Continuous flow chemistry process for manufacture of spherical polymer beads

Abstract

A method of forming spherical polymer beads for use in chromatography applications includes preparing an organic phase comprising a monomer and a polymerization initiator, mixing the organic phase with an aqueous phase to form a coarse emulsion, pumping the coarse emulsion through an emulsification chamber, which is a microfluidizer, to produce a stable microemulsion comprising emulsion microdroplets of a defined size, and polymerizing the organic phase particles to form the spherical polymer beads.

Description

[0001]

[0002] CONTINUOUS FLOW CHEMISTRY PROCESS FOR MANUFACTURE OF SPHERICAL POLYMER BEADS

[0003] CROSS-REFERENCE TO RELATED APPLICATION(S)

[0004] This application claims the benefit of U.S. Provisional Application No. 63 / 695,596, filed September 17, 2024, and entitled “CONTINUOUS FLOW CHEMISTRY PROCESS FOR MANUFACTURE OF SPHERICAL POLYMER BEADS,” the disclosure of which is hereby incorporated by reference in its entirety.

[0005] BACKGROUND

[0006] The present disclosure is related generally to the manufacture of spherical polymer beads for various scientific, medical, and industrial applications and, more particularly, to the production of polymer beads having particle sizes within a narrow distribution range to reduce waste.

[0007] Polymer beads are micron-sized polymer particles commonly used in column packings for chromatography applications. Chromatography applications generally require polymer beads of uniform size with variations in diameter no greater than 15 to 30 microns. Current manufacturing methods often include batch emulsion processes in which a monomer microemulsion is formed using high shear mixing with a rotor / stator homogenizer. This process produces polymer beads having a broad particle size distribution (e.g., diameters ranging from 10-180 microns). The polymer beads are classified by size to remove those having diameters outside of a desired range. In some batch emulsion polymerization processes, the yield can be as low as 30%. In addition to low yield, the batch emulsification process using conventional rotor / stator homogenizers is slow, which can result in insufficient manufacturing capacity.

[0008] New manufacturing processes are needed to produce polymer beads of uniform size with reduced waste and with increased manufacturing throughput.

[0009] SUMMARY

[0010] A method of forming spherical polymer beads for use in chromatography applications includes preparing an organic phase comprising a monomer and a polymerization initiator, mixing the organic phase with an aqueous phase to form a coarse emulsion, pumping the coarse emulsion through an emulsification chamber, which is a microfluidizer, to produce a stable microemulsion comprising emulsion microdroplets of a defined size, and polymerizing the organic phase particles to form the spherical polymer beads. A system for forming spherical polymer beads for use in chromatography applications includes a source of an organic phase, the organic phase comprising a monomer and a polymerization initiator, an aqueous phase premix vessel in fluid communication with the source of the organic phase, the aqueous phase premix vessel configured to mix the organic phase and an aqueous phase to form a coarse emulsion, a pump in fluid communication with the aqueous phase premix vessel and configured to receive the coarse emulsion, an emulsification chamber in fluid communication with an outlet of the pump and configured to convert the coarse emulsion into a stable microemulsion comprising emulsion microdroplets of a defined size, and a polymerization reactor in fluid communication with an outlet of the emulsification chamber. The emulsification chamber is a microfluidizer. The polymerization reactor is configured to polymerize the emulsion microdroplets of the microemulsion to form the spherical polymer beads.

[0011] The present summary is provided only by way of example, and not limitation. Other aspects of the present disclosure will be appreciated in view of the entirety of the present disclosure, including the entire text, claims and accompanying figures.

[0012] BRIEF DESCRIPTION OF THE DRAWINGS

[0013] FIG. 1 is a schematic diagram of a system for forming spherical polymer beads.

[0014] FIG. 2 is a flowchart of a method for forming spherical polymer beads.

