Selective labeling of oligonucleotide monolayers by metallic nanobeads for fast optical readout of DNA-chips (original) (raw)

2001, Sensors and Actuators B: Chemical

Chemically modi®ed nanobeads are used for the labeling of molecular objects in ultramicroscopic techniques. In addition to this application, we found that the cooperative effect of densely immobilized ensembles of metallic nanobeads on micropatterned molecular mono®lms can be used for an optical measurement of speci®c binding events. So, a reproducible readout of hybridization on DNA chips becomes easily possible. The technique can substitute¯uorescence methods for the readout, which are commonly used in most applications. Functionalized beads of a certain size are large enough to in¯uence light ways considerably, but small enough for speci®c chemical reactions with molecules on chip surfaces. It was found that gold particles with diameters between 15 and 60 nm are particularly suited for such a labeling of DNA-DNA-interactions on DNA-chips. Their immobilization density and sequence speci®city is very high, so that transmitted light at glass chips is reduced considerably or re¯ected light is increased, resulting in a very strong contrast. This effect can be quantitatively readout by light scanners, optical cameras or microscopes on a very small time scale. Usually, exposure times less than 10 ms are suf®cient. The chips can be stored for a long time without loss of information about the degree of hybridization. The surface chemistry for DNA immobilization and for the bead labeling as well as the readout procedure are discussed.

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