Theoretical Modeling and Experimental Evaluation of a Microscale Molecular Mass Sensor

A theoretical model for a recently developed microscale molecular mass sensor (μ-MMS) is presented. The μ-MMS employs a widely applicable technique of measuring the refractive index gradient (RIG) in a microchannel created after two adjacent streams merge: a “sample stream” containing analyte(s) of interest in a host solvent and a “mobile-phase” stream containing only the host solvent. Because the flow in the microchannel is laminar, the analytes in the sample stream mix with the mobile-phase stream primarily by diffusion. The diffusion-induced RIG in the microchannel is measured by monitoring the deflection angle of a diode laser probe beam, which is orthogonal to both the direction of flow and the direction of analyte diffusion. The μ-MMS samples the RIG with probe beams at two positions along the direction of flow, and the ratio of the downstream to the upstream signal monitors the diffusion coefficient. Following calibration for a given class of compounds, the molecular mass of an analyte of interest can be determined. Along with the analyte diffusion coefficient, the theoretical model indicated three other specific parameters are important to interpret the μ-MMS output: the radius of the interrogating light probe beams, the time intervals between each of the detection positions, and the merge point relative to the detection positions. A series of experiments were conducted at different beam radii and flow rates to investigate these parameters, and the results are consistent with the model. The model shows that by using smaller beam radii and altering flow rates the molecular mass range of the μ-MMS can be, in principle, tuned from less than 102 g/mol to greater than 108 g/mol. The ratio data from the μ-MMS is also demonstrated to readily provide a “universal calibration”, from which the determination of unknown diffusion coefficients can be readily obtained.