Andreas Guber

High-voltage contactless conductivity-detection for lab-on-chip devices using external electrodes on the holder

The detection of ionic species in a polymeric planar electrophoresis device by contactless conductivity measurement is described. To our knowledge this is the first report of such measurements carried out with external electrodes which are part of the holder rather than the separation chip itself. The approach allows the use of bare devices as used for optical measurements, which greatly simplifies the method. The use of a sine wave of 100 kHz of a high amplitude of 500 V for cell excitation assures high sensitivity which is demonstrated with electropherograms for alkali and heavy metal ions as well as inorganic anions and carboxylates at concentrations between 10 and 50 µM. The determination of underivatized amino acids was also possible by using a buffer in the alkaline region where these species are present in anionic form. Detection limits were found to be in the order of 1–5 µM for the inorganic ions and between about 5 and 50 µM for the organic species.

Fabrication of microlenses by plasmaless isotropic etching combined with plastic moulding

Abstract In appropriate mixtures of bromine and fluorine BrF3 is generated, which can then be used for the structuring of silicon under room conditions without plasma support. Direct reaction of the intermediary BrF3 with silicon results in the formation of SiF4 and bromine. By further addition of fluorine, the etching reaction can be started again. Bromine then acts as a catalyst. In spite of the high etching rate, the roughness of the etched surfaces remains small. By adding xenon to the etching gases, the roughness can be reduced to a minimum. Thermally produced SiO2 can be applied as the etching mask. Complete isotropy of the etching process allows underetching of closely adjacent LIGA structures. Moreover, optical application is possible due to the good quality of the etched surfaces. When underetching small circular holes in the SiO2 mask, spherical depressions are generated. After the SiO2 mask has been removed, these structures can be moulded in plastic and used as microlenses.

Gas / Liquid Microreactors for Direct Fluorination of Aromatic Compounds Using Elemental Fluorine

Two different concepts of contacting gas and liquid media were realized in miniaturized reaction devices. The first one, a micro bubble column, utilizes dispersed systems consisting of small gas bubbles in a liquid phase. A large specific interfacial area of about 9,000 m2/m3 was determined by applying the sulfite oxidation method. Flow equipartition of a high number of parallel operating channels was achieved by using a pressure barrier. First visual observations of the liquid and gaseous flows indicate that this principle leads to a uniform flow equipartition. The second concept was based on the generation of thin stable films in a falling film microreactor. Very narrow residence time distributions of the flows in the channels were achieved also by using a pressure barrier.

Polymer Lab-on-a-Chip System With Electrical Detection

Two important challenges of the rapid development of microfluidic chip systems are addressed in this paper: 1) new polymer materials and technologies for chip preparation and 2) a label-free method for analyte detection in microchannels. One of the general pacemakers in lab-on-a-chip concepts, capillary electrophoresis (CE) in chip format, was used as workhorse for demonstration. CE chips were fabricated and characterized using polymers such as PMMA, polystyrene and polycarbonate, cycloolefine copolymer, and for the first time, the outstanding high-performance polymer polyether ether ketone (PEEK). Especially for one of the most critical steps in microchannel preparation, bonding of the cover layer to the microstructured substrate, an advanced plasma preconditioning process has been developed. An electrical detection method, capacitively coupled contactless conductivity measurement (CCD), was transferred to the chip level. A high signal-to-noise ratio was obtained by using sputtered thin-film electrodes. It was additionally improved by the very thin channel cover layer thickness, which could be easily obtained by polymer technology. CCD was used for analyte detection near the outlet of the CE separation channel. Further, to demonstrate generally the benefit of CCD for microfluidic flow control, measurement electrodes were positioned at the CE chip injection cross to monitor the reliability of the sophisticated injection processes. A completely miniaturized CE device (ldquoMinCErdquo), was developed for low cost application. Potential applications were demonstrated on selected typical examples: for in situ food analysis, the determination of saccharides in beverages, for medical point-of-care diagnostics, the quantitative determination of antidepressant lithium in blood serum, and for bio analytics, the detection of proteinogenic amino acids. Biological macro molecules-in particular, for life sciences fundamental DNA-have not been in focus of contactless conductivity measurements until now. However, it was possible for the first time to detect DNA highly sensitive by conductivity measurement. The extremely low detection limits achieved are competitive with laser induced fluorescence (LIF) in commercial CE-chip-devices and could provide a highly cost-efficient alternative.

