We are interested in probing biological systems at the nanoscale level which is the building block of life but cannot be easily interpreted without engineering appropriate toolboxes. We believe that the means to detect, quantify and visualize the nanoscale world in real-time is the first step towards bottom-up understanding of biology. Hence our group’s overarching research theme is to design synthetic molecular systems comprising of nanoscale materials (such as DNA, enzymes and nanoparticles) which are responsive to biological entities and processes.
Engineering Molecular and Nanoscale Toolbox
We engineer molecular circuits powered by nanoscale building blocks, such as DNA, enzymes and nanoparticles, to perform pre-programmed operations. The first step involves the elucidation of the working mechanism of each modular building block which are then generalized into design heuristics. Some building blocks include (1) DNA circuits driven by Watson Crick hybridization, (2) controlled assembly of DNA-conjugated gold nanoparticles, (3) CRIPSR Cas systems with enhanced strand-cleaving specificity. Each module can be cascaded within itself or integrated with other modules into a toolbox to probe specific biological questions.
Representative Publications:
Y. S. Ang and L. Y. L. Yung, “Dynamically elongated associative toehold for tuning DNA circuit kinetics and thermodynamics,” Nucleic Acids Res. 49, 4258-4265 (2021) DOI: https://doi.org/10.1093/nar/gkab212
Y. S. Ang and L. Y. L. Yung, “Rational design of hybridization chain reaction monomers for robust signal amplification,” Chem. Commun., 52, 4219-4222 (2016) DOI: 10.1039/C5CC08907G
Biosensing Applications
One of our research goals is to steer our basic design concepts closer towards real-world application which we demonstrate over various biosensing works, such as for disease diagnostics and bioimaging. On the disease diagnostics front, we have applied our well-defined DNA-gold nanoparticle conjugates as well as DNA circuit assay for probing various disease biomarkers including DNA single nucleotide polymorphism for G6PD condition, microRNA family. On bioimaging, we have applied our DNA circuit assay to visualize estrogen receptors (ER) binding and HER2 clustering patterns on breast cancer cells.
Representative Publications:
Y. S. Ang, P. S. Lai, L. Y. L. Yung, “Design of Split Proximity Circuit as a Plug-and-Play Translator for Point Mutation Discrimination,” Anal. Chem. 92, 11164-11170 (2020) DOI: 10.1021/acs.analchem.0c01379
Y. S. Ang, J. J. Li, P. J. Chua, C. T. Ng, B. H. Bay, L. Y. L. Yung, “Localized Visualization and Autonomous Detection of Cell Surface Receptor Clusters Using DNA Proximity Circuit,” Anal. Chem., 90, 6193-6198 (2018) DOI: 10.1021/acs.analchem.8b00722
Microfluidics Separation
One of the challenges in translating techniques developed in research lab for practical application is the matrix effect in patient samples. We have developed microfluidic separation methods based on different physical principles, such as standing wave acoustics, dielectrophoresis and inertia. An example is the design of spiral microfluidic chips to isolate intracellular bacterial colonies (IBCs) responsible for recurrent urinary tract infection (rUTI). We have since applied the device for isolating infected epithelial cells containing IBCs from clinical urine samples (Urology Clinic and Emergency, National University Hospital).
Representative Publications:
S. Duraiswamy and L. Y. L. Yung, “Dean migration of unfocused micron sized particles in low aspect ratio spiral microchannels,” Biomed. Microdevices 23, 1 – 16 (2021) DOI: https://doi.org/10.1007/s10544-021-00575-y
N. Allahrabbi, Y. S. M. Chia, M. S. Saifullah, K. M. Lim, L. Y. L. Yung, “A hybrid dielectrophoretic system for trapping of microorganisms from water,” Biomicrofluidics, 9, 034110 (2015) DOI: 10.1063/1.4922276