Measuring the transverse concentration gradient between adjacent laminar flows in a microfluidic device by a laser-based refractive index gradient detector

A detection scheme that probes the refractive index gradient (RIG) between adjacent laminar flows in microfluidic devices has been developed and evaluated. The behavior of low Reynolds number flows has been well documented and shows that molecular transport (mixing) between adjacent laminar flows occurs by molecular diffusion between the flow boundaries. A diode laser has been used to probe the transverse concentration gradient at a selected position along a microchannel. The concentration gradient is affected by the transverse diffusion from a flow with analyte into a flow initially without analyte. To optimize sensitivity, the RIG is probed at a position in which molecular diffusion across the boundary of the two flows has been minimal, i.e. just after the flow initially without analyte merges with the flow initially containing the analyte at a given concentration. The RIG formed causes the laser beam, impinging orthogonal to the RIG through the microchannel, to be deflected. The angle of deflection is then monitored on a position sensitive detector (PSD). Currently, this detection scheme is demonstrated to provide quantitative detection of sucrose, as a test analyte, with a concentration limit of detection (LOD) of 96 ppm (w/v) or 280 μM, corresponding to 1.3×10−5 ΔRI units using 3σ baseline noise. A dynamic range of 96 ppm to 50% sucrose is obtained. This detection method provides universal detection selectivity for microfluidic analysis systems that are becoming increasingly useful in monitoring chemical systems, particularly for the polymer, pharmaceutical and life sciences fields. For a larger molecular weight analyte with a smaller diffusion coefficient, lower concentration and RI LODs were achieved since detection sensitivity is a function of analyte diffusion. For example, for the polymer poly (ethylene glycol) with a molar mass of 11 840 g mol−1, the LOD was experimentally determined to be 56 ppm (4.7 μM), equivalent to a RI LOD of 4.5×10−6 ΔRI (3σ). The detection limit for proteins was also found to be favorable. For example, with the current configuration, ribonuclease A (RNAse) had a LOD of 46 ppm (3.4 μM), and bovine serum albumin (BSA) had a LOD of 54 ppm (780 nM).