[0015] While the above-identified figure sets forth an embodiment of the present invention, other embodiments are also contemplated, as noted in the discussion. In all cases, this disclosure presents the invention by way of representation and not limitation. It should be understood that numerous other modifications and embodiments can be devised by those skilled in the art, which fall within the scope and spirit of the principles of the invention. The figures may not be drawn to scale, and applications and embodiments of the present invention may include features, steps and / or components not specifically shown in the drawings.

[0016] DETAILED DESCRIPTION

[0017] FIG. 1 is a schematic diagram of system 10 for forming spherical polymer beads. System 10 can produce polymer beads of a desired size and within a narrow particle size distribution without the need for particle size classification. For example, system 10 can be used to produce polymer beads having a particle size distribution D90 / D10 equal to or less than 1.5 and, in some examples, lower than 1.3, where D90 is the particle diameter below which 90% of the particles fall and DIO is the particle diameter below which 10% of the particles fall. This is in contrast to prior art emulsion polymerization processes using conventional rotor / stator homogenizers, which can have particle size distributions D90 / D10 of greater than 2, which can be unacceptable for chromatography applications absent particle size classification. System 10 can be configured as a continuous flow chemistry process that can provide continuous and high manufacturing throughput.

[0018] System 10 can include organic phase source 12, aqueous phase premix vessel 14, pump 16, emulsification chamber 18, polymerization reactor 20, and wash / dry system 22. Organic phase source 12, aqueous phase premix vessel 14, emulsification chamber 18, polymerization reactor 20, and wash / dry system 22 can be arranged in flow series. In some examples, wash / dry system 22 can be excluded from system 10 or features of wash / dry system 22 can be included in polymerization reactor 20 as described further herein. Aqueous phase premix vessel 14 can be fluidly connected to organic phase source 12 and configured to receive an organic phase from organic phase source 12. Pump 16 can be fluidly connected to an outlet of aqueous phase premix vessel 14 and fluidly connected to an inlet of emulsification chamber 18. Polymerization reactor 20 can be fluidly connected to an outlet of emulsification chamber 18. Wash / dry system 22 can be fluidly connected to an outlet of polymerization reactor 20. Various fluid lines (not shown) can be included to provide fluid communication between organic phase source 12, aqueous phase premix vessel 14, pump 16, emulsification chamber 18, polymerization reactor 20, and wash / dry system 22. Various valves (not shown) can be included in some embodiments to control fluid flow between components.

[0019] Organic phase source 12 can be a premix vessel configured to receive and mix organic phase constituents 24. Organic phase source 12 can include mixer 26 configured to mix organic phase constituents 24 to produce organic phase 28. Mixer 26 can be, for example, a motor-driven mechanical mixer. Organic phase constituents 24 include one or more monomers and a polymerization initiator. Monomers can include, for example, styrene and divinylbenzene. The polymerization initiator can include, for example, azobisisobutyronitrile (AIBN) or benzoyl peroxide. In some embodiments, the organic phase can include a porogen to form porous polymer beads. Porogens can include, for example, low molecular weight organic compounds such as toluene and dodecane. Organic phase constituents 24 can be loaded in the premix vessel by vacuum, pump, or any other suitable transfer mechanism. Concentrations of each of the organic phase constituents 24 can be selected to provide polymer beads having desired characteristics (e.g., total surface area, pore structure, pore size, etc.). The premix vessel volume of organic phase source 12 can be selected based on a desired production capacity of system 10. The amount of polymer beads produced in a single operation can be determined by the volume of organic phase 28 available in organic phase source 12 as described further herein.

[0020] Organic phase 28 can be transferred from organic phase source 12 to aqueous phase premix vessel 14 to initiate synthesis of the polymer beads. Aqueous phase premix vessel 14 can be fluidly connected to organic phase source 12 by fluid line indicated by the organic phase 28 flow arrow. The organic phase fluid line can be any suitable piping or tubing configured to deliver the organic phase from an outlet of organic phase source 12 to an inlet of aqueous phase premix vessel 14.

