Flip-chip assembly of an integrated optical sensor

For enabling low cost mass production for photonic circuits, the application of flipchip technology creates huge expectations. We report on the results of a project, having the goal to demonstrate standard packaging technology in combination with integrated optics, entailing demands and limitations different from IC technology. Mainly fiber attachment, but also special features as sensor window accessibility at the top-side of the chip are prohibiting the positioning of the optical layer stack and solder pads at the same side of the silicon wafer. Therefore, feed through technology had to be included. Compatibility issues in combining feed through technology with integrated optics processing have been solved and the feasibility of feed-through metallization and flip-chip assembly in combination with an integrated optical sensor has been demonstrated

Multi-wavelength fluorescence sensing with integrated waveguides in an optofluidic chip

Femtosecond-laser-written integrated waveguides enable multi-wavelength fluorescence sensing of flowing biomolecules in an optofluidic chip. Fluorescence from differently labeled biomolecules with distinct absorption wavelengths, encoded by uniquely modulating each excitation beam, is detected by a color-blind photodetector, and the origin of each signal is unraveled by Fourier analysis

Multi-color fluorescent DNA analysis in an integrated optofluidic lab-on-a-chip

Sorting and sizing of DNA molecules within the human genome project has enabled the genetic mapping of various illnesses. By employing tiny lab-on-a-chip devices for such DNA analysis, integrated DNA sequencing and genetic diagnostics have become feasible. However, such diagnostic chips typically lack integrated sensing capability. We address this issue by combining microfluidic capillary electrophoresis with laser-induced fluorescence detection resulting in optofluidic integration towards an on-chip bio-analysis tool [1,2]. We achieve a spatial separation resolution of 12 μm, which can enable a 20-fold enhancement in electropherogram peak resolution, leading to plate numbers exceeding one million. We demonstrate a high sizing/calibration accuracy of 99% [3], and ultrasensitive fluorescence detection (limit of detection = 65 femtomolar, corresponding to merely 2-3 molecules in the excitation/detection volume) of diagnostically relevant double-stranded DNA molecules by integrated-waveguide laser excitation. Subsequently, we introduce a principle of parallel optical processing to this optofluidic lab-on-a-chip. Different sets of exclusively color-labeled DNA fragments – otherwise rendered indistinguishable by their spatio-temporal coincidence – are traced back to their origin by modulation-frequency-encoded multi-wavelength laser excitation, fluorescence detection with a color-blind photomultiplier, and Fourier-analysis decoding. As a proof of principle, fragments from independent human genomic segments, associated with genetic predispositions to breast cancer and anemia, are extracted by multiplex ligation-dependent probe amplification, and simultaneously analyzed. Such multiple yet unambiguous optical identification of biomolecules opens new horizons for “enlightened” lab-on-a-chip devices

Fluorescence monitoring of capilarry electrophoresis separation in a lab-on-a-chip with monolithically integrated waveguides

Femtosecond-laser-written optical waveguides were monolithically integrated into a commercial lab-on-a-chip to intersect a microfluidic channel. Laser excitation through these waveguides confines the excitation window to a width of 12 μm, enabling high-spatial-resolution monitoring of different fluorescent analytes, during their migration/separation in the microfluidic channel by capillary electrophoresis. Wavelength-selective monitoring of the on-chip separation of fluorescent dyes is implemented as a proof-of-principle. We envision well-controlled microfluidic plug formation, waveguide excitation, and a low limit of detection to enable monitoring of extremely small quantities with high spatial resolution

Optical sensing in microchip capillary electrophoresis by femtosecond laser written waveguides

