Integrated membrane-free thermal flow sensor for silicon-on-glass microfluidics.

Lab-on-a-chip (LOC) forms the basis of new-generation portable analytical systems. LOC allows the manipulation of ultralow flows of liquid reagents and multistep reactions on a microfluidic chip, which requires a robust and precise instrument to control the flow of liquids on a chip. However, commercially available flow meters appear to be a standalone option adding a significant dead volume of tubes for connection to the chip. Furthermore, most of them cannot be fabricated within the same technological cycle as microfluidic channels. Here, we report on a membrane-free microfluidic thermal flow sensor (MTFS) that can be integrated into a silicon-glass microfluidic chip with a microchannel topology. We propose a membrane-free design with thin-film thermo-resistive sensitive elements isolated from microfluidic channels and a 4'' wafer silicon-glass fabrication route. It ensures MTFS compatibility with corrosive liquids, which is critically important for biological applications. MTFS design rules for the best sensitivity and measurement range are proposed. A method for automated thermo-resistive sensitive element calibration is described. The device parameters are experimentally tested for hundreds of hours with a reference Coriolis flow sensor demonstrating a relative flow error of less than 5% within the range of 2-30 µL min-1 along with a sub-second time response.

Cyclic on-chip bacteria separation and preconcentration.

Nanoparticles and biological molecules high throughput robust separation is of significant interest in many healthcare and nanoscience industrial applications. In this work, we report an on-chip automatic efficient separation and preconcentration method of dissimilar sized particles within a microfluidic platform using integrated membrane valves controlled microfiltration. Micro-sized E. coli bacteria are sorted from nanoparticles and preconcentrated on a microfluidic chip with six integrated pneumatic valves (sub-100 nL dead volume) using hydrophilic PVDF filter with 0.45 µm pore diameter. The proposed on-chip automatic sorting sequence includes a sample filtration, dead volume washout and retentate backflush in reverse flow. We showed that pulse backflush mode and volume control can dramatically increase microparticles sorting and preconcentration efficiency. We demonstrate that at the optimal pulse backflush regime a separation efficiency of E. coli cells up to 81.33% at a separation throughput of 120.45 µL/min can be achieved. A trimmed mode when the backflush volume is twice smaller than the initial sample results in a preconcentration efficiency of E. coli cells up to 121.96% at a throughput of 80.93 µL/min. Finally, we propose a cyclic on-chip preconcentration method which demonstrates E. coli cells preconcentration efficiency of 536% at a throughput of 1.98 µL/min and 294% preconcentration efficiency at a 10.9 µL/min throughput.