18 May saw the launch of the hDMT (Institute for human Organ and Disease Model technologies), which aims to fast-track research into organ and disease model on chips. TU Delft, one of the founders of hDMT, has already succeeded in making a flexible chip on which living, beating heart cells can be placed. Organ-on-a-chip technology is helping to build up knowledge of the way organs work and to speed up drug research, for example.
Organ and disease models on chips are micro-devices fitted with mechanical, electrical and optical sensors and actuators, with micro-grooves for growing organ tissue in micro-physiological conditions. The chips mimic the functions, dynamics and structure of human organs.
The most striking example of this type of research at TU Delft is Cytostretch, which focuses on heart cells. Research in the Else Kooi Lab (formerly the Dimes Technology Centre) has already enabled living heart cells to be placed on a flexible chip. Micro-grooves in the membrane allow the cells to arrange themselves to form a piece of tissue that, if provided with nutrients, can grow, live and beat. The chips on which the heart cells are placed must be flexible and elastic so that they can accommodate the beats and form a realistic model for real heart cells. This is accomplished using a thin film of membranes and an air pressure pump. ‘It was no mean feat’, says Prof. Ronald Dekker (Philips and TU Delft). ‘We not only had the technological challenge of making flexible chips, but we also had to ensure that the chips could be mass produced’, says Dekker, who has acquired vast industrial experience in manufacturing commercial medical micro-electronics in his work at Philips.
The Cytostretch technique allows researchers to analyse living heart cells and determine the effect of mechanical stress on the electrical activity. This will provide insight into the exact way that heart cells work. In theory, it will also make it possible to test routinely the effect of new drugs on the cells, allowing researchers to identify certain drugs with side-effects before the clinical trial stage. This could save the pharmaceutical industry a lot of time and money. Another huge potential advantage is that it would reduce the need for animal testing. One of the main conditions for developing organ-on-a-chip technology was the progress being made in stem cell research. Breakthroughs include the technique for growing other organs from skin cells, which has been already been put into practice.
The tests on heart cells are promising and are expected to lead to similar tests using other organs. Project leader Prof. Lina Sarro: ‘There is no reason to suppose that the principles we have proved could not be applied to other organs, such as the liver or kidneys. This is just the beginning of the road for this technology. The Cytostretch research project represents an important first step. Although the devices we have developed are geared specifically towards heart cells, it would be reasonable to assume that the basic concept can be modified to suit the functionality and structure of other organs.’
The plans also include imitating cancer on a chip. Prof. Marileen Dogterom from the Bionanoscience Department: ‘We can already imitate and manipulate cellular processes important to cell division on a chip. The insight we gain may soon enable us to influence cell division and movement in 'fake' tumours.’ hDMT
TU Delft is by no means alone in this field. The recently launched, broad-based research initiative hDMT (human Organ and Disease Model technologies) focuses exclusively on this new area. hDMT was founded by nine partners, each with its own area of expertise: TU Delft, the University of Twente, TU Eindhoven, Hubrecht Institute, Leiden University, Leiden University Medical Centre, Erasmus Medical Centre, Galapagos and Genmab. The initiative will initially focus on three lines of research: heart, cancer and blood vessels on chips.