Fraunhofer Institute for Production Technology IPTResearch project "FLITS"
The project “FLITS” gives the base for a new generation of high-speed fluorescence microscopy. The aim is to dramatically reduce acquisition times for large fluorescence images while maintaining high image quality.
In cell biology, cancer research, and pharmaceutical development, large sample areas, such as entire microplates, must be analyzed automatically. Conventional fluorescence microscopes operate in stop-and-go mode: the sample is stopped for each image, exposed, and then moved on. This is time-consuming, limits throughput, and hinders scalable, automated processes, for example in personalized medicine or quality control of cell and gene therapies.
High-speed microscopy for increased throughput
To overcome these bottlenecks, the FLITS research project focuses on developing a novel high-throughput fluorescence microscopy method. A microtiter plate should be captured in a few minutes instead of up to several hours: the acquisition time at 4x magnification should drop from about 55 minutes to under 8 minutes, and at 10x magnification from about 250 minutes to under 20 minutes - without sacrificing sharpness, contrast, or signal-to-noise ratio.
The core approach is a continuous scanning method: the sample moves smoothly past the objective during image acquisition and does not need to be stopped. A specialized Time-Delay-Integration (TDI) camera exposes each image line multiple times and integrates the weak fluorescence signal over several extremely short exposures. Short pulsed LED light sources and adapted illumination geometry ensure that, despite high speed, enough signal is collected and phototoxicity for living samples is minimized.
Sharp Images Despite Movement
Sharp Images Despite Movement Additionally, an inline autofocus system is being developed to continuously adjust the distance between objective and sample in real time during movement. An optical distance sensor continuously measures the height of the sample, and a piezo Z-axis corrects focus on the micrometer range. This enables fast and sharp imaging of uneven or differently shaped samples - such as various microplates - without additional focus scans.
With the high-speed fluorescence microscopy developed in the project, large-area cellular and tissue samples can be analyzed much faster and more resource-efficiently. This generates new possibilities for high-throughput screenings in drug development, automated quality control in cell and gene therapy, as well as applications in bioproduction and diagnostic-related research.
The FLITS research project focuses on high throughput and automation in fluorescence microscopy and complements existing work that has so far concentrated mainly on higher resolution or additional image contrasts.
Funding
The research project “FLITS – High-speed fluorescence microscopy for quality control in life sciences” is funded under the "Scientific Preliminary Projects: Photonics and Quantum Technologies (WiVoPro)” program.
Funding code: 13N17512
Project sponsor: VDI
Project duration: 11/2025 - 10/2028
Project Management
Fraunhofer-Institut für Produktionstechnologie IPT, Aachen