similarly, the second piercing element 514 is configured to form a second hole in the outlet chamber 528 by piercing a first sealing layer 536 located below the outlet chamber 528 (when the capsule 520 is oriented with the first sealing layer 536 facing down).

[0109] As shown in Figure 8, the first piercing element 512 is configured to form a first hole in fluid communication with the first conduit 502. In the example shown in Figure 8, the first conduit 502 extends through the first piercing element 512 to define a first port in the first piercing element 512, meaning that the first hole, once formed by the first piercing element 512, is in fluid communication with the first port (and thus the first conduit 502).

[0110] Similarly, the second piercing element 514 is configured to form a second hole in fluid communication with the second conduit 504. In the example shown in Figure 8, the second conduit 504 extends through the second piercing element 514 to define a second port in the second piercing element 514, meaning that the second hole, once formed by the second piercing element 514, is in fluid communication with the second port (and thus the second conduit 504).

[0111] The first piercing element 512 and the second piercing element 514 are configured to form holes in the capsule 520 by relative movement of the piercing elements 512, 514 towards the capsule 520. In the example shown in Figure 8, the relative movement of the piercing elements 512, 514 towards the capsule 520 is achieved by compression of the compressible layer 506, which causes the piercing elements 512, 514 to contact and pierce the first sealing layer 536.

[0112] 9 illustrates the compressible layer 506 in a compressed state. As shown in FIG. 9, compression of the compressible layer 506 provides relative movement of the piercing elements 512, 514 toward the capsule 520, thereby causing the piercing elements 512, 514 to pierce the first sealing layer 536.

[0113] The compressible layer 506 may be compressed (similar to the embodiments described with reference to Figures 1 to 7) by a force applied to the capsule body 534. For example, if the capsule body 534 comprises a stiff material (or a material that is less compressible than the compressible layer 506), the force applied to the capsule body 534 is transferred to the compressible layer 506, thereby causing the compressible layer 506 to compress.

[0114] Alternatively, the compressible layer 506 may extend beyond the footprint of the capsule body 534, in which case the compressible layer 506 may be compressed by a force applied to the top of the compressible layer 506 in the area beyond the footprint of the capsule body 534.

[0115] The compressible layer 506 shown in Figures 8 and 9 may be incorporated into the capsule shown in Figures 1 to 4. In this case, the relative movement of the piercing element towards the capsule may be provided partly by deformation of the capsule body and partly by compression of the compressible layer. As an alternative to being included in a capsule, the compressible layer may instead be incorporated into the liquid treatment device 100,500.

[0116] Semi-teardrop shaped liquid reservoir Figures 10A-10C show a configuration of a capsule 620 that may be used in the capsules shown generally in Figures 1-9. Figure 10A is an isometric view of capsule 620, Figure 10B is a top view of capsule 620, and Figure 10C is a side view of capsule 620.

[0117] Similar to the capsules shown in Figures 1 to 9, the capsule 620 comprises an inlet chamber 624, a liquid storage chamber 626, and an outlet chamber 628. The inlet chamber 624 is in fluid communication with the liquid storage chamber 626 via a first restriction 630. The outlet chamber 628 is in fluid communication with the liquid storage chamber 626 via a second restriction 632. The shapes of the inlet chamber 624, the liquid storage chamber 626, and the outlet chamber 628 are defined by a capsule body 634. The capsule body 634 is sealed using a sealing layer 636.

[0118] As shown in Figures 10A to 10C, the inlet chamber 624 and the outlet chamber 628 each have a hemispherical shape. The liquid storage chamber 626 has a semi-teardrop shape, where the semi-teardrop shape should be taken to mean a teardrop split in half along a plane parallel to and coinciding with the longitudinal axis of the teardrop. The semi-teardrop shape can be approximated by a semi-cone shape (i.e., a cone split in half along a plane parallel to and coinciding with its longitudinal axis) joined to a semi-ellipsoid shape (i.e., a semi-ellipsoid (e.g., a deformed hemisphere) split in half along a plane parallel to and coinciding with its longitudinal axis) using a continuously smooth surface.

[0119] The semi-teardrop shaped liquid storage chamber 626 has a bulbous portion 638 (approximated as a semi-ellipsoid) located at the first restriction 630 and an apex portion 640 (corresponding to the apex of the approximation of a semi-cone) located at the second restriction 632. The apex portion 640 provides a taper between the bulbous portion 638 and the second restriction 632. The bulbous portion 638 and the apex portion 640 each have a concave surface.

[0120] The use of a semi-teardrop shape for the liquid storage chamber 626 minimizes the free surface of the liquid reagent within the liquid storage chamber 626 while maximizing the volume of the liquid storage chamber 626 and maximizing the tendency of the liquid reagent to remain in a uniform volume that coalesces towards the second restriction 632 during ejection of the liquid reagent from the capsule 620 (in other words, minimizing the tendency of the liquid reagent to split within the liquid storage chamber 626 during ejection of the reagent).

