WO2005123241A1

WO2005123241A1 - Apparatus and method for performing photochemical reactions

Info

Publication number: WO2005123241A1
Application number: PCT/GB2005/002436
Authority: WO
Inventors: Robert Huw Davis; Daniel David Palmer
Original assignee: Q Chip Limited
Priority date: 2004-06-21
Filing date: 2005-06-21
Publication date: 2005-12-29

Abstract

There is provided an apparatus for the performance of photochemical reactions, the apparatus comprising (i) a microfluidic device (1) comprising a first inlet (2a) for the introduction of a first fluid, the first inlet being in fluid communication with an irradiation zone conduit (14) having an irradiation zone inlet (17) where a fluid enters the irradiation zone and an irradiation zone outlet (15) where a fluid leaves the irradiation zone, the irradiation zone conduit extending in an indirect manner from the irradiation zone inlet to the irradiation zone outlet, (ii) a source of electromagnetic radiation operable to illuminate the irradiation zone with electromagnetic radiation.

Description

Apparatus and Method for performing photochemical reactions

The present invention relates to a method and apparatus for performing photochemical reactions, including an apparatus and method producing a segmented flow of liquid.

Photochemistry is an extremely powerful tool for the synthetic chemist, providing a route to synthetically demanding chemical functionalities and moieties. However, lab-scale photochemical reactions have some disadvantages, for example, long reaction times, and attenuation of incident light by large (often stationary) solvent volumes.

It is therefore desirable to provide a micro-photochemical reactor device which allows the production of a precisely defined, alternating fluid quanta, which experience rapid "internal-vortex" mixing.

One disadvantage of prior art devices for manufacture of segmented flow is that (typically) the fluid content of each segment is mixed earlier than is required by the user. Premature mixing may be disadvantageous to the reaction process .

It is therefore an aim of the present invention to alleviate at least some of the disadvantages identified above . It is a further aim of the present invention to provide a method and apparatus for producing segmented flow of a liquid.

In accordance with a first aspect of the present invention there is provided an apparatus for the performance of photochemical reactions, the apparatus comprising (i) a microfluidic device comprising a first inlet for the introduction of a first fluid, the first inlet being in fluid communication with an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, the irradiation zone conduit extending in an indirect manner from the irradiation zone inlet to the irradiation zone outlet, (ii) a source of electromagnetic radiation operable to illuminate the irradiation zone with electromagnetic radiation.

Such an apparatus is effective in performing photochemical reactions, the photochemical reaction primarily being carried out in the irradiation zone when reaction components are exposed to the electromagnetic radiation from the source of electromagnetic radiation. The term "indirect" refers to the irradiation zone conduit taking a path that is not a straight line or shortest path between the irradiation zone inlet and the irradiation zone outlet .

The term "microfluidic" is well-understood by those skilled in the art and in particular includes those devices having conduits having diameters of about 1mm or less. The conduits preferably have a diameter of from 0.05 to 0.5mm and more preferably of from 0.05 to 0.1mm.

The irradiation zone outlet is preferably in communication with a device outlet for the egress of reaction products.

It is preferred that the irradiation zone conduit comprises one or more curved portions or bends in the flow path between the irradiation zone inlet and the irradiation zone outlet .

In accordance with a second aspect of the present invention there is provided an apparatus for the performance of photochemical reactions, the apparatus comprising (i) a icrofluidic device comprising a first inlet for the introduction of a first fluid, the first inlet being in fluid communication with an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, the irradiation zone conduit comprises one or more bends or curved portions in the flow path between the irradiation zone inlet and the irradiation zone outlet, (ii) a source of electromagnetic radiation operable to illuminate the irradiation zone with electromagnetic radiation .

It is further preferred that the irradiation zone conduit forms an S or Z shape in the flow path between the irradiation zone inlet and the irradiation zone outlet.

The irradiation zone conduit may comprise a serpentine, spiral or tortuous formation in the flow path between the irradiation zone inlet and the irradiation zone outlet.

The irradiation zone conduit may comprise a switchback formation in the flow path between the irradiation zone inlet and the irradiation zone outlet.

It is preferred that, if the irradiation zone has an area of A² (units)², then the length of the irradiation zone conduit between the irradiation zone inlet and the irradiation zone outlet is from 2A to 20A units, more preferably from 5A to 20A units and further more preferably from 8A to 15A units.

The length of the irradiation zone conduit between the irradiation zone inlet and the irradiation zone outlet may, for example, be fr-o 5cm to 40cm, when the irradiation zone has a maximum diameter of from 0.5 to 4cm.

It is preferred that the device is provided with a means for inhibiting transmission of electromagnetic radiation between the irradiation zone and the first inlet. The means for inhibiting transmission of electromagnetic radiation may comprise one or more bend or bends in a conduit (typically upstream of the irradiation zone and downstream of the first inlet), a switchback arrangement in a conduit (typically upstream of the irradiation zone and downstream of the first inlet) , an internal surface of a conduit being coating with non-reflective material or a discontinuity in a conduit, such as a drop or fall from one level to another.

The apparatus is preferably provided with a means for urging reagents from the first inlet to the irradiation zone outlet, such as a pump.

The fluid path between the first inlet and the irradiation zone outlet may be formed by one or more conduits.

