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Title:
ASSEMBLY OF A MICROFLUIDIC DEVICE AND A CAP, CAP, MICROFLUIDIC DEVICE AND METHOD FOR INTRODUCING FLUID INTO A MICROFLUIDIC DEVICE
Document Type and Number:
WIPO Patent Application WO/2023/003469
Kind Code:
A1
Abstract:
The invention relates to an assembly of a microfluidic device and a cap, the microfluidic device comprising a microfluidic circuit comprising an inlet, a functional component and a vent fluidically connected to each other. The cap is configured to seal the inlet and the vent. The invention also relates to such a cap and such a microfluidic device, and to a method for introducing fluid into a microfluidic device.

Inventors:
BLOM MARKO THEODOOR (NL)
VAN 'T OEVER RONNY (NL)
CONDE ALVARO JOSE (NL)
Application Number:
PCT/NL2022/050430
Publication Date:
January 26, 2023
Filing Date:
July 22, 2022
Export Citation:
Click for automatic bibliography generation   Help
Assignee:
MICRONIT HOLDING B V (NL)
International Classes:
B01L3/00
Domestic Patent References:
WO2012123750A12012-09-20
WO2016069091A12016-05-06
WO2014087149A22014-06-12
WO2016069091A12016-05-06
Foreign References:
US20180272342A12018-09-27
Other References:
S. BEGOLO ET AL., LAB ON A CHIP, September 2014 (2014-09-01)
Attorney, Agent or Firm:
KAMPHUIS, Alex (NL)
Download PDF:
Claims:
Claims

1. Assembly of a microfluidic device and a cap, the microfluidic device comprising a microfluidic circuit comprising an inlet, a functional component and a vent fluidically connected to each other, characterized in that the cap is configured to seal the inlet and the vent.

2. Assembly according to claim 1, wherein the cap comprises a circumferential wall and an end surface connected to the circumferential wall.

3. Assembly according to any of the preceding claims, wherein the cap comprises a protrusion for sealing the vent, the protrusion optionally protruding from a free end of the circumferential wall for sealing the vent and/or wherein the protrusion comprises a first zone and a second zone, both defined in the direction in which the protrusion protrudes, wherein the second zone is position on the side of the first zone that is closest to the free end of the protrusion, wherein the first zone has a non-zero draft angle and wherein the second zone has substantially no draft angle.

4. Assembly according to claim 2 and optionally claim 3, wherein the circumferential wall has a height defined from the end surface to its free end, wherein the local height of the circumferential wall is at a maximum at and/or near the protrusion.

5. Assembly according to any of the preceding claims, further comprising a pumping mechanism, optionally comprising the cap, wherein the pumping mechanism is arranged to introduce fluid through the inlet into the microfluidic circuit, wherein preferably the cap is movable between a first position, in which it leaves free at least the inlet and optionally the vent, a second position, in which the pumping mechanism engages the microfluidic device and seals the inlet but not the vent, and a third position in which the cap seals the inlet and the vent.

6. Assembly according to the previous claim, wherein in the second position of the cap, the pumping mechanism together with the microfluidic device defines an enclosed volume fluidically connected to the inlet, and wherein as the cap is moved towards its second and third position, the enclosed volume is reduced, thereby creating a pumping action.

7. Assembly according to claim 5 or 6, the assembly further comprising at least one stop defining a respective intermediate position of the cap between the second and third position. 8. Assembly according to the previous claim, wherein the cap is movable from the at least one intermediate position towards the third position by rotating the cap with respect to the microfluidic device.

9. Assembly according to any of claims 5 - 8, wherein the pumping mechanism comprises an internal rim extending from a or the end surface of the cap, the internal rim defining an interspace between the internal rim and the circumferential wall, wherein optionally the internal rim has a free edge that protrudes radially outwards.

10. Assembly according to the previous claim, wherein the interspace decreases in size in a direction from the free end of the internal rim to the end surface.

11. Assembly according to any of claims 9 - 10, wherein the pumping mechanism further comprises a web spanning the internal rim.

12. Assembly according to the previous claim, the web being arranged at a distance from the end surface.

13. Assembly according to claim 11 or 12, the web being arranged at a distance from a free end of the internal rim.

14. Assembly according to any of claims 11 - 13, wherein the web has a convex shape as seen from the free end of the internal rim.

15. Assembly according to any of the preceding claims, wherein the microfluidic device comprises a receiving space for receiving the cap, wherein the inlet and the vent are arranged in the receiving space.

16. Assembly according to any of the preceding claims, wherein the microfluidic device comprises an open reservoir, the reservoir comprising the inlet, wherein the cap is configured to seal the inlet by sealing the reservoir.

17. Assembly according to the previous claim, wherein the inlet is arranged at a bottom of the reservoir.

18. Assembly according to any of claims 16 - 17, the reservoir being defined by an upstanding edge.

19. Assembly according to the previous claim, wherein the upstanding edge and the internal rim and/or the circumferential wall are configured to engage when the cap seals the inlet and the vent.

20. Assembly according to any of claims 18 - 19, wherein the upstanding edge has a thickness which decreases in a direction from the inlet to a free end of the upstanding edge.