[0021] Organic phase 28 is mixed with an aqueous phase 30 in aqueous phase premix vessel 14 to form a coarse emulsion 34. Aqueous phase constituents 31 can be loaded into aqueous phase premix vessel 14 through a charging port or other suitable transfer mechanism. Aqueous phase constituents 31 can include deionized water, an emulsion stabilizer, and a surfactant. Emulsion stabilizers can include, for example, salts, such as sodium phosphate and calcium chloride. Surfactants can include, for example, Aerosol®. Aqueous phase constituents 31 can be provided to aqueous phase premix vessel 14 and mixed prior to delivery of organic phase 28. A volume ratio of aqueous phase 30 to organic phase 28 in aqueous phase premix vessel 14 can be selected to provide a stable emulsion. Coarse emulsion 34 can comprise, for example, up to 50% by volume organic phase 28. In some non-limiting embodiments, a ratio of aqueous phase 30 to organic phase 28 by volume can be within a range of 5:1 to 5:2. The ratio of aqueous phase 30 to organic phase 28 can vary based on the chemical compositions of organic phase 28 and aqueous phase 30 (e.g., monomer, surfactant, porogen, etc.).

[0022] Aqueous phase premix vessel 14 includes mixer 32 configured to mix aqueous and organic phases to form coarse emulsion 34. Mixer 32 can be, for example, a motor-driven mechanical mixer. Coarse emulsion 34 includes emulsion droplets 35, comprising organic phase 28, dispersed in a continuous aqueous phase 30. Emulsion droplets 35 can have a broad particle size distribution with particle diameters exceeding 100 microns. Mixing can be provided for a defined period of time after organic phase 28 and aqueous phase 30 are added to aqueous phase premix vessel 14. In a non-limiting example, coarse emulsion 34 can be formed via mixing organic phase 28 and aqueous phase 30 for 5-10 minutes, however, mixing time may be increased based on the selection of organic phase constituents 24 and aqueous phase constituents 31. It is not necessary that the particle size distribution be narrowed prior to entering emulsification chamber 18. Once coarse emulsion 34 is formed, mixing can be discontinued provided coarse emulsion 34 is stable for the duration of the polymer bead production process.

[0023] Aqueous phase premix vessel 14 is fluidly connected to emulsification chamber 18 via pump 16. Coarse emulsion 34 can be pumped from aqueous phase premix vessel 14 to emulsification chamber 18 by pump 16. Aqueous phase premix vessel 14 can be fluidly connected to pump 16 via a fluid line generally indicated by the coarse emulsion 34 flow arrow between aqueous phase premix vessel 14 and pump 16. The fluid line can be any suitable piping or tubing configured to deliver coarse emulsion 34 from an outlet of aqueous phase premix vessel 14 to an inlet of pump 16. An outlet of pump 16 is fluidly connected to an inlet of emulsification chamber 18. Pump 16 can be fluidly connected to emulsification chamber 18 by fluid line generally indicated by the coarse emulsion 34 flow arrow between pump 16 and emulsification chamber 18. The fluid line can be any suitable piping or tubing configured to deliver coarse emulsion 34 from pump 16 to emulsification chamber 18 at a desired pressure or flow rate.

[0024] Pump 16 is configured to deliver coarse emulsion 34 from aqueous phase premix vessel 14 to emulsification chamber 18 with continuous flow of coarse emulsion 34 to emulsification chamber 18 at a substantially constant operating pressure and a substantially constant flow rate (i.e., with minimal pulsation). Pump 16 can be a metering pump. Emulsification chamber 18 reduces the size of the emulsion droplets forming emulsion microdroplets. The pressure and / or flow rate exiting pump 16 and entering emulsification chamber 18 can be selected to provide a desired emulsion microdroplet size and thereby polymer bead size. Generally, pressure and / or flow rate can be increased to produce smaller emulsion microdroplets and decreased to produce larger emulsion microdroplets. Operating pressures can range from 100 to 1000 psi for the application disclosed herein. The flow rate is a function of pressure.

