Recording thousands of nerve cell impulses at high resolution

For over 15 years, ETH Professor Andreas Hierlemann and his group have been developing microelectrode-​array chips that can be used to precisely excite nerve cells in cell cultures and to measure electrical cell activity. These developments make it possible to grow nerve cells in cell-​culture dishes and use chips located at the bottom of the dish to examine each individual cell in connected nerve tissue in detail. Alternative methods for conducting such measurements have some clear limitations. They are either very time-​consuming – because contact to each cell has to be individually established – or they require the use of fluorescent dyes, which influence the behaviour of the cells and hence the outcome of the experiments.

Close-​up of the new dual-​mode chip. The measurement area in the centre of the image (green) is 2 x 4 millimetres. Image credit: ETH Zurich / Xinyue Yuan

Now, researchers from Hierlemann’s group at the Department of Biosystems Science and Engineering of ETH Zurich in Basel, together with Urs Frey and his colleagues from the ETH spin-​off MaxWell Biosystems, developed a new generation of microelectrode-​array chips. These chips enable detailed recordings of considerably more electrodes than previous systems, which opens up new applications.

Stronger signal required

As with previous chip generations, the new chips have around 20,000 microelectrodes in an area measuring 2 by 4 millimetres. To ensure that these electrodes pick up the relatively weak nerve impulses, the signals need to be amplified. Examples of weak signals that the scientists want to detect include those of nerve cells, derived from human pluripotent stem cells (iPS cells). These are currently used in many cell-​culture disease models. Another reason to significantly amplify the signals is if the researchers want to track nerve impulses in axons (fine, very thin fibrous extensions of a nerve cell).

However, high-​performance amplification electronics take up space, which is why the previous chip was able to simultaneously amplify and read out signals from only 1,000 of the 20,000 electrodes. Although the 1,000 electrodes could be arbitrarily selected, they had to be determined prior to every measurement. This meant that it was possible to make detailed recordings over only a fraction of the chip area during a measurement.

Measuring chip at the base of a cell-​culture dish. Image credit: ETH Zurich / Xinyue Yuan

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