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Our article in Science Advances about an approach to make mesoporous MOFs in a microfluidic channel

Our article “Defect-induced Activity Enhancement of Enzyme-Embedded Metal-Organic Frameworks Revealed in Microfluidic Gradient Mixing Synthesis” has been published in Science Advances.


Link to the article (open access): https://advances.sciencemag.org/content/6/5/eaax5785




Enzyme has important applications in catalysis, biosensors, drug delivery, molecular machines, etc., but the implementation is challenged by the reduced lifetime and efficiency of enzymes in general working conditions which are far different from the cellular environment. One way to tackle such challenges is directed evolution of enzymes via altering the protein molecular structure. Another way is to design a biomimicking microenvironment to protect the enzymes so that their functionality can be retained. Mimicking the cellular environment, metal-organic frameworks (MOFs) are promising for encapsulating enzymes for general applications in environments often unfavourable for native enzymes.


The de novo approach such as co-precipitation and biomimetic mineralization is simply mixing the enzymes, metal ions, and organic ligands at ambient condition in bulk solution to produce enzyme-encapsulated MOF composites. This approach is an efficient, straightforward, and scalable way to prepare MOF bio-composites. The activity of enzyme-MOF composites synthesized via such co-precipitation method, however, is still far from satisfactory (usually less than 10% of native enzyme). In this work, we synthesized enzyme-MOF composites via a special mixing manner in microfluidic flow, which, to our surprise, generated products with dramatically improved enzymatic activity (around one order of magnitude than conventional methods). The gradient mixing environment generated defects in MOF particles formed in co-precipitation process, leading to particles containing both micropores and mesopores, which not only protect the incorporated enzymes, but also give much higher enzymatic activities compared to conventional enzyme-MOF nanocomposites because of the improved mass transfer through mesopores. We believe this mechanism can be used as a general new strategy to produce enzyme-inorganic nanocomposites with improved activity.


This work provided a strategy to effectively study complicated aqueous reactions such as co-precipitation process, which begins with a fast mixing (and reaction) of enzyme, metal ions, and organic ligands in solution and could be largely dependent on the mixing process. It could be useful for a wide range of reactions where such effects have been generally ignored. The spontaneous formation of defects in crystalline nanoparticles in a dynamic gradient mixing environment could be a general new strategy in the synthesis of nanoparticles. We think this finding is useful to researchers in a wide range of chemistry, nanotechnology, materials chemistry, enzymatic catalysis and etc.



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