Separations at the Micro Scale: Recommended Reading

Contemporary Microscale Separation Technology1 summarizes the development and state-of-the-art of liquid phase separation technology as of about 2010. This is a complex topic, since there are many subsegments, each with a different name and associated idiosyncrasies. But there is a consistent driving force favoring the development of ever-smaller separation units. Scale factors are often nonlinear with feature size. Reducing size uncovers idiosyncrasies that can be exploited for assays or microscale prep.

Capillary LC

The author, Prof. Chao Yan, Ph.D., got his start in liquid phase separations with capillary columns while working as a postdoc with Dr. Fritz Erni in 1991 at Sandoz Pharmaceutical, and later with Prof. Richard Zare at Stanford University. Yan developed and patented electrokinetic packing technology for capillary LC columns, a process that is still used commercially in global chromatography. Capillary liquid phase separations have been his focus ever since. The last three chapters, which comprise the last half of the book, focus on liquid chromatography. The first chapter is on LC with capillary columns; the second reviews LC in microfabricated devices; and the third reports on advances in multidimensional techniques, including cLC×cLC (2-D capillary liquid chromatography), LC-CEC (liquid chromatography-capillary electrochromatography), LC-CE (liquid chromatography-capillary electrophoresis), and CE×CE (capillary electrophoresis-capillary electrophoresis). All appear to be up to date, with references as recent as 2010.

Capillary electrophoresis

Capillary electrophoresis is the first chapter in the book. As with all the chapters, it starts with a short summary of the historical development, including work in 1967 by Stellan Hjertén (University of Uppsala, Sweden [now retired]) using 300-μm-i.d. glass capillaries. However, this was ahead of its time. One had to wait more than a decade for the introduction of fused-silica capillaries for capillary GC and then CE to make CE really practical.

The chapter on CE analyzes topics such as instrumentation and injection techniques. The author describes the use of a four-port valve for injection in quantitative CE. A short section on modifying the surface activity of the capillaries, especially fused silica, should be useful for the novice. Sections on capillary zone electrophoresis (CZE), micellar electrokinetic chromatography (MEKC), capillary isoelectric focusing (cIEF), capillary gel electrophoresis (CGE), and capillary isotachophoresis (cITP) are clearly explained. Numerous references to recent advances will help novices pick up the thread.

Capillary electrochromatography

The chapter on capillary electrochromatography is appropriately sandwiched between the chapters on CE and cLC since it is a hybrid of both. CEC is much more popular in China than elsewhere. Important advantages are rapid, efficient separations and low consumption of mobile phase, which minimizes the environmental footprint. Dr. Yan’s description reflects his quarter century’s experience with CEC and pressurized CEC. Some of the sections are: “Monolithic Columns,” “Open Tubular Columns,” and “Mass Spectrometry Coupling.” MS avoids the problem with optical detection in short-pathlength detection cells. The chapter concludes with an expansive review of applications.


Microscale liquid separations is a very fragmented technology. Understanding these micro segments is important in achieving very useful separations and assays. Each merits its own name. An index of abbreviations used in the book is nine pages long.

One might take a much more expansive view of microscale separations, including topics such as atomic force microscopy, laser tweezers, and other trapping technology. But there seems to be a general consensus that capillaries are the future of analytical separations, especially in the liquid phase.

More experienced readers will enjoy the history included in the book, but we are a limited market. For those new to this segment, it will be their first choice when looking for basic theory, experimental idiosyncrasies, and selected applications. The book seems to be ideally suited for focused courses on capillary separations at the graduate school level, or for intense short courses.


  1. Yan, C. Contemporary Microscale Separation Technology. HNB Publishing: New York, NY, 2013; ISBN 978-0-9728874-2-4.

Robert L. Stevenson, Ph.D., is a Consultant and Editor of Separation Science for American Laboratory/Labcompare; e-mail: [email protected].