Fabrication of microlenses by combining silicon technology, mechanical micromachining and plastic molding

Silicon can be subjected to plasmaless isotropic etching in mixtures of elemental bromine and fluorine. BrF3 is generated in the etching process. This ensures a high etching rate on smooth surfaces. The addition of noble gases, e.g. xenon, allows extremely smooth surfaces to be etched. Thermally oxidized SiO2 layers are applied as the etching mask. Among other applications, this technique can be used to manufacture microlenses. As a consequence of the complete isotropy of the etching process, spherical depressions of 100 to 500 micrometers in diameter are produced in the silicon when small circular holes of 5 to 50 micrometers are underetched in the SiO2 mask. After removal of the SiO2 mask the silicon sample can be used as a mold insert for plastic molding. The molded microlenses have been checked dimensionally and verified optically. The microlenses are planned for technical use in a miniaturized endoscope. This requires further processing of the silicon sample. As no hemispherical recesses but calotte shells are needed, the silicon surface must be machine prior to molding. This is done by microgrinding with variable-grain diamond tools on CNC high- precision machines. To generate adjusting devices, stoppers, and holding structures, the ground silicon sample and a mechanically microstructured perforated plate are combined in a modular multi-level mold insert. The microlenses molded by hot embossing or injection molding are separated mechanically. They can then be integrated in the endoscope with a holding unit manufactured independently.

Formation of a Polymer Surface with a Gradient of Pore Size Using a Microfluidic Chip

Here we demonstrate the generation of polymer monolithic surfaces possessing a gradient of pore and polymer globule sizes from ~0.1 to ~0.5 μm defined by the composition of two polymerization mixtures injected into a microfluidic chip. To generate the gradient, we used a PDMS microfluidic chip with a cascade micromixer with a subsequent reaction chamber for the formation of a continuous gradient film. The micromixer has zigzag channels of 400 × 680 μm(2) cross section and six cascades. The chip was used with a reversible bonding connection, realized by curing agent coating. After polymerization in the microfluidic chip the reversible bond was opened, resulting in a 450 μm thick polymer film possessing the pore size gradient. The gradient formation in the microfluidic reaction chamber was studied using microscopic laser-induced fluorescence (μLIF) and different model fluids. Formation of linear gradients was shown using the fluids of the same density by both diffusive mixing at flow rates of 0.001 mL/min and in a convective mixing regime at flow rates of 20 mL/min. By using different density fluids, formation of a two-dimensional wedge-like gradient controlled by the density difference and orientation of the microfluidic chip was observed.

FTIR spectroscopy for the analysis of selected exhaust gas flows in silicon technology

Abstract Fabrication of highly integrated circuits or microstructures is presently accomplished above all by means of dry chemical etching processes with mostly halogen containing etching gases being used. As a result of the decomposition of these gases in a plasma reactive radicals are formed. They react with solid silicon compounds to gaseous SiF 4 . Furthermore, partly highly toxic substances are generated in the exhaust gas flow by the recombination of other molecule fragments. For this reason, selected exhaust gases of RIE and PECVD facilities have been investigated by FTIR spectroscopy and evaluated with regard to their hazard potential and possible HF emission rate.

Potential of microsystems in medicine

SummaryIn numerous fields of medicine and in particular in minimally invasive therapy, functionality of the existing medico-technical equipment can be improved considerably by increasing use of microstructures or microsystem components. Furthermore, completely new medical instruments (endosystems) are feasible on the basis of microsystem fabrication technologies. With the LIGA technique and mechanical microengineering two novel technologies for medical technology shall be presented. The advantages and opportunities offered by microstructure and microsystems technology shall be illustrated by the examples of microshaped X-ray intensifying screens, micro host structures for cell cultures, microvalve systems for catheter systems and a novel endoscopic operation system for neurosurgery.

Development of a novel two-channel microfluidic system for biomedical applications in cancer research

In this paper we present a novel two-channel microfluidic system which acts as an artificial blood capillary vessel to examine the migration steps of cancer cells in the microvasculature. The system consists of polycarbonate and is fabricated by combining hot embossing and thermal bonding. The optically transparent polycarbonate allows the use of live cell and fluorescence microscopy. The main feature of this device is that all processes take place under continuous laminar flow conditions at distinct tuneable shear rates.

Further development of microstructured culture systems and their use in tissue engineering.

The Forschungszentrum Karlsruhe aims at improving its CellChip. Its main feature is the 1 cm2 core, subdivided into 900 cubic microcontainers (300 x 300 x 300 microns). It is manufactured by injection molding using biodegradable (polylactide) as well as non-degradable (PMMA or PC) polymers. The CellChips will be modified such that membranes will be mounted at the bottom of the CellChip, thus facilitating backend processing. Furthermore, the membranes can be adapted ideally to the assay system of interest by various surface modification techniques.