[0121] The first restriction 630 has a larger cross-sectional area than the second restriction 632. The larger cross-sectional area of ​​the first restriction 630 is provided to allow air supplied through the holes in the inlet chamber 624 to flow into the bulbous portion 638 of the liquid storage chamber 626.

[0122] The first restriction 630 is sized to minimize the flow of the liquid reagent into the inlet chamber 624. Similarly, the second restriction 632 is sized to minimize the flow of the liquid reagent into the outlet chamber 628. To minimize the flow of the liquid reagent, the first and second restrictions 630,632 are sufficiently narrow such that the surface tension of the liquid reagent prevents the liquid reagent from flowing through the restrictions 630,632.

[0123] When the capsule 620 is filled with liquid reagent, the surface of the liquid reagent will overflow into the inlet chamber 624 and the outlet chamber 628, even in the ideal case. This is because the volume of the liquid reagent in the liquid storage chamber 626 results in a pressure head that partially pushes the liquid reagent into the inlet chamber 624 and the outlet chamber 628. When the capsule 620 is sealed, the inlet chamber 624 and the outlet chamber 628 contain air, which is compressed by the liquid reagent that is pushed into the inlet chamber 624 and the outlet chamber 628 by the pressure head of the liquid reagent in the liquid storage chamber 626. The compression of the air in the inlet chamber 624 and the outlet chamber 628 exerts a compression force on the surface of the liquid reagent. This compression force counteracts the force acting on the liquid reagent as a result of the pressure head of the liquid reagent in the liquid storage chamber 626. As a result, the surface of the liquid reagent has a first equilibrium position located in the inlet chamber 624 slightly beyond the end of the first restriction 630, and a second equilibrium position located in the outlet chamber 628 slightly beyond the end of the second restriction 632, as shown in FIG. 10D.

[0124] In the ideal case, the surface of the liquid reagent does not extend to the position where the inlet chamber 624 and the outlet chamber 628 are perforated (as shown in FIG. 10D). This means that air supplied through the holes in the inlet chamber 624 (e.g. as described in connection with FIGS. 2 and 3) does not flow through the body of the liquid reagent. This prevents the formation of micro-bubbles in the liquid reagent.

[0125] The bulbous portion 638 of the liquid storage chamber 626 ensures that the free surface of the liquid reagent is minimized, which reduces the tendency of the liquid reagent to split during ejection from the capsule 620. As shown in Figure 10D, this minimized free surface results in the center of gravity 680 of the volume of liquid reagent in the liquid storage chamber 626 (shown in Figure 10D) being biased towards the second restriction 632 (i.e. closer to the second restriction 632 than to the first restriction 630).

[0126] The apex portion 640 of the liquid storage chamber 626 serves to minimize the free surface of the liquid reagent during the ejection of the liquid reagent from the capsule 620. In particular, the apex portion 640 provides a taper of the liquid storage chamber 626 between the bulbous portion 638 and the second restriction 632, which means that the free surface of the liquid reagent decreases continuously as the liquid is ejected from the capsule 620. The continuous decrease in the free surface of the liquid reagent during the ejection of the reagent encourages the liquid reagent in the liquid storage chamber 626 to remain in a uniform volume that coalesces towards the second restriction 632 as the liquid reagent is ejected. This reduces the tendency of the liquid reagent in the liquid storage chamber 626 to split during the ejection of the liquid reagent.

[0127] The shape of the liquid storage chamber 626 may be defined by an inlet angle 642 and an outlet angle 644. As shown generally in FIG. 10C, the inlet angle 642 is the minimum angle between (i) a line located on the centerline (or plane of symmetry) of the liquid storage chamber 626 and tangent to the surface of the bulbous portion 638, and (ii) vertical (i.e., perpendicular to the base of the sealing layer 636 or capsule 620). Similarly, the outlet angle 644 is the minimum angle between (i) a line located on the centerline (or plane of symmetry) of the liquid storage chamber 626 and tangent to the surface of the apex portion 640, and (ii) vertical (i.e., perpendicular to the base of the sealing layer 636 or capsule 620).

[0128] The values ​​of the inlet angle 642 and the outlet angle 644 depend on the type of liquid reagent in the capsule 620. That is, different inlet angle 642 and outlet angle 644 values ​​(and thus different shapes of the liquid storage chamber 626) are used for different liquid reagents to reduce the tendency of the liquid reagent to split during ejection of the reagent from the capsule 620.

[0129] The values ​​used for the inlet angle 642 and the outlet angle 644 depend on the material used for the capsule body 634, the flow rate of air into the inlet chamber 634, and various properties of the liquid reagent, including surface tension, wettability, and viscosity. For liquid reagents with higher surface tension, the inlet angle 642 may be made larger and the outlet angle 644 may be made smaller (as further explained below).

