Reflective interferometric detection of label-free oligonucleotides

New chip-based methods for the detection of unmodified biomolecular targets have significant potential as enabling technology in fundamental biology and biomedical analysis. We report a method based on changes in reflectivity from specially fabricated substrates that is capable of detecting the binding of as little as an average of 0.2 nm (i.e., a fraction of a monolayer) of biomolecules. We demonstrate the method on detection of femtomole quantities of untagged oligonucleotides in an array format, showing that the amount of target bound can be determined quantitatively. The simplicity of the approach promises to make it broadly applicable for any biomolecule for which suitable molecular recognition chemistry is available.