[0025] Emulsification chamber 18 is a microfluidization device configured to convert coarse emulsion 34 to a stable microemulsion 36 having uniform emulsion microdroplet sizes with microdroplet size defined by operational parameters of pump 16 (i.e., pressure or flow rate) and the configuration of emulsification chamber 18. As used herein, “uniform emulsion microdroplet sizes” allows for a very narrow particle size distribution as discussed herein. Emulsification chamber 18 can produce emulsion microdroplets (not shown) with a very narrow particle size distribution such that downstream polymer bead particle size classification is unnecessary. Emulsification chamber 18 can produce emulsion microdroplets having diameters ranging from 2 microns to 50 microns and with a particle size distribution D90 / D10 equal to or less than 1.5 and, in some examples, lower than 1.3. Pump parameters can be selected to produce emulsion microdroplets tailored to particular polymer bead applications. For example, pump parameters can be selected to produce emulsion microdroplets with diameters ranging from 5 to 7 microns to produce polymer beads of substantially the same size, as commonly used for a non -porous polymer bead used in high-performance liquid chromatography (HPLC) columns. By adjusting the pressure or flow rate from pump 16, emulsification chamber 18 can produce, in another example, emulsion microdroplets having diameters ranging from 33 to 35 microns to produce polymer beads of substantially the same size, which are commonly used for porous polymer beads used in the manufacture of sample preparative consumables.

[0026] Emulsification chamber 18 has a tortuous internal pathway configured to reduce the size of emulsion droplets of coarse emulsion 34 by shear forces and impact. High pressure, shear forces, and collisions break down the emulsion droplets of coarse emulsion 34 into smaller emulsion microdroplets of uniform size forming a stable microemulsion comprising emulsion microdroplets of a desired size in a continuous aqueous phase. Emulsification chamber 18 can be, for example, a Y-type or Z-type microfluidizer. In a Y-type microfluidizer, two-fluid streams of coarse emulsion 34 can be introduced into separate inlets of emulsification chamber 18. The two streams can intersect at high velocities and high pressure before being delivered to a tortuous microchannel. In a Z-type microfluidizer, a single fluid stream of coarse emulsion 34 is forced into a zigzag microchannel. Emulsification chamber 18 is capable of producing a microemulsion with uniform emulsion microdroplets of a desired size, for example, a size selected within the range of 2 to 50 microns, in a single pass.

[0027] In contrast to prior art high shear mixing rotor / stator homogenizers, which are large (e.g., multiple cubic feet) and include moving parts that must be cleaned and maintained, Emulsification chamber 18 is a sealed body with no moving parts and a small footprint (e.g., multiple inches). Furthermore, emulsification chamber 18 provides continuous high-volume throughput, producing a volume of emulsion microdroplets in a fraction of the time it takes to produce the same volume using the prior art rotor / stator homogenizers (e.g., minutes vs. days). For example, in a non-limiting embodiment, emulsification chamber 18 can be used to produce one kilogram of polymer beads per minute as compared to 30 kilograms over a two-day emulsification process using a conventional rotor / stator homogenizer.

[0028] Microemulsion 36 is discharged from emulsification chamber 18 to polymerization reactor 20. An outlet of emulsification chamber 18 can be fluidly connected to an inlet of polymerization reactor 20 via a fluid line generally indicated by the microemulsion 36 flow arrow. The fluid line can be any suitable piping or tubing capable of delivering microemulsion 36 to polymerization reactor 20.