[0130] 10A-10C, the capsule 620 comprises a base plate 650 that defines an opening in the capsule body 634 (i.e., an opening sealed by the sealing layer 636). The base plate 650 may be integrally formed with the capsule body 634. The base plate 650 provides a surface for mounting the capsule 620 to a surface of a liquid treatment device or to a compressible layer of the capsule, as described above.

[0131] The tendency of certain liquid reagents to split during the release of the liquid reagent from the capsule 620 is shown in FIG. 10E, which also shows the inlet angle 642 and the outlet angle 644 in a schematic manner. With reference to FIG. 10D, it can be seen that the free surface of the liquid reagent is minimized before the formation of the holes. When air is supplied through the holes in the inlet chamber 624, the liquid reagent is forced out of the liquid storage chamber 626 into the outlet chamber 628. This increases the free surface of the liquid reagent in the liquid storage chamber 626. The increase in the free surface may result in the liquid reagent reaching an equilibrium position where its free surface is minimized by splitting into two parts located on either side of the liquid storage chamber 626, as shown in FIG. 10E. When splitting occurs, air may be introduced into the liquid reagent that is forced out of the holes in the outlet chamber 628.

[0132] As explained above, the values ​​of the inlet angle 642 and the outlet angle 644 may be adjusted to reduce the tendency of a particular liquid reagent to split. For example, to reduce the splitting of the liquid reagent in the capsule 620 shown in FIG. 10E, the value of the inlet angle 642 may be increased and the value of the outlet angle 644 may be decreased, as shown in FIG. 10F. This results in a greater volume of liquid reagent being released from the liquid storage chamber 626 before the liquid reagent splits. As a result, the volume of the split portion is reduced, which means that a higher percentage of the liquid reagent in the capsule may be utilized.

[0133] Different half-teardrop shapes for different reagents 11A-11C show alternative capsule shapes used for liquid reagents different from those used in capsule 620 shown in FIGS. 10A-10C. As shown in FIGS. 11A-11C, capsule 720 includes a liquid storage chamber 726 having an inlet angle 742 smaller than the inlet angle 642 of capsule 620 and an outlet angle 744 larger than the outlet angle 644 of capsule 620. This means that the curvature of the curve defining the top of bulbous portion 738 in FIGS. 11A-11C is greater (i.e. has a smaller radius of curvature) than the curvature of the curve defining the top of bulbous portion 638 in FIGS. 10A-10C. Capsule 720 shown in FIGS. 11A-11C may be used for liquid reagents having a lower surface tension than the liquid reagents used with capsule 620.

[0134] As shown in Figures 11A to 11C, the capsule 720 may include one or more regions 746 having a convex curvature (i.e., at the top portion 740 of the liquid storage chamber 726) to provide a continuous reduction in the free surface of the liquid reagent as the reagent is released from the capsule 720.

[0135] Filleted edges (cut edges) 12A-12C show a further alternative capsule shape, where the capsule 820 comprises a capsule body 834 having a fillet edge 848. Specifically, the fillet edge 848 is provided at the junction between the capsule body 834 and a base plate 850. Thus, the fillet edge 848 is provided at the base of the inlet chamber 824, the liquid storage chamber 826 and the outlet chamber 828. Providing the fillet edge 848 between the capsule body 834 and the base plate 850 improves the manufacturability of the capsule 820 for manufacturing methods such as cold forming.

[0136] When the fillet edge 848 is provided, a portion of the liquid reagent is drawn into the inlet chamber 824 by capillary action and forms a ring around the edge of the inlet chamber 824 (as shown in FIG. 12D). Furthermore, a portion of the liquid reagent is drawn into the outlet chamber 828 by capillary action, thereby forming a ring around the edge of the outlet chamber 828. As shown in FIG. 12D, the liquid reagent drawn into the inlet chamber 824 and the outlet chamber 828 by capillary action does not extend to the position where the inlet chamber 824 and the outlet chamber 828 are perforated. This means that air supplied through the holes in the inlet chamber 824 (e.g., as described in connection with FIGS. 2 and 3) does not flow through the body of the liquid reagent. This prevents the formation of microbubbles in the liquid reagent.

[0137] Large draft angle and nipple for manufacturing 13A-13C show a further alternative capsule shape in which capsule 920 comprises a capsule body 934 joined to a base plate 950 with a joint 952 having a larger draft angle than the fillet edge 848 of capsule 820 shown in Figures 12A-12C. The joint 952 having a larger draft angle increases the manufacturability of capsule 920 for manufacturing methods (such as cold forming) that may not be able to provide the fillet edge 848 of capsule 820.

[0138] When a joint 952 having a larger draft angle is used, the volume of liquid reagent in the inlet chamber 924 and the outlet chamber 928 of the capsule 920 is larger than the volume of liquid reagent in the inlet chamber 824 and the outlet chamber 828 of the capsule 820 having the fillet edge 848. As a result, air supplied through the holes in the inlet chamber 924 may pass through the volume of liquid reagent, forming microbubbles in the liquid reagent.