The device may be provided with a second inlet for the introduction of a second fluid. The first inlet is preferably associated with a first conduit and the second inlet is preferably associated with a second conduit. It is preferred that the first and second conduits merge to form a third conduit, which is preferably upstream of the irradiation zone. The third conduit would typically be in communication with the irradiation zone conduit so that fluid could be moved from the third conduit to the irradiation zone. Those skilled in the art should note that the third conduit and the irradiation zone conduit may not be distinguishable from one another as separate conduits, for example, in the case where the third conduit and irradiation zone conduit have the same diameter or internal size .

It is preferred, in one embodiment, that the first fluid is immiscible with the second fluid, and that the first conduit and the second conduit merge to form a third conduit (or the third conduit is formed with a constriction or other discontinuity) such that fluid in the first and second conduits form into a flow of alternate segments in the third conduit. The third conduit would typically be in communication with the irradiation zone conduit so that the flow of alternate segments could be moved to the irradiation zone conduit for exposure to electromagnetic radiation .

The device may further be provided with a third inlet for the introduction of a third fluid. The third inlet is preferably associated with a fourth conduit. It is preferred that the fourth conduit merges with one or more of the first, second and third conduits, preferably upstream of the irradiation^' zone. It is preferred that the fourth conduit merges with the third conduit to form a fifth conduit. The first, second, third and fourth conduits would typically be arranged so that fluids may be transferred from those conduits (possibly via other conduits, such as ^'the fifth conduit) to the irradiation zone conduit.

Alternatively or additionally, the third fluid may be immiscible with the first and second fluids, and the third conduit may merge with the fourth conduit to form a fifth conduit (or the fifth conduit is provided with a constriction or other discontinuity) , such that fluid in the third and fourth conduits form into a flow of alternate segments in the fifth conduit. The fifth conduit would typically be in communication with the irradiation zone conduit so that the flow of alternate segments could be moved to the irradiation zone conduit for exposure to electromagnetic radiation. Those skilled in the art should note that the fifth conduit and the irradiation zone conduit may not be distinguishable from one another as separate conduits, for example, in the case where the fifth conduit and irradiation zone conduit have the same diameter or internal size.

It is preferred that, upstream of the irradiation zone, a conduit is provided with an enlargement in cross-section. Such an enlargement in cross-section may allow segments in a segmented flow to form a more spherical shape prior to irradiation.

The surfaces of the conduits mentioned above that come into contact with the fluids used in the device may be provided with low energy materials. This may be achieved by forming channels or conduits into a substrate of low energy material or by forming channels or conduits into a substrate of relatively high energy material and coating the channels or conduits so formed with a low energy material .

Alternatively, partial channels or conduits may be formed in two substrates such that, when the substrates are mounted together, the partial channels of one substrate cooperate with the respective partial channels of the other substrate to form complete channels or conduits.

The microfluidic device may comprise two substrates having low energy surfaces (typically around that of fluoropolymers, below 22 mN/m, and preferably below 18 mN/m) , the two substrates preferably being placed co- facially one against the other. One or more (preferably the irradiation zone conduit and more preferably all) of the conduits provided in the device may be formed in one of the substrates (this being known as the base substrate) . This may typically be achieved by milling the conduit or conduits using conventional milling technology, or by using laser ablation for example. The low energy surfaces may be provided by fluoropolymer based substrate layers, which may be composed of bulk fluoropolymer, or fluoropolymer or fluoropolymer-based coatings applied to other non-fluoropolymer bulk material substrate layers. One of the substrates (preferably the substrate not being the base substrate) may be at least partially transparent to the said electromagnetic radiation.

It is preferred that the source of electromagnetic radiation is a source of ultra-violet radiation.

It is further envisaged that two or more^" devices may be present together. This is particularly advantageous when it is desirable to produce a segmented flow in a confined or restricted space. It is preferable that a plurality of devices is present, for example more than five.

A third aspect of the present invention provides an apparatus for the performance of photochemical reactions, the apparatus comprising (i) a microfluidic device comprising a plurality of first inlets for the introduction of a first fluid, and a plurality of irradiation zone conduit, each first inlet being in fluid communication with an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, wherein one, and preferably each, of the irradiation zone conduits extend in an indirect manner from the respective irradiation zone inlet to the respective irradiation zone outlet, (ii) a source of electromagnetic radiation operable to illuminate each irradiation zone with electromagnetic radiation.

One or more of the irradiation zone conduits may be provided with one or more bends or curved portions in the flow path between the respective irradiation zone inlet and the respective irradiation zone outlet.

A fourth aspect of the present invention provides an apparatus for the performance of photochemical reactions, the apparatus comprising (i) a microfluidic device comprising a plurality of first inlets for the introduction of a first fluid, and a plurality of irradiation zone conduit, each first inlet being in fluid communication with an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, wherein one, and preferably each, of the irradiation zone conduits comprises one or more bends or curved portions in the flow path between the irradiation zone inlet and the irradiation zone outlet (ii) a source of electromagnetic radiation operable to illuminate each irradiation zone with electromagnetic radiation.

It is preferred that each irradiation zone outlet is in communication with a device outlet for the egress of reaction products.

The device of the apparatus of the third and fourth aspects of the present invention may incorporate those features described above with respect to the apparatus and device of the first and second aspects of the present invention.

