Most label-free techniques rely on
measuring refractive
index or
mass change on the sensor surface. Thus, it is challenging for them
to measure small molecules or enzymatic processes that only induce
a minor mass change on the analyte molecules. Here, we have developed
a technique by combining Surface Plasmon Resonance sensing with an
Oscillating Biomolecule Layer approach (SPR-OBL) to enhance the sensitivity
of traditional SPR. In addition to the inherent mass sensitivity,
SPR-OBL is also sensitive to the charge and conformational change
of the analyte; hence it overcomes the mass limit and is able to detect
small molecules. We show that the multimetric SPR-OBL measurement
allows for sensing any changes regarding mass, charge, and conformation,
which expands the detection capability of SPR