Reagent cartridge

Abstract

A fluidic system is provided. The system comprises: a rigid housing (12), a plurality of flexible reagent containers (14) contained within the housing (12); wherein each reagent container (14) has a connection port (16) through which a reagent can flow, in use, on the application of pressure. The system further comprises a single pressure source (18) configured to apply pressure to the interior of the rigid housing (12); a microfluidic device configured to analyse one or more fluids provided from the plurality of reagent containers; and a plurality of channels (20) configured to transfer fluid from the plurality of reagent containers (14) to the microfluidic device. The ratio of resistances provided by a combination of the connection ports and the plurality of channels dictates the ratio of flow rates of the reagents. The claimed system allows for an accurate control of the various reagent flow rates while minimizing fluctuations in the relative flow rates.

Claims

1. A fluidic system comprising: a rigid housing, a plurality of flexible reagent containers contained within the housing; wherein each reagent container has a connection port through which a reagent can flow, in use, on the application of pressure; a single pressure source configured to apply pressure to the interior of the rigid housing; a microfluidic device configured to analyze one or more fluids provided from the plurality of reagent containers; and a plurality of channels configured to transfer fluid from the plurality of reagent containers to the microfluidic device; wherein the ratio of resistances provided by a combination of the connection ports and the plurality of channels dictates the ratio of flow rates of the reagents; and wherein a plurality of reagents contained within the plurality of flexible reagent containers are configured to be actuated simultaneously by the single pressure source.

2. The fluidic system according to claim 1, further comprising an actuator configured to control the flow of the plurality of reagents by modulating the pressure from the single pressure source.

3. The fluidic system according to claim 1, wherein the reagent containers are fluid impermeable.

4. The fluidic system according to claim 1, wherein the resistances of the channel and port network are substantially equal so that the flow rates of the reagents are substantially equal.

5. The fluidic system according to claim 1, wherein the resistances of the channel network differ so that the flow rates of the reagents are different.

6. The fluidic system according to claim 1, wherein the plurality of channels is connected to the connection ports of the reagent containers using normally closed valves that open upon connection, including, but not limited to, needle-free valves, swabable valves, and Luer activated valves.

7. The fluidic system according to claim 1, wherein the plurality of channels is connected to the connection ports of the reagent containers using quick-connection connectors or adaptors, including, but not limited to, Luer connectors, barbed connectors or push-in connectors.

8. The fluidic system according to claim 1, further comprising a sump for collecting waste fluid flowing out from the microfluidic device.

9. The fluidic system according to claim 8, further comprising a drain tube configured to feed waste fluid from the sump into the rigid housing as actuating fluid.

10. The fluidic system according to claim 1, wherein the microfluidic device is chip based.

Description

(1) The invention will now be further and more particularly described, by way of example only, and with reference to the accompanying drawings, in which:

(2) FIG. 1 provides an illustration of a reagent cartridge according to the present invention; and

(3) FIG. 2 provides a further embodiment of the reagent cartridge.

(4) Referring to FIG. 1 there is provided a reagent cartridge 10 comprising a rigid housing 12, a plurality of flexible reagent containers 14 contained within the rigid housing 12. Each reagent container is configured to hold between 1 ml and 2500 ml of fluid, for example 100 ml. Each reagent container 14 has a connection port 16 through which a reagent can flow upon the application of pressure. The reagent may be a fluid such as a gas or a liquid. As an alternative, the reagent may be a suspension, emulsion or a mixture. The reagent may contain biological or chemical components such as DNA, proteins, carbohydrates and/or organic compounds thereof. The flexible reagent containers may be configured to host the same reagents. Alternatively, the reagent containers may be configured to host different reagents.

(5) The rigid housing may further comprise a tube (not shown) for introducing additional actuating fluid into the interior of the housing. The actuating fluid can be liquid or gaseous for example, air, nitrogen or liquid waste from the reagent cartridge.

(6) By using flexible reagent containers contained within the rigid housing, the reagent containers provide a fluid impermeable barrier. The barrier can be utilised to prevent the reagents mixing with liquids or gases, such as the actuating fluids, within the rigid housing. Additionally, the reagent containers may also provide a means to prevent the reagents entering or leaking out into the interior of the rigid housing. The reagent containers may be made from multilayer plastics. In one embodiment the reagent containers are made from multi-layered plastics with aluminised film or other barrier layers.

(7) A single pressure source 18 is configured to apply pressure to the interior of the rigid housing. The single pressure source is a flexible container 18 as illustrated in FIG. 1. The single pressure source may be a pump 13, in particular a pressure pump or peristaltic pump. An actuator can be provided which is configured to control the flow of the plurality of reagents by modulating the pressure from the single pressure source 18. In some embodiments, the actuator can be user-controlled, for instance with a syringe or an external flexible container in pneumatic or hydraulic connection with the interior of the rigid container.

