WO2017096414A1 - Microfluidic chips and uses thereof - Google Patents

Abstract

A microfluidic chip suitable for use in liquid-liquid or liquid-gas phase transfer applications is disclosed. The microfluidic chip comprises a contact zone comprising a high aspect ratio channel in fluid connection with at least one liquid or gas inlet whereby, in use, at least two immiscible or partially immiscible liquid and/or gas streams exiting the at least one liquid or gas inlet flow adjacent one another and in contact with one another through the contact zone under conditions to allow transfer of at least some of a chemical entity from one stream to the other before the streams exit the high aspect ratio channel at a microchip outlet.

Description

MICROFLUIDIC CHIPS AND USES THEREOF

PRIORITY DOCUMENT

[0001 ] The present application claims priority from Australian Provisional Patent Application No. 2015905059 titled "MICROFLUIDIC CHIPS AND USES THEREOF" and filed on 7 December 2015, the content of which is hereby incorporated by reference in its entirety.

TECHNICAL FIELD

[0002 ] The present disclosure relates to microfluidic chips suitable for use in solvent-solvent or solvent-gas phase transfer applications.

BACKGROUND

[0003] The field of microfluidics typically involves the manipulation of picolitre to microlitre volumes of fluid(s) in channels having height and width that is typically in the range of hundreds of nanometres to hundreds of micrometres. Microfluidic chips incorporating microfluidic channels have been used in a variety of applications, including microreactors, separators, inkjet printers, biochemical assays, chemical synthesis, drug screening, environmental and health monitoring, and immuno specific processes.

Microfluidic devices and processes are becoming increasingly popular as they offer a number of advantages over conventional macro-scale devices and processes, such as compact size, automatability, reduced sample volumes, reduced processing times, integratability, increased utility, and ability to perform several processes simultaneously.

[0004] Most microfluidic chips are laminates consisting of two or more substrate plates bonded together. The elements that form the fluid networks, such as channels, chambers, wells and the like through which fluids flow are disposed between the substrate plates. For example, U.S. Patent No.

6,322,753 (Lindberg et al.) and U.S. Patent No. 5,932,3 15 (Lum et al.) each describes a microfluidic chip composed of juxtaposed plates that are bonded together, wherein one or more of the plates has an etched pattern of grooves on the surface facing the other plate so as to form sealed microchannels when the plates are bonded together. The plates are typically bonded together using an adhesive and/or by thermal bonding.

[0005 ] Microfluidic chips can be used in a range of applications, including solvent-solvent extraction, solvent-gas extraction, phase transfer reactions, microreactions, assays, etc. For example, in an earlier application (International Patent Application WO 2010/022441 ) there is described a process for extracting an analyte (e.g. a metal ion or complex) from an analyte-containing fluid phase using a microfluidic device. The process includes passing the analyte-containing fluid phase along a first fluid microchannel of a microfluidic extraction device and passing an extractant fluid phase that is at least partially immiscible with the analyte-containing fluid phase along a second fluid microchannel of the microfluidic extraction device. The process results in extraction of the analyte from one phase into another and has some advantages over conventional, "bulk" extraction processes. In other applications, different reagents and/or reactants may each be included in immiscible phases and the immiscible phases brought into contact with one another in a microfluidic device in order to bring about a reaction or interaction between the reagent(s) or reactant(s) in each phase.

[0006] Despite their many advantages, commercial success of microfluidic devices and processes has been slow. One reason for this is that microfluidic devices can be difficult and costly to produce due to the high levels of precision required in order to accurately and reliably reproduce the various microscale features of the devices. Other problems with microfluidic devices and processes include clogging of the channels and accumulations of air bubbles that interfere with proper microfluidic system operation.

[0007] There is a need for microfluidic devices that can be used for solvent-solvent extraction, solvent-gas extraction and/or phase transfer applications that are relatively easy to use and/or are scalable and suitable for use on an industrial scale.

SUMMARY

[0008] According to a first aspect, there is provided a microfluidic chip suitable for use in liquid-liquid or liquid-gas phase transfer applications, the microfluidic chip comprising a contact zone comprising a high aspect ratio channel in fluid connection with at least one liquid or gas inlet whereby, in use, at least two immiscible or partially immiscible liquid and/or gas streams exiting the at least one liquid or gas inlet flow adjacent one another and in contact with one another through the contact zone under conditions to allow transfer of at least some of a chemical entity from one stream to the other before the streams exit the high aspect ratio channel at a microchip outlet.

[0009] According to a second aspect, there is a provided a microfluidic chip suitable for use in liquid- liquid or liquid-gas phase transfer applications, the microfluidic chip comprising: one or more liquid or gas inlet(s), each inlet configured to receive one or more liquids and/or gases; a contact zone comprising a high aspect ratio channel in fluid communication with the one or more liquid or gas inlet(s), said channel having a length and defining a flow path along the length of the channel, the channel being configured to receive at least two immiscible or partially immiscible liquid and/or gas streams from the one or more liquid or gas inlet(s) such that, in use, the at least two immiscible or partially immiscible liquids and/or gases flow in contact with one another along the flow path under conditions to allow transfer of at least some of a chemical entity from one of the liquids or gases to the other liquid or gas; and an outlet configured to allow the at least two immiscible or partially immiscible liquids and/or gases to exit the channel.

[0010] In embodiments, the high aspect ratio channel has a width and a depth and is configured such that each liquid or gas stream formed in the channel has a width to depth ratio of > 1.

[0011] In embodiments, multiple streams of each of the two immiscible or partial ly immiscible liquids and/or gases flow in contact with one another in the contact zone or flow path. Streams of each immiscible or partially immiscible liquid and/or gas may alternate with one another across the width of the channel. However, streams of each immiscible or partially immiscible liquid and/or gas do not need to alternate in type or composition across the width of the channel and, for example, two aqueous streams (which are miscible) could meet between organic streams (which are immiscible or partially immiscible with the aqueous stream) for an aqueous phase reaction to occur and the product of the reaction may then transfer immediately into the organic stream. Thus, multiple liquid or gas streams may be used provided at least one of the streams is immiscible or partially immiscible with the other stream(s).

[0012] In certain embodiments, the microfluidic chip further comprises a collection chamber in fluid connection with the outlet, the collection chamber configured to receive the at least two immiscible or partially immiscible liquids and/or gases exiting the microfluidic chip. In these embodiments, the immiscible or partially immiscible liquids and/or gases may separate or disengage into separate phases in the collection chamber.

