Researchers from the University of Oxford’s Department of Chemistry have made a significant step towards developing miniature powered bio-integrated devices that can interact with and stimulate cells, published today, Aug. 30, in an open-access paper in the journal Nature.

The researchers have developed a miniature power source capable of altering the activity of cultured human nerve cells. Inspired by how electric eels generate electricity, the device uses internal ion gradients to generate energy, rather than electrons.

Important therapeutic applications include delivering targeted drug therapies and speeding up wound healing.

How the technology works

The miniaturized soft-power source is produced by depositing a chain of five nanoliter-sized droplets of a conductive hydrogel (a 3D network of polymer chains containing a large quantity of absorbed water.

Each droplet has a different composition so that a salt concentration gradient is created across the chain. The droplets are separated from their neighbors by lipid bilayers, which provide mechanical support while preventing ions from flowing between the droplets.

The power source is turned on by cooling the structure to 4°C and changing the surrounding medium: this disrupts the lipid bilayers and causes the droplets to form a continuous hydrogel.

This allows the ions to move through the conductive hydrogel, from the high-salt droplets at the two ends to the low-salt droplet in the middle. By connecting the end droplets to electrodes, the energy released from the ion gradients is transformed into electricity, enabling the hydrogel structure to act as a power source for external components.

In the study, the research team demonstrated how living cells could be attached to one end of the device so that their activity could be directly regulated by the ionic current. The team attached the device to droplets containing human neural progenitor cells that had been stained with a fluorescent dye to indicate their activity. When the power source was turned on, time-lapse recording demonstrated waves of intercellular calcium signaling* in the neurons, induced by the local ionic current.

“The miniaturized soft power source represents a breakthrough in bio-integrated devices, Dr. Yujia Zhang (Department of Chemistry, University of Oxford), the lead researcher for the study, said. By harnessing ion gradients, we have developed a miniature, biocompatible system for regulating cells and tissues on the microscale, which opens up a wide range of potential applications in biology and medicine.”

Next-generation wearable devices, bio-hybrid interfaces, implants, synthetic tissues, and microrobots

According to the researchers, the device’s modular design would allow multiple units to be combined to increase the voltage and/or current generated. This could open the door to powering next-generation wearable devices, bio-hybrid interfaces, implants, synthetic tissues, and microrobots.

By combining 20 five-droplet units in series, they were able to illuminate a light-emitting diode, which requires about 2 Volts. They envisage that automating the production of the devices by using a droplet printer, for instance, could produce droplet networks composed of thousands of power units.

“This work addresses the important question of how stimulation produced by soft, biocompatible devices can be coupled with living cells. The potential impact on devices, including bio-hybrid interfaces, implants, and microrobots is substantial,” said Professor Hagan Bayley, University of Oxford.

* Calcium signaling is a key mechanism through which neurons communicate to one another to coordinate biological activities such as neurotransmitter release, neuronal firing, synaptic plasticity, and gene transcription.

Citation: Zhang, Y., Riexinger, J., Yang, X., Mikhailova, E., Jin, Y., Zhou, L., & Bayley, H. (2023). A microscale soft ionic power source modulates neuronal network activity. Nature, 620(7976), 1001-1006. https://doi.org/10.1038/s41586-023-06295-y

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