Detection of biomolecular surface interactions by transit time measurements with a coplanar transmission line probe

Changes in the transit time of a short electrical pulse propagating through a coplanar transmission line (CTL) are used to sense protein interactions at an aqueous-solid interface. The effective permittivity of the CTL is lowered as a result of protein binding at the interface. This decrease is sensed by the relative decrease in propagation transit time of a baseband picosecond electrical pulse through the probe. It is shown that the microwave probe is sensitive to protein binding at a liquid-solid interface and can be used for measuring dissociation constants in the nM range. In comparison with previous microwave sensors, this sensor is relatively insensitive to temperature fluctuations. It has the capability of operating in non-optical environments such as porous capillaries, capillaries filled with separation media, or opaque substrates.