Reconfigurable Optical Sensor for Metal-Ion-Mediated Label-Free Recognition of Different Biomolecular Targets

Reconfiguration of chemical sensors, intended as the capacity of the sensor to adapt to novel operational scenarios, e.g., new target analytes, is potentially game changing and would enable rapid and cost-effective reaction to dynamic changes occurring at healthcare, environmental, and industrial levels. Yet, it is still a challenge, and rare examples of sensor reconfiguration have been reported to date. Here, we report on a reconfigurable label-free optical sensor leveraging the versatile immobilization of metal ions through a chelating agent on a nanostructured porous silica (PSiO₂) optical transducer for the detection of different biomolecules. First, we show the reversible grafting of different metal ions on the PSiO₂ surface, namely, Ni²⁺, Cu²⁺, Zn²⁺, and Fe³⁺, which can mediate the interaction with different biomolecules and be switched under mild conditions. Then, we demonstrate reconfiguration of the sensor at two levels: 1) switching of the metal ions on the PSiO₂ surface from Cu²⁺ to Zn²⁺ and testing the ability of Cu²⁺-functionalized and Zn²⁺-reconfigured devices for the sensing of the dipeptide carnosine (CAR), leveraging the well-known chelating ability of CAR toward divalent metal ions; and 2) reconfiguration of the Cu²⁺-functionalized PSiO₂ sensor for a different target analyte, namely, the nucleotide adenosine triphosphate (ATP), switching Cu²⁺ with Fe³⁺ ions to exploit the interaction with ATP through phosphate groups. The Cu²⁺-functionalized and Zn²⁺-reconfigured sensors show effective sensing performance in CAR detection, also evaluated in tissue samples from murine brain, and so does the Fe³⁺-reconfigured sensor toward ATP, thus demonstrating effective reconfiguration of the sensor with the proposed surface chemistry.