A coplanar waveguide biosensor and methods of use include a coplanar waveguide transmission line and a sample containment structure. The coplanar waveguide transmission line is operable to support the propagation of an electromagnetic signal and includes a signal line and one or more spaced apart ground elements. The signal line is configured to conduct a time-varying voltage, and the one or more ground elements are configured to maintain a time-invariant voltage, a detection region being formed between a portion of the signal line and a portion of at least one of the one or more ground elements. Detection methods are improved through the enhancement of the electric field in the detection region via impedance discontinuities in the signal line and ground elements. The sample containment structure intersects the detection region of the coplanar waveguide transmission line and includes a cavity configured to hold 1 ml or less of sample solution within the detection region.