Microfluidic liquid dispensing system

Abstract

An innovative microfluidic liquid dispensing system is disclosed, comprising a base with multiple receptacles designed to hold liquid. The system features an actuating arrangement configured to displace liquid from the receptacles when activated. The system's design ensures that relative movement between the actuating arrangement and the base enables at least partially sequential displacement of liquid from the receptacles.

Description

[0001] MICROFLUIDIC LIQUID DISPENSING SYSTEM

[0002] BACKGROUND TO THE INVENTION

[0003] This invention relates to a liquid dispensing system, and more particularly, though not exclusively, to a microfluidic liquid dispensing system suitable for medical use.

[0004] Laboratory-on-Chip (LOC) technologies involve the miniaturization of biological and chemical processes onto a device or “chip” approximately the size of a credit card. Microchannels engraved in the chip transport minute volumes of one or multiple liquids into mixers, incubators, reactors, and sensing areas to detect and diagnose chemicals and pathogens. Even human or animal cells can be deposited in an LOC device for researchers to study their behaviour, in which case such devices are referred to as “organ-on-chip.” In essence, LOC technology enables multiple laboratory functions to be miniaturized into a compact diagnostic package. An LOC device is effectively a small-scale laboratory integrated onto a chip, typically ranging from a few millimetres to several square centimetres in size, utilizing microfluidic technology to control tiny fluid volumes, from picolitres to microlitres. LOCs aim to streamline high-throughput screening, analyses, and experiments by miniaturizing operations, thereby reducing reagent and sample usage, cutting down processing times, and potentially lowering overall costs. By automating and integrating various laboratory processes — such as mixing, reacting, separating, and detecting — within a single chip, LOC devices provide a versatile tool across multiple fields.

[0005] The small size and relatively low cost of such microfluidic devices make them ideal for point-of-care (PoC) diagnostic applications for both humans and animals, as well as for environmental sensing applications. As a result, this field has gained significant interest over the past two decades, with heightened attention during the COVID-19 pandemic, when millions of diagnostic tests were conducted worldwide each day. However, the widespread implementation of LOC technology, particularly the development of large-scale manufacturing processes, still requires advancements in key components of these diagnostic systems.

[0006] One such area requiring improvement is the introduction of chemicals and liquids into the device. Currently, this is achieved by connecting multiple syringes via tubing, where the plungers are either manually operated or actuated, for example, using motorized systems. This approach is cumbersome and, compared to lateral flow devices (e.g., over-the-counter pregnancy or drug tests that use capillary flow along a strip containing all necessary reagents), highly impractical. Additionally, errors may arise from incorrect syringe connections, leading to inaccurate diagnostic results. Furthermore, improper sequencing of syringe actuation can occur if the system is not specifically designed for sequential or partially sequential liquid dispensing.

[0007] Although various alternatives have been proposed, including on-chip blister units, micro-pumps, and peristaltic or other pumping systems, no simple and well-controlled liquid dispensing system currently exists for LOC technology — particularly one that is an integral part of the LOC itself. Clearly, advancements in manufacturability, cost reduction, and ease of use remain necessary, especially in PoC settings in developing countries.

[0008] For context, on-chip blister units refer to integrated reservoirs or compartments that store reagents in a sealed manner until needed for an assay or reaction. These blisters are typically made of flexible materials and are bonded to the chip. They can be actuated (opened) mechanically, thermally, or chemically to release the stored reagents into the microfluidic channels of the LOC device at the appropriate stage of the experiment or diagnostic test. However, in cases where multiple blisters are incorporated into an LOC — such as in processes requiring multiple reactions and specific sequences — the user must actuate the blisters in the correct order and / or with the appropriate delay between activations to ensure that chemical processes proceed correctly.

[0009] There remains a significant lack of low-cost diagnostic devices suitable for PoC applications, particularly for remote clinics in Africa and other regions. The need for improved PoC diagnostics in both human medical and veterinary fields has been underscored on a macro scale by the COVID-19 pandemic, during which millions of tests were conducted daily. Given that PoC applications often involve medical personnel with limited laboratory facilities, LOC devices must be easy to use and minimize the risk of errors associated with complex connections and procedures, such as those posed by on-chip blister units.

