Microphysiological Systems

Real-Time Monitored Organ-on-Chip Systems for Personalized Drug Development

We develop microphysiological systems, such as organ-on-chip platforms, that are flexible and thus customizable – providing a sustainable alternative to animal testing. With integrated real-time monitoring, we precisely analyze cell viability and the metabolic activity of various cell models, including tissues, spheroids, and organoids.

Our systems enable dynamic, stable short- and long-term studies to evaluate the efficacy and safety of drugs, cosmetics, and chemicals (REACH). Compared to conventional endpoint measurements, they provide direct access to mechanism-of-action analyses, thereby optimizing therapy screening and the development of combination therapies.

With our customizable microphysiological systems, we are shaping the future of preclinical drug development and personalized oncology.

Characteristics und Benefits

Enhanced information density through continous real-time monitoring
- Precise analysis of dynamic biological processes
- Correlation of cellular drug responses for insights into mechanisms of action
Development of physiological profiles for drug concentrations and repeated dosing
Flexible adaptation to various cell models (e.g., liver, tumor, skin)
Long-term culture for up to 30 days
Predictive in vitro models to reduce animal testing in drug development

Empower your development pipeline with cutting edge technology.

Our Contribution to Your Project

Design and fabrication of microphysiological systems tailored to cell-specific requirements
Contract measurements to assess the efficacy and safety of active compounds
Sensor integration into microfluidic systems

More Precise Screening to Accelerate Drug Development

Discover further offers and information on specific use cases and specific applications of the technology!

Learn more about our offers for industry

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Projects

SkinMonitor: Microfluidic System Platform

Based on full-skin models for sensor-monitored real-time analyses

SkinMonitor Skin-on-Chip — Microfluidic lab-on-a-chip system for sensor-based investigation of skin cell models (skin-on-a-chip)

In collaboration with Fraunhofer IGB, we developed a test system for the investigation of cosmetic substances on skin models (skin-on-chip). For this purpose, 3D in vitro full skin models (Fraunhofer IGB) were linked via a microfluidic system with cell- and sensor-based analytics (Fraunhofer IZI-BB). The integration of optical oxygen sensors enables real-time analytics of cell viability, while reporter cells of the IGB indicate, for example, interleukin expression or activation of sensitizing signaling pathways. This combination enables the collection of detailed data on the toxicity of test substances.

TumOC: Colon Carcinoma Organoid-on-Chip.

Assessment of the efficacy of anticancer drugs by real-time measurements of cell viability

In cooperation with CELLphenomics GmbH, we have developed an organoid-on-a-chip system (TumOC) that enables (a) physiological long-term cultivation of organoids, (b) dynamic treatments, and (c) real-time measurements of cellular respiration.

It serves as an alternative to animal models in the context of preclinical drug development and personalized oncology.

Project (GErman)

HepatoTox: Microfluidic Bioreactors

In vitro toxicity measurements (Liver-on-a-Chip)

The microphysiological system (liver-on-a-chip) developed in this project for assessing the long-term toxicity of active compounds is intended to replace animal testing in the medium term. Real-time measurements of parameters such as glucose and oxygen concentrations and pH levels enable both quality control of the culture conditions and the acquisition of valuable time-resolved information on the metabolic activity of hepatocytes when they are exposed to drug candidates or chemical substances.

ParOptiSens: Development of Particle-Based Optical Sensors

Real-time analysis of metabolic processes for in vitro test systems

This project focused on the development of microsensor particles for real-time monitoring of the state of living cells cultured in artificial (in vitro) environments. This approach enables rapid and detailed assessment of the effects of drugs or toxic compounds on cell samples under physiological conditions.

Methods & Equipment

Methods

Design and development of microbioreactors for long-term cultivation of complex cell models.
Integration of microsensors into microfluidic systems for real-time detection of parameters in close proximity to cells and cell media (e.g. oxygen, pH, glucose, lactate)
Development of in vitro test systems for the evaluation of toxicity of chemicals, active pharmaceutical ingredients and components of cosmetics
Analysis of cells using fully automated fluorescence microscopy (CellSens + ScanR, Olympus)
Cell characterization: cell staining techniques (e.g., immunofluorescence), transfection with fluorescent fusion proteins, live-cell staining, proliferation assays
Data analysis using deep learning technology (ScanR + AI, Olympus), for example, to characterize and quantify cell populations and labeled cell structures or proteins

