HILIC After the Hype: A Separation Technology Here to Stay

Today Hydrophilic Interaction Liquid Chromatography (HILIC) is by far the fastest growing HPLC separation mode, currently being used by almost 20% of the HPLC instrument owners [1], although the relative number of applications still is considerably fewer.
Does this mean HILIC is yet another technology-hype on the separation science scene, and that the interest will soon vanish? We believe not. This paper reviews the reasons behind the remarkable rise of HILIC and based on that, tries to predict future development within this separation technology. For an introduction to the basic separation requirements and mechanisms, we refer to previous texts [2] on the subject.

HILIC History
The story about modern HILIC started with a publication [3] more than 20 years ago: ‘Hydrophilic-Interaction Chromatography for the Separation of Peptides, Nucleic Acids and other Polar Compounds’. The HILIC separation technique had actually by then been used for about 15 years for sugar analysis on aminopropyl silica columns, but it was with his landmark paper in 1990 that Andrew Alpert showed HILIC to be a universal separation mode, potentially applicable to separation of all types of polar compounds. The publication went by relatively unnoticed by the HPLC community, and for the next 12 years the number of people using HILIC were rather limited [2], many of whom did not even use the term HILIC. By 2002 the number of publications in the scientific literature using HILIC was still only a handful, but the dormant phase of HILIC was now passed and within two years the scene changed dramatically. The small company SeQuant, a spin-off from Umeå University in
northern Sweden, launched a new zwitterionic HILIC phase (the ZIC®-HILIC), Waters launched their plain silica Atlantis® HILIC column and Tosoh re-braded their TSKgel® Amide-80 column as a HILIC column. The number of HILIC publications (and with some delay also column sales) have since then been increasing by 30-40% each year and today scientific papers on new HILIC stationary phases are published in unmatched numbers and every HPLC column manufacturer have at least one HILIC stationary phase in their program.