[0010] PDMS (polydimethylsiloxane) is currently one of the most commonly used materials in the manufacture of LOC devices. PDMS is a silicon-based organic polymer widely employed in microfluidics, as well as various medical and industrial applications, due to its unique properties. It is particularly favored in LOC fabrication for its biocompatibility, flexibility, transparency to visible light, and gas permeability. These characteristics make PDMS an excellent material for creating microfluidic devices and structures that require precise control over fluid movement at a microscopic scale. However, the current PDMS casting approach is not scalable, is too expensive for mass production, and is difficult to implement. While PDMS remains essential for prototype development, alternatives such as injection molding require significant investment in tooling (molds), making them unsuitable for prototyping. Therefore, there is a need for designs that enable the use of different materials for the commercial manufacturing of LOC devices.

[0011] It is accordingly an object of the invention to provide a microfluidic liquid dispensing system that will, at least partially, alleviate the above shortcomings.

[0012] It is also an object of the invention to provide a microfluidic liquid dispensing system which will be a useful alternative to existing microfluidic liquid dispensing systems.

[0013] It is a further object of the invention to provide a LOC device including a new microfluidic liquid dispensing system that will, at least partially, alleviate the above shortcomings.

[0014] It is a still further object of the invention to provide a LOC device including a new microfluidic liquid dispensing system, which will be a useful alternative to existing LOC devices.

[0015] SUMMARY OF THE INVENTION

[0016] According to the invention there is provided a microfluidic liquid dispensing system including: a base; a plurality of receptacles suitable for holding a liquid located in or on the base; and an actuating arrangement, configured to displace liquid from the receptacles when actuated; wherein the configuration is such that relative movement between the actuating arrangement and the base results in the at least partially sequential displacement of liquid from the receptacles.

[0017] There is provided for the actuating arrangement to be linearly displaceable relative to the receptacles.

[0018] In one embodiment the receptacles may be staggered along the direction of displacement in order for the receptacles to be engaged by the actuating arrangement at different stages of the displacement of the actuating arrangement.

[0019] In another embodiment the actuating arrangement may include a plurality of actuator elements that are staggered along the direction of displacement, in order for the actuator elements to be configured to engage the receptacles at different stages of the displacement of the actuating arrangement.

[0020] There is provided for the receptacles to be in the form of cavities formed in the base, with the actuating arrangement being displaceable relative to the base.

[0021] In one embodiment, the cavities are, in use, filled with a liquid to be dispensed, with each cavity being sealed by a sealing element, for example a membrane.

[0022] In another embodiment, there is provided for the cavities to be configured to receive discrete pouches containing the liquid to be dispensed. There is provided for the pouches to be removable, and for the pouches to be complementary shaped and dimensioned in order snugly to fit inside the receptacles.

[0023] Alternatively, there is also provided for the receptacles to be in the form of pouches that are not located in cavities, but which are located on and protrude from the base. These pouches may, for example, be in the form of blister containers as is known in the art.

[0024] In the embodiments where the microfluidic liquid dispensing system includes pouches, there is provided for the pouches to be covered by a membrane which has an adhesive layer on one side. The membrane may constitute polymers and may or may not be metal containing.

[0025] A further feature of the invention provides for the actuator arrangement to include an actuator base, with a plurality of actuator elements extending from the actuator base.

[0026] In one embodiment the actuator base may be in the form of elongate strip, with one or more actuator elements extending substantially laterally from the elongate strip.

[0027] In another embodiment, the actuator base may be in the form of a cylinder, with one or more actuator elements extending radially outwardly from the cylinder.

[0028] There is provided for each actuator element to terminate in a protrusion configured and dimensioned to engage a receptacle. When the receptacle includes a cavity, there is provided for the protrusion at least partially to fit inside the cavity. In one specific example, the actuator arrangement furthermore includes a cam surface configured to urge the protrusions towards the receptacles when the protrusions are displaced relative to the receptacles. There is provided for the cam surface to be complementary shaped relative to the cavity profiles in embodiments where the receptacles include cavities.

[0029] There is provided for the cam surface to be located adjacent the receptacles, and alternatively above the receptacles.

[0030] The cam surface may form part of a cover or a bridge section of the microfluid dispensing system.

[0031] There is provided for the actuation arrangement to be manually actuated, or alternatively to be motorized.

