Biology subjects

Wong, J. S. J.

Publications and source records attributed to Wong, J. S. J..

3 recordsLinked to original sources

bioRxiv2025

On-The-Fly Live-Cell Intrinsic Morphological Drug and Genetic Screens by Gigapixel-per-second Spinning Arrayed Disk Imaging

Next-generation drug discovery and functional genomics require rapid, unbiased single-cell profiling at scale--demands that exceed the limited speed, throughput, and labor-intensive labeling constraints of conventional high-content image-based screening. We introduce spinning arrayed disk (SpAD), a high-throughput, label-free imaging platform for live-cell imaging that integrates continuous circular scanning, ultrafast quantitative phase imaging (QPI), and a novel circular array of 96 culture chambers. SpAD achieves an order-of-magnitude reduction in imaging time compared to traditional fluorescence-based workflows, while remaining compatible with standard cell culture workflows. By extracting rich biophysical features using intrinsic morphological (InMorph) profiling and machine learning, SpAD enables sensitive, large-scale screening of drug responses and CRISPR gene knockouts without labeling. Critically, label-free biophysical readouts from SpAD reveal mechanism-linked changes in mass, refractive index, subcellular textures, and light scattering that fluorescent labels often obscure. SpAD thereby resolves subtle phenotypes and heterogeneous subpopulations with high reproducibility, providing a robust, scalable foundation for precision cellular morphological assays.

bioengineering↗

bioRxiv2025

FACED 2.0 enables large-scale voltage and calcium imaging in vivo

Monitoring neuronal activity at large scale and high spatiotemporal resolution is crucial for understanding information processing within the brain. We optimized a kilohertz-frame-rate two-photon fluorescence microscope with all-optical megahertz line-scan rate to achieve ultrafast imaging across large areas and volumes at subcellular resolution. Applying this technique to voltage and calcium imaging in vivo, we demonstrated simultaneous recording of voltage activity over 200 neurons and calcium activity over 14,000 neurons.

neuroscience↗

bioRxiv2023

Information-Distilled Generative Label-Free Morphological Profiling Encodes Cellular Heterogeneity

Image-based cytometry faces constant challenges due to technical variations arising from different experimental batches and conditions, such as differences in instrument configurations or image acquisition protocols, impeding genuine biological interpretation of cell morphology. Existing solutions, often necessitating extensive pre-existing data knowledge or control samples across batches, have proved limited, especially with complex cell image data. To overcome this, we introduce Cyto-Morphology Adversarial Distillation (CytoMAD), a self-supervised multi-task learning strategy that distills biologically relevant cellular morphological information from batch variations, enabling integrated analysis across multiple data batches without complex data assumptions or extensive manual annotation. Unique to CytoMAD is its "morphology distillation", symbiotically paired with deep-learning image-contrast translation - offering additional interpretable insights into the label-free morphological profiles. We demonstrate the versatile efficacy of CytoMAD in augmenting the power of biophysical imaging cytometry. It allows integrated label-free classification of different human lung cancer cell types and accurately recapitulates their progressive drug responses, even when trained without the drug concentration information. We also applied CytoMAD to jointly analyze tumor biopsies across different non-small-cell lung cancer patients and reveal previously unexplored biophysical cellular heterogeneity, linked to epithelial-mesenchymal plasticity, that standard fluorescence markers overlook. CytoMAD holds promises to substantiate the wide adoption of biophysical cytometry for cost-effective diagnostic and screening applications.

bioengineering↗