Technology

Technologies and probes for the questions we ask.

We innovate, combine, and utilize cutting-edge fluorescence imaging technologies, smarter probes, and computational tools that push the limits of spatiotemporal resolution, imaging speed, imaging depth, smarter labeling approaches, and molecular quantification.

Single molecule localization microscopy (SMLM) in fixed and live cells

Molecular mapping and quantification of target receptor/protein/organelle organization using multiplexed two-dye imager (TDI)-DNA-PAINT, dSTORM in fixed cells, and ProteinPAINT in live cells. We exploit widefield and TIRF illumination, quencher probes, and biplane detection for 3D localization.

Superresolved reconstruction of whole-cell volumes

By combining lattice lighsheet or single objective lighsheet microscopy with SMLM, we aim to implement multiplexed volumetric molecular resolution imaging of receptor organization across whole live and fixed cells.

Volumetric fluorescence lifetime imaging microscopy (vFLIM)

Lighsheet based volumetric FLIM imaging via time-gated detection to map whole-cell molecular interactions, phase-separation mediated receptor clustering, and force sensing.

Graphene/Metal-induced energy transfer (GIET/MIET)

By exploting standalone GIET or MIET imaging, we aim to quantify membrane fluctuations at nanosecond temporal and sub-nanometer axial resolution. By combining GIET/MIET with SMLM, 3D imaging at isotropic resolution can be realized. We will exploit these technologies for quantifying protein organization in vitro synapse models.

Organoid-SMLM

Implementing SMLM, in particular, TDI-DNA-PAINT imaging of immunotherapies deep inside disease model organoids. We are building a MOSAIC setup, following the Betzig design which allows adaptive optics-empowered lattice lighsheet-DNA-PAINT implementation.

Expansion microscopy (ExM)-SMLM

Ultra-resolution imaging of fixed and physically expanded cells in a swellable gel. We combine the power of SMLM and ExM together for true molecular resolution imaging across all three dimensions.

Fluorescence Correlation Spectroscopy (FCS) and variants

By utilizing FCS and many of its variants, such as, FLCS, FCCS, Imaging-FCS, in combination with GIET/MIET, Lightsheet microscopy, our goal is to investigate global receptor dynamics and protein mobility in 3D on cell membranes.

4D Single Particle Tracking (SPT)

By exploiting the extraordinary temporal resolution of lattice lighsheet microscopy, we will track individual receptor mobility, coordinated CAR-antigen movements, in space and time (4D) at different T cell activation states.

Machine-learning (ML) enabled assay development

We are building a pipeline for high-throughput ML-enabled assay to characterize under-trial emerging CAR T therapies and antibodies at the NCT WERA. The core idea is to classify the new drugs' efficacy based on their spatiotemporal binding properties, synapse architecture, quality, and correlated cytotoxicity.