CHANNEL PRIMING AT CHANNEL JUNCTIONS IN A MICROFLUIDIC

SYSTEM

This invention relates to microfluidic devices and in particular to the problem of moving fluids through micro-channels in a controllable manner.

BACKGROUND TO THE INVENTION

We have described a microfluidic device in our co-pending international publication number WO2006/034525. The patent application describes a closed loop device incorporating one or more pumps for moving fluid samples around a loop of microchannels. The device finds particular application for compact bioassay devices, sometimes referred to as chips.

A potential problem with microfluidic devices is priming of channels at channel junctions. Priming is the process of filling a channel with the fluid of interest by purging the channel from other residual liquids or gases. This process is necessary to control the properties of the fluids flowing downstream of the junction, for example towards an active zone such as a capture or detection zone.

A typical example is the detection of a species using an enzymatic label and a substrate. The assay process generally involves several steps, with the substrate being flowed over the detection zone in the final steps to provide the signal. Any contamination of the channel bringing the substrate to the detection zone by gases or other fluids can disrupt the detection process and affect the signal. Similarly, any leak of substrate on the detection zone before the detection step can generate unwanted background signal. It is therefore critical to control that the channel containing the substrate is primed and does not contain unwanted gas or fluids and does not release substrate in the main flow unnecessarily.

At a channel junction where no mechanical valve is present, there is the possibility of contamination of the primary flow by leakage of fluid from

one channel to the other or by diffusion of molecules from one channel to the other. In the case of an incoming channel filled with a gaseous fluid, such as air often used to separate liquids and avoid cross-contamination in microfluidic devices, it is often critical to purge the channel to avoid the insertion of bubbles in the main flow.

The problem of fluid flow contamination at channel junctions which do not incorporate a mechanical valve has not previously been addressed.

OBJECT OF THE INVENTION It is an object of the present invention to provide a method of channel priming at the junction of microchannels.

Further objects will be evident from the following description.

DISCLOSURE OF THE INVENTION In one form, although it need not be the only or indeed the broadest form, the invention resides in a method of channel priming in a microfluidic device having at least two channels each with a variable flow rate pump and a common channel by: operating a first pump to impel a first fluid through a first microchannel while operating at least a second pump to impel a second fluid through a second microchannel, wherein the second pump generates a flow rate less than the first pump so that only the first fluid passes through the common microchannel; then varying the flow rate of either the first pump or the second pump such that the second pump generates a flow rate greater than the first pump so that only the second fluid passes through the common microchannel.

BRIEF DETAILS OF THE DRAWINGS

To assist in understanding the invention preferred embodiments will now be described with reference to the following figures in which:

Fig 1 shows a first stage of channel priming; Fig 2 shows a second stage of channel priming;

Fig 3 shows a third stage of channel priming;

Fig 4 shows a fourth stage of channel priming;

Fig 5 shows a first stage of bubble removal;

Fig 6 shows a second stage of bubble removal; and Fig 7 shows a third stage of bubble removal.

DETAILED DESCRIPTION OF THE DRAWINGS

In describing different embodiments of the present invention common reference numerals are used to describe like features. Referring to Figs 1 - 4, there is shown a simple schematic of a closed loop microfluidic device 10 comprising two pumps (P1, P2) that drive fluids (F1 , F2) through a closed loop comprising two channels (C1 , C2) and a common channel (C3). The pumps P1 , P2 are controllable to vary the rate of flow in the channels. Suitable pumps are described in our co-pending international application and include ferrofluidic pumps, peristaltic pumps and the like.

The schematics of Figs 1 -4 are simplified for ease of description. It will be readily apparent how the inventive concepts described below are applicable to more complex devices, such as those described in our earlier co-pending application. For instance, the common channel C3 may include an active zone at which various chemical reactions occur and from which measurements are recorded. Although the schematics are shown as closed loops the invention may not necessarily be limited to this embodiment.

However, it is important that a pump is used that both "pulls" and "pushes".