[0029] Polymerization reactor 20 can be a continuous reactor, configured to receive a continuous feed of microemulsion 36 from emulsification chamber 18 for continuous production of polymer beads. Polymerization reactor 20 can be, for example, a microfluidic reactor configured for high throughput polymerization (i.e., matching a flow rate from emulsification chamber 18) for continuous production of polymer beads. Microemulsion 36 can be passed through a network of small diameter microchannels 37 arranged in parallel and / or in series in the microfluidic reactor. In some embodiments, heat may be applied to an exterior surface of the microfluidic reactor by a heat source (e.g., hot water jacket, etc.) to initiate the polymerization reaction. In other embodiments, continuous polymerization reactor 20 may include an ultraviolet (UV) light source for photopolymerization. Polymerization reactor 20 can be sized (e.g., by varying a length of microchannels) to provide a residence time necessary to complete the polymerization process. A diameter of microchannels can be selected to improve a polymerization rate. Because the emulsion microdroplets are conveyed in small diameter microchannels 37, as opposed to a large vessel as used for batch polymerization, the residence time required for polymerization can be significantly reduced.

[0030] Polymerization can produce polymer beads having a size substantially matching the size of the emulsion microdroplets received from emulsification chamber 18. While some swelling can occur with polymerization, the volume change is generally negligible and does not impact the design (i.e., diameter of microchannels) of polymerization reactor 20.

[0031] Following polymerization, a polymer bead effluent 38 exiting polymerization reactor 20 can be transferred to wash / dry system 22 via a supply line generally indicated by the polymer bead effluent 38 flow arrow. The supply line can be any suitable transport tubing or mechanism capable of transferring polymer bead effluent 38 from polymerization reactor 20 to wash / dry system 22. Polymer bead effluent 38 contains polymer beads 40 and waste materials as described further herein. Wash / dry system 22 can be configured to receive a continuous stream of polymer bead effluent 38 from polymerization reactor 20. Wash / dry system 22 can include, for example, holding reactor 42, continuous carousel filter 44, washing solvents 46, drying gas 47, and polymer bead receptacle 48.

[0032] Holding reactor 42 can be a vessel configured to receive polymer bead effluent 38 from polymerization reactor 20 and deliver polymer bead effluent 38 to a plurality of vessels (e.g., tubes) of continuous carousel filter 44. Continuous carousel filter 44 can include a plurality of vessels or tubes configured to receive polymer bead effluent 38 from holding reactor 42, washing solvent 46, and drying gas 47. Continuous carousel filter 44 can be configured to move the tubes through a plurality of washing and drying stages. Following polymerization, washing solvents 46 can be provided to remove waste products including emulsion stabilizers (e.g., salts), surfactants, and other residual materials, including unreacted monomers, from the polymer beads. Multiple washing cycles can be conducted (e.g., as the tube moves to different stages in continuous carousel filter 44) to remove all residuals. Washing solvent 46 can include, for example, a dilute hydrochloric acid, methanol, tetrahydrofuran, and acetone.

[0033] Tubes of continuous carousel filter 44 can include a filter to collect polymer beads 40, while the washing solvent, residuals (e.g., salts, surfactants, other residuals) removed from polymer beads 40, and any remaining aqueous phase can pass through the filter for collection and disposal. In one or more stages following washing, polymer beads 40 can undergo a drying process. Polymer beads 40 can be dried with drying gas 47. For example, polymer beads 40 can be dried by supplying a heated stream of nitrogen to the tubes in continuous carousel filter 44. In other embodiments, polymer beads 40 can be dried by other suitable means, e.g., under vacuum at room temperature.

[0034] Once dried, polymer beads 40 can be collected in polymer bead receptacle 48. Collected polymer beads 40 are ready for functionalization or further processing and packaging. Because polymer beads 40 formed using the disclosed system are of uniform size, no classification based on size is required. Polymer beads 40 can have a particle diameter substantially matching a diameter of the emulsion microdroplets in the microemulsion provided to polymerization reactor 20. While some swelling can occur with polymerization, the amount of swelling is generally considered negligible (e.g., an organic phase particle having a diameter of 30 microns may produce a polymer bead of approximately 30.5 microns). Operational parameters of pump 16 can be selected as previously described to account for particle swelling in polymerization if needed. Polymer bead size can be determined by a particle size analyzer (e.g., a Beckman Coulter Multisizer), as known in the art.

