WO2009060202A1

WO2009060202A1 - Microfluidic device and method for producing sheathed fluid

Info

Publication number: WO2009060202A1
Application number: PCT/GB2008/003750
Authority: WO
Inventors: Daniel David Palmer; Owen Leslie Shadick
Original assignee: Q Chip Ltd
Current assignee: Midatech Pharma Wales Ltd
Priority date: 2007-11-09
Filing date: 2008-11-07
Publication date: 2009-05-14
Anticipated expiration: 2010-05-09
Also published as: GB0722092D0

Abstract

A method of sheathing a first fluid by one or more fluids with which the first fluid is immiscible is provided, the method comprising: (i) providing a first fluid(6); (ii) providing second(3)and third(9) fluids with which the first fluid is immiscible; (iii) forming parallel laminar flows of the first (6) and second (3) fluids with the second fluid contacting the first fluid on a first side of the first fluid; (iv) subsequent to step (iii), contacting the third (9) fluid with the second fluid and the first fluid so that the first fluid is sheathed by the second and third fluids. Devices for performing the above-mentioned methods are also provided.

Description

Microfluidic device and method for producing sheathed fluid

The present invention relates to a method and microfluidic device for producing sheathed fluids .

There are many known apparatus which control the flow of fluids. Methods are known which enable the production of a first fluid sheathed by a second fluid with which the first fluid is immiscible. Such methods typically involve the use of coaxial cylinders, for example, as described in WO2004/091763. Devices using small dimension coaxial cylinders may be difficult to construct, and such devices may be difficult to multiplex together.

The present invention seeks to address one or more of the problems of the prior art.

There is provided in accordance with a first aspect of the present invention a microfluidic device for sheathing a first fluid by one or more fluids with which the first fluid is immiscible, the device comprising: a parallel flow conduit for carrying parallel flows of the first fluid and a second fluid with which the first fluid is immiscible; an inlet for the first fluid and an inlet for the second fluid, said inlets being in fluid communication with the parallel flow conduit so that the respective fluids may be delivered through the respective inlet to the parallel flow conduit so that the first and second fluid may form parallel laminar flows in the parallel flow conduit with the second fluid in contact with, and on one side of, the first fluid; and an inlet for a third fluid, the inlet for the third fluid being downstream of the inlet for the first fluid and the inlet for the second fluid, the inlet for the third fluid arranged so that the third fluid is deliverable through the inlet for the third fluid to contact the second fluid and the first fluid so that the first fluid is sheathed by the second and third fluids.

Such a device facilitates lab-on-a-chip type technology to produce sheathed flows. Those skilled in the art will realise that the sheathed fluid may be further manipulated using the device, for example, to form segmented flow.

The term "fluid" as used in the present application is intended to cover liquids, gases and supercritical fluids. It is preferred that the fluids used in the present application are in liquid form.

The word "sheathed" does not mean "sandwiched", in which case the first fluid may contact a surface of the device or an air interface. That is, in practice, a sheathed fluid will generally refer to a fluid that is within a sheath, especially a circumferentially extending wall, formed by one or more other fluids . The sheathed fluid may flow within a sheath formed by one or more other fluids .

The third fluid is typically immiscible with the first fluid.

The sheathed fluid may be in the form of a flow of first fluid which is sheathed by a flow of second and third fluids . It is preferred that the inlet for the second fluid is upstream of the inlet for the first fluid.

The parallel flow conduit may be substantially straight.

The device may further comprise a delivery conduit for delivering the second fluid to the parallel flow conduit. The delivery conduit may be immediately upstream of the parallel flow conduit. The inlet for the second fluid may be provided in the delivery conduit.

The parallel flow conduit may comprise a first channel for the flow of the first fluid and a second channel for the flow of the second fluid. If this is the case, it is preferred that the inlet for the first fluid is provided in the first channel. The second channel and first channel are preferably elongate and the longitudinal axis of the first channel is preferably parallel to the longitudinal axis of the second channel. The second channel may have a larger cross-sectional area than the first channel. Those skilled in the art will realise that the first channel is typically in fluid communication with the second channel so that a laminar flow of the first fluid (which may be substantially in the first channel) may contact a laminar flow of the second fluid (which may be substantially in the second channel) along the length of the first channel. Hence, the first channel is preferably in fluid communication with the second channel along the length of the first channel.

The device may further comprise a sheath-forming region into which the third fluid is deliverable. The sheath-forming region is preferably so configured that the third fluid, when it is introduced, contacts the first fluid and the second fluid such that the first fluid is sheathed by the second and third fluids. The sheath-forming region, if present, is downstream (and preferably immediately downstream) of the parallel flow conduit. The sheath-forming region may be provided by a sheath-forming conduit. The sheath-forming conduit may have a larger cross-sectional area than the parallel flow conduit. This may typically be achieved with a sheath-forming conduit that is deeper than the parallel flow conduit. It is preferred that the inlet for the third fluid is adjacent to, or proximate to, the sheath-forming region. The region where the inlet for the third fluid admits the third fluid may be considered to be a junction.

