WO2013163246A2

WO2013163246A2 - Polymerization reactions within microfluidic devices

Info

Publication number: WO2013163246A2
Application number: PCT/US2013/037895
Authority: WO
Inventors: Maximilian ZIERINGER; Christian Holtze; David A. Weitz; Joerg Max Georg Erich SIEBERT
Original assignee: President And Fellows Of Harvard College; Basf Se
Priority date: 2012-04-25
Filing date: 2013-04-24
Publication date: 2013-10-31
Also published as: WO2013163246A3

Abstract

The present invention generally relates to polymerization reactions within microfluidic devices. In certain cases, the invention allows for precise control of the polymerization of different types of monomers to form a copolymer by controlling the steps of polymerization and/or controlling the addition of monomers at various time scales within a microfluidic droplet and/or a microfluidic environment, often to a degree that is unattainable by other block polymerization techniques. For example, in one aspect, the present invention is directed to systems and methods for producing polymers such as block copolymers, gradient polymers, random copolymers, etc. For instance, in one set of embodiments, a first monomer contained within a channel, such as a microfluidic channel, is allowed to polymerize to form a first block of a block copolymer. Additional blocks may be added, for example, by flowing the first block and other monomers through a second channel (which may be an extension of the first channel), by polymerizing additional blocks of the copolymer in other channels, by creating droplets containing one or more blocks and allowing the blocks to polymerize, or the like. In some embodiments, a droplet, such as a multiple emulsion droplet, may be creating containing two or more monomers, which are allowed to polymerize together. Still other embodiments of the invention are generally directed to methods of creating such devices, methods of using such devices, kits involving such devices, or the like.

Description

POLYMERIZATION REACTIONS WITHIN MICROFLUIDIC DEVICES

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Patent Application Serial No. 61/638,436, filed 04/25/12, entitled "Polymerization Reactions within Microfluidic Devices," by Zieringer, et al., incorporated herein by reference.

FIELD OF INVENTION

The present invention generally relates to microfhiidics and, in particular, to polymerization reactions within microfluidic devices.

BACKGROUND

Block copolymers and gradient polymers with well-controlled molecular structure are traditionally produced by ionic or controlled radical polymerization.

However, ionic polymerization typically requires costly or high-purity reagents, and accordingly is difficult and expensive to use to produce polymers in commercial quantities. Accordingly, improvements in producing block copolymers and gradient polymers, e.g. at commercial quantities, are needed.

SUMMARY

The present invention generally relates to polymerization reactions within microfluidic devices. The subject matter of the present invention involves, in some cases, interrelated products, alternative solutions to a particular problem, and/or a plurality of different uses of one or more systems and/or articles.

In one aspect, the present invention is generally directed to a method of producing a block copolymer comprising at least a first block and a second block. The method, in one set of embodiments, comprises acts of producing the first block of the block copolymer by flowing a first monomer in a microfluidic channel, and causing at least some of the first monomer to polymerize to form the first block, and producing the second block of the block copolymer by creating droplets containing the first block and a second monomer, and causing polymerization of the second monomer to form the second block of the block copolymer.

In another set of embodiments, the method includes acts of producing the first block of the block copolymer by flowing a first monomer in a first microfluidic channel, and causing at least some of the first monomer to polymerize to form the first block, and producing the second block of the block copolymer by flowing the first block and a second monomer in a second microfhiidic channel, and causing polymerization of the second monomer to form the second block of the block copolymer.

The method, in yet another set of embodiments, includes acts of producing the first block of the block copolymer by flowing a first monomer in a first microfhiidic channel, and causing at least some of the first monomer to polymerize to form the first block, producing the second block of the block copolymer by flowing a second monomer in a second microfhiidic channel, and causing at least some of the second monomer to polymerize to form the second block, forming a multiple emulsion droplet comprising an inner fluid, a middle fluid surrounding the inner fluid, and an outer fluid surrounding the middle fluid, where the inner fluid comprises the first block and the middle fluid comprises the second block, and polymerizing the first block and the second block to form the block copolymer.

In still another set of embodiments, the method includes acts of producing the first block of the block copolymer by flowing a first monomer and/or macromonomer in a microfhiidic channel, and causing at least some of the first monomer and/or macromonomer to polymerize to form the first block, and producing the second block of the block copolymer by creating droplets containing the first block and a second monomer and/or macromonomer, and causing polymerization of the second monomer and/or macromonomer to form the second block of the block copolymer.

The method, in another set of embodiments, includes acts of producing the first block of the block copolymer by flowing a first monomer and/or macromonomer in a first microfhiidic channel, and causing at least some of the first monomer and/or macromonomer to polymerize to form the first block, and producing the second block of the block copolymer by flowing the first block and a second monomer and/or macromonomer in a second microfhiidic channel, and causing polymerization of the second monomer and/or macromonomer to form the second block of the block copolymer.

The method, in yet another set of embodiments, includes acts of producing the first block of the block copolymer by flowing a first monomer and/or macromonomer in a first microfhiidic channel, and causing at least some of the first monomer and/or macromonomer to polymerize to form the first block, producing the second block of the block copolymer by flowing a second monomer and/or macromonomer in a second microfluidic channel, and causing at least some of the second monomer and/or macromonomer to polymerize to form the second block, forming a multiple emulsion droplet comprising an inner fluid, a middle fluid surrounding the inner fluid, and an outer fluid surrounding the middle fluid, wherein the inner fluid comprises the first block and the middle fluid comprises the second block, and polymerizing the first block and the second block to form the block copolymer.

In another aspect, the method is a method of producing a copolymer. According to one set of embodiments, the method includes acts of forming a multiple emulsion droplet comprising an inner fluid, a middle fluid surrounding the inner fluid, and an outer fluid surrounding the middle fluid, where the inner fluid comprises a first monomer and the middle fluid comprises a second monomer, the inner fluid and the middle fluid being substantially miscible, and polymerizing the first monomer and the second monomer to form a copolymer.

In accordance with another set of embodiments, the method includes acts of forming a multiple emulsion droplet comprising an inner fluid, a middle fluid

surrounding the inner fluid, and an outer fluid surrounding the middle fluid, wherein the inner fluid comprises a first monomer and/or macromonomer and the middle fluid comprises a second monomer and/or macromonomer, the inner fluid and the middle fluid being substantially miscible, and polymerizing the first monomer and/or macromonomer, and the second monomer and/or macromonomer, to form a copolymer.

In one aspect, the method is a method of producing a copolymer comprising at least a first monomer and a second monomer. The method, in one set of embodiments, includes acts of creating droplets containing at least a first monomer and a second monomer, and polymerizing the first monomer and the second monomer within the droplets to form the copolymer. The copolymer, in certain embodiments, may be a star copolymer, a graft copolymer, a branched copolymer, and/or a gradient copolymer.

The method, in yet another aspect, is a method of producing a copolymer comprising at least a first portion and a second portion. In accordance with one set of embodiments, the method includes acts of producing the first portion of the copolymer by flowing a first monomer and/or macromonomer in a microfluidic channel, and causing at least some of the first monomer and/or macromonomer to polymerize to form the first portion, and producing the second portion of the copolymer by creating droplets containing the first portion and a second monomer and/or macromonomer, and causing polymerization of the second monomer and/or macromonomer to form the second portion of the copolymer.

The method, in another set of embodiments, includes acts of producing the first portion of the copolymer by flowing a first monomer and/or macromonomer in a first microfluidic channel, and causing at least some of the first monomer and/or

macromonomer to polymerize to form the first portion, and producing the second portion of the copolymer by flowing the first portion and a second monomer and/or

macromonomer in a second microfluidic channel, and causing polymerization of the second monomer and/or macromonomer to form the second portion of the copolymer.

In still another set of embodiments, the method includes acts of producing the first portion of the copolymer by flowing a first monomer and/or macromonomer in a first microfluidic channel, and causing at least some of the first monomer and/or macromonomer to polymerize to form the first portion, producing the second portion of the copolymer by flowing a second monomer and/or macromonomer in a second microfluidic channel, and causing at least some of the second monomer and/or macromonomer to polymerize to form the second portion, forming a multiple emulsion droplet comprising an inner fluid, a middle fluid surrounding the inner fluid, and an outer fluid surrounding the middle fluid, wherein the inner fluid comprises the first portion and the middle fluid comprises the second portion, and polymerizing the first portion and the second portion to form the copolymer.

In another aspect, the present invention encompasses methods of making one or more of the embodiments described herein. In still another aspect, the present invention encompasses methods of using one or more of the embodiments described herein.

Other advantages and novel features of the present invention will become apparent from the following detailed description of various non-limiting embodiments of the invention when considered in conjunction with the accompanying figures. In cases where the present specification and a document incorporated by reference include conflicting and/or inconsistent disclosure, the present specification shall control. If two or more documents incorporated by reference include conflicting and/or inconsistent disclosure with respect to each other, then the document having the later effective date shall control.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting embodiments of the present invention will be described by way of example with reference to the accompanying figures, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the invention shown where illustration is not necessary to allow those of ordinary skill in the art to understand the invention. In the figures:

Figs. 1A-1B illustrate schematic diagrams of various embodiments of the invention useful for producing polymers such as block copolymers or gradient polymers;

Figs. 2A-2B illustrate the production of a polymer in a double emulsion droplet, in accordance with certain embodiments of the invention;

Fig. 3 illustrates a channel-within-a-channel junction useful for producing polymers in accordance with certain embodiments of the invention; and

Figs. 4A and 4B illustrate various schematic diagrams of certain embodiments of the invention useful for producing polymers such as block copolymers or gradient polymers.

DETAILED DESCRIPTION

For example, certain aspects of the present invention are generally directed to systems and methods for producing a block copolymer comprising at least a first block and a second block. Although block copolymers are discussed here, this is by way of example only, and other types of polymers and polymerization reactions can be used in other embodiments, e.g., to produce block copolymers, gradient polymers, random copolymers, or other types of polymers as discussed herein. Referring now to Fig. 1A, fluidic system 10 is shown that includes inlet port 1 for introducing a first fluid, e.g., one containing a first monomer. Upon entering inlet port 1, the first fluid flows through channel 11 to initiator region 2, where the monomer may be exposed to an initiator. The initiator can be, for example, ultraviolet light, heat, and/or a chemical initiator, for example, a radical initiator such as azobisisobutyronitrile (AIBN) or benzoyl peroxide. Exposure to the initiator is used to start polymerization of the first monomer.

While the first monomer polymerizes after being exposed to the initiator, it flows through channel 3. The duration of polymerization of the first monomer can be controlled by controlling the length of channel 3; for example, for longer polymerization times, a longer channel can be used. Channel 3 may have any suitable shape. For instance, where relatively long channels and/or long polymerization times are desired, channel 3 may have a convoluted pathway, such as the serpentine pathway shown in Fig. 1A. In some embodiments, within channel 3, only the first monomer is present, thereby resulting in a substantially homogeneous polymer (which, as discussed below, may form a first block of a block copolymer).

Upon exiting channel 3, the first fluid containing the first monomer (which may now be partially or completely polymerized to form a first block) enters fluid junction 14. At junction 14, a second monomer or a second polymer may be introduced. For instance, as is shown in Fig. 1A, two inlet ports 4 are used to introduce a second monomer via channels 15. The second monomer can be contained within a second fluid, which may be substantially miscible or substantially immiscible with the first fluid. In certain instances, the second fluid may even be substantially identical to the first fluid. In addition, although two inlet ports 4 are shown in Fig. 1 A, this is by way of example only. In other embodiments, there may be more or fewer inlet ports, and the

configuration of channels 15 entering junction 14 may be different. For example, junction 14 may be a flow-focusing junction, a T-junction, a coaxial junction, or the like.

In Fig. 1A, inlet ports 4 and channels 15 are positioned such that both the first fluid from channel 3 and the second fluid from channels 15 flow through channel 5. In some cases, the first and second fluids may be arranged such that the second fluid partially or completely surrounds the first fluid within channel 5, e.g., as is shown in Fig. 1A. However, in other embodiments, the first and second channels may flow collinearly, or in some cases, droplets of first fluid and/or second fluid may be created within channel 5.

A non-limiting example of such a configuration is shown in Fig. IB. In this figure, a similar fluidic system 10 is illustrated, adapted for producing droplets comprising a first fluid and a second fluid at junction 14. In this system, two inlet ports 4 are used to introduce a second fluid. The second fluid flows through channels 15 towards junction 14. In addition, two further inlet ports 24 are used to introduce a third, carrying fluid via channels 25 towards junction 22. At junction 22, a plurality of droplets 23 may be formed in channel 26. The droplets may be formed from the first and second fluids, contained within the third, carrying fluid. The first fluid and the second fluid may be substantially miscible or substantially immiscible. For example, if the first fluid and the second fluid are substantially miscible, mixing and/or reaction may occur within the droplets, as discussed below.

Referring again to Fig. 1A, the channel exiting the junction where the first and second fluids meet (i.e., channel 5) may have any suitable length. For example, in some embodiments, the duration of polymerization may be controlled by controlling the length of channel 5. Thus, for instance, for longer polymerization times, a longer channel may be used. Accordingly, channel 5 may have any suitable shape, e.g., channel 5 may be a straight channel as is shown in Fig. 1A, or channel 5 may have a convoluted pathway, such as a serpentine pathway as is shown in Fig. 4. The first block (i.e., substantially formed from the first monomer) may be exposed to the second monomer, e.g., under conditions in which the second monomer is able to polymerize to the first block. Thus, for example, a second block of a block copolymer may be formed, comprising or consisting essentially of the second monomer. In some cases, the second block that is formed is substantially homogenous. However, in other cases, there may be some first monomer present within the second block, e.g., if some unreacted first monomer is still present when the second monomer is introduced. In addition, in certain embodiments, the second blocks may also polymerize with other first (or second) blocks, e.g., to form more complex block copolymers, for example, having an ABA structure, an ABAB structure, an ABABA structure, etc.). Other structures are also possible in some embodiments, e.g., having more types of monomers, and/or branched configurations, star configurations, comb configurations, graft configurations, or the like.

