Nanoliter-scale non-invasive flow-rate quantification using micro-interferometric back-scatter and phase detection

The current trend toward miniaturization of fluid-handling systems, particularly those of micro-fluidic devices on the capillary-scale, will certainly lead to improvements in chemical and biochemical analyses. Unfortunately, when fluid volumes reach nano- and picoliter scale it is problematic to perform non-invasive fast and accurate volume flow or flow velocity measurements. Here a simple, non-invasive method is presented for detecting and measuring linear flow velocity within fluid-filled capillaries. A small fluid volume is repeatedly heated locally by means of an infrared laser diode and using the micro-interferometric back-scatter detector (MIBD) at a fixed distance downstream, a thermally induced change in refractive index is observed when the heated volume traverses the probe volume of the detector. Fluid velocity is calculated by monitoring the phase difference between the second harmonic of the heating function and the resulting MIBD output in the Fourier domain. In a probe volume of 40 nL flow rates between I and 10 microL min(-1) are quantifiable, with 3sigma detection limits determined to be 42.8 nL min(-1).