Concentric annular liquid–liquid phase separation for flow chemistry and continuous processing

Abstract

A low-cost, modular, robust, and easily customisable continuous liquid–liquid phase separator has been developed that uses a tubular membrane and annular channels to allow high fluidic throughputs while maintaining rapid, surface wetting dominated, phase separation. The system is constructed from standard fluidic tube fittings and allows leak tight connections to be made without the need for adhesives, or O-rings. The units tested in this work have been shown to operate at flow rates of 0.1–300 mL min⁻¹, with equivalent residence times from 80 to 4 seconds, demonstrating the simplicity of scale-up with these units. Further scale-up to litre per minute scales of operation for single units and tens of litres per minute through limited numbering up should allow these low cost concentric annular tubular membrane separators to be used at continuous production scales for pharmaceutical applications for many solvent systems. In principle this approach may be sufficiently scalable to be utilized in-line, in batch pharmaceutical manufacturing also, through further scale-up and numbering up of units. Several solvent systems with varying interfacial tensions have been investigated, and the critical process parameters affecting successful separation have been identified. An additively manufactured diaphragm based back pressure regulator was also developed and printed in PEEK, allowing highly accurate, adjustable, and chemically compatible pressure control to be accessed at low cost.