The device may further comprise one or more (and preferably two) flow-enhancing conduits for delivering a flow-enhancing fluid with which the second and third liquids are miscible. The flow-enhancing conduit (s) may be arranged to deliver the flow-enhancing fluid at, and/or upstream of, the sheath- forming region downstream, and preferably at and/or immediately upstream of the sheath-forming region.

The cross-sectional area of the flow-enhancing conduit (s) may be substantially the same as the sheath-forming conduit. The flow-enhancing conduit (s) may be lateral conduits.

The device may further be provided with one or more (and preferably two) carrier fluid conduits for delivering a carrier fluid to impinge on the sheathed flow. The carrier fluid is typically immiscible with the second and third fluids, and may be used to form segmented flow, the segments comprising an inner region of first fluid encapsulated by an outer region comprising fluid with which the first fluid is immiscible, the segments being carried by the carrier fluid, the carrier fluid being immiscible with the fluid from which the outer region of the segments is formed.

The carrier fluid conduit (s) may be arranged to deliver carrier fluid substantially at or downstream of the sheath- forming region. If the carrier fluid conduit (s) is arranged to deliver carrier fluid downstream of the junction, it is preferred that the carrier fluid conduit (s) is arranged to deliver carrier fluid immediately downstream of the sheath forming region. One or more of the carrier fluid conduits may be lateral conduits.

A discontinuity may be provided at or downstream of the region where the carrier fluid conduit (s) delivers carrier fluid to the sheathed flow. The discontinuity promotes the formation of segmented flow. The discontinuity is typically in the form of a flow constriction.

The device may further comprise an outlet conduit downstream of the sheath-forming region. If one or more carrier fluid conduits are present, the outlet conduit may be downstream of the one or more carrier fluid conduits and the discontinuity (if present) . If one or more carrier fluid conduits are present, the outlet conduit may be provided with an enlargement at or downstream of the discontinuity. The enlargement has been found to promote the formation of spherical segments. A step may be provided in the outlet conduit. The step may be provided at the enlargement (if present) . The outlet conduit does not necessarily provide an outlet from the device and may lead to other conduits.

The device of the first aspect of the present invention is a microfluidic device and hence facilitates very small volumes of material to be brought together in a controlled manner. The conduits in such microfluidic devices typically have widths of less than 2mm, preferably less than lmm and more preferably from 0.1 to 0.5mm. The depths of the conduits are typically less than 2mm, preferably less than lmm and more preferably from 0. lmm to 0.5mm. The flow rates of the fluids will depend, inter alia, on the cross-sectional area of the conduits, and the preferred values given here relate to conduits having depths less than lmm and widths less than lmm. The flow rate, for example, of the second fluid through the delivery conduit or the parallel flow conduit may advantageously be from about 0.02 to 5 ml/hour, more preferably be from about 2 to 4 ml/hour. The flow rate of the first fluid may, for example, be from about 0.1 to 5 ml/hour, preferably from about 0.2 to 1 ml/hour.

The conduits may be formed as profiled flow passages in a substrate. This may typically be achieved by removing substrate material from the substrate so as to form passages, for example, by machining substrate material from the substrate.

The surfaces of the conduits mentioned above may be low energy surfaces. Low energy surfaces may be obtained by forming passages in a substrate of low energy material, such as polytetrafluoroethylene (PTFE or Teflon®) . Alternatively, a coating providing a low energy surface may be deposited onto a substrate which, in the absence of the coating, does not have a low energy surface.

In accordance with a second aspect of the present invention, there is provided a microfluidic device for sheathing a first fluid with one or more fluids with which the first fluid is immiscible, the device comprising

(i) a delivery conduit for delivering a second fluid, (ii) an inlet for delivering the second fluid to the delivery conduit,

(iii) a parallel flow conduit downstream of the delivery conduit, the parallel flow conduit comprising a second channel for the carriage of the second fluid and a first channel for the carriage of a first fluid, and

(iv)an inlet for delivering the first fluid to the first channel, the first channel being in fluid communication with the second channel so that a laminar flow of first fluid in the first channel may contact a laminar flow of second fluid in the second channel along the length of the first channel, the device further comprising a sheath-forming region downstream of the parallel flow conduit and an inlet for the delivery of a third fluid to the sheath-forming region.

It is preferred that the second channel and first channel are elongate. It is further preferred that the longitudinal axis of the first channel is preferably parallel to the longitudinal axis of the second channel. The second channel may have a larger cross-sectional area than the first channel . The sheath-forming region may be provided by a sheath- forming conduit.

In use, the second fluid is delivered via the inlet for the delivery of the second fluid into the delivery conduit. Second fluid travels along the delivery conduit to the parallel flow conduit. The first fluid is introduced into the first channel of the parallel flow conduit via the inlet for the delivery of the first fluid to the first channel. wherein the parallel flow conduit the second fluid forms parallel laminar flows with the first fluid. The second fluid is in contact with, and on one side of, the first fluid (typically the upper side of the first fluid) . The inlet for the delivery of the third fluid is located downstream of the parallel flow conduit, and is arranged so that the third fluid can be brought into contact with both the first and second fluids, thereby sheathing the first fluid. This may be achieved, for example, by arranging the third inlet to deliver the third fluid to the lower side of the first fluid. This may be achieved by the third inlet admitting third fluid from below the first fluid.

The microfluidic device of the second aspect of the present invention may comprise those features described above with reference to the microfluidic device in accordance with the first aspect of the present invention. To this end, "the inlet for delivering the first fluid to the first channel" of the device of the second aspect of the invention may be considered to be the same as "the inlet for the first fluid" of the device of the first aspect of the present invention. Likewise, "an inlet for delivering the second fluid to the delivery conduit" of the device of the second aspect of the invention may be considered to be the same as "the inlet for the second fluid" of the device of the first aspect of the present invention. Furthermore, "an inlet for the delivery of the third fluid to the sheath-forming conduit" may be considered to be the same as "the inlet for the third fluid" of the device of the first aspect of the present invention.

The device of the first and second aspects of the present invention facilitate lab-on-a-chip technology to provide a flow arrangement in which a laminar flow of a first fluid is surrounded by a laminar flow of another fluid with which the first fluid is immiscible. This "co-axial" flow arrangement may then be manipulated as desired. Such lab-on-a-chip technology is simple and easy to manufacture and use.

The second and third fluids used in the devices of the first and second aspects of the present invention may be substantially the same.

In accordance with a third aspect of the present invention, there is provided a method of sheathing a first fluid by one or more fluids with which the first fluid is immiscible, the method comprising: (i) providing a first fluid; (ii) providing second and third fluids with which the first fluid is immiscible;

(iii) forming parallel laminar flows of the first and second fluids with the second fluid contacting the first fluid on a first side of the first fluid; (iv) subsequent to step (iii), contacting the third fluid with the second fluid and the first fluid so that the first fluid is sheathed by the second and third fluids. Those skilled in the art will realise that the steps (i) to (iv) are not necessarily performed sequentially. For example, some steps may be performed simultaneously.

It is preferred that the second and third fluids are aqueous fluids and the first fluid is therefore immiscible with aqueous fluids (and may typically comprise an organic-based fluid, such as an oil) .

Step (iv) may comprise contacting the third fluid with the first fluid on a second side of the first fluid. Typically, in step (iii) a flow of second fluid is arranged above the first fluid. In this case, in step (iv) , the third fluid may contact the first fluid from below the first fluid.

This provides a simple method for producing a laminar flow of a first fluid which is surrounded by a laminar flow of one or more fluid with which the first fluid is immiscible. This method facilitates the production of the desired flow arrangement using lab-on-a-chip technology, for example.

It is preferred that step (iii) comprises providing a laminar flow of the second fluid, and contacting the laminar flow of the second fluid with the first fluid. The formation of a laminar flow of the second fluid prior to contacting the second fluid with the first fluid has been found to be advantageous in encouraging the formation of the parallel laminar flows of the second fluid and the first fluid.

The method may produce parallel laminar flows of the first, second and third fluids. This is an effective method of providing a fluid (in this case, the first fluid) which is sheathed by other fluids (in this case, the second and third fluids) with which the first fluid is immiscible.

It is preferred that the third fluid may be substantially the same as the second fluid. Alternatively, the third fluid may be different from the second fluid.

It is preferred that the third fluid is miscible with second fluid.

The second and third fluids may be aqueous. In this case, it is preferred that the first fluid is immiscible with aqueous fluids and may be an organic-based fluid. Alternatively, the first fluid may be aqueous. In this case, it is preferred that the second and third fluids are immiscible with aqueous fluids .

It is preferred that the aqueous fluid (s) comprise water and a viscosity enhancer. The viscosity enhancer may comprise a water-soluble polymer. The viscosity enhancer may comprise a polysaccharide, such as pectin or starch. The viscosity of the aqueous fluid may be from 3OmPa. s to 50OmPa. s, preferably from 5OmPa. s to 30OmPa. s and more preferably from lOOmPa.s to 25OmPa. s. These values of viscosity are those of the fluids when in the device itself. Such viscosities have been found to be effective in helping to form parallel laminar flows of the first and second fluids. If the viscosity of an aqueous second fluid is too low, then in certain circumstances the viscous shear applied by the second fluid to the first fluid is insufficient to maintain a parallel laminar flow of the first fluid, in which case the first fluid migrates to a fluid-air interface or a fluid-solid interface.