For example, each irradiation zone conduit may comprise a spiral formation.

One or more of the irradiation zone outlets may be arranged to be in communication with a common device outlet. It is preferred that such a device outlet is provided by an aperture and that a plurality of, and preferably all, of the irradiation zone outlets are located at said aperture.

For the device in accordance with the third and fourth aspects of the present invention, it may be preferred that if the irradiation zone has an area of A² (units)², then the sum of lengths of each of the irradiation zone conduits between the respective irradiation zone inlets and the respective irradiation zone outlets is from 2A to 20A units, more preferably from 5A to 20A units and further ' more preferably from 8A to 15A units.

In accordance with a fifth aspect of the present invention, there is provided a microfluidic device suitable for use in the apparatus of the first, second, third and fourth aspects of the present invention.

In accordance with a sixth aspect of the present invention there is provided a method for performing a photochemical reaction, the method comprising (i) providing a microfluidic device comprising an • irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, the irradiation zone conduit extending in an indirect manner from the irradiation zone inlet to the irradiation zone outlet, (ii) providing a reagent or reagents for a photochemical reaction (iii) causing the reagent or reagents to flow from the irradiation zone inlet to the irradiation zone outlet (iv) irradiating the reagent or reagents as they pass from the irradiation zone inlet to the irradiation zone outlet so as to promote the photochemical reaction . In accordance with a seventh aspect of the present invention there is provided a method for performing a photochemical reaction, the method comprising (i) providing a microfluidic device comprising an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, wherein the irradiation zone conduit comprises one or more bends or curved portions in the flow path between the irradiation zone inlet and the irradiation zone outlet, (ii) providing a reagent or reagents for a photochemical reaction (iii) causing the reagent or reagents to flow from the irradiation zone inlet to the irradiation zone outlet (iv) irradiating the reagent or reagents as they pass from the irradiation zone inlet to the irradiation zone outlet so as to promote the photochemical reaction.

It is preferred that the time taken for the reagent or reagents to pass from the irradiation zone inlet to the irradiation zone outlet is from 10 seconds to 2 minutes, for example, when the path length from the irradiation zone inlet to the irradiation zone outlet is from 5cm to 40cm, more preferably when said path length is from 10cm to 20cm. The reagents may be mixed prior to the introduction of the reagents into the device.

Alternatively or additionally, a first reagent may be introduced via a first conduit, and a second reagent (being miscible with the first reagent) may be introduced via a second conduit, the first and second conduits merging at a third conduit.

Alternatively, if the first and second reagents are immiscible then it is preferred that the first conduit and the second conduit merge to form a third conduit such that fluids in the first and second conduits form into a flow of alternate segments in the third conduit. Alternatively, the third conduit may be formed with a constriction or other discontinuity such that fluids in the first and second conduits form into a flow of alternate segments in the third conduit.

The method may further comprise introducing a third reagent via a fourth conduit, wherein the third fluid may be immiscible with the first and second fluids, and the third conduit may merge ^'with the fourth conduit such that fluid in the third and fourth conduits form into a flow of alternate segments in the fourth conduit. Alternatively, the fourth conduit may be provided with a constriction or other discontinuity such that fluids in the third and fourth conduits form into a flow of alternate segments in the fourth conduit.

An eighth aspect df the present invention provides a method for performing a photochemical reaction, the method comprising: (i) providing a microfluidic device comprising an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, the irradiation zone conduit extending in an indirect manner from the irradiation zone inlet to the irradiation zone outlet, (ii) providing two or more miscible reagents for a photochemical reaction (iii) mixing the two or more miscible reagents to form a mixture (iv) causing the mixture to flow from the irradiation zone inlet to the irradiation zone outlet (v) irradiating the mixture as it passes from the ^■ irradiation zone inlet. to the irradiation zone outlet so as to promote the photochemical reaction.

A ninth aspect of the present invention provides a method for performing a photochemical reaction, the method comprising: (i) providing a microfluidic device comprising an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, the irradiation zone conduit comprising one or more bends or curved portions in the flow path between the irradiation zone inlet and the irradiation zone outlet, (ii) providing two or more miscible reagents for a photochemical reaction (iii) mixing the two or more miscible reagents to form a mixture (iv) causing the mixture to flow from the irradiation zone inlet to the irradiation zone outlet (v) irradiating the mixture as it passes from the irradiation zone inlet to the irradiation zone outlet so as to promote the photochemical reaction.

The mixture is preferably irradiated with ultraviolet radiation.

A tenth aspect of the present invention provides a method for making polymeric particulates, the method comprising: (i) providing a microfluidic device comprising an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, the irradiation zone conduit extending in an indirect manner from the irradiation zone inlet to the irradiation zone outlet (ii) providing a polymeric precursor and an initiator that, on exposure to electromagnetic radiation, initiates the polymerisation of the precursor (iii) providing a carrier fluid that is immiscible with the polymeric. precursor and the initiator (iv) mixing the polymeric precursor and the initiator to form a mixture (v) causing the mixture and the carrier fluid to form a segmented flow (vi) causing the segmented flow to pass from the irradiation zone inlet to the irradiation zone outlet (vii) irradiating the segmented flow as it passes from the irradiation zone inlet to the irradiation zone outlet so as to form polymeric particulate.

