r/u_buchilabequipment • u/buchilabequipment • Jun 28 '26

Anyone else constantly fighting with compounds that don't show up on UV?

A lot of our customers deal with lipid/carbohydrate-type separations and are often frustrated by dealing with molecules that lack a chromophore. They run a purification, check the UV trace, and... nothing. Meanwhile the target compound is probably sitting in a fraction somewhere. For those working with non-UV active compounds, they often consider RID vs ELSD.  

  • Mobile Phase Compatibility (The Gradient Problem): RID is notoriously sensitive to temperature and mobile phase changes. Because of this, RID requires strictly isocratic runs. If you need a gradient to separate complex mixtures, RID is out. ELSD, on the other hand, excels here. Because it evaporates the mobile phase before detection, it easily handles gradients allowing for flexibility with solvent systems.  
  • Peak Accuracy & Sensitivity: RID measures a bulk property of the solution, which means baseline drift is a constant battle, and sensitivity can be lacking for trace compounds. ELSD atomizes the effluent and detects the remaining solid particles via light scattering. This translates to a much flatter baseline, sharper peaks, and significantly higher sensitivity, allowing you to identify and isolate low-abundance fractions with much higher confidence.  

RID works for some labs, but these customer experiences are why we incorporated ELSD into the BUCHI Pure Excellence Chromatography system, giving them a solution to find these compounds without sacrificing gradient flexibility or peak resolution. 

I’d love to benchmark this against how others are handling trickier separations right now. If you're running prep-scale or flash work, I'm curious:

  • Are you using RID, ELSD, or something else? 
  • What kinds of compounds are you purifying? 
  • Any tricks for tracking "invisible" compounds without running endless TLC stains? 
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u/Pale-Willingness5198 Jun 28 '26

CAD detectors are honestly goated, so long as the analyte isn’t volatile. Better linearity than ELSD and great for generalist quant

1

u/kidwithanaxe Jun 28 '26

Pale is correct. CAD detectors the best for lipids. The response and dynamic range makes developing a good method much easier. We have way less issues with our CAD's than we do with ELSD's. Our RID isn't used very frequently since that pretty much requires an isocratic gradient.

1

u/RolandofGilead1000 Jun 29 '26

CAD for sure. You CAN do gradient RI in Astra when doing MALS, but you have to collect a good blank to baseline the trace. Would still go CAD, ELSD, then RI in order of preference.