One or more of the first fluid, the second fluid and the third fluid may comprise an agent for reducing interfacial tension between the first fluid and one or both of the second and third fluids. It has been found to be advantageous to introduce an agent to reduce interfacial tension between the first fluid and one or both of the second and third fluids, particularly between the first fluid and the second fluid so that parallel laminar flows of the first and second fluids may be formed. The agent for reducing interfacial tension may comprise a surfactant. Such a surfactant may be a non-ionic surfactant; this is typically advantageously used in a non-aqueous fluid (such as a non-aqueous first fluid) . Alternatively, the surfactant may be an ionic surfactant; this is typically advantageously used in an aqueous fluid. The concentration of the surfactant in the respective first, second or third fluid may be from 0.1% to 10% w/w surfactant : respective fluid, preferably 0.5% to 5% w/w, more preferably 0.8% to 4% w/w, further more preferably 1% to 3% w/w and most preferably about 1.5% w/w.

The preferred difference in interfacial tension between the first and second fluids will differ from system to system. A preferred approach is to reduce the interfacial tension between the two fluids (for example, by the suitable addition of surfactants) until the parallel laminar flows of the two fluids may be achieved. The flow rate of the first fluid may be lower than the flow rate of at least one of (and preferable both) the second fluid and the third fluid. The flow rate of the respective fluid is the rate at which the respective fluid is introduced into a device.

It is preferred that the flow rate of the first fluid is from 10% to 50%, preferably 10% to 25% and more preferably 15% to 30% of the flow rate of the second fluid.

It is preferred that the flow rate of the first fluid is from 10% to 50%, preferably 10% to 25% and more preferably 15% to 30% of the flow rate of the third fluid.

The method may further comprise providing a microfluidic device comprising an inlet for the second fluid. The device may further comprise an inlet for the first fluid.

It is preferred that the inlet for the second fluid is upstream of the inlet for the first fluid. This is so that a laminar flow of the second fluid may be formed prior to the second fluid contacting the first fluid. This has proved to be an effective way of forming parallel laminar flows of the first and second fluids.

The device may comprise a delivery conduit for delivering the second fluid. The inlet for the second fluid may be in fluid communication with the delivery conduit.

The device may further comprise a parallel flow conduit for forming parallel laminar flows of the first and second fluids. The parallel flow conduit is preferably downstream (and more preferably immediately downstream) of the delivery conduit (if present) . The parallel flow conduit may comprise a second channel for the flow of the second fluid and a first channel for the flow of the first fluid. The first and second channels are preferably elongate and the longitudinal axis of the first channel is preferably parallel to the longitudinal axis of the second channel. The cross-sectional area of the second channel is greater than the cross-section area of the first channel. Those skilled in the art will realise that the first channel is typically in fluid communication with the second channel so that a laminar flow of the first fluid may contact a laminar flow of the second fluid along the length of the first channel.

The device may further comprise an inlet for the third fluid.

The device may further comprise a sheath-forming region into which the third fluid may be delivered so as to contact the first fluid and the second fluid in order that the first fluid is sheathed by the third fluid. The sheath-forming region, if present, is typically downstream of the parallel flow conduit. The sheath-forming region may be provided by a sheath-forming conduit. The sheath forming conduit may have a larger cross-sectional area than the parallel flow conduit. This may typically be achieved with a sheath- forming conduit that is deeper than the parallel flow conduit .

The device may further comprise one or more flow-enhancing conduits for delivering a fluid with which the second and third liquids are miscible. The flow-enhancing conduit (s) may be arranged to deliver the flow-enhancing fluid at, and/or upstream of, the sheath-forming region downstream, and preferably immediately upstream of the sheath-forming region.

In accordance with a fourth aspect of the present invention, there is provided a method of producing a segmented flow of a first fluid encapsulated within a fluid with which the first fluid is immiscible, the method comprising providing a sheathed flow comprising a first fluid sheathed by a fluid with which the first fluid is immiscible and forming segments from said flow.

The sheathed flow comprising a first fluid sheathed by a fluid with which the first fluid is immiscible may be provided by a method in accordance with the third aspect of the present invention. The fluid with which the first fluid is immiscible may be second and third fluids of the method of the third aspect of the present invention.

The method may further comprise impinging one or more flows of carrier fluid on the sheathed flow. The fluid with which the first fluid is immiscible is preferably immiscible with the carrier fluid. The flow rate of the carrier fluid may be greater than the sheathed flow. It is preferred that the flow rate of the carrier fluid is from 1 to 4 times, more preferably 1 to 3 times and further more preferably 1.5 to 2.5 times greater than the flow rate of the sheathed flow

The segments formed may be slug-shaped or may be substantially spherical.

