New tool allows researchers to reproduce conditions of embryonic development in lab

Microfluidic gradient generating device with four independently addressed source/sinks. Three coloured dyes were used to demonstrate gradient profiles generated within the microdevice. The octagonal chamber in view spans 1.5mm at its widest point.

An interdisciplinary team of developmental biologists and engineers at the Francis Crick Institute and the University of Maine have developed a new microfluidic tool that allows them to reproduce – in the laboratory – the same environments that cells are exposed to during the earliest stages of embryonic brain and spinal cord development.

The tool, designed and fabricated by the MicroInstruments and Systems Laboratory at the University of Maine, is based on a technology called microfluidics. It has many potential applictions for embryonic development studies, as well as applications in diagnostics and theraputics development for embryonic and neuromusculature diseases.

Using the same equipment and techniques that are used to make integrated circuits and computer chips, the microfluidic device contains tiny chambers with interconnected channels that introduce growth media and signaling cues in a controlled and precise manner. The arrangement is intentionally reminiscent of the organisation found within developing embryonic tissue.

Dr Christopher Demers, an engineer who developed the technology at the University of Maine, now a postdoctoral research fellow in Dr James Briscoe’s group at the Crick, said: “If you want to recapitulate an organ or process in vitro, you have to recreate the same environment that produced the original organ or tissue. Cells in an embryo are exposed to differing quantities of external signals, which are usually produced in defined regions of the embryo and dispersed from their origin to form gradients. The amount and the timing of exposure to these signals controls how the cells will develop.”

It is well known that the spinal cord is carefully organised topographically for speed and efficiency. How, precisely, the spinal cord obtains this organisation is poorly understood. With this new tool,the team is able to artificially establish gradients of signals in a chamber containing living cells in order to re-create the precise spatial organisation of the spinal cord. Using this approach, the researchers were able to re-create a spatially discreet domain of motor neurons, similar to that found in the developing spinal cord.

Differentiated motor neurons (green) after seven days in culture in a microfluidic gradient generator. The fluorescent dye Rhodamine (red) is used to visualize the morphogen that led to the radial differentiation of motor neurons. 

Dr Scott Collins, co-director of the MicroInstruments and Systems Laboratory at the University of Maine, said: “By utilising expertise from microelectronics and engineering we are able to provide novel technologies to help grow the field of tissue engineering and stem cell developmental biology. These tools will help us understand how tissues develop and how cells make differentiation decisions in embryos.”

“It will also help us develop new in vitro models,” added Dr Demers. “For example it might be possible to use these types of devices to recreate diseased or damaged tissue outside of an embryo to study what goes wrong or to test potential therapies. This will be particularly important in cases where a disease is poorly understood or where interactions between different cells in a tissue are implicated in the cause of a disease.”

The paper, Development-on-chip: In vitro neural tube patterning with a microfluidic device, is published in Development.