An eleventh aspect of the present invention provides a method for making polymeric particulates, the method comprising: (i) providing a microfluidic device comprising an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, the irradiation zone conduit comprising one or more bends or curved regions in the flow path between the irradiation zone inlet and the irradiation zone outlet, (ii) providing a polymeric precursor and an initiator that, on exposure to electromagnetic radiation, initiates the polymerisation of the precursor (iii) providing a carrier fluid that is immiscible with the polymeric precursor and the initiator (iv) mixing the polymeric precursor and the initiator to form a mixture (v) causing the mixture and the carrier fluid to form a segmented flow (vi) causing the segmented flow to pass from the irradiation zone inlet to the irradiation zone outlet (vii) irradiating the segmented flow as it passes from the irradiation zone inlet to the irradiation zone outlet so as to form polymeric particulate.

It is preferred for all aspects of the invention mentioned above that the device is arranged for laminar flow throughout. This is usually achieved using low energy surfaces such as those discussed above to define the fluid flow paths through the device.

According to a twelfth aspect of the present invention, there is provided a device for producing a segmented flow of liquid, which device includes: a first conduit arranged to receive a first fluid and a second conduit arranged to receive a second fluid, the first conduit and the second conduit merging to form a further flow conduit, in which, in use, the first fluid and the second fluid are permitted to flow, preferably to form a laminar flow, the further flow conduit merging with a carrier fluid conduit to form a segmented flow conduit, the segmented flow conduit being formed with a constriction or other discontinuity such that, in use, fluid in the further flow conduit and the carrier fluid conduit form into a flow of alternate segments in the segmented flow conduit.

It is particularly preferred that the first fluid and the second fluid are miscible. The carrier fluid conduit is preferably arranged to contain a carrier fluid which is typically immiscible with the first and second fluid. A typical carrier fluid is an organic fluid.

Typically, the discontinuity includes a region of changed or alterable surface energy, or a further conduit which joins the segmented flow conduit. The constriction may preferably include the internal configuration of the segmented flow conduit. It is therefore further preferred that the cross-sectional area of the segmented flow conduit is substantially less than the sum of the cross-sectional area of the further flow conduit and the carrier fluid conduit .

Preferably, the segmented flow conduit is shaped or dimensioned to include one or more curve, bend or indentation. Advantageously, the curve, bend or indentation assists in the mixing of the contents of each segment which, prior to reaching a bend, indentation or curve, may still have a substantially laminar structure. The curve, indentation or bend is preferably downstream from the constriction or other discontinuity.

Preferably, a portion of the segmented flow conduit is shaped and dimensioned to provide an irradiation zone. The irradiation zone is arranged to maximise exposure to, for example, an external radiation source. The irradiation zone is typically downstream from the constriction or other discontinuity, further preferably down stream from the curve or bend.

The constriction or other discontinuity is preferably substantially at, or close to, the juncture where the further flow conduit merges with the carrier fluid conduit.

The irradiation zone may therefore be laid out in a spirallike shape or a z-shape. Preferably, segmental flow conduit has a length of between 5cm and 40cm when in the spiral-like shape or z-shape. However, it is envisaged that the irradiation zone can be any shape that has the desired effect of maximising exposure to an external source .

Typically, the segmented flow conduit may have an internal- reflection coating. Advantageously, the internal- reflection coating enhances the "increased-exposure" effect . Preferably, the device may further include an external radiation source. The external radiation source may be a light source which further preferably is arranged to be delivered via a light guide, which may be adapted to produce a collinated light beam.

It is particularly preferred that, with the exception of the irradiation zone, the device is masked with a reflective shield (which may or may not be an integral part of the device) . Advantageously, the reflective shield prohibits, or at least substantially reduces, the uncontrolled local absorption of radiation in the first conduit, the second conduit, the further flow conduit and/or the segmented flow conduit.

The device may be a unitary device, or alternatively may be manufactured from a plurality of separate conduits which are fused or joined together.

It is further envisaged that the device may include a third and optionally a fourth conduit arranged to merge with the first and second conduit to form the further flow conduit, or alternatively to merge with the further flow conduit. However, it is envisaged that the device may include more conduits arranged to merge with the further flow conduit. Each conduit is preferably arranged to receive a fluid (further preferably a miscible fluid). It is self evident to a person skilled in the art, that the number of fluid conduits feeding to the further flow conduit is dependent on the number of fluids that it is desired to combine in each segment .

The device offers a number of advantages over conventional devices for photochemical reactions, one such advantage includes decreased reaction times. This is due to the high surface/volume ratio of the fluid circuit in the device. In addition, as only small (typically nano or pico litre) volumes are exposed to a radiation source at any one time, there is significantly less attenuation of incident light by solvent, making the reaction more efficient per photon. Furthermore, efficient mixing can be achieved without the need for external agitation, producing homogenised reaction mixtures, which can be exposed to a tuned radiation source for a controlled time.

It is further envisaged that two or more devices may be present together. This is particularly advantageous when it is desirable to produce a segmented flow in a confined or restricted space. It is preferable that a plurality of devices are present, for example more than five.