It is preferred that the method comprises providing a microfluidic device. The microfluidic device may comprise those features described above in relation to the third aspect of the present invention.

The microfluidic device may comprise one or more carrier fluid conduits for delivering carrier fluid so as to impinge on the sheathed flow.

The microfluidic device may comprise a discontinuity at or downstream of the region where the one or more carrier fluid conduits delivers carrier fluid so as to impinge on the sheathed flow. The discontinuity may be in the form of a flow constriction.

The methods of the third and fourth aspects of the present invention may use the microfluidic devices of the first and second aspects of the present invention.

In accordance with a fifth aspect of the present invention, there is provided a composition comprising a carrier fluid and segments formed using a method in accordance with the fourth aspect of the present invention. The present invention will now be described by way of example only with reference to the following figures of which:

Figure 1 is a plan view of an example of an embodiment of a microfluidic device in accordance with the first and second aspects of the present invention;

Figure 2 is cross-sectional view through the microfluidic device of Figure 1, the cross-section being taken along AA in Figure 1;

Figure 3 is a stylised three-dimensional view of part of the device of Figures 1 and 2, looking from the discontinuity 14 of Figures 1 and 2 in an upstream direction; Figure 4 is a schematic cross-section through the device of Figures 1 and 2, the cross-section being taken along BB in Figure 1, the schematic showing how it is thought the first fluid is sheathed by the second and third fluids; and Figure 5 is a plan view of a further example of an embodiment of a microfluidic device in accordance with the first and second aspects of the present invention.

An example of an embodiment of a microfluidic device in accordance with the first and second aspects of the present invention shown in Figures 1, 2 and 3, and is generally denoted by reference numeral 1. The device 1 comprises a parallel flow conduit 4 for forming parallel flows of first and second fluids, an inlet 7 for the first fluid and an inlet 3 for the second fluid, said inlets being in fluid communication with the parallel flow conduit so that the respective fluids may be delivered through the respective inlet to the parallel flow conduit so that the first and second fluid may form parallel laminar flows with the second fluid in contact with, and on one side of, the first fluid. The device 1 further comprises an inlet 9 for a third fluid, the inlet for the third fluid being downstream of the inlet 7 for the first fluid and the inlet 3 for the second fluid, the inlet 9 for the third fluid positioned so that the third fluid is deliverable through the inlet for the third fluid so as to contact the second fluid and the first fluid so that the first fluid is sheathed by the second and third ■ fluids. Inlet 9 for the third fluid is circular and has a diameter of 1.5mm.

The device 1 further comprises a delivery conduit 2. The inlet 3 for the second fluid is located at the upstream end of the delivery conduit 2. The delivery conduit 2 has a substantially rectangular cross-section and has a depth of 0.35 mm and a width of 1.5mm. Second fluid is delivered via port 19 and delivery passage 22 to inlet 3. Second fluid then moves along the delivery conduit 2 to parallel flow conduit 4. Parallel flow conduit 4 comprises a second channel 5 and a first channel 6. The second channel 5 is substantially rectangular in cross-section, and has a depth of 0.35mm and a width of 1.5mm. The first channel 6 is substantially square in cross-section, having a width and depth of 0.35mm. The inlet 7 for the second fluid is provided at the upstream end of first channel 6. In use, second fluid is provided via port 20 through delivery passage 23 to inlet 7. The first fluid moves along the first channel 6 in a laminar flow. Second fluid flows along the second channel 5 in a laminar flow, parallel to the laminar flow of the first fluid. The arrangement of the first 5 and second 6 channels ensures that the second fluid is in contact with the first fluid on one side of the first fluid. The inlet 9 for the third fluid is located immediately downstream of the parallel flow conduit 4. Third fluid is delivered to the inlet 9 via port 21 and delivery passage 24. Third fluid is delivered into sheath-forming region 8 which is located immediately downstream of the parallel flow conduit 4. This is best seen in Figure 3. The third fluid contacts the first and second fluids from below so that the first fluid is sheathed by the second and third fluids. Whilst not wishing to be bound by the theory, the arrangement of the fluids is believed to be as shown in Figure 4. In the schematic arrangement of Figure 4, first fluid F is sheathed by second fluid S and third fluid T. The dotted lines indicate the features that are visible in Figure 3. In the present case, the second and third fluids are the same, but this may not be the case.

