Continuous-Flow Synthesis of ZIF-8 Biocomposites with Tunable Particle Size

Francesco Carraro, Jason D. Williams, Mercedes Linares-Moreau, Chiara Parise, Weibin Liang, Heinz Amenitsch, Christian Doonan, C. Oliver Kappe*, Paolo Falcaro*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Zeolitic imidazolate framework (ZIF) biocomposites show the capacity to protect and deliver biotherapeutics. To date, the progress in this research area is based on laboratory batch methods. Now, the first continuous flow synthetic method is presented for the encapsulation of a model protein (bovine serum albumin, BSA) and a clinical therapeutic (α1-antitrypsin, AAT) in ZIF-8. The in situ kinetics of nucleation, growth, and crystallization of BSA@ZIF-8 were studied by small-angle X-ray scattering. By controlling the injection time of ethanol, the particle growth could be quenched by 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, this procedure was used for the encapsulation of AAT in ZIF-8. Upon release of the biotherapeutic from the composite, the trypsin inhibitor function of AAT was preserved.

Original languageEnglish
Pages (from-to)8123-8127
Number of pages5
JournalAngewandte Chemie - International Edition
Issue number21
Publication statusPublished - 18 May 2020


  • flow chemistry
  • in situ SAXS
  • metal–organic frameworks
  • MOF biocomposites
  • particle size

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)


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