[0032] According to a further aspect of the invention there is provided a microfluidic liquid dispensing system including: a base; and at least one receptacle suitable for holding a liquid located in or on the base; characterized in that the receptacle includes a cavity formed in the base, and a separate pouch locatable inside the cavity formed in the base. The microfluidic liquid dispensing system may include a plurality of receptacles, and an actuating arrangement configured to displace liquid from the receptacles when actuated, wherein the configuration is such that relative movement between the actuating arrangement and the base results in the at least partially sequential displacement of liquid from the receptacles.

[0033] In accordance with a further aspect of the invention there is provided a labon-chip (LOC) device including a microfluidic liquid dispensing system as described above. There is provided for the LOC device to include microchannels, and for the receptacles of the microfluidic liquid dispensing system to be in flow communication with the microchannels.

[0034] BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Embodiments of the invention are described by way of a non-limiting examples, and with reference to the accompanying drawings in which:

[0036] Figure 1 is a schematic plan view of a LOC device including a microfluidic dispensing system in accordance with one embodiment of the invention;

[0037] Figure 2(a) shows a first configuration of the relationship between receptacles and an actuating arrangement of the microfluidic dispensing system;

[0038] Figure 2(b) shows a second configuration of the relationship between receptacles and an actuating arrangement of the microfluidic dispensing system;

[0039] Figure 3 is a perspective view of an embodiment where the receptacles of the microfluidic dispensing system include discrete pouches;

[0040] Figure 4 shows a pouch of Figure 3 in more detail;

[0041] Figure 5 is a cross-sectional side view of the interface between the microfluidic dispensing system of Figures 3 and 4 and the remainder of a LOC device; and Figure 6 is a cross-sectional side view of the microfluidic dispensing system utilizing one type of actuating arrangement.

[0042] DETAILED DESCRIPTION OF INVENTION

[0043] Before any embodiments of the invention are explained in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of "including," "comprising," or "having" and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Unless specified or limited otherwise, the terms "mounted," "connected," "supported," and "coupled" and variations thereof are used broadly and encompass both direct and indirect mountings, connections, supports, and couplings and are thus intended to include direct connections between two members without any other members interposed therebetween and indirect connections between members in which one or more other members are interposed therebetween. It is noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the," and any singular use of any word, include plural referents unless expressly and unequivocally limited to one referent. As used herein, the term “include” and its grammatical variants are intended to be non-limiting, such that recitation of items in a list is not to the exclusion of other like items that can be substituted or added to the listed items. Referring to the drawings, in which like numerals indicate like features, a non-limiting and simplified example of a microfluidic dispensing system in accordance with the invention is generally indicated by reference numeral 20. The system 20 is designed for use with a lab-on-chip (LOC) device 10.

[0044] The LOC device 10 typically includes a base 11 on which is provided a plurality of microchannels 12 that may feed into micro flow devices such as a mixer 13 and a reaction cavity 14. LOC devices are known in the art, and the gist of the present invention does not relate to a LOC per se, but rather a microfluidic dispensing system 20 for use in dispensing fluids to the rest of the LOC, for example into the microchannels 12 of the LOC. The invention does, however, extend to a LOC 10 that includes the new microfluidic dispensing system 20. The new microfluidic dispensing system 20 can be integrally formed with the remainder of the LOC 10, or may be a separate component that can in use engage the remainder of the LOC 10.

[0045] The microfluidic dispensing system 20 comprises a base 21 (which may also be the base 11 of the LOC 10, but which can be a discrete base), with a plurality of receptacles 22 provided therein. The receptacles 22 are broadly referred to as the arrangements that contain the liquids to be dispensed but may take various different forms.

[0046] Although this embodiment is not shown in the drawings, the receptacles 22 may be in the form of cavities 23 which can in use hold a liquid to be dispensed, with each cavity 23 being covered by a pliable or frangible cover.

[0047] Alternatively, and as generally shown in the figures, the receptacle 22 can be in the form of a cavity 23, but with the cavity configured and dimensioned for receiving a separate pouch 24 therein. In this embodiment, the cavity 23 and the pouch 24 in combination define the receptacle 22. This is a preferred embodiment, but the invention is not limited to this embodiment. There is provision for the pouches 24 to be colour-coded or shaped in a way that a pouch 24 can only fit inside a desired cavity 23. This implies that there could either be colour markings in the cavities or that all the cavities 23 will also not have the same shape.

[0048] In a further embodiment, not shown in the figures, the cavities 23 can be done away with, and receptacles in the form of blister packs can be secured to the base. In this case, the receptacles will protrude from the base 21 , and no cavities will be provided in the base.

