Monday, September 2, 2013

New concept of organs on a chip may help study cancer metastasis

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New concept of organs on a chip may help study cancer metastasis -

The recent development of the concept of organs on a chip opens the possibility to study realistically human organs without the use of patients or animal testing. Professor Jaap den Toonder, who gave his inaugural lecture at the University of Technology Eindhoven (TU / e) June 20, goes even further: he intends to microsystems in which several "bodies" are connected by "blood vessels". It will for example allow a precise investigation of how cancer spreads. This could possibly make the development of medical drugs much cheaper and faster. TU / e started a special microfabrication laboratory to develop the necessary technology.

Breast cancer usually spreads to the bone marrow, brain or lungs. But it is difficult to track exactly how this process - it can not be observed directly in the human body. This is exactly the question Jaap den Toonder, Professor of Microsystems, wants to help answer, in collaboration with other Dutch institutes. Den Toonder was involved early on in the development of organs on a chip, in collaboration with other researchers, including Donald Ingber of the Wyss Institute at Harvard.

Metastasis
The TU / e professor working to develop a microsystem in which the organs are represented as an "organ on a chip", connected by a system of "blood vessels". Breast tissue sample contains the primary tumor. Because the microsystem is totally transparent, researchers can see with great precision when and how cancer cells spread, or metastasize, to other organs. For a sense of how it will work, please see this video: https://www.youtube.com/watch?v=DOvDMut0Vx4

individual organs on a chip are tiny pieces of tissue live grown with artificial blood. The goal is to allow the tissue to study, for example to study how the disease develops and how the tissue responds to medication. However the disease and drugs often involve interaction between multiple organs. A typical example is the interaction between different drugs in the liver, through which the substances are produced which can be toxic to other organs. This is the reason to move a body on a micro chip with several organs. A microsystem typically several centimeters and contains a network of channels and microchambers with sizes varying from 1 to 100 micrometers.

No animal testing
systems of this type can help to get a great reduction in the cost of the development of medical drugs. The test is now often done on human cells in petri dishes, but these do not provide a realistic natural environment. In addition, animal tests are carried out, but they often react differently humans. In addition, in animals, it is impossible to observe in real time exactly what is happening. And the fact that a drug does not work as expected is often not discovered until it was actually tested on humans, in which a lot of expensive work may already have been done. Using a micro with organs on a chip, researchers will be in the near future be able to carry out tests more quickly and realistically, without the need to use animals or humans. Den Toonder believes that the first applications will be ready for use within four to eight years.

Microsystems must provide an environment is present in the human body to ensure the validity of test results, Den Toonder explains. The environment of the cell must produce such bioactive signals right, so that the cells display true (pathogenesis) physiological behavior. In addition, the deformation and the rigidity of the environment are very important. "There is strong evidence that increasing the rigidity of the environment can make cancer cells trigger invasiveness, which is the first phase of metastases."

Not expensive cleanroom
To make microsystems, Den Toonder uses a technique derived from the production of semiconductor chip: lithography. He refers to this as "everyday lithography", because the smaller dimensions are much larger than those in the production of microchips. "Our smaller dimensions are 1 to 10 micrometers. At this scale, you do not need an expensive clean room, and there is no need to use smaller dimensions than that. The smaller scale in which we work is that of red blood cells and micro blood vessels size and these are of the order of a few micrometers. "in addition, the fluid flow in these narrow vessels is laminar by definition, so that it can be easily controlled.

TU / e will be in the near future to build a "laboratory MICROFAB" specially for the development of microsystems and research with these systems. The 700 square meter laboratory will be the best equipped center of its kind in the Netherlands, and represents an investment of over one million euros.


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