Phage display against 2D metal–organic nanosheets as a new route to highly selective biomolecular recognition surfaces

Peptides are important biomarkers for various diseases, however distinguishing specific amino-acid sequences using artificial receptors remains a major challenge in biomedical sensing. This study introduces a new approach for creating highly selective recognition surfaces using phage display biopanning against metal–organic nanosheets (MONs). Three MONs (ZIF-7, ZIF-7-NH2, and Hf-BTB-NH2) are added to a solution containing every possible combination of seven-residue peptides attached to bacteriophage hosts. The highest affinity peptides for each MON are isolated through successive bio-panning rounds. Comparison of the surface properties of the MONs and high-affinity peptides provide useful insights into the relative importance of electrostatic, hydrophobic, and co-ordination bonding interactions in each system, aiding the design of future MONs. Coating of the Hf-BTB-NH2 MONs onto a quartz crystal microbalance (QCM) produced a five-fold higher signal for phage with the on-target peptide sequence compared to those with generic sequences. Surface plasmon resonance (SPR) studies produce a 4600-fold higher equilibrium dissociation constant (KD) for on-target sequences and are comparable to those of antibodies (KD = 4 x 10−10 m). It is anticipated that insights from the biopanning approach, combined with the highly tunable nature of MONs, will lead to a new generation of highly selective recognition surfaces for use in biomedical sensors.