Tag Archives: Mary J. Donahue

Growing electrodes in your brain?

This isn’t for everybody. From a February 23, 2023 news item on Nanowerk, Note: A link has been removed,

The boundaries between biology and technology are becoming blurred. Researchers at Linköping, Lund, and Gothenburg universities in Sweden have successfully grown electrodes in living tissue using the body’s molecules as triggers. The result, published in the journal Science (“Metabolite-induced in vivo fabrication of substrate-free organic bioelectronics”), paves the way for the formation of fully integrated electronic circuits in living organisms.

Caption: The injectable gel being tested on a microfabricated circuit. Credit: Thor Balkhed

I have two news releases for this research. First, the February 23, 2023 American Association for the Advancement of Science (AAAS) news release on EurekAlert,

Researchers have developed a way to make bioelectronics directly inside living tissues, an approach they tested by making electrodes in the brain, heart, and fin tissue of living zebrafish, as well as in isolated mammalian muscle tissues. According to the authors, the new method paves the way for in vivo fabrication of fully integrated electronic circuits within the nervous system and other living tissue. “Safety and stability analyses over long periods will be essential to determining whether such technology is useful for chronic implantations,” writes Sahika Inal in a related Perspective. “However, the strategy … suggests that any living tissue can turn into electronic matter and brings the field closer to generating seamless biotic-abiotic interfaces with a potentially long lifetime and minimum harm to tissues.” Implantable electronic devices that can interface with soft biological neural tissues offer a valuable approach to studying the complex electrical signaling of the nervous system and enable the therapeutic modulation of neural circuitry to prevent or treat various diseases and disorders. However, conventional bioelectronic implants often require the use of rigid electronic substrates that are incompatible with delicate living tissues and can provoke injury and inflammation that can affect a device’s electrical properties and long-term performance. Overcoming the incompatibility between static, solid-state electronic materials and dynamic, soft biological tissues has proven challenging. Here, Xenofon Strakosas and colleagues present a method to fabricate polymer-based, substrate-free electronic conducting materials directly inside a tissue. Strakosas et al. developed a complex molecular precursor cocktail that, when injected into a tissue, uses endogenous metabolites (glucose and lactate) to induce polymerization of organic precursors to form conducting polymer gels. To demonstrate the approach, the authors “grew” gel electrodes in the brain, heart, and fin tissue of living zebrafish, with no signs of tissue damage, and in isolated mammalian muscle tissues, including beef, pork and chicken. In medicinal leeches, they showed how the conducting gel could interface nervous tissue with electrodes on a tiny flexible probe.

The second is the February 23, 2023 Linköping University press release on EurekAlert, which originated the news item, and it provides further insight,

“For several decades, we have tried to create electronics that mimic biology. Now we let biology create the electronics for us,” says Professor Magnus Berggren at the Laboratory for Organic Electronics, LOE, at Linköping University.

Linking electronics to biological tissue is important to understand complex biological functions, combat diseases in the brain, and develop future interfaces between man and machine. However, conventional bioelectronics, developed in parallel with the semiconductor industry, have a fixed and static design that is difficult, if not impossible, to combine with living biological signal systems.

To bridge this gap between biology and technology, researchers have developed a method for creating soft, substrate-free, electronically conductive materials in living tissue. By injecting a gel containing enzymes as the “assembly molecules”, the researchers were able to grow electrodes in the tissue of zebrafish and medicinal leeches.

“Contact with the body’s substances changes the structure of the gel and makes it electrically conductive, which it isn’t before injection. Depending on the tissue, we can also adjust the composition of the gel to get the electrical process going,” says Xenofon Strakosas, researcher at LOE and Lund University and one of the study’s main authors.

The body’s endogenous molecules are enough to trigger the formation of electrodes. There is no need for genetic modification or external signals, such as light or electrical energy, which has been necessary in previous experiments. The Swedish researchers are the first in the world to succeed in this.

Their study paves the way for a new paradigm in bioelectronics. Where it previously took implanted physical objects to start electronic processes in the body, injection of a viscous gel will be enough in the future.

In their study, the researchers further show that the method can target the electronically conducting material to specific biological substructures and thereby create suitable interfaces for nerve stimulation. In the long term, the fabrication of fully integrated electronic circuits in living organisms may be possible.