21. Assembly according to any of claims 18 - 20, wherein the internal rim and/or the upstanding edge are shaped to deform under engagement when the cap seals the inlet and the vent.

22. Assembly according to any of the preceding claims, wherein the microfluidic device and the cap comprise mutually cooperating connecting elements, preferably configured for allowing connection but not disengagement, wherein optionally the mutually cooperating connecting elements are arranged at a distance from any part of the pumping mechanism.

23. Assembly according to the previous claim, wherein the mutually cooperating connecting elements comprise snap-hooks on the cap and/or the microfluidic device.

24. Assembly according to any of the preceding claims, the microfluidic device comprising at least one guide guiding the cap with respect to the microfluidic device to a sealing position.

25. Cap for sealing a microfluidic device with a microfluidic circuit having at least an inlet and a vent, the cap being configured for sealing the inlet and the vent.

26. Cap according to the previous claim, having the features described in relation to the assembly of any of claims 1 - 24.

26. Microfluidic device, having the features described in relation to the assembly of any of claims 1 - 24.

27. Method for introducing fluid into a microfluidic device, preferably using an assembly as defined in any of claims 1 - 24, the method comprising: a) providing the fluid in or near an inlet of the microfluidic device; b) forcing the fluid into a microfluidic circuit of the microfluidic device through the inlet, whilst allowing fluid to vent through a vent of the microfluidic circuit; c) sealing the inlet and the vent using a cap.

28. Method according to the previous claim, wherein step c) and/or step b) is performed using the cap.

Description:
ASSEMBLY OF A MICROFLUIDIC DEVICE AND A CAP, CAP, MICROFLUIDIC DEVICE AND METHOD FOR INTRODUCING FLUID INTO A MICROFLUIDIC DEVICE

The invention relates to a microfluidic device and a cap, the microfluidic device comprising a microfluidic circuit comprising an inlet, a functional component and a vent fluidically connected to each other.

Microfluidic devices having such microfluidic circuits are known by themselves. Microfluidic devices may be used in lab on a chip or point of care applications, as well as in other fields of use owing to their unique characteristics. As a non-limitative example, microfluidic devices can be used to carefully control the circumstances in which a chemical reaction takes place, so that a chemical test based on the reaction can be performed relatively accurately or quickly.

An assembly of a microfluidic device and a cap is known from international PCT-application with publication number W02016/069091 and “The pumping lid: Investigating multi-material 3D printing for equipment-free, programmable generation of positive and negative pressures for microfluidic applications” by S. Begolo et al., DOI: 10.1039/C4LC00910J (Lab on a Chip, September 2014). Begolo et al. disclose the use of a lid in order to seal an inlet of a microfluidic circuit on a microfluidic device. The lid is used at the same time to force fluid into the microfluidic circuit. The microfluidic circuit also comprises a vent, which allows air present in the microfluidic circuit to exit on the other end of the microfluidic device as the fluid is introduced.

The assembly of Begolo et al. has the disadvantage that after and/or during use, the microfluidic device may leak, and/or that functionality of the microfluidic device may be impaired by material escaping or entering through the vent. Accordingly, the microfluidic assembly of Begolo et al. must be used carefully and as such has limited use outside of laboratory environments.

The application therefore has as its object, next to other objects, to improve the assembly of Begolo et al. by making it more suitable for home and/or point of care use.

The object, next to other objects, is achieved using an assembly according to the preamble, wherein the cap is configured to seal the inlet and the vent.

By sealing both the inlet and the vent, leaking of the microfluidic device is reduced or prevented entirely. Moreover, when the cap seals the inlet and the vent, no material may enter or exit through the inlet or the vent, thereby allowing a better control of any functioning of the microfluidic device. This is particularly important when using nucleic acid amplification such as PCR or LAMP. If the amplified products would leak, or evaporate, from the device, they can contaminate a whole room and result in false positives for further tests. Accordingly, the assembly may be used relatively easily even outside lab environments, such as home or point of care environments.

The microfluidic circuit may include the inlet on one end, the vent on another end, with the functional component in between. More than one functional component may be present. The functional component may for instance include a reaction chamber, for instance provided with a reactant, a sensor, or any other component allowing functioning of the microfluidic device. The microfluidic circuit may have one or more other components such as channels, reservoirs, valves, MEMS’s, etc.

The microfluidic device may also comprise a plurality of inlets and/or vents. The cap is then preferably arranged to seal the plurality of inlets and/or vents. It is for instance possible that the microfluidic device comprises a microfluidic circuit with a plurality of vents. The device may also comprise a plurality of microfluidic circuits, for instance each provided with a respective inlet and vent.

Details of cap and the microfluidic device will be described below by referring to specific embodiments of the assembly. The application however also relates to the cap and the microfluidic device outside of the context of the assembly. As such, all details described below with reference to the cap and/or the microfluidic device may be applied to the cap and device respectively as described herein, alone or in any suitable combination. Embodiments of the cap and/or microfluidic device may overlap with embodiments of the assembly.

The vent may be open to the exterior of the microfluidic device, so as to allow e.g. air to exit from the microfluidic circuit when fluid is introduced at the inlet.

