Chiral Separation by a Pseudo Membrane in a Triple‐Laminar Flow with a Microfluidic Contactor

Abstract

A split personality: The first simultaneous reaction/separation of chiral compounds in a continuous process in an inorganic polymer‐chip device affords the rapid and continuous separation of chiral compounds. Selective esterification of (S)‐ibuprofen by lipase in organic mediums was followed by transportation of the (S)‐ibuprofen ester through an ionic liquid as a pseudo‐membrane and finalized by hydrolytic recovery in the aqueous layer.

Toward microfluidic continuous-flow and intelligent downstream processing of biopharmaceuticals

“…77,78 In a microfluidic system, small molecules like ibuprofen racemate undergo simultaneous enzymatic esterification and chiral-specific separation in a triple-laminar flow of organic, ionic liquid, and aqueous phases as a pseudo-membrane. 79 In several studies, TFF was demonstrated as an alternative to dead-end filtration, facilitating the sustained maintenance of high flux by minimizing concentration polarization and cake formation. 80 In a study, a modular reactor and in-line TFF microscale system has demonstrated complete substrate conversion, complete enzyme retention and prevention of macromolecule buildup on the membrane.…”

Microreaction and membrane technologies for continuous single-enantiomer production: A review

“…Surprisingly, only a few papers on membrane-based microfluidic or nanofluidic chiral or enantioselective separations have been published thus far, especially considering how appealing simultaneous reaction and chiral separations of racemic ibuprofen in an inorganic polymer micro-contactor are from a technological point of view. [147] In fact, one of the ibuprofen enantiomers has been transported through a pseudo-membrane through a stream of an ionic liquid separating an aqueous and organic phase inside a microchannel under laminar flow conditions. The enzymatic reaction in the organic phase flow yielded the S-ibuprofen-ester intermediate.…”

“…The conversion of the enzymatic reaction depended on the thickness of the ionic-liquid membrane and increased up to 92.5% at 100 μm thickness, reaching an enantiomeric excess of 99.9%. [147] A different approach to microfluidic device-based enantioselective separations can be found in a paper by Wang et al [148] They replaced a stationary chromatography phase with a porous enantioselective membrane. The porous PVDF membrane functionalized with BSA separated tryptophan/thiopental mixtures.…”