In experiments conducted at Lund University, the team successfully achieved electrode formation in the brain, heart, and tail fins of zebrafish and around the nervous tissue of medicinal leeches. The animals were not harmed by the injected gel and were otherwise not affected by the electrode formation. One of the many challenges in these trials was to take the animals’ immune system into account.

“By making smart changes to the chemistry, we were able to develop electrodes that were accepted by the brain tissue and immune system. The zebrafish is an excellent model for the study of organic electrodes in brains,” says Professor Roger Olsson at the Medical Faculty at Lund University, who also has a chemistry laboratory at the University of Gothenburg.

It was Professor Roger Olsson who took the initiative for the study, after he read about the electronic rose developed by researchers at Linköping University in 2015. One research problem, and an important difference between plants and animals, was the difference in cell structure. Whereas plants have rigid cell walls which allow for the formation of electrodes, animal cells are more like a soft mass. Creating a gel with enough structure and the right combination of substances to form electrodes in such surroundings was a challenge that took many years to solve.

“Our results open up for completely new ways of thinking about biology and electronics. We still have a range of problems to solve, but this study is a good starting point for future research,” says Hanne Biesmans, PhD student at LOE and one of the main authors.

Here’s a link to and a citation for the paper,

Metabolite-induced in vivo fabrication of substrate-free organic bioelectronics by Xenofon Strakosas, Hanne Biesmans, Tobias Abrahamsson, Karin Hellman, Malin Silverå Ejneby, Mary J. Donahue, Peter Ekström, Fredrik Ek, Marios Savvakis, Martin Hjort, David Bliman, Mathieu Linares, Caroline Lindholm, Eleni Stavrinidou, Jennifer Y. Gerasimov, Daniel T. Simon, Roger Olsson, and Magnus Berggren. Science 23 Feb 2023 Vol 379, Issue 6634 pp. 795-802 DOI: 10.1126/science.adc9998

This paper is behind a paywall.

Artificial organic neuron mimics characteristics of biological nerve cells

There’s a possibility that in the future, artificial neurons could be used for medical treatment according to a January 12, 2023 news item on phys.org,

Researchers at Linköping University (LiU), Sweden, have created an artificial organic neuron that closely mimics the characteristics of biological nerve cells. This artificial neuron can stimulate natural nerves, making it a promising technology for various medical treatments in the future.

Work to develop increasingly functional artificial nerve cells continues at the Laboratory for Organic Electronics, LOE. In 2022, a team of scientists led by associate professor Simone Fabiano demonstrated how an artificial organic neuron could be integrated into a living carnivorous plant [emphasis mine] to control the opening and closing of its maw. This synthetic nerve cell met two of the 20 characteristics that differentiate it from a biological nerve cell.

I wasn’t expecting a carnivorous plant, living or otherwise. Sadly, they don’t seem to have been able to include it in this image although the ‘green mitts’ are evocative,

Caption: Artificial neurons created by the researchers at Linköping University. Credit: Thor Balkhed

A January 13, 2023 Linköping University (LiU) press release by Mikael Sönne (also on EurkeAlert but published January 12, 2023), which originated the news item, delves further into the work,

In their latest study, published in the journal Nature Materials, the same researchers at LiU have developed a new artificial nerve cell called “conductance-based organic electrochemical neuron” or c-OECN, which closely mimics 15 out of the 20 neural features that characterise biological nerve cells, making its functioning much more similar to natural nerve cells.

“One of the key challenges in creating artificial neurons that effectively mimic real biological neurons is the ability to incorporate ion modulation. Traditional artificial neurons made of silicon can emulate many neural features but cannot communicate through ions. In contrast, c-OECNs use ions to demonstrate several key features of real biological neurons”, says Simone Fabiano, principal investigator of the Organic Nanoelectronics group at LOE.

In 2018, this research group at Linköping University was one of the first to develop organic electrochemical transistors based on n-type conducting polymers, which are materials that can conduct negative charges. This made it possible to build printable complementary organic electrochemical circuits. Since then, the group has been working to optimise these transistors so that they can be printed in a printing press on