The refractive index (RI) is the only universal detector in HPLC. The detection principle involves measuring the variation of the refractive index of the effluent from the column passing through the flow cell.
The greater the RI difference between the sample and the mobile phase, the greater the imbalance. Therefore, the sensitivity will be greater for the higher RI difference between the sample and the mobile phase.
On the other hand, in complex mixtures, sample components can cover a wide range of refractive index values, and some may closely coincide with that of the mobile phase, becoming invisible to the detector.
The RI detector is a purely differential instrument and any change in the composition of the eluent requires the rebalancing of the detector. This factor severely limits the application of the RI detector to gradient elution analyzes in which the composition of the mobile phase is modified during the analysis to perform the separation.
Two types of RI detectors are available on the market today. Both require the use of a two-way cell in which the part containing samples is constantly compared with the non-sample reference part.