Focal Molography: Coherent Microscopic Detection of Biomolecular Interaction

Focal Molography: Coherent Microscopic Detection of Biomolecular Interaction Journal Article


Current state-of-the-art molecular sensing devices have a number of shortcomings and limited sensitivity. In particular, nonbiospecific interactions of solute and solvent molecules to the sensor surface can interfere with the measurement of a biospecific molecular interaction. Our novel analytical method “focal molography” can overcome these limitations; focal molography relies on using diffraction-limited focusing of light.

Focal molography combines state-of-the-art lithography, molecular self-assembly, and optical technology into one powerful technique. The technique allows biospecific molecular binding to be observed by cleverly exploiting the weak diffraction of light by a coherent pattern of molecules (or nanoparticles). Molecules that bind nonspecifically to the sensor surface contribute only incoherently to the sensor signal, and the coherent signal from analyte molecules on the sensor surface is much stronger than the signal from molecules that contribute incoherently. The focal molography method has two unique advantages in comparison with existing molecular sensing methods: (i) it eliminates the effect of nonbiospecific binding, which is the limiting factor in all current state-of-the-art molecular sensing devices, and (ii) it has a very high sensitivity that can be amplified by increasing the size of the sensor.

Focal molography is expected to open new investigative possibilities in the analysis of biospecific affinity binding with broad application potentials in molecular biology and diagnostics. Our method may furthermore enable the detection of diagnostic biomarkers by a small optoelectronic device.