Breaking the 10-7 barrier for RI measurements in nanoliter volumes

Refractive index (RI) detection is a common technique used in chemical and biochemical analysis. It can be employed to perform universal solute detection in muHPLC and CE, as well as temperature measurements. However, accurate RI measurements in nanoliter volumes still present a significant challenge. Here we present an alternative method to extract RI information encoded in spatial distribution of the backscattered fringes produced by a microinterferometric backscatter detector (MIBD) based on spatial Fourier analysis. By monitoring the phase in the Fourier domain, we were able to obtain detection limits of 7 x 10(-8) RIU. It was also shown that such calculations could be performed in real time, thus making MIBD with Fourier analysis compatible with muHPLC, CE, and FIA.