Charge Modulation at the Liquid Crystal Droplet‐Aqueous Interface Enables Ultrasensitive, Nonspecific Protein Detection

• Published in: Small (Weinheim an der Bergstrasse, Germany) p. e2407077
• Main Authors: Maheshwari, Harsha, Naveenkumar, Parinamipura M., Singh, Raju Kumar, Soni, Lokesh, Sharma, Kamendra P.
• Format: Journal Article
• Language: English
• Published: 02-11-2024
• ISSN: 1613-6810; 1613-6829; 1613-6829
• DOI: 10.1002/smll.202407077

Abstract Thermotropic nematic liquid crystals (LC) have been utilized to sense/detect various analytes such as polymers, surfactants, lipids, etc. However, their use for protein detection depends on pre‐adsorbed molecules, co‐nematogens, or biomolecular agents for specificity. This approach impedes the platform's sensitivity with a detection limit for the folded proteins generally reported in the micromolar concentration range. Here, this work provides fundamental insights into the type of molecular interactions and their modulation that can drive ultrasensitive protein detection at an LC microdroplet/aqueous interface formed without adding an auxiliary co‐nematogen. Using ultraviolet (UV) light treated 4‐cyano‐4′‐pentylbiphenyl (5CB) LC and a flow‐focused microfluidic device, we prepared different populations of monodisperse and highly negatively charged microdroplets in water. Adding an aqueous solution of various model proteins (α‐synuclein, α‐chymotrypsin, myoglobin, or bovine serum albumin, BSA) with different secondary structures and surface charges triggers a rapid radial‐ to bipolar‐defect transition in these microdroplets. Isothermal titration calorimetry measurement and molecular dynamic simulation studies attribute this to the dominant electrostatic force‐mediated adsorption of proteins at the LC/aqueous interface. Further, bioconjugation‐based variation of protein surface charge allows tuning their detection limit. These findings can provide crucial physical cues for designing responsive LC systems and establishing a foundation for developing versatile, molecularly tailored, and highly specific biomolecular detection platforms.