Biosensing with lyotropic chromonic liquid crystals: From molecular recognition to quantitative diagnostics and real-time kinetic monitoring
Mon-Juan Lee1, Wei Lee2*
1Department of Biomedical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan
2Institute of Imaging and Biomedical Photonics, National Yang Ming Chiao Tung University, Tainan, Taiwan
* Presenter:Wei Lee, email:Wei.Lee@nycu.edu.tw
Lyotropic chromonic liquid crystals (LCLCs) have emerged as versatile platforms for label-free biosensing, offering unique optical and dielectric properties that respond sensitively to biomolecular interactions. This talk reviews four recent studies that demonstrate the application of LCLCs in detecting cancer biomarkers and viral proteins, with a focus on real-time monitoring and kinetic analysis. By integrating spectrometric, haze-based, and electrical readouts, these systems achieve high sensitivity and quantitative precision without the need for fluorescent or enzymatic labels. The work highlights the physical principles underlying LCLC alignment changes, the role of surface anchoring, and the potential for scalable, low-cost diagnostics.
Our group has explored the potential of various LCLC-based platforms for immunoassays targeting disease biomarkers, with a particular emphasis on real-time monitoring and kinetic analysis of molecular binding. Below, we briefly highlight four recent publications that illustrate the versatility and sensitivity of these systems:
(1) CA125 Detection via Spectrometric Analysis (2021)
In our first study, we demonstrated label-free detection of the ovarian cancer biomarker CA125 using the nematic phase of disodium cromoglycate (DSCG), a representative LCLC. Spectrometric analysis of transmitted light revealed quantifiable changes in optical intensity that correlated with biomarker concentration, achieving a detection limit of 0.1 ng/mL.
(2) Real-Time Optical and Dielectric Immunoassays (2023)
Building on this foundation, our second study introduced a dual-mode biosensing approach that combined optical and electrical signals. Real-time monitoring of antigen–antibody interactions with a LCLC made of an aqueous solution of disodium 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonate (i.e., sunset yellow, SSY) enabled extraction of kinetic parameters such as association and dissociation rates. Disruptions in LCLC alignment served as sensitive transducers for both modalities.
(3) Haze-Based Quantitation in Protein Assays (2024)
The third study compared nematic thermotropic and lyotropic LCs for protein detection, employing haze measurement as a quantitative readout. The haze index exhibited a linear correlation with protein concentration on a logarithmic scale, offering a straightforward and effective method for immunoassay quantification.
(4) SARS-CoV-2 Nucleocapsid Detection in Saliva (2025)
Our most recent work applied SSY-based LCLCs for detecting the SARS-CoV-2 (i,e,, COVID-19) nucleocapsid protein in saliva samples. Optical and dielectric responses enabled highly sensitive detection down to 0.1 ng/mL, demonstrating the platform’s applicability to real-world diagnostic scenarios.
Looking ahead, the continued development of LCLC-based biosensors holds promise for scalable, low-cost, and multiplexed platforms that can be tailored to a wide range of biomarkers. Their simplicity, sensitivity, and physical elegance position them as compelling candidates for next-generation point-of-care diagnostics and interdisciplinary research at the interface of physics, chemistry, and biomedicine.
Keywords: Liquid Crystals, Label-Free Biosensing, Binding Kinetics, Haze Measurement