[0013] In certain embodiments, the microfluidic chip further comprises an inlet channel zone comprising a plurality of microchannels with each microchannel in fluid connection with a liquid or gas inlet and with the high aspect ratio channel. In certain of these embodiments, the plurality of

microchannels are substantially parallel to one another immediately adjacent the contact zone.

[0014] In certain embodiments, the plurality of microchannels are configured so that the

microchannels carrying the at least two immiscible liquids and/or gases are alternately disposed in the inlet channel zone with each microchannel configured to form a discrete liquid and/or gas stream, respectively within each channel. [0015] According to a third aspect, there is provided a microfluidic device comprising one or more microfluidic chip(s) according to either the first or the second aspect, a housing containing said microfluidic chip(s), connection means for connecting said microfluidic chip(s) with one another, at least one inlet for the at least two immiscible liquids and/or gases, and an outlet.

[0016] According to a fourth aspect, there is provided a process for extracting a chemical entity from a first liquid or gas containing the chemical entity, the process comprising: passing the first liquid or gas through at least one liquid or gas inlet of a microfluidic chip of either the first aspect or the second aspect; passing a second liquid or gas that is immiscible or partially immiscible with the first liquid or gas through at least one liquid or gas inlet of the microfluidic chip of either the first aspect or the second aspect; allowing the first liquid or gas and the second liquid or gas to contact one another in the contact zone to allow transfer of at least some of the chemical entity from the first liquid or gas to the second liquid or gas; and separating the second liquid or gas from the first liquid or gas.

[0017] The first liquid or gas and the second liquid or gas may each be an organic solution, an aqueous solution, an ionic liquid solution or a gas provided that the two liquids or gases are immiscible.

[0018] The second liquid or gas may comprise an extractant, or it may comprise the substantially no extractant (relying, instead, on a preferential solubility of the chemical entity in the second liquid or gas).

[0019] According to a fifth aspect, there is provided a use of a microfluidic chip of the first or second aspects or a microfluidic device of the third aspect in a solvent extraction or an ion exchange process.

BRIEF DESCRIPTION OF DRAWINGS

[0020] Embodiments of the present invention will be discussed with reference to the accompanying drawings wherein:

[0021] Figure 1 is a plan view of a prior art microfluidic chip 10 as described in WO 2010/022441 ;

[0022] Figure 2 is a plan view of an embodiment of a microfluidic chip 20 of the present disclosure containing 25 organic and 24 aqueous inlets/streams and a single high aspect ratio outlet; [0023 ] Figure 3 is a plan view of another embodiment of a microfluidic chip 20 of the present disclosure containing 25 organic and 24 aqueous inlets/streams and a single high aspect ratio outlet;

[0024] Figure 4 is a side view of the embodiment of the microfiuidic chip 20 shown in Figure 3;

[0025] Figure 5 shows images of flow in the chip design of the present disclosure visualised with blue dye in water and organic solvent (left) and for precious metal feed solution and secondary amine extractant in organic solvent (right);

[0026] Figure 6 shows images showing the widths of the organic (colourless) and aqueous (brown) streams for various aqueous inlet pressures and fixed organic inlet pressure (50 kPa). The aqueous inlet pressures were (a) 30, (b) 35, (c) 40, (d) 42.5, (e) 45, (f) 47.5, (g) 50, (h) 55, (i) 60, (j) 65, and (k) 70 kPa;

[0027] Figure 7 shows: Left: Calculated organic/aqueous flow rate ratio, R, plotted against the inlet pressure ratio. Inset images are taken from Figure 6. The horizontal dotted line corresponds to the condition R~ when the pressure ratio is 1 . Right: Measured stream widths plotted against the measured R, showing good agreement with the theoretical prediction (· aqueous, organic, - theoretical);

[0028] Figure 8 shows plots of the concentration of platinum group metal left in solution after extraction plotted against R for bulk SX (variable R), a Y-Y chip with symmetrical channels (R ~ 0.56), and the chip design of the present disclosure ('same P' means R ~ 0.56; 'variable P' means that the relative inlet pressures were altered to vary R) (■ Bulk, A Symmetrical Y-Y,● Asymmetric Y-Y,♦ New chip design (fixed P), * New chip design (variable P)) ;

[0029] Figure 9 shows plots of the extraction efficiency versus contact time for Y-Y chips and the chip design of the present disclosure at R = 0.58 and 0.56, respectively. The horizontal line represents the extraction equilibrium for the bulk SX at similar R (0.50) (· Y-Y microchip (R = 0.58), New chip design (R = 0.56), - Bulk (R = 0.5));

[0030] Figure 10 shows an illustration of a counter-current circuit using the chip design of the present disclosure;

[003 1 ] Figure 11 shows (a) vials containing the aqueous phase: loaded (before extraction, A), after one extraction stage (B), and after two stages (C). (b) Vials containing the organic phase: fresh (before extraction, D), after one stage extraction (C), and after two stages extraction (B); and

[0032] Figure 12 shows aqueous platinum group metal concentrations in a two-stage counter-current microSX circuit using the chip design of the present disclosure. DESCRIPTION OF EMBODIMENTS

[0033] The present disclosure has resulted from the inventors' continued research in the application of microfluidic solvent-solvent and solvent-gas extraction processes to industrial extractions and, particularly, in solvent-solvent and solvent-gas extraction processes used in mineral processing industries, such as in the extraction of leach solutions. For ease of description and understanding, reference will be made to illustrated embodiments that are suitable for use in such microfluidic solvent extraction processes. However, it will be appreciated that the disclosure herein is not limited to any one specific application and the person skilled in the art will appreciate that the microfluidic chips, devices and processes described herein can also be used in other processes that exploit microfluidic technology, for example, extraction of particulate biomaterials, extraction of environmental samples, synthetic chemistry, and immunospecific and other biological purification processes. Furthermore, the illustrated embodiments refer to liquid-liquid extraction processes but the present disclosure is equally applicable to liquid-gas or gas-gas extraction processes in which the liquid and gas, or the two gases are immiscible or partially immiscible. The microfluidic chips, devices and processes described herein could be used for two phase reactions where a different reagent is present in each immiscible or partially immiscible liquid or gas. Such applications are collectively referred to herein as "liquid-liquid phase transfer applications" or "solvent-gas phase transfer applications".

