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Applications of Polymer, Composite, and Coating Materials

From Batch to Continuous Precipitation Polymerization of Thermo-responsive Microgels Hanna J. M. Wolff, Michael Kather, Hans Breisig, Walter Richtering, Andrij Pich, and Matthias Wessling ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.8b06920 • Publication Date (Web): 28 Jun 2018 Downloaded from http://pubs.acs.org on June 30, 2018

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ACS Applied Materials & Interfaces

From Batch to Continuous Precipitation Polymerization of Thermo-responsive Microgels Hanna Wolff,†,k Michael Kather,†,‡,¶,k Hans Breisig,† Walter Richtering,§ Andrij Pich,‡,¶ and Matthias Wessling∗,† †RWTH Aachen University, AVT.CVT - Chair of Chemical Process Engineering, 52074 Aachen, Germany ‡DWI - Leibniz Institute for Interactive Materials, 52074 Aachen, Germany ¶RWTH Aachen University, ITMC - Institute of Technical and Macromolecular Chemistry, 52074 Aachen, Germany §RWTH Aachen University, IPC - Institute of Physical Chemistry, 52074 Aachen, Germany kThese authors contributed equally. E-mail: [email protected] Abstract Microgels are commonly synthesized in batch experiments yielding quantities sufficient to perform characterization experiments for physical property studies. With increasing attention on the application potential of microgels, little attention is yet payed to the question whether (a) they can be produced continuously on a larger scale, (b) whether synthetic routes can be easily transferred from batch to continuous synthesis and (c) their properties can be precisely controlled as a function of synthesis parameters under continuous flow reaction conditions. We present a new continuous synthesis process of two typical but different microgel systems. It is compared in depth their size, size distribution and temperature responsive behavior to

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microgels synthesized using batch processes, as well as the influence of premixing and surfactant. For the surfactant-free Poly(N -vinylcaprolactam) (PVCL) and Poly(N isopropylacrylamide) (PNIPAm) systems, microgels are systematically smaller, while the actual size is depending on the premixing of the reaction solutions. But by use of a surfactant, the size difference between batch and continuous preparation diminishes, resulting in equal-sized microgels. Temperature-induced swelling-deswelling of microgels synthesized under continuous flow conditions was similar to their analogues synthesized in batch polymerization process. Additionally, investigation of the internal microgel structure using static light scattering (SLS) showed no significant changes between microgels prepared under batch and continuous conditions. The work encourages synthetic concepts of sequential chemical conditions in continuous flow reactors to prepare precisely tuned new microgel systems.

1

Keywords

thermo-responsive microgel, tubular reactor, precipitation polymerization, continuous synthesis, microgel, tailored microgel size

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Introduction

Microgels are functional macromolecules exhibiting controlled swelling, adaptability to environment, high chemical functionality and stimuli-responsiveness. 1,2 This unique combination of properties in microgels was mainly the reason for intensive fundamental research as well as growing application potential in drug delivery, 3–5 catalysis, 6,7 functional coatings, 8,9 bioactive fibers, 10 optical devices, 11 electronics 2 and switchable membranes. 12 The functional properties of microgels can be influenced at the synthesis stage and are determined by the molecular structure of polymer chains, amount/distribution of cross-links and microgel surface topology. Different approaches for synthesis of microgels were developed

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in last decades including cross-linking in emulsions, 13,14 coacervation, 15 lithography 16 and precipitation polymerization. 17 Precipitation polymerization is a common method applied nowadays to synthesize temperature-responsive microgels. 18 This method is widely used for the synthesis of temperature-responsive Poly(N -isopropylacrylamide) (PNIPAm) 19 and Poly(N -vinylcaprolactam) (PVCL) 20 microgels. It offers following advantages: (a) integration of different co-monomers; 21,22 (b) controlled microgel size in a broad range (radius from 100 nm to 3 µm) by use of surfactants or amphiphilic comonomers; 23 (c) narrow particle size distribution; 24 (d) preparation of hybrid microgels by encapsulation of nanoparticles during microgel formation; 25–27 (e) microgels with different morphologies (core-shell; 28 raspberry; 29 hollow sphere; 30,31 etc.) by polymerization in batch or semibatch processes. Additionally, precipitation polymerization can be considered as a flexible, sustainable and environmentally friendly synthesis route operating at moderate temperatures in aqueous solutions. So far precipitation polymerization was employed in batch or semi-batch mode for microgel synthesis resulting in small quantities of samples (typically 50 - 300 mL). 32 To overcome the increasing demand on monodisperse, reproducible and quality controlled microgels for different applications, a scale up of the production process is necessary. Since the production volume in a batch reactor is limited by its size making it less flexible to the varying demand on microgels a continuous process is required. A tubular flow-reactor is chosen for its following advantages over continuously stirred tank reactors: a narrow range of residence time, small particle size distribution, high conversion, product uniformity and heat transfer. 33 Besides, microreactors have several advantages over conventional reactors including fast mixing, fast heat and mass transfer due to high surfaceto-volume ratio, higher safety and advanced optimization due to small volumes, precise temperature control and therefore increased yield and selectivity. 34 Hence, a tubular flowmicroreactor is investigated. In previous studies the polymerization of styrene and butyl acrylate in (mini)emulsions

