Dual-Capillary Backscatter Interferometry for HighSensitivity Nanoliter-Volume Refractive Index Detection with Density Gradient Compensation

A simple, stable, ultrasensitive dual-capillary dual-bicell (DCDB) microinterferometic backscattering detection (MIBD) system was developed. In DCDB MIBD, a He-Ne laser beam passes through a half-wave plate onto the cross section of two capillaries, one for reference and another for sensing analyte. The position of the backscattered fringe from each capillary, which are in proximity or essentially identical thermal environments, was detected with matched bicell photodetectors. The configuration was found to effectively compensate for thermal drift, which is normally the major source of noise in refractive index (RI) detection systems. It is shown that passive environmental compensation leads to greatly enhanced signal in nanoscale refractometry preformed by MIBD. An order of magnitude improvement in detection limits over single channel configurations is possible. Performance reaches the 10-9 RIU level for like solvents in the presence in extremely large thermally induced RI gradients. At this level of detectability, DCDB MIBD could facilitate nanoliter-volume, femtomole-level universal detection in applications ranging from -HPLC and on-chip CE to scanning microcalorimetry.