Focal molography – a new method for Biomolecular Interaction Analysis (BIA)

Biomolecular interaction analysis (BIA), i.e. the direct and label-free monitoring of binding events between molecules on a sensor surface, is a key method in molecular biology. Over the past 30 years, refractometric biosensors, and in particular surface plasmon resonance (SPR), have matured to the de facto standard of BIA despite their significant cross reactivity to environmental and experimental noise sources.

Two publications regarding focal molography introduce and demonstrate the concept of the “spatial affinity lock-in” as a novel design principle to overcome the drawbacks of established BIA methods. The spatial affinity lock-in is analogous to the time-domain lock-in. Instead of a time-domain signal, it modulates the binding signal at a high spatial frequency to separate it from the low spatial frequency environmental noise in Fourier space. Focal molography applies this fundamental detection principle to BIA. Combined with the right surface chemistry and recognition elements on the sensor surface focal molography enables robust, sensitive and fundamentally new BIA assays such as the direct and label-free monitoring of biomolecular interaction on the cell membrane.


Further reading: Ultra-stable molecular sensors by sub-micron referencing and why they should be interrogated by optical diffraction —


Part I. The Concept of a Spatial Affinity Lock-in Amplifier:


Part II. Experimental Demonstration: