Multilayer pressure driven microfluidic platform - µFLATLab (2011)

In this work a new pressure driven microfluidic platform (µFLATLab) is presented, consisting of a lab on a chip device and a processing instrument for functional control. The disposable lab on a chip device consists of a multilayer polymer stack made of structured polycarbonate (PC) bulk welded to a thermoplastic elastomer membrane (TPE). Fluid management is realized by integrated active membrane microvalves with a high sealing quality and short switching times in the range of 100 ms. The concept of a sealing membrane works reliable and independent from liquid viscosity or surface tension. Membrane micropumps with a broad controllable flow rate from 0.1 µl&#8729;s-1 to 55.8 µl&#8729;s-1 are realized for liquid transportation and circulation for mixing discrete liquid plugs. Compared to microfluidic platforms based on polydimethylsiloxane (PDMS) the working principle of this platform is characterized by a comparably low actuation pressure and a remarkable level of design flexibility. A full three dimensional fluidic network is created by lasercutting through the membrane layer. Basic operations for microfluidic applications such as valving, pumping and mixing can be realized using this lab on a chip device concept. In addition a liquid reagent storage method is implemented, where a liquid reagent is tightly sealed without any additional production process step. By applying pressure on the storage chamber the seal is broken and the liquid reagent is pushed into the fluidic network. The used materials PC and TPE can be manufactured and structured by mass production processes like injection molding and extrusion. A cost-efficient and production chain consistent way of manufacturing a disposable lab-on-a-chip device is achieved by using laserwelding as a joining technology. <br>A transportable processing instrument for the control and automation of the lab on a chip device forms the second part of the microfluidic platform. It includes a carrier for the lab-on-a-chip device, eight fluidic and twelve pneumatic interconnections to the macro world for fluid management, two resistive heaters, fan air coolers and temperature sensors for thermal management. Twelve pilot valves are independently controlled for the actuation of the integrated microvalves. Heating rates of 4 K&#8729;s-1 and cooling rates of -1.3 K&#8729;s-1 enable fast thermal cycling. This portable processing instrument with the size of a shoe box has a graphical user interface (GUI) for programming parameters as temperature, duration and pressure switch for each assay step. <br>With this microfluidic platform, a lab-on-a-chip device was developed for the processing of a diagnostic example assay. The assay detects the resistance of Escherichia coli (E coli) against fluoroquinolone-based antibiotics. The required sub functions include the accumulation of E. coli bacteria directly from a 10 ml sample, their thermal lysis, a DNA amplification step using a polymerase chain reaction (PCR), before detection of the resistance information with a DNA microarray. An integrated silica filter is used for the accumulation of bacteria out of a 10 ml sample with a filter efficiency of over 90 %. The processable number of bacteria range from 104 to 107. The bacteria lysis is made as an initial thermal step at 95°C before the PCR. The 31 amplification cycles of the PCR are performed in less than 2 h with the processing instrument. The reaction time for the detection microarray could be accelerated from 60 min down to 30 min using an integrated micropump as an active circular mixer. At the same time the signal-to-noise-ratio could be increased. This fully automatable assay for the example application takes only 3 h from sample input to result. A diagnostic relevant bacteria concentration threshold of 104 bac/10 ml could be proven to be detected with the assay integrated on chip. The concept of this cost-efficient mass producible microfluidic platform promises a broad range of future applications with the benefit of a robust, fast and reproducible results.<br>