[0034 ] Liquid-liquid extraction (also known as "solvent extraction" or "SX") is a process that is commonly used for the recovery or removal of analytes or solutes from solution. Typical solvent extraction processes involve contacting an analyte-containing aqueous phase with an organic liquid phase having an affinity for a solute and mixing the two phases to distribute small droplets of one phase in the other phase, and subsequently separating the two phases by gravity. When the phases are mixed, there is diffusive transfer of solute from the small droplets into the other phase or vice versa.

[0035] On an industrial scale, solvent extraction is usually carried out using a large volume, two stage vessel known as a mixer-settler. At the mixer stage, the two immiscible liquid phases are mutually dispersed under turbulent flow conditions so that the chemical entity of interest can transfer by diffusion from one liquid into the second liquid. The mutually dispersed phases then flow into the settler where they are allowed to coalesce and settle by gravity whereupon at least a portion of the chemical entity is dispersed in the second liquid.

[0036] Solvent extraction is used in a number of areas, including the extraction of metals from leach solutions and environmental samples, as well as in synthetic chemistry. Mineral processing, in particular, is a widely used application of solvent extraction. Many mineral processing plants utilise

hydrometallurgical processes as part of an extractive metallurgical operation and solvent extraction is an important step in the recovery of economically significant metals from ores. A typical solvent extraction process in this context entails preferentially removing a target metal or metal complex (i.e. a chemical entity of interest) from an aqueous phase, and transferring it to an organic phase so that the metal can ultimately be recovered.

[0037] In some other solvent extraction processes one or more metal species present in an aqueous solution may be removed so that the aqueous solution itself can be re-used. Solvent extraction processes of this type are used in the remediation of contaminated soils, tannery effluent, and galvanic sludge, which contain harmful levels of heavy metals, such as chromium.

[0038 ] At least some of the present inventors has previously developed a "Y-Y" microfluidic chip 10 as described in published international patent application WO 2010022441 and shown in Figure 1.

Briefly, an analyte-containing fluid phase is passed along a first fluid microchannel 12 and an extractant fluid phase that is at least partially immiscible with the analyte-containing fluid phase is also passed along a second fluid microchannel 14. The analyte-containing fluid phase and the extractant fluid phase contact one another at a contact zone 16 formed between the first and second fluid microchannels 12 and 14 so that the solute is able to diffuse from the analyte-containing fluid phase into the extractant fluid phase. The chip 10 is particularly effective at separations from particle laden phases but is less suitable for use in some applications.

[0039] Referring to Figures 2 to 4, the present disclosure relates to an improved microfluidic chip 20. The chip 20 is suitable for use in solvent extraction but could also be used in other liquid-liquid phase transfer applications or liquid-gas phase transfer applications, as described previously.

[0040] The microfluidic chip 20 comprises a contact zone 22 comprising a high aspect ratio channel 24 in fluid connection with at least one liquid or gas inlet 26. In use, at least two immiscible or partially immiscible liquid and/or gas streams 28 and 30 exiting the at least one liquid or gas inlet 26 flow adjacent one another and in contact with one another through the contact zone 22 under conditions to allow transfer of at least some of a chemical entity from one stream to the other before the streams exit the high aspect ratio channel 24 at a microchip outlet 32.

[ 0041 ] The at least two immiscible or partially immiscible liquid and/or gas streams 28 and 30 can be any combination of organic liquids, aqueous liquids, ionic liquids or gases provided that at least two of the liquids or gases are not miscible or are only partially miscible with one another. Thus, the at least two immiscible or partially immiscible liquid and/or gas streams 28 and 30 may be two liquid streams, two gas streams or a liquid stream and a gas stream, provided they are not miscible or are only partially miscible with one another. It is also contemplated that more than two liquids and/or gases can be used with two of the liquids or gases miscible with one another and two of the liquids or gases immiscible. As used herein, the term "immiscible", and variants thereof, as used throughout the specification means that two phases, if mixed together, will separate and not form a homogeneous mixture. The term "partially immiscible", and variants thereof, as used throughout the specification means that two phases may have some (albeit relatively low) solubility of one phase in the other phase. For the purposes of this description, two liquids can be considered "partially miscible" if shaking equal volumes of the liquids together results in a meniscus visible between two layers of liquid, but the volumes of the layers are not identical to the volumes of the liquids originally mixed.

[0042 ] The high aspect ratio channel 24 has a length 34 and defines a flow path along the length of the channel 24. The channel 24 is configured to receive the at least two immiscible or partially immiscible liquids and/or gases 28 and 30 such that, in use, the at least two immiscible or partially immiscible liquids and/or gases 28 and 30 flow in contact with one another along the flow path under conditions to allow transfer of at least some of a chemical entity from one of the liquids or gases to the other liquid or gas.

[0043] As used herein, the term "high aspect ratio channel" means a channel that is configured such that each liquid or gas stream 28 or 30 formed in the channel 24 has a width to depth ratio of more than 1. These conditions apply to all streams but some streams may be much wider than others. The width of the contact zone 22 must be at least = (number of streams, ie. first liquid streams + second liquid streams) x (depth of the contact zone). In the illustrated embodiments, the depth of the high aspect ratio channel 24 is either 32 or 34 μm and the width of each stream 28 or 30 formed in the channel is larger than 32 or 34 μιη and smaller than 268 or 266 μηι giving the contact zone a total width of ~7.3 mm (ie. width to depth ratios of more than 1 for each stream formed).

[0044 ] Whilst the illustrated embodiments show a single contact zone 22, it is contemplated that there could be more than one contact zone in series or parallel. For example, two or more microfluidic chips 20 may be connected in series or parallel to allow larger scale processing.