Since the vent can be sealed by the cap, there is no need to place a liquid impermeable membrane, capillary stop valve or other liquid stopping means such as an additional cap at the vent, thereby making the microfluidic device relatively elegant in design.

In a practical embodiment of the assembly or the cap, the cap comprises a circumferential wall and an end surface connected to the circumferential wall.

In another embodiment of the assembly or the cap, the cap comprises a protrusion for sealing the vent, the protrusion optionally protruding from a free end of the circumferential wall for sealing the vent.

The cap having a protrusion may allow a positive engagement of the vent, thereby creating a relatively reliable seal. The protrusion may protrude from any part of the cap, however it is particularly advantageous if the protrusion protrudes from said free end, as this may allow introducing the protrusion into the vent using the same motion as applying the cap to the device. Accordingly, a single movement may suffice for sealing the inlet and the vent. The protrusion may have an external dimension exceeding an internal dimension of the vent. Accordingly, the protrusion can be forced at least partly into the vent upon deformation of the protrusion and/or the vent, thereby achieving a relatively reliable sealing.

The protrusion may comprise a first zone and a second zone, both defined in the direction in which the protrusion protrudes, wherein the second zone is positioned on the side of the first zone that is closest to the free end of the protrusion, wherein the first zone has a non-zero draft angle and wherein the second zone has substantially no draft angle.

Accordingly, the protrusion comprises a straight section in its second zone, and a skewed section above (i.e. away from the free end) the second zone, in the first zone. The second zone may have a constant cross sectional size, e.g. a constant cross section.

When sealing the vent, the protrusion may engage the edge of the vent with the first zone, thereby possibly slightly deforming it. In the event the cap would move somewhat away from the microfluidic device, a gap could be made between the (deformed) edge of the vent and the protrusion. The second zone being straight, i.e. having a zero draft angle, may aid in sealing the vent even if the cap is move somewhat away from the microfluidic device, since the protrusion may still be in contact with the inside of the vent even in this position. In the configuration described herein, the protrusion thus more securely seals the vent.

The protrusion may be shaped such that as seen from the second zone towards the free end of the protrusion, the protrusion only diminishes in width or remains the same size. The second zone may thus be the wides or largest zone from the second zone onwards towards the free end. In the opposite direction, the protrusion may become somewhat wider or larger at the first zone, due to the draft angle thereof. Further yet, the protrusion may have another zone of substantially constant cross sectional size, e.g. of constant cross section.

In yet another embodiment of the assembly or the cap, the circumferential wall has a height defined from the end surface to its free end, wherein the local height of the circumferential wall is at a maximum at and/or near the protrusion.

In this embodiment, the circumferential wall is highest at or near the protrusion. Accordingly, said part of the circumferential wall is closest to the microfluidic device when the cap is applied to the microfluidic device.

As a result, the protrusion may contact the vent first, i.e. before other parts of the cap contacting the vent. As such, a relatively large amount or even all of the pressure with which the cap is applied to the microfluidic device is transferred to the protrusion and the vent. Accordingly, the protrusion may seal the vent relatively reliably. In yet another embodiment of the assembly or the cap, a pumping mechanism is provided, the pumping mechanism optionally comprising the cap, wherein the pumping mechanism is arranged to introduce fluid through the inlet into the microfluidic. The cap may function as a piston of the pumping mechanism, while a part of the microfluidic device, such as the upstanding edge or inlet, may function as a pumping chamber.

Preferably, the cap is movable between a first position, in which it leaves free at least the inlet and optionally the vent, a second position, in which the pumping mechanism engages the microfluidic device and seals the inlet but not the vent, and a third position in which the cap seals the inlet and the vent.

The pumping mechanism may be used to introduce fluid into the microfluidic circuit. Accordingly, the cap and the microfluidic device may be relatively easy to use, as no other appliances, such as pumps, are needed in order to introduce fluid into the microfluidic circuit. This embodiment therefore further relates to the original object of the invention of allowing use of the assembly in home or point of care environments by increasing its ease of use.

Although the pumping mechanism has been described in relation to the cap sealing the inlet and the vent, the pumping mechanism may also be applied to the assembly according to the preamble of claim 1 , or to an assembly with a cap that seal only the inlet and/or the vent.

Additionally or alternatively, using the pumping mechanism of the cap may allow a relatively controlled introduction of the fluid into the microfluidic circuit, for instance, the amount of liquid introduced may be limited by the design of the cap.

According to this embodiment, the cap performs a threefold functionality of sealing the inlet, sealing the vent, and pumping fluid into the microfluidic circuit.

In yet another embodiment of the assembly, the pumping mechanism together with the microfluidic device defines an enclosed volume fluidically connected to the inlet in the second position of the cap, and the enclosed volume is reduced as the cap is moved towards its third position, thereby creating a pumping action.

Reduction of the volume may bring about an increase in pressure, thereby providing a pumping action for introducing the fluid into the microfluidic circuit. The amount of reduction of the volume can be suitably chosen to limit the maximum volume of fluid introduced, so that the introduction can be controlled.

