Kristelle Bougot-Robin

High-throughput particle manipulation by hydrodynamic, electrokinetic, and dielectrophoretic effects in an integrated microfluidic chip

Integrating different steps on a chip for cell manipulations and sample preparation is of foremost importance to fully take advantage of microfluidic possibilities, and therefore make tests faster, cheaper and more accurate. We demonstrated particle manipulation in an integrated microfluidic device by applying hydrodynamic, electroosmotic (EO), electrophoretic (EP), and dielectrophoretic (DEP) forces. The process involves generation of fluid flow by pressure difference, particle trapping by DEP force, and particle redirect by EO and EP forces. Both DC and AC signals were applied, taking advantages of DC EP, EO and AC DEP for on-chip particle manipulation. Since different types of particles respond differently to these signals, variations of DC and AC signals are capable to handle complex and highly variable colloidal and biological samples. The proposed technique can operate in a high-throughput manner with thirteen independent channels in radial directions for enrichment and separation in microfluidic chip. We evaluated our approach by collecting Polystyrene particles, yeast cells, and E. coli bacteria, which respond differently to electric field gradient. Live and dead yeast cells were separated successfully, validating the capability of our device to separate highly similar cells. Our results showed that this technique could achieve fast pre-concentration of colloidal particles and cells and separation of cells depending on their vitality. Hydrodynamic, DC electrophoretic and DC electroosmotic forces were used together instead of syringe pump to achieve sufficient fluid flow and particle mobility for particle trapping and sorting. By eliminating bulky mechanical pumps, this new technique has wide applications for in situ detection and analysis.

2D label-free imaging of resonant grating biochips in ultraviolet

2D images of label-free biochips exploiting resonant waveguide grating (RWG) are presented. They indicate sensitivities on the order of 1 pg/mm2 for proteins in air, and hence 10 pg/mm2 in water can be safely expected. A 320x256 pixels Aluminum-Gallium-Nitride-based sensor array is used, with an intrinsic narrow spectral window centered at 280 nm. The additional role of characteristic biological layer absorption at this wavelength is calculated, and regimes revealing its impact are discussed. Experimentally, the resonance of a chip coated with protein is revealed and the sensitivity evaluated through angular spectroscopy and imaging. In addition to a sensitivity similar to surface plasmon resonance (SPR), the RWGs resonance can be flexibly tailored to gain spatial, biochemical, or spectral sensitivity.

Resonant waveguide sensing made robust by on-chip peak tracking through image correlation

We demonstrate a solution to make resonant-waveguide-grating sensing both robust and simpler to optically assess, in the spirit of biochips. Instead of varying wavelength or angle to track the resonant condition, the grating itself has a step-wise variation with typically few tens of neighboring “micropads.” An image capture with incoherent monochromatic light delivers spatial intensity sequences from these micropads. Sensitivity and robustness are discussed using correlation techniques on a realistic model (Fano shapes with noise and local distortion contributions). We confirm through fluid refractive index sensing experiments an improvement over the step-wise maximum position tracking by more than 2 orders of magnitude, demonstrating sensitivity down to 2 × 10−5 RIU, giving high potential development for bioarray imaging.

Resonant spatial tracking using nanostructured resonant waveguide grating for multispectral sensing by imaging

Resonant profile shift resulting from a change of resonant conditions is classically used for sensing, either liquid refractive index or immobilized biological layer effective thickness. Resonant waveguide gratings (RWG) allow sensing over a large spectral domain, depending on the materials and geometrical parameters of the grating. Profiles measurements usually involve scanning instrumentation. We recently demonstrated that direct imaging multi-assay RWGs sensing may be rendered more robust using spatial Fano profiles from “chirped” RWG chips. The scheme circumvents the classical but demanding scans: instead of varying angle or wavelength through fragile moving parts or special optics, a RWG structure parameter is varied. Our findings are illustrated with resonance profiles from nanostructured silicon nitride waveguide on glass. A sensitivity down to Δn=2x10-5 or biomolecules mass density of 10 pg/mm2 is demonstrated through theory and experiments. To assess different sensing wavelength, the period might also vary within the same chip support. We discuss guiding properties and sensing sensitivities of RWG sensing over the whole visible spectral range. Resonant profiles are analyzed using a correlation approach, correlating the sensed signal to a zero-shifted reference signal. This analysis was demonstrated to be more accurate than usual fitting, for analyzing signals including noise contribution. The current success of surface plasmon imaging suggests that our work could leverage an untapped potential to extend such techniques in a convenient and sturdy optical configuration. Moreover, extended spectral range sensing can be addressed by dielectric waveguide structures. This allows sensitive sensing of small volumes of analyte, which can be circulated close from the resonant waveguide. Together with the demonstration of highly accurate fits through correlation analysis, our scheme based on a “Peak-tracking chip” demonstrates a new technique for multispectral sensitive sensing through nanostructured chip imaging.

Hybrid silicon photonics using oxide-free bonding and nanostructured effective materials

Oxide-free bonding of indium phosphide epitaxial layers onto silicon-on-insulator (SOI) offers good thermal and electrical contact. These properties are retained if guidance engineering of the resulting stack is performed by nanostructuring the silicon layer to produce a lower effective index layer. We discuss the optical characterization of such a system by a simple prism deviation method for a thin stack, or diffraction to the air for a more multimode stack, adding a superperiod to the nanostructure.

Fano Lineshapes of "Peak-tracking chip" Spatial Profiles Analyzed with Correlation Analysis for Bioarray Imaging and Refractive Index Sensing

The asymmetric Fano resonance lineshapes, resulting from interference between background and a resonant scattering, is archetypal in resonant waveguide grating (RWG) reflectivity. Resonant profile shift resulting from a change of refractive index (from fluid medium or biomolecules at the chip surface) is classically used to perform label-free sensing. Lineshapes are sometimes sampled at discretized “detuning” values to relax instrumental demands, the highest reflectivity element giving a coarse resonance estimate. A finer extraction, needed to increase sensor sensitivity, can be obtained using a correlation approach, correlating the sensed signal to a zero-shifted reference signal. Fabrication process is presented leading to discrete Fano profiles. Our findings are illustrated with resonance profiles from silicon nitride RWGs operated at visible wavelengths. We recently demonstrated that direct imaging multi-assay RWGs sensing may be rendered more reliable using “chirped” RWG chips, by varying a RWG structure parameter. Then, the spatial reflectivity profiles of tracks composed of RWGs units with slowly varying filling factor (thus slowly varying resonance condition) are measured under monochromatic conditions. Extracting the resonance location using spatial Fano profiles allows multiplex refractive index based sensing. Discretization and sensitivity are discussed both through simulation and experiment for different filling factor variation, here Δf=0.0222 and Δf=0.0089. This scheme based on a “Peak-tracking chip” demonstrates a new technique for bioarray imaging using a simpler set-up that maintains high performance with cheap lenses, with down to Δn=2×10-5 RIU sensitivity for the highest sampling of Fano lineshapes.

UV imaging of biochips based on resonant grating

In the frame of biological threat, security systems require label free biochips for rapid detection. Biosensors enable to detect biological interactions, between probes localized at the surface of a chip, and targets present in the sample solution. Here, we present an optical transduction, enabling 2D imaging, and consequently parallel detection of several reactions. It is based on the absorption of biological molecules in the UV domain. Thus, it is based on an intrinsic property of biological molecules and does not require any labelling of the biological molecules. DNA and proteins absorb UV light at 260 and 280 nm respectively. Sensitivity is a major requirement of biosensing devices. Configurations leading to enhancement of the interaction between light and biological molecules are of interest. For a better sensitivity, resonant grating structures are then studied. They enable to confine the electric field close to the biological layer. Imaging of resonant grating is not largely studied, even for visible wavelengths, but it results in good sensitivity. The protein used in this study is the methionyl-tRNA synthetase. Its absorption is representative of protein absorption, and it can then serve as a model for immunological detection. The best experimental contrast due to a monolayer of proteins is 40%. With data processing currently employed for biochip imaging: average on several acquisitions and on all the pixels imaging the biological spots, the device is able to detect a surface density of proteins in the 10 pg/mm range.