Modular microreactor with integrated reflection element for online reaction monitoring using infrared spectroscopy.

We report on the fabrication of an internal reflection element (IRE) combined with a modular polymer microfluidic chip that can be used for attenuated total reflection (ATR) infrared spectroscopy. The IRE is fabricated from a silicon wafer. Two different polymers are used for the fabrication of the two types of modular microfluidic chips, namely polydimethylsiloxane (PDMS) and cyclic olefin copolymer (COC). The microfluidic chip is modular in the sense that several layers of mixing channels, using the herringbone mixer principle, and reactions chambers, can be stacked to facilitate the study of the desired reaction. A model Paal-Knorr reaction is carried out to prove that the chip works as intended. Furthermore, we highlight the strength of IR spectroscopy as a tool for reaction monitoring by identifying the peaks and showing the different reaction orders at the different steps of the Paal-Knorr reaction. The reduction of the aldehyde groups indicates a (pseudo) first order reaction whereas the vibrational modes associated with the ring formation indicate a zero order reaction. This zero order reaction can be explained with literature, where it is suggested that water acts as a catalyst during the dehydration step, which is the final step in the pyrrole ring formation.

Integrated microfluidic biosensing platform for simultaneous confocal microscopy and electrophysiological measurements on bilayer lipid membranes and ion channels.

Combining high-resolution imaging and electrophysiological recordings is key for various types of experimentation on lipid bilayers and ion channels. Here, we propose an integrated biosensing platform consisting of a microfluidic cartridge and a dedicated chip-holder to conduct such dual measurements on suspended lipid bilayers, in a user-friendly manner. To illustrate the potential of the integrated platform, we characterize lipid bilayers in terms of thickness and fluidity while simultaneously monitoring single ion channel currents. For that purpose, POPC lipid bilayers are supplemented with a fluorescently-tagged phospholipid (NBD-PE, 1% mol) for Fluorescence Recovery After Photobleaching (FRAP) measurements and a model ion channel (gramicidin, 1 nM). These combined measurements reveal that NBD-PE has no effect on the lipid bilayer thickness while gramicidin induces thinning of the membrane. Furthermore, the presence of gramicidin does not alter the lipid bilayer fluidity. Surprisingly, in lipid bilayers supplemented with both probes, a reduction in gramicidin open probability and lifetime is observed compared to lipid bilayers with gramicidin only, suggesting an influence of NBD-PE on the gramicidin ion function. Altogether, our proposed microfluidic biosensing platform in combination with the herein presented multi-parametric measurement scheme paves the way to explore the interdependent relationship between lipid bilayer properties and ion channel function.

Exploiting biased reptation for continuous flow preparative DNA fractionation in a versatile microfluidic platform.

A new approach is presented for preparative, continuous flow fractionation of sub-10-kbp DNA fragments, which exploits the variation in the field-dependent mobility of the DNA molecules based on their length. Orthogonally pulsed electric fields of significantly different magnitudes are applied to a microchip filled with a sieving matrix of 1.2% agarose gel. Using this method, we demonstrate a high-resolution separation of 0.5, 1, 2, 5, and 10 kbp DNA fragments within 2 min. During the separation, DNA fragments are also purified from other ionic species. Preparative fractionation of sub-10-kbp DNA molecules plays an important role in second-generation sequencing. The presented device performs rapid high-resolution fractionation and it can be reliably manufactured with simple microfabrication procedures.

Pressure-driven ballistic Kelvin's water dropper for energy harvesting.

In this paper, we introduce a microfluidic-based self-excited energy conversion system inspired by Kelvin's water dropper but driven by inertia instead of gravity. Two micro water jets are produced by forcing water through two micropores by overpressure. The jets break up into microdroplets which are inductively charged by electrostatic gates. The droplets land on metal targets which are gradually charged up to high voltages. Targets and electrostatic gates are cross-connected in a way similar to Kelvin's water dropper. Application of pressure as driving force instead of gravity as in Kelvin's dropper allows for much higher energy densities. To prevent overcharging of the droplets by the inductive mechanism and consequent droplet loss by repulsion from the target as in Kelvin's water dropper, a voltage divider using inversely connected diodes was introduced in our system to control the charge induction providing self-limiting positive feedback by the diode characteristics. A maximal 18% energy conversion efficiency was obtained with the diode-gated system.

Microstamped Petri dishes for scanning electrochemical microscopy analysis of arrays of microtissues.

While scanning electrochemical microscopy (SECM) is a powerful technique for non-invasive analysis of cells, SECM-based assays remain scarce and have been mainly limited so far to single cells, which is mostly due to the absence of suitable platform for experimentation on 3D cellular aggregates or microtissues. Here, we report stamping of a Petri dish with a microwell array for large-scale production of microtissues followed by their in situ analysis using SECM. The platform is realized by hot embossing arrays of microwells (200 µm depth; 400 µm diameter) in commercially available Petri dishes, using a PDMS stamp. Microtissues form spontaneously in the microwells, which is demonstrated here using various cell lines (e.g., HeLa, C2C12, HepG2 and MCF-7). Next, the respiratory activity of live HeLa microtissues is assessed by monitoring the oxygen reduction current in constant height mode and at various distances above the platform surface. Typically, at a 40 µm distance from the microtissue, a 30% decrease in the oxygen reduction current is measured, while above 250 µm, no influence of the presence of the microtissues is detected. After exposure to a model drug (50% ethanol), no such changes in oxygen concentration are found at any height in solution, which reflects that microtissues are not viable anymore. This is furthermore confirmed using conventional live/dead fluorescent stains. This live/dead assay demonstrates the capability of the proposed approach combining SECM and microtissue arrays formed in a stamped Petri dish for conducting cellular assays in a non-invasive way on 3D cellular models.

High-efficiency ballistic electrostatic generator using microdroplets.

The strong demand for renewable energy promotes research on novel methods and technologies for energy conversion. Microfluidic systems for energy conversion by streaming current are less known to the public, and the relatively low efficiencies previously obtained seemed to limit the further applications of such systems. Here we report a microdroplet-based electrostatic generator operating by an acceleration-deceleration cycle ('ballistic' conversion), and show that this principle enables both high efficiency and compact simple design. Water is accelerated by pumping it through a micropore to form a microjet breaking up into fast-moving charged droplets. Droplet kinetic energy is converted to electrical energy when the charged droplets decelerate in the electrical field that forms between membrane and target. We demonstrate conversion efficiencies of up to 48%, a power density of 160 kW m(-2) and both high- (20 kV) and low- (500 V) voltage operation. Besides offering striking new insights, the device potentially opens up new perspectives for low-cost and robust renewable energy conversion.