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using tubular flow reactors has been investigated. 33,35–38 However, the major problems when using tubular reactors for emulsion polymerization are coalescence 36 and fouling or clogging of the reactor. 33 Furthermore, the problem of coalescence, time and energy consuming preparation of the emulsion as well as using toxic solvents for the continuous phase is circumvented in precipitation polymerization. Considering its outstanding advantages, precipitation polymerization is the most suitable process for the large-scale synthesis of microgels. 33,35,36 In the present work the continuous synthesis of PVCL and PNIPAm based microgels by precipitation polymerization under flow conditions in a tubular flow-reactor is investigated for the first time. The produced microgels are compared with microgels produced in batch processes under comparable reaction conditions.

3 3.1

Experimental Materials

N -vinylcaprolactam (VCL) (98%, Sigma-Aldrich) was purified by distillation under vacuum and recrystallized in hexane (99%, VWR). N -isopropylacrylamide (NIPAm) (98%, Acros Organics) was recrystallized in hexane (99%, VWR). 2,2’-azobis(2-methylpropioamidine) dihydrochloride (AMPA) (97%, Sigma-Aldrich), N, N 0 -methylenebis(acrylamide) (BIS) (99%, Sigma-Aldrich), hexadecyltrimethylammonium bromide (CTAB) (≥ 97%, Merck) and 4methoxyphenol (≥ 98%, Sigma-Aldrich) were used as received.

3.2

Microgel Synthesis in Batch Reactor

In the batch synthesis, deionized water (179 mL), the monomer VCL or NIPAm (15.91 mmol, 88.39 mmol/L), the cross-linker BIS (0.39 mmol, 2.17 mmol/L) and the surfactant CTAB (0.06 mmol, 0.28 mmol/L) (if any), are filled in the stirred tank batch reactor, which is kept 4


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at 70 ◦ C (cf. Table 1). In order to remove the oxygen from the reaction system, the solution is purged for 60 min with nitrogen. The initiator AMPA (0.18 mmol, 1.00 mmol/L in the reactor) dissolved in 1 mL of deoxygenated water is added, to start the polymerization. The stirrer Reynolds number is approx. 21,000 and therefore the reactor is turbulently mixed. Samples taken at different reaction times are immediately filled in a fixed volume of inhibitor solution to stop the polymerization.

3.3

Microgel Synthesis in Flow Reactor

In the continuous synthesis, two stock solutions are necessary to feed the reactor (cf. Figure 1a and 1c). One stock solution contains the monomer, cross-linker and if used surfactant. The other one contains the initiator. Stock solutions are prepared similar to batch ones, but in a higher concentration due to dilution in the reactor (cf. Table 1). Overall concentrations in the flow reactor are the same in the batch reactor. HPLC pumps (Azura P 4.1S, Knauer) feed the stock solutions to a y-connector in volume ratio from 5 to 1 monomer solution to initiator solution. If a kenix mixer is used for mixing the reaction solutions, it replaces the y-connector. After the y-connector a pressure sensor (P-31, Wika) is used to measure the pressure drop over the length of the reactor. Sudden increase of the pressure drop indicates a blocking of the reactor tube. From the pressure sensor the mixed solution is filled into the tubular reactor. Continuous polymerization takes place in a coiled stainless steel tubular reactor (inner diameter 1 mm) of 5 m and 10 m length for VCL and NIPAm monomer, respectively. The tubular reactor is heated over the entire length to 70 ◦ C by the external heating bath (white box in Figure 1a and 1b). The residence time is adjusted by volume ratio of the solutions which leads to laminar flow conditions with Reynolds numbers between 30 and 400. At the end of the tubular reactor, samples are filled in an inhibitor solution to stop the polymerization, similar to batch. The fluid temperature in the flow reactor is determined by 5