The reduction of the volume may be approximately equal to or exceed a combined volume of the functional element, or if more functional elements are provided, of the functional elements, and the channels leading up to the functional element(s) from the inlet. Optionally, the reduction in volume may not exceed a total volume of the microfluidic circuit. In yet another embodiment of the assembly, the assembly further comprises at least one stop defining a respective intermediate position of the cap between the second and third position.

Defining an intermediate position using a stop allows a user to notice relatively easily when the intermediate position is reached. The intermediate position can be used for instance to have the user wait for a predetermined period before moving the cap further towards the third position, i.e. before pumping further.

As such, a multi-step pumping process may be achieved with the aid of the stop. The waiting period may be used to allow sample material to progress into the microfluidic circuit, thereby reducing pressure in the microfluidic circuit. The reduced pressure may prevent or reduce damage to the microfluidic circuit, or may be advantageous to the functioning of e.g. the functional element.

The stop may be formed by a mechanical interaction between the cap and the microfluidic device. As an example, one of the microfluidic device and the cap may comprise a guide slot, the other of the microfluidic device and the cap comprising a follower engaging the slot, wherein the slot defines an arcuate or angled shape, so that the stop is formed by the arcuate or angled shape of the slot. As such, it is possible to move the cap towards the third position initially in a first direction until the arcuate or angled shape is reached. The shape of the slot prevents further movement in the same direction at this position of the cap, thereby thus providing a stop and defining the intermediate position. Changing a direction of the cap in accordance with the shape of the slot allows moving beyond the intermediate position further towards the third position.

In an embodiment, the cap is movable from the at least one intermediate position towards the third position by rotating the cap with respect to the microfluidic device.

Allowing the cap to move beyond the intermediate position only after rotation thereof, may aid in preventing inadvertently bypassing the at least one intermediate position.

Referring to the slot-and-follower example above, a first segment of the slot may extend in an axial direction of the cap to allow moving the cap towards the microfluidic device from the second position to an intermediate position. Then, a second segment of the slot may extend in a circumferential direction of the cap, requiring rotation of the cap to move beyond the intermediate position. Finally, a third segment of the slot may extend in the axial direction, allowing moving the cap closer to the microfluidic device again.

Multiple such intermediate positions may be defined, each having their own stop.

In an embodiment of the assembly or the cap, the pumping mechanism comprises an internal rim extending from a or the end surface of the cap, the internal rim defining an interspace between the internal rim and the circumferential wall. The internal rim may allow engagement of the pumping mechanism before the cap has reached the third position. Moreover, the internal rim may provide a surface for sealing against a part of the microfluidic device, such as the upstanding edge described below. The upstanding edge may be arranged in the interspace, thereby creating a relatively reliable seal.

A particularly reliable seal can be created if a free edge of the internal rim protrudes radially outwards. In this case, it may not be necessary to provide e.g. an O-ring for providing sufficient sealing performance. Moreover, by providing a radially outward protruding free end of the internal rim, the internal rim may be made of a relatively stiff material, such as HDPE. HPDE is normally unsuitable for manufacturing parts that would need to seal against each other, however, due to the shape as described herein, it becomes possible to use more stiff materials, such as HDPE, for the internal rim.

As other parts of the cap may also be manufactured from HDPE, the particular radially outwardly protruding shape may also allow manufacturing the cap integrally out of one part, for instance of HPDE.

The interspace may decrease in size in a direction from the free end of the internal rim to the end surface.

Owing to such a decreasing size, the interspace has a tapering shape which allows creating a more and more reliable seal on the upstanding edge when it is moved further into the interspace. In order to provide the decrease in size of the interspace, the internal rim may have an outer dimension which increases in said direction. It is possible to apply the increasing outer dimension of the internal rim regardless of the increase or decrease in size of the interspace.

In yet another embodiment of the assembly or the cap, the pumping mechanism further comprises a web spanning the internal rim.

The web spanning the rim may seal the internal rim, thereby allowing the internal rim to enclose a volume together with the microfluidic device when the internal rim engages on the microfluidic device, e.g. in the second position of the cap. Then, by reducing said enclosed volume a pressure can be created which generates a pumping action.

The web may be arranged at a distance from the end surface in order to limit the size of the enclosed volume. Limiting the size of the enclosed volume limits the amount of air in the enclosed volume when pumping starts. By limiting the amount of air, a buildup of energy in the air required for compressing of the air during pumping is limited. Accordingly, less pressure is needed for pumping the fluid, further contributing to the ease of use of the cap and/or assembly.

The web may be arranged at a distance from a free end of the internal rim. As a result, the free end of the internal rim may deform relatively easily. Accordingly, a deformation of the free end of internal rim may be used to create a reliable seal against a part of the microfluidic device. Allowing deformation of the internal rim in turn allows fabrication of the cap and/or the microfluidic device with more room for tolerance, whilst still providing a relatively reliable sealing.

The web may have a convex shape as seen from the free end of the internal rim. The convex shape may aid in providing sufficient strength of the web for providing pressure for pumping.

Preferably, the cap is manufactured from a plastic, for instance using an injection moulding process. The configuration of the cap and the inlet allows an efficient pumping and sealing mechanism without requiring softer, elastomeric sealing means as used in Begolo et al.

In yet another embodiment of the assembly or the microfluidic device, the microfluidic device comprises a receiving space for receiving the cap, wherein the inlet and the vent are arranged in the receiving space.

