Attempts to correlate particle size distribution and column dispersion characteristics (specifically, eddy dispersion – Van Deemter’s “A-term”) go back to the 1950s and have prompted reoccurring debates within the chromatography community. Whether in the form of theoretical modeling or experimental investigation published in journals, or in vendors’ brochures, these efforts are illuminating the path towards the next generation stationary phases and column technologies. They also serve as Damocles’ Sword – demonstrating how far we are from knowing everything about the mysterious “A-term.” Although most recent discussions on the narrow-distributed fully-porous particles remain unsettled, we aim to bring more food for thought to the table…
Our group at Xiamen University, China, has opened a new way to synthesize chromatographic microspheres using droplet microfluidics. Our strategy, which we describe in Angewandte Chemie International Edition, enables precision manufacturing of monodispersed separation mediums and, more importantly, the independent tuning of particle morphology, pore structure, and material chemistry – the foundation of advanced separation performance.
To manufacture the monodisperse microspheres, we designed a 120-channel array droplet microfluidic chip made of polydimethylsiloxane and fabricated by a soft lithography process. With the multi-lane platform, uniform droplets were generated in parallel at a super throughput of up to 240,000 Hz per chip, enabling the synthesis of packing materials at sufficient quantities for the preparation of HPLC columns.
These droplets serve as billions of independent micro-reaction vessels, solidifying into micrometer scale porous microspheres. By controlling droplet size and the type or amount of porogen/monomer within the droplets, particle morphology, pore architecture, and material chemistry can be independently regulated while maintaining monodispersity (CV < 3 percent).
We were also able to mass-produce these droplet-synthesized microspheres, achieving comprehensive coverage of current chromatographic material scopes, including: particle size (sub-2 μm to tens of micrometers), pore size (nonporous, mesoporous, macroporous, and throughporous), and material chemistry (silica, hybrid silica, zirconia and titania). We realized zero defective index and 100 percent production yield during synthesis – eliminating waste discharge from sieving processes and potential environment pollution.
In testing, we packed the microspheres into HPLC columns for separating small molecules, such as alkylbenzene. They exhibit superior separation efficiency compared to commercial polydisperse microspheres of the same size. Notably, the lowest reduced plate height broke through what is thought to be the state-of-the-art (hmin = 2), reaching values as low as 1.89 and even 1.67. This excellent chromatographic performance is primarily attributed to reduced eddy diffusion (reduced by 60 percent), as evidenced by the fitted van Deemter curve.
Looking ahead, we’re excited about the potential to use precision manufacturing to develop the next generation chromatographic material to support green and precision processing – demanded by the chemical and (bio)pharmaceutical industries. I’m also in awe of the beauty of chromatographic science – the way we were able to create these dancing droplets and convert them into high-performance chromatographic microspheres.
But our research also raises a number of intriguing questions:
Have we made a significant breakthrough in separation performance?
If so, can this be explained by a decrease in eddy diffusion (A-term), or are other explanations more plausible?
What do we – and others – need to do to test our hypothesis?
Given the chromatography community’s love of spirited debate, we welcome your perspectives. What do you make of our findings? Join the discussion.
If you would like to share your thoughts on Bo Zhang’s findings as part of a follow-up piece in The Analytical Scientist, please contact [email protected].
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