Latchable microfluidic valve arrays based on shape memory polymer actuators.

We report arrays of latching microfluidic valves based on shape memory polymers (SMPs), and show their applications as reagent mixers and as peristaltic pumps. The valve design takes advantage of the SMP's multiple stable shapes and over a hundred-fold stiffness change with temperature to enable a) permanent zero-power latching in either open or closed positions (>15 h), as well as b) extended cyclic operation (>3000 cycles). The moving element in the valves consists of a tri-layer with a 50 µm thick central SMP layer, 25 µm thick patterned carbon-silicone (CB/PDMS) heaters underneath, and a 38 µm thick styrene ethylene butylene styrene (SEBS) impermeable film on top. Each valve of the array is individually addressable by synchronizing its integrated local Joule heating with a single external pressure supply. This architecture significantly reduces the device footprint and eliminates the need for multiplexing in microfluidic large scale integration (mLSI) systems.

Integration of an optical CMOS sensor with a microfluidic channel allows a sensitive readout for biological assays in point-of-care tests.

In this manuscript, a microfluidic detection module, which allows a sensitive readout of biological assays in point-of-care (POC) tests, is presented. The proposed detection module consists of a microfluidic flow cell with an integrated Complementary Metal-Oxide-Semiconductor (CMOS)-based single photon counting optical sensor. Due to the integrated sensor-based readout, the detection module could be implemented as the core technology in stand-alone POC tests, for use in mobile or rural settings. The performance of the detection module was demonstrated in three assays: a peptide, a protein and an antibody detection assay. The antibody detection assay with readout in the detection module proved to be 7-fold more sensitive that the traditional colorimetric plate-based ELISA. The protein and peptide assay showed a lower limit of detection (LLOD) of 200 fM and 460 fM respectively. Results demonstrate that the sensitivity of the immunoassays is comparable with lab-based immunoassays and at least equal or better than current mainstream POC devices. This sensitive readout holds the potential to develop POC tests, which are able to detect low concentrations of biomarkers. This will broaden the diagnostic capabilities at the clinician's office and at patient's home, where currently only the less sensitive lateral flow and dipstick POC tests are implemented.

A pressure driven injection system for an ultra-flat chromatographic microchannel.

A pressure-actuated on-chip injection system has been developed that is compatible with shallow microchannels with a very large aspect ratio, i.e. 1 microm deep and up to 1000 microm wide. Such channels offer potential advantages in the miniaturisation of liquid chromatography and other separation methods as they allow high loadability and low sample dispersion at the same time. Computational fluid dynamics simulations were performed to predict the flow profiles and the transport of a sample in the system and to justify the injection principle. Based on these simulations, a prototype integrated into a chip for hydrodynamic chromatography has been realised and tested experimentally. The performance of the device is satisfactory and the results are in qualitative agreement with the numerical models.

Zebrafish embryo development in a microfluidic flow-through system.

The zebrafish embryo is a small, cheap, whole-animal model which may replace rodents in some areas of research. Unfortunately, zebrafish embryos are commonly cultured in microtitre plates using cell-culture protocols with static buffer replacement. Such protocols are highly invasive, consume large quantities of reagents and do not readily permit high-quality imaging. Zebrafish and rodent embryos have previously been cultured in static microfluidic drops, and zebrafish embryos have also been raised in a prototype polydimethylsiloxane setup in a Petri dish. Other than this, no animal embryo has ever been shown to undergo embryonic development in a microfluidic flow-through system. We have developed and prototyped a specialized lab-on-a-chip made from bonded layers of borosilicate glass. We find that zebrafish embryos can develop in the chip for 5 days, with continuous buffer flow at pressures of 0.005-0.04 MPa. Phenotypic effects were seen, but these were scored subjectively as 'minor'. Survival rates of 100% could be reached with buffer flows of 2 µL per well per min. High-quality imaging was possible. An acute ethanol exposure test in the chip replicated the same assay performed in microtitre plates. More than 100 embryos could be cultured in an area, excluding infrastructure, smaller than a credit card. We discuss how biochip technology, coupled with zebrafish larvae, could allow biological research to be conducted in massive, parallel experiments, at high speed and low cost.

On-chip hydrodynamic chromatography separation and detection of nanoparticles and biomolecules.

For the first time, on-chip planar hydrodynamic chromatography is combined with UV absorption detection. This technique is suitable for size characterization of synthetic polymers, biopolymers, and particles. Possible advantages of an on-chip hydrodynamic chromatography system over conventional techniques, such as size exclusion chromatography, and field-flow fractionation are fast analysis, high efficiency, reduced solvent consumption, and easy temperature control. The hydrodynamic separations are performed in a planar configuration realized in fused silica using a mixture of fluorescent and nonfluorescent polystyrene particles with sizes ranging from 26 to 155 nm. The planar chip configuration consists of a 1-microm-high, 0.5-mm-wide, and 69-mm-long channel, an integrated 150-pL injection structure, and a 30-microm-deep and 30-microm-wide detection cell, suitable for UV absorption detection. By combination of the separation data obtained in the new fused-silica chip with those obtained using a previously presented planar hydrodynamic chromatography chip, which was realized using silicon and glass microtechnology, a description of the retention and dispersion behavior of planar hydrodynamic chromatography is obtained. Especially the influence of the sidewalls on the dispersion is investigated. Furthermore a hydrodynamic separation within 70 s of several biopolymers is shown in the glass-silicon chip.

A chip system for size separation of macromolecules and particles by hydrodynamic chromatography.

For the first time, a miniaturized hydrodynamic chromatography chip system has been developed and tested on separation of fluorescent nanospheres and macromolecules. The device can be applied to size characterization of synthetic polymers, biopolymers, and particles, as an attractive alternative to the classical separation methods such as size exclusion chromatography or field-flow fractionation. The main advantages are fast analysis, high separation efficiency, negligible solvent consumption, and easy temperature control. The prototype chip contains a rectangular flat separation channel with dimensions of 1 microm deep and 1000 microm wide, integrated with a 300-pL injector on a silicon substrate. The silicon microtechnology provides precisely defined geometry, high rigidity, and compatibility with organic solvents or high temperature. All flows are pressure driven, and a specific injection system is employed to avoid excessive sample loading times, demonstrating an alternative way of lab-on-a-chip design. Separations obtained in 3 min show the high performance of the device and are also the first demonstration of flat channel hydrodynamic chromatography in practice.