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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.
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2 min read
Microscopic images show cells with bright, branching structures extending outwards; a 4 μm scale bar is present in the lower left corner.
A middle-aged man with short gray hair and light stubble, wearing a blue shirt and dark jacket, looks at the camera with a neutral expression against a pale background.
A 3D microscopic image showing clusters of spherical cells highlighted in yellow and pink on a black background with grid lines.A 3D microscopic image showing clusters of spherical cells highlighted in yellow and pink on a black background with grid lines.
A 3D microscopic image showing clusters of spherical cells highlighted in yellow and pink on a black background with grid lines.

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.

Four 3D fluorescence microscopy images show cell clusters with green and magenta-stained structures, displayed within grid backgrounds and 5 μm scale bars.
Four 3D fluorescence microscopy images show cell clusters with green and magenta-stained structures, displayed within grid backgrounds and 5 μm scale bars.

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.

A middle-aged man with short gray hair wearing a dark polo shirt stands in front of a staircase with a curved railing.

Lattice Lightsheet 7 makes whole-cell imaging accessible – no complex alignments, just powerful results.

3D scatter plot with red/orange data points clustered in the center, labeled axes in micrometers: X (0–25), Y (0–15), and Z (0–10), on a black background.3D scatter plot with red/orange data points clustered in the center, labeled axes in micrometers: X (0–25), Y (0–15), and Z (0–10), on a black background.

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.

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Two women work in a lab; one operates a large machine on a table, while the other sits at a computer desk with multiple monitors.
Two women work in a lab; one operates a large machine on a table, while the other sits at a computer desk with multiple monitors.

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.

https://www.zeiss.com/microscopy/en/resources/insights-hub/life-sciences/cd20-imaging-with-lattice-lightsheet-7--single-molecule-localization.html?mkt_tok=ODk2LVhNUy03OTQAAAGeElmcqqH5XN2skm-sLA0DwUbIMX3zz7iT13OFaFOhVCyDaHd3WO4hpftWqaPCAfB8K4yS5X4_-1uXYCILOTPdSF9ufZs8BYVfF9T2VSixHNFcWcI4CpQ
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