Molecular nanotechnology and biochemistry

Mobile Organ-on-Chip Analytics

Organ-on-chip technology enables the exploration of complex cellular processes in lab-on-chip systems with minimal cell material. It accelerates drug development, enhances safety and cost efficiency, and reduces the risk of failure due to species differences by utilizing human models. The combination of microfluidics, 3D cell culture, spheroids, and organoids creates in vivo-like conditions. However, this currently requires elaborate infrastructure (e.g., hypoxic environments), which complicates access to high-resolution, multiparametric analytics (microscopy, spectroscopy).

MOCHA aims to develop a compact, chip-based analysis unit that integrates optical and non-optical methods to enable comprehensive monitoring. Through intelligent fluidic design and appropriate material combinations, long-term cultivation of spheroids over weeks to months is intended. A microfluidic platform will be developed to ensure in vivo-like supply, controlled nutrient and gas delivery, efficient metabolite removal, interactions between spheroids, and targeted drug delivery. Spheroid layouts, fluidic routing and actuation modules, and sensor integration interfaces will be developed. Additionally, an operating device for thermal and fluid control with integrated sensors and real-time data retrieval via suitable interfaces will be created.

Duration
07/2024 – 06/2027

MIC-PreCell established a technology hub at the Fraunhofer Center Erfurt FZE for precise quality assurance and process control in the production of cell-based therapeutics (ATMPs). Under the leadership of the Fraunhofer Institutes IZI (Cell Therapies), IPMS (Microelectronics / MEMS), and IOF (Optics / Photonics), novel, automatable analytical methods are being developed and made transferable to GMP-compliant workflows. The goal is to reduce manufacturing costs, detect process risks at an early stage, and enhance product consistency for patient-specific and off-the-shelf therapies (e.g., CAR-T, CAR-NK, stem cells). This approach addresses key bottlenecks in current quality control: Many tests are currently performed sequentially, invasively, and are not inline-capable, meaning that errors often only become apparent at the end of costly processes. MIC-PreCell closes this gap with three complementary technology modules:

• Mechanomics: Real-time deformability cytometry (RT-DC) captures label-free biomechanical cell parameters as sensitive functional markers (activation, stress, differentiation) and enables stop / go decisions during expansion and transduction.
• Volatilomics: GC-IMS-based gas analytics quickly, robustly, and non-invasively detects volatile metabolites (VOCs) from cell cultures – for density / growth monitoring, stress and contamination detection, as well as the optimization of cultivation conditions.
• Micro-manipulation: A modular probe station with high-resolution imaging and MEMS micro-grippers / micro-injectors allows for precise interventions and functional tests on single cells, spheroids, and organoids.

Additionally, the cell culture infrastructure at Fraunhofer FZE is being expanded for complex human cells (T / NK cells, stem cells, tumor material), and standardized SOPs are being implemented. Data analysis pipelines using machine learning link mechanical, metabolic, and imaging signatures to practical QC parameters.

Duration
09/2021 – 06/2023

AutoImmunCAR investigated the transferability of the successful CAR T-cell therapy from oncology to B cell-mediated autoimmune diseases. Building on the MIC-PreCell infrastructure available at the Fraunhofer Center Erfurt (FZE) and in close collaboration with the Central German Cancer Center (CCC Jena Leipzig), proof of concept results were achieved for new analytical methods that characterize interactions between T- and B-cells in high resolution. The goal was to create an integrated picture of immunological, biomechanical, and metabolic parameters to capture activation, function, and potential efficacy markers of native and CAR-transduced immune cells.

Key methods included:

• Flow Cytometry with a customized panel (based on the clinical panel of the University Hospital Leipzig) for phenotyping and activation analysis.
• Real-time Deformability Cytometry (RT-DC) for label-free capture of biomechanical cell signatures.
• Gas Chromatography-Ion Mobility Spectrometry (GC-IMS) for non-invasive metabolic profiling (VOC analytics).

