Project: PremoCell – Photonic Analytics Platform for Real-Time Monitoring of Stem Cell-Based In Vitro Models

As part of the Fraunhofer PREPARE program, four Fraunhofer Institutes are developing a modular biophotonic platform that enables the real-time visualization of drug effects in complex in vitro models such as stomach and liver organoids.

How do human cells respond to a drug, and how does their response change over time? In the PremoCell project, the four Fraunhofer Institutes IPMS, IGB, IBMT and IZI-BB are developing a new photonic analytics platform based on specially developed photonic sensor chips. The platform is designed to continuously monitor selected biomarkers in real time, providing insights into how living cell models and organoids – three-dimensional, organ-like structures – respond to drugs. The aim is to support preclinical drug development.

The contribution of Fraunhofer IPMS

Fraunhofer IPMS is developing novel silicon nitride (Si₃N₄)-based photonic integrated circuits (PICs) that combine three detection principles. They enable the rapid detection of cell-secreted biomarkers in complex media with high sensitivity and specificity, significantly exceeding the capabilities of conventional endpoint methods.

To integrate the PIC sensors into preclinical test models, the three partner institutes are developing relevant in vitro drug testing models of the liver and stomach with different levels of complexity. Their flexibility is intended to address a broad range of preclinical testing strategies. Fraunhofer IZI-BB focuses on generating liver organoids from hiPS cells and further developing them into a MASLD/MASH model by combining genetic risk alleles with defined environmental factors. Embedded in a microphysiological system with integrated real-time sensing, these models are intended to be used for toxicity and efficacy testing of drug candidates in the future.

Through close collaboration within PremoCell, new approaches are being developed for preclinical research and for in vitro testing systems for material assessment, for example in the context of REACH.

“By integrating multiple photonic biosensing elements on a single chip, different biomarkers can be detected in parallel with high sensitivity and specificity – within a very small footprint. Our aim is to continuously and simultaneously monitor relevant biomarkers directly from complex biological models and track their changes over time.”

Dr. Florenta Costache, PremoCell Project Manager, Fraunhofer IPMS

Technological approach

At the heart of the development are silicon nitride-based photonic integrated circuits (PICs) and their integration into the PremoCell analytics platform. The technological foundation is a silicon nitride waveguide platform developed and established at Fraunhofer IPMS on 200 mm silicon wafers, enabling particularly low-loss light guiding. For PremoCell, the sensor surfaces are functionalized with specific recognition molecules and tailored to the selected biomarkers and biological samples.

The photonic biosensor chips use the evanescent field of light guided through nanoscale waveguide structures to detect the binding of biomarkers to the biofunctionalized sensor surface. The sensor surface is in direct contact with the biological sample. The platform also integrates microfluidics and scalable readout architectures, enabling multiple biomarkers to be monitored in parallel under physiologically relevant conditions. In addition, spectroscopic methods and reporter spheroids – spherical cell aggregates with biological reporter functions – are used to provide complementary information about the biological models, which is combined with the PIC-based analysis.

This enables dynamic biological responses to be monitored in real time, whereas conventional endpoint measurements provide only a snapshot at a specific point in time.

Scalability and industrial relevance

A key advantage of the PIC-based approach is the use of established semiconductor manufacturing processes. The PremoCell technology is being developed on an industrial 200 mm silicon wafer platform. This established wafer format provides important prerequisites for reproducible and scalable manufacturing at higher volumes. The project thus lays the foundation for the future transfer of the technology to new applications, particularly in the field of preclinical drug testing.

The PremoCell analytics platform addresses key challenges in biomedical research and aims to open up new opportunities for characterizing complex in vitro models. In the future, the approaches developed could help to:

• better understand drug effects in cell-based models such as organoids,
• systematically analyze differences between healthy and disease-associated organoids,
• monitor changes in relevant biomarkers over time,
• enable more efficient and informative testing procedures.