Microfluidic device

Abstract

A microfluidic device includes a block having at least one reservoir, a base layer attached to the bottom of the block and a microfluidic channel formed in the base layer or at the interface between the block and base layer. The microfluidic channel is in fluid communication with the at least one reservoir. A static pressure source is operatively coupleable to the reservoir. A flow path extends from the reservoir to the microfluidic channel. The flow path has a first portion which extends upwardly away from the base layer over a barrier and into a second portion which extends downwardly towards the base layer and leads to the microfluidic channel. The flow path is configured such that it prevents flow from the reservoir to the microfluidic channel under the influence of gravity alone when the reservoir is filled to a level below the level of the top of the barrier.

Claims

1. A microfluidic device, comprising: a block comprising at least one reservoir; a base layer attached to a bottom of the block; a microfluidic channel formed in the base layer or at an interface between the block and base layer, the microfluidic channel being in fluid communication with the at least one reservoir; a static pressure source operatively coupleable to the at least one reservoir; and a flow path from the at least one reservoir to the microfluidic channel, the flow path having a first portion which extends upwardly away from the base layer over a barrier and into a second portion which extends downwardly towards the base layer and leads to the microfluidic channel, the flow path being configured such that it prevents flow from the at least one reservoir to the microfluidic channel under the influence of gravity alone when, in use, the at least one reservoir is filled to a level below a level of a top of the barrier.

2. The device according to claim 1, wherein the block comprises at least one projection which forms a tortuous path from the at least one reservoir into the flow path.

3. The device according to claim 2, wherein one of the at least one projection is an upwardly extending projection which extends away from the base layer.

4. The device according to claim 1, wherein the block is injection moulded.

5. The device according to claim 1, wherein the microfluidic channel is formed in a groove in the bottom of the block, the microchannel being closed by a top surface of the base layer.

6. The device according to claim 1, wherein a lower face of the flow path is formed by a top surface of the base layer.

7. The device according to claim 1, wherein part of the flow path is formed by a gasket which seals a top of the block.

8. The device according to claim 1, wherein the at least one reservoir is formed as a bore in the block.

9. The device according to claim 1, wherein the flow path has a minimum diameter of at least 1 mm for at least a portion of its length.

10. The device according to claim 1, wherein the at least one reservoir contains an oil-based liquid.

11. The device according to claim 1, wherein the block comprises a plurality of reservoirs at least one of which has the flow path and at least one of which has an outlet at a bottom to the base layer.

12. The device according to claim 1, wherein a magnetic stirrer is rotatably suspended in the at least one reservoir, the magnetic stirrer terminating above a bottom of the at least one reservoir.

13. The device according to claim 1, further comprising a manifold block above the block, via which pressure is applied to the at least one reservoir.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Examples of microfluidic devices will now be described with reference to the accompanying drawings, in which:

(2) FIGS. 1A to 1D are schematic plan views of a portion of the microchannel illustrating the problem addressed by the present invention;

(3) FIG. 2 is a schematic cross-section through the microfluidic device without the manifold block and the gasket showing the reservoirs in an initially filled state;

(4) FIG. 3 is a view similar to FIG. 2 showing the complete microfluidic device in an operational state;

(5) FIG. 4 is a schematic plan view of the microfluidic device of FIGS. 2 and 3;

(6) FIG. 5 is a view similar to FIG. 2 showing a second microfluidic device with an alternative reservoir construction;

(7) FIG. 6 is a view similar to FIG. 2 showing a third microfluidic device with a further alternative reservoir construction;

(8) FIG. 7 is a view similar to FIG. 2 showing a fourth microfluidic device;

(9) FIG. 8 is a view similar to FIG. 2 showing a fifth microfluidic device;

(10) FIG. 9 is a view similar to FIG. 2 showing a sixth microfluidic device; and

(11) FIG. 10 is a view similar to FIG. 2 showing a seventh microfluidic device.