The device is provided with two flow-enhancing conduits 10, 11, each of which is arranged to deliver a flow of second or third fluid at, or slightly upstream of, the sheath-forming region. The flow-enhancing conduits 10, 11 meet the parallel flow conduit 4 at or near the end of the parallel flow conduit 4. It has been found that the μse of the flow- enhancing conduits discourages migration of the first fluid to a nearby fluid-solid interface or a fluid-air interface. The flow enhancing conduits 10, 11 are substantially rectangular in cross-section, having a width of lmm and a depth of 1.2mm.

At or immediately downstream of the junction where the inlet 9 meets the sheath-forming region 8, there are provided two lateral carrier fluid conduits 12, 13. The carrier fluid conduits 12, 13 deliver a carrier fluid to impinge on the sheathed flow. The carrier fluid is immiscible with the second and third fluids- The carrier fluid conduits 12, 13 are substantially rectangular in cross-section, having a width of lmm and a depth of 1.2mm.

Immediately downstream of the point at which the lateral carrier fluid conduits 12, 13 meet the sheathed flow, there is provided a discontinuity 14. The discontinuity is in the form of a flow constriction. The flow constriction causes the formation of segmented flow comprising segments dispersed in the carrier fluid. The segments comprise an inner portion of first fluid encapsulated within an outer portion of fluid with which the first fluid and the carrier fluid are immiscible (the fluid with which the first fluid and the carrier fluid are immiscible is the second and third fluids) . The segmented flow is formed downstream of the constriction in second delivery conduit 15. The outlet conduit 15 comprises a first portion 17 upstream of a second portion 16, with an enlargement 18 in cross-section being provided between the first portion and the second portion. The first portion 17 is substantially rectangular in cross- section^', having a depth of 1.2mm and a width of 1.5mm. The second portion 16 is substantially rectangular in cross- section, having a depth of 1.8mm and a width of 2.5mm. A step 29 is provided at the enlargement. It has been found that the enlargement enhances the formation of spherical segments, presumably by causing deceleration of the- flow due to the larger volume of the outlet conduit 15 downstream of the enlargement.

The conduits and passages are made by machining material from a block of polytetrafluoroethylene (PTFE) . The device 1 also comprises two further lateral conduits 50, 51 which meet the outlet conduit 15 downstream of the enlargement 18. The two further lateral conduits 50, 51 may be used to introduce species which react with one or more species in the segments. The two further lateral conduits 50, 51 are substantially rectangular in cross-section, having a width of lmm and a depth of 1.8mm.

It has been found that for satisfactory operation of the device 1 the second fluid should have a relatively high viscosity. This viscosity may typically be from lOOmPa.S to 25OmPa. s and may be achieved by adding a viscosity enhancer to water. Such viscosity enhancers are well-known, but may include polysaccharides. The viscosity range that is required for any given device will depend on the geometry of the device, the size of the inlets, the flow rates of the first and second fluids and the interfacial tension between the second fluid and the first fluid. It will be apparent to those skilled in the art when the desired viscosity range has been achieved because parallel flows of the first and second fluids will be achieved in the parallel flow conduit 4. In the event that the desired viscosity range has not been met, the first fluid will not be constrained in a parallel laminar flow, and the first fluid will migrate to a fluid-air or fluid-solid interface.

It may be desirable for one or more of the first, second and third fluids to comprise an agent for reducing interfacial tension between respective fluids. This may typically be achieved by adding 1.5% to 3% w/w non-ionic surfactant to the first fluid (assuming that the first fluid is a non- aqueous phase) . Again, a person skilled in the art can readily determine whether a desired value of the interfacial tension has been reached because parallel flows of the first and second fluids will be achieved in the parallel flow conduit. In the event that the desired interfacial tension has not been met, the first fluid will not be constrained in a parallel laminar flow, and the first fluid will migrate to a fluid-air or fluid-solid interface.

Use of the device of Figure 1 is now described by way of example only. An aqueous solution of 2% alginate and 0.5% calcium carbonate was introduced into delivery conduit 2, flow enhancing-conduits 10, 11 and inlet 9 at a rate of 2.5- 3ml/hour. The aqueous solution also comprised a small amount of procion blue dye to enable simple visualisation and characterisation of the end-product segments. An oil-based phase comprising Triton X-100 surfactant and sudan red dye dissolved in high oleic acid sunflower oil was introduced into first channel 6 of parallel flow conduit 4 at a rate of about 0.45 to 0.75ml /hour . The surfactant was present from 1.5 to 3% of the weight of the sunflower oil, and was' used to reduce the interfacial tension between the aqueous solution introduced into the delivery conduit 2 and the oil- based phase. The sudan red dye was added to enable simple visualisation and characterisation of the end-product segments. High oleic acid sunflower oil was passed through the two lateral carrier fluid conduits 12, 13 at a flow rate of about 24 to 32 ml/hour. An oil-based solution of 5% acetic acid in high oleic acid sunflower oil was passed into the two further lateral fluid conduits 50, 51 at a flow rate of about 6 to 24ml/hour. Parallel laminar flows of two immiscible phases were seen to form in the parallel flow conduit 4. Spherical segments were seen to form downstream of the discontinuity 14. These segments comprise an inner oil-based portion comprising the red dye and Triton X-100, and an outer (aqueous) portion comprising alginate and calcium carbonate. The introduction of the acetic acid solution causes the formation of gelled segments which are capable of being handled. The acetic acid in the oil phase migrates into the outer portion of the segments and reacts with the calcium carbonate to release calcium ions. The calcium ions react with the alginate ions to produce water-insoluble calcium alginate which is in the form of a gel .