[0045] As shown in Figure 2, the microfluidic chip 20 may comprise one liquid or gas inlet 26 through which both liquid streams 28 and 30 enter the high aspect ratio channel 24. In alternative embodiments, the microfluidic chip 20 may comprise a plurality of liquid or gas inlets 26. In these embodiments, there may be at least one first liquid or gas stream inlet 44 and at least one second liquid or gas stream inlet 46 with each inlet 44 and 46 configured to deliver a respective stream of liquid or gas into the high aspect ratio channel 24. In the embodiment illustrated in Figure 3, a plurality of first liquid stream inlets 44 are alternately disposed between a plurality of second liquid stream inlets 46 at an upstream end of the high aspect ratio channel 24. In this way , alternating first l iquid streams and second liquid streams are formed across the width of the high aspect ratio channel 24. However, it is not necessary for the first and second liquid streams to alternate across the channel 24 and it is possible that two miscible first liquid streams 44a and 44b (e.g. two aqueous streams) could meet between second liquid streams 46 which are immiscible with the first liquid streams. A phase reaction may occur when the two miscible streams 44a and 44b combine and mix and the product thus formed can then transfer into the second liquid stream 46. Alternatively, aqueous streams having different pH could mix and initiate a reaction and then the reaction product could transfer to an immiscible or partially immiscible liquid.

[0046] The first liquid and second liquid can be transferred from a source of each liquid to the at least one liquid or gas inlet 26 using any suitable method. For example, a channel may be in fluid connection with a reservoir of liquid and the one or more inlets 26 or a reservoir of liquid may be in direct fluid connection with one or more liquid or gas inlets 26.

[0047] The liquid or gas inlets 26 can take any suitable form. In the illustrated embodiments, the inlets 26 are in the form of apertures or openings in an end wall of the high aspect ratio channel 24. It is contemplated that one or more of the inlets 26 could be located in a top or bottom wall of the high aspect ratio channel 24 provided said inlets 26 are generally located at an upstream end of the high aspect ratio channel 24 (ie. an end of the high aspect ratio channel 24 that is most distant from the outlet 32).

[0048] In the embodiment illustrated in Figures 3 and 4, the chip 20 comprises a substrate 36 comprising an inlet channel zone 38 comprising at least two microchannels 40 with each microchannel 40 in fluid connection with a liquid or gas inlet 26. For example, the inlet channel zone 38 may comprise a plurality of first liquid stream microchannels 44 each in fluid connection with a first liquid stream inlet 26a and a plurality of second liquid stream microchannels 46 each in fluid connection with a second liquid stream inlet 26b, wherein the first liquid and second liquid are immiscible with one another. For example, the first liquid stream may be an aqueous stream and the second liquid stream may be an organic stream. Other immiscible or partially immiscible liquid combinations that could be used include organic/ionic liquid, ionic liquid/aqueous, gas/liquid, etc. The first liquid stream microchannels 44 and the second liquid stream microchannels 46 are substantially parallel to one another and are configured so that the first liquid stream microchannels 44 and the second liquid stream microchannels 46 are alternately disposed in the inlet channel zone 38 with each microchannel 44 and 46 configured to form discrete streams within each microchannel. Each microchannel 44 and 46 comprises an outlet 48 adjacent to and upstream of the contact zone 22.

[0049] As used herein, the term "microfluidic", and variants thereof, means that the chip, device, apparatus, substrate or related apparatus contains fluid control features that have at least one dimension that is sub-millimetre and, typically less than 100 μιη, and greater than 1 μιη. Furthermore, the term "microchannel", and variants thereof, means a channel having at least one dimension that is sub- millimetre and, typically less than 100 μιη, and greater than I μm.

[0050] As used herein, the term "microfluidic extraction", and variants thereof, means an extraction in which the volume of fluids involved in the liquid-liquid contact stage of an extraction are in the picolitre, nanolitre or microlitre range. However, it will be appreciated that a network of microfluidic chips and/or devices can be connected together in series and/or parallel and used to process large volumes (millilitres to litres) of fluids using continuous throughput processing.

[0051 ] The substrate 36 may take any suitable form and be made from any suitable material. In the illustrated embodiments, the substrate is formed from plates 50 and 52 that are held together in a face to face manner to form the microfluidic chip 20. The plates 50 and 52 are thin, rectangular plates that are formed from a suitable material. Materials suitable for the manufacture of plates for microfluidic chips are known in the art and may be chosen based on considerations such as cost, inertness or reactivity toward fluids and other materials that will be in contact with the chip, etc. Some examples of suitable substrate materials include glass, quartz, metal (e.g. stainless steel, copper), silicon, and polymers. In certain embodiments, the substrate is a glass substrate. For example, Pyrex glass microfluidic chips may be suitable. Suitable polymeric substrates include polydimethylsiloxane (PDMS), polytetrafluoroethylene (PTFE), other perfluoropolyether (PFPE) based elastomers, polymethylmethacrylate (PMMA), silicone, and the like. The plates 50 and 52 in the illustrated embodiments are rectangular in plan view but it is envisaged that they can be other shapes in plan view, such as circular, square, etc. The plates 50 and 52 have a thickness adequate for maintaining the integrity of the microfluidic chip assembly. In the illustrated embodiments, the plates 50 and 52 are about 1.1 mm thick.

[0052 ] The first liquid stream microchannels 44 and the second liquid stream microchannels 46 are formed on the plate 50 and that plate is then capped with the second plate 52 to form covered

microchannels. Methods for forming fluid microchannel networks are known in the art. For example, the microchips can be fabricated using standard photolithographic and etching procedures including soft lithography techniques (e.g. see Shi J., et al., Applied Physics Letters 91 , 153 1 14 (2007); Chen Q., et al., Journal of Microelectromechanical Systems, 16, 1 193 (2007); or Duffy et al, Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane), Anal. Chem., 70 (23), 4974-4984 ( 1998)), such as near- field phase shift lithography, microtransfer molding, solvent-assisted microcontact molding, microcontact printing, and other lithographic microfabrication techniques employed in the semiconductor industry. Direct machining or forming techniques may also be used as suited to the particular chip. Such techniques may include hot embossing, cold stamping, injection moulding, direct mechanical milling, laser etching, chemical etching, reactive ion etching, physical and chemical vapour deposition, and plasma sputtering. The particular methods used will depend on the function of the particular microfluidic network, the materials used as well as ease and economy of production.

[0053] Optionally, the first liquid stream microchannels 44 may be formed from or lined with a first material and the second liquid stream microchannels 46 may be formed from or lined with a second material, the first and second materials being different. For example, the materials may be hydrophilic materials or hydrophobic materials. The first material may be glass which provides a relatively hydrophilic surface in the microchannels 44 suitable for use with an aqueous stream and the second material may be polytetrafluoroethylene which provides a relatively hydrophobic surface in the microchannels 46 suitable for use with an organic stream.

