Carraro, F.Williams, J.D.Linares-Moreau, M.Parise, C.Liang, W.Amenitsch, H.Doonan, C.Kappe, C.O.Falcaro, P.2020-05-112020-05-112020Angewandte Chemie International Edition, 2020; 59(21):1-61433-78511521-3773http://hdl.handle.net/2440/124649Zeolitic Imidazolate Framework (ZIF) biocomposites show the capacity to protect and deliver bio-therapeutics. To date, the progress in this research area is based on laboratory batch methods. To further explore the potential of ZIF-biocomposites for application to biomedicine and biotechnology, the continuous production of ZIF-biocomposites of specific particle size is desirable. Here we report the first continuous flow synthetic method for the encapsulation of a model protein (bovine serum albumin, BSA) and a clinical therapeutic (α1-antitrypsin, AAT) in ZIF-8. We studied the in situ kinetics of nucleation, growth and crystallization of BSA@ZIF-8 by small angle X-ray scattering. By controlling the injection time of ethanol, we could quench the particle growth via ethanol-induced crystallization from amorphous particles to ZIF-8 crystals. The particle size of the biocomposite was tuned in the 40-100 nm range by varying residence time prior to introduction of ethanol. As a proof-of-concept, we used this protocol for the encapsulation of AAT in ZIF-8. Upon release of the bio therapeutic from the composite, the trypsin inhibitor function of AAT was preserved.en© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.MOF biocompositesSmall Angle X-ray ScatteringZIF-8flow chemistryJournal article100001789110.1002/anie.2020006780005369531000262-s2.0-85081922279521667