The microfluidic device may be a microfluidic chip.

Arranging the vent and the inlet in the receiving space may allow sealing the inlet and the vent with the same, single cap.

The inlet and the vent being arranged in the receiving space may mean the microfluidic circuit debouches to the exterior of the microfluidic device at the receiving space at its inlet and at its vent.

In order to arrange the vent close to the inlet, for instance sufficiently close to the inlet to seal the inlet and the vent with the same cap, the microfluidic circuit may comprise a return channel leading to the vent from e.g. a position further away from the inlet, for instance downstream of the functional component.

In yet another embodiment of the assembly or the microfluidic device, the microfluidic device comprises an open reservoir, the reservoir comprising the inlet, wherein the cap is configured to seal the inlet by sealing the reservoir.

By providing a reservoir, a user can relatively easily load the microfluidic device with a fluid. In particular, a user may be able to provide a sample, such as a saliva, blood or other sample in the reservoir. The reservoir comprising the inlet may allow moving the sample through the inlet into the microfluidic circuit upon application of a pumping force on the reservoir. When the reservoir comprises the inlet, the inlet can be sealed by sealing the reservoir.

When pumping fluid into the microfluidic circuit, it is not strictly necessary to completely empty the reservoir. In particular, some air may remain. Additionally, when a relatively large amount of sample material is provided in the reservoir, only a part of the sample material may be introduced into the microfluidic circuit when the cap is attached thereto. The reservoir may therefore also act as a way to store superfluous sample material and/or remaining air.

The inlet may be arranged at a bottom of the reservoir. Arranging the inlet at the bottom of the reservoir allows at least partly draining the reservoir whilst introducing little or no air to the microfluidic circuit.

The reservoir may be defined by an upstanding edge. The upstanding edge may provide a suitable surface for engaging the cap thereon. The upstanding edge may protrude from a surface, optionally a top surface of the microfluidic device.

In yet another embodiment of the assembly, the upstanding edge and the internal rim and/or the circumferential wall are configured to engage when the cap seals the inlet and the vent. A positive sealing may be achieved by engagement of the internal rim and the upstanding edge.

The upstanding edge may have a thickness which decreases in a direction from the inlet to a free end of the upstanding edge. Accordingly, the upstanding edge may have a tapering shape. The tapering shape allows increasing the engagement of the upstanding edge with the cap when the cap is moved from the free end of the upstanding edge towards the inlet. Accordingly, a more and more reliable seal may be achieved by forcing the cap against the tapering upstanding edge.

In particular, the internal rim and/or the upstanding edge may be shaped to deform under engagement when the cap seals the inlet and the vent.

When the rim and/or edge are shaped in order to deform under engagement, either one or both elements may be designed with a relatively large tolerance without hindering the sealing action of the engagement. Moreover, the deformation may cause the cap and microfluidic device to clamp onto each other, thereby making it more difficult to remove the cap.

In yet another embodiment of the assembly, the microfluidic device and the cap comprise mutually cooperating connecting elements, preferably configured for allowing connection but not disengagement.

Using the mutually cooperating connecting elements, inadvertent disengagement of the cap may be prevented. Moreover, the connecting elements may allow a user to easily ascertain the cap has been connected properly to the microfluidic device.

When the mutually cooperating connecting elements are configured for allowing connection but not disengagement, one time use of the assembly can be guaranteed or encouraged. Moreover, by preventing or discouraging removal of the cap, inadvertent influences on the functioning of the microfluidic device and/or may be prevented. Alternatively of additionally tampering may be complicated or prevented. The mutually cooperating connecting elements may comprise snap-hooks on the cap and/or the microfluidic device.

Snap-hooks can be used to provide the above-described single use configuration, and may at the same time provide haptic and/or audible feedback indicating to a user the cap has been properly connected.

The mutually cooperating connecting elements are preferably arranged at a distance from any part of the pumping mechanism, in particular the pumping chamber of the pumping device, more in particular an upstanding edge of the microfluidic device which optionally serves as a pumping chamber.

Arranging said connecting elements at a distance from the pumping mechanism prevents or reduces influence of any deformations caused by the connection elements on the pumping or sealing performance of the cap and the microfluidic device. Accordingly, the connecting elements on the microfluidic device can also be provided at a distance from a sealing part of the microfluidic device, for instance the upstanding edge, even if the upstanding edge is not part of a pumping mechanism.

In the cap, the mutually cooperating connecting elements are preferably arranged at a distance from any part of the pumping mechanism and/or at a distance form any part that seals the inlet and/or vent. For instance, said connecting elements may be arranged in the circumferential wall of the cap, as opposed to e.g. the internal rim of the cap.

The distance from the sealing elements and/or the pumping mechanism to the connecting elements may be increased (on the device and/or the cap) by providing the cap with a first relatively long dimension and an orthogonal relatively short dimension, as seen in plan view of the cap, and by providing the connecting elements one or both ends along the relatively long dimensions. As an example, the cap may have an oblong shape in plan view, and the connecting elements may be arranged at one or both of its longitudinal ends. The corresponding parts in the microfluidic device may be provided at corresponding positions.

