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-NH_2, 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 (K_D) for on-target sequences and are comparable to those of antibodies (K_D = 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.