Teaching a chip to see

  

All of which can lead to the failure of drug trials and adds to the growing expense of new drug development.

As a result, the pharmaceutical industry is looking at techniques that will improve the drug development process and one of these involves organ-on-a-chip (OoC) technology, that has the potential to revolutionise drug development.

Imec in Belgium unveiled an organ-on-chip platform last year that combined a high-density multi-electrode array chip and a microfluidic well plate to provide an environment where cells can be cultured that are similar to the human physiology.

Now researchers at the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB have succeeded in putting various types of tissue onto chips.

The team have recreated the human retina in the form of a retinal organoid and they also have hopes that organ-on-a-chip technology will open up the field of gender-specific medicine.

The development of organ-on-a-chip technology marks a huge advance for medical research and offers a real alternative to animal experimentation.

An OoC comprises of polymer chambers in which small amounts of tissue cultures and organoids are fed with nutrients via a system of microchannels. Researchers use these live cultures to test active ingredients, investigate the etiology of diseases and research new drug therapies.

OoC systems have been developed for a broad range of tissue types, such as cardiac muscle, liver, kidney and even brain tissue.

Prof. Peter Loskill at the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB in Stuttgart has been spearheading this research and his team has pioneered a number of unique developments, including the recreation of white adipose tissue and human retinal tissue on a chip. Now that scientists have mastered the technique of placing a whole variety of tissue cultures on a chip, the next challenge is to accelerate throughput of the various substances being tested.

So-called organ-on-a-disk systems will combine hundreds of human tissue samples in one format, helping to turn this technology into a routine procedure.

The latest breakthrough to emerge from Loskill’s lab is a retina-on-a-chip system, featuring the complex stratified tissue of the human retina as an organoid.

Working with partners from the University of Tübingen, they have been able to differentiate stem cells and incorporate them in a chip in such a way that they recreate a multilayer tissue. This tissue comprises, among other things, light-sensitive rods and cones, retinal pigment epithelium and ganglion cells, which make up the optic nerve.

“When we shine light on the retina-on-a-chip, we register an electrophysical signal in the rods and cones,” Loskill explains. “And now we’re working on a system with which we can quantitatively measure these signals.”

Such a system will make it possible to measure the extent to which a substance influences the “visual capacity” of the retina-on-a-chip.

“The pharmaceutical industry is showing a big interest in retina-on-a-chip technology,” said Loskill. “Lots of modern drugs have retinopathic side effects.” According Loskill model systems are still rare in this field, apart from animal models, which are only of limited use, since the retina of the animals used tends to have a different structure to that of the human retina.

In addition, retina-on-a-chip technology will also facilitate research into diseases of the retina and the development of drugs to treat conditions such as age-related macular degeneration and diabetic retinopathy.

Loskill also expects organ-on-a-chip technology to open up a further field of research – that of sex-specific medicine.

“Many diseases manifest themselves in different ways in male and female patients,” he explains. “It’s an aspect that has not yet received enough attention in medical research and drug development.”

In the future, organ-on-a-chip systems will enable researchers to investigate male or female tissue separately. For example, a female organ-on-a-chip system could be used to simulate the menstrual cycle and observe whether it has an impact on a specific disease and potential drug therapies.