Tiny flows, big insights: microfluidics system boosts super-resolution microscopy

The compressed-air-driven microfluidics system tailored for multiplexed super-resolution microscope developed by the research team to provide accessible, cost-efficient, high-quality imaging of cells, including fragile biological samples.
Photo Credit: Roman Tsukanov

Scientific Frontline: Extended "At a Glance" Summary: Multiplexed Super-Resolution Microfluidics System

The Core Concept: A highly adaptable and cost-efficient microfluidics system designed to automate fluid exchange in multiplexed super-resolution microscopy, allowing scientists to simultaneously visualize multiple molecular components inside a single cell with nanometer precision.

Key Distinction/Mechanism: Unlike conventional imaging methods that rely on manual pipetting and are prone to variability, this platform precisely injects and removes solutions using a compressed-air-driven mechanism. This automated fluid handling maintains consistent conditions across long imaging cycles without deforming or detaching fragile biological samples, such as isolated heart muscle cells.

Major Frameworks/Components:

• Multiplexed Super-Resolution Microscopy: An advanced optical imaging framework that resolves cellular details far beyond the physical limits of conventional light microscopes.
• Automated Microfluidics Platform: A customizable hardware component that standardizes labeling and washing steps, operable in both manual and automated modes.
• DNA-Targeted Labeling: A technique utilizing DNA sequences to tag different target molecules with the same color, allowing high-precision location tracking and complex image overlay.

Branch of Science: Biophysics, Cellular Biology, Microfluidics, and Optical Microscopy.

Future Application: Standardizing multiplexed super-resolution imaging to make it broadly accessible for laboratory research and advanced medical diagnostics, enabling high-quality structural analysis of human cancer cells and highly fragile biological tissues.

Why It Matters: Understanding how cellular components interact cooperatively is essential to modern life sciences. This technological advancement overcomes major reproducibility and sample-preservation barriers, providing unprecedented, clear visualization of complex protein networks and cellular structures.

Multiplexed super-resolution image of targets inside the same U2OS cell taken using the newly developed microfluidics system. Target molecules in the sample are labelled with DNA featuring different sequences but the same color. Different target proteins can be located with nanometer precision, and overlaid to create a final image.   
Photo Credit: Adapted from the original publication in ACS Nano (2026). DoI: 10.1021/acsnano.5c18697

Understanding how cells are organized and how their molecular components interact in a coordinated and cooperative manner is a central goal of modern life sciences. To answer these questions, researchers need to observe many structures inside the same cell at once and map how they are arranged and interact. This requires “multiplexed super-resolution microscopy” – an advanced imaging approach that reveals cellular details far beyond the limits of conventional light microscopes. However, existing methods are often technically demanding, difficult to reproduce, and not well suited for fragile biological samples. An international research team led by the University of Göttingen, together with the University Medical Center Göttingen (UMG), as part of the Göttingen Cluster of Excellence “Multiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells” (MBExC), set out to overcome these limitations. The team developed a dedicated microfluidics system that makes multiplexed super-resolution microscopy easier, more reproducible, and accessible to a broader community.

Super-resolution image of cytoskeleton and focal adhesion proteins taken using the new versatile and cost-effective microfluidics system. The “overlay” of all the different target molecules reveals exquisite and complex detail up to 100 times sharper than conventional microscopy.
Photo Credit: adapted from the original publication in ACS Nano (2026). DoI: 10.1021/acsnano.5c18697

To truly understand how a cell functions, scientists must visualize not just one component at a time, but many proteins and specialized structures simultaneously and see how they interact inside the cell. In addition, these experiments become increasingly complex and sensitive to small variations, which can limit reproducibility. The new microfluidics system precisely injects and removes solutions from the sample chamber, replacing manual pipetting with controlled and reproducible fluid handling. “The system we have developed means we can maintain high image quality throughout long imaging cycles,” says Dr Samrat Basak, joint first author and Postdoctoral researcher now based at LMU Munich. “By keeping conditions consistent across the different labelling and washing steps, the microfluidics platform allows information from different targets to be directly mapped, making it possible to image proteins, specialized structures and complex interactions within the cell.” The researchers demonstrated this technique in human cancer cells, revealing the organization of protein filaments inside the cell. The team also applied the method to isolated specialized muscle cells from the ventricles of a mouse heart. “The fragile, specialized muscle cells of the heart are particularly challenging to image,” explains joint first author Kim-Chi Vu, UMG and MBExC. “The microfluidics system was essential to complete the imaging without deforming the cells or detaching them from the surface.” 

The new machine can be operated in manual or automated modes and is compatible with a wide range of imaging systems. “The core idea was to develop a system which is cost-efficient, adaptable, and can be redesigned according to specific imaging needs of complex biological systems,” explains Dr Roman Tsukanov, senior Postdoctoral researcher at Göttingen University. “By automating fluid exchange, we removed a major source of variability and made complex imaging protocols much more user-friendly.”  

“This approach will help standardize multiplexed super-resolution imaging and make it broadly accessible, benefiting both research and medical applications,” adds Professor Jörg Enderlein at Göttingen University’s Physics Faculty. 

Published in journal: ACS Nano

Title: Versatile Microfluidics Platform for Enhanced Multitarget Super-Resolution Microscopy

Authors: Samrat Basak, Kim-Chi Vu, Nikolaos Mougios, Nazar Oleksiievets, Yoav G. Pollack, Sören Brandenburg, Felipe Opazo, Stephan E. Lehnart, Jörg Enderlein, and Roman Tsukanov

Source/Credit: Georg-August-Universität Göttingen

Reference Number: cbio030426_01

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