Therefore, according to a thirteenth aspect of the present invention, there is provided a device for producing two or more segmented flows of liquid, said device including: two or more first conduits arranged to receive a first fluid and two or more second conduits each arranged to receive a second fluid, each first conduit merging with a respective second conduit to form a further flow conduit, each further flow conduit merging with a respective carrier fluid conduit to form a respective segmented flow conduit, each segmented flow conduit being formed with a constriction or other discontinuity such that fluid in each further flow conduit and each carrier fluid conduit form into a flow of alternate segments in each respective segmented flow conduit.

Accordingly, it is further envisaged that the device includes a plurality of first conduits, a plurality of second conduits merging to form respective further flow conduits, each further flow conduit being for merging with a respective carrier fluid conduit to form a respective segmented flow conduit, each segmented flow conduit being formed with a constriction or other discontinuity such that fluid in each further flow conduit and each carrier fluid conduit form into a flow of alternate segments.

The first conduits, the second conduits, the further flow conduits and segmented flow conduits are substantially as described hereinbefore with reference to the first aspect of the present invention.

It is preferable that fluid entering each first fluid conduit is the same fluid, however, it is envisaged that the device is arranged such that a different fluid enters each first conduit.

It is preferable that fluid entering each second fluid conduit is the same fluid, however, it is envisaged that the device is arranged such that a different fluid enters each first conduit.

It is preferred that the segmented flow conduits are orientated such that they have a relatively small surface area in the plane of the device. It is particularly preferred that the segmented flow conduits are arranged in a spiral. Advantageously, having the segmented flow conduits arranged in such an orientation permits the size of an irradiation zone (thereby the photochemical reaction takes place) to be substantially reduced.

According to a fourteenth aspect of the present invention, there is provided a method for producing a segmented flow of a fluid, which method includes: introducing a first liquid into a first inlet conduit and a second liquid into a second inlet conduit, the first conduit and the second conduit merging to form a further flow conduit; permitting the first liquid and the second liquid to achieve a laminar flow in the further flow conduit; merging the laminar flow with a carrier fluid in a segmented flow conduit, the segmented flow conduit including a constriction or discontinuity which causes the laminar flow and the carrier fluid to form a flow of alternate segments.

The method is preferably carried out in a device, substantially as described hereinbefore.

It is particularly preferred that the constriction or discontinuity is substantially in an area where the laminar flow and the carrier fluid meets.

It is particularly preferred that the first fluid and the second fluid are miscible liquids. Therefore, potentially reactive mixtures may be kept separate until such time that mixing is required. The carrier fluid is further preferably a fluid which is immiscible.

For example, the first fluid may include a dissolved photosensitivity compound (such as naphthalene, orthracene, POPOP) , whose purpose is to accelerate the photochemical reaction.

The present invention may be utilised in a number of chemical reactions to which a micro-photochemical reactor might be applicable. A non-exhaustive list may include:

The Paterno-Buchi reaction for the synthesis of oxetanes, Woodward-Hoffman, thermally disallowed, cyclo-addition reactions, Synthesis of pinacols, Olefin epimerisation reactions, UV polymerisations, Photo-oxidations, Photolysis of organo etallics to provide reactive intermediates for synthesis, Deprotection reactions.

The devices and methods of the present invention may preferably use fluids having liquid or liquid-like (as opposed to gaseous) properties.

The present invention will now be described by way of example only with reference to the following Figures of which:

Figure 1 represents a device according to the twelfth aspect of the present invention and a device as used in an apparatus according to the first and second aspects of the present invention; Figure 2 represents a device according to the thirteenth aspect of the present invention and a device as used in an apparatus according to the third and fourth aspects of the present invention, such a device having a plurality of irradiation zones.

Referring to Figure 1, the device is generally indicated by the numeral 1. The first inlet conduit 2 (provided with first inlet 2a) merges with the second inlet conduit 3 (provided with second inlet 3a) at point 4 to form a further flow conduit 5.

A carrier fluid conduit 6 merges at point 7 with further flow conduit 5 to form a segmented flow conduit 8. A discontinuity 9 (in the form of a constricted internal cross sectional area of the conduit) is substantially at the junction where conduits 5 and 6 merge.

Segmented flow conduit 8 bends at points 10, 11 and 12.

These bends are to aid internal mixing in the segments of flow and help inhibit transmission of radiation from the irradiation zone to the first and second inlets 2a, 3a. Transmission of radiation to regions upstream of the irradiation zone causes premature reactions to occur. This may be unacceptable, for example, if the reaction is a polymerisation reaction because this may cause one or more of the upstream conduits to become blocked. The segmented flow conduit 8 is formed into an irradiation zone conduit 14 in the form of a spiral in an irradiation zone 13. The irradiation zone conduit 14 has a greater cross-sectional area than the segmented flow conduit 8, the enlargement in cross-section at point 16 allowing long, slug-like flow segments to form into a more spherical shape. The irradiation zone conduit 14 has an irradiation zone inlet 17 where fluid enters the irradiation zone 13 and an irradiation zone outlet 15 where fluid leaves the irradiation zone 13. The irradiation zone conduit extends in a spiral (and therefore in an indirect manner) from the irradiation zone inlet 17 to the irradiation zone outlet 15, "indirect" meaning that the irradiation zone conduit takes a path that is not a straight line or shortest path between the irradiation zone inlet and the irradiation zone outlet. Such an arrangement increases the time in which the reagents are in the irradiation zone and therefore increases the concentration of reaction products.

