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Supercritical fluid chromatography (SFC) provides a beneficial substitute for gas chromatography (GC) and liquid chromatography (LC) for certain samples because it merges the top attributes of both techniques. SFC allows the separation and analysis of compounds that GC or LC does not easily manage. These compounds are traditionally nonvolatile or thermally unstable, making GC unsuitable and lacking functional groups required for HPLC analysis.
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Chiral Chromatography Resolution Can Be Enhanced by Using Microfluidic Precision Manufactured Macroporous Silica

Jikai Chen1, Hanchen Cao1, Ruichen An1

  • 1Department of Chemistry and the MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Xiamen University, Xiamen 361005, China.

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|March 20, 2026
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Summary

Researchers developed a new microfluidic method to create uniform macroporous silica microspheres for chiral stationary phases (CSPs). This precision manufacturing significantly improves chiral separation performance and retention in high-performance liquid chromatography (HPLC).

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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.