Investigating the 8CB Liquid Crystal–Insulin Interaction: The Role of the Smectic A Phase in Enhancing Detection Sensitivity

Liquid crystal (LC) biosensors have emerged as a viable platform for protein detection due to their distinct optical and dielectric features. These biosensors make use of LC's responsiveness to external stimuli, which includes interactions with biomolecules such as proteins. LC’s molecular alignment and order are extremely sensitive to changes in their surroundings, allowing for highly sensitive and selective protein identification. This study presents the first comprehensive multi-technique investigation of human insulin (HI) detection using octyl-4-biphenylcarbonitrile (8CB) liquid crystal, highlighting the enhanced sensitivity achieved when 8CB operates in its smectic A phase compared to its nematic homologs. The importance of this work rests in providing basic insights into how LC-phase molecular ordering governs protein–LC interactions, rather than in establishing a new standard for biosensing sensitivity. Polarizing optical microscopy (POM) revealed two primary configurations, focal conic and radial, in 8CB-LC upon interaction with HI at concentrations of 20 μM–300 μM. Dielectric studies showed significant changes in impedance, loss tangent, relaxation time, and capacitive behavior, while Raman spectroscopy revealed shifts in vibrational modes, correlating with HI interactions. Molecular docking provided insights into the binding behavior of 8CB-LC with HI. Among cyanobiphenyl LCs, 8CB’s smectic A phases enhanced molecular ordering and sensitivity, detecting HI at concentrations of 20 μM, which is lower than the LOD of other cyanobiphenyl LCs. These findings demonstrate 8CB’s high specificity and sensitivity, positioning it as a strong candidate for label-free insulin biosensing.