The first inlet conduit 2, second inlet conduit 3, further flow conduit 5, carrier flow conduit 6, segmented flow conduit 8 and irradiation zone conduit 14 are formed by machining the said conduits from a block of polytetrafluoroethylene (PTFE) polymer using a conventional milling machine. The conduits typically have a square cross-section and typically have a channel width of between 50 to 300 microns. Smaller conduits may be produced using other techniques, such as laser ablation, photolithography and deep reactive ion etching. A cover made from a low energy material (in this case a 0.005 inch thick film of

PFA (a perfluoroalkoxy copolymer, supplied by DuPont) that is at least partially transparent to ultraviolet radiation is provided on top of the PTFE block.

A non-UV transmissive blocking plate is arranged over the

PFA cover in order to prevent unwanted exposure of parts of the device other than irradiation zone to UV radiation. A suitable aperture is provided in the blocking plate so that UV light can be transmitted to the irradiation zone.

A source of electromagnetic radiation is arranged in relation to the device 1 so that it illuminates the irradiation zone with the appropriate electromagnetic radiation. This will typically be ultra-violet radiation (for example, that used to cure UV-sensitive polymers), but may be any type of electromagnetic radiation. The materials forming the cover and blocking plate would be chosen appropriately, given the nature of the electromagnetic radiation used.

Those skilled in the art will realise that low energy materials other than PTFE may be used to form the block and materials other than PFA may be used to form the cover. Alternatively, a coating of low energy material may be formed on a machined or otherwise channelled block of a relatively high energy material. Such a coating may be formed, for example, by plasma deposition, dipping, spin coating, lithography or Langmuir Blodgett deposition.

Referring to Figure 2, there is provided a device 100 according to the ninth aspect of the present invention and a device as used in an apparatus according to the third aspect of the present invention. The device 100 comprises a plurality (in this case ten) of circuits (each labelled as 101) in which reactions can occur. The device comprises a plurality of first inlet conduits 102 (only one of which is labelled for clarity) , each provided with a first inlet 102a, each first inlet conduit merging with a second inlet conduit 103 at point 104 to form a further flow conduit 105. Each second inlet conduit is provided with a second inlet 103a.

A carrier fluid conduit 106 merges at point 107 with further flow conduit 105 to form a segmented flow conduit 108. A discontinuity 109 (in the form of a constricted internal cross sectional area of the conduit) is substantially at the junction where conduits 105 and 106 merge.

Segmented flow conduit 108 bends at points 110, 111, 112, 113, 114, 115, 116. These bends increase mixing and help prevent transmission of electromagnetic radiation from irradiation zone 117 to any of the aforementioned conduits upstream of the irradiation zone.

Each segmented flow conduit 108 is formed into an irradiation zone conduit 119 in the form of a spiral in an irradiation zone 117. The irradiation zone conduit 119 has a greater cross-sectional area than the segmented flow conduit 108, an enlargement in cross-section (not shown) upstream of the irradiation zone 117 allowing long, sluglike flow segments to form into a more spherical shape. The irradiation zone conduit 119 has an irradiation zone inlet 120 where fluid enters the irradiation zone 117 and an irradiation zone outlet 121 where fluid leaves the irradiation zone 117. The irradiation zone conduit extends in a spiral (and therefore in an indirect manner) from the irradiation zone inlet 120 to the irradiation zone outlet 121, "indirect" meaning that the irradiation zone conduit takes a path that is not a straight line or shortest path between the irradiation zone inlet and the irradiation zone outlet. Such an arrangement increases the time in which the reagents are in the irradiation zone and therefore increases the concentration of reaction products.

In the irradiation zone, all irradiation zone conduits 119 form a spiral thereby reducing the necessary overall surface area of the irradiation zone 117. The contents of each irradiation zone conduit 119 exit via corresponding irradiation zone outlet 121.

All of the irradiation zone outlets are arranged around the periphery of a device outlet 118. In this manner, the fluids from each of the irradiation zone outlets may readily be collected together for removal from the device.

First inlet conduit 102, second inlet conduit 103, further flow conduit 105, carrier fluid conduit 106, segmented flow conduit 108 and irradiation zone conduit 119 are formed by machining the said conduits from a block of polytetrafluoroethylene (PTFE) polymer using a conventional milling machine. A cover made from a low energy material (in this case a 0.005 inch thick film of PFA (a perfluoroalkoxy copolymer, supplied by DuPont) that is at least partially transparent to ultraviolet radiation is provided on top of the PTFE block.

The diameter of the irradiation zone is about 68mm, with the length of each irradiation zone conduit being about 150mm.

A source of electromagnetic radiation is arranged in relation to the device 100 so that it illuminates the irradiation zone with the appropriate electromagnetic radiation.

Example 1

The present invention will further be exemplified in the following example wherein the photochemical polymerisation of acrylamide / bisacrylamide mixtures was carried out.

