Chiral Chromatography Resolution Can Be Enhanced by Using Microfluidic Precision Manufactured Macroporous Silica...

Area of Science:

• Materials Science
• Analytical Chemistry
• Chemical Engineering

Background:

• Polysaccharide-functionalized macroporous silica microspheres are key chiral stationary phases (CSPs) in High-Performance Liquid Chromatography (HPLC).
• Conventional CSPs, prepared via pore-widening post-treatments, exhibit broad pore size distributions and multimodal pore structures, limiting chiral separation performance.
• Existing manufacturing strategies and pore structures hinder the efficiency and resolution of chiral separations.

Purpose of the Study:

• To develop a precision manufacturing method for monodisperse macroporous silica with a monomodal pore structure and narrow pore size distribution.
• To create a novel monodisperse chiral stationary phase (Mono-CSP) using a droplet microfluidic synthesis platform.
• To evaluate the performance of the Mono-CSP in enantioseparation compared to conventional polydispersed CSPs.

Main Methods:

• Utilized a droplet microfluidic synthesis platform integrating sol-gel chemistry and phase separation.
• Synthesized monodisperse macroporous silica microspheres in a single step.
• Functionalized the synthesized silica with cellulose tris(3,5-dimethylphenylcarbamate) to create the Mono-CSP and compared it with a commercial Chiralcel OD-H column.

Main Results:

• The microfluidic synthesis yielded monodisperse macroporous silica with a monomodal pore structure and narrow pore size distribution.
• The Mono-CSP exhibited significantly improved peak efficiencies, attributed to reduced eddy diffusion, as shown by Van Deemter curves.
• Compared to the conventional Chiralcel OD-H, the Mono-CSP demonstrated enhanced resolution for 93% of 42 investigated enantiomers and increased retention factors for 90.5%.

Conclusions:

• The microfluidic precision manufacturing approach enables the creation of high-performance chiral stationary phases with superior enantioseparation capabilities.
• The Mono-CSP offers enhanced retention and resolution across diverse compound classes (acidic, neutral, basic alcohols, ketones, etc.).
• This microfluidic methodology shows potential for broad application in preparing various types of advanced chiral chromatographic stationary phases.