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Table 1. Used chemicals and final concentrations for the batch and continuous synthesis and stock solution concentrations for the reservoirs of the continuous setup. (g/L) Batch Continuous (mmol/L) 12.31 12.31 VCL 88.39 88.39

Stock solution continuous 14.77 106.07

NIPAm

10.00 88.39

10.00 88.39

12.01 106.07

BIS

0.33 2.17

0.33 2.17

0.4 2.59

CTAB (if any)

0.10 0.28

0.10 0.28

0.12 0.33

AMPA

0.28 1.00

0.28 1.00

1.67 6.00

the simulations using Comsol Multiphysics 5.0. Based on this, Figure 1d shows the amount of time, after which the entering reactants reach the reaction temperature of 70 ◦ C. For all experiments, the reaction temperature can be assumed as constant since it is reached in less than 10 s. During the operation of the flow reactor, the phenomenon of blocking the reactor appeared. Since investigation of this phenomenon proves to be challenging in the stainless steel reactor (1 mm inner diameter), it was investigated with a glass reactor with a bigger inner diameter (4 mm). This setup allowed monitoring the process over time, showing a microgel film formation on the reactors wall over time. Possible steps to avoid microgel growth on the reactors wall could be smoothing, hydrophilization or charging of the surface and will be addressed in the future.

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3.4

Dynamic Light Scattering

DLS measurements were performed using an ALV/CGS-3 Compact Goniometer System with an ALV/LSE 5004 Tau Digital Correlator and a 1 mV JDS Uniphase laser operating at 632.8 nm. The experiments were carried out at a fixed scattering angle θ = 90◦ with an acquisition time of 90 s and repeated at least three times. The temperature trends were measured in a temperature range of 20-50 ◦ C in steps of 1 ◦ C.

3.5

Static Light Scattering

To measure form factors of the synthesized microgels, a new SLS Type 3 goniometer from SLS-Systemtechnik GmbH was used. Wavelengths of 404 nm and 642 nm were used and the scattering angle θ was varied from 15◦ to 155◦ in 1◦ increments. All samples were diluted from the purified dispersions, filtered through a 1.2 µm PET filter to remove dust and measured in 20 mm diameter cuvettes at 20 ◦ C in water. Solvent trace was subtracted from all the measurements. For each batch a minimum two datasets with different wavelengths were acquired. At high scattering vectors (q) a rise in signal intensity could be observed. This originates from back reflection of the laser from the cuvette and has been removed as it does not contain sample relevant information. 39 To avoid multiple scattering in the measurements with the blue laser, different concentrations for blue and red lasers were used. The scattering traces were imported to the program FitIt!† and inverted using 20 point discretization.

3.6

Reaction Calorimetry

The calorimetric measurements were carried out in a reaction calorimeter RC1e from Mettler R Toledo with a 500 mL 3-wall AP01-0.5-RTCal reactor equipped with a Hastelloy stirrer, †

https://github.com/ovirtanen/fitit

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a baffle and a TurbidoTM turbidity probe from Solvias. The measurements were performed in the isothermal mode, in which the desired reaction temperature (Tr ) is set at a constant value and the jacket temperature (Tj ) changes automatically to maintain Tr at the desired value. Data evaluation was performed with the software iControl RC1eTM 5.0. For the determination of the net reaction time the end of the reaction was defined to be when the heat flow was back to a value close to zero and steady state. The fractional conversion was obtained by integrating the reaction heat curve.

4

Results and discussion

We integrated a tubular reactor into a modular process platform (Ehrfeld Microtechnik BTS) (cf. Figure 1a and 1b), to synthesize microgels in a continuous way. The tubular reactor was fed with two stock solutions to control the initiation of the polymerization. One contained the monomer (VCL or NIPAm), cross-linker (BIS) and if used surfactant (CTAB), while the other contained the initiator (AMPA) (cf. Figure 1c and 1a). The setup allows the variation of reagent concentration and reaction time, meanwhile one can premix the reaction solutions before entering the reactor using a static mixer. The reaction temperature is assumed constant in all experiments, as heating the reactants to the desired temperature of 70 ◦ C takes less than 10 s (Figure 1d). To achieve an efficient industrial process, one has to scale up the production of microgels towards a continuous process. For this, one has to consider the trade-off in costs between a high conversion and a low reaction duration. A higher conversion leads to higher amounts of product, meanwhile leading to longer reaction duration. The higher amount of product can be sold at the expense of longer reaction duration causing higher production costs. As the main conversion of the microgel synthesis takes place in the first 5 (PVCL) to 10 min (PNIPAm) of the reaction, 40,41 the applied residence times in the flow reactor are kept in that

