Smart organ-on-a-chip platform for drug testing


Recently, Micronit Microtechnologies and Imec, the international research and innovation hub in nanoelectronics, collaborated on the development of a smart organ-on-a-chip platform for pharmacological research. Organ-on-a-chip devices simulate the physiological and chemical response of (human) organs and are therefore of increasing importance in, for example, drug development.

Partnership

With this collaboration the prime competences of both parties were combined: Imecs specialism in digital technologies and Micronit’s expertise in the field of microfluidics. Micronit developed the polymer microfluidic well plate with integrated micropneumatic pumps and the interposer. Part of the bonding of this high-density multi-electrode array chip was also carried out by Micronit. Imec was responsible for the PCB with the assembled CMOS to complete the transformation into a smart lab-on-a-chip device.

Outstanding signal quality

In this smart organ-on-a-chip platform cell material is grown in the 16 cavities in the well plate. Because the surface of the well plate is patterned with nanogrooves, the development of the cells evolves in a more natural way and the grown tissue will behave more like that of the actual organ. The chip handles signal processing and analog-to-digital conversion. It holds 1.024 electrodes for each of the 16 microfluidic wells (a total of 16.384 electrodes). This allows single cell resolution at an unprecedented signal quality. Each of the 16 wells can be individually assessed, so multiple tests can be performed in parallel.

Miniature hearts-on-chip

For instance, heart cells were grown on the well plate. Because of the nanogrooved surface, the heart cells grew into more heart-like tissue, thus creating miniature hearts-on-a-chip. This way, it is possible to test the effect of drugs in a more biologically relevant context. Veerle Reumers, project leader at Imec explains: ‘This organ-on-a-chip platform is the first system that enables on-chip multi-well assays, which means that you can perform different experiments or – in other words – analyse different compounds, in parallel on a single chip. This is a considerable increase in throughput compared to current single-well MEAs.’ The further aim is to increase the throughput by adding more wells in a system.
 

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Drug development

This smart organ-on-a-chip platform promises to become essential in the field of drug development. Large sums of money are involved here, and the risk of a new drug not making it to the market is extremely high. A great amount of time and money is spent on pre-clinical and clinical testing. Tests on animals and humans are not only ethically questionable, but also lengthy and expensive. Organ-on-a-chip devices could vastly improve the testing process by producing high quality data in a fast and non-controversial way. ‘Altogether the platform is a big step closer to mimic a real heart without using animals’, says Reumers. ‘It becomes clear that our device heralds a new generation of drug screening tools for the pharmaceutical industry.’

Promising specifications

This smart multi-electrode array-chip offers the opportunity for multiparametric analysis. It provides improvements in usability and scalability and a significant increase in intracellular resolution and throughput. For this device a package size was chosen that is standard in pharmaceutical research, in order to be compatible with existing automated pipetting systems.

For now, tests were performed with heart cells, but will be followed by other organ cells, like that of the liver and the brain.

Imec and Micronit Microtechnologies developed this chip in the InForMed project, funded by the ECSEL Joint-undertaking (ECSEL2014-2-662155).