[0139] In order to prevent micro-air bubbles in the liquid reagent in the inlet chamber 924 from passing to the liquid storage chamber 926, the inlet chamber 924 comprises a nipple portion 954. The nipple portion 954 is defined in the inlet chamber 924 by a step change in curvature 956 between the surfaces of the capsule body 934 that define the inlet chamber 924. The step change in curvature 956 provides a sharp edge that extends around the interior of the inlet chamber 924. This means that the inlet chamber 924 comprises a lower portion 958 at the base of the inlet chamber 924, which has a truncated dome shape with a concave surface, and an upper portion 960, which has a dome shape with a concave surface, that provides the upper surface of the inlet chamber 924 (which is also the upper surface of the nipple portion 954). The upper portion 960 has a different curvature than the lower portion 958, which results in the step change in curvature 956 between the lower portion 958 and the upper portion 960. The upper portion 960 and the lower portion 958 may alternatively be joined by an intermediate portion where the surface of the inlet chamber 924 curves away from the interior of the inlet chamber 924 (instead of a sharp edge caused by the step change in curvature 956).

[0140] 13A-13C, the step change in curvature 956 extends around the periphery of the surface of the inlet chamber 924 above the height of the first restriction 930. This means that the first restriction 930 joins the liquid storage chamber 926 to a lower recess 958 of the inlet chamber 924.

[0141] The nipple portion 954 ensures that any microscopic gas bubbles in the liquid within the inlet chamber 924 are trapped within the inlet chamber 924. Specifically, when air is supplied through the holes in the inlet chamber 924, any microscopic gas bubbles are trapped around the step change in curvature 956. When the volume of the liquid reagent within the inlet chamber 924 is reduced (i.e., when the liquid reagent is released from the capsule 920), the microscopic gas bubbles trapped within the inlet chamber 924 are held around the periphery of the inlet chamber 924 at the base of the lower recess 958.

[0142] The ratio of the overall height of the inlet chamber 924 to the height of the step change in curvature 956 can be selected to minimize microbubbles. This ratio will depend on the flow rate of air supplied through the holes in the inlet chamber 924 and the properties of the liquid reagent when the capsules 920 are broken and the liquid reagent is formed on the base of the inlet chamber 924. For example, if the flow rate of broken capsules is high, the step change in curvature 956 may be located higher on the surface of the inlet chamber 924 (i.e., the ratio of the height of the inlet chamber 924 to the height of the step change in curvature 956 will be low).

[0143] The outlet chamber 928 may also include a nipple 962 defined by a step change in curvature 964 that extends around the surface of the capsule body 934 that defines the outlet chamber 928. In this case, the outlet chamber 928 also includes a lower portion 966 having a truncated dome shape with a concave surface, and an upper portion 968 having a dome shape with a concave surface and defining the top of the nipple 962 (i.e., the top of the outlet chamber 928). The upper portion 968 has a different curvature than the lower portion 966, which results in a step change in curvature 964 between the lower portion 966 and the upper portion 968. The upper portion 968 and the lower portion 966 may alternatively be joined by an intermediate portion where the surface of the outlet chamber 928 curves away from the interior of the outlet chamber 928 (instead of a sharp edge resulting from the step change in curvature 964). The step change in curvature 964 extends around the surface of the outlet chamber 928 above the height of the second restriction 932.

[0144] If the liquid reagent includes a surfactant and / or other bubble generating and / or foaming agent, micro-bubbles may form on the surface of the liquid reagent in the liquid storage chamber 926 when the capsule 920 is struck or broken. The nipple portion 962 of the outlet chamber 928 traps any micro-bubbles in the outlet chamber 928. Specifically, as the liquid reagent moves from the liquid storage chamber 926 to the outlet chamber 928, any micro-bubbles are trapped around the step change in curvature 964. When the volume of the liquid reagent in the outlet chamber 928 decreases (i.e., when the liquid reagent is released from the capsule 920), the micro-bubbles trapped in the outlet chamber 928 are held around the periphery of the outlet chamber 928 at the base of the lower recess 966.

[0145] It will be appreciated that the nipples 954, 962 would have a diminishing effect with a deformable capsule body, since the nipples 954, 962 would be crushed by forces applied to the inlet chamber 924 and the outlet chamber 928. Therefore, preferably, the capsule 920 is used with a hard capsule. For example, the sealing layer 936 of the capsule 920 may be attached to a compressible layer (e.g., as described with reference to Figures 8 and 9).