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(a)

(b)

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N2

70 °C

monomer crosslinker

P

(

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Outlet

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5

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0 0

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(c)

(d)

Figure 1. Details of the experimental setup. (a) Top view onto BTS Ehrfeld System with sensors (pressure, temperature) and the capillary reactor being incorporated into the white heating device. Pumps are not shown. (b) Capillary reactor, 10 m stainless steel tube with inner diameter of 1 mm. (c) Schematic representation of the continuous microgel fabrication process. (d) Point of reaching the reaction temperature in the center of capillary reactor, determined by comsol simulation of heat transfer. range. Nevertheless, the investigated range covers more than 90 % of the final conversion in the batch reactor (Figure 2). Monomer conversion during the polymerization was derived from the calorigrams of PVCL and PNIPAm microgels synthesized in batch. The heat generated during the polymerization originates from the cleavage of double bonds from monomer

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and cross-linker molecules. Knowing the heat of polymerization for VCL (76 kJ/mol) 42 and NIPAm (85 kJ/mol), 43 one can calculate the conversion over time by integration of the calorigrams (Figure 2b, 2c and 2d). Comparing the calorigrams of PVCL (Figure 2b) to the one of PNIPAm (Figure 2d and 2f), one can see a small peak appearing at the beginning of the reaction of PVCL. In our previous works, this has been attributed to differences in reactivity between the cross-linker BIS and the monomers. 41,44 The copolymerization parameters of the VCL-BIS, BIS-VCL reaction are significantly higher than the ones of VCL-VCL and BIS-BIS. Therefore, the lower amount of BIS is consumed faster than the VCL, resulting in a peak at the beginning of the VCL calorigram. After BIS is consumed, VCL can only react with itself, leading to the main peak of the calorigram. In case of NIPAm synthesis, the copolymerization parameters are similar, resulting in a single peak. The three methods of microgel production (batch, continuous and continuous with premixing) are compared by collecting samples at specific reaction times in the batch and the continuous flow reactor. The resulting hydrodynamic radii are shown in Figure 2 (left) for PVCL and PNIPAm microgels as a function of reaction time in batch and continuous flowreactors. Each radius shown represents the mean radius and the standard deviation from three independent syntheses, showing the robustness and good reproducibility of all three methods. For PVCL and PNIPAm microgels, the increase of the hydrodynamic radii with the reaction time is evident indicating the growth of microgels by precipitation of oligomer chains on pre-formed nuclei. 45 As shown in Figure 2a and 2c, the size of the PVCL and PNIPAm microgels synthesized under surfactant-free conditions in flow are smaller compared to the analogously synthesized microgels from the batch process. The difference in the microgel size is obvious at low reaction times and becomes stronger as reaction time increases. Premixing the reaction solutions previous to the flow reactor increases the size of the microgels compared to the non-premixed operation, showing that premixing of the reaction solutions is necessary. A longer static mixer might further reduce the size of microgels synthesized in the flow

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(a)

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Figure 2. Hydrodynamic radius of microgels at 20 ◦ C (left) comparing flow and batch reactor conditions and calorigrams and conversions over time (right) based on PVCL (a-b), PNIPAm synthesized without CTAB (c-d) and PNIPAm synthesized with CTAB (e-f). Each radius symbolizes the mean radius of three independent syntheses.

