Microfabrication Techniques to Generate Miniaturized Chip Components

Based on conventional microfabrication technologies (which include photolithography technology), it is now possible to generate a large variety of complex structured biochips (e.g., planar MEAs and multi-microcapillary arrays) comprising microchannels (for hydrodynamic cell and tissue positioning), interconnects, and up to thousands of microelectrodes and/or field-effect transistors (FETs) for the detection of morphological and physiological alterations induced by drug and compound applications.

At present, a large number of tested and biocompatible materials are available. In general, glass, silicon, and polymers are utilized as substrates for the fabrication of biosensor chips. If used for biological applications, glass is the material of choice since, in contrast to silicon, it is transparent and thus the quality and growth of cells can be monitored directly on the surface of the chip by light or, if required, by fluorescence microscopy. In this way, it is possible to discriminate covered from uncovered electrodes, and also to identify genetically manipulated cells if they are marked by a reporter gene (e.g., green fluorescent protein, GFP) prior to measurement. Electrodes and interconnects - mostly noble metals such as iridium, gold, or platinum - are coated onto the surface of glass or silicon substrates, which are subsequently isolated by a thin film (passivation) of, for example, silicon nitrite, silicon oxide or organic polymers (Fig. 3.1). Subsequently, the passivation layer above the electrode is removed to provide direct contact with cells or tissues. In order to facilitate and to direct the positioning of cells on electrodes, the surfaces can be further modified by soft-lithography of repellent (e.g., silane) or attractant coatings (e.g., laminin, fibronectin) and/or by microcavities with implemented microelectrodes and/or suction holes (Fig. 3.2).

insulation (SiN) suction channel silicon or glass substrate

Fig. 3.1 Schematic drawing of a microstructure containing thin-film electrodes using gold or platinum in a geometry in the micrometer (^m) range. The electrode diameter is 10 |jm, the suction hole diameter 6 |m; the thickness of the SiN insulation is 0.2 |m, the gold conductor 0.3 |m, and the SiN passivation 0.3 |m. (Copyright © BBZ/Andrea Robitzki, Maik Schmidt).

Fig. 3.2 (a) Positioning of cells in a square-like arrangement on micro-electrodes can be achieved by surface coating with repellent and attractive substances.

(b) Implementation of microcavities and suction channels on a planar chip allows the hydrodynamic positioning of suspended cells by applying a negative pressure. The tighter the contact of cells and electrodes, the higher the signal-to-noise ratio and sensitivity. Scale bars: left, 90 |m; right 10 |jm.

(Copyright © Center for Biotechnology and Biomedicine, Leipzig).

Fig. 3.2 (a) Positioning of cells in a square-like arrangement on micro-electrodes can be achieved by surface coating with repellent and attractive substances.

(b) Implementation of microcavities and suction channels on a planar chip allows the hydrodynamic positioning of suspended cells by applying a negative pressure. The tighter the contact of cells and electrodes, the higher the signal-to-noise ratio and sensitivity. Scale bars: left, 90 |m; right 10 |jm.

(Copyright © Center for Biotechnology and Biomedicine, Leipzig).

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