Capillary electrophoresis separation in an on-chip integrated microfluidic channel is typically monitored with bulky, bench-top optical excitation/detection instrumentation. Optical waveguides allow confinement and transport of light in the chip directing it to a small volume of the microfluidic channel and collecting the emitted/transmitted radiation. However, the fabrication of optical waveguides or more complex photonic components integrated with the microfluidic channels is not a straightforward process, since it requires a localized increase of the refractive index of the substrate.\ud Recently, a novel technique has emerged for the direct writing of waveguides and photonic circuits in transparent glass substrates by focused femtosecond laser pulses.\ud In this work we demonstrate the integration of femtosecond laser written optical waveguides into a commercial microfluidic chip. We fabricate high quality waveguides intersecting the microchannels at arbitrary positions and use them to optically address with high spatial selectivity their content. In particular, we apply our technique to integrate optical detection in microchip capillary electrophoresis. Waveguides are inscribed at the end of the separation channel in order to optically excite the different plugs reaching that point; fluorescence from the labelled biomolecules crossing the waveguide output is efficiently collected at a 90° angle by a high numerical aperture optical fiber. The sensitivity of the integrated optical detection system was first evaluated filling the chip with a dye solution, obtaining a minimum detectable concentration of 40 pM. \ud After dynamic coating of the microchannels with an EPDMA polymer we demonstrate electrophoresis of an oligonucleotide plug with concentration down to 1 nM and wavelength-selective monitoring of on-chip separation of three fluorescent dyes. Work is in progress on separation and detection of fluorescent-labeled DNA fragments, targeting specific, diagnostically relevant regions of a template DNA, for application to the detection of chromosome aberrations

Multi-point, multi-wavelength fluorescence monitoring of DNA separation in a lab-on-a-chip with monolithically integrated femtosecond-laser-written waveguides

Electrophoretic separation of fluorescently labeled DNA molecules in on-chip microfluidic channels was monitored by integrated waveguide arrays, with simultaneous spatial and wavelength resolution. This is an important step toward point-of-care diagnostics with multiplexed DNA assays

Fluorescence monitoring of capillary electrophoresis separation of biomolecules with monolithically integrated optical waveguides

Monolithic integration of optical waveguides in a commercial lab-on-a-chip by femtosecond-laser material processing enables arbitrary 3D geometries of optical sensing structures in combination with fluidic microchannels. Integrated fluorescence monitoring of molecular separation, as applicable in point-of-care diagnostic bioassays is demonstrated

Monitoring of DNA molecules in a lab on a chip with femtosecond laser written waveguides

Using femtosecond laser writing, optical waveguides were monolithically integrated into a commercial microfluidic lab-on-a-chip device, with the waveguides intersecting a microfluidic channel. Continuous-wave laser excitation through these optical waveguides confines the excitation window to a width of 12 um, enabling high-resolution monitoring of the passage of different types of fluorescent analytes, when migrating and being separated in the microfluidic channel by microchip capillary electrophoresis. We demonstrate on-chip-integrated waveguide excitation and detection of a biologically relevant species, fluorescently labeled Deoxyribonucleic acid (DNA) molecules, as well as separation of different dyes, Rhodamine-6G and Rhodamine-B during microchip capillary electrophoresis. Well-controlled plug formation as required for on-chip integrated capillary electrophoresis separation of DNA molecules, and the combination of waveguide excitation and a low detection limit will enable monitoring of extremely small quantities with high spatial resolution

Observation of open scattering channels

The existence of fully transmissive eigenchannels ("open channels") in a random scattering medium is a counterintuitive and unresolved prediction of random matrix theory. The smoking gun of such open channels, namely a bimodal distribution of the transmission efficiencies of the scattering channels, has so far eluded experimental observation. We observe an experimental distribution of transmission efficiencies that obeys the predicted bimodal Dorokhov-Mello-Pereyra-Kumar distribution. Thereby we show the existence of open channels in a linear optical scattering system. The characterization of the scattering system is carried out by a quantum-optical readout method. We find that missing a single channel in the measurement already prevents detection of the open channels, illustrating why their observation has proven so elusive until now. Our work confirms a long-standing prediction of random matrix theory underlying wave transport through disordered systems.Comment: 9 pages including methods and supplementary materials. 3 figure