In a seven-month project timeframe, simple yet meaningful cell models were established: baseline T-cells and hyperactive B-cells as an autoimmune phenotype, supplemented by mixed T / B cell cultures. Based on this, reference profiles of resting and activated cell populations (native and CAR-modified) were created, along with initial datasets on changes following direct cell-cell interactions. The combination of surface marker expression (flow cytometry), mechanical properties (RT-DC), and metabolic signatures (GC-IMS) demonstrated the potential to complementarily and early capture activation states, stress responses, and functional differences.

Duration
05/2024 – 11/2024

The aim of LIFE KOOP 2024 is to investigate the relationship between microclots in the blood and the brain health of participants in the LIFE Adult studies. To this end, the quantity, concentration, and characteristics of microclots in existing LIFE Adult samples from the Leipzig Medical Biobank (LMB) will be analyzed and linked with data from the LIFE database. Microclots are insoluble, very small blood clots overloaded with inflammatory molecules that can be detected in the blood capillaries of patients with severe courses of COVID-19 and Long-COVID. They can severely disrupt the supply of oxygen and nutrients, potentially triggering COVID-associated neurological and psychiatric symptoms such as muscle pain, fatigue, or brain fog. Microclots are also detectable in patients with Type 2 diabetes, Alzheimer’s, or Parkinson’s disease.

The focus of the current project is to investigate a possible correlation between the concentration of microclots in the blood, cognitive parameters, and the structure and function of the brain, further specified through the inclusion of MRI parameters from the LIFE cohorts. It is expected that microclots will be associated with aging processes in the brain and mediate vascular-related neurodegenerative structural and functional changes. The planned investigations will contribute to predicting and better understanding cognitive decline and an increased risk of dementia.

Duration
05/2024 – 12/2027

The goal of Smart-µ-Plate is to develop a fast, cost-effective analysis system for bedside detection of specific biomarkers in human samples. Miniaturized sensor components will be integrated with customized bioassays and user-friendly hardware into a portable solution.

Duration
01/2024 – 12/2026

Glyco3Display focused on the integration of synthetically produced sugar / glycan molecules into DNA-based nanoparticles to create hybrid nanostructures that target bacteria and viruses for both diagnostic and therapeutic purposes. Sugar molecules such as mannose or sialic acid are common molecules for recognition and binding between biological organisms, including cells, viruses, and bacteria. In Glyco3Display, DNA-based nanoscaffolds were used to generate nanometer-precise arrangements of sugar molecules, which were then utilized to bind bacteria such as E. coli and integrated into various systems for the detection and analysis of binding to different bacteria, viruses, and sugar-binding proteins known as lectins.

Duration
01/2018 – 06/2023

The project focuses on the development of technologies for cell- and tissue-specific nanocarriers. Various targeting components are integrated into nanocarriers made of lipids or amphiphilic polymers to enable the targeted delivery of cargos to target cells.

Duration
07/2022 – 12/2025

In CoronaSense, nanostructures made from a combination of DNA strands and peptides were used to investigate the binding of the SARS-CoV-2 spike protein to target protein sequences. A peptide fragment mimicking the binding site of the spike protein on the ACE2 antigen was chemically conjugated to a DNA nanostructure in a multivalent arrangement that resembles the natural geometry of the spike protein. This DNA-templated binding was utilized to study the cooperativity between the subunits of the spike protein during binding and to assess the effects of natural mutation variants that occur during SARS-CoV-2 infections.

Duration
06/2020 – 05/2021

The goal of the AsphyxDX project is to translate extensive existing preliminary work in the detection of oxygen deprivation (asphyxia) in newborns into diagnostic applications. The diagnostic approach is based on the quantification of small endogenous metabolites (molecular weight <1200 Da); this will be performed for diagnostics (independently of large devices such as mass spectrometers) using nanopore-based and other rapid tests. Novel point-of-care (PoC)-capable testing systems are to be developed for this purpose. The role of Fraunhofer IZI is to develop functionalized DNA-based nanostructures that bind to the selected metabolites through specific ligand-receptor interactions.

Funding
Forum Gesundheitsstandort Baden-Württemberg

Duration
06/2020 – 05/2022