After polymerization, the final block polymer may be collected at exit port 8, and/or directed to other uses, e.g., subsequent reaction, purification, or the like. As a non-limiting example, in some embodiments, the fluid within channel 5 may pass through filter 6 as is shown in Fig. 1A. Filter 6 may be used, for example, to remove unreacted monomer and/or polymer having too low of a molecular weight. For instance, filter 6 may comprise an ultrafiltration membrane or a membrane having a certain molecular weight cut-off, for example, producing a permeate stream that is discarded (not shown in Fig. 1 A). The retentate may then exit filter 6 towards exit port 8.

Also shown in Fig. 1A is sensor 7. Sensor 7 is optional, but if present, may be used for various functions, e.g., for determining the amount and/or quality of polymer formed within fluidic system 10, for determining flowrate, for determining system conditions such as pressure, temperature, pH, etc., or the like. In addition, in some cases, more than one sensor may be used.

The above discussion is a non-limiting example of one embodiment of the present invention that can be used to produce a block copolymer, e.g., using a fluidic system comprising channels such as microfluidic channels. However, other

embodiments are also possible. Accordingly, more generally, various aspects of the invention are directed to various systems and methods for producing polymers such as block copolymers, gradient polymers, random copolymers, etc., for example, by flowing various fluids containing monomers or macromonomers through channels and allowing polymerization of these to occur. For example, in certain embodiments of the invention, polymerization of monomers and/or macromonomers to form various blocks of block copolymers and other types of polymers can be controlled by controlling the properties of channels containing the monomers and/or macromonomers, by creating droplets containing monomers, and/or any suitable combination of these.

It should be understood that, although many examples and embodiments discussed herein describe the use of monomers, that is by way of convenience only, and that in other embodiments, a monomer as used herein may be replaced with a

macromonomer, e.g., to be polymerized to form a copolymer. In addition, in some cases, a solution comprising a monomer may also comprise polymerizable macromonomers of that monomer. Thus, for example, in some embodiments as discussed herein, a first solution comprising a first monomer and/or a first polymer may be contained within a fluidic droplet and/or a channel, and be allowed to react with a second solution comprising a second monomer and/or second polymer to form a copolymer of the first monomer and/or first macromonomer, and the second monomer and/or second macromonomer. "Macromonomers" as used herein may have a relatively low number of monomers forming the macromonomer, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 monomers. In some embodiments, the macromonomers may be used to form a copolymer, e.g., to be polymerized to form a block of a block copolymer, or other copolymers as is discussed herein.

As a specific non-limiting example of an embodiment directed to a copolymer, a first portion of a copolymer (e.g., a first block of a block copolymer) may be created by flowing a fluid containing a first monomer (and/or macromonomer) through a first channel and causing the first monomer to polymerize to form a first portion (e.g., by exposing the first monomer to a suitable initiator), then flowing the first portion through a second channel containing a second monomer (and/or macromonomer) and causing the second monomer to polymerize, e.g., forming a second portion on the first portion (e.g., a second block of a block copolymer). The second channel may be, in some cases, an extension of the first channel. As another example, a first portion may be created by flowing a first monomer (and/or macromonomer) through a first channel and

polymerizing it to form the first portion, creating droplets containing the first portion and a second monomer (and/or macromonomer), then polymerizing the second monomer to form a second portion on the first portion. In still another example, first and second portions of a copolymer may be created by flowing first and second monomers (and/or macromonomer) through different channels and causing each of them to separately polymerize, then joining the polymers together to form a copolymer, for example, in a channel and/or in a droplet. As yet another example, a first fluid containing a first monomer (and/or macromonomer) and a second fluid containing a second monomer (and/or macromonomer) may simultaneously flow through a microfluidic channel under conditions in which the first monomer and the second monomer are able to polymerize, e.g., to form a copolymer. For example, the first fluid and second fluid may be present within a droplet contained within the microfluidic channel.

Any polymerization mechanism or reaction may be used to form a portion, or all, of the overall copolymer. For example, monomers may be polymerized using free or controlled radical polymerization reactions, living polymerization reactions, anionic polymerization reactions, cationic polymerization reactions, coordination polymerization reactions, or the like. These and other suitable polymerization reactions will be well- known to those of ordinary skill in the art. For example, in a living polymerization system, the ability of a growing polymer chain to terminate may be removed, for example, by reducing and/or eliminating any chain termination or chain transfer reactions that may alter chain propagation. Examples of living polymerization reactions include, but are not limited to, ATRP (atom transfer radical polymerization), RAFT (reversible addition-fragmentation chain transfer polymerization), NMP reactions (nitroxide-mediated polymerization), and TEMPO reactions. Thus, for example, a first portion of a copolymer may be synthesized by a living polymerization reaction, and/or a second portion of a copolymer may be synthesized by a living polymerization reaction. In addition, in some cases, more than one type of polymerization reaction may be used. For example, one portion may be synthesized using a first polymerization reaction (e.g., a free radical polymerization), while a different portion may be synthesized using a second polymerization reaction (e.g., a living polymerization reaction and/or a controlled polymerization reaction). Other examples of suitable polymerization reactions include catalytic polymerization (e.g., using metallocenes), coordinative polymerization, insertive polymerization, ROMP reactions, or the like. As discussed above, many embodiments of the invention are directed to copolymers such as block copolymers, gradient polymers, random copolymers, etc. A copolymer is typically thought of as being formed from two (or more) monomers.

Although many of the examples discussed herein use only two monomers, this is for ease of presentation; in other embodiments, additional fluids containing additional monomers may be used; for example, a third fluid could be used, containing a third monomer, to produce a third portion of the copolymer, a fourth fluid could also be used, containing a fourth monomer, to produce a fourth portion, etc. These fluids may each be added, for example, using the techniques discussed in detail herein, or using other techniques. For example, a droplet may be formed comprising a first fluid, a second fluid, and a third fluid; to a fluid stream of a copolymer of the first and second monomers may be added a third fluid stream comprising a third monomer, etc.

In a block copolymer, the monomers are typically positioned within the polymer such that a majority of the monomers forming the block copolymer are positioned next to an identical monomer. Thus, a block copolymer may have a structure comprising blocks of a first monomer and blocks of a second monomer, and the block copolymer may be thought of as being formed from blocks of homogenous (or substantially homogenous) monomers that have been polymerized together. In some embodiments, the block copolymer may consist of a first block and one or two second blocks, e.g., produced as discussed above. In other embodiments, however, there may be several blocks of first and or second monomer present within the block copolymer, e.g., having an ABAB structure, an ABABA structure, etc. (where A and B each stand for a block of monomers within the copolymer). Thus, there may be more than one first block and more than one second block present.

If only two such types of blocks are present, the polymer may be referred to as a

"diblock copolymer." However, in other embodiments of the invention, more types of blocks may be copolymerized together. For example, a block copolymer consisting essentially of three types of monomers is generally referred to as a "triblock copolymer." For instance, the triblock copolymer may have a structure ABCABC, ABACABAC, a random assortment of blocks, or any other structure. In addition, a block within a block copolymer may comprise one or more "impurities" (for instance, an isolated monomer unit of a first monomer may be present with a string of second monomers units, a first monomer in a string of otherwise identical first monomer units may be defective, etc.).

A gradient copolymer is similar in structure, but typically exhibits a gradual change in monomer composition from predominantly a first monomer to predominantly a second monomer along the length of the polymer. In some cases, the gradient copolymer may also be a block copolymer. In contrast, in a random copolymer, the monomers forming it are typically distributed randomly (or substantially randomly). In addition, in some cases, copolymers may be formed that are combinations of these forms, and/or have other distributions of monomers.

In still other embodiments, other copolymer structures are also possible, e.g., terpolymers, branched configurations, star configurations, comb configurations, graft configurations, etc. For example, in a comb configuration or a graft configuration, a first monomer (and/or macromonomer) may be polymerized to form the backbone portion, while a second monomer (and/or macromonomer) may be polymerized to form some or all of the side chains. As another example, in a branched configuration, a first monomer (and/or macromonomer) may be polymerized to form a first branch, while a second monomer (and/or macromonomer) may be polymerized to form a second branch. Such polymers may be prepared using any of the techniques discussed herein.

Examples of copolymers that may be formed in various embodiments include, but are not limited to, copolymers of styrene, n-butyl methacrylate, acrylonitrile, isoprene, ethylene, vinyl acetate, and butadiene, including combinations of any of these and/or other suitable monomers. Specific non-limiting examples of copolymers include acrylonitrile-butadiene-styrene, styrene-butadiene, acrylonitrile-butadiene, styrene- acrylonitrile, styrene-isoprene- styrene, or ethylene-vinyl acetate. As discussed, the copolymers may be block copolymers, gradient polymers, random copolymers, etc. The momoners forming the copolymer may be present in any suitable ratio, and may be added in any suitable order, e.g., as discussed above. For example, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% of the copolymer may comprise one monomer with the remainder of the copolymer comprising a different monomer (or more than one different monomer, in some cases). Additional examples of monomers that can be used for copolymers (e.g., star, graft, branched, etc. copolymers) include, but are not limited to N-isopropyl acrylamide (NIP A Am), N,N-dimethylaminoethyl acrylate (DMAEA), vinyl acetate (VAc), vinyl propionate (VPr), methyl acrylate (MA), ethyl acrylate (EA), butyl acrylate (BA), vinyl pivalate (VPi), vinyl neodecanoate (VND), 6-ovinyladipoyl-d-glucopyranose (VAG), acryloyl glucosamine (AGA), vinyl pyrrolidone (VP), styrene (St), etc. In some cases, a multifunctional core may also be used. Non-limiting examples of such cores include ruthenium tris(bipyridyl), pentaerythritol, benzene, l,l,l-tris(hydroxymethyl)ethane, thiourethane-isocyanurate, cyclodextrin, etc. In some cases, cross-linkers may also be used, such as divinylbenzene, ethane- 1,2-diyl diacrylate, ethane- 1,2-diyl bis(2- methylacrylate), 2,2'-disulfanediylbis(ethane-2,l-diyl) bis(2-methylacrylate), etc.

According to one aspect of the invention, a first portion of a copolymer (e.g., a first block of a block copolymer) may be created by flowing a fluid containing a first monomer (and/or macromonomer) through a first channel and causing the first monomer to polymerize therein to form the first portion of the copolymer. In some embodiments, the channel is a microfluidic channel, e.g., having an average or characteristic cross- sectional diameter of no more than about 1000 micrometers, no more than about 800 micrometers, no more than about 500 micrometers, no more than about 300 micrometers, no more than about 200 micrometers, no more than about 100 micrometers, no more than about 50 micrometers, etc. In some cases, for example, if only a first monomer is present within the first channel, the resulting first portion may be substantially homogenous. For example, in the first portion of the copolymer, at least about 95%, at least about 97%, or at least about 99% of the monomers may be the first monomer.

In some cases, one or more properties of the first fluid and/or the first channel may be used to control polymerization of the first monomer to form the first portion of the copolymer. For instance, by controlling the rate of fluid flow through the first channel and/or the dimensions of the channel, the amount and/or degree of

polymerization of the first monomer within the first channel may be controlled.

For example, the amount of polymerization of the first monomer (e.g., after initiation of polymerization) may be controlled by controlling the length of the first channel. Thus, as examples, the length of the first channel may be at least about 1 mm, at least about 2 mm, at least about 3 mm, at least about 5 mm, at least about 10 mm, at least about 20 mm, at least about 30 mm, at least about 50 mm, at least about 100 mm, at least about 200 mm, at least about 500 mm, or at least about 1000 mm. The first channel may have any suitable shape, e.g., a straight or a curved pathway, a serpentine pathway, a spiral pathway, etc. In some cases, the aspect ratio (the ratio of the length of the channel to its average or characteristic cross- sectional diameter taken perpendicular to fluid flow within the channel) may be about 10: 1, at least about 20: 1, at least about 30: 1, at least about 50: 1, at least about 100: 1, at least about 200: 1, at least about 300: 1, at least about 500: 1, or at least about 1000: 1. The characteristic diameter of a non-circular channel may be taken as the diameter of a perfect circle having the same area as the cross- sectional area of the channel.

A longer channel may allow a longer residence time and thus allow more polymerization of the first monomer to occur, thereby allowing a longer first portion of the copolymer to be formed. For example, the residence time, or the average time it takes for the first monomer to flow through the first channel, may be at least about 5 minutes, at least about 10 minutes, at least about 15 minutes, at least about 30 minutes, at least about an hour, etc., depending on the application. In some cases, however, the residence time may be held to be no more than about 60 minutes, no more than about 45 minutes, no more than about 35 minutes, no more than about 25 minutes, no more than about 15 minutes, no more than about 10 minutes, no more than about 5 minutes, etc.

For example, the residence time can be controlled to facilitate an optimal or desired amount of polymerization of the monomer to form a first portion of the copolymer. Unlike a batch or "one-pot" system, the residence time of fluid within the channel may be controlled in various embodiments to a relatively tight distribution. Thus, the first portion of copolymer that is formed may have relatively low

polydispersity, or the first portion may have a relatively narrow distribution in the number of monomers that are present within the first portion. For example, the first portion of the copolymer may have a polydispersity index of less than about 4, less than about 3, less than about 2, less than about 1.9, less than about 1.8, less than about 1.7, less than about 1.6, less than about 1.5, less than about 1.4, less than about 1.3, less than about 1.2, or less than about 1.1. Typically, the polydispersity index is defined as the weight- average molecular weight of the polymer over its number-average molecular weight (M_w/M_n), and can be readily determined by those of ordinary skill in the art, for example, using techniques such as size exclusion chromatography, light scattering techniques, MALDI, electrospray mass spectrometry, or the like.

