Development of a novel disposable flowcell for spectroscopic bioprocess monitoring

Abstract

Regulatory authorities require product control for market release, especially for medical products due to legal regulations. Thus, end product control is conducted before drug market release. For real-time release in terms of Process Analytical Technology (PAT), product quality must be designed into the process. Process sensors are needed to monitor critical process parameters (CPP) for immediate control. Conventional sensors lack interfaces for disposable bioreactors, but new flow cell systems enable spectroscopic bioprocess monitoring via a bypass system. The flow cell is gamma-sterilized and clamped into a reusable holder, allowing spectroscopic techniques like turbidity, UV/VIS spectroscopy, and fluorescence.

The cell setup and biocompatibility are presented, with in-vitro toxicity of various 3D printable materials evaluated per ISO 10993 to find suitable materials. Polyamide (PA), Acrylonitrile Butadiene Styrene (ABS) and Polymethyl Methacrylate (PMMA) were used for manufacturing flow cells and tested for in vitro biocompatibility. Results confirm the suitability of these materials and processes, with UV–VIS spectroscopy providing key insights. Selectivity and sensitivity for three different important bioprocess variables were evaluated and enables precise sensor system characterization across various analytes, advancing flow cell and sensor technology in biosensing and analytical chemistry.