Klaus Bo Mogensen

Integration of polymer waveguides for optical detection in microfabricated chemical analysis systems.

Multimode polymer waveguides and fiber-to-waveguide couplers have been integrated with microfluidic channels by use of a single-mask-step procedure, which ensured self-alignment between the optics and the fluidics and allowed a fabrication and packaging time of only one day. Three fabrication procedures for obtaining hermetically sealed channels were investigated, and the spectrally resolved propagation loss (400-900 nm) of the integrated waveguides was determined for all three procedures. Two chemical absorbance cells with optical path lengths of 100 and 1000 microm were furthermore fabricated and characterized in terms of coupling loss, sensitivity, and limit of detection for measurements of the dye bromothymol blue.

Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements.

Flow cytometry is widely used for analyzing microparticles, such as cells and bacteria. In this paper, we report an innovative microsystem, in which several different optical elements (waveguides, lens and fiber-to-waveguide couplers) are integrated with microfluidic channels to form a complete microchip flow cytometer. All the optical elements, the microfluidic system, and the fiber-to-waveguide couplers were defined in one layer of polymer (SU-8, negative photoresist) by standard photolithography. With only a single mask procedure required, all the fabrication and packaging processes can be finished in one day. Polystyrene beads were measured in the microchip flow cytometer, and three signals (forward scattering, large angle scattering and extinction) were measured simultaneously for each bead. To our knowledge this is the first time forward scattered light and incident light extinction were measured in a microsystem using integrated optics. The microsystem can be applied for analyzing different kinds of particles and cells, and can easily be integrated with other microfluidic components.

Lab-on-a-chip with integrated optical transducers

Taking the next step from individual functional components to higher integrated devices, we present a feasibility study of a lab-on-a-chip system with five different components monolithically integrated on one substrate. These five components represent three main domains of microchip technology: optics, fluidics and electronics. In particular, this device includes an on-chip optically pumped liquid dye laser, waveguides and fluidic channels with passive diffusive mixers, all defined in one layer of SU-8 polymer, as well as embedded photodiodes in the silicon substrate. The dye laser emits light at 576 nm, which is directly coupled into five waveguides that bring the light to five different locations along a fluidic channel for absorbance measurements. The transmitted portion of the light is collected at the other side of this cuvette, again by waveguides, and finally detected by the photodiodes. Electrical read-out is accomplished by integrated metal connectors. To our knowledge, this is the first time that integration of all these components has been demonstrated.

Monolithic integration of optical waveguides for absorbance detection in microfabricated electrophoresis devices.

The fabrication and performance of an electrophoretic separation chip with integrated optical waveguides for absorption detection is presented. The device was fabricated on a silicon substrate by standard microfabrication techniques with the use of two photolithographic mask steps. The waveguides on the device were connected to optical fibers, which enabled alignment free operation due to the absence of free‐space optics. A 750 νm long U‐shaped detection cell was used to facilitate longitudinal absorption detection. To minimize geometrically induced band broadening at the turn in the U‐cell, tapering of the separation channel from a width of 120 down to 30 νm was employed. Electrical insulation was achieved by a 13 νm thermally grown silicon dioxide between the silicon substrate and the channels. The breakdown voltage during operation of the chip was measured to 10.6 kV. A separation of 3.2 νM rhodamine 110, 8 νM 2,7‐dichlorofluorescein, 10 νM fluorescein and 18 νM 5‐carboxyfluorescein was demonstrated on the device using the detection cell for absorption measurements at 488 nm.

Optical detection in microfluidic systems

Optical detection schemes continue to be favoured for measurements in microfluidic systems. A selection of the latest progress mainly within the last two years is critically reviewed. Emphasis is on integrated solutions, such as planar waveguides, coupling schemes to the outside world, evanescent‐wave based detectors and the field of optofluidics. The perspectives and limitations of the different solutions are discussed in terms of analytical performance and fabrication costs. There has been an increased focus on cheap solutions in polymer materials that are amenable for mass production in order to ease commercialisation of the devices. This work will hopefully result in more commercial products that benefit from integrated optics, because the impact on commercial devices so far has been modest.