[0146] Removal of liquid reagent from a semi-teardrop shaped liquid storage chamber Figure 14 is a schematic diagram of a capsule 1020 having a semi-teardrop shaped liquid storage chamber 1026 mounted on the liquid treatment device 100 shown in Figures 1 to 4. The capsule 1020 stores a liquid reagent 1022 that is primarily held in the liquid reservoir 1026. As described in relation to Figures 1 to 4, the liquid treatment device 100 includes a capsule interface mechanism configured to form a first opening in an entrance chamber 1024 of the capsule 1020 and a second opening in an exit chamber 1028 of the capsule 1020. The liquid reagent 1022 may be released from the capsule 1020 in a similar manner as described above in relation to Figures 1 to 4.

[0147] Alternatively, the capsule 1020 may further comprise a compressible layer (e.g., as described in connection with Figures 8 and 9). As a further alternative, the capsule 1020 may be attached to a liquid treatment device that does not comprise a piercing element (e.g., as described in connection with Figures 5 to 7), in which case the inlet chamber 1024 and the outlet chamber 1028 of the capsule 1020 may comprise a recess (which may be filled) and preferably do not include a nipple portion.

[0148] Alternative Liquid Storage Chamber Shapes 15A-15C show an alternative capsule design in which the capsule 1120 comprises a liquid storage chamber 1126 having a flattened dome shape. The capsule 1120 can be used with any of the liquid handling devices described above. The capsule 1120 comprises an inlet chamber 1124 and an outlet chamber 1128. The inlet chamber 1124 and the outlet chamber 1128 are shown in FIGS. 15A-15C as comprising recesses that allow holes to be formed in the capsule 1120. The inlet chamber 1124 and the outlet chamber 1128 may alternatively have a concave shape having the features of the inlet and outlet chambers of the capsule described with reference to FIGS. 10A-14.

[0149] The liquid storage chamber 1126 has a flattened dome shape. In a further alternative capsule design, the liquid storage chamber 1126 may have a rounded cone shape (or a non-flattened dome shape) whose apex defines the capsule height. These shapes of the liquid storage chamber 1126 may be easier to manufacture using cold forming, since less material needs to be deformed to provide the final capsule shape. Thus, these shapes of the liquid storage chamber 1126 may better accommodate the 3:1 draw ratio recommended for foil capsules (where the draw ratio is defined as the surface area of ​​the formed foil divided by the surface area of ​​the foil before forming).

[0150] Figures 16A to 16C show a further alternative capsule design in which the capsule 1220 comprises a liquid storage chamber 1226 having an elongated shape. The capsule 1220 can be used with any of the liquid treatment devices described above. The capsule 1220 comprises an inlet chamber 1224 and an outlet chamber 1228 which may comprise features of the inlet and outlet chambers of the capsule described with reference to Figures 10A to 14. When the capsule 1220 is used with the liquid treatment device 300 shown in Figures 5 to 7, the inlet and outlet chambers 1224, 1228 may alternatively comprise recesses (which may be filled).

[0151] The liquid storage chamber 1226 of the capsule 1220 has an elongated shape. Specifically, the liquid storage chamber 1226 comprises two semi-conical portions 1272 (their tips define the height of the capsule 120) separated by an elongated portion 1274 having a constant cross section. Again, this shape of the liquid storage chamber 1226 may be easier to manufacture using cold forming, as less material needs to be deformed to provide the final capsule shape.

[0152] 17A and 17B show a further alternative capsule design in which the capsule 1320 comprises a U-shaped liquid storage chamber 1326 between adjacent inlet and outlet chambers 1324 and 1328. The capsule 1320 may be used with any of the liquid treatment devices described above (although it will be appreciated that the separation between the piercing elements and / or recesses shown in FIGS. 1 to 9 is reduced). The inlet and outlet chambers 1324 and 1328 may comprise features of the inlet and outlet chambers of the capsules described with reference to FIGS. 10A to 14. When the capsule 1320 is used with the liquid treatment device 300 shown in FIGS. 5 to 7, the inlet and outlet chambers 1324 and 1328 may alternatively comprise recesses (which may be filled).

[0153] The liquid storage chamber 1326 of the capsule has a U-shaped portion 1376 with a constant cross-section. The liquid storage chamber 1326 also has rounded ends 1378 that join the U-shaped portion 1376 to the restrictions 1330, 1332. This shape allows the inlet and outlet holes to be closer together than with other shapes. This means that it is easier to form the two holes in a single motion (e.g. using a single actuator). The capsule 1320 is also a compact design that efficiently uses the footprint available in the liquid handling device.

[0154] How to take out liquid reagents Figure 18 is a flow chart of a method 1400 of extracting a liquid reagent from a capsule (e.g. as described in relation to the previous figures). The method 1400 may be implemented using a liquid treatment device (e.g. as shown in Figures 1 to 9) to which the capsule is attached, in combination with a liquid treatment system in which the liquid treatment apparatus (i.e. the liquid treatment device and capsule) is received. In particular, the liquid treatment system may comprise one or more actuatable elements configured to apply a force to the liquid treatment device or to one or more parts of the capsule attached to the liquid treatment device. The liquid treatment system may also comprise a variable pressure source (e.g. a pump) configured to supply air via an air supply conduit (e.g. air supply conduit 70 shown in Figure 3).