A 40% aqueous mixture of acrylamide / bisacrylamide (ratio 19:1) was introduced into conduit 2. A solution of the water soluble photo-initiator 2, 2-azobis (aminopropane) - dihydrochloride (approximately 200:1 by weight) was introduced into second inlet conduit 3. Laminar flow streams of these two fluids were established in further flow conduit 5. An immiscible, organic fluid was introduced into carrier fluid conduit 6, and was allowed to contact the laminar flow in further flow conduit 5. As the immiscible organic fluid contacted the laminar fluid at discontinuity 9 a "slug-like" flow was produced. Rapid internal mixing of the fluid "slugs" as a result of bends 10, 11 and 12 produced homogenised reaction volumes, which were then irradiated with UV light ( λ = 370nm) . Homolytic cleavage of 2, 2-azobis (aminopropane) - dihydrochloride, and subsequent production of free-radicals was therefore achieved. The radical polymerisation reaction produced solid, cross-linked spheres, which were then carried out of the device through irradiation zone outlet 15 by the fluid flow of the immiscible, organic fluid.

Example 2

Polyethylene glycol spheres with excellent uniformity of size were made as follows. A 20% aqueous mixture of polyethylene glycol dimethacrylate was introduced into first inlet conduit 2. A solution of water-soluble photo- initiator 2, 2-azobis (aminopropane) -dihydrochloride (approximately 200:1 by weight) was introduced into second inlet conduit 3. Laminar flow streams of these two fluids were established in further flow conduit 5. An immiscible, organic fluid was introduced into carrier fluid conduit 6, and was allowed to contact the laminar flow in further flow conduit 5. As the immiscible organic fluid contacted the laminar fluid at discontinuity 9 a "slug-like" segmented flow was produced, with "slugs" of polyethylene glycol dimethacrylate and photo-initiator being carried along in the carrier fluid. Rapid internal mixing of the fluid "slugs" occurred as a result of the "slugs" passing bends 10, 11 and 12, therefore producing homogenised reaction volumes. The enlargement in cross-section as point 16 caused the "slugs" to form a substantially spherical shape. Once in the irradiation zone 13 the spheres were exposed to UV radiation with a wavelength of 370nm. This caused homolytic cleavage of 2 , 2-azobis (aminopropane) - (dihydrochloride) , and subsequent production of free- radicals was therefore achieved. The radical polymerisation reaction produced solid, cross-linked spheres, which were then carried out of the device through irradiation zone outlet 15 by the fluid flow of the immiscible, organic fluid.

The spheres had a diameter of 578±6μm as measured using a calibrated microscope.

Example 3

Photochemical reactions are often prone to having long reaction times due to the attenuation of large, often stationary solvent volumes. The present example will help to demonstrate the efficacy of the apparatus and method of the present invention relating to the photochemical synthesis of benzopinacol by photoreduction of benzophenone . This example also demonstrates that the apparatus and the method of the present invention may be used for miscible reagents, not merely in the manufacture of particulates.

A 0.01M solution of benzophenone was dissolved in a 50:50 homogeneous mixture of 2-propanol and xylenes, and was degassed by bubbling oxygen-free nitrogen through the solution for 15 minutes. The photo-reactive solution was then continuously pumped into the device 1 via first inlet conduit 2, second inlet conduit 3 and carrier fluid conduit 6 at a flow-rate of 15ml/h. One or two of these three conduits need not have been used. The irradiation zone 13 was illuminated with UV light (λ = 370nm) with an incident energy of 4.54 W/cm². The reaction products were collected from the irradiation zone outlet 15 and subsequently analysed by G.C.M.S using a Thermoquest MD 800 with GC 8000 and AS 300, using a Varian column: 30m, 0.25 mm I.D., 0.25μm FactorFour VF - 23ms at 70 kPa He.

The photo-reduction reaction took place as expected, delivering benzopinacol in 82% overall yield.

Claims

1. An apparatus for the performance of photochemical reactions, the apparatus comprising (i) a microfluidic device comprising a first inlet for the introduction of a first fluid, the first inlet being in fluid communication with an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, the irradiation zone conduit extending in an indirect manner from the irradiation zone inlet to the irradiation zone outlet, (ii) a source of electromagnetic radiation operable to illuminate the irradiation zone with electromagnetic radiation .

2. An apparatus according to claim 1 wherein the irradiation zone outlet is in communication with a device outlet for the egress of reaction products

3. An apparatus according to claim 1 or claim 2 wherein the irradiation zone conduit comprises one or more curved portions or bends in the flow path between the irradiation zone inlet and the irradiation zone outlet.

4. An apparatus according to any preceding claim wherein the irradiation zone conduit forms an S or Z shape in the region between the irradiation zone inlet and the irradiation zone outlet.

5. An apparatus according to any preceding claim wherein the irradiation zone conduit comprises a serpentine, spiral or tortuous formation in the flow path between the irradiation zone inlet and the irradiation zone outlet.

6. An apparatus according to any preceding claim wherein the irradiation zone conduit comprises a switchback formation between the irradiation zone inlet and the irradiation zone outlet.

7. An apparatus according to any preceding claim wherein the irradiation zone has an area of A² (units)², and the length of the irradiation zone conduit between the irradiation zone inlet and the irradiation zone outlet is from 2A to 20A units.

8. An apparatus according to any preceding claims wherein the device is provided with a means for inhibiting transmission of electromagnetic radiation from the irradiation zone to the first inlet.

9. An apparatus according to claim 8 wherein the means for inhibiting transmission of electromagnetic radiation comprises one more bend or bends in a conduit, a switchback arrangement in a conduit or a surface of a conduit being coating with non-reflective material or a discontinuity in a conduit.

