Fast and Environmentally Friendly Microfluidic Technique for the Fabrication of Polymer Microspheres Yanlin Zhang, Robert W. Cattrall, and Spas D. Kolev* School of Chemistry, The University of Melbourne, Victoria 3010, Australia * S Supporting Information ABSTRACT: This paper reports on a novel microfluidic technique for the fabrication of microspheres of synthetic polymers including poly(vinyl chloride) (PVC), poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF- HFP), poly(lactic acid) (PLA), and polystyrene (PS). The polymers are dissolved in tetrahydrofuran (THF) and the method is based on the diminished solubility of THF in a 20% (w/v) NaCl solution which allows the formation of droplets of the polymer solution. These polymer solution droplets are generated in a microfluidic system and their desolvation is accomplished within seconds by allowing the droplets to rise by buoyancy through a NaCl solution with a concentration lower than 15%. The size and morphology of the resultant polymer microspheres have been investigated by optical and scanning electron microscopy. Apart from the elimination of the use of highly toxic solvents as in conventional methods for manufacturing of polymer microspheres, the newly developed technique has the advantages of providing faster desolvation of the polymer solution droplets and a higher yield of microspheres compared to emulsification-based techniques. ■ INTRODUCTION Microspheres, also known as microbeads, have found wide applications in different areas such as drug delivery, 1-6 biotechnology, 7,8 catalysis, 9 coatings, 10 chemical sensing, 11 and bead injection analysis (BIA). 12-14 Microspheres of a synthetic polymer can be prepared either by polymerization of its monomers 15 or from a solution of the polymer using various physical fabrication techniques. 16 Compared to the polymer- ization approaches which are only applicable to some polymers, the physical fabrication techniques using polymer solutions can be applied to any polymer as long as a suitable solvent is available to dissolve the polymer. Such approaches have attracted wide interest because they utilize fewer chemicals and involve a simple 2-stage operational procedure. The first stage results in the generation of microdroplets of the polymer solution which is followed by the second desolvation stage in which solid microspheres are obtained. A number of protocols have been reported for the fabrication of microspheres by using different droplet generation approaches, such as stirring, 17 static mixing, 18 extrusion, 19,20 and dripping. 21,22 Droplet desolvation is usually performed using solvent evaporation 23,24 or solvent extraction/evaporation. 25 All these techniques are based on emulsification in which the polymer is first dissolved in an organic solvent such as dichloromethane, 18,19 chloroform, 20,26 acetonitrile, 27 or toluene, 28 and the solution is then dispersed in the form of microdroplets in a continuous phase, usually an aqueous surfactant solution. These approaches exhibit a number of disadvantages, i.e., (i) a key limitation of these techniques is the difficulty in controlling the size of the microspheres, and this normally gives rise to polydispersity, 22,28,29 which causes unsatisfactory performance in applications (e.g., nonuniform rate of release of the loaded in the microspheres therapeutics); 30 (ii) the desolvation of the polymer droplets is generally a slow process, typically taking hours for the removal of the solvent unless reduced pressure is applied; 31,32 (iii) recovery of the solvents is not economical and they are normally released into the atmosphere during the microdroplet desolvation process, which is of considerable environmental and health concern; (iv) complete removal of the solvent from the microspheres is difficult to achieve, thus making them undesirable for medical applications (e.g., drug delivery 33 ); and (v) the most commonly used stirring emulsification approach often yields only 50% to 80% of microspheres due to aggregation and agglomeration and therefore a significant fraction of the raw materials including the polymer and the additives is wasted. 26,34,35 A spray-drying approach eliminates some of the above-mentioned problems. However, the high temperature needed for the evaporation of the organic solvent may cause degradation of some thermosensitive components such as proteins and peptides. 36 Microfluidic techniques have provided novel approaches for the fabrication of microspheres. 29,31,32,37-44 These techniques have several advantages including the use of simple and robust devices and the fabrication of microspheres with a low degree of polydispersity. However, most of the reported microfluidic approaches still involve an emulsification step and therefore suffer from most of the disadvantages of the batch-wise emulsification techniques. In addition, the microfluidic devices Received: October 13, 2017 Revised: November 28, 2017 Article pubs.acs.org/Langmuir Cite This: Langmuir XXXX, XXX, XXX-XXX © XXXX American Chemical Society A DOI: 10.1021/acs.langmuir.7b03574 Langmuir XXXX, XXX, XXX-XXX