Amplification of Refractometric Biosensor Response through Biomineralization of Metal–Organic Framework Nanocrystals

Plasmonic biosensors based on the refractive index sensitivity of localized surface plasmon resonance (LSPR) are highly promising for on-chip and point-of-care diagnostics. In particular, plasmonic biosensors that rely on artificial antibodies are highly attractive for applications in resource-limited settings due to the excellent thermal, chemical, and environmental stability of these biorecognition elements. In this work, a universal LSPR response amplification strategy based on the biomineralization of a metal–organic framework (MOF) on the captured analyte proteins is demonstrated. The amplification relies on the differential ability of abiotic recognition elements and captured biomolecules to induce biomineralization of a MOF. The rapid amplification process (less than 10 min) demonstrated here results in nearly 100% higher sensitivity and three times lower limit of detection compared to the innate sensor. The amplification approach can be broadly applied to a wide variety of bioanalytes and can be rapidly implemented in real-world conditions without compromising the assay time or reusability of the plasmonic biochip.