In addition, in certain embodiments, the channel and/or the flow of fluid within the channel may be controlled in some fashion. For example, the channel may be selected such that flow conditions of a fluid within the channel, such as the viscosity, the flow profiles (e.g., laminar, turbulent, plug, Poiseuille flow, etc.), etc., may be controlled, for example by controlling the shape and/or size of the channel. In some instances, the temperature of the channel may be controlled, for example, using heat sources such as those described herein, e.g., with respect to initiators.

In some cases, the first portion may have a relatively narrow distribution in the number of monomers that are present. For example, the distribution of monomers in the first portion may be such that no more than about 10%, no more than about 5%, no more than about 3%, no more than about 2%, or no more than about 1% of the first portions that are formed have a number of monomers less than about 90% (or less than about 95%, less than about 97%, or less than about 99%) and/or greater than about 110% (or greater than about 101%, greater than about 103%, or greater than about 105%) of the overall average number of monomers present in the first portions that are formed. In some embodiments, the number of monomers present in the first portions that are formed are such that the coefficient of variation in the number of monomers is less than about 10%, less than about 5%, less than about 2%, between about 1% and about 10%, between about 1% and about 5%, or between about 1% and about 2%. The coefficient of variation may be defined as the standard deviation divided by the mean, and can be determined by those of ordinary skill in the art.

Flow within the channel may be laminar or turbulent. Laminar flow may be used in some embodiments, for example, to allow better control over reaction within the channel since mixing (e.g., of monomers) within laminar flow typically occurs via diffusion only. However, turbulent flow may be used in some embodiments, for example, to ensure even residence times of fluid within the channel, more uniform reaction of the monomers within the channel, etc.

Reaction of the first monomer (and/or macromonomer) within the channel to form the first portion of the copolymer may be complete or partial. For example, the reaction may be allowed to proceed until at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95% of the first monomer has reacted or polymerized. The first portion may be present as a single molecule or as a plurality of different molecules. In some cases, e.g., as discussed below, a second monomer may be added before the first monomer has fully reacted. For instance, the second monomer may be added when less than about 90%, less than about 80%, less than about 70%, less than about 60%, less than about 50%, less than about 40%, less than about 30%, less than about 20%, or less than about 10% of the first monomer has not yet reacted and present as individual monomer.

Reaction of the first monomer (and/or macromonomer) to form the first portion of the copolymer may be initiated, in some cases, upon exposure to a suitable initiator, which may be introduced in some embodiments at an initiator region present within the device. The exact choice of initiator used depends on the polymers being polymerized, and can be readily chosen by those of ordinary skill in the art. In addition, in some cases, no initiator may be required to initiate polymerization (e.g., due to self-initiation of the chemical reaction). Non-limiting examples of initiators include ultraviolet light, heat, a chemical initiator, or any combination of these and/or other initiators, e.g., as discussed herein. The first monomer may be exposed to the initiator for a brief time (e.g., within an initiator region), or for longer periods of time (e.g., a portion, or all, of the overall device may be exposed to initiator). For example, the duration of exposure may in some cases be less than about 30 minutes, less than about 15 minutes, less than about 10 minutes, less than about 5 minutes, less than about 3 minutes, less than about 1 minute, less than about 30 s, less than about 15 s, less than about 10 s, less than about 5 s, etc., depending on factors such as the type of initiator that is used. In some cases, the time of exposure to the initiator may be short relative to the polymerization time, e.g., as determined when the polymerization reaction initiated by the initiator is stopped or altered, for instance, due to exiting the microfluidic system, or adding another reagent (e.g., another monomer), etc. For example, the exposure time may be less than about 50%, less than about 40%, less than about 30%, less than about 20%, less than about 10%, less than about 5%, or less than about 2% of the overall polymerization time of the polymer. In certain embodiments, a portion of a first channel may pass through an initiator region where at least some of the fluid within the first channel is exposed to an initiator, which can be used to initiate a polymerization reaction involving the first monomer (and/or macromonomer). In some embodiments, however, there may be no specific initiator region present (e.g., due to self-initiation of the chemical reaction), or because substantially all of the first channel may be exposed to a suitable initiator (e.g., ambient light, ambient temperature, an ultraviolet light directed to the entire first channel, etc.). The initiator region may be present at any suitable location within the device, e.g., covering a portion of the first channel, or in some cases, more than one portion of the first channel.

As mentioned, the specific initiator that is used may be chosen based on the specific polymerization reaction. In one set of embodiments, the initiator may be ultraviolet light, and the initiator region may be a location where the first channel passes under the ultraviolet light. For example, ultraviolet light from an ultraviolet light source may be directed at a portion (or more than one portion) of the first channel. The ultraviolet light may arise from any suitable light source (e.g., an ultraviolet lamp) and may be at any suitable frequency (e.g., at a frequency of between about 10 nm and about 400 nm, between about 40 nm and about 400 nm, etc.). As additional non-limiting examples, the ultraviolet light may have a frequency of between about 315 nm and about 400 nm, between about 280 nm and about 315 nm, between about 100 nm and about 280 nm, between about 10 nm and about 200 nm, or the like. One or a combination or range of frequencies may also be used.

As another example, heat may be used to initiate the polymerization reaction, and the initiator region may be a location where a heat source is directed at one or more portions of the first channel. The heat source may be within the channel (e.g., an electrically resistive heater), or the heat source may be external to the channel but contained within the device (e.g., a heating fluid in a separate compartment within the device that is in thermal communication with the first channel, such as via a heat exchanger), or the heat source may be external to the device (e.g., an infrared light directed at a portion of the first channel). For example, the channel (and/or fluids within the channel, e.g., monomers) may be exposed to a temperature of at least about 20 °C, at least about 25 °C, at least about 30 °C, at least about 35 °C, at least about 40 °C, at least about 50 °C, at least about 60 °C, etc. For instance, in one embodiment, the channel may be exposed to a temperature of between about 20 °C and about 50 °C.

As yet another example, a chemical initiator may be used to initiate the polymerization reaction. Non-limiting examples of chemical initiators include radical initiators such as azobisisobutyronitrile, l,l'-azobis(cyclohexanecarbonitrile), benzoyl peroxide, di-tert-butyl peroxide, methyl ethyl ketone peroxide, acetone peroxide, 2,2- dimethyoxy-2-phenylacetophenone, acryloyl chloride, etc. The initiator region may be a region where initiator is introduced into the fluid within the channel, e.g., to expose the first monomer to the initiator. For instance, the initiator region may comprise a junction with a side channel through which an initiator is introduced (e.g., a T-junction or a coaxial junction), a mixing chamber (e.g., through which one or more fluids may be introduced, at least one of which contains a chemical initiator), or the like. The side channel may be in fluid communication with an inlet port for introducing the initiator. In certain cases, however, a chemical initiator may be introduced into the channel with the fluid and the first monomer.

More than one initiator may also be used in certain cases. Thus, for example, any one or more of the initiator regions discussed above (or elsewhere herein) may be used within a device. For instance, a chemical initiator may be used that is activated upon exposure to ultraviolet radiation, and thus, a device in one embodiment may include an initiator region where ultraviolet radiation is directed to a channel, and a location where the chemical initiator is introduced. The chemical initiator may be introduced at the same location where ultraviolet light is directed, or at a different location, e.g., at a separate junction, simultaneously with introduction of the fluid containing the first monomer, etc.

In one aspect, the first monomer (and/or macromonomer) may be present within one or more droplets contained within the first channel. Within the droplets, the first monomer may be allowed to polymerize to form a first portion of a copolymer (e.g., a first block of a block copolymer). The droplets may be formed of a first fluid, and may be contained within a carrying fluid. The carrying fluid may in some cases be substantially immiscible with the first fluid. Droplets may be used in certain

embodiments of the invention to control the amount or degree of polymerization of first monomer that occurs. For instance, due to the limited and finite amount of first monomer that is present within a droplet, only a certain amount of polymerization of the first monomer may be able to occur. In addition, in some cases, as discussed below, a plurality of substantially monodisperse droplets may be used, e.g., such that the resulting first portions of the copolymer that are formed have relatively low polydispersity, or have a relatively narrow distribution in the number of monomers, e.g., as was previously discussed above.

The droplets may be contained in a microfluidic channel. For example, in certain embodiments, the droplets may have an average dimension or diameter of less than about 1 mm, less than about 500 micrometers, less than about 300 micrometers, less than about 200 micrometers, less than about 100 micrometers, less than about 75 micrometers, less than about 50 micrometers, less than about 30 micrometers, less than about 25 micrometers, less than about 10 micrometers, less than about 5 micrometers, less than about 3 micrometers, or less than about 1 micrometer in some cases. The average diameter may also be at least about 1 micrometer, at least about 2 micrometers, at least about 3 micrometers, at least about 5 micrometers, at least about 10 micrometers, at least about 15 micrometers, or at least about 20 micrometers in certain instances. The droplets may be spherical or non- spherical. The average diameter or dimension of a droplet, if the droplet is non- spherical, may be taken as the diameter of a perfect sphere having the same volume as the non- spherical droplet.

The droplets may be produced using any suitable technique. For example, a junction of channels may be used to create the droplets. The junction may be, for instance, a T-junction, a Y-junction, a channel-within-a-channel junction (e.g., in a coaxial arrangement, or comprising an inner channel and an outer channel surrounding at least a portion of the inner channel), a cross (or "X") junction, a flow-focus junction, or any other suitable junction for creating droplets. See, for example, International Patent Application No. PCT/US2004/010903, filed April 9, 2004, entitled "Formation and Control of Fluidic Species," by Link, et ah, published as WO 2004/091763 on October 28, 2004, or International Patent Application No. PCT/US2003/020542, filed June 30, 2003, entitled "Method and Apparatus for Fluid Dispersion," by Stone, et ah, published as WO 2004/002627 on January 8, 2004, each of which is incorporated herein by reference in its entirety. In some embodiments, the junction may be configured and arranged to produce substantially monodisperse droplets. The droplets of first fluid may be substantially monodisperse in some

embodiments, or the droplets may have a homogenous distribution of diameters, e.g., the droplets may have a distribution of diameters such that no more than about 10%, no more than about 5%, no more than about 3%, no more than about 2%, or no more than about 1% of the droplets have a diameter less than about 90% (or less than about 95%, less than about 97%, or less than about 99%) and/or greater than about 110% (or greater than about 101%, greater than about 103%, or greater than about 105%) of the overall average diameter of the plurality of droplets. In some embodiments, the plurality of droplets has an overall average diameter and a distribution of diameters such that the coefficient of variation of the cross- sectional diameters of the droplets is less than about 10%, less than about 5%, less than about 2%, between about 1% and about 10%, between about 1% and about 5%, or between about 1% and about 2%. The coefficient of variation may be defined as the standard deviation divided by the mean, and can be determined by those of ordinary skill in the art.

In some embodiments, the first fluid forming the droplets is substantially immiscible with the carrying fluid. For example, the first fluid may be hydrophilic or aqueous, while the carrying fluid may be hydrophobic or an "oil," or vice versa.

Typically, a "hydrophilic" fluid is one that is miscible with pure water, while a

"hydrophobic" fluid is a fluid that is not miscible with pure water. It should be noted that the term "oil," as used herein, merely refers to a fluid that is hydrophobic and not miscible in water. Thus, the oil may be a hydrocarbon in some embodiments, but in other embodiments, the oil may be (or include) other hydrophobic fluids (for example, octanol). It should also be noted that the hydrophilic or aqueous fluid need not be pure water. For example, the hydrophilic fluid may be an aqueous solution, for example, a buffer solution, a solution containing a dissolved salt, or the like. A hydrophilic fluid may also be, or include, for example, ethanol or other liquids that are miscible in water, e.g., instead of or in addition to water.

As discussed above, various aspects of the invention are generally directed to systems and methods for producing polymers such as block copolymers, gradient polymers, random copolymers, etc. For instance, non-limiting examples of techniques for forming a first portion of a copolymer were previously described. In addition, however, a second portion of the copolymer may also be fabricated, e.g., serially or simultaneously with the first portion of the copolymer, for instance, as discussed below. Any of the above techniques for forming a first portion of the copolymer may be combined with any of the techniques discussed below for forming a second portion of the copolymer.

For example, a second monomer (and/or macromonomer) may be added to the first fluid to form a second portion of the copolymer (for example, as a second block of a block copolymer, as a second portion that contains a random sequence of the first and second monomers, etc.), e.g., in a second channel, which may be an extension of the first channel. The second portion may comprise the second monomer, and in some cases, the first monomer as well. For example, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or substantially all of the monomers present in the second portion of the copolymer may be the second monomer. In some embodiments, the second block may be a gradient of the first monomer and the second monomer. In some cases, the other monomers present with the second portion of the copolymer may be the first monomer and/or other monomers, or some of the monomers may be defective, etc.

One way that the second portion of the copolymer may include some first monomer is if, at a point of introduction, the second monomer (and/or macromonomer) is introduced or added to the channel without removal of the first monomer.

Accordingly, upon addition of the second monomer to the channel, the first monomer and the second monomer may compete for addition to the second portion of the copolymer. Depending on the relative abilities or affinities of the first monomer and the second monomer to be added to the copolymer, the resulting second portion may form a portion of the copolymer that is homogenous or substantially homogenous in the second monomer, or the second portion may comprise a random distribution of first monomer and the second monomer. For example, if the copolymer is a block copolymer, as previously discussed, a majority of the second monomers forming the second portion (i.e., the second block) of the block copolymer may be positioned next to another second monomer.