10. An apparatus according to any preceding claim wherein the device is provided with a second inlet for the introduction of a second fluid, the first inlet being associated with a first conduit and the second inlet being associated with a second conduit.

11. An apparatus according to claim 10 wherein the first and second conduits merge to form a third conduit upstream of the irradiation zone.

12. An apparatus according to claim 10 or 11 further provided with a third inlet for the introduction of a third fluid, the third inlet being associated with a fourth conduit .

13. An apparatus according to claim 12 wherein the fourth conduit merges with the third conduit.

14. An apparatus according to any of claims 10 to 13 wherein the first fluid is immiscible with the second fluid, and the first conduit and the second conduit merge to form a third conduit (or the third conduit is formed with a constriction or other discontinuity) such that fluid in the first and second conduits form into a flow of alternate segments in the third conduit.

15. An apparatus according to claim 13 wherein the third fluid is immiscible with the first and second fluids, and the third conduit merges with the fourth conduit to form a fifth conduit (or the fifth conduit is provided with a constriction or other discontinuity) , such that fluid in the third and fourth conduits form into a flow of alternate segments in the fifth conduit.

16. An apparatus according to any preceding claim wherein, upstream of the irradiation zone, a conduit is provided with an enlargement in cross-section.

17. An apparatus according to any preceding claim wherein the device is composed of, at least, two distinct fluoropolymer based substrate layers which may be composed of bulk fluoropolymer, or fluoropolymer or fluoropolymer-based coatings applied to other non-fluoropolymer bulk material substrate layers.

18. An apparatus according to claim 17 wherein one of the substrate layers is at least partially transparent to the said electromagnetic radiation.

19. An apparatus according to any preceding claim wherein the source of electromagnetic radiation is a source of ultra-violet radiation.

20. An apparatus according to any preceding claim comprising two or more microfluidic devices.

21. An apparatus for the performance of photochemical reactions, the apparatus comprising (i) a microfluidic device comprising a plurality of first inlets for the introduction of a first fluid, and a plurality of irradiation zone conduit, each first inlet being in fluid communication with an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, each irradiation zone conduit extending in an indirect manner from the respective irradiation zone inlet to the respective irradiation zone outlet, (ii) a source of electromagnetic radiation operable to illuminate each irradiation zone with electromagnetic radiation.

22. A microfluidic device suitable for use in the apparatus of any one of claims 1 to 21.

23. A method for performing a photochemical reaction, the method comprising (i) providing a microfluidic device comprising an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, the irradiation zone conduit extending in an indirect manner from the irradiation zone inlet to the irradiation zone outlet, (ii) providing a reagent or reagents for a photochemical reaction (iii) causing the reagent or reagents to flow from the irradiation zone inlet to the radiation zone outlet (iv) irradiating the reagent or reagents as they pass from the irradiation zone inlet to the irradiation zone outlet so as to promote the photochemical reaction.

24. A method according to claim 23 wherein the reagents are mixed prior to the introduction of the reagents into the device .

25. A method according to claim 24 wherein a first reagent is introduced via a first conduit into the device, and a second reagent (being miscible with the first reagent) is introduced via a second conduit into the device, the first and second conduits merging at a third conduit.

26. A method according to claim 25 wherein the first and second reagents are immiscible, and the first conduit and the second conduit merge to form a third conduit (or the third conduit is formed with a constriction or other discontinuity) such that fluid in the first and second conduits form into a flow of alternate segments in the third conduit.

27. A method according to claim 25 or claim 26 wherein the method further comprises introducing a third reagent via a fourth conduit, the third reagent being immiscible with the first and second reagents, the third conduit merging with the fourth conduit to form a fifth conduit (or the fifth conduit being provided with a constriction or other discontinuity) , such that fluid in the third and fourth conduits form into a flow of alternate segments in the fifth conduit.

28. A method for performing a photochemical reaction, the method comprising: (i) providing a microfluidic device comprising an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, the irradiation zone conduit extending in an indirect manner from the irradiation zone inlet to the irradiation zone outlet, (ϋ) providing two or more miscible reagents for a photochemical reaction (iii) mixing the two or more miscible reagents to form a mixture (iii) causing the mixture to flow from the irradiation zone inlet to the irradiation zone outlet (iv) irradiating the mixture as it passes from the irradiation zone inlet to the irradiation zone outlet so as to promote the photochemical reaction.

29. A method for making polymeric particulates, the method comprising: (i) providing a microfluidic device comprising an irradiation zone conduit having an irradiation zone inlet where a fluid enters the irradiation zone and an irradiation zone outlet where a fluid leaves the irradiation zone, the irradiation zone conduit extending in an indirect manner from the irradiation zone inlet to the irradiation zone outlet, (ii) providing a polymeric precursor and an initiator that, on exposure to electromagnetic radiation, initiates the polymerisation of the precursor (iii) providing a carrier fluid that is immiscible with the polymeric precursor and the initiator (iv) mixing the polymeric precursor and the initiator to form a mixture (v) causing the mixture to and the carrier fluid to form a segmented flow (vi) causing the segmented flow from the irradiation zone inlet to the radiation zone outlet (v) irradiating the segmented flow as it passes from the irradiation zone inlet to the irradiation source outlet so as to form polymeric particulate.