[0155] At 1402, a first hole in the capsule and a second hole in the capsule are formed. As described above, the first hole and the second hole may be formed by relative movement between the capsule and the capsule interface feature. The relative movement may be provided by applying a force to one or more of the capsule and the liquid treatment device with the liquid treatment system. For example, a force may be applied to the capsule by the liquid treatment system to deform the capsule. As another example, a force may be applied to the liquid treatment device and / or the capsule by the liquid treatment system to compress a compressible layer of the capsule.

[0156] At 1404, gas is supplied through a first hole in the capsule to expel the liquid reagent from a second hole in the capsule. Supplying the gas through the first hole may comprise coupling a gas supply port of the liquid treatment device to a variable pressure source (e.g., a pump) configured to supply gas (e.g., air) and supplying gas from the variable pressure source to the first hole through a conduit of the liquid treatment device in fluid communication with the gas supply port and the first hole.

[0157] When the liquid treatment device is inserted into the liquid treatment system, the liquid treatment system may be able to perform the steps of method 1400. The liquid treatment system may also include software that enables one or more fluid operations to be performed on the liquid treatment device. The software may also be configured to enable the liquid treatment system to perform the steps of method 1400. Thus, the described methods may be implemented using computer executable instructions. A computer program product or computer readable medium may comprise or store computer executable instructions. A computer program product or computer readable medium may comprise a hard disk drive, a flash memory, a read only memory (ROM), a CD, a DVD, a cache, a random access memory (RAM), and / or any other storage medium in which information is stored for any period of time (e.g., long term, permanent, short term, for temporary buffering, and / or for caching of information). A computer program may comprise computer executable instructions. A computer readable medium may be a tangible or non-transitory computer readable medium. The term "computer readable" encompasses "machine readable."

[0158] Capsule Construction FIG. 19 is a schematic diagram illustrating the construction of a capsule 1520 (e.g., the capsule shown in FIG. 8 and FIG. 9). As shown in FIG. 19, the capsule 1520 comprises a capsule body 1534 comprising a first opening 1538 and one or more second openings 1540 (two second openings are shown in FIG. 19). The capsule body 1534 defines an inlet chamber 1524 separated from a liquid storage chamber 1526 by a first restriction 1530, and an outlet chamber 1528 separated from the liquid storage chamber 1526 by a second restriction 1532. The first opening 1538 extends across the base of the inlet chamber 1524, the liquid storage chamber 1526 and the outlet chamber 1528, as well as the area in which the restrictions 1530, 1532 are located.

[0159] The area of ​​the first opening 1538 is greater than the area of ​​the one or more second openings 1540. For example, the total area of ​​the one or more second openings 1540 may be 50% less than the area of ​​the first opening 1538, preferably 90% less, or more preferably 95% less.

[0160] The capsule 1520 comprises a first sealing layer 1536 configured to seal the first opening 1538 and one or more second sealing layers 1542 each configured to seal a corresponding one of the one or more second openings 1540 (two second sealing layers 1542 are shown in FIG. 19). Alternatively, one of the one or more second sealing layers may be configured to seal multiple second openings. For example, a tape-like sealing layer may seal multiple second openings adjacent to each other (e.g., when the capsule body 1334 of FIG. 17A and FIG. 17B comprises an opening at the top of each of the inlet and outlet chambers 1324, 1328).

[0161] Additionally, the capsule 1520 includes a compressible layer 1506 having a first passageway 1508 and a second passageway 1510. The compressible layer 1506 is attached to a first sealing layer 1536 using an adhesive layer 1518.

[0162] How to build a capsule FIG. 20 is a flow chart of a method 1600 of constructing a capsule (e.g., capsule 1520 shown in FIG. 19). That is, the capsule comprises a capsule body comprising a first opening and one or more second openings. As an example, the first opening extends across the base of the capsule body, while the one or more second openings are provided on a surface of the capsule body (e.g., an opening at the top of the inlet chamber and / or the outlet chamber). As a result, the area of ​​the one or more second openings is smaller than the area of ​​the first opening.

[0163] At 1602, a first opening in the capsule body is heat sealed with a first seal. This step forms a container configured to hold a volume of a liquid reagent.

[0164] At 1604, the container is filled with a liquid reagent through at least one of the one or more second openings. Specifically, the container may be filled with a liquid reagent through a second opening in a top surface of the inlet chamber, such that the container can be filled with the liquid reagent without the liquid reagent flowing into the outlet chamber due to a capillary stop provided by a restriction between the liquid storage chamber and the outlet chamber.