[0035] While use of polymerization reactor 20 for continuous polymerization is preferred, in alternative embodiments, polymerization can take place in a batch filter reactor, configured to combine the process of polymerization and filtration. For example, a polymerization reactor vessel can include a filter configured for use in washing polymer beads and an agitator (e.g., mechanical stirrer) configured to provide gentle agitation to the microemulsion during the polymerization process. Following polymerization, a washing solvent, as described above, can be provided to remove emulsion stabilizers (e.g., salts), surfactants, and other residual materials, including unreacted monomers, from the polymer beads. Multiple washing cycles can be conducted to remove all residuals. Polymer beads can be collected on the filter, while the washing solvent, residuals (e.g., salts, surfactants, other residuals) removed from the polymer beads, and any remaining aqueous phase can pass through the filter for collection and disposal. In some embodiments, the polymer beads can undergo a drying process in the filter reactor following washing. Polymer beads can be dried, for example, by supplying a heated stream of nitrogen to the filter reactor. In other embodiments, polymer beads can be dried by other suitable means, e.g., under vacuum at room temperature.

[0036] FIG. 2 is a flowchart of method 50 for forming polymer beads. Polymer beads can be formed according to method 50 using system 10 as described above. Method 50 includes steps 52-62.

[0037] In a first step 52, an organic phase, including one or more monomers and a polymerization initiator, is prepared. The organic phase can be prepared by mixing organic phase constituents in a vessel as described above. In some embodiments, the organic phase can additionally include a porogen and / or other materials contributing to emulsification and / or polymerization.

[0038] In step 54, an aqueous phase can be separately prepared by mixing aqueous phase constituents in a vessel as described above. The aqueous phase can include deionized water, an emulsion stabilizer, and a surfactant suitable for forming a stable emulsion.

[0039] In step 56, the organic phase is mixed with the aqueous phase to form a coarse emulsion. The organic phase can be added to the aqueous phase, for example, in aqueous phase premix vessel 14 (shown in FIG. 1). In one example, a volume of the organic phase can be provided to the aqueous phase in aqueous phase premix vessel 14 such that a ratio of aqueous phase to organic phase by volume can be within a range of 5: 1 to 5:2. The total volume of the organic phase and the aqueous phase in aqueous phase premix vessel 14 can be selected based on a desired production capacity of the system. The amount of polymer beads produced in a single operation can be determined by the volume of organic phase available in the organic phase source and mixed with the aqueous phase. Once the coarse emulsion from the premix vessel is depleted, a new batch of the coarse emulsion can be prepared and the process can be restarted.

[0040] The organic phase and aqueous phase can be mixed with a mechanical mixer in aqueous phase premix vessel 14 as described above to form the coarse emulsion with emulsion droplets of non-uniform size dispersed in a continuous aqueous phase. In one non-limiting example, a volume of 220 liters aqueous phase can be mixed with a volume of 60 liters organic phase in a 300-liter vessel with a turbine mixer operating at 200-300 rpm for about 5 minutes to about 30 minutes to form a coarse emulsion that is generally stable for at least the period of time required to form the microemulsion from the coarse emulsion. As previously described, mixing can be ceased once the coarse emulsion is formed and before pumping the coarse emulsion to the emulsification chamber. Mixing time and operational parameters of the mixer (i.e., mixing speed) can be selected based, for example, on a combined volume of the organic phase and aqueous phase. It is not necessary that mixing produce uniformly sized emulsion droplets. As previously described, the coarse emulsion can include emulsion droplets of varying sizes including diameters greater than 100 microns.