[0054 ] A plurality of the first liquid stream microchannels 44 and a plurality of the second liquid stream microchannels 46 together form the inlet channel zone 38. The first liquid stream microchannels 44 and the second liquid stream microchannels 46 are substantially parallel to one another immediately prior to connecting with the high aspect ratio channel 24. In this context, the term "substantially parallel" means that the microchannels 44 and 46 are mutually aligned and generally disposed with the same orientation with respect to one another. The skilled person will appreciate that it is not technically necessary for the microchannels to be strictly parallel to one another and that a longitudinal axis of one microchannel may be angled slightly (e.g. at an angle of less than about 5°) with respect to an adjacent microchannel without affecting the operation of the microfluidic chip 20. Furthermore, prior to the microchannels 44 and 46 becoming substantially parallel to one another immediately prior to connecting with the high aspect ratio channel 24 the microchannels 44 and 46 can be any arrangement, configuration, shape and/or angle with respect to one another.

[0055] The first liquid stream microchannels 44 and the second liquid stream microchannels 46 are alternately disposed in the inlet channel zone 38. This means that the inlet channel zone 38 comprises alternate first liquid 44 and second liquid 46 stream microchannels. When the microfluidic chip 20 is used for solvent extraction there may be n microchannels for the stream that contains the solute (ie. first liquid or second liquid depending on the solute) and «+ / microchannels for the other stream. For example, when the microfluidic chip 20 is used for extraction of metal ions from an aqueous phase, there may be n aqueous stream microchannels 44 and n+J organic stream microchannels 46. In this way, each aqueous stream is flanked by an organic stream in the contact zone 22, although this is not a necessary condition. In the embodiment illustrated in Figure 2, there are twenty five organic stream microchannels 46 and twenty four aqueous stream microchannels 44 (ie. n is 24). In these embodiments, n may be an integer from 1 to 1000.

[0056] Each microchannel 44 and 46 is configured to form a discrete liquid stream within each microchannel. As described previously, the microchannels 44 and 46 are formed in one of the plates 50 and then capped by the second plate 52 to form enclosed microchannels 44 and 46. The microchannels 44 and 46 may have a depth (ie. height) of 1 to 500 μm, such as 10 to 50 μm . In the illustrated embodiments, the microchannels 44 and 46 have a height of 32 μm or 34 μm .

[0057] Each first liquid stream microchannel 44 is in fluid connection with a first liquid stream inlet 26a and each second liquid stream microchannel 46 is in fluid connection with a second liquid stream inlet 26b. The inlets 26a and 26b may be in the form of holes or apertures in the top of the microfluidic chip 20. Thus, there is one first liquid stream inlet 26a for each first liquid stream microchannel 44 and one second liquid stream inlet 46 for each second liquid stream microchannel 26b. The aqueous first liquid inlets 26b may be in fluid connection with a first liquid phase reservoir 54. The second liquid stream inlets 56 may be in fluid connection with a second liquid phase reservoir 56. The reservoirs 54 and 56 may be any suitable form. In the illustrated embodiments the reservoirs are cut out sections formed on top of the microfluidic chip 20. Each reservoir 54 and 56 can be connected to inlet tubing (not shown) and fed with the first liquid and second liquids on a continuous basis, as required.

[0058 ] Variations of the size, shape and/or configuration of the microchannels 42 and 44 from those described are also envisaged. For example, the inlet microchannels may be from 1 μιη to 1000 μιη in depth or width. The size of the microchannels may also differ from one another in both dimensions.

[0059 ] An inner surface of one or more of the microchannels 42 and 44 may be modified to minimise or prevent adsorption of particles to the surface. For example, the inner surface may be modified with a chemical agent. Suitable chemical agents are known in the art and include, for example, poly(ethylene glycol), chlorosilanes, methoxysilanes, hydroxysilanes, and their amine, hydroxy, fluorine, carboxylic, derivatives, amine compounds, polyelectrolytes such as poly(methacrylic acid), poly(allylamine), poly(N- vinylpyrrolidone) etc. Alternatively, or in addition, an inner surface of one or more of the microchannels 42 and 44 may be modified with nanostructures, such as nanoprotrusion or nanoholes. Methods for modifying microchannels are known in the art.

[0060] In use, the aqueous and organic streams flow in the first liquid stream microchannels 44 and the second liquid stream microchannels 46, respectively, until they reach an inlet 26 adjacent to and upstream of a contact zone 22.

[0061 ] The streams in each microchannel 44 and 46 are initially separate streams (e.g. aqueous and organic) in the inlet channel zone 38 until they reach the inlets 26 adjacent to and upstream of a contact zone 22. The first and second liquid streams exiting the respective microchannels 44 and 46 then flow alongside one another and in contact with each adjacent stream(s) through the contact zone 22. The streams 44 and 46 are free to broaden or narrow at the entrance of the contact zone 22 depending on flow conditions.

[0062] In the contact zone 22, transfer of at least some of a chemical entity from one stream to the other occurs before the streams exit the microfluidic chip 20 at a microchip outlet 32.

[0063] Typically, phase disengagement occurs when the first and second (immiscible) streams exit the microchip 20 at the outlet 32. Both phases can be collected in a collection chamber 58, such as a settler, after which the phases can be separated in the normal manner. Thus, in certain embodiments the microfluidic chip 20 further comprises a collection chamber 58 configured to receive the at least two immiscible liquids exiting the microfluidic chip. When the microfluidic chip 20 is used for solvent extraction (such as liquid-liquid extraction) extraction of all of the chemical entity present in one liquid into the other liquid may occur completely in the contact zone 22. If extraction is not complete in the contact zone 22 there may also be some off-chip extraction that takes place in the collection chamber 58.

[0064] The processing steps are carried out under continuous flow conditions. A range of processing parameters can be precisely controlled by adjusting flow rate alone, e.g. volumetric throughput, extraction efficiency, and extraction time. Typical flow rates for either the first liquid or the second liquid may be between 1 μL/h to 100 mL/h per stream.

[0065 ] The first and second liquids may be transferred to the inlets 26 and along the contact zone 22 under positive pressure provided by a suitable pump (in which case the first liquid and second liquid can be delivered independently of one another and their respective flow rates may be different), by drawing the liquids through the chip 20 under vacuum, or by gravity feed. Devices for transferring liquids and gases to and through microfluidic networks are known in the art.