In some embodiments, the ratio of second monomer and first monomer within the second portion of the copolymer may be controlled by controlling the relative ratios or concentrations of the first monomer and the second monomer during formation of the second portion. For example, by using a relatively high or "excess" concentration of second monomer, relative to the first monomer, a majority of the monomers in the second portion of the copolymer may be the second monomer. For instance, at the point of introduction of the second monomer, e.g., at the start of the second channel, the second monomer may have a concentration that is at least 2 times greater, at least 5 times greater than the concentration of the first monomer, or in some cases, the concentration of the second monomer may be at least about 10 times, at least about 20 times, at least about 30 times, at least about 50 times, or at least about 100 times greater than the concentration of the first monomer.

After introducing the second monomer (and/or macromonomer), the second monomer may immediately begin to polymerize (for example, due to the presence of an initiator that is already present, or because the reaction occurs spontaneously such that no initiator is needed, etc.), or in some embodiments, an initiator may be needed to initiate reaction of the second monomer and polymerization of the second portion of the copolymer. The second monomer may begin to polymer to the first portion of the copolymer (e.g., thereby forming a second portion of the copolymer), and/or the second monomer may begin to react to form a separate portion that later is reacted to the first portion to form a copolymer.

As mentioned, in some embodiments, an initiator is needed to initiate reaction of the second monomer. Thus, there may be an initiator region present in the second channel after a point of introduction of the second monomer. The initiator region may be the same region, or a different region than the initiator region of the first channel, as described above. Examples of initiators and initiator regions useful for the second monomer include any of those previous described with respect to the first monomer, e.g., ultraviolet light, heat, a chemical initiator, and the like, and such parameters and values are also independently applicable to the second monomer. The initiator for the second monomer can be the same or different than the initiator for the first monomer. The second monomer may also be exposed to the initiator for a relatively brief period of time (e.g., as discussed herein), or for a longer period of time, and the exposure time may be the same or different than the exposure time of the initiator (if any) used for the first monomer. The amount of polymerization of the second monomer and/or macromonomer (e.g., after initiation of polymerization) may be controlled similarly to the first monomer, as previously discussed. Thus, for example, the amount of polymerization of the second monomer may be controlled by controlling one or more properties of the second fluid and/or the second channel, and/or by controlling one or more properties of the first fluid. For instance, by controlling the rate of fluid flow of the first and/or second fluids through the second channel, and/or by controlling the dimensions of the second channel, the amount and/or degree of polymerization of the second monomer may be controlled. Non-limiting examples include controlling the average or characteristic cross-sectional diameter of the second channel, the length of the second channel, the aspect ratio of the second channel, the residence time through the second channel (e.g., the average time it takes for the second monomer to flow through the second channel), the shape of the second channel (e.g., a straight or a curved pathway, a serpentine pathway, a spiral pathway, etc.), or the like. Examples of suitable parameters and values for any of these previously described above with respect to the first monomer should also be understood as being applicable to the second fluid or second channel. In addition, the parameters or values as applied to the second fluid or second channel may be the same or different than applied to the first fluid or first channel.

As mentioned, any suitable method may be used to form the second portion of the copolymer, for example, by flowing a second fluid containing the second monomer through a second channel alongside a first fluid (e.g., containing the first monomer and/or the first portion of the copolymer), or by creating droplets containing a second fluid (containing the second monomer) and a first fluid (e.g., containing the first monomer and/or the first portion of the copolymer). For example, the second fluid may be introduced such that it flows alongside the first fluid in a second channel, such as is shown in Fig. 1A. In this figure, channels 15 containing the second fluid intersect channel 3 at junction 14. After junction 14, the second fluid is shown flowing alongside the first fluid within channel 5. In some cases, there may be more than one stream of the first fluid and/or the second fluid may present within the second channel.

As a non-limiting example, a second portion of a copolymer (e.g., a second block of a block copolymer) can be created in certain aspects by flowing a second fluid containing a second monomer through a second channel, alongside a first fluid containing a first monomer and/or a first portion of the copolymer (produced as previously discussed), and causing the second monomer to polymerize to form a first portion of the copolymer. The second portion may be fully or partially reacted prior to introduction to the first fluid. For example, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95% of the second monomer may have reacted or polymerized to from the second portion prior to introduction to the first fluid.

Within the second channel, the first fluid and the second fluid may be

substantially miscible or substantially immiscible. For example, if the first fluid and the second fluid are substantially miscible, the second monomer may be able to react with the first portion of the copolymer, and form thereon the second polymer. However, if the first fluid and the second fluid are substantially immiscible, the second polymer may be able to diffuse from the second fluid into the first fluid, and react with the copolymer upon entering the first fluid. This may be desirable in certain embodiments, for instance, to control reaction times.

The flow of the second fluid within the second channel may be laminar or turbulent, and may the same or different than the flow of the first fluid within the first channel. For example, the flow of the first fluid and/or second fluid may be turbulent, e.g., to promote mixing of the fluids. Exposure of the first fluid and the second fluid may also allow reaction of the first portion of the copolymer and/or unreacted first monomer (contained within the first fluid) and the second monomer (contained in the second fluid) to occur in certain embodiments.

The second channel may also have the same or different dimensions than the first channel. For example, the average or characteristic cross-sectional diameter of the second channel, the length of the second channel, the aspect ratio of the second channel, the residence time through the second channel, or the like may be the same or different dimensions than the first channel, and examples of suitable parameters and values for any of these have been given above with respect to the first channel. In some

embodiments, for example, the second channel may be a microfluidic channel having any of the dimensions (e.g., shape, length, average or characteristic cross-sectional diameter, etc.) previously described above with respect to the dimensions of the first channel. As another example, the amount of polymerization may be controlled by controlling the length of the second channel. A longer channel may allow a longer residence time and thus allow more polymerization to occur, thereby allowing a longer second portion of the copolymer to be formed.

The second portion of the copolymer may be formed to have a relatively tight distribution, in certain embodiments of the invention. For example, the second portion may be formed to have a relatively low polydispersity, or have a relatively narrow distribution in the number of monomers that are present within the second portion. As an example, the second portion of the copolymer may have a polydispersity index of less than about 4, less than about 3, less than about 2, less than about 1.9, less than about 1.8, less than about 1.7, less than about 1.6, less than about 1.5, less than about 1.4, less than about 1.3, less than about 1.2, or less than about 1.1. In addition, the polydispersity index of the second portion may be the same or different than the polydispersity index of the first portion. The second portion may also have a distribution of monomers such that no more than about 10%, no more than about 5%, no more than about 3%, no more than about 2%, or no more than about 1% of the second portions that are formed have a number of monomers less than about 90% (or less than about 95%, less than about 97%, or less than about 99%) and/or greater than about 110% (or greater than about 101%, greater than about 103%, or greater than about 105%) of the overall average number of monomers present in the second portions that are formed. In some embodiments, the number of monomers present in the second portions that are formed are such that the coefficient of variation in the number of monomers is less than about 10%, less than about 5%, less than about 2%, between about 1% and about 10%, between about 1% and about 5%, or between about 1% and about 2%.

In some embodiments, the overall polymer that is thereby formed (e.g., comprising first and second portions) may also have a relatively tight distribution. For example, the copolymer may have an overall polydispersity index of less than about 4, less than about 3, less than about 2, less than about 1.9, less than about 1.8, less than about 1.7, less than about 1.6, less than about 1.5, less than about 1.4, less than about 1.3, less than about 1.2, or less than about 1.1. The copolymer may also have a distribution of monomers such that no more than about 10%, no more than about 5%, no more than about 3%, no more than about 2%, or no more than about 1% of the copolymers that are formed have a number of monomers less than about 90% (or less than about 95%, less than about 97%, or less than about 99%) and/or greater than about 110% (or greater than about 101%, greater than about 103%, or greater than about 105%) of the overall average number of monomers present. In some embodiments, the number of monomers present are such that the coefficient of variation in the number of monomers is less than about 10%, less than about 5%, less than about 2%, between about 1% and about 10%, between about 1% and about 5%, or between about 1% and about 2%.

In certain aspects, as discussed, the second fluid is introduced into the second channel as a plurality of droplets, e.g., contained within a carrying fluid. For example, a plurality of droplets containing the first fluid (e.g., containing the first monomer and/or the first portion of the copolymer) and the second fluid may be formed. The second fluid may comprise a second monomer, or in some cases, a second, polymerized portion of the copolymer (e.g., produced in a manner similar to that discussed above with respect to the first portion). For instance, droplets may be formed containing the first fluid and the second fluid, e.g., to expose the first monomer and the second monomer to each other. As previously discussed, the first fluid and the second fluid may be substantially miscible or substantially immiscible. If the first fluid and the second fluid are immiscible, the first and second fluids may form nested a nested inner droplet contained within an outer droplet, with either the first fluid or the second fluid being the innermost droplet and the other fluid surrounding it, thereby forming a double emulsion droplet.

As an illustrative example, Fig. 2A shows a schematic of a double emulsion droplet. In this figure, double emulsion droplet 40 is shown including carrying fluid 49, outer fluid 41 containing a first monomer 45, and inner fluid 42 containing a second monomer 46. The first monomer and the second monomer may each independently be present in their respective fluids as individual monomers, and/or some of the monomers may have polymerized to form polymers, e.g., chain 53 as shown in Fig. 2. Inner fluid 42 and outer fluid 41 may be substantially immiscible or substantially miscible. For example, if inner fluid 42 and outer fluid 41 are substantially miscible, upon the formation of double emulsion droplet 40, these fluids may mix, causing first monomer 45 and second monomer 46 to become exposed to each other. Chain growth may continue, for example, by polymerization of the first and second monomers, e.g., to form a random copolymer, a block copolymer, a gradient copolymer, or the like, as is shown in Fig. 2B. Within the droplets, the second monomer (and/or macromonomer) may be allowed, in some embodiments, to polymerize to form a second portion of the copolymer. Thus, the droplets may be used to control the amount or degree of polymerization of second monomer that occurs. For instance, due to the limited and finite amount of second monomer that is present within the droplet, only a certain amount of polymerization of the second monomer may be allowed to occur, e.g., to form the second portion of the copolymer. In some embodiments, for example, the second portion that is formed may be a second block of a block copolymer. As another example, the second portion may be a gradient copolymer, e.g., as the ratio of first monomer to second monomer changes within the droplet (e.g., due to preferential reaction of one monomer versus the other to the copolymer), the ratio of first monomer to second monomer within the second portion of the copolymer may also change, thereby forming a gradient.

In various embodiments where a third, carrying fluid is present, the second fluid may be substantially immiscible with the carrying fluid. For instance, the second fluid may be hydrophilic or aqueous, while the carrying fluid may be hydrophobic, or vice versa. In some embodiments, a first fluid, a second fluid, and a carrying fluid may all be substantially mutually immiscible. As a non-limiting example, a system of three substantially mutually immiscible liquids is a silicone oil, a mineral oil, and an aqueous solution (i.e., water, or water containing one or more other species that are dissolved and/or suspended therein). Another example of a system is a silicone oil, a fluorocarbon oil, and an aqueous solution. Yet another example of a system is a hydrocarbon oil (e.g., hexadecane), a fluorocarbon oil, and an aqueous solution. Non-limiting examples of suitable fluorocarbon oils include HFE7500, octadecafluorodecahydronaphthalene:

or l-( 1,2,2,3, 3, -undecafluorocyclohexyl)ethanol:

The droplets themselves may be spherical or non- spherical, and may have an average dimension or diameter of less than about 1 mm, less than about 500

micrometers, less than about 300 micrometers, less than about 200 micrometers, less than about 100 micrometers, less than about 75 micrometers, less than about 50 micrometers, less than about 30 micrometers, less than about 25 micrometers, less than about 10 micrometers, less than about 5 micrometers, less than about 3 micrometers, or less than about 1 micrometer in some cases. The average diameter may also be at least about 1 micrometer, at least about 2 micrometers, at least about 3 micrometers, at least about 5 micrometers, at least about 10 micrometers, at least about 15 micrometers, or at least about 20 micrometers in certain instances.

The droplets may, in some embodiments, be substantially monodisperse droplets, or the droplets may have a homogenous distribution of diameters. For instance, the droplets may have a distribution of diameters such that no more than about 10%, no more than about 5%, no more than about 3%, no more than about 2%, or no more than about 1% of the droplets have a diameter less than about 90% (or less than about 95%, less than about 97%, or less than about 99%) and/or greater than about 110% (or greater than about 101%, greater than about 103%, or greater than about 105%) of the overall average diameter of the plurality of droplets. In some embodiments, the plurality of droplets have an overall average diameter and a distribution of diameters such that the coefficient of variation of the cross- sectional diameters of the droplets is less than about 10%, less than about 5%, less than about 2%, between about 1% and about 10%, between about 1% and about 5%, or between about 1% and about 2%.

In addition, in many of the embodiments previously described, the first fluid and the second fluid may be substantially miscible such that reaction between the first portion (and/or unreacted first monomer) and the second monomer and/or second portion is able to occur. In some embodiments, however, the first fluid and the second fluid may be substantially immiscible, e.g., forming separate inner droplets. In some cases, reaction between the first portion (and/or unreacted first monomer) and the second monomer (and/or second portion) is still able to occur, e.g., due to diffusion of one or both into the other fluid.

The droplets may be produced using any suitable technique, including any of those previously discussed. For instance, a junction of channels may be used to create the droplets, e.g., a T-junction, a Y-junction, a channel-within-a-channel junction (e.g., in a coaxial arrangement, or comprising an inner channel and an outer channel surrounding at least a portion of the inner channel), a cross (or "X") junction, a flow- focus junction, or any other suitable junction. In some embodiments, the junction may be configured and arranged to produce substantially monodisperse droplets. If more than one droplet maker is present (e.g., for initially creating droplets of first fluid, as described above), the droplet makers may be the same or different. Any of the above systems and techniques for producing droplets of first fluid (e.g., contained within a carrying fluid) are also applicable to systems and methods of creating droplets of first fluid and second fluid discussed here.

