Abstract

Column efficiency is critical in high performance liquid chromatography (HPLC), in which the size of packing particles plays an essential role. According to the van Deemter equation, the use of smaller particle size of packing materials leads to higher column efficiency. So far, this basic law has driven the evolution of packing materials in HPLC for several generations. The column efficiency has been improved from 60, 000 to 100, 000 plates/m for HPLC up to 250, 000 plates/m since the invention of ultra-performance liquid chromatography (UHPLC) with the use of 1.7 μm porous particles. However, further turning down the size of packing materials to nanoscale has been severely hampered by extremely high back pressure, which poses a huge technical hinderance. The prediction that the minimum particle size in HPLC would not be less than 1 μm had been broken in 2002 using 670-nm nonporous spherical silica particles in a packed capillary for UHPLC separation. Since then, efforts to further reduce the particle size have been made, but practical applications have remained rare. Up to now, the extreme high back-pressure caused by decrease in size of nanoscale packing materials has still remained not well solved from the root. This review starts from the theoretical considerations about the design of nanoscale packing materials to achieve separations with high efficiency. Structural consideration, early efforts and recent advances of nanoscale packing materials are discussed. The newly developed dendritic mesoporous silica nanospheres (DMSNs) are introduced, which has shown unique potential to be a new record towards the ultimate generation of packing materials for ultra-efficient liquid chromatographic separation. Further evolutions of nanoscale packing materials with smaller size for improved column efficiency are concerned about new structure of packing materials, which call for newly advanced packing materials as well as technology innovations on related hardware towards never-reached performance.

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