Chip platform · Mosig Lab

Technology

The organ-on-chip platform

Organ-on-chip technology reconstructs the structure and function of human tissue on a miniaturised microfluidic biochip. Human cells are arranged in tissue-like configurations within defined culture chambers and held under continuous perfusion, so that the models reproduce processes that static culture cannot. Unlike conventional two-dimensional cell culture and animal models, these systems combine perfusion, tissue interfaces, an immune component and a resident microbiota in one human and controllable context. This makes them suited to the study of infection and inflammation in human tissue and supports the replacement, reduction and refinement of animal experiments in the spirit of the 3Rs.

Cross-section of an immunocompetent intestine-on-chip model, showing the perfused epithelial and vascular compartments with resident and circulating immune cells, alongside the biochip and the physical and molecular readouts used to follow the tissue.

Biochip

The microfluidic biochip

At the centre of the platform is a microengineered biochip with defined channel geometries, biocompatible membranes and dedicated culture chambers. The membranes act as scaffolds that separate and connect adjacent tissue compartments, for example an epithelial and a vascular side. Human cells are seeded into the chambers and organised into layered tissues that are perfused through the channel system.

The biochips used in our group were developed in Jena and are produced in two-channel and three-channel formats. Each chip measures around 74 by 24 millimetres at a height of 1.5 millimetres, with a tissue chamber addressed through separate perfusion and sampling ports. The small footprint keeps cell numbers and reagent volumes low and gives direct optical access to the tissue.

Footprint74 × 24 × 1.5 mm

Formatstwo- and three-channel

Portsperfusion and sampling

Biochip held between two fingers — The assembled biochip held between two fingers, roughly the size of a microscope slide, with the transparent culture channels and ports visible.

Perfusion

Perfusion and biomechanical stimulation

Continuous perfusion through microfluidic pumps supplies the tissue with nutrients and removes metabolites, and at the same time applies defined mechanical forces. Pulsatile and laminar flow patterns reproduce conditions found in the healthy body. The resulting shear forces act on the cell surface, most notably on the cells of the vasculature, where they influence receptor presentation and shape cellular behaviour such as growth, signalling and metabolism.

Human tissue is also in constant motion, from the blood vessels and muscle to the lung and the intestine. On chip, this motion is reproduced by applying strain and stretch to the cells, either through flow or through controlled deformation of biochip components. Cells sense these forces through the mechanosensory complex, which feeds into a range of signalling pathways that remain inactive in standard static culture.

Watch the flow animation →

Perfusion setup with tubing and medium reservoirs — A biochip under perfusion, with medium reservoirs and tubing connected to the ports over the culture dish.

Pipetting medium into a biochip — Medium being introduced into a biochip through one of its ports.

Defined and reproducible operation

The tissue is assembled and maintained through a small number of addressable ports, so that seeding, medium exchange and sampling follow a defined protocol. Dynamic culture of this kind preserves tissue architecture and function over extended periods, in our liver models for up to two weeks.

Composition

Composition of the tissue models

The composition of a model can be adjusted to the question under study, from a single cell type to a multicellular arrangement with an immune component and a microbiota.

Adjustable complexity

A model can be built from one cell type or extended to several, so that the contribution of an individual population is examined by adding or omitting it. This graded complexity keeps the experimental design defined while tissue interfaces are assembled step by step.

Molecular gradients

Spatial patterns of soluble molecules guide many tissue responses. The perfused chip allows such gradients to be established and controlled through the flow pattern, the layering of cells and the geometry of the chamber, which is particularly relevant in vascular tissue.

Microbiota and pathogens

More complex models incorporate a microbiota or defined pathogens, so that infection and disease processes are reconstructed in a human context that approaches the situation in the living tissue. This is central to our work on enteric and respiratory infection.

Immune component

By including resident and circulating immune cells, the models reproduce part of the cellular complexity of the human immune system and make it possible to follow the immune response within the tissue rather than in isolation.

Analysis

Readouts and analysis

Because the tissue remains accessible, the models are followed by several complementary readouts. Live and high-resolution microscopy resolves cells and pathogens directly in the chamber, and the transparent biochip gives the optical access this requires.

Integrated sensors report oxygen tension, glucose and barrier integrity over the course of an experiment, while the sampling ports give access to secreted metabolites and chemokines for downstream transcriptomic and metabolomic analysis. Together these readouts resolve how a tissue responds to infection and inflammation in space and over time.

Biochip under a microscope during live imaging — A biochip mounted for live microscopy, with the perfused tissue channels under observation.

Tissue models based on organ-on-chip platform technology

On this platform we develop immunocompetent gut, lung and liver models for infection and inflammation research. The biochip technology developed in the group is carried into industrial drug and safety testing by Dynamic42, the organ-on-chip spin-off founded in Jena in 2018.

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