Still other examples of techniques for producing droplets are disclosed in International Patent Application No. PCT/US2004/010903, filed April 9, 2004, entitled "Formation and Control of Fluidic Species," by Link, et ah, published as WO

2004/091763 on October 28, 2004, or International Patent Application No.

PCT/US2003/020542, filed June 30, 2003, entitled "Method and Apparatus for Fluid Dispersion," by Stone, et ah, published as WO 2004/002627 on January 8, 2004, each of which is incorporated herein by reference in its entirety.

As a non-limiting example of a technique of forming a droplet containing a first fluid and a second fluid, in one set of embodiments, a channel-within-a-channel junction may be used to create droplets, e.g., containing the first fluid and the second fluid within a third, carrying fluid. One example of a channel-within-a-channel junction is now described with respect to Fig. 3. In this example, the first fluid may be used as the inner fluid and the second fluid may be used as the outer fluid of the double emulsion droplet, or vice versa. The schematic diagram shown in Fig. 3 shows junction 100 having outer conduit 110, first inner conduit (or injection tube) 120, and second inner conduit (or collection tube) 130. The first, inner fluid 140 is shown flowing in a right to left direction and outer fluid 150 flows in a right to left direction in the space outside of injection tube 120 and within conduit 110. Carrying fluid 160 flows in a left to right direction in the pathway provided between outer conduit 110 and collection tube 130. After carrying fluid 160 contacts outer fluid 150, it changes direction and starts to flow in substantially the same direction as inner fluid 140 and outer fluid 150, i.e., right to left.

Injection tube 120 includes an exit orifice 164 at the end of tapered portion 170. Collection tube 130 includes an entrance orifice 162, an internally tapered surface 172, and exit channel 168. Thus, the inner diameter of injection tube 120 decreases in a direction from right to left, as shown, and the inner diameter of collection tube 130 increases from entrance orifice 162 in a direction from right to left. These constrictions, or tapers, can provide geometries that aid in producing consistent double emulsions. The rate of constriction may be linear or non-linear.

As illustrated in Fig. 3, inner fluid 140 exiting from orifice 164 can be completely surrounded by outer fluid 150, as there is no portion of inner fluid 140 that contacts the inner surface of conduit 110 after its exit from injection tube 120. Thus, for a portion between exit orifice 164 to a point inside of collection tube 130 (to the left of entrance orifice 162), inner fluid 140 is concentrically surrounded by outer fluid 150.

Additionally, outer fluid 150 may not come into contact with a surface of collection tube 130, at least not until after the multiple emulsion droplets have been formed, because it is concentrically surrounded by carrying fluid 160 as it enters collection tube 130. Thus, from a point to the left of exit orifice 164 to a point inside of collection tube 130, a composite stream of three fluid streams is formed, including inner fluid 140

concentrically surrounded by outer fluid 150, which in turn is concentrically surrounded by carrying fluid 160. The inner and outer fluids may not break to form individual droplets until they are inside of collection tube 130 (i.e., to the left of entrance orifice 162). For additional details, see, e.g., International Patent Application No.

PCT/US2006/007772, filed March 3, 2006, entitled "Method and Apparatus for Forming Multiple Emulsions," by Weitz, et al, published as WO 2006/096571 on September 14, 2006, incorporated herein by reference in its entirety.

As another non-limiting example of a technique of forming a droplet containing a first fluid and a second fluid, a second fluid may be directly injected into a first droplet containing the first monomer. The first fluid and the second fluid may be substantially miscible or substantially immiscible. For example, electrodes may be used to apply an electric field to one or more fluidic channels, e.g., proximate an intersection of at least two fluidic channels. In some cases, a second fluid may be urged into a droplet of first fluid, facilitated by the electric field. For example, the electric field may be created using electrodes positioned on one side of a first channel near the junction, opposite an entering second channel. The electric field may disrupt the interface between the first fluid and the second fluid, e.g., upon contact of the first and the second fluid. As the fluid (e.g., as droplets) flow past the junction, a fluidic interface is formed between the droplets of first fluid and the second fluid in the second channel. The electrodes may be used to create an electric field that disrupts the interface between the droplet of first fluid and the second fluid, thus allowing the second fluid to flow from the second channel into the droplet. Properties such as the volume, flow rate, etc. of the second fluid entering the droplet can be controlled, for example, by controlling various properties of the fluid and/or the droplet, and/or by controlling the applied electric field. For additional details, see, for example, International Patent Application No. PCT/US2010/040006, filed June 25, 2010, entitled "Fluid Injection," by Weitz, et al, published as WO 2010/151776 on December 29, 2010, incorporated herein by reference in its entirety.

As yet another non-limiting example of a technique of forming a droplet containing a first fluid and a second fluid, a first droplet containing the first fluid and a second droplet containing a second fluid may be merged or fused together to create a combined droplet containing both the first fluid and the second fluid. For example, the separate droplets of first fluid and second fluid may each be given opposite electric charges (i.e., positive and negative charges, not necessarily of the same magnitude), which may increase the electrical interaction of the two droplets such that fusion or coalescence of the droplets can occur due to their opposite electric charges, e.g., to produce the combined droplet. For instance, an electric field may be applied to the droplets, the droplets may be passed through a capacitor, a chemical reaction may cause the droplets to become charged, etc.

In another set of embodiments, the separate droplets may not necessarily be given opposite electric charges (and, in some cases, may not be given any electric charge), and the droplets may instead be fused through the use of dipoles induced in the fluidic droplets that causes the fluidic droplets to coalesce. The dipoles may be induced using an electric field which may be an AC field, a DC field, etc., and the electric field may be created, for instance, using one or more electrodes. The induced dipoles in the fluidic droplets may cause the fluidic droplets to become electrically attracted towards each other due to their local opposite charges, thus causing the droplets to fuse.

Still other examples of fusing or coalescing separate droplets to produce combined droplets are described in International Patent Application No.

PCT/US2004/010903, filed April 9, 2004, entitled "Formation and Control of Fluidic Species," by Link, et al, published as WO 2004/091763 on October 28, 2004, and International Patent Application No. PCT/US2004/027912, filed August 27, 2004, entitled "Electronic Control of Fluidic Species," by Link, et ah, published as WO

2005/021151 on March 10, 2005, each incorporated herein by reference in its entirety.

In another aspect of the invention, a filter may be used to remove unreacted monomer from a fluidic stream containing a polymer comprising the monomer. It should be noted that such a filter may be used in any situation where unreacted monomer is to be removed from a fluidic stream, not necessarily limited to only the copolymer systems described herein. For example, in one set of embodiments, for example, the filter may be an in-line filter comprising a microfiltration membrane, an ultrafiltration membrane, a nanofiltration membrane, a reverse osmosis membrane, or a dialysis membrane. Prior art techniques have used membranes to purify polymers from residual monomers by ultrafiltration, but not within microfluidic channels or systems. However, it is not trivial to adapt such membranes to a microfluidic system due to the small sizes and high pressure drops that would be needed within a microfluidic channel.

In one set of embodiments, the filtration membrane is a semipermeable membrane able to retain suspended solids and solutes of high molecular weight (e.g., polymers), while water and low molecular weight solutes (e.g., unreacted or partially reacted monomers) are able to pass through the membrane. The exact type of membrane may be selected, for example, based on the polymer size (or molecular weight) and the size of the monomers used to form the polymer. For example, the membrane may be selected to have a molecular weight cut-off (MWCO) of less than about 10 kDa, less than about 7 kDa, less than about 5 kDa, less than about 3 kDa, or less than about 1 kDa, and/or a nominal pore size of less than 100 nm, less than about 50 nm, less than about 30 nm, less than about 10 nm, less than about 5 nm, less than about 3 nm, or less than about 1 nm. The filtration membrane, in various embodiments, is polymeric, e.g., comprising one or more polymers such as polyamide, polycarbonate, polyisoprene, polysulfone, polytetrafluoroethylene, cellulose acetate, polystyrene, etc., as well as combinations of these and/or other polymers.

In one aspect, one or more sensors may be used to determine or monitor the amount and/or quality of polymer that is formed. Examples of sensors include sensors for determining the pressure, temperature, pH, etc., or the like. The sensor may be embedded within or integrally connected to the device, or positioned remotely but with physical, electrical, and/or optical connection with the device so as to be able to sense a portion of the device, for instance, a channel containing a polymer. For example, the sensor may be positioned so as to detect electromagnetic radiation, e.g., infrared, ultraviolet, or visible light. As a specific non-limiting example, a laser may be directed to a channel, e.g., to determine light scattering. As another example, a sensor may be positioned on or within the device, and may sense a portion of a channel by being connected optically to the channel. The sensor may be, for example, a pH sensor, an optical sensor, a pressure sensor, a sensor able to detect the concentration of a substance, or the like. Non-limiting examples of sensors useful in the invention include CCD cameras, optical detectors, fluorescence detection systems, optical microscopy systems, electrical systems, thermocouples and thermistors, pressure sensors, ion-selective electrodes, etc. Those of ordinary skill in the art will be able to identify other sensors for use in the invention, and many such sensors can be readily obtained commercially. In other cases, however, there may be no sensor present.

A variety of materials and methods, according to certain aspects of the invention, can be used to produce fluidic systems such as those described herein. In some cases, the various materials selected lend themselves to various methods. For example, various components of the invention can be formed from solid materials, in which the channels can be formed via micromachining, film deposition processes such as spin coating and chemical vapor deposition, laser fabrication, photolithographic techniques, etching methods including wet chemical or plasma processes, and the like. See, for example, Scientific American, 248:44-55, 1983 (Angell, et al). In one embodiment, at least a portion of the fluidic system is formed of silicon by etching features in a silicon chip. Technologies for precise and efficient fabrication of various fluidic systems and devices of the invention from silicon are known. In another embodiment, various components of the systems and devices of the invention can be formed of a polymer, for example, an elastomeric polymer such as polydimethylsiloxane ("PDMS"), polytetrafluoroethylene ("PTFE" or Teflon^®), or the like.

Different components can be fabricated of the same or different materials. For example, a base portion including a bottom wall and side walls can be fabricated from an opaque material such as silicon or PDMS, and a top portion can be fabricated from a transparent or at least partially transparent material, such as glass or a transparent polymer, for observation and/or control of the fluidic process. Components can be coated so as to expose a desired chemical functionality to fluids that contact interior channel walls, where the base supporting material does not have a precise, desired functionality. For example, components can be fabricated as illustrated, with interior channel walls coated with another material. Material used to fabricate various components of the systems and devices of the invention, e.g., materials used to coat interior walls of fluid channels, may desirably be selected from among those materials that will not adversely affect or be affected by fluid flowing through the fluidic system, e.g., material(s) that is chemically inert in the presence of fluids to be used within the device.

In one embodiment, various components of the invention are fabricated from polymeric and/or flexible and/or elastomeric materials, and can be conveniently formed of a hardenable fluid, facilitating fabrication via molding (e.g. replica molding, injection molding, cast molding, etc.). The hardenable fluid can be essentially any fluid that can be induced to solidify, or that spontaneously solidifies, into a solid capable of containing and/or transporting fluids contemplated for use in and with the fluidic network. In one embodiment, the hardenable fluid comprises a polymeric liquid or a liquid polymeric precursor (i.e. a "prepolymer"). Suitable polymeric liquids can include, for example, thermoplastic polymers, thermoset polymers, or mixture of such polymers heated above their melting point. As another example, a suitable polymeric liquid may include a solution of one or more polymers in a suitable solvent, which solution forms a solid polymeric material upon removal of the solvent, for example, by evaporation. Such polymeric materials, which can be solidified from, for example, a melt state or by solvent evaporation, are well known to those of ordinary skill in the art. A variety of polymeric materials, many of which are elastomeric, are suitable, and are also suitable for forming molds or mold masters, for embodiments where one or both of the mold masters is composed of an elastomeric material. A non-limiting list of examples of such polymers includes polymers of the general classes of silicone polymers, epoxy polymers, and acrylate polymers. Epoxy polymers are characterized by the presence of a three- membered cyclic ether group commonly referred to as an epoxy group, 1,2-epoxide, or oxirane. For example, diglycidyl ethers of bisphenol A can be used, in addition to compounds based on aromatic amine, triazine, and cycloaliphatic backbones. Another example includes the well-known Novolac polymers. Non-limiting examples of silicone elastomers suitable for use according to the invention include those formed from precursors including the chlorosilanes such as methylchlorosilanes, ethylchlorosilanes, phenylchlorosilanes, etc.

Silicone polymers are preferred in one set of embodiments, for example, the silicone elastomer polydimethylsiloxane. Non-limiting examples of PDMS polymers include those sold under the trademark Sylgard by Dow Chemical Co., Midland, MI, and particularly Sylgard 182, Sylgard 184, and Sylgard 186. Silicone polymers including PDMS have several beneficial properties simplifying fabrication of the microfluidic structures of the invention. For instance, such materials are inexpensive, readily available, and can be solidified from a prepolymeric liquid via curing with heat. For example, PDMSs are typically curable by exposure of the prepolymeric liquid to temperatures of about, for example, about 65 °C to about 75 °C for exposure times of, for example, about an hour. Also, silicone polymers, such as PDMS, can be elastomeric, and thus may be useful for forming very small features with relatively high aspect ratios, necessary in certain embodiments of the invention. Flexible (e.g., elastomeric) molds or masters can be advantageous in this regard.