[0041] In step 58, the coarse emulsion is pumped through an emulsification chamber as described above to form a stable microemulsion having emulsion microdroplets of a desired size. As previously described, the coarse emulsion is pumped through emulsification chamber 18 (shown in FIG. 1), which is a microfluidizer configured to reduce the size of emulsion droplets in the coarse emulsion and to form emulsion microdroplets of substantially uniform size (i.e., with a particle size distribution D90 / D10 equal to or less than 1.5). The operational parameters of the pump (i.e., pressure or flow rate) can be selected to form a desired particle size. The internal arrangement of microchannels in the emulsification chamber may also be selected to provide a desired particle size, however, both Z- and Y-type microfluidizers are capable of producing emulsion microdroplets within the desired 2-micron to 50-micron diameter range. In one non-limiting embodiment, a coarse emulsion was provided to a Z-type microfluidizer at a pressure of around 250 psi and flow rate of 1 liter per minute to produce emulsion microdroplets having a diameter of 33 to 35 microns with a particle distribution D90 / D10 between 1.3 and 1.5. Similar results were observed with a Y-type microfluidizer.

[0042] In step 60, the microemulsion is provided to a polymerization reactor to polymerize the emulsion microdroplets to form polymer beads. In one example, the microemulsion can be provided to polymerization reactor 20 (shown in FIG. 1), which can be configured to receive a continuous stream of the microemulsion from the emulsification chamber such that the emulsification process is uninterrupted and continues as long as the coarse emulsion is available for delivery to the emulsification chamber. Polymerization reactor 20 can be a microfluidic reactor configured to convey the microemulsion through microchannels in the presence of heat or UV light to initiate polymerization and form polymer beads. The length, diameter, and / or arrangement of the microchannels can be selected to allow the polymerization reactor to receive a continuous stream of the microemulsion from the emulsification chamber and to provide a continuous output of polymer beads from the polymerization reactor.

[0043] In step 62, the polymer beads can be washed to remove residual materials and dried. The steps of washing and drying can be conducted in wash / dry system 22 (shown in FIG. 1) as previously described. Wash / dry system 22 can be configured to receive a continuous stream of polymer beads and remaining aqueous phase from the polymerization reactor. The polymer beads can be washed with wash solvents to remove emulsion stabilizers (e.g., salts), surfactants, and other residual materials, including unreacted monomers, from the polymer beads. Multiple washing cycles can be conducted in a continuous carousel filter to remove all residuals as previously described. The polymer beads can be retained, for example, by a filter in the washing process while the washing solvent, residuals (e.g., salts, surfactants, other residuals) removed from the polymer beads, and any remaining aqueous phase can be removed and disposed of. Once washed, the polymer beads can be dried, for example, by supplying a heated stream of nitrogen to the tubes of the continuous carousel filter as previously described. Once dried, the polymer beads can be collected in a polymer bead receptacle. Because the polymer beads collected in the receptacle are of uniform size, no size classification is necessary. The polymer beads collected can be ready for functionalization or other processing and packaging.

[0044] The disclosed the continuous flow chemistry process and system can produce polymer beads of a desired size and within a narrow particle size distribution without the need for particle size classification, which can result in significant increases in yield and reduction in waste compared to prior art emulsion polymerization processes. Furthermore, the disclosed process and system can provide significantly higher manufacturing throughput than the prior art emulsion polymerization processes to meet increasing demands in manufacturing capacity.

[0045] While the invention has been described with reference to an exemplary embodiment(s), it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment(s) disclosed, but that the invention will include all embodiments falling within the scope of the appended claims.

[0046] Any relative terms or terms of degree used herein, such as “substantially”, “essentially”, “generally”, “approximately” and the like, should be interpreted in accordance with and subject to any applicable definitions or limits expressly stated herein. In all instances, any relative terms or terms of degree used herein should be interpreted to broadly encompass any relevant disclosed embodiments as well as such ranges or variations as would be understood by a person of ordinary skill in the art in view of the entirety of the present disclosure, such as to encompass ordinary manufacturing tolerance variations, standard error of measurements, incidental alignment variations, transient alignment or shape variations induced by thermal, rotational or vibrational operational conditions, and the like. Moreover, any relative terms or terms of degree used herein should be interpreted to encompass a range that expressly includes the designated quality, characteristic, parameter or value, without variation, as if no qualifying relative term or term of degree were utilized in the given disclosure or recitation.