[0165] For example, a liquid reagent may be supplied to a first of the one or more second openings (e.g. in the inlet chamber) and another of the one or more second openings (e.g. in the outlet chamber) is used to evacuate air displaced from the capsule as it is filled with the liquid reagent. Alternatively or additionally, the first of the one or more second openings (e.g. in the inlet chamber) may be large enough to accommodate the supply of liquid reagent and the evacuation of air displaced from the capsule (in which case only one second opening may be necessary).

[0166] At 1606, once the container is filled with a desired volume of liquid reagent, the one or more second openings may be sealed with a second seal. For example, the one or more second openings may be sealed with one or more sealing layers covering the one or more second openings and a pressure sensitive adhesive between the sealing layer(s) and the capsule body.

[0167] By constructing a capsule using the method 1600 described above, the liquid reagent within the capsule is not subjected to the heat sealing process because the heat sealing of the capsule is performed before the capsule is filled with the liquid reagent. Therefore, if the liquid reagent is sensitive to temperature changes, it is not subjected to the heat sealing step which would cause damage to the liquid reagent.

[0168] Prior to sealing the one or more second openings at 1606, air may be supplied through a first of the one or more openings (e.g., in the inlet chamber) to fill the inlet chamber with air and transfer the liquid reagent from the inlet chamber to the liquid storage chamber.

[0169] The method 1600 may be implemented as part of a computer-implemented manufacturing process. Thus, the described methods may be implemented using computer-executable instructions. A computer program product or computer-readable medium may comprise or store computer-executable instructions. The computer program product or computer-readable medium may comprise a hard disk drive, a flash memory, a read-only memory (ROM), a CD, a DVD, a cache, a random access memory (RAM), and / or any other storage medium in which information is stored for any period of time (e.g., long term, permanent, short term, for temporary buffering, and / or for caching information). A computer program may comprise computer-executable instructions. A computer-readable medium may be a tangible or non-transitory computer-readable medium. The term "computer-readable" encompasses "machine-readable."

[0170] Although the example capsule described above includes three chambers and first and second restrictions, capsules with fewer chambers may be used with the liquid treatment device and capsule interface mechanism described above. When fewer chambers are used, the liquid reagent released from the capsule may be drained into a chamber in fluid communication with a second hole in the liquid treatment device before being transported to a specific location in the liquid treatment device. This allows any air bubbles in the liquid reagent to be drained. Capsules with fewer chambers provide the above-mentioned advantage of releasing a greater proportion of the liquid reagent from the capsule (e.g., by feeding air through one hole in the capsule to drain the liquid reagent from another hole in the capsule).

[0171] The singular terms "a" and "an" should not be construed to mean "only one." Rather, unless otherwise specified, they should be construed to mean "at least one" or "one or more." "Comprising," including "comprises" and "comprises," and derivatives thereof, includes each of the listed features but does not exclude the inclusion of one or more additional features.

[0172] The above-described embodiments have been described by way of example only, and the described embodiments are to be considered in all respects only as illustrative and not restrictive. It will be understood that modifications may be made to the described embodiments without departing from the scope of the invention. It will also be apparent that there are many variations which have not been described but which are within the scope of the appended claims.

Claims

1. a capsule configured to store a liquid reagent; a liquid treatment device having a first conduit in fluid communication with the first port and a second conduit in fluid communication with the second port; a capsule interface mechanism configured to form a first hole in the capsule in fluid communication with the first port and a second hole in the capsule in fluid communication with the second port; Equipped with A liquid handling device, wherein forming the first hole and the second hole allows the liquid reagent to be removed from the capsule.

2. The liquid treatment device further comprises a gas supply port configured to receive gas supplied by a variable pressure source; the gas supply port is in fluid communication with the first conduit; 2. The liquid handling apparatus of claim 1, wherein the first conduit is configured to supply gas received through the gas supply port to the first hole and to exhaust liquid reagent from the second hole after the first and second holes are formed.

3. 3. A liquid handling apparatus according to claim 1 or claim 2, wherein the capsule interface feature is configured to form the second hole while forming the first hole.

4. 3. A liquid handling apparatus according to claim 1 or claim 2, wherein the capsule interface feature is configured to form the first and second holes on the same side of the capsule.

5. 3. A liquid handling apparatus according to claim 1 or claim 2, wherein the capsule interface feature is configured to form the second hole in a base of the capsule.

6. 3. A liquid handling apparatus according to claim 1 or claim 2, wherein the capsule comprises a deformable material, and the capsule interface feature is configured to form the second hole in the capsule when the deformable material is deformed.

7. one or more of the capsule and the liquid treatment device comprises a compressible layer configured to bias the capsule away from the capsule interface feature; 3. A liquid handling apparatus according to claim 1 or claim 2, wherein the capsule interface feature is configured to form the second aperture in the capsule when the compressible layer is compressed.