In yet another embodiment of the assembly or the microfluidic device, the microfluidic device comprises at least one guide guiding the cap with respect to the microfluidic device to a sealing position.

The guide may be used to align the cap with the microfluidic device, e.g. for allowing the protrusion to align with the vent, thereby making it relatively easy to apply the cap.

The sealing position may correspond to the above-describe third position.

The invention also relates to a cap for sealing a microfluidic device with a microfluidic circuit having at least an inlet and a vent, the cap being configured for sealing the inlet and the vent. The cap may be used to create a relatively easy to use assembly, in which only one cap needs to be used for sealing the inlet and the vent, thereby preventing leaks.

In particular, the cap may be used in the assembly as described above. The cap may therefore have the features described above in relation to the assembly or the cap in particular, alone or in any suitable combination.

The invention also relates to a microfluidic device which has the features pertaining to the microfluidic device described above in relation to the assembly or to the microfluidic device in particular. The features may be applied to the microfluidic device alone or in any suitable combination.

Such a microfluidic device may in particular allow relatively easy use thereof, since the inlet and vent may be sealed using a single cap.

The invention also relates to a method for introducing fluid into a microfluidic device, preferably using an assembly as described above, the method comprising: a) providing the fluid in or near an inlet of the microfluidic device; b) forcing the fluid into a microfluidic circuit of the microfluidic device through the inlet, whilst allowing fluid to vent through a vent of the microfluidic circuit; c) sealing the inlet and the vent using a cap.

By sealing both the inlet and the vent, leaking of the microfluidic device is prevented. Accordingly, the method may be relatively easy to perform outside lab conditions, thereby making it suitable for use in e.g. home or point of care environments.

In an embodiment of the method, step c) is performed using the cap.

By forcing the liquid into the microfluidic circuit using the cap, a pumping action can be achieved by the cap, for instance when it is applied to the microfluidic device. As a result, no further equipment may be needed to use the microfluidic device, thereby making the method of this embodiment even more easy to perform in home or point of care environments.

The invention will be further elucidated with reference to the drawings, in which:

Figures 1A and IB schematically show perspective views of a microfluidic device and a cap, wherein in figure 1A the cap is removed from the microfluidic device, and in figure IB the cap is applied to the microfluidic device;

Figures 2A - 2C schematically show a perspective, top and bottom view of the microfluidic device respectively; Figures 3A - 3C schematically show a perspective view, a side view and another perspective view respectively, wherein in figure 3C the cap is viewed upside-down;

Figures 4A and 4B schematically show cross sections of the cap and the microfluidic device;

Figures 5A - 5C schematically show cross sections of the cap and the microfluidic device, with the cap in a first, second and third position respectively;

Figures 6A - 6D schematically show a simplified cross section and simplified perspective views of another embodiment of an assembly of a cap and a microfluidic device, in which the cap has been drawn in different positions

Figures 7A and 7B schematically show perspective views of yet another embodiment of a microfluidic device and a cap of an assembly as described herein;

Figure 8 shows a detailed cross section of the cap of figures 7A and 7B;

Figures 9A - 9C show schematically and for illustrative purposes a problem that may occur when sealing a vent with a cap with a protrusion; and

Figures 10A and 10B schematically show a simplified cross section of a protrusion and a vent and a detailed perspective view of the protrusion respectively of the assembly of figures 7A and 7B.

Throughout the figures, like elements will be referred to using like reference numerals. Like elements across different embodiments are referred to using reference numerals increased by one hundred (100).

Figures 1A and IB show an assembly 1 comprising a microfluidic device 2 and a cap 3. The microfluidic device 2 comprises a body 4 which defines a microfluidic circuit. The microfluidic circuit is not visible in figures 1A and IB and will therefore be described further below. The cap 3 can be applied to the microfluidic device 2 in order to seal it. The cap 3 is therefore placed over an upstanding edge 5 extending upwards from the body 4 of the microfluidic device 2. The upstanding edge 5 defines a reservoir 99, in which a fluid, for instance a liquid can be received. Snap hooks 6 are provided on two opposing sides of the upstanding edge 5. When the cap 3 is applied, the cap 3 extends over the snap hooks 6 and engages them. The snap hooks 6 accordingly allow the cap 3 to be applied to the microfluidic device 2, but not removed without significant effort and/or the use of tools. Further, two guide plates 7 extend upwards from the body 4 near the upstanding edge 5. The guide plates 7 are configured to engage the cap 3 in order to guide it towards a sealing position shown in figure IB. the guide plates have a slanted surface 7’ which direct the cap 3 to the sealing position cap 3 has an end surface 8, which forms the top of the cap 3, and a circumferential wall 9. More details of the cap 3 will be described below.

