The benefit of coupling droplet microfluidics and multiphoton optical microscopy to study the crystallization of polymorphic substances: a case study with ortho-aminobenzoic acid

Abstract

A new crystallization platform coupling droplet-based microfluidics with two photon and second harmonic generation microscopy operating with a femtosecond pulsed wave laser of tunable wavelength is presented. The present paper demonstrates the performance of this set-up by conducting a large number of independent crystallization experiments in small (nL) unstirred reactors. We used ortho-aminobenzoic acid (o-ABA) as a model substance: it is a polymorphic substance known to exhibit concomitant polymorphism. It was possible to rapidly image and discriminate crystals with a centrosymmetric structure from crystals with a non-centrosymmetric structure by using this new coupling system. By conducting thorough crystallization studies, our set up allowed the impact of small volume on the nucleation behavior of o-ABA polymorphs to be investigated and the occurrence of both solvent mediated transformation and solid–solid transition to be evidenced. In particular, we show that small volume favors the nucleation of the most stable crystal form of o-ABA.