The experiment was performed at room temperature.

A further example of an embodiment of an alternative device in accordance with the first and second aspects of the present invention is shown in Figure 5, with the features in Figure 5 bearing reference numerals are essentially the same as those features bearing the same reference numerals as described with reference to the device of Figures 1, 2 and 3. The device is very similar to that shown in Figures 1 and 2, except that the lateral conduits 12, 13 in the device of Figure 5 are further upstream than in the device of Figures 1, 2 and 3. Upstream of enlargement 18, the device operates in essentially the same manner as the device shown in Figures 1, 2 and. The device of Figure 5 is different from that of Figures 1, 2 and 3 in that the device of Figure 5 is not provided' with the two further lateral conduits 50, 51 which meet the second delivery conduit 15 downstream of the enlargement 18. Furthermore, the device of Figure 5 is used in essentially the same manner as the device of Figures 1 and 2, in that the device is used to create a flow of spherical segments in the outlet conduit 15.

Those skilled in the art will realise the other arrangements and geometries may be used to provide a microfluidic device and method in accordance with the present invention. For example, it is anticipated that delivery passage 24 may be angled so as to provide a larger component of flow in the downstream direction; in this case, the two flow-enhancing conduits may not be necessary.

The devices of Figures 1 to 5 are arranged to manufacture segmented flow. It is not necessary for a device and method of the present invention to produce segmented flow. This device may be readily adapted so that the sheathed flow is uninterrupted, for example, by removing the carrier fluid conduits.

Claims

1. A method of sheathing a first fluid by one or more fluids with which the first fluid is immiscible, the method comprising:

(i) providing a first fluid;

(ii) providing second and third fluids with which the first fluid is immiscible;

(iii) forming parallel laminar flows of the first and second fluids with the second fluid contacting the first fluid on a first side of the first fluid;

(iv) subsequent to step (iii), contacting the third fluid with the second fluid and the first fluid so that the first fluid is sheathed by the second and third fluids.

2. A method according to claim 1 wherein the second and third fluids are aqueous fluids and the first fluid is immiscible with aqueous fluids.

3. A method according to claim 1 or claim 2 wherein step (iii) comprises providing a laminar flow of the second fluid, and contacting the laminar flow of the second fluid with the first fluid.

4. A method according to any one preceding claim, wherein the third fluid is substantially the same as the second fluid.

5. A method according to any one preceding claim, wherein one or more of the first, second and third fluids is aqueous, and said aqueous fluid comprise waters and a viscosity enhancer.

6. A method according to claim 5 wherein the viscosity enhancer may comprise a water-soluble polymer.

7. A method according to claim" 5 or claim 6 wherein the viscosity of the aqueous fluid is from 3OmPa. s to 50OmPa. s.

8. A method according to claim 5 or claim 6 wherein the viscosity of the aqueous fluid is from lOOmPa.s to 25OmPa. s.

9. A method according to any one preceding claim wherein one or more of the first fluid, the second fluid and the third fluid comprises an agent for reducing interfacial tension between the first fluid and one or both of the second and third fluids.

10. A method according to claim 9 wherein the agent for reducing interfacial tension comprises a surfactant.

11. A method according to claim 10 wherein the concentration of the surfactant in the respective first, second or third fluid is from 0.1% to 10% w/w surfactant : respective fluid.

12. A method according to claim 10 wherein the concentration of the surfactant in the respective first, second or third fluid is from 1% to 3% w/w surfactant : respective fluid.

13. A method according to any one preceding claim, wherein the flow rate of the first fluid is lower than the flow rate the second fluid and the third fluid.

14. A method according to claim 13 wherein the flow rate of the first fluid is from 15% to 30% of the flow rate of the second fluid.

15. A method according to any one preceding claim comprising providing a microfluidic device, the device comprising an inlet for the second fluid.

16. A method according to any one preceding claim, the method comprising providing a sheathed flow, the method further comprising impinging one or more flows of carrier fluid on the sheathed flow, wherein the fluid with which the first fluid is immiscible is immiscible with the carrier fluid.