[0049] An example where the fluid receptacle 22 comprises the combination of a cavity 23 and a pouch 24 is shown in Figures 3, 4, and 5. The pouch 24 consists of a container 25, which is configured and dimensioned snugly to fit inside the cavity 23 provided in the base 21 , and a frangible and / or pliable cover 26 that seals the container 25. The cover 26 may, for example, be in the form of a plastic film or metal-containing membrane or both. An adhesive layer 27 may be provided to assist in securing the pouch

[0050] 24 in the cavity 23, and hence relative to the LOC device 10. The container

[0051] 25 has a fluid outlet that in use aligns with the microchannels 12 of the LOC device 10.

[0052] Upon removal of the cover layer or adhesive layer 27, a channel or hole to the container 25 is opened, and upon securing the pouch 24 to the LOC 11 , the liquid may freely flow into the LOC 11 upon emptying the pouch 24.

[0053] The microfluidic liquid dispensing system 20 also includes an actuating arrangement 30 for use in displacing liquid from the receptacles 22. The actuating arrangement may take various forms, and in the examples shown in Figures 1 , 2, and 6 is in the form of an actuating arrangement having an actuator base 31 with a plurality of actuating elements 32 extending laterally therefrom. The actuating elements 32 extend from the base 31 in the direction that the actuating arrangement 30 will in use be displaced. Each actuating element 32 terminates in a protrusion 33, which is configured and dimensioned to fit inside the container 25 of the pouch 24 (in the case where a separate pouch is used) or just inside the cavity 23 on the base 21 (in the case where no separate pouch is used), in order for the protrusion to urge liquid from the receptacle 22 when it is urged into or towards a receptacle 22. The protrusions 33, or at least their operatively lower surfaces, may, for example, be shaped like spoons. In one example, shown in Figure 6, a cam formation 34 is provided, which forces the protrusions 33 of the actuator elements 32 towards the pouches 24 located in the base 21 when the actuating elements are longitudinally displaced relative to the microfluidic liquid dispensing system 20.

[0054] An important aspect of this invention is that the configuration between the actuating arrangement 30 and the receptacles 22 is such that relative movement between the actuating arrangement 30 and the base 21 results in at least partially sequential displacement of liquid from the receptacles, instead of simultaneous displacement (and hence dispensing) of liquid. In the example shown in Figure 2(a), this is achieved by staggering (arrow A) the receptacles 22 along the displacement axis of the actuating arrangement. In the example shown in Figure 2(b), this is achieved by staggering the length of the actuating elements 32 (arrow B). In both examples, linear displacement of the actuating arrangement 30 will result in the receptacles 22 being emptied in a pre-configured order, with the delay further being determined by the difference in relative spacing. A combination of the two approaches is also feasible.

[0055] The actuating arrangement 30 may also take other forms. In one example, not shown in the drawings, the actuator base may be in the form of a cylinder, with one or more actuator elements extending radially outwardly from the cylinder. The actuator elements may be spaced apart about the circumference of the cylinder, thus resulting in sequential engagement with the receptacles when the cylinder rolls forward relative to the base 21 of the microfluidic liquid dispensing system 20.

[0056] The actuating arrangement 30 may be manually operated, but it is also foreseen for the actuating arrangement 30 to be motorised and to be electrically or pneumatically operated.

[0057] The LOC device 10 may be made from a synthetic material, and more particularly a suitable plastic material, such as polymethyl methacrylate (PMMA). The LOC device 10 may be covered by a membrane, glass, or plastic sheet.

[0058] The pouch dimensions are between 1cm x 2cm to 1cm x 5cm, depending on the liquid volume required, and the volume of a pouch will typically be between 100 pl and 1 ml. The liquid in the pouch will depend on the application but can be selected from the group comprising reagents, sample solutions, buffer solutions, detection reagents, washing solutions, control fluids, carrier fluids, and controlled-release agents.

[0059] There are two significant benefits associated with the new design. The first is the fact that the system 20 and LOC device 10 are designed inherently to dispense liquids in a predetermined sequential and / or delayed manner. This is a function of the design of the article, and not the skill or experience of the user. A second benefit is the use of the separate pouches, which means that one only has to supply one device for use with multiple pouches, and with some or all pouches that can then also be stored in a fridge without the requirement to store entire LOC devices.

