ELSD (Evaporative Light Scattering Detection) employs a unique method of detection. The process involves the nebulization of the column eluent, transforming it into an aerosol cloud. As this cloud travels through a heated zone within the instrument, the more volatile mobile phase evaporates, leaving a smaller cloud of analyte particles. These particles pass through a beam of light, scattering some of the light, which is converted into an electronic signal, per Figure 1.
ELSD can be used with mobile phases that absorb UV light and, unlike refractive index, is gradient friendly. Solvent additives or modifiers must be chosen carefully, as non-volatile compounds will interfere with detection and may accumulate in the detector.
Examples of volatile buffers and solvent modifiers include trifluoroacetic acid, formic and acetic acids, ammonium formate, ammonium acetate, ammonium carbonate, or ammonium hydroxide. These can be used in concentration up to ~25 mMol.
The melting point of a compound plays a role in detection. For good analyte response, the melting point of a compound should be significantly higher than the nebulization/ evaporation temperatures used in the ELSD.1
ELSD is a “lossy" technique, whereby the sample that passes through the ELSD can't be recovered for fractionation, so a splitter of some sort is required to send a small amount of sample to the detector to trigger peak detection. Some manufacturers boast that their system has better recovery than others with ELSD detection because they split less sample to the detector, but this often comes at reduced sensitivity, as there are fewer analyte particles, causing smaller peaks.
1Webster GK, Jensen JS, Diaz AR.
An investigation into detector limitations using evaporative light-scattering detectors for pharmaceutical applications. J Chromatographic Sci. 2004 Oct;42(9):484-90. doi: 10.1093/chromsci/42.9.484. PMID: 15693189.