One advantage of forming structures such as microfluidic structures of the invention from silicone polymers, such as PDMS, is the ability of such polymers to be oxidized, for example by exposure to an oxygen-containing plasma such as an air plasma, so that the oxidized structures contain, at their surface, chemical groups capable of cross-linking to other oxidized silicone polymer surfaces or to the oxidized surfaces of a variety of other polymeric and non-polymeric materials. Thus, components can be fabricated and then oxidized and essentially irreversibly sealed to other silicone polymer surfaces, or to the surfaces of other substrates reactive with the oxidized silicone polymer surfaces, without the need for separate adhesives or other sealing means. In most cases, sealing can be completed simply by contacting an oxidized silicone surface to another surface without the need to apply auxiliary pressure to form the seal. That is, the pre- oxidized silicone surface acts as a contact adhesive against suitable mating surfaces. Specifically, in addition to being irreversibly sealable to itself, oxidized silicone such as oxidized PDMS can also be sealed irreversibly to a range of oxidized materials other than itself including, for example, glass, silicon, silicon oxide, quartz, silicon nitride, polyethylene, polystyrene, glassy carbon, and epoxy polymers, which have been oxidized in a similar fashion to the PDMS surface (for example, via exposure to an oxygen-containing plasma). Oxidation and sealing methods useful in the context of the present invention, as well as overall molding techniques, are described in the art, for example, in an article entitled "Rapid Prototyping of Microfluidic Systems and

Polydimethylsiloxane," Anal. Chem., 70:474-480, 1998 (Duffy, et al), incorporated herein by reference.

In some embodiments, certain microfluidic structures of the invention (or interior, fluid-contacting surfaces) may be formed from certain oxidized silicone polymers. Such surfaces may be more hydrophilic than the surface of an elastomeric polymer. Such hydrophilic channel surfaces can thus be more easily filled and wetted with aqueous solutions.

In one embodiment, a bottom wall of a microfluidic device of the invention is formed of a material different from one or more side walls or a top wall, or other components. For example, the interior surface of a bottom wall can comprise the surface of a silicon wafer or microchip, or other substrate. Other components can, as described above, be sealed to such alternative substrates. Where it is desired to seal a component comprising a silicone polymer (e.g. PDMS) to a substrate (bottom wall) of different material, the substrate may be selected from the group of materials to which oxidized silicone polymer is able to irreversibly seal (e.g., glass, silicon, silicon oxide, quartz, silicon nitride, polyethylene, polystyrene, epoxy polymers, and glassy carbon surfaces which have been oxidized). Alternatively, other sealing techniques can be used, as would be apparent to those of ordinary skill in the art, including, but not limited to, the use of separate adhesives, thermal bonding, solvent bonding, ultrasonic welding, etc. As mentioned, in some, but not all embodiments, the systems and methods described herein may include one or more microfluidic components, for example, one or more microfluidic channels. The "cross- sectional dimension" of a microfluidic channel is measured perpendicular to the direction of fluid flow within the channel. Thus, some or all of the microfluidic channels may have a largest cross-sectional dimension less than 2 mm, and in certain cases, less than 1 mm. In one set of embodiments, the maximum cross- sectional dimension of a microfluidic channel is less than about 500 micrometers, less than about 300 micrometers, less than about 200 micrometers, less than about 100 micrometers, less than about 50 micrometers, less than about 30 micrometers, less than about 10 micrometers, less than about 5 micrometers, less than about 3 micrometers, or less than about 1 micrometer. In certain embodiments, the microfluidic channels may be formed in part by a single component (e.g. an etched substrate or molded unit). Of course, larger channels, tubes, chambers, reservoirs, etc. can also be used to store fluids and/or deliver fluids to various components or systems in other embodiments of the invention.

A microfluidic channel can have any cross-sectional shape (circular, oval, triangular, irregular, square or rectangular, or the like) and can be covered or uncovered. In embodiments where it is completely covered, at least one portion of the channel can have a cross-section that is completely enclosed, or the entire channel may be completely enclosed along its entire length with the exception of its inlet(s) and/or outlet(s). A channel may also have an aspect ratio (length to average cross sectional dimension) of at least 2: 1, more typically at least 3: 1, 5: 1, 10: 1, 15: 1, 20: 1, or more.

In some embodiments, at least a portion of one or more of the channels may be hydrophobic, or treated to render at least a portion hydrophobic. For example, one non- limiting method for making a channel surface hydrophobic comprises contacting the channel surface with an agent that confers hydrophobicity to the channel surface. For example, in some embodiments, a channel surface may be contacted (e.g., flushed) with Aquapel® (a commercial auto glass treatment) (PPG Industries, Pittsburgh, PA). In some cases, a channel surface contacted with an agent that confers hydrophobicity may be subsequently purged with air. In some embodiments, the channel may be heated (e.g., baked) to evaporate solvent that contains the agent that confers hydrophobicity. Thus, in some aspects of the invention, a surface of a microfluidic channel may be modified to facilitate the production of emulsions such as multiple emulsions. In some cases, the surface may be modified by coating a sol-gel onto at least a portion of a microfluidic channel. As an example, the sol-gel coating may be made more

hydrophobic by incorporating a hydrophobic polymer in the sol-gel. For instance, the sol-gel may contain one or more silanes, for example, a fluorosilane (i.e., a silane containing at least one fluorine atom) such as heptadecafluorosilane, or other silanes such as methyltriethoxy silane (MTES) or a silane containing one or more lipid chains, such as octadecylsilane or other CH₃(CH₂)_n- silanes, where n can be any suitable integer. For instance, n may be greater than 1, 5, or 10, and less than about 20, 25, or 30. The silanes may also optionally include other groups, such as alkoxide groups, for instance, octadecyltrimethoxy silane. In general, most silanes can be used in the sol-gel, with the particular silane being chosen on the basis of desired properties such as hydrophobicity. Other silanes (e.g., having shorter or longer chain lengths) may also be chosen in other embodiments of the invention, depending on factors such as the relative hydrophobicity or hydrophilicity desired. In some cases, the silanes may contain other groups, for example, groups such as amines, which would make the sol-gel more hydrophilic. Non- limiting examples include diamine silane, triamine silane, or N-[3- (trimethoxysilyl)propyl] ethylene diamine silane. The silanes may be reacted to form macromonomers or polymers within the sol-gel, and the degree of polymerization (e.g., the lengths of the polymer) may be controlled by controlling the reaction conditions, for example by controlling the temperature, amount of acid present, or the like. In some cases, more than one silane may be present in the sol-gel. For instance, the sol-gel may include fluorosilanes to cause the resulting sol-gel to exhibit greater hydrophobicity, and/or other silanes (or other compounds) that facilitate the production of polymers. In some cases, materials able to produce Si0₂ compounds to facilitate polymerization may be present, for example, TEOS (tetraethyl ortho silicate). It should be understood that the sol-gel is not limited to containing only silanes, and other materials may be present in addition to, or in place of, the silanes. For instance, the coating may include one or more metal oxides, such as Si0₂, vanadia (V₂0₅), titania (Ti0₂), and/or alumina (A1₂0₃).

In some instances, the microfluidic channel is constructed from a material suitable to receive the sol-gel, for example, glass, metal oxides, or polymers such as polydimethylsiloxane (PDMS) and other siloxane polymers. For example, in some cases, the microfhiidic channel may be one in which contains silicon atoms, and in certain instances, the microfhiidic channel may be chosen such that it contains silanol (Si-OH) groups, or can be modified to have silanol groups. For instance, the

microfhiidic channel may be exposed to an oxygen plasma, an oxidant, or a strong acid cause the formation of silanol groups on the microfhiidic channel.

The following documents are incorporated herein by reference in their entireties: International Patent Application No. PCT/US2004/010903, filed April 9, 2004, entitled "Formation and Control of Fluidic Species," by Link, et al, published as WO

2004/091763 on October 28, 2004; International Patent Application No.

PCT/US2003/020542, filed June 30, 2003, entitled "Method and Apparatus for Fluid Dispersion," by Stone, et al, published as WO 2004/002627 on January 8, 2004;

International Patent Application No. PCT/US2006/007772, filed March 3, 2006, entitled "Method and Apparatus for Forming Multiple Emulsions," by Weitz, et al, published as WO 2006/096571 on September 14, 2006; International Patent Application No.

PCT/US2004/027912, filed August 27, 2004, entitled "Electronic Control of Fluidic Species," by Link, et al, published as WO 2005/021151 on March 10, 2005; and International Patent Application No. PCT/US2007/002063, filed January 24, 2007, entitled "Fluidic Droplet Coalescence," by Ahn, et al, published as WO 2007/089541 on August 9, 2007.

The following examples are intended to illustrate certain embodiments of the present invention, but do not exemplify the full scope of the invention.

EXAMPLE 1

This example demonstrates the production of a block copolymer in accordance with certain embodiments of the invention. In particular, this example illustrates the production of copolymers with well-defined structure through free-radical

polymerization in microfhiidic channels. The spatial confinement and control over residence times in microfhiidic channels allows manipulation of structural composition of the growing polymer chains. In a continuous process, at subsequent positions along the microfhiidic channel, radicals are generated, polymer chains are allowed to grow, other monomers are added to the growing polymer radicals flowing down the channel, and the product is purified in a single channel. Ref erring to the schematic diagram shown in Fig. 1, a first monomer and an initiator are introduced into fluidic system 10 through inlet port 1. Initiation can take place, for example, by shining ultraviolet light onto the device and decomposing photoinitiator molecules to produce free radicals to initiate the polymerization process. As other examples, thermal initiation and/or radical initiation could be used. In some cases, a short initiation time compared to chain growth may be desirable for good product quality, e.g. with a narrow molecular weight distribution, and/or a good yield of block/gradient polymer.

The propagation of the chain reaction takes place in channel 3. Radical termination may be avoided here, e.g., to avoid the formation of homopolymer. Thus, in some cases, the addition of mediators, e.g. for controlled radical polymerization, may be beneficial for product quality and yield. However, other additives than used in conventional living systems may also be used in some cases, for example, to boost the process. In some cases, cheaper mediators or less toxic catalysts could be used. For example, one benefit from confining the reaction in a microfluidic channel is temporal control of the reaction. Furthermore, control of the flows may allow direct manipulation of mixing within the channels (e.g. laminar flows lead to mixing by diffusion only). Thus, the residence time in the channel also affords control over monomer conversion.

After sufficient conversion a second monomer may be added via inlet ports 4 and mixed with the polymer solution from the first polymerization step. Growing radicals contained in the first fluid may continue to grow by the addition of monomer units of the second monomer. Again, the length of the following channel 5 may be chosen as a function of the desired final conversion.

After sufficient conversion, residual monomer may be removed using filter 6. For example, this can be done by size exclusion in an ultrafiltration step. In addition, the polymer that is produced may be analyzed in some cases using sensor 7 to find suitable processing conditions and quality control.

Heterophase flow can be used in combination with the above process.

Heterophase systems include, for example, coflowing jets or dispersal systems.

Heterophase flow can be used, for example, to realize narrow residence time

distributions, or mixing of chemicals. In one set of embodiments, heterophase flow may be achieved by flowing two or more fluids laminarly within a channel. Laminar flow is attractive because flow lines do not cross; thus, the primary way for molecules to cross flow lines is by diffusion. Gradients (including concentration gradients) can be used, for example, to drive mass transport across flow lines. The different fluid streams can also be chosen to be miscible in each other or immiscible with low interfacial tension. As another example, the jetting of immiscible phases in anisotropic microchannel geometries and/or at high flow rates may be used to achieve laminar coflow.

EXAMPLE 2

As another example, microfluidic devices may be used to perform

copolymerizations in droplets. For example, picoinjectors may be used to add a second monomer to a droplet containing growing polymer radicals. See, e.g., International Patent Application No. PCT/US2010/040006, filed June 25, 2010, entitled "Fluid Injection," by Weitz, et al, published as WO 2010/151776 on December 29, 2010, incorporated herein by reference in its entirety. This example illustrates the formation of a block copolymer using a double emulsion droplet.

Fig. 2 shows a schematic of double emulsion droplets for the synthesis of gradient and block copolymers. A double emulsion droplet 40 is shown in Fig. 2A, including carrying fluid 49, an outer fluid 41 containing a first monomer 45, and an inner fluid 42 containing a second monomer 46. The first monomer and the second monomer may each independently be present in their respective fluids as individual monomers, and/or some of the monomers may have polymerized to form polymers, e.g., chain 53 as shown in Fig. 2.

In some cases, inner fluid 42 and outer fluid 41 may be substantially miscible. Upon formation of double emulsion droplet 40, the fluids may mix, causing first monomer 45 and second monomer 46 to become exposed to each other. Chain growth may continue, for example, by polymerization of the first and second monomers, e.g., to form a random copolymer, a block copolymer, or the like, as is shown in Fig. 2.

This example illustrates that synthesis of a copolymer (e.g., a gradient or a block copolymer) can occur by free radical polymerization. Usually, free radical

copolymerization results in a broad variety of polymer compositions including a significant amount of homopolymers. These drawbacks may be avoided, as discussed in these examples, by copolymerization within microfluidic channels. The temporal control over the reaction, the control over the flows (e.g. laminar or turbulent), and/or control of the mixing speed may be used to allow facile synthesis of copolymer compositions that are difficult or impossible to access by traditional free radical polymerization processes. Furthermore, the use of additives typically used in controlled radical polymerizations may be avoided or at least reduced, and thus costs and potential pollution of the polymeric product may be reduced. Various applications of the products may involve stabilization of emulsions, solubilization, associative thickening, promoting adhesion, improved mechanical properties, etc.

EXAMPLE 3

This example illustrates the synthesis of a diblock copolymer. In this example, the

first block is formed from a single monomer only. The second block is formed primarily of a second monomer, but can also contain the first monomer in some cases. The synthesis is a continuous process and is performed in a microfluidic device in this example.

The first block may be synthesized by polymerizing a first monomer in a single stream in a tube or channel of a certain length. The reaction solution contains monomer and initiator. Additionally, it may contain solvent or additives. Initiation can occur, for example, thermally or by exposure to UV light. Chain growth can be controlled by controlling the channel length, the solvent concentration, the flow rate, and/or the initiator concentration and/or the exposure to UV light or heat. Polymerization in single stream leads to low PDI (M_w/M_n) values, as compared to similar reactions conducted in batch. The growing polymer chains form the first block.

The second block may be synthesized by adding the second monomer to the solution that contains the growing polymer chains. The first monomer need not be completely polymerized upon addition of the second polymer. For instance, the conversion of the first monomer at point of the addition may be between 60-90% to avoid termination reactions and to form a relatively large amount of homopolymer. However, an excess of the second monomer can be added, which allows the formation of the second block. The second monomer may be added, for example, in droplets or in a stream. The final polymer can also be formed either in the same fluidic system (e.g., as droplets and/or streams), and/or in an external reaction chamber. Polymerization of the second monomer may occur in a stream, or in droplets. A double-emulsion device (e.g. glass or PDMS) may be used in some cases to control the composition of the polymer. In the droplets further, chain growth occurs by reaction of the second monomer with the growing chains formed by the first monomer.

Such techniques may lead to relatively low PDI values compared to reactions in batch. The size of the resulting copolymer can be controlled, for example, by controlling the channel length, the flow rates, the fluid ratio, and/or the control of flow (e.g., laminar or turbulent flow). This may occur as a continuous process.

EXAMPLE 4

As a specific example, a copolymerization reaction between n-butyl methacrylate and styrene is now demonstrated. A fluidic system similar to the one shown in Fig. 4A was used, with polymerization of the first fluids and second fluids occurring within a channel in separate streams.

This figure shows fluidic system, comprising an inlet port 1 for introducing a first fluid. In this example, more than one inlet port 1 is shown. For example, one inlet port may be used to introduce a first monomer while a second inlet port may be used to introduce a solvent, an initiator, etc. The fluids flow through channel 11 which, in this example, is shown as having a serpentine profile, e.g., to promote mixing of fluids therein. After flowing through channel 11, the fluids flow through initiator region 2, which may be used to initiate a polymerization reaction involving the first monomer. For example, ultraviolet light may be directed at initiator region 2. After initiation, polymerization occurs as the fluid flows through channel 3. At junction 14, a second fluid may be introduced via inlet ports 4 and channels 15. The first and second fluids may flow together, e.g., laminarly, through channel 5 to exit port 8. In this example, channel 5 is shown as having a serpentine profile, e.g., to promote mixing and/or reaction of the fluids and/or the monomers therein, e.g., to facilitate formation of a copolymer.

In this experiment, the irradiation time was 2 min and the reaction time was 32 min. The resulting copolymer was found to have a M_n of 12,882 g/mol and a M_w of 21,200 g/mol, for a PDI (M_w/M_n) of 1.65. The conversion was found to be 40%.

EXAMPLE 5 As another example, a copolymerization reaction between styrene and pBMA is demonstrated in droplets, using a fluidic system similar to the one shown in Fig. 4B. This embodiment is similar to Fig. 4A; however, in this figure, a carrying fluid is introduced through inlet ports 24 and channels 25 towards junction 22. At junction 22, the first fluid and the second fluid form droplets contained by the carrying fluid. The droplets and the carrying fluid then proceed through channel 5 towards exit port 8.

The carrying fluid was 10% PVA in water, the outer fluid contained styrene, and the inner fluid contained pBMA (poly(butyl methacrylate)). Flowrates used were 6,000 microliters/h for the carrying fluid, 1,500 microliters/h for the outer fluid, and 500 microliters/h for the inner fluid. The resulting copolymer was found to have a M_n of

166,559 g/mol, a M_w of 243,472 g/mol, and a PDI (M_w/M_n) of 1.46, with a yield of 25%.

EXAMPLE 6

This non-limiting example illustrates a device useful for producing polymers in accordance with some embodiments of the invention.

Materials. The monomers and PVA (polyvinyl alcohol) were purchased from

Sigma- Aldrich, and filtered through a basic alumina column to remove radical inhibitor. Darocure 1173 (BASF), Irgacure 2959 (BASF), 2,2-azobis(isobutylronitrile) (AIBN) (Aldrich) are used as obtained. Argon gas was bubbled through all monomers and solvents for 45 minutes before use.

Glass devices. The microfluidic double emulsion devices were formed of four

Teflon tubes (three inlets, one outlet), three glass capillaries (two glass (OD: 1.0 mm), one square (OD: 1.5 mm, ID: 1.05 mm)), and three needles. The device was fabricated by inserting the glass capillaries into the square capillary and adjusting one needle two the end of inner phase capillary and the other needles to the interconnections of the glass capillaries and the square capillary, followed by sealing with epoxy adhesive. The total length of the device was about 6 inches (15.2 cm). The three phases— carrying aqueous phase, outer, and inner organic phases— were infused at independently adjustable flow rates by syringe pumps. The inner phase contained the growing polymer chains of the first monomer and a certain amount of appropriate solvent. The outer phase contained the second monomer and a certain amount of appropriate solvent. Usually, an aqueous 10 wt% PVA solution was used as the continuous or carrying phase. The initiation of chain growth occurred in a separate capillary (OD: 1.0 mm). FEP (fluorinated ethylene propylene) devices. The FEP devices were produced either using a laser engraving system or by hot embossing. Hot embossing of

commercial FEP plates (thickness: 3/32 inches, or 2.4 mm) against PDMS

(polydimethylsiloxiane) masters was conducted under pressure at 214 °C. First, the FEP plate and the PDMS master were placed between two pieces of 5 mm thick alumina plates. The stack was fixed with four C-clamps and kept in a 214 °C oven for 30 min. Second, two FEP substrates were placed between two pieces of 5 mm thick alumina plates and the entire stack was fixed with four C-clamps. Then the whole stack was placed into a 204 °C oven. After bonding for 1 hour, the system was allowed to cool down to room temperature, and Teflon tubes were connected to the device for inlets and outlets. Typically, the dimensions of such a device were 3 inches x 2 inches (7.62 cm x 5.08 cm).

Laser engraving of commercial FEP plates (thickness: 3/32 inches, or 2.4 mm) was performed using a VersaLaser cutting/engraving system. First, microstructures were cut into the FEP plates using a HPDFO (High-Power Density- Focusing Optics) lens. Second, two FEP substrates were placed between two pieces of 5 mm thick alumina plates and the entire stack fixed with four C-clamps. Then, the whole stack was placed into a 204 °C oven. After bonding for 1 hour, the system was allowed to cool down to room temperature, and Teflon tubes were connected to the device for inlets and outlets. Typically, the dimensions of such a device were 3 inches x 2 inches (7.62 cm x 5.08 cm).

Usually, the channel width and depth in the device were about 25 to 500 micrometers. Such devices are used either as drop-makers or for reactions in laminar flow. Such devices exhibited chemical robustness and the thermal stability up to 204 °C. The employed phases were infused at independently adjustable flow rates by syringe pumps.

General procedure for copolymerization in microfluidic devices at room temperature. Since polymerization rates were relatively low for most monomers at room temperature, initiation of chain growth occured before injection of the phase containing the growing polymer chains into the microfluidic device. Therefore, a single glass capillary was used. Teflon tubes were connected to the capillary's inlet and outlet. In the capillary, the solution was exposed to UV-irradiation (OmniCure, Series 1000, Mercury ARC, 100 W, wavelength of 320-500 nm) for time intervals varying from 30 s to 4 min. The outlet tube was connected to the microfluidic device used for

copolymerization as inlet tube. In addition to the initiator concentration, the tube length and flow rates were used to determine the percentage of conversion of the monomers.

General procedure for copolymerization in microfluidic devices at elevated temperatures. A solution containing monomer, initiator, and solvent was introduced to a microreactor (stainless steel tube, OD: 0.25 inches (0.64 cm), length: 10 feet (3.0 m), wall thickness: 0.035 inches (0.89 mm)) heated at the desired temperature (e.g. 80 °C for AIBN as the initiator), where the polymerization of the first monomer takes place. Also, the phase containing the second monomer was heated in a micro-reactor (stainless tube, 0.25 inches (0.64 cm), length: 5 feet (1.5 m), wall thickness: 0.035 inches (0.89 mm)) to the same temperature as the first solution. The same procedure was followed if further phases were employed (e.g. continuous). Consecutively, these solutions were injected into a microfluidic device (glass capillary or FEP), in which the copolymerization takes place. Optionally, tubing or a further micro-reactor could be attached to the device outlet.

EXAMPLE 7

This example illustrates the production of a copolymer in accordance with one embodiment of the invention. The copolymerization reaction occurred at room temperature.

In this example, a microfluidic double emulsion device similar to the one described in Example 6 was used. The carrying phase here was PVA (10 wt in water), fed at a flow rate of 6000 microliter s/h. The outer phase was n-butyl methacrylate with a flow rate of 1500 microliter s/h. The inner phase contained styrene (6 mL/h), toluene (0.6 mL/h), and Darocur 1173 (1.2 mL/h). The irradiation time in the capillary was 2.5 minutes. The length of the outlet tubing was 150 cm. This produced a polymer having a M_n of 89 kDa and a M_w = 106.2 kDa, for a PDI (M_w/M_n) of 1.19.

EXAMPLE 8

This example illustrates the synthesis of polystyrene-block-poly(butyl methacrylate (pST-b-pBMA), in accordance with yet another embodiment of the invention, using copolymerization in a glass device at an elevated temperature.

The microfluidic double emulsion devices were formed of four Teflon tubes (three inlets, one outlet), three glass capillaries (two glass (OD: 1.0 mm), one square (OD: 1.5 mm, ID: 1.05 mm)), and three needles. The device was fabricated by inserting the glass capillaries into the square capillary and adjusting one needle two the end of inner phase capillary and the other needles to the interconnections of the glass capillaries and the square capillary, followed by sealing with epoxy adhesive. The total length of the device was about 6 inches (15.2 cm). The three phases— carrying aqueous phase, outer, and inner organic phases— were infused at independently adjustable flow rates by syringe pumps. The inner phase contained the growing polymer chains of the first monomer and a certain amount of appropriate solvent. The outer phase contained the second monomer and a certain amount of appropriate solvent. Usually, an aqueous 10 wt% PVA solution was used as the continuous or carrying phase. The initiation of chain growth occurs in the inlet tubing of the inner phase. This tubing was kept at 86 °C using an oil bath.

The carrying fluid was PVA (10 wt% in water) with a flow rate of 10000 microliter s/h. The outer phase comprised 5 ml of n-butyl methacrylate and 5 ml of toluene at a flow rate of 2000 microliter s/h. The inner phase comprised 5 ml of styrene, 10 ml of toluene, and 75 mg of AIBN (2,2-azobis(isobutylronitrile)) at a flow rate of 1000 microliters/h. The polymerization time in tubing for the first block, at 86 °C, was 14 min. The length of outlet tubing was 150 cm.

The first block of the block copolymer (i.e., the polystyrene portion) was found to have a M_n of about 14 kDa, a M_w of about 16 kDa, and a PDI (M_w/M_n) of 1.15 with a conversion of 20%. The entire block copolymer (i.e., pSt-b-pBMA) was found to have a M_n of 44 kDa, an M_w of 66 kDa, a PDI (M_w/M_n) of 1.50, with a yield of 15%.

While several embodiments of the present invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the functions and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the present invention. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, article, material, kit, and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and/or methods, if such features, systems, articles, materials, kits, and/or methods are not mutually inconsistent, is included within the scope of the present invention.

All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and/or ordinary meanings of the defined terms.

The indefinite articles "a" and "an," as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean "at least one."

The phrase "and/or," as used herein in the specification and in the claims, should be understood to mean "either or both" of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases.

Multiple elements listed with "and/or" should be construed in the same fashion, i.e., "one or more" of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the "and/or" clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to "A and/or B", when used in conjunction with open-ended language such as "comprising" can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

As used herein in the specification and in the claims, "or" should be understood to have the same meaning as "and/or" as defined above. For example, when separating items in a list, "or" or "and/or" shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as "only one of or "exactly one of," or, when used in the claims, "consisting of," will refer to the inclusion of exactly one element of a number or list of elements. In general, the term "or" as used herein shall only be interpreted as indicating exclusive alternatives (i.e. "one or the other but not both") when preceded by terms of exclusivity, such as

"either," "one of," "only one of," or "exactly one of." "Consisting essentially of," when used in the claims, shall have its ordinary meaning as used in the field of patent law.

As used herein in the specification and in the claims, the phrase "at least one," in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase "at least one" refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, "at least one of A and B" (or, equivalently, "at least one of A or B," or, equivalently "at least one of A and/or B") can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.

It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited.

In the claims, as well as in the specification above, all transitional phrases such as "comprising," "including," "carrying," "having," "containing," "involving," "holding," "composed of," and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases "consisting of and

"consisting essentially of shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.

What is claimed is:

Claims

1. A method of producing a block copolymer comprising at least a first block and a second block, the method comprising:

producing the first block of the block copolymer by flowing a first monomer in a microfluidic channel, and causing at least some of the first monomer to polymerize to form the first block; and

producing the second block of the block copolymer by creating droplets containing the first block and a second monomer, and causing polymerization of the second monomer to form the second block of the block copolymer.

2. The method of claim 1, wherein at least about 20% of monomers forming the second block are the second monomer. 3. The method of any one of claims 1 or 2, wherein at least about 50% of monomers forming the second block are the second monomer.

4. The method of any one of claims 1-3, wherein at least about 90% of monomers forming the second block are the second monomer.

5. The method of any one of claims 1-4, wherein the second block comprises a gradient of the first monomer and the second monomer.

6. The method of any one of claims 1-5, wherein the block copolymer has a

polydispersity index of less than about 2.