[0060] It will be appreciated that the above is only one embodiment of the invention and that there may be many variations without departing from the spirit and / or the scope of the invention. It is easily understood from the present application that the particular features of the present invention, as generally described and illustrated in the figures, can be arranged and designed according to a wide variety of different configurations. In this way, the description of the present invention and the related figures are not provided to limit the scope of the invention but simply represent selected embodiments.

[0061] The skilled person will understand that the technical characteristics of a given embodiment can in fact be combined with characteristics of another embodiment, unless otherwise expressed or it is evident that these characteristics are incompatible. Also, the technical characteristics described in a given embodiment can be isolated from the other characteristics of this embodiment unless otherwise expressed.

Claims

CLAIMS1 . A microfluidic liquid dispensing system including: a base; a plurality of receptacles suitable for holding a liquid located in or on the base; and an actuating arrangement, configured to displace liquid from the receptacles when actuated; wherein the configuration is such that relative movement between the actuating arrangement and the base results in the at least partially sequential displacement of liquid from the receptacles.

2. The microfluidic liquid dispensing system of claim 1 wherein the actuating arrangement is linearly displaceable relative to the receptacles.

3. The microfluidic liquid dispensing system of claim 1 or 2 wherein the receptacles are staggered along the direction of displacement in order for the receptacles to be engaged by the actuating arrangement at different stages of the displacement of the actuating arrangement.

4. The microfluidic liquid dispensing system of claim 1 or 2 wherein the actuating arrangement includes a plurality of actuator elements that are staggered along the direction of displacement, in order for the actuator elements to be configured to engage the receptacles at different stages of the displacement of the actuating arrangement.

5. The microfluidic liquid dispensing system of any one of the preceding claims wherein the receptacles are in the form of cavities formed in the base, with the actuating arrangement being displaceable relative to the base.

6. The microfluidic liquid dispensing system of claim 5 wherein the cavities are, in use, filled with a liquid to be dispensed, with each cavity being sealed by a sealing element, for example a membrane.

7. The microfluidic liquid dispensing system of claim 5 wherein the cavities are configured to receive discrete pouches containing the liquid to be dispensed.

8. The microfluidic liquid dispensing system of claim 7 wherein the pouches are removable, and wherein the pouches are complementary shaped and dimensioned in order snugly to fit inside the receptacles.

9. The microfluidic liquid dispensing system of any one of claims 1 to 4 wherein the receptacles are in the form of pouches that are not located in cavities, but which are located on and protrude from the base.

10. The microfluidic liquid dispensing system of claim 9 wherein the pouches are in the form of blister containers.

11. The microfluidic liquid dispensing system of any one of the preceding claims wherein the actuator arrangement includes an actuator base, with a plurality of actuator elements extending from the actuator base.

12. The microfluidic liquid dispensing system of claim 11 wherein the actuator base is in the form of elongate strip, with one or more actuator elements extending substantially laterally from the elongate strip.

13. The microfluidic liquid dispensing system of claim 11 wherein the actuator base is in the form of a cylinder, with one or more actuator elements extending radially outwardly from the cylinder.

14. The microfluidic liquid dispensing system of any one of claims 11 to 13 wherein each actuator element terminates in a protrusion configured and dimensioned to engage a receptacle.

15. The microfluidic liquid dispensing system of claim 14 wherein the actuator arrangement includes a cam surface configured to urge the protrusions towards the receptacles when the protrusions are displaced relative to the receptacles.

16. The microfluidic liquid dispensing system of claim 15 wherein the cam surface is located adjacent the receptacles or above the receptacles.

17. The microfluidic liquid dispensing system of any one of the preceding claims wherein the actuation arrangement is manually actuated or motorized.

18. A microfluidic liquid dispensing system including: a base; and at least one receptacle suitable for holding a liquid located in or on the base; characterized in that the receptacle includes a cavity formed in the base, and a separate pouch locatable inside the cavity formed in the base.

19. The microfluidic liquid dispensing system of claim 18 including a plurality of receptacles, and an actuating arrangement configured to displace liquid from the receptacles when actuated, wherein the configuration is such that relative movement between the actuating arrangement and the base results in the at least partially sequential displacement of liquid from the receptacles.

20. A lab-on-chip (LOC) device including a microfluidic liquid dispensing system as claimed in any one of claims 1 to 19.

21. The lab-on-chip (LOC) device of claim 20 including microchannels, wherein the receptacles of the microfluidic liquid dispensing system are in flow communication with the microchannels.

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