Claims

CLAIMS:

1. A method of forming spherical polymer beads, the method comprising: preparing an organic phase comprising a monomer and a polymerization initiator; mixing the organic phase with an aqueous phase to form a coarse emulsion; pumping the coarse emulsion through an emulsification chamber to produce a stable microemulsion comprising emulsion microdroplets of a defined size, wherein the emulsification chamber is a microfluidizer; and polymerizing the emulsion microdroplets to form the spherical polymer beads.

2. The method of claim 1, wherein the microfluidizer is configured to produce emulsion microdroplets having a uniform size with a diameter within a range of 2 to 50 microns.

3. The method of any of the preceding claims, wherein the spherical polymer beads have a particle size distribution D90 / D10 of less than 1.5.

4. The method of any of the preceding claims, wherein the spherical polymer beads have a diameter ranging from 2 to 50 microns.

5. The method of any of claims 1 to 3, wherein the spherical polymer beads have a diameter ranging from 5 to 7 microns.

6. The method of any of claims 1 to 3, wherein the spherical polymer beads have a diameter ranging from 33 to 35 microns.

7. The method of any of the preceding claims, wherein a pump provides continuous flow of the coarse emulsion to the emulsification chamber at a constant operating pressure and a constant flow rate.

8. The method of claim 7, wherein the operating pressure is within a range of 100 to 1000 psi.

9. The method of any of the preceding claims, wherein the coarse emulsion comprises up to 50% by volume of the organic phase.

10. The method of any of the preceding claims, wherein the microemulsion is provided to a polymerization reactor for polymerization of the emulsion microdroplets.

11. The method of claim 10, wherein the polymerization reactor is a continuous polymerization reactor configured to receive a continuous stream of the microemulsion from the emulsification chamber.

12. The method of claim 11, wherein the polymerization reactor is a microfluidic reactor comprising a plurality of microchannels.

13. The method of any of claims 10-12, wherein the polymerization reactor comprises a UV light or heat source for initiating polymerization of the emulsion microdroplets in the microemulsion.

14. The method of any of the preceding claims and further comprising washing the spherical polymer beads and drying the spherical polymer beads in a wash / dry system configured to receive a continuous stream of the polymer beads from the polymerization reactor.

15. A system for forming spherical polymer beads, the system comprising: a source of an organic phase, the organic phase comprising a monomer and a polymerization initiator; an aqueous phase premix vessel in fluid communication with the source of the organic phase, the aqueous phase premix vessel configured to mix the organic phase and an aqueous phase to form a coarse emulsion; a pump in fluid communication with the aqueous phase premix vessel and configured to receive the coarse emulsion; an emulsification chamber in fluid communication with an outlet of the pump and configured to convert the coarse emulsion into a stable microemulsion comprising emulsion microdroplets of a defined size, wherein the emulsification chamber is a microfluidizer; and a polymerization reactor in fluid communication with an outlet of the emulsification chamber, the polymerization reactor configured to polymerize the emulsion microdroplets of the stable microemulsion to form the spherical polymer beads.

16. The system of claim 15 , wherein the pump is configured to provide continuous flow of the coarse emulsion to the emulsification chamber at a constant operating pressure and a constant flow rate.

17. The system of any of claims 15 to 16, wherein the polymerization reactor is a continuous polymerization reactor configured to receive a continuous stream of the microemulsion from the emulsification chamber.

18. The system of any of claims 15 to 16 and further comprising a wash / dry system configured to: receive a continuous stream of the spherical polymer beads from the polymerization reactor; wash the spherical polymer beads; anddry the spherical polymer beads.

19. The system of any of claims 15 to 18, wherein the spherical polymer beads have a particle size distribution D90 / D10 of less than 1.5.

20. The system of any of claims 15 to 18, wherein the microfluidizer is configured to produce emulsion microdroplets having a uniform size with a diameter within a range of 2 to 50 microns.

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