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Content archived on 2024-05-27

DIagnosis tOol Based on the measurement of molecular interactions

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Microsensors integrated on a chip

The integration of cantilever arrays in a single chip along with signal processing electronic circuits, achieved by the BIOFINGER project, may open the way for miniaturised sensing systems.

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Recent advances in silicon micromachining technology have boosted the discovery of new applications for micro- and nanotools. Cantilever beams with length and thickness in the tens of micrometres range have been demonstrated to be a most promising class of biosensor. Due to their intrinsic flexibility, combined with the availability of advanced techniques designed to monitor bending, they have become versatile tools for molecular and biomolecular recognition. Micromachined cantilevers can recognise proteins with exquisite sensitivity, as well as detect small amounts of materials, especially pathogenic bacteria. Directed micro- and nano-electro-mechanical systems have also been used as immunospecific and multifunctional biological detectors. The ultimate aim of the BIOFINGER project was to integrate cantilever arrays in one chip with signal processing electronic circuits, and thereby enhance the device's performance. More specifically, an array-based approach was adopted by researchers at the Swiss Federal Institute of Technology to allow parallel screening of different analytes and increase the overall analysis speed. The resonant cantilever system comprises four equally-spaced cantilevers, into which the read out scheme has been integrated to allow their fully autonomous operation. The resonating cantilevers are actuated by means of electromagnetic forces generated by a permanent magnet and an AC current flowing in a metal loop. The binding of the analytes changes the mechanical properties of the cantilevers, which can be detected by piezoresistors, or stress-sensitive transistors, arranged in a Wheatstone bridge configuration. The cantilevers act as frequency-determining elements in a feedback oscillation circuit, with a counter. Microfabrication techniques and, in particular, complementary metal-oxide semiconductor (CMOS) technology was used to devise the small-size sensor system. Post-processing and packaging of the CMOS chip was necessary to prepare the biosensor for the harsh culture environments, in which it was designed to operate. Epoxy was first applied to stabilise the chip bonds on the chip and polydimethylsiloxane (PDMS) was used to isolate them from the liquid environment. The sensitivity of the sensor system was evaluated by exposing the coated cantilevers in sample fluids with varying concentrations of prostate specific antigen where less than 10ng/ml was detectable.

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