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reactor, allowing for microgel sizes similar to the ones achieved in the batch reactor. Presence of surfactant in polymerization mixture strongly influences the microgel formation mechanism. 46,47 Microgel nuclei formed at early stages of polymerization can be more efficiently stabilized by surfactant molecules, leading to an increased number of growing microgels. The increased number of microgel nuclei results in smaller microgels (cf. Figure 2c and 2e). As the surfactant concentration lies below the critical micellar concentration (cmc) of CTAB (0.8 mM), 48 this cannot be attributed to the formation of micelles during the synthesis. Additionally, NIPAm microgels synthesized with surfactant (Figure 2e) show no difference in radius between continuous, premixed continuous and batch synthesis for t > 180 s. Meaning, that the presence of surfactant has a significant influence on the resulting radii. The surfactant provides better electrostatic stabilization of the growing microgel nuclei due to its charged head group. 49,50 Analyzing the experimental data in Figure 2, we can conclude that the synthesis of microgels under flow conditions is possible and the premixing of the reaction solutions strongly influences the microgel growth process. At the same time the use of surfactant leads to microgels of the same size, independent of the reaction method (continuous, premixed continuous or batch). Furthermore, it can be seen that the microgel size can be tuned by variation of the residence time inside the tubular flow reactor (see Figure 2a, 2c and 2e). The shorter the residence time, the smaller the microgel radius. With this, the radius of the microgel can be tailored from 70 to 370 nm, depending on the monomer and use of surfactant. This brings us within the range of extremely small microgels with radii below 100 nm. These kind of microgels are hard to prepare by classical precipitation polymerization without the use of higher amounts of surfactants. 51 In one of our previous studies, we were able to achieve microgels with radii down to 45 nm using a confined impinging jet reactor (CIJR) in a non-continuous process. 52 High shear forces and high pressures during the surfactant-free precipitation polymerization of PVCL resulted in the reduction of the microgel radius. Since

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the size of a microgel also depends on the reaction temperature, 52–54 it might be possible to reach radii below 50 nm by raising the reaction temperature in our setup. These kind of microgels are of high interest for drug delivery systems, as they are able to be internalized by cells 55 or even pass the blood-brain barrier if smaller than 50 nm. 56 The influence of the reaction temperature on the microgel synthesis in the continuous flow reactor will be investigated in the future. 400

PVCL

PNIPAm Batch

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300 Hydrodynamic radius [nm]

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Figure 3. Thermo-responsive behavior of microgels made of (left) PVCL, (right) PNIPAm (synthesised with CTAB and without CTAB) comparing flow reactor and batch reactor conditions. Addressing the question if polymerization operation influences temperature-responsive properties of microgels, we analyzed the radii of the different microgels depending on temperature. As shown in Figure 3 all synthesized PNIPAm and PVCL microgels exhibit their typical behaviour in aqueous solutions reflected in the change of the size with temperature. All microgels exhibit volume phase transition temperature (VPTT) around 32-33 ◦ C and reversibly change their hydrodynamic radii as response to the temperature. This behaviour is caused by hydrophobic and hydrophilic interactions between the polymer chains and water molecules. When the temperature exceeds a certain value (VPTT), the hydrogen bonds between water molecules and polymer chains break and the microgel collapses while expelling

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most of its water. 18 From Figure 3 it is evident that microgel synthesized in flow reactor, premixed or not, exhibit quite similar properties to their analogues synthesized in batch reactor. This indicates a structural similarity of the microgels, independent of preparation method. Direct comparison of the microgel properties for the three different reaction methods proofs to be challenging due to the varying microgel sizes. Therefore, the swelling ratio (Q) is calculated by dividing the microgel radii in the fully swollen (20 ◦ C) by the collapsed (50 ◦ C) state (Table 2). Since the swelling ratio is influenced by the composition and cross-linker distribution of the microgel, 57,58 a change in internal structure should result in a change of the swelling ratio. Comparing the PNIPAm microgels synthesized with and without surfactant, only negligible changes in the swelling ratio can be seen, showing that the (premixed) continuous method allows the synthesis of microgels with the same properties as the batch method. Although the use of a static mixer results in larger microgels, it does not affect the swelling behaviour of the microgels in regard to the non-mixed ones. Furthermore, it can be seen that even if the use of surfactant influences the microgel size, it does not influence the internal structure of the microgel. The same conclusion can be drawn for microgels synthesized with VCL. Table 2. Comparison of swelling ratios of PNIPAm and PVCL microgels synthesized with and without CTAB. Determined using microgel sizes from DLS measurements in the collapsed (50 ◦ C) and swollen state (20 ◦ C). Microgel

Batch

Continuous premixed

Continuous

PNIPAm

2.5

2.6

2.5

PNIPAm CTAB

2.5

2.3

2.3

PVCL

2.4

2.2

2.2

In previous works it could be shown that PVCL and PNIPAm homopolymer microgels possess a heterogeneous morphology with a higher cross-linking density in the core of the 14


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Fuzzy sphere fit

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Figure 4. Scattering profiles of PNIPAm microgels synthesized in batch and flow (premixed and non-premixed) without (a) and with CTAB (b). Extrapolated particle size distributions without (c) and with CTAB (d) and relative volume fractions without (e) and with CTAB (f) from fuzzy sphere fits of the scattering profiles.

