The research at Julius-Maximilians-University Würzburg focuses on using Lattice Lightsheet 7 and single-molecule localization to study the dynamic interactions of CD20 with therapeutic antibodies. This approach has unveiled new insights into antibody-induced CD20 clustering on B cells, potentially reshaping immunotherapy strategies.
Revolutionizing Immunotherapy Imaging with Lattice Lightsheet 7
Key Takeaways
Research focus: Single-molecule imaging and super-resolution microscopy with Lattice Lightsheet 7.
Model system: Whole B cells visualizing CD20 interactions.
Research goal: Understand CD20 clustering dynamics and improve immunotherapy.
Presented by: Prof. Dr. Markus Sauer’s team at Julius-Maximilians-University Würzburg.
Content type: Customer Highlight on advanced microscopy techniques.
The team’s research focuses on single-molecule sensitive fluorescence detection and super-resolution microscopy. By combining TDI-DNA-PAINT with Lattice Lightsheet 7, they achieved fast, volumetric imaging of whole B cells – capturing the dynamic interplay between CD20 and therapeutic antibodies like Rituximab (RTX), Ofatumumab (OFA), and Obinutuzumab (OBZ).
This approach revealed that both type I and type II antibodies induce CD20 clustering and B cell polarization – challenging long-standing classifications and offering new perspectives on how immune responses are triggered.
Guided by the pursuit of molecular precision, the team at JMU focuses on single-molecule sensitive fluorescence detection and super-resolution microscopy – uncovering how cellular behavior unfolds at the nanoscale.
Single-molecule imaging reveals the individuality of cells – it’s the foundation for personalized treatment.
ZEISS Lattice Lightsheet 7 was chosen for its intuitive design and compatibility with single-molecule localization techniques. While the team had access to a Betzig LLS system, they found ZEISS Lattice Lightsheet 7 to be more efficient and easier to use.
Its ability to image entire cells in 3D with minimal photobleaching enabled the team to visualize CD20 distributions at apical sites and cell-cell contact zones – areas previously difficult to access without surface-induced artifacts.
Lattice Lightsheet 7 makes whole-cell imaging accessible – no complex alignments, just powerful results.
To overcome limitations in traditional DNA-PAINT, the team developed two-dye imager strands that form non-fluorescent dimers in the unbound state. This technique – an advanced version of DNA-PAINT single-molecule localization microscopy – reduces background noise and allows for higher probe concentrations, resulting in imaging speeds up to 15 times faster.
They also adopted the introduction of astigmatism with the system's inherent custom-engineered optics, diverting their intended use for aberration control to enable precise 3D localization. This solution was first introduced by the group of Lukas Kapitein, a leading cell biologist at Utrecht University known for pioneering lattice light-sheet motor-PAINT to study microtubule orientation in whole cells.
We minimized background and boosted speed – now we can image whole cells in hours, not days.
The future is molecular clarity – seeing every detail in 3D, in living cells.
At the Julius-Maximilians-University Würzburg (JMU), Prof. Dr. Markus Sauer leads a research group specializing in single-molecule fluorescence detection and super-resolution microscopy. With a strong foundation in dye chemistry and photophysics, the team develops advanced imaging techniques such as
Their work bridges fundamental biophysics with translational applications, aiming to improve diagnostics and immunotherapy – particularly through the molecular characterization of therapeutic antibodies and CAR-T cells.
As one of the first groups to publish in this field, they continue to push the boundaries of resolution and real-world impact – positioning JMU as one of the leaders in single-molecule biophysics.