(8) The pressure generated from the single pressure source may be used for pressurising the actuating fluids contained within the interior of the rigid housing. The pressurised actuating fluids can in turn, compress the plurality of flexible reagent containers. This causes the simultaneous actuation of reagents contained within the plurality of reagent containers. As a result, the reagents may be discharged or flow from the reagent containers into a device such as a microfluidic device 25. This configuration aids the operation of the device in a steady state operation where simultaneous rather than sequential dosing of reagents is required.

(9) As illustrated in FIG. 1, each flexible reagent containers is connected to a connection port 16. The connection ports of the reagents containers further comprises a plurality of connecting channels or capillaries 20. The resistances in the channel network 20 are used to provide a connection between the connection ports of the reagent containers with the microfluidic device. The microfluidic device can be chip based. The channel network 20 may be connected to the connection ports using quick-connection connectors or fittings such as Luer connectors. Alternatively or additionally, the channel network 20 may be connected to the connection ports of the reagent containers using normally closed valves that open upon connection.

(10) The channel network 20 connected to the connection ports 16 is configured to allow the reagents to flow from the reagent containers into the microfluidic device 25. The microfluidic device may be configured to analyse one or more fluids provided from the plurality of reagent containers.

(11) Conversely, the channel network 20 connected to the connection ports 16 may be configured to allow the reagents to be transferred from the microfluidic device into the flexible reagent containers 14.

(12) Each arm of the channel network 20 that is connected to a port of the reagent container may comprise an internal resistance which can be configured to dictate the flow rates of the reagents. The resistances attached to the connection ports are dictated by at least one of the cross sectional area of the port, the length of the port, and the surface roughness of the channel network or the viscosity of the fluid. The resistances of the channel network connected to the ports of the reagent container may be substantially equal so that the flow rates of the reagents are substantially equal. This may provide a continuous flow of reagents between the reagent containers and the microfluidic device. Alternatively, the resistances of the channel network attached to each port may be substantially different so that the flow rates of the reagents are different. In all of the above mentioned embodiments, the use of a single actuation source and the setting of the resistance values, whether matched or divergent, provides a high-precision control of the flow of all of the reagents into the microfluidic device.

(13) Each channel or capillary has a hydrodynamic resistance which can contribute to the flow rates of the reagents. The hydrodynamic resistances of the channels or capillaries are dictated by the geometry of the capillaries such as the cross sectional area of the channel or capillary, the length of the channel or capillary, and the surface roughness of the channel or capillary.

(14) The flow of the reagents between the reagent containers and the microfluidic device can be a laminar flow or it can be a turbulent flow. Furthermore, the flow rates of the reagents can be affected by the viscosity of the reagents.

(15) Additionally, as illustrated in the embodiment shown in FIG. 2, there may be provided a sump 30 for collecting waste fluid flowing out from the microfluidic device 25. The sump 30 may be a hollow or a depressed surface in which the waste fluids are collected. A drain tube 32 connected to the sump 30 can be configured to transport the waste fluids from the sump into the interior of the rigid housing as actuating fluids.

(16) Feeding waste fluids such as liquids into the rigid housing may allow for compensation in a change of hydrostatic pressure upon reagents flowing out of the reagent containers. Therefore, the actuating fluids can provide a constant hydrostatic pressure within the rigid housing, which may help to minimise drift of the flow rates of the reagents. Maintaining the hydrostatic pressure within the housing also aids the high precision control of flows of reagents into the microfluidic device

(17) Furthermore, surrounding the flexible containers with liquid may further reduce their permeability to gases. Alternatively, the reagent containers may be permanently immersed in liquid by having a container with a large amount of head room and long, impermeable connectors that attach the reagent containers to the top of the cartridge, or by connecting the reagent containers at the side or bottom of the rigid container.

(18) Moreover, the rigid housing may comprise a plurality of pneumatically or hydrostatically connected containers (not illustrated in the drawings) for storing the reagents. Each pneumatically or hydrostatically connected container may have a connection port. The application of pressure to the pneumatically or hydrostatically connected containers may permit the reagents to flow from the containers into a device such as a microfluidic device. The pneumatically or hydrostatically connected containers can be used as an addition to the flexible reagent containers.

(19) It will further be appreciated by those skilled in the art that although the invention has been described by way of example with reference to several embodiments, it is not limited to the disclosed embodiments and that alternative embodiments could be constructed without departing from the scope of the invention as defined in the appended claims.