Enhanced Chiral Sensing at the Few-Molecule Level Using Negative Index Metamaterial Plasmonic Nanocuvettes

Chirality is a fundamental property of biological molecules and some pharmaceutical molecules. Chiral molecules have a pair of chiral isomers (enantiomers) with opposite handedness. Although both enantiomers of the same molecule have identical chemical and physical properties, one enantiomer may be toxic to living organisms while the other one is harmless. The detection of these enantiomers is done using their small differential absorption between right and left circularly polarized light, known as circular dichroism (CD). Considering the macroscopic size of these molecules, combined with their small differential absorption, the obtained CD signal is very small, imposing a severe limitation on the minimal concentration that can be detected. Chiral plasmonic and metamaterial structures have been used to enhance the sensitivity of CD measurements by orders of magnitude through chiral density hot spots (super chiral fields). However, the large background signal due to these structures' intrinsic chirality limits the effectiveness of these methods. Contrary to absorption-based chiral sensing measurements (CD), fluorescence detection circular dichroism (FDCD) sensing can greatly improve chiral measurement sensitivity, down to the ultimate limit of a few and even a single chiral molecule. Like differential absorption, differential fluorescence also produces a weak signal at the few-chiral-molecule limit. However, here we demonstrate a negative-index metamaterial (NIM) cavity that acts as a "plasmonic nanocuvette" with globally enhanced volume super chiral fields. Moreover, the achiral structure of the plasmonic nanocuvette allows for completely background-free chiral sensing. We show that with NIM-cavity-enhanced FDCD, we can detect as low as a few tens of chiral molecules, well within the zeptomole range.