Label-free attomolar protein detection using a MEMS optical interferometric surface-stress immunosensor with a...

We demonstrated an optical interferometer-based surface-stress immunosensor using freestanding polymethyl methacrylate (PMMA)/parylene-C nanosheet with high sensitivity for detection of biomolecules. PMMA/parylene-C nanosheets were transferred onto a silicon substrate with microcavities to fabricate freestanding submicron-thick membrane with a sealed cavity structure. The adhesive force between the transferred parylene-C and binder parylene-C layer was measured to be 1.06-2.4 N/10 mm by tape test. Evading Debye shielding, these nanomechanical sensors allow detection of the adsorption on the membrane surface through changes in surface stress transduced by the electric charge. We optimized the density of receptors and mode of immobilization for high sensitivity. To evaluate the selectivity of the sensor, membrane deflections induced by various proteins were measured and the spectral shifts showed high selectivity only for the target antigen. The minimum limit of detection (LOD) of the sensor for human serum albumin antigen was 0.1-1 fg/mL (1.5-15 aM), which was 20,000 times lower than that of the conventional micro-cantilever sensor.