Integrated optical measurement system for fluorescence spectroscopy in microfluidic channels

A transportable miniaturized fiber-pigtailed measurement system is presented which allows quantitative fluorescence detection in microliquid handling systems. The microliquid handling chips are made in silica on silicon technology and the optical functionality is monolithically integrated with the microfluidic channel system. This results in inherent stability and photolithographic alignment precision. Permanently attached optical fibers provide a rugged connection to the light source, detection, and data processing unit, which potentially allows field use of such systems. Fluorescence measurements with two dyes, fluorescein, and Bodipy 650/665 X, showed good linear behavior over a wide range of concentrations. Minimally detected concentrations were 250 pM for fluorescein and 100 nM for Bodipy.

Monolithic integration of microfluidic channels and optical waveguides in silica on silicon

Sealing of the flow channel is an important aspect during integration of microfluidic channels and optical waveguides. The uneven topography of many waveguide-fabrication techniques will lead to leakage of the fluid channels. Planarization methods such as chemical mechanical polishing or the etch-back technique are possible, but troublesome. We present a simple but efficient alternative: By means of changing the waveguide layout, bonding pads are formed along the microfluidic channels. With the same height as the waveguide, they effectively prevent leakage and hermetically seal the channels during bonding. Negligible influence on light propagation is found when 10-mum-wide bonding pads are used. Fabricated microsystems with application in absorbance measurements and flow cytometry are presented.

Performance of an in‐plane detection cell with integrated waveguides for UV/Vis absorbance measurements on microfluidic separation devices

A microfluidic device with integrated waveguides and a long path length detection cell for UV/Vis absorbance detection is presented. The 750 νm U‐cell detection geometry was evaluated in terms of its optical performance as well as its influence on efficiency for electrophoretic separations in the microdevice. Stray light was found to have a strong effect on both, the sensitivity of the detection and the available linear range. The long path length U‐cell showed a 9 times higher sensitivity when compared to a conventional capillary electrophoresis (CE) system with a 75 νm inner diameter (ID) capillary, and a 22 times higher sensitivity than with a 50 νm ID capillary. The linear range was comparable to that achieved in a 75 νm ID capillary and more than twice as large as in a 50 νm ID capillary. The use of the 750 νm U‐cell did not contribute significantly to band broadening; however, a clear quantification was made difficult by the convolution of several other band broadening sources.

Nanofluidic Devices with Two Pores in Series for Resistive-Pulse Sensing of Single Virus Capsids

We report fabrication and characterization of nanochannel devices with two nanopores in series for resistive-pulse sensing of hepatitis B virus (HBV) capsids. The nanochannel and two pores are patterned by electron beam lithography between two microchannels and etched by reactive ion etching. The two nanopores are 50-nm wide, 50-nm deep, and 40-nm long and are spaced 2.0-μm apart. The nanochannel that brackets the two pores is 20× wider (1 μm) to reduce the electrical resistance adjacent to the two pores and to ensure the current returns to its baseline value between resistive-pulse events. Average pulse amplitudes differ by <2% between the two pores and demonstrate that the fabrication technique is able to produce pores with nearly identical geometries. Because the two nanopores in series sense single particles at two discrete locations, particle properties, e.g., electrophoretic mobility, are determined from the pore-to-pore transit time.

Photonic crystal resonator integrated in a microfluidic system

We report on a novel optofluidic system consisting of a silica-based 1D photonic crystal, integrated planar waveguides, and electrically insulated fluidic channels. An array of pillars in a microfluidic channel designed for electrochromatography is used as a resonator for on-column label-free refractive index detection. The resonator was fabricated in a silicon oxynitride platform, to support electro-osmotic flow, and operated at lambda=1.55 microm. Different aqueous solutions of ethanol with refractive indices ranging from n=1.3330 to 1.3616 were pumped into the column/resonator, and the transmission spectra were recorded. Linear shifts of the resonant wavelengths yielded a maximum sensitivity of Deltalambda/Deltan=480 nm/RIU (refractive index unit), and a minimum difference of Deltan=0.007 RIU was measured.