17. A method according to any one preceding claim, wherein the flow rate of the carrier fluid is greater than the sheathed flow.

18. A method according to claim 17 wherein the flow rate of the carrier fluid is from 1.1 to 4 times that of the flow rate of the sheathed flow.

19. A composition comprising a carrier fluid and segments formed using a method in accordance any one of claims 16 to

18.

20 . A microfluidic device for performing a method as claimed in any one of claims 1 to 18 , the device comprising : a parallel flow conduit for carrying parallel flows of the first fluid and a second fluid with which the first fluid is immiscible; an inlet for the first fluid and an inlet for the second fluid, said inlets being in fluid communication with the parallel flow conduit so that the respective fluids may be delivered through the respective inlet to the parallel flow conduit so that the first and second fluid may form parallel laminar flows in the parallel flow conduit with the second fluid in contact with, and on one side of, the first fluid; and an inlet for a third fluid, the inlet for the third fluid being downstream of the inlet for the first fluid and the inlet for the second fluid, the inlet for the third fluid arranged so that the third fluid is deliverable through the inlet for the third fluid to contact the second fluid and the first fluid so that the first fluid is sheathed by the second and third fluids .

21. A device according to claim 20 wherein the inlet for the second fluid is upstream of the inlet for the first fluid.

22. A device according to claim 20 or claim 21, wherein the parallel flow conduit comprises a second channel for the flow of the second fluid and a first channel for the flow of the first fluid.

23. A device according to claim 22 wherein the inlet for the first fluid is provided in the first channel.

24. A device according to claim 22 or claim 23 wherein the second channel and first channel are elongate and the longitudinal axis of the first channel is parallel to the longitudinal axis of the second channel, the first channel ^■ being in fluid communication with the second channel so that a laminar flow of the first fluid contacts a laminar flow of the second fluid along the length of the first channel.

25. A device according to any one of claims 22 to 24 wherein the second channel has a larger cross-sectional area than the first channel.

26. A device according to any one of claims 20 to 25 further comprising a delivery conduit for delivering the second fluid to the parallel flow conduit, wherein the delivery conduit is immediately upstream of the parallel flow conduit.

27. A device according to claim 26 wherein the inlet for the second fluid is provided in the delivery conduit.

28. A device according to any one of claims 20 to 27 comprising a sheath-forming region into which the third fluid is deliverable.

29. A device according to claim 28 wherein the sheath- forming region is so configured that the third fluid, when it is introduced, so contacts the first fluid and the second fluid that the first fluid is sheathed by the second and third fluids.

30. A device according to claim 28 or claim 29 wherein the sheath-forming region is downstream of the parallel flow conduit .

31. A device according to any one of claims 29 to 30 wherein the sheath-forming region is provided by a sheath-forming conduit having a larger cross-sectional area than the parallel flow conduit.

32. A device according to any one of claims 20 to 31 further comprising one or more flow-enhancing conduits for delivering a fluid with which the second and third liquids are miscible.

33. A device according to claim 32 when dependent on claim 9, wherein the flow-enhancing conduit (s) is arranged to deliver the flow-enhancing fluid at, and/or upstream of, the sheath-forming region.

34. A device according to any one of claims 20 to 33 comprising one or more carrier fluid conduits for delivering carrier fluid to impinge on the sheathed flow.

35. A device according to claim 34 when dependent on claim 28 wherein the carrier fluid conduit (s) is arranged to deliver carrier fluid substantially at and/or downstream of the sheath-forming region.

36. A device according to claim 34 or claim 35, the device being provided with a discontinuity at or downstream of the region where the carrier fluid conduit (s) delivers carrier fluid to the sheathed flow.

37. A device according to claim 28 or any one of claims 29 to 36 when dependent on claim 28, further comprising an outlet conduit downstream of the sheath-forming region.

38. A device according to claim 37 when dependent on any one of claims 34 to 36, wherein the outlet conduit is downstream of the one or more carrier fluid conduits.

39. A device according to claim 38 wherein the outlet conduit is provided with an enlargement at or downstream of the discontinuity.

40. A microfluidic device for performing a method as claimed in any one of claims 1 to 18, the device comprising: (i) a delivery conduit for delivering a second fluid, (ii) an inlet for delivering the second fluid to the delivery conduit,

(iii) a parallel flow conduit downstream of the delivery conduit, the parallel flow conduit comprising a second channel for the carriage of the second fluid and a first channel for the carriage of the first fluid, (iv) an inlet for delivering the first fluid to the first channel, the first channel being in fluid communication with the second channel so that a laminar flow of the first fluid in the first channel may contact a laminar flow of the second fluid in the second channel along the length of the first channel, the device further comprising a sheath-forming region downstream of the parallel flow conduit and an inlet for the delivery of a third fluid to the sheath-forming region.