Referring now to figures 2A - 2C, more details of the microfluidic device 2 are described. The body 4 defines a microfluidic circuit, which in this example comprises an inlet 10, channels 12, a reaction chamber 13, an overflow, a return channel 15 and a vent 11. The reaction chamber 13 constitutes a functional element, which may be used for instance to perform an assay. A sample can be introduced in the reaction chamber 13 via a channel 12 which is fed via the inlet 10. Another channel 12 downstream of the channel allows superfluous sample material to flow towards the overflow 14. The overflow 14 is connected to the vent 11 via a return channel 12. The vent 11 allows air in the microfluidic circuit, e.g. in the channels 12, the reaction chamber 13, the overflow 14 and the return channel 15 to escape when sample material is introduced via the inlet 10. The channels 12, reaction chamber 13, overflow 14 and return channel 15 are composed of recesses produced in the body 4 of the microfluidic device 2. Suitable techniques for creating such structures are e.g. etching and casting, but other techniques may be employed. In practice, a sealing layer may be applied on the bottom 17 of the body 4 in order to close the recesses, thereby closing the channels 12, the reaction chamber 13, the overflow 14 and the return channel 15. As such, the only way in and out of the microfluidic circuit is via the inlet 10 and vent 11 respectively. In order to show details of the microfluidic circuit, no such sealing layer has been shown in the figures. The inlet 10 and the vent 11 are constituted by bores extending from the top surface 16 to the bottom 17 of the body 4. The bores for the inlet 10 and the vent 11 are placed such that they connect fluidically to the microfluidic circuit. The sealing layer seals one end of the bores, at the bottom 17 of the body 4. The other end of the bores is open at the top surface 16 of the body 4, so that fluid may be let in at the inlet 10, and air may be vented at the vent 11.

Referring to figures 3A - 3C, more details of the cap 3 are described. The cap 3 comprises, at a free end of its circumferential wall 9 a protrusion 18. The protrusion 18 protrudes from the free end in a direction away from the end surface 8 of the cap 3. It is noted that this position of the protrusion 18 is preferred, but can be chosen differently if desired. The protrusion 18 is arranged on a thicker portion 22 of the circumferential wall 9. The thicker portion 22 creates an engagement for the guides 7, and allows sufficient space for the protrusion 18. The circumferential wall 9 has a height h defined from the end surface 8 to the free end of the circumferential wall 9. The height h is maximal at the thicker portion 22, i.e. close to the protrusion 18. At that point, the circumferential wall 9 has a maximum height h m . The cap 3 further comprises a pumping mechanism, which in this example comprises an internal rim 19, which in this example is arranged generally concentrically with the circumferential wall 9. The internal rim 19 extends from the end surface, substantially in the same direction as the circumferential wall 9. The pumping mechanism further comprises a web 20 spanning the internal rim 20, which is arranged at a distance dl from the end surface 8 and at a distance d2 form a free end of the internal rim 19. The web 20 has a convex shape as seen from the free end of the internal rim 19. The end surface 8 defines a blind hole 21 in a central area thereof, the blind hole 21 ending in the web 20. Side walls of the blind hole 21 form a part of the internal rim 19.

With reference to figures 4A and 4B the interaction between the microfluidic device 2 and the cap 3 is described in more detail. In figure 4, it can be seen how a size s of an interspace 23 between the internal rim 19 and the circumferential wall 9 decreases towards the end surface 8 of the cap 3. The size s is made to decrease by the external diameter D of the internal rim increasing towards the end surface 8. The internal rim 8 engages the upstanding edge 5, and creates a sealing connection against it. Accordingly, the reservoir 99 defined by the upstanding edge 5 is sealed, thereby sealing the inlet 10. The upstanding edge 5 has a thickness t which decreases in a direction away from the inlet 10.

With reference to figures 5A - 5C the pumping action of the cap 3 will be described in more detail. As shown in figure 5 A, the cap 3 can be brought in a first position in which it leaves free the inlet 10 and the vent 11. Accordingly, both ends of the microfluidic circuit are open. A sample material 24, in this example a liquid, for instance saliva, blood, or another fluid, is provided in the reservoir 99. The cap 3 is brought to a second position shown in figure 5B, in which it seals the reservoir 99 but not the vent 11. By sealing the reservoir 99, the inlet 10 is sealed from the exterior of the microfluidic device. The cap 3 and microfluidic device 2 together enclose a volume in the reservoir, which holds the sample material 24. Then, by moving the cap 3 further down, i.e. towards the third position in figure 5C, the enclosed volume is decreased. The internal rim 19 remains sealed against the upstanding edge 5, so that the enclosed volume remains sealed. Accordingly, the pressure inside the reservoir 99 is increased, causing the sample material 24 to be pumped into the microfluidic circuit. As can be seen in figure 5C, the cap 3 still seals the reservoir 99 and thus the inlet the situation in figure 5C corresponds to that in figure 4B, in which it can be seen that the cap 3 also seals the vent, by having forced the protrusion 18 into the vent 11. In the assembly 1 shown, the protrusion 18 has an external diameter which is larger than an internal diameter of the vent 11. Thus, the situation in figure 4B reflects a deformation of the protrusion 18 and the vent 11. Similarly, the internal rim 19 and the upstanding edge 5 are slightly deformed, in order to seal against each other in the second and third positions of figures 5B and 5C.