[0066] Following extraction, the extraction efficiency can be determined using any suitable technique. UV-visible spectroscopy (off-line or on-line analysis), ICP (off-line), and/or thermal lens microscopy (online analysis) may be suitable.

[0067] In addition to solvent-solvent extraction (as described in more detail later), the microfluidic chip and device described herein can be used in processes where a physical or chemical reaction takes place between reagents that are initially separate in immiscible or partially immiscible liquids (a phase- transfer reaction), processes where a physical or chemical reaction takes place in one of the liquids (which may be one or more merged miscible or immiscible streams) and the product transfers to another immiscible liquid, extraction/mass transfer or transfer of reaction products from one phase to another. In all cases, the product is referred to herein as a "chemical entity".

[0068] In certain embodiments, the either the first liquid or the second liquid contains a chemical entity to be extracted. In these cases, the chemical entity may be referred to as a solute. For example, the first liquid may be an aqueous phase comprising an ore sample (or more specifically a leach solution derived therefrom), mineral tailings, a refinery waste stream, a tannery waste stream, an aqueous soil sample, etc containing metal ions of interest. The extraction process may be used to recover the metal ions (such as in mineral processing) or to remove the metal ions from the aqueous stream so that it can be further processed (such as in remediation of soil or tannery waste streams). The first liquid or the second liquid may or may not comprise an extractant. An extractant may not be required where the mass transfer is due to a preferential solubility in one of the liquids or ion exchange. [0069] The metal ion may be selected from one or more ions of the group of metals consisting of: Be, Mg, Al, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag, Cd, In, Sn, Sb, Te, Cs, Ba, Hf, Ta, W, Re, Os, Ir, Pt, Au, Hg, Tl, Pb, Bi, Po, At, Rn, Fr, Ra, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Er, Tm, Yb, Lu, Ac, Th, Pr, U, Np, Pu, Am, Cm, Bk, and Cf. In certain embodiments, the metal ion is a platinum group metal.

[0070] Typically the metal ion will be partitioned when it is in the form of a metal complex. The metal complex may be formed by treating the aqueous solution with a ligand for the metal of interest. For example, a sample containing Pt⁴ may be treated with a solution of HCl to form an aqueous solution containing [PtCl₆]^2- which is then subjected to the extraction process described herein. In another example, a sample containing Cu² may be treated with a solution of 2-hydroxy-5-nonylacetophenone oxime (LIX) to form an aqueous solution containing Cu(LIX)₂ which is then subjected to the extraction process described herein. Alternatively, the organic phase may contain the ligand so that when the aqueous phase (containing the metal ion of interest) and the organic phase come in to contact at the contact zone 22 the ligand is able to diffuse into the aqueous phase or to the liquid-liquid interface where it can form a complex with the metal ion of interest. The metal complex thus formed may then diffuse in to organic phase. The ligand used will depend on the metal ion of interest but may be selected from the group consisting of (but not limited to): alkyl sulfides, alkyl phosphates, alkyl amines, alkyl phosphoric acids, ketoximes, aldoximes, and derivatives of any of the aforementioned.

[0071] In embodiments in which at least one of the liquids is an organic liquid, the organic phase is a non-aqueous fluid phase that is at least partially immiscible with the aqueous phase. In certain embodiments, the organic phase is chloroform. In some other embodiments, the organic phase is a hydrocarbon liquid. However, other solvents could also be used including: alkanes, alkenes, alkynes, alcohols, aldehydes, ketones, acids, esters, aromatics and their halogen, sulfur, phosphorous, and nitrogen-containing derivatives, silicone oils and their halogen, sulfur, phosphorous, and nitrogen- containing derivatives, petroleum (all commercial grades) and petroleum-based products, and mixtures thereof. The solubility of the metal or metal complex in a particular solvent may guide the choice of solvent.

[0072] The solubility of the metal ligand complex in the aqueous phase is strongly dependent on the metal ion. This enables selective separation of low solubility metal complexes, e.g. Cr and Be. Selectivity can also be achieved by selective metal ligand complex formation. The ligand might bind to only one (or a few) of the metal ions.

[0073] The process may also include a further step of recovering the solute from the organic or aqueous phase, as required. [0074] Advantageously, use of the methods of the present disclosure may lead to reduced footprints for solvent extraction unit operations and, because the microchannels are closed systems, greater potential for recycling of volatile liquids and reduced human and environmental exposure to potentially hazardous chemicals.

[0075 ] Various engineering approaches, including scale-out or numbering-up, where many microchips operate in parallel, have been used in microfluidics and can be used with the apparatus and processes of the present disclosure.

[0076] The microfluidic chip 20 may be part of a microfluidic device comprising one or more microfluidic chips 20, a housing containing said microfluidic chip(s) 20, connection means for connecting said microfluidic chip(s) with one another, at least one inlet for the at least two immiscible liquids and/or gases, and an outlet. Optionally, the microfluidic device further comprises a collection chamber in fluid connection with the outlet, the collection chamber configured to receive the at least two immiscible liquids and/or gases exiting the microfluidic chip.

[0077 ] The microfluidic device may further comprise at least one flow controller for introducing the first liquid and/or the second liquid to the microfluidic chip 20. The flow controller may include one or more valves, flow diverters, or fluid diodes. The microfluidic device may further comprise a flow detector or sensor. There may be a feedback loop between the flow detector or sensor and the flow controller whereby the flow detector or sensor is configured to produce a signal which is transmitted to the flow controller in order to control the flow rate of the first liquid and/or second liquid via the flow controller.

[0078 ] The microfluidic device may be used, for example, in an apparatus for extracting an analyte from a sample.

[0079 ] Also provided herein is process for extracting a chemical entity from a first liquid or gas containing the chemical entity, the process comprising: passing the first liquid or gas through at least one liquid or gas inlet of a microfluidic chip of either the first aspect or the second aspect; passing a second liquid or gas that is immiscible or partially immiscible with the first liquid or gas through at least one liquid or gas inlet of the microfluidic chip of either the first aspect or the second aspect; allowing the first liquid or gas and the second liquid or gas to contact one another in the contact zone to allow transfer of at least some of the chemical entity from the first liquid or gas to the second liquid or gas; and separating the second liquid or gas from the first liquid or gas.

[0080] Also provided herein is a use of the microfluidic chip 20 or a microfluidic device comprising at least one microfluidic chip 20 in a solvent extraction process.