7. The method of any one of claims 1-6, wherein polymerization of the first

monomer to form the first block comprises a free radical polymerization reaction. 8. The method of any one of claims 1-7, wherein polymerization of the second

monomer to form the second block comprises a free radical polymerization reaction.

9. The method of any one of claims 1-8, wherein polymerization of the first monomer to form the first block comprises a living polymerization reaction.

The method of any one of claims 1-9, wherein polymerization of the second monomer to form the second block comprises a controlled polymerization reaction.

The method of any one of claims 1-10, wherein polymerization of the second monomer to form the second block comprises a living polymerization reaction.

12. The method of claim 11, wherein the living polymerization reaction comprises an ATRP reaction. 13. The method of any one of claims 11 or 12, wherein the living polymerization reaction comprises an RAFT reaction.

14. The method of any one of claims 11-13, wherein the living polymerization

reaction comprises an TEMPO reaction.

15. The method of any one of claims 11-14, wherein the living polymerization

reaction comprises an NMP reaction.

16. The method of any one of claims 1-15, wherein the act of producing the first block of the block copolymer comprises exposing at least some of the first monomer to an initiator.

17. The method of claim 16, wherein the initiator comprises ultraviolet light. 18. The method of any one of claims 16 or 17, wherein the initiator comprises heat. The method of any one of claims 16-18, wherein the initiator comprises a radical initiator.

The method of any one of claims 16-19, wherein the first monomer is exposed to the initiator for no more than about 5 minutes.

The method of any one of claims 16-20, wherein the first monomer is exposed to a temperature of at least about 25 °C.

The method of any one of claims 16-21, wherein the first monomer is exposed to a temperature of at least about 40 °C.

The method of any one of claims 16-22, wherein the first monomer is exposed a temperature of between about 20 °C and about 50 °C.

The method of any one of claims 16-23, further comprising flowing the first monomer through the microfluidic channel for at least about 5 minutes after the exposure to the initiator and prior to the creation of droplets.

The method of any one of claims 1-24, wherein the flow in the microfluidic channel during polymerization of the first monomer to form the first block is laminar.

The method of any one of claims 1-25, wherein the flow in the microfluidic channel during polymerization of the first monomer to form the first block is turbulent.

27. The method of any one of claims 1-26, wherein the flow in the microfluidic channel during polymerization of the second monomer to form the second block is laminar. The method of any one of claims 1-27, wherein the flow in the microfluidic channel during polymerization of the second monomer to form the second block is turbulent.

The method of any one of claims 1-28, wherein less than about 90% of the first monomer has polymerized upon the creation of droplets.

The method of any one of claim 1-29, wherein at least about 60% of the first monomer has polymerized upon the creation of droplets.

The method of any one of claims 1-30, wherein at least about 90% of monomers forming the first block are the first monomer.

The method of any one of claims 1-31, wherein, when the droplets are created, the second monomer has a concentration within the droplets that is at least 5 times greater than a concentration of the first monomer within the droplets.

The method of any one of claims 1-32, wherein the droplets are created at a flow focusing junction.

The method of any one of claims 1-33, wherein the droplets are created at a T- junction.

The method of any one of claims 1-34, wherein the droplets are created at a coaxial junction.

The method of any one of claims 1-35, wherein the droplets comprise at least a first fluid containing the first block and a second fluid containing the second monomer.

The method of claim 36, wherein the first fluid is substantially immiscible with the second fluid.

38. The method of claim 36, wherein the first fluid is substantially miscible with the second fluid. 39. The method of any one of claims 36-38, wherein the first fluid is present within the droplet as an inner droplet.

40. The method of any one of claims 36-39, wherein the second fluid is present within the droplet as an inner droplet.

41. The method of any one of claims 36-40, wherein the droplets comprising the first fluid and the second fluid are contained within a third fluid.

42. The method of claim 41, wherein at least some of the droplets are formed from the second fluid, and contain therein an inner droplet formed from the first fluid.

43. The method of any one of claims 41 or 42, wherein at least some of the droplets are formed from the first fluid, and contain therein an inner droplet formed from the second fluid.

44. The method of any one of claims 1-43, wherein the second block comprises at least some of the first monomer.

45. The method of any one of claims 1-44, wherein at least about 30% of the first monomer is present in the block copolymer.

46. The method of any one of claims 1-45, wherein at least about 30% of the second monomer is present in the block copolymer. 47. The method of any one of claims 1-46, wherein the block copolymer is formed in a time of at least about 15 minutes. The method of any one of claims 1-47, wherein the block copolymer comprises at least the first block, the second block, and a third block, and wherein the method further comprises:

producing the third block of the block copolymer by fusing droplets containing the first block and the second block of the block copolymer with droplets containing a third monomer, and causing polymerization of the third monomer to form the third block of the block copolymer.

The method of any one of claims 1-48, further comprising separating at least some of the block copolymer from unreacted first monomer and/or unreacted second monomer.

The method of claim 49, comprising passing fluid containing the block copolymer through a filter.

The method of claim 50, wherein the filter comprises an ultrafiltration membrane.

A method of producing a block copolymer comprising at least a first block and a second block, the method comprising:

producing the first block of the block copolymer by flowing a first monomer in a first microfluidic channel, and causing at least some of the first monomer to polymerize to form the first block; and

producing the second block of the block copolymer by flowing the first block and a second monomer in a second microfluidic channel, and causing polymerization of the second monomer to form the second block of the block copolymer.

The method of claim 52, wherein the second microfluidic channel is an extension of the first microfluidic channel. The method of any one of claims 52 or 53, comprising creating droplets within the second microfluidic channel, wherein the droplets contain the first block and the second monomer. 55. The method of any one of claims 52-54, wherein the block copolymer has a

polydispersity index of less than about 2.

The method of any one of claims 52-55, wherein the second block comprises a gradient of the first monomer and the second monomer.

The method of any one of claims 52-56, wherein at least about 60% of the first monomer has polymerized upon entry of the first monomer in the second microfluidic channel.

The method of any one of claims 52-57, wherein upon entry of the first monomer in the second microfluidic channel, the second monomer has a concentration that is at least 5 times greater than a concentration of the first monomer.

The method of any one of claims 52-58, wherein the second microfluidic channel comprises at least a first fluid containing the first block and a second fluid containing the second monomer.

The method of any one of claims 52-59, further comprising separating at least some of the block copolymer from unreacted first monomer and/or unreacted second monomer.

61. The method of any one of claims 52-60, wherein the block copolymer comprises at least the first block, the second block, and a third block, and wherein the method further comprises:

producing the third block of the block copolymer by flowing the first block, the second block, and a third monomer in a third microfluidic channel, and causing polymerization of the third monomer to form the third block of the block copolymer.

A method of producing a copolymer, the method comprising:

forming a multiple emulsion droplet comprising an inner fluid, a middle fluid surrounding the inner fluid, and an outer fluid surrounding the middle fluid, wherein the inner fluid comprises a first monomer and the middle fluid comprises a second monomer, the inner fluid and the middle fluid being substantially miscible; and

polymerizing the first monomer and the second monomer to form a copolymer.

The method of claim 62, wherein the middle fluid and the outer fluid are substantially immiscible.

The method of any one of claims 62 or 63, wherein the middle fluid and the inner fluid are substantially immiscible.

The method of any one of claims 62-64, wherein polymerizing the first monomer and the second monomer comprises exposing the first monomer and/or the second monomer to an initiator.

66. The method of any one of claims 62-65, further comprising flowing the multiple emulsion droplet through a microfluidic channel.

67. The method of any one of claims 62-66, wherein the inner fluid further comprises a third monomer, and the method comprises polymerizing the first monomer, the second monomer, and the third monomer to form a copolymer. 68. The method of any one of claims 62-67, wherein the middle fluid further

comprises a third monomer, and the method comprises polymerizing the first monomer, the second monomer, and the third monomer to form a copolymer. The method of any one of claims 62-68, wherein the copolymer is a random copolymer.

The method of any one of claims 62-68, wherein the copolymer is a block copolymer.

71. The method of any one of claims 62-68, wherein the copolymer is a gradient copolymer.

72. The method of any one of claims 62-68, wherein the copolymer is a star

copolymer.

73. The method of any one of claims 62-68, wherein the copolymer is a graft

copolymer.

74. The method of any one of claims 62-68, wherein the copolymer is a branched copolymer.

producing the first block of the block copolymer by flowing a first monomer in a first microfluidic channel, and causing at least some of the first monomer to polymerize to form the first block;

producing the second block of the block copolymer by flowing a second monomer in a second microfluidic channel, and causing at least some of the second monomer to polymerize to form the second block;

forming a multiple emulsion droplet comprising an inner fluid, a middle fluid surrounding the inner fluid, and an outer fluid surrounding the middle fluid, wherein the inner fluid comprises the first block and the middle fluid comprises the second block; and polymerizing the first block and the second block to form the block copolymer.

76. The method of claim 75, wherein the second microfluidic channel is an extension of the first microfluidic channel.

77. The method of any one of claims 75 or 76, wherein the first microfluidic channel and the second microfluidic channel intersect at a junction. 78. The method of claim 77, wherein the junction is a flow-focusing junction.

79. The method of claim 77, wherein the junction is a coaxial junction.

80. A method of producing a block copolymer comprising at least a first block and a second block, the method comprising:

producing the first block of the block copolymer by flowing a first monomer and/or macromonomer in a microfluidic channel, and causing at least some of the first monomer and/or macromonomer to polymerize to form the first block; and

producing the second block of the block copolymer by creating droplets containing the first block and a second monomer and/or macromonomer, and causing polymerization of the second monomer and/or macromonomer to form the second block of the block copolymer. 81. A method of producing a block copolymer comprising at least a first block and a second block, the method comprising:

producing the first block of the block copolymer by flowing a first monomer and/or macromonomer in a first microfluidic channel, and causing at least some of the first monomer and/or macromonomer to polymerize to form the first block; and

producing the second block of the block copolymer by flowing the first block and a second monomer and/or macromonomer in a second microfluidic channel, and causing polymerization of the second monomer and/or

macromonomer to form the second block of the block copolymer.

A method of producing a copolymer, the method comprising:

forming a multiple emulsion droplet comprising an inner fluid, a middle fluid surrounding the inner fluid, and an outer fluid surrounding the middle fluid, wherein the inner fluid comprises a first monomer and/or macromonomer and the middle fluid comprises a second monomer and/or macromonomer, the inner fluid and the middle fluid being substantially miscible; and

polymerizing the first monomer and/or macromonomer, and the second monomer and/or macromonomer, to form a copolymer.

producing the first block of the block copolymer by flowing a first monomer and/or macromonomer in a first microfluidic channel, and causing at least some of the first monomer and/or macromonomer to polymerize to form the first block;

producing the second block of the block copolymer by flowing a second monomer and/or macromonomer in a second microfluidic channel, and causing at least some of the second monomer and/or macromonomer to polymerize to form the second block;

forming a multiple emulsion droplet comprising an inner fluid, a middle fluid surrounding the inner fluid, and an outer fluid surrounding the middle fluid, wherein the inner fluid comprises the first block and the middle fluid comprises the second block; and

polymerizing the first block and the second block to form the block copolymer.

A method of producing a copolymer comprising at least a first monomer and a second monomer, the method comprising:

creating droplets containing at least a first monomer and a second monomer; and

polymerizing the first monomer and the second monomer within the droplets to form the copolymer, wherein the copolymer is a star copolymer, graft copolymer, a branched copolymer, and/or a gradient copolymer.

The method of claim 84, wherein the droplets are microfhiidic droplets.

The method of any one of claims 84 or 85, wherein the droplets comprise an inner fluid and a middle fluid.

The method of claim 86, wherein the inner fluid comprises the first monomer and the middle fluid comprises the second monomer.

The method of any one of claims 84-87, wherein polymerizing the first monomer and the second monomer comprises exposing the first monomer and/or the second monomer to an initator.

The method of any one of claims 84-88, further comprising flowing the droplets through a microfhiidic channel.

A method of producing a copolymer comprising at least a first portion and a second portion, the method comprising:

producing the first portion of the copolymer by flowing a first monomer and/or macromonomer in a microfhiidic channel, and causing at least some of the first monomer and/or macromonomer to polymerize to form the first portion; and producing the second portion of the copolymer by creating droplets containing the first portion and a second monomer and/or macromonomer, and causing polymerization of the second monomer and/or macromonomer to form the second portion of the copolymer.

The method of claim 90, wherein the copolymer is a block copolymer.

92. The method of claim 90, wherein the copolymer is a gradient copolymer.

93. The method of claim 90, wherein the copolymer is a star copolymer. 94. The method of claim 90, wherein the copolymer is a graft copolymer.

95. The method of claim 90, wherein the copolymer is a branched copolymer.

96. A method of producing a copolymer comprising at least a first portion and a second portion, the method comprising:

producing the first portion of the copolymer by flowing a first monomer and/or macromonomer in a first microfluidic channel, and causing at least some of the first monomer and/or macromonomer to polymerize to form the first portion; and

producing the second portion of the copolymer by flowing the first portion and a second monomer and/or macromonomer in a second microfluidic channel, and causing polymerization of the second monomer and/or

macromonomer to form the second portion of the copolymer. 97. A method of producing a copolymer comprising at least a first portion and a second portion, the method comprising:

producing the first portion of the copolymer by flowing a first monomer and/or macromonomer in a first microfluidic channel, and causing at least some of the first monomer and/or macromonomer to polymerize to form the first portion;

producing the second portion of the copolymer by flowing a second monomer and/or macromonomer in a second microfluidic channel, and causing at least some of the second monomer and/or macromonomer to polymerize to form the second portion;

forming a multiple emulsion droplet comprising an inner fluid, a middle fluid surrounding the inner fluid, and an outer fluid surrounding the middle fluid, wherein the inner fluid comprises the first portion and the middle fluid comprises the second portion; and

polymerizing the first portion and the second portion to form the copolymer.