Figures 6 A - 6D show another embodiment of an assembly with a cap 103 and a microfluidic device. Figures 6A - 6D have been simplified to more clearly explain their differences with respect to the earlier described embodiment. In figure 6A the cap 103 can be seen in cross section, in a position in which it seals the inlet 110 of a microfluidic device (partly shown). The body 104 of the microfluidic device is shown in dashed lines. The body 104 and thus the microfluidic circuit may be laid out for instance as described in relation to the embodiment of figures 1A - 5C. The cap 103 has an end surface 108 and a circumferential wall 109, as well as an internal rim 119. The web 120 spanning the internal rim 119 is in this embodiment arranged relatively close to the end surface 108 of the cap 103. Further, a protrusion 118 is shown for sealing the vent 118 in the body 104. Unique to this embodiment are snap hooks 129 arranged on the cap, which comprise at their end followers 130. In figures 6B - 6D, the circumferential wall 109 is not shown in order to expose the snap hooks 129. The body 104 of the microfluidic device is also not shown. The followers 130 are configured to cooperate with respective slots provided in the upstanding edge 105 of the microfluidic device. The slots each comprise, in this embodiment as an example, three sections 125, 126, 127. The slot acts as a guide for the followers 130. The first section 125 of the slot extends substantially parallel to an axial direction of the cap 103, i.e. vertically. This allows moving the cap 103 from a position away from the microfluidic device, shown in figure 6B (e.g. a first position) down towards the microfluidic device. When the internal rim 119 first engages the upstanding edge 105, the reservoir 199 defined between the cap 103 and the microfluidic device is sealed (e.g. a second position). As described above, a pumping action starts from this position onwards, as the cap 103 is moved further towards the microfluidic device. A second section 126 of the slot 126 extends in the circumferential direction of the cap 103, i.e. at an angle with respect to the first section 125. As a result, when moving the cap 103 along the slot (figure 6C), the followers 130 are blocked when they reach the second section 126. The second section 126 has a depth which is larger than that of the first section 125. Accordingly, the followers 130 snap into the second section 126, thereby creating a haptic and audible feedback for a user. The feedback may be used to indicate the cap 103 is at an intermediate position, which indicates for the user e.g. a waiting period. Next, the cap 103 can be rotated with respect to the upstanding edge 105, so that the followers 130 move along the second section 126 of the slot. At the end of the second section 126, a third section 127 extends further towards the body 104 of the microfluidic device. This, when reaching the end of the second section 126 (figure 6D), the cap 103 can be moved further towards a sealing position, in which both the inlet 110 and the vent 111 are sealed (figure 6E), for instance corresponding to the third position described above. The third section 127 has a portion 128 of an even greater depth, so that the followers again snap into place. The depth and shape of the portion 128 in the third section 127 are shaped so that without the application of excessive and/or destructive force, the cap 103 can not be removed from the microfluidic device. Because the reservoir 199 is sealed by the internal rim 119 even before the second section 126 is reached by the followers 130, there is a pumping action before, but also after said moment. Thus, the assembly of figures 6A - 6E may be used to create a two-step pumping process.

In figures 7A and 7B an assembly 202 is shown, which is similar to that described above. As such, only differences will be described herein. Instead of at the internal rim, connecting elements 206 are applied on a separate wall of the microfluidic device. The connecting elements 206 are configured for mutual cooperation with connecting elements 206’ on the cap. The connecting elements 206’ on the cap are provided on its circumferential wall, and take the shape of snap-hooks 206’. In order to provide space for the snap hooks 206’ to engage, a wall protruding from the main body of the microfluidic device is provided, which defines and for example surrounds a receiving space for the cap. It is noted other ways of providing space for engagement can be considered. Figure 8 shows in cross section the internal rim 219 of the cap. As shown with respect to the dashed line, the internal rim protrudes radially outwards at its free edge 219’. Accordingly, its external diameter increases in a relatively short zone near its free end. Also the internal diameter increases in a relatively short zone near its free end. It is noted that with respect to the earlier described shape of the internal rim 219, nothing else has changed in figure 8.

Figures 9 A - 9C show a protrusion 18 engaging a vent 11. In figure 9 A, the protrusion 18 is ready to engage. In figure 9B, the protrusion is pushed into the vent 11, thereby engaging its edge. Since the protrusion 18 is somewhat larger than the vent in order to create a positive sealing, the edge of the vent is slightly deformed, in this particular example chamfered. This is shown in figure 9B by highlighted deformed area’s 1 G. The deformed areas 11 ’ can be seen in figure 9C as chamfered parts of the edge of the vent 11. Due to the chamfer, the vent 11 may be opened, or run the risk of opening, if after sealing, the protrusion 18 is pulled back slightly. A solution is shown in figures 10A and 10B, where a protrusion 218 is shown which as a first zone 218-1 and a second zone 218-2. The second zone 218-2 is placed further towards the free end of the protrusion than the first zone 218-2. The second zone 218-2 has no draft angle, i.e. is straight, having a parallel surface to the direction of protrusion, whereas the first zone 218-1 has a draft angle a shown with respect to the direction of protrusion using parallel dashed lines. If the protrusion 218, in particular the first zone 218-1 thereof, creates chamfers in the edge of the vent 211, the protrusion 218 may still seal the vent 211 even if it is pulled back somewhat, due to the shape of the second zone 218-2.

Although the invention has been described above with reference to specific examples and embodiments, the scope of this application is not limited thereto. In fact, the scope is also defined by the following claims.