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microgel than in its corona. 58–60 To get information about the internal structure of the microgels synthesized via batch or continuous method, the microgels were investigated using SLS (Figure 4a and 4b). The scattering profiles were fitted with a fuzzy sphere fit, describing the denser cross-linked core and fuzzy corona of a microgel. 60 From these fits, the particle size distribution can be derived, showing that (premixed) continuous polymerization only leads to a slight increase in polydispersity compared to the batch synthesis (Figure 4c and 4d). PNIPAm microgels synthesized with the surfactant CTAB exhibit no significant difference in particle size distribution compared to microgels synthesized without surfactant. Only for the batch synthesis a slightly narrower distribution can be observed. Similar effects have been previously described in literature. 49,50 In addition to the particle size distribution, the relative volume fraction can be calculated over the radial distance from the microgel core. 60 This correlates to the density of the microgel, showing changes in the internal structure from the core to the corona of the microgel (Figure 4e and 4f). Taking a closer look at the core-corona ratios of the microgels in Table 3, one can see a slight increase in the size of the corona for the microgels synthesized with the (premixed) continuous method compared to the batch method. Table 3. Radius and core-corona ratio of PNIPAm microgels synthesized with and without CTAB. Determined at 20 ◦ C from SLS measurements using the fuzzy sphere model for microgels. 60 Microgel PNIPAm

PNIPAm CTAB

Radius Corona Core (nm) (%) (%) Batch 372 47 53 Premixed 325 55 45 Flow 312 60 40 Reactor

Batch Premixed Flow

200 208 184

63 84 79

37 16 21

This supports the conclusions drawn from the swelling ratios in Table 2, that the internal structure is only slightly affected by the continuous method compared to the batch synthesis. 16


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In contrast to that, the synthesis of microgels in inverse miniemulsions at 20 ◦ C results in a different internal structure compared to batch synthesis. 61 This shows that the polymerization process (precipitation or miniemulsion polymerization) has a stronger influence on the internal structure compared to the type of reactor used in this study.

5

Conclusion

In this work temperature-responsive microgels have been synthesized in a continuous tubular reactor via precipitation polymerization for the first time. Microgels were prepared with temperature-responsive behavior, internal structure and particle size distribution comparable to the ones typically prepared in batch. These similarities can be explained by the properties of the reaction solution inside the tubular flow reactor. If one separates the reaction solution into defined sections, it behaves like a batch reactor where the monomer is consumed over time as the section moves along the length of tubular flow reactor. 62,63 Residence times inside the continuous reactor could be adjusted very precisely, allowing for a strict and reproducible tailoring of the microgel size. Furthermore, the set-up allows regulating concentration of reagents and temperature, making it a versatile tool for the synthesis of microgel. Without the use of a static mixer in the flow reactor, microgel sizes were smaller compared to the ones prepared in batch. Premixing the reaction solution prior to the initiation of the polymerization resulted in an increase in microgel size. Still, the premixed continuous method results in slightly smaller microgels compared to the batch method. But, the use of surfactant diminishes these differences and results in microgels with nearly identical sizes. We demonstrate that microgels synthesized under flow conditions exhibit very similar temperature-responsive properties and internal structures compared to their analogues synthesized in batch process, making the continuous flow reactor a valid alternative for the upscale of microgel syntheses for industrial scale

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applications. The presented versatile and modular platform for microgel synthesis opens a wide field of applications. Functional groups can be easily introduced by addition of comonomers to the monomer stock solution. Additionally, defined structures like core/shell or hollow microgels can be prepared by adapting the reactor setup and feeding a stock solution with comonomer into the tubular reactor at different stages of the polymerization.

Acknowledgement Authors thank the Deutsche Forschungsgemeinschaft (DFG) for funding within the SFB 985 “Functional Microgels and Microgel Systems” and the Volkswagen Stiftung for financial support.

Supporting Information Available All related data and information to this publication can be found in the persistent identifier of SFB 985 - “Functional Microgels and Microgel Systems”: https://hdl.handle.net/21.11102/2b7fe86d-10d9-11e8-80f7-e41f1366df48. This material is available free of charge via the Internet at http://pubs.acs.org/.

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From Batch to Continuous Precipitation ... - ACS Publications

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