8. 8. The liquid handling apparatus of claim 7, wherein the compressible layer comprises a passage in fluid communication with the second conduit, the passage configured to allow flow of liquid reagent from the second hole through the compressible layer.

9. 3. Liquid handling apparatus according to claim 1 or claim 2, wherein the capsule interface feature comprises a piercing element configured to pierce the capsule to form the second hole.

10. The capsule interface mechanism includes a piercing element configured to pierce the capsule to form the second hole; The liquid handling apparatus of claim 8 , wherein the piercing element is disposed within the passageway.

11. 3. A liquid handling apparatus according to claim 1 or claim 2, wherein the liquid handling apparatus comprises the capsule interface mechanism.

12. The capsule comprises: a liquid storage chamber configured to store the liquid reagent; an inlet chamber and an outlet chamber, each of the inlet chamber and the outlet chamber being in fluid communication with the liquid storage chamber; a first restriction configured to impede the flow of liquid between the liquid storage chamber and the outlet chamber prior to formation of a hole in the capsule; a second restriction configured to impede the flow of liquid between the liquid storage chamber and the inlet chamber prior to formation of a hole in the capsule; A liquid handling apparatus according to claim 1 or 2, comprising:

13. The liquid handling apparatus of claim 12 , wherein the capsule interface feature is configured to form the second aperture in the outlet chamber.

14. 13. Liquid handling apparatus according to claim 12, wherein a cross-sectional area of ​​the first restriction is greater than or equal to a cross-sectional area of ​​the second conduit.

15. The liquid handling apparatus of claim 12 , wherein the capsule interface feature is configured to form the first aperture in the inlet chamber.

16. The liquid handling apparatus of claim 12 , wherein the outlet chamber comprises a recess in a surface of the capsule body that defines the outlet chamber.

17. 17. The liquid handling apparatus of claim 16, wherein the recess is filled with a rigid material.

18. the capsule comprises a sealing layer configured to seal an opening of the capsule body; 17. The liquid handling apparatus of claim 16, wherein an inner surface of the recess is in contact with the sealing layer prior to formation of the hole in the capsule.

19. 20. The liquid handling apparatus of claim 18, wherein an inner surface of the recess is sealed against the sealing layer prior to formation of the hole in the capsule.

20. 13. The liquid handling apparatus of claim 12, wherein the liquid storage chamber has a semi-teardrop shape with a bulbous portion adjacent the first restriction and an apex portion providing a taper between the bulbous portion and the second restriction.

21. the shape of the bulbous portion is defined by an inlet angle, the inlet angle being the minimum angle between a first line lying on a plane of symmetry of the liquid storage chamber and tangent to a surface of the bulbous portion and a second line perpendicular to the base of the capsule; the shape of the apex portion is defined by an exit angle, the exit angle being the minimum angle between a third line lying on a plane of symmetry of the liquid storage chamber and tangent to a surface of the apex portion and a fourth line perpendicular to the base of the capsule; The exit angle is greater than the entrance angle.

21. Liquid handling apparatus according to claim 20.

22. The outlet chamber comprises: a lower portion having a truncated dome shape with a concave surface having a first curvature; an upper portion joined to the lower portion, the upper portion having a dome shape with a concave surface having a second curvature different from the first curvature; a difference between the first curvature and the second curvature providing a gradual change in curvature at a junction between the upper portion and the lower portion.

13. Liquid handling apparatus according to claim 12.

23. The capsule comprises: a capsule body having a first opening and a second opening; a first sealing layer configured to seal the first opening; and a second sealing layer configured to seal the second opening. The area of ​​the second opening is smaller than the area of ​​the first opening.

3. A liquid processing device according to claim 1 or 2.

24. 24. The liquid handling apparatus of claim 23, wherein the capsule interface feature is configured to form the first and second holes in the first sealing layer.

25. 1. A method for extracting a liquid reagent stored in a capsule attached to a liquid handling device, comprising: forming a first hole in the capsule and a second hole in the capsule; supplying a gas through the first aperture to expel a liquid reagent from the second aperture; A method comprising:

26. Supplying a gas through the first hole includes: coupling a gas supply port of the liquid treatment device to a variable pressure source configured to supply a gas; supplying gas from the variable pressure source to the first bore via a conduit in fluid communication with the gas supply port and the first bore; 26. The method of claim 25 comprising:

27. A computer readable medium comprising instructions which, when executed by a processor of a liquid handling system configured to receive liquid handling equipment, cause the liquid handling system to perform the method of claim 25 or claim 26.

28. heat sealing the first opening of the capsule body with a first seal, thereby forming a container; filling the container with a liquid reagent through a second opening of the capsule, the area of ​​the second opening being smaller than the area of ​​the first opening; sealing the second opening with a second seal; A method for manufacturing a liquid reagent capsule comprising:

29. 30. The method of claim 28, wherein the second opening is sealed with a pressure sensitive adhesive.

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