Organs-on-a-chip:
laboratory models of living tissues

Petri dish cell culture has long been a fundamental tool in biology, and the convenience of this method doesn’t negate its limitations. The conditions in a dish are far removed from those found inside living tissue: there’s no constant flow of nutrient medium, no pressure changes or mechanical stretching, and no signaling between the different cell types working side by side in the body.

An organ-on-a-chip solves precisely this problem. It’s a compact laboratory system with microchannels, chambers, and living cells that reproduces specific properties of a specific tissue — barrier function, fluid movement, muscle cell contraction, or response to a chemical compound. The chip is often comparable in size to a glass slide, and inside, fluid moves through channels tens or hundreds of micrometers wide.

The flow supplies the cells with oxygen and nutrients and removes waste products. By controlling this flow, the researcher can precisely adjust experimental conditions: increase the flow rate of the medium, set the membrane stretching rhythm, and change the temperature or composition of the solution. Working with such systems requires precise technique — from cell preparation and sterile chip assembly to environmental control and recording of results.

The medical and laboratory equipment in such a lab completes this entire cycle: incubators maintain temperature, pumps set the flow, microscopes provide images of the cell layer, and pressure sensors and dispensers ensure that conditions inside the chip remain stable throughout the experiment.

The chip isn’t designed to completely replicate the body, and in this sense, its capabilities are best understood without exaggeration. It addresses a more specific question: how substances pass through cellular barriers or how cardiac tissue reacts to changes in the composition of a solution. It’s precisely this specificity that makes the results reproducible.

How a microfluidic chip works

The base is a plate made of transparent, biocompatible material, in which channels, chambers, and openings for connecting tubes are formed. The transparent walls are not merely decorative — they allow cells to be observed under a microscope without disassembling the device, thus eliminating the risk of losing a sample mid-run.

Some models are more complex: two chambers are separated by a thin porous membrane, with cells of one type growing on one side and another on the other. This setup is suitable for studying tissue boundaries because the membrane allows water and small molecules to pass through, but keeps each cell confined to its own zone.

A micropump generates the fluid flow, and its mode is tailored to the task. For the vascular model, a smooth flow of the medium, similar to the movement of blood in a small vessel, is essential, while for some other tissues, a pulsating flow is suitable. The channels also require clean assembly: even a small air bubble can block the fluid flow or damage the cell layer. Therefore, before starting the system, it is flushed with the medium, the connections are checked, and the air is removed from the tubes.

This procedure takes time. But it reduces the risk of sample loss so significantly that laboratories view it as a mandatory step rather than a formality. Temperature, pH, and oxygen sensors transmit readings to the software directly during the experiment, and the lab technician can monitor parameter changes as the experiment progresses, comparing them with cell images on the screen.

Lung and heart models

A lung model is often built around a flexible membrane: on one side, cells with properties similar to those of respiratory tract cells are placed, while on the other, conditions resembling the wall of a capillary are created. Fluid and gas mixtures are introduced through adjacent channels, and the side chambers periodically change pressure, causing the membrane to slightly stretch and relax.

The cells experience mechanical stress, which is difficult to create in a static culture, and this rhythm helps observe the state of the cell layer under given conditions. The "lung-on-a-chip" doesn’t breathe like an entire organ — it provides a controlled experimental environment in which it’s easier to isolate the effects of one substance from the influence of other factors.

Cardiomyocytes — cells capable of contracting spontaneously — are used in the cardiac model. They are placed on a surface with microelectrodes or optical markers, and each contraction changes the electrical signal, the movement of the cell layer, or the brightness of the calcium indicator.

The contraction rhythm itself is important. If cells begin to beat slower, faster, or irregularly after adding a substance, the device immediately detects this change. Such data does not replace clinical trials, but it helps early on in selecting compounds for further testing. For this purpose, a cardiac chip is often designed with several parallel chambers, one containing a control solution, while the others contain solutions with different concentrations of the substance being studied at the same temperature and flow rate.

Related tissue systems

A single model works well when the question concerns a single tissue, but some experiments require a different scale — tracing the path of a substance after contact with several cellular barriers in a row. To do this, several chips are connected by thin tubes into a common system, and the fluid passes through the chambers in a predetermined order.

The order of the chambers is selected for a specific task, with reservoirs, valves, and sampling points placed between the modules. The more modules in the chain, the higher the requirements for experimental stability, as liver cells and heart cells may have different environmental, temperature, and flow rate requirements — and the regime must be adjusted to ensure all samples remain viable for the required period.

The "human-on-a-chip" system is a provisional term and shouldn’t be interpreted literally. It doesn’t create a miniature replica of a human being; rather, it’s a connected cellular model that can monitor the transfer of substances between multiple chambers. Some setups also allow for the automatic collection of small samples: analysis reveals how much of the substance remains in the environment, whether its degradation products have appeared, and how the proteins secreted by the cells have changed. The sample volume is often so small that measurement methods must work with microliters of liquid.

Where are such platforms used?

Pharmaceutical laboratories use chips in the initial evaluation of drug candidates: the compound is first tested in a cell model under specified conditions, and then the results are compared with data from other methods, because one system does not provide a complete answer to the drug’s effect.

Cosmetic and chemical compounds are studied in a similar manner, but using skin barrier models. Skin cells are placed on a membrane, their growth is supported, the test compound is applied to the test surface, and then the integrity of the cell layer, the composition of the environment, and markers of the inflammatory response are assessed.

Personalized models are constructed from a specific person’s cells, provided the material was obtained legally and with informed consent: the cells are first grown and then placed on a chip. This approach helps study cell responses to known metabolic conditions or hereditary variants that are otherwise difficult to reproduce in the laboratory.

There’s also a practical aspect to laboratory routine. Chips consume few reagents and samples, and each experiment takes up a small amount of space in the incubator. However, preparation requires skill: the channels need to be filled without bubbles, the cells need to be evenly distributed, and the flow needs to be maintained within specified limits.

Results are obtained in a variety of ways: microscopy reveals cell shape and layer density, biochemical analysis evaluates substances in the medium, and electrodes report the conductivity and activity of the cell layer. When these measurements are consistent, the experimental picture becomes clearer and the conclusion more substantiated.

Standards for such systems are still being developed, and laboratories still detail the chip material, cell type, medium composition, experiment duration, and flow parameters. Without this information, it’s difficult to replicate the experiment elsewhere, so an observation log is just as important in such work as a pump or a microscope.