EXAMPLES

[0081 ] Example 1 - Preparation and use of microfluidic chip

[0082 ] An embodiment of a microfluidic chip 20 of the present disclosure is shown in Figure 3. Inlet tubing (not shown) is connected to rectangular reservoirs 54 and 56 which, in turn, feed twenty five organic phase inlets 26a and twenty four aqueous phase inlet holes 26b located in the plate 50. The extra organic inlet hole 26a (and therefore stream within the chip) is required to ensure that each aqueous phase stream is flanked by an organic phase stream in the contact zone 22. The aqueous and organic streams flow in separate channels until they meet in a large high aspect ratio channel (height = 32 or 34 μιη (two different chips were used); width ~ 7.3 mm) and flow parallel until they arrive at the chip outlet 32. Phase disengagement occurs on exiting the chip and the chip was suspended over a small beaker for collection of both phases (the beaker is analogous to the 'settler' in a mixer-settler).

[0083] Two chips with average channel height of 32 and 34 μιη were prepared. Figure 5 shows two examples of the parallel streams that form in the contact zone (indicated in the figure). The only preferred criterion for effective extraction is continuous (unbroken) streams, which occurs when the stream width is greater than the channel height¹, so the variability of the width of the streams shown in the figures is unimportant.

[0084 ] An advantage of the microfluidic chip design is the ability to vary the flow rate ratio using a single chip. In this case, the streams adjust their relative widths according to the relative flow rate and relative viscosity.

[0085] The contact zone under consideration is rectangular and the flow is in the x-axis direction. The total channel width (W) is in the y-axis, while the channel height (h) is in the z-axis. The analytical and numerical models are reduced to two dimensions. The width of the aqueous and organic channels are w_a and w_o, respectively. Due to the large channel aspect ratio, W/h > 2000, the flow behaviours can be described by a Hele-Shaw cell approximation. If one examine the bulk of any of the liquid streams away from an interface or wall, the Napier-Stokes equation reduces to:^2-5

[0087] where μ is viscosity, U is velocity and P is pressure. This shows that the velocity is parabolic on the z-axis and the average velocity

follows:

[0089 ] Assuming a constant pressure in the yz-plane, i.e. at any point along the x-axis the pressure is balanced in all the liquid streams, the velocity in each liquid is related as follows:

[0091] And as the height is equal for all streams:

[0093] Due to the Hele-Shaw approximation, the relationship between velocity and flow rate (Q) is Q = AU

[0095] Where A is the cross-sectional area. As the height is equal for all streams, the relationship

[0097] If we define w_o = W - w_a, the width of the aqueous stream can be calculated from:

[0099] Indicating that the width of the respective organic and aqueous streams are determined by the flow rate ratio and viscosity ratio. [00100] As shown in Figure 6, the aqueous stream widens from a very thin stream at low aqueous:organic inlet pressure ratio (30 kPa : 50 kPa) to a wide aqueous stream (narrow organic stream) at high inlet pressure ratio (70 kPa : 50 kPa). The organic phase inlet pressure was kept constant at 50 kPa throughout these experiments.

[00101 ] The above equations show that it is possible to calculate R based on the known viscosity ratio and the measured stream dimensions (Figure 7, left). When the inlet pressures are equal, R is estimated by the aqueous/organic viscosity ratio (~ 0.56). In Figure 7 (right), the measured stream widths are plotted against the theoretical curves for the two streams, showing good agreement. It can be predicted that the narrow streams become unstable when their width is less than the height of the channel (as indicated in Figure 7 by the shaded region). This is due to the stream becoming a free 'jet', rather than a stream confined in two dimensions. A Rayleigh instability can form in the case of a free jet, eventually forming droplets in the channel. The break-down of the organic phase streams was observed in Figure 6(k) where the inlet pressure ratio was ~ 0.7. This is approximately what is estimated from Figure 6 and Figure 7.

[ 00102] Example 2 - Platinum extractions using the microfluidic chip

[00103] Platinum extractions were earned out using the microfluidic chip (depth = 32 μm) and compared to bulk and Y-Y microchip extractions for a range of R values. A general comparison of the microSX (Y-Y chip and new chip design) with the bulk SX extraction efficiencies shows reasonable agreement over the range of R values studied, as shown in Figure 8. Considering the microSX results alone, the Y-Y chip and chip design of the present disclosure are almost identical for R = 0.56, within the uncertainty of these measurements. The blue symbols in Figure 8 represent a significant development: it is possible to tune R in a single chip by altering the relative inlet pressures. R was successfully varied from 0.56 (identical inlet pressures) to 3.6. As we can see the trend broadly follows that of the bulk experiment with a small difference that is likely to be due to the short residence times (several seconds) that prevent equilibrium being reached.

[00104] The extraction efficiency in the Y-Y chip and the chip design of the present disclosure for various residence times was then considered. In these experiments R is fixed at ~ 0.56, i.e. the viscosity ratio. Figure 9 shows that the new chip design out performs the Y-Y chip, which is unexpected given that the equilibrium concentration should not differ for fixed R. When compared with the extraction equilibrium in bulk SX (at very similar R), one could argue that the chip design of the present disclosure is more representative of the bulk extraction, despite the scatter in the Y-Y chip results. The extraction rate, however, is expected to increase because every aqueous stream is bordered by two organic streams (approximately double the interfacial area available for extraction). [00105] Several advantages of the chip design of the present disclosure over the Y-Y chip have been identified: (1) higher volumetric throughput on a single chip, (2) increased stability and ease of use, (3) tuneable flow rate ratio, (4) improved extraction, which appears to be more representative of bulk SX equilibria.

[00106] Example 3 - Counter-current microfluidic extraction

[00107] Two chips (designs of the present disclosure) were setup in a counter-current flow circuit, as shown in Figure 10(a) with the aqueous phase flowing from A to D and the organic phase flowing from D to A. As in a conventional bulk SX circuit, the fully loaded aqueous phase meets the partially loaded organic phase in the first chip (shown at B). In the second chip (shown at C), the fresh organic phase meets partially extracted aqueous phase. After each chip, the two phases were collected in the same vessel (a 10 mL vial) and each phase is continuously drawn from the vial into the next chip or, if the fluid has completed the circuit, to a separate collection vessel for analysis. The latter ensures that the system can reach steady-state (avoiding accumulation of sample during start-up) and mimics a typical industrial circuit. The flow was started and allowed to reach steady-state before samples were collected, isolated and analysed. The flow rate ratio used for the system was set to R ~ 1. Figure 1 1 shows the collected samples. The fully loaded aqueous phase is shown to the left of picture (a). The fresh organic phase is shown to the right of picture (b). The aqueous and organic phase outputs from the chips at positions B and C are shown in separate vials (see figure caption for details). The platinum concentration of each aqueous solution is plotted in Figure 12. After one stage the concentration of platinum is reduced to approximately 40% of the original concentration after one stage and to approximately 8 % of original after two stages.