Referring to Fig 1, the pump P1 is operated to impel fluid F1 through channel C1. Because the channels form a loop system the fluid F1 will continue through common channel C3 and into the remainder of channel C1 , as depicted by the arrows. The pump is operated at a steady flow rate of, say, 20 arbitrary units. The pump P2 is held static thus generating a resistance to flow into channel C2. Nonetheless, it has been found that diffusion occurs at the junctions J1 and J2 such that fluid F1 is contaminated by fluid F2 and vice versa. The inventors have found that this diffusion can be controlled if pump

P2 is operated at a lower flow rate than pump P1 and in the opposite flow direction to pump P1 as shown in Fig 2. Pump P1 continues to operate with a flow rate of 20 units and pump P2 is operated with a flow rate of 5 units. Some of fluid F1 flows into channel C2 at junction J1 while the bulk of fluid F1 moves through channel C3. Fluid F2 is impelled from channel C2 to channel C1 at junction J2, but does not enter channel C3 because the greater flow of fluid F1 is dominant. This schema ensures that fluids pass through channel C3 (and hence into the active zone of the device) in a controlled manner without contamination. It is instructive to note the respective flow rates in each part of each channel. The part 11 of channel C1 will have a flow of 20 units of fluid F1 and the lower part 12 of channel C1 will have a flow of 15 units of F1 and 5 units of F2. The flow through channel C3 will be 15 units of F1. The upper part 13 of channel C2 will have a flow of 5 units of F1 and the lower part 14 will have a flow of 5 units of F2. At a point 15 there will be an interface between fluids F1 and F2, but this interface never passes through channel C3 and so does not cause any problems for operation of the device.

Many microfluidic devices are designed to perform a bioassay or other chemical test. In these applications the next step after flowing fluid F1 across an active zone in channel C3 is to flow fluid F2 across the same active zone.

Once again, it is important that this is done without contamination from fluid

F1. The simplest approach is to stop pump P1 and hold it static. Pump P2 continues to pump at 5 units (or some other flow rate as desired). Static pump P1 generates a resistance to flow in channel C1 so that fluid F2 flows into channel C3 as shown in Fig 3. An alternate approach is shown in Fig 4. In this case pump P1 is slowed to generate a flow rate less than that of pump P2 (or the flow rate from pump P2 is increased) such that the fluid F1 now flows into channel C2 at junction J1 and the flow through channel C3 is entirely from fluid F2. For the purpose of discussion the flow rate of pump P1 is set to 1 arbitrary unit. Looking at the flow rates in each channel it can be seen that the upper part 11 of channel C1 will have a flow of fluid F1 at an arbitrary flow rate of 1 unit. The lower part 12 of channel C1 will have only flow from fluid F2 at a rate of 1 unit. The flow through channel C3 will be only fluid F2 at a flow rate of 4 units. The upper part 13 of channel C2 will have both fluid F1 and fluid F2 at a flow rate of 1 unit and 4 units, respectively. The lower part 14 of channel C2 will have only fluid F2 at a flow rate of 5 units. As discussed above, the interface between fluids F1 and F2 in channel C2 does not affect any measurements conducted in channel C3.

One important application of the method is to purge gas from a channel in front of a fluid before flowing the fluid through common channel

C3. Referring to Fig 5, consider an air gap 16 trapped in front of fluid F2 near junction J2. Following the step described by reference to Fig 6 the air is purged from channel C2 into channel C1 without interfering with the common channel C3 or the flow of fluid F1 through C3. Once all the air is removed from channel C2 before junction J2, pump P1 is stopped or slowed down so that fluid F2 now replaces fluid F1 in channel C3 as per Fig 7. This application is extremely important since air is often used to separate fluids and prevent diffusion but most capture or detection systems are not meant to be exposed to air bubbles. It is often a requirement to prevent any air from passing over an active zone in a common channel C3.

The inventors have also realised that the pumping schema can be

used to insert fluids, specifically bubbles, into a fluid in a channel or to remove bubbles or contaminants from a fluid. Careful control of the pumps allows diversion of flow at specific times to 'switch' a segment of a fluid stream from one channel to another. The inventors speculate that this microcontrol ability has a wide range of applications in microfluidic systems.

Although the pumping schema has been described for the relatively simple example of a closed loop system of two microchannels it will be readily apparent to persons skilled in the art how the methodology can be scaled for more complex devices. Throughout the specification the aim has been to describe the invention without limiting the invention to any particular combination of alternate features.