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Detection of small molecules using interferometry

Amarna Suzanne Pels (TNW-MNF), Jurriaan Huskens (TNW-MNF)

Abstract

The detection of small molecules, typically organic molecules less than 1000 Da in size, is an important field of study of biological processes and in biotechnology. One way of doing this is using biosensing. Interferometry is a relatively new technique among optical sensing techniques, but shows a lot of promise. This is because it is very sensitive, label free and can be used in real-time measurements. It uses a similar principle to Surface Plasmon Resonance by detecting changes in the refractive index near the surface. However, interferometry is not limited to metal surfaces and can be considerably more sensitive. We are investigating the limitations of interferometry for weight-based biosensing. We used biotin-Streptavidin as a model ligand-receptor combination because of its strong interaction, thus allowing the use of low concentrations of biotin as an analyte. We performed sensing experiments using a Mach-Zehnder interferometer with a silicon nitride surface. We used PLL-OEG-biotin as a platform for binding Streptavidin and antifouling purposes. Here we show the binding of different biotinylated compounds to Streptavidin detected using interferometry. The measured signal appears to be weight-based between 0-5000 Da. Larger molecules do not bind to all available binding sites, most likely due to steric hindrance.