Equipment

Fully automated setups consisting of fluorescence microscopes (Olympus, cellSens), oxygen measurement systems (Opal, Colibri), and fluidic control (valves, pumps)
Confocal laser scanning microscope (Zeiss LSM 980 with NLO laser), incubation chamber, multiphoton excitation, fluorescence/phosphorescence lifetimes and correlations using lifetime imaging (FLIM/PLIM) and fluorescence correlation spectroscopy (FCS)
Fully automated fluorescence microscopes for time-lapse imaging of living cells under physiological conditions (time-lapse microscopy with incubation chambers) (cellSens; ScanR with AI)
TIRF microscopy (Olympus)
Laser tweezers / optical tweezers with laser microdissection (Palm / Zeiss)
Flexible microfluidic setups

Publications and Patents

Gehre C, Flechner M, Kammerer S, Küpper J-H, Coleman C D, Püschel G P, Uhlig K, Duschl C. Real time monitoring of oxygen uptake of hepatocytes in a microreactor using optical microsensors. Sci Rep (2020) 10, 13700.
Bavli D, Prill P, Ezra E, Levy G, Cohen M, Vinken M, Vanfleteren J, Jaeger MS, Nahmias Y. Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction. PNAS (2016) 113, S. E2231-E2240.
Prill S, Bavli D, Jaeger MS, Schmälzlin E, Levy G, Schwarz M, Duschl C, Ezra E, Nahmias Y. A Real-Time Monitoring of Oxygen Uptake in Hepatic Microwell Bioreactor Reveals CYP450-Independent Direct Mitochondrial Toxicity of Acetaminophen multilayers. Archives of Toxicology, 90 (2016) 1181-1191. DOI dx.doi.org/10.1007/s00204-015-1537-2
Prokopovic VZ, Vikulina AS, Sustr D, Duschl C, Volodkin D. Towards an artificial extracellular matrix: Biopolymer based multilayers coated with gold nanoparticles. Assessment of biodegradation, molecular transport, and protein mobility. ACS Applied Materials and Interfaces 8 (2016) S. 24345-24349.
Prill S, Jaeger, MS, Duschl C. Long-term microfluidic glucose and lactate monitoring in hepatic cell culture. Biomicrofluidics. (2014) 8, 034102.
Renner A, Jaeger MS, Lankenau A, Duschl C. Position-dependent chemotactic response of slowly migrating cells in sigmoidal concentration profiles. Appl Phys A. (2013), 112(3), 637-645.
Madaboosi N, Uhlig K, Schmidt S, Jaeger MS, Möhwald H, Duschl C, Volodkin D. Microfluidics meets soft layer-by-layer films: selective cell growth in 3D polymer architectures. Lab Chip. (2012), 12, S. 1434-1436.
Felten M, Staroske W, Jaeger MS, Schwille P, Duschl C. Accumulation and filtering of nanoparticles in microchannels using electrohydrodynamically induced vortical flows. Electrophoresis. (2008), 29, 2987-2996.
Jaeger MS, Uhlig K, Clausen-Schaumann H, Duschl C. The structure and functionality of contractile forisome protein aggregates. Biomaterials. (2008), 29, 247–256.
Uhlig K, Jaeger MS, Lisdat F, Duschl C. A biohybrid microfluidic valve based on forisome protein complexes. J MEMS. (2008), 17(6), 1322-1328
Felten M, Geggier P, Jaeger M, Duschl C. Controlling electrohydrodynamic pumping in microchannels through defined temperature fields. Phys Fluids. (2006), 18, 051707.
Gast FU, Dittrich PS, Schwille P, Weigel M, Mertig M, Opitz J, Queitsch U, Diez S, Lincoln B, Wottawah F, Schinkinger S, Guck J, Käs J, Smolinski J, Salchert K, Werner C, Duschl C, Jäger M, Uhlig K, Geggier P, Howitz S. The microscopy cell (MicCell), a versatile modular flowthrough system for cell biology, biomaterial research, and nanotechnology. Microfluid Nanofluid. (2006), 2, 21–36.

Patents

Jaeger M, Prill S, Nahmias Y, Bavli D. Method and system for continous monitoring of toxicity. EP15160661.3 / US 2015/0268224 A1