Entwicklung eines linsenfreien Fluoreszenzmikroskops zur online Bioprozessanalytik - Skripte

In order to comply with the regulatory quality requirements of the U.S. Food and Drug Administration (FDA), the use of Process Analytical Technologies (PAT) is essential in pharmaceutical manufacturing. The goal is to ensure end-product quality by defining, measuring, and controlling critical process parameters. A central aspect of modern PAT strategies is the continuous, non-invasive monitoring of bioprocesses. This enables the timely acquisition of relevant parameters directly within the process, without the need for manual sampling.
In this context, a universal, single-use measuring cell was developed that combines scattered light and absorption measurement in a compact system. The sensor technology is based on a pre-sterilised, biocompatible disposable design and can be flexibly integrated into various reactor systems via a bypass. Scattered light measurement allows reliable determination of cell concentration, while absorption measurement can be used to monitor product formation and cell growth. The 3D-printed measuring cell is biocompatible, autoclavable, and highly adaptable to different process requirements.
For complementary process monitoring, a lensfree microscopy technology was developed that enables real-time imaging of biological components. This optical measurement method is based on the reconstruction of holographic images using numerical algorithms and allows high-resolution visualization of cellular structures. The technology enables direct determination of cell concentration within the process and thus allows continuous monitoring without manual sampling.
Based on initial successful trials, the system was extended with an additional light source for spatially resolved fluorescence measurement. This component is intended to enable a differentiated analysis of cellular states in real time and to further enhance the informational value of the data. The combination of single-use measuring cell, multimodal sensor technology, and lensfree microscopy thus forms a powerful platform for efficient and automated bioprocess monitoring. It represents a significant advancement in the implementation of modern PAT strategies in biopharmaceutical production.