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Abstract More than half of pharmaceutical drugs in use are chiral, necessitating accurate techniques for their characterization. Enantiomers, molecules with mirrored symmetry, often exhibit similar physical traits but possess distinct chemical and biological implications. This study harnesses the strong light‐matter interaction induced by “superchiral” light to perform Surface‐Enhanced Infrared Absorption (SEIRA) induced vibrational circular dichroism measurements in the mid‐infrared spectral region. Utilizing a nanopatterned pixelated array of achiral plasmonic nanostructures, the system allows unique identification of enantiomers and biomolecules. Tunability of plasmon resonance facilitates spectral variation of the optical chirality over a wide infrared range, enabling development of a unique chiral “barcoding” scheme to distinguish chiral molecules based on their infrared fingerprint. This simple, yet robust sensor presents a low‐cost solution for chiral mapping of drugs and biomolecules. 

Neurotransmitters are crucial for the proper functioning of neural systems, with dopamine playing a pivotal role in cognition, emotions, and motor control. Dysregulated dopamine levels are linked to various disorders, underscoring the need for accurate detection in research and diagnostics. Single-stranded DNA (ssDNA) aptamers are promising bioreceptors for dopamine detection due to their selectivity, improved stability, and synthesis feasibility. However, discrepancies in dopamine specificity have presented challenges. Here, we surface-functionalized a nano-plasmonic biosensing platform with a dopamine-specific ssDNA aptamer for selective detection. The biosensor, featuring narrowband hybrid plasmonic resonances, achieves high specificity through functionalization with aptamers and passivation processes. Sensitivity and selectivity for dopamine detection are demonstrated across a wide range of concentrations, including in diverse biological samples like protein solutions, cerebrospinal fluid, and whole blood. These results highlight the potential of plasmonic “aptasensors” for developing rapid and accurate diagnostic tools for disease monitoring, medical diagnostics, and targeted therapies. 

The accurate detection, classification, and separation of chiral molecules are pivotal for advancing pharmaceutical and biomolecular innovations. Engineered chiral light presents a promising avenue to enhance the interaction between light and matter, offering a noninvasive, high-resolution, and cost-effective method for distinguishing enantiomers. Here, we present a nanostructured platform for surface-enhanced infrared absorption–induced vibrational circular dichroism (VCD) based on an achiral plasmonic system. This platform enables precise measurement, differentiation, and quantification of enantiomeric mixtures, including concentration and enantiomeric excess determination. Our experimental results exhibit a 13 orders of magnitude higher detection sensitivity for chiral enantiomers compared to conventional VCD spectroscopic techniques, accounting for respective path lengths and concentrations. The tunable spectral characteristics of this achiral plasmonic system facilitate the detection of a diverse range of chiral compounds. The platform’s simplicity, tunability, and exceptional sensitivity holds remarkable potential for enantiomer classification in drug design, pharmaceuticals, and biological applications.