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

The current trend toward miniaturization of fluid-handling systems, particu larly 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 per form non-invasive fast and accurate volume flow or flow velocity measuremen ts. Here a simple, non-invasive method is presented for detecting and measu ring linear flow velocity within fluid-filled capillaries. A small fluid vo lume is repeatedly heated locally by means of an infrared laser diode and u sing the micro-interferometric back-scatter detector (MIBD) at a fixed dist ance downstream, a thermally induced change in refractive index is observed when the heated volume traverses the probe volume of the detector. Fluid v elocity is calculated by monitoring the phase difference between the second harmonic of the heating function and the resulting MIBD output in the Four ier domain. In a probe volume of 40 nL flow rates between I and 10 muL min( -1) are quantifiable, with 3 sigma detection limits determined to be 42.8 n L min(-1).