Resistive pulse analysis of chiral amino acids utilizing metal-amino acid crystallization differences

Here, we report a proof-of-concept resistive pulse method for analyzing chiral amino acids utilizing metal-amino acid crystallization differences. This method involves introducing an amino acid sample solution into a micropipette through a pressure-driven flow. The sample then mixes with a metal ion solution inside the pipette, forming metal-amino acid crystals. The crystal size depends on the enantiomeric excess (x) of chiral amino acid samples. Large x values lead to large crystals. The crystal size difference is then reflected in the resistive pulse size as they block the ionic transport in a micropipette to different extents. We used Cd-cystine crystallization as a model system and found approximately five times the mean current pulse size difference for racemic (x = 0) and L-only (x = +1) cystine samples. A similar result was observed for aspartate. Our discovery opens up new opportunities for micro/nanoscopic chiral amino acid analysis, which can potentially be used in single-cell analysis.