A global trend in the field of biomedical research is the expansion of the range of bioanalytical methods based on the integrated use of biosensors and microfluidic systems. The FMN Laboratory is currently developing a new generation of bioanalytical devices – lab-on-a-chip and other personalized medicine devices, which will significantly reduce the volume of samples and expensive reagents, increase the speed of analyzes, expand the range of detected biomarkers, and miniaturize devices. Altogether, it will make laboratory methods diagnostics available for the most remote settlements, on long-term expeditions, and for telemedicine.
The FMN team has been developing in the field of microfluidics since 2016. For 5 years, a technological platform for creating multilayer microfluidic chips with integrated valves, integrated devices for high-precision flow control of liquid reagents on a chip, a series of microfluidic devices for precision mixing of reagents on a chip, as well as several prototypes of a universal laboratory control device-on-a-chip has been developed. Today the team is developing silicon-on-glass bioMEMS technology.
Membrane-free flow sensor for a microfluidic lab-on-chip
The FMN Laboratory has developed a new membrane-free flow sensor integrated into the microfluidic chip, based on the modified principle of a constant temperature anemometer with a temperature compensation system. The main advantage of the developed sensor is the lack of a membrane in the structure, due to which it is possible to reduce significantly the cost and complexity of its manufacture. In addition, due to the transition from silicon to glass as a substrate material, it became possible to create optically transparent microfluidic chips with integrated flow sensors.
The developed flow sensor made it possible to reduce the dead volume of the measuring unit by almost 1000 times (from 148.5 μl to 0.15 μl) in comparison with the use of an external measuring device, which is the best result in the world today. The sensitivity of the sensors reached 12 mV / (μL / min), while the measurement accuracy was more than 4 μL / min in the range of 0-80 μL / min. These parameters correspond to the best world analogs from Dolomite (England) and Elveflow (France).
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. A team of researchers from the Bauman Moscow State Technical University and the Institute of Biochemical Physics, Russian Academy of Sciences has developed an on-chip automatic efficient bacteria separation and preconcentration method with the use of pressure-driven flow-controlled microfluidics.
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.
More detailed information available here.
Microfluidic mixer chip
The FMN team has developed a microfluidic mixer chip that solves one of the most common problems in analysis systems – accurate dilution of reagents in a given ratio with subsequent mixing. Such manipulations are carried out millions of times a day, for example, when mixing a patient's blood and reagents to detect diseases or to check a patient's compatibility with drugs.
The chip consists of a microfluidic part with channels 50 and 200 micrometers in height and a detection system of metal electrodes on a glass substrate. The manufacturing process of such a device includes dozens of technological operations: from lithography of the device layer topology to precision multilayer assembly (bonding).
Silicon-on-glass bioMEMS are made of biocompatible materials that provide the ability to study living cells. These microfluidic chips (unlike PDMS microfluidic devices) allow maintaining the geometry of microfluidic channels for a long time. They are durable, enable the manufacture of chips with smaller structures, and are suitable for commercial use.
The bioMEMS developed by the FMN team has a number of active elements on board, including heaters and temperature sensors and performs the function of high-precision measurement of the flow inside the channel. The chip is made using the team’s own technology, including plasma-chemical etching of silicon and etching of through holes in one cycle, followed by anodic bonding to pack a stack.