Flash Chromatography
Part 3 of our "What is Chromatography Series"

A principle of “green engineering" is: maximize efficiency, meet the need, minimize excess. Flash chromatography covers those bases and more.

In column chromatography, the chemist applies a sample on top of a bed of silica gel or other material (stationary phase) loaded in a glass column. A solvent mixture (mobile phase) is poured over the sample and it is carried by gravity through the vertical column of silica gel, “eluting" the sample as it separates into its individual compounds.

In flash chromatography, invented by organic chemist W. Clark Still in 1978, the mobile phase can be pushed down through the stationary phase using air pressure or, more recently, using a solvent pump, to accelerate solvent flow and achieve superior chemical separations in less time and at higher resolution than traditional, gravity-based column chromatography.

The advantages of using automated flash chromatography are many. It's easy, fast, relatively inexpensive, requires minimal development time, uses less solvent and offers more exacting results. These advantages make flash one of the most popular techniques for purifying pharmaceutical intermediates, as well as final organic products. It is also widely used in natural products research.

In addition, automated flash offers green advantages over manual flash columns, as automated systems can deliver changing solvent composition more easliy than in manual methods.  This enables users to vary the solvent composition increase the gradient strength throughout the run, forcing strongly retained compounds to elute off the column more quickly.

How it works

Today, Flash Chromatography is a completely automated preparative technique influenced by the CombiFlash® equipment designed and manufactured by Teledyne ISCO. Modern flash chromatography systems use pumps to replace the air pressure, detection, and fraction collection in a single package.

In the photo at right is a CombiFlash Torrent large scale flash chromatography instrument. The smaller cartridge on the left is loaded with the sample to be purified. The large column on the right contains silica gel (the stationary phase).

Teledyne ISCO's disposable RediSep® columns for flash chromatography are precision-packed for high resolution and reproducibility. They come in a variety of sizes, from .5 to 5 inches in diameter, and 2.4 to 16.25 inches in length. 


Now, let's go with the flow:

About the detector, chromatogram, and fraction collection

Once the compounds in the test sample elute, or separate, in the stationary phase, the individual compounds are ready to flow to the detector. The prevalent type uses ultraviolet light. Because each compound absorbs a different wavelength of UV light, each compound has its own “signature." The UV reading is sent to the computer, where a graph of the sample's components is generated.

The UV signal for each component in the sample is displayed as peaks on a graph. In this instance, the highest peak is the compound we're looking to purify and isolate. The others are impurities we want to avoid in our purified sample. Instruments from Teledyne ISCO have the computer and screen built right into the unit, saving lab space otherwise taken up by a separate system.

As the compounds are detected via UV light, the signal can then be used to trigger fractionation in test tubes using a fraction collector.  Once each compound is isolated in a tube, the solvent can be evaporated, leaving only the compound itself. That isolated, purified compound can then be used for developing and manufacturing foods, pharmaceuticals, and many other things.


Correlation Between TLC and Chromatograph Readings



Effective Organic Compound Purification Handbook:
Guidelines & Tactics for Flash Chromatography

Download your free copy of our flash chromatography handbook he​re. This 150-page book provides a deep understanding of flash chromatography and is of value to all skill levels, from beginner to expert.

CombiFlash® NextGen Systems
The CombiFlash NextGen line of systems takes the guesswork out of your purifications and increases productivity, whether you are purifying synthetic compounds, natural products, peptides, or polymers. Check out the CombiFlash EZ Prep to discover Teledyne ISCO's latest advances in chromatography, which offers Flash and Prep High-Performance Liquid Chromatography in one compact system. Learn more at Comb​iFlash NextGen Systems.

Be sure to check out the other blogs in this 4 part series: