Date: 30 May 2025 | Category: News
Authors: Gayathri Dev Ammini, Lakshani J. Weerarathna, and Tanja Junkers*
The Junkers group from Monash University in Australia have successfully used the Vapourtec SF-10 peristaltic laboratory pumps to formulate block copolymers (BCPs) into nanoparticles as well as further purify them using flow dialysis [1]. This approach provides significant advantages over traditional batch-based processes due to higher rates of nanoparticle formation and purification, improved consistency between outputs and more environmentally friendly conditions.
Figure 1: Overview of the Junkers group’s BCP synthesis and purification, adapted from [1].
Block copolymers (BCPs), a versatile tool within polymer science and technology
BCPs are able to self-aggregate into precise nanostructures, which means that they are extremely useful within polymer science and technology. On industrial scale these materials are often prepared through use of living anionic batch polymerizations [2], but development of reversible-deactivation radical polymerization (RDRP) techniques has allowed more reliable means of preparing customisable block copolymers [3]. Self-assembly structures formed include micelle-type spheres, vesicles, lamellae, or cylinders, with the possibility of including a chemical payload for specific applications [4].
Key challenges in BCP formation
Formation of these nanostructures is governed by both thermodynamic and kinetic factors. Kinetic factors become especially important when one partner has limited mobility, which can then prevent rearrangement to the most thermodynamically stable state. During traditional batch synthesis, discrepancies in mixing volumes, stirring speed, order of reagent addition and duration of addition can all impact upon the final nanoparticle morphology and lead to inconsistencies between batches [5]. Flow self-assembly offers exquisite control of these nanoaggregation parameters, enabling production of consistent product alongside faster nanoparticle production [6].
As well as challenges during preparation, removal of excess organic solvents during purification can be troublesome and is critical for BCPs intended for medical use. A routine technique for solvent removal is traditional batch dialysis – small molecules such as solvents are able to diffuse through a cellulose membrane with pre-determined pore size, leaving the BCPs behind. However, this process can be slow, often requiring more than 24 hours to complete. In addition, a concentration gradient must be maintained to effect satisfactory separation, and often multiple solvent replacements must be made. Finally, the crude solution must be placed in dialysis bags, rendering the process unsuitable for automation and large-scale application [1].
The Junker Group’s approach
The Junker group’s innovative approach to nanoaggregate formation using continuous flow was achieved with a micromixer, designed to create defined turbulence while mixing, Figure 2a. In addition, a tubular reactor and two Vapourtec SF-10 peristaltic laboratory pumps were required, with the peristaltic pumps chosen for their ability to minimise pulsation of the liquid phase and their continuous mode of operation. Optimized conditions used block copolymer concentration of 10 mg/mL in THF, with water:THF ratio maintained at 90:10 v/v. The flow rates could be adjusted to tune particle sizes and stable nanoaggregates were formed instantaneously upon mixing of the organic and aqueous streams – a significant reduction in duration compared to traditional batch methods which routinely require up to 12 hours.
Purification subsequently was performed using continuous flow dialysis, Figure 2b. In this case, the nanoparticle purification set-up comprised of a looped flow dialysis unit, where the dialysis units had two inlets: one for water, and one for a solution of BCP nanoparticles in THF/water. Fresh water was continually pumped through the system, while the nanoparticle solution was looped to allow several passes through the dialysis unit to facilitate complete removal of all undesired small molecules, such as residual monomers or solvent. Overall, THF concentration was reduced from 90 to 2.1 mmol/L after 3 hours of dialysis, where 3-hour dialysis corresponds to approximately 12 loops, approximately a 97% reduction in organic solvent content.
![Figure 2: Schematic representation of (a) nanoaggregate formation set-up in continuous flow; (b) particle purification using flow dialysis. Image taken from [1].](https://www.vapourtec.com/wp-content/uploads/2025/05/Figure-2-Schematic-representation-of-a-nanoaggregate-formation-set-up-in-continuous-flow-b-particle-purification-using-flow-dialysis-Image-taken-from-1.jpg "Figure 2: Schematic representation of (a) nanoaggregate formation set-up in continuous flow; (b) particle purification using flow dialysis. Image taken from [1].")
Figure 2: Schematic representation of (a) nanoaggregate formation set-up in continuous flow; (b) particle purification using flow dialysis. Image taken from [1].
Flow chemistry: an enabling technology with application in engineering
Overall, the process designed by Ammini et al., leveraging continuous flow chemistry, provided significant advantage when compared with traditional batch chemistry. BCP nanoparticle formation could be precisely controlled, allowing facile tuning of particle sizes and rapid formation of stable nanoaggregates. Subsequent flow dialysis was highly efficient at removing undesired components in a more efficient manner than traditional batch techniques using dialysis bags. The overall approach provides access to a robust and scalable approach that could be used on commercial scale.
References:
[1] Continuous Flow Block Copolymer Nanoaggregate Synthesis and Their Flow Dialysis Purification. (G. D. Ammini, L. J. Weerarathna, T. Junkers, Chemistry-Methods, 2025, e202500025). https://doi.org/10.1002/cmtd.202500025
[2] Living polymers. Their discovery, characterization, and properties. (M. Szwarc, Journal of Polymer Science Part A: Polymer Chemistry, 1998, 36, IX–XV). https://doi.org/10.1002/(SICI)1099-0518(19980115)36:1%3CIX::AID-POLA2%3E3.0.CO;2-9
[3] Improved Livingness and Control over Branching in RAFT Polymerization of Acrylates: Could Microflow Synthesis Make the Difference? (P. Derboven, P. H. M. Van Steenberge, J. Vandenbergh, M.-F. Reyniers, T. Junkers, D. R. D’hooge, G. B. Marin, Macromolecular Rapid Communications, 2015, 36, 2149–2155). https://doi.org/10.1002/marc.201500357
[4] Self-Assembled Block Copolymer Aggregates: From Micelles to Vesicles and their Biological Applications. (A. Blanazs, S. P. Armes, A. J. Ryan, Macromolecular Rapid Communications, 2009, 30, 267–277). https://doi.org/10.1002/marc.200800713
[5] (a) Morphological Phase Diagram for a Ternary System of Block Copolymer PS310–b-PAA52/Dioxane/H2O. (H. Shen, A. Eisenberg, The Journal of Physical Chemistry B, 1999, 103, 9473–9487). https://doi.org/10.1021/jp991365c (b) Techniques To Control Polymersome Size. (R. Bleul, R. Thiermann, M. Maskos, Macromolecules, 2015, 48, 7396–7409). https://doi.org/10.1021/acs.macromol.5b01500 (c) Biocompatible and Biodegradable Poly(trimethylene carbonate)-b-Poly(L-glutamic acid) Polymersomes: Size Control and Stability. (C. Sanson, C. Schatz, J.-F. Le Meins, A. Brulet, A. Soum, S. Lecommandoux, Langmuir, 2010, 26, 2751–2760). https://doi.org/10.1021/la902786t
[6] (a) Controllable synthesis of functional nanoparticles by microfluidic platforms for biomedical applications – a review. (J. Ma, S. M.-Y. Lee, C. Yi, C.-W. Li, Lab on a Chip 2017, 17, 209–226). https://doi.org/10.1039/C6LC01049K (b) Toward the scale-up production of polymeric nanotherapeutics for cancer clinical trials. (M. M. Mahmud, N. Pandey, J. A. Winkles, G. F. Woodworth, A. J. Kim, Nano Today 2024, 56, 102314). https://doi.org/10.1016/j.nantod.2024.102314