[00108] Conclusion

[00109] A new microfluidic chip was designed and prepared, which enables tuning of R, greater flow stability, higher volumetric throughput, and can operate in continuous flow. Furthermore, the extraction appears to be very efficient, giving an equilibrium concentration of platinum closer to that expected based on bulk SX experiments. Finally, a two-stage counter-current coupling of microSX chips was achieved.

[00110] It will be appreciated by those skilled in the art that the invention is not restricted in its use to the particular application described. Neither is the present invention restricted in its preferred embodiment with regard to the particular elements and/or features described or depicted herein. It will be appreciated that the invention is not limited to the embodiment or embodiments disclosed, but is capable of numerous rearrangements, modifications and substitutions without departing from the scope of the invention as set forth and defined by the following claims. REFERENCES

[001 1 1 1 ( 1 ) Priest, C; Herminghaus, S.; Seemann, R. Applied Physics Letters 2006, 88, 024106.

[00112] (2) Gondret, P. and M. Rabaud, Shear instability of two-fluid parallel flow in a Hele -Shaw cell. Physics of Fluids, 1997. 9(1 1 ): p. 3267-3274.

[001 13] (3) Larsen, M.U. and N.C. Shapley, Stream Spreading in Multilayer Microfluidic Flows of Suspensions. Analytical Chemistiy, 2007. 79(5): p. 1947- 1953.

[00114] (4) Wu, Z. and N.-T. Nguyen, Hydrodynamic focusing in microchannels under consideration of diffusive dispersion: theories and experiments. Sensors and Actuators B: Chemical, 2005. 107(2): p. 965-974.

[00115] (5) Cubaud, T. and T.G. Mason, Formation of miscible fluid micros tructures by hydrodynamic focusing in plane geometries. Physical Review E, 2008. 78(5): p. 056308.

[001 16 ] Throughout the specification and the claims that follow, unless the context requires otherwise, the words "comprise" and "include" and variations such as "comprising" and "including" will be understood to imply the inclusion of a stated integer or group of integers, but not the exclusion of any other integer or group of integers.

[001 17] The reference to any prior art in this specification is not, and should not be taken as, an acknowledgement of any form of suggestion that such prior art forms part of the common general knowledge.

Claims

1. A microfluidic chip suitable for use in liquid-liquid or liquid-gas phase transfer applications, the microfluidic chip comprising a contact zone comprising a high aspect ratio channel in fluid connection with at least one liquid or gas inlet whereby, in use, at least two immiscible or partially immiscible liquid and/or gas streams exiting the at least one liquid or gas inlet flow adjacent one another and in contact with one another through the contact zone under conditions to allow transfer of at least some of a chemical entity from one stream to the other before the streams exit the high aspect ratio channel at a microchip outlet.

2. A microfluidic chip suitable for use in liquid-liquid or liquid-gas phase transfer applications, the microfluidic chip comprising: one or more liquid or gas inlet(s), each inlet configured to receive one or more liquids and/or gases; a contact zone comprising a high aspect ratio channel in fluid communication with the one or more liquid or gas inlet(s), said channel having a length and defining a flow path along the length of the channel, the channel being configured to receive at least two immiscible or partially immiscible liquid and/or gas streams from the one or more liquid or gas inlet(s) such that, in use, the at least two immiscible or partially immiscible liquids and/or gases flow in contact with one another along the flow path under conditions to allow transfer of at least some of a chemical entity from one of the liquids or gases to the other liquid or gas; and an outlet configured to allow the at least two immiscible or partially immiscible liquids and/or gases to exit the channel.

3. The microfluidic chip according to either claim 1 or claim 2, further comprising a collection chamber in fluid connection with the outlet, the collection chamber configured to receive the at least two immiscible or partially immiscible liquids and/or gases exiting the microfluidic chip.

4. The microfluidic chip according to any one of claims 1 to 3, wherein the high aspect ratio channel has a width and a depth and is configured such that each liquid or gas stream formed in the channel has a width to depth ratio of >1.

5. The microfluidic chip according to any one of claims 1 to 4, wherein the microfluidic chip further comprises an inlet channel zone comprising a plurality of microchannels with each microchannel in fluid connection with a liquid or gas inlet.

6. The microfluidic chip according to claim 5, wherein the plurality of microchannels are substantially parallel to one another immediately adjacent the contact zone.

7. The microfluidic chip according to any one of claims 5 to 6, wherein the plurality of microchannels are configured so that the microchannels carrying the at least two immiscible liquids and/or gases are alternately disposed in the inlet channel zone with each microchannel configured to form a discrete liquid and/or gas stream, respectively within each channel.

8. A microfluidic device comprising one or more microfluidic chip(s) according to any one of claims 1 to 7, a housing containing said microfluidic chip(s), connection means for connecting said microfluidic chip(s) with one another, at least one inlet for the at least two immiscible liquids and/or gases, and an outlet.

9. A microfluidic device comprising one or more microfluidic chip(s) according to any one of claims 1 to 7 connected in series.

10. A process for extracting a solute from a first liquid containing the solute, the process comprising: passing the first liquid or gas through at least one liquid or gas inlet of a microfluidic chip of any one of claims 1 to 7; passing a second liquid or gas that is immiscible or partially immiscible with the first liquid or gas through at least one liquid or gas inlet of the microfluidic chip of any one of claims 1 to 7; allowing the first liquid or gas and the second liquid or gas to contact one another in the contact zone to allow transfer of at least some of the chemical entity from the first liquid or gas to the second liquid or gas; and separating the second liquid or gas from the first liquid or gas.

1 1. A use of a microfluidic chip according to chip of any one of claims 1 to 7 or a microfluidic device according to claim 8 in a solvent extraction or an ion exchange process.