DETAILED DESCRIPTION

(12) The microfluidic device 10 comprises a number of main components as best shown in FIG. 3. The device is supported on an instrument interface 11 including all necessary information including temperature control, a user interface and optical access. The device 10 comprises a base layer 12 which has a number of microchannels 1 formed on its upper surface as described below. Bonded to this is a block 13 which accommodates the reservoirs. The microchannels 1 may alternatively or additionally be provided in the bottom of the block 13. The top of the block is sealed by a gasket 14 and sandwiched between the block 13 and a manifold block 15 via which pressure can be applied to the reservoirs.

(13) In this example, there is a single oil reservoir 20 containing an oil-based liquid 21 and a pair of aqueous reservoirs 22, 23 which, in this example, contain a cell suspension and a bead suspension respectively. The oil is fed along the oil channels 4 and the aqueous solutions are fed along the aqueous channels 2 which meet and combine at junction 5 as discussed above in relation to FIGS. 1A to 1D. This forms an emulsion in outlet line 6 which is fed to outlet reservoir 24.

(14) Within the aqueous reservoirs 22, 23 are magnetic stirrers 25 which are suspended on a ledge 26 and are held with their impellers 27 above the bottom of the reservoir. A magnet 28 at the top of each stirrer 25 interacts with a magnet 29 in the manifold block 15 so as to rotate the magnetic stirrers 25. Each of the reservoirs 22, 23 is provided with an inclined portion 30 to allow the reservoirs to be readily filled.

(15) The oil reservoir 20 comprises a main chamber 31 at the top of which is an opening 32 which leads to a pressure line 33. The pressure line 33 is connected to a pneumatic pump to allow the reservoir 20 to be pressurised. Similar lines lead from the manifold block 15 via openings in the gasket 14 to the other reservoirs 22, 23 and 24.

(16) The chamber 31 has an outlet 34 at the bottom which leads into flow path 35. It should be noted that the lower surface of the chamber 31 is formed by the base layer 12. This is a portion of the base layer 12 which does not contain a microfluidic channel. The microfluidic channel 1 is shown in dotted lines in FIG. 4 from which it is apparent that access to the microfluidic channel 1 is downstream of the flow path 35. The flow path 35 has an upwardly extending portion 36 which leads over a barrier 37 into a downwardly extending portion 38 which communicates with the microfluidic channel 1. This provides an inverted U-shape channel 37. The barrier partition 37 extends to a height which is above the normal maximum fill level of the oil 21 in the chamber 20.

(17) Before the manifold block 15 and gasket 14 are in place, the oil reservoir 20 is filled via a pipette 40 as shown in FIGS. 5 and 6. As can be seen in FIGS. 5 and 6, additional features 50 are formed as projections into the reservoir 20 to form a tortuous path between the reservoir 20 and the flow path 35. If a user applies undue pressure to the pipette such that the oil 21 is ejected at a relatively high velocity, these features 50 will impede the jetting of this liquid over the barrier 37.

(18) Once all of the reservoirs are filled, gasket 14 and manifold block 15 are put in place, the controller in the instrument interface 11 applies the pressure along line 33 to the oil and aqueous reservoirs 21, 22, 23 at different times and with slightly different pressure levels. By controlling the timing of the pressure application and the pressure levels, it is possible to ensure that the two liquids arrive at the droplet junction 5 at approximately the same time as shown in FIG. 1B.

(19) FIG. 7 shows an alternative design in which like reference numerals have been used for the same components.

(20) In this case, the base layer 12 is in two parts with an injection moulded top layer 70 and a bottom capping layer 71 which form the microchannel 1 between them. A gasket 72 seals the base layer 12 to the block 13 and the two layers are bonded with an adhesive in a recess 73 and the block.

(21) FIG. 8 is similar to FIG. 2 but includes a step 80 to indicate the maximum fill height to a user.

(22) FIG. 9 is similar to FIG. 2. However, rather than forming the entry to the flow path 35 in the block 13, this is, instead, formed as a recess 90 in the base layer 12.

(23) FIG. 10 is a view similar to FIG. 2. Rather than being formed integrally in the block 13, the reservoir is a separate component 100 which is sealed via an O-ring 101 to a channel 102 leading into the flow path 35.

(24) The term microfluidic channel is one which is now well understood in the art. According to one definition, it can be considered as a channel with, at its narrowest part, a maximum internal dimension in a plane perpendicular to the direction of flow of 5-500 m (preferably 5-250 m).