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.
We have previously shown that a polymeric (PMMA) chip with medium perfusion and integrated heat regulation provides sufficiently precise heat regulation, pH-control and medium exchange to support cell growth for weeks. However, it was unclear how closely the cells cultured in the chip resembled cells cultured in the culture flask. In the current study, gene expression profiles of cells cultured in the chip were compared with gene expression profiles of cells cultured in culture flasks. The results showed that there were only two genes that were differently expressed in cells grown in the cell culture chip compared to cell culture flasks. The cell culture chip could without further modification support cell growth of two other cell lines. Light coming from the microscope lamp during optical recordings of the cells was the only external factor identified, that could have a negative effect on cell survival. Low grade light exposure was however compatible with optical recordings as well as cell viability. These results strongly indicate that a cell culture chip could be constructed that allowed for on-line optical recording of cellular events without affecting the cell culturing condition compared to cell cultured in culture flasks incubated in a dark and CO2 conditioned incubator.
This paper presents the results of an investigation of the influence of soft baking temperature on the lithographic performance of the negative photoresist SU-8. The work was initiated in order to obtain a lithographic resolution suitable for integration of diffractive optical components for near-infrared wavelengths. The study was carried out on 40 µm SU-8 layers on thermally oxidized silicon wafers, a widespread platform for integration of microfluidic systems and waveguides. A series of experiments covering soft bake temperatures in the range 65–115 °C were performed under otherwise identical processing conditions. The influence of the soft bake temperature on polymerization temperature as well as cracking, lithographic resolution and hardness of the resist was investigated. The kinetics of the polymerization process were observed to change with soft bake temperature, leading to changes in sensitivity and contrast of the resist, as well as changes in the material strength of the developed structures. Soft baking at 65 °C proved superior with respect to all the inspected properties, providing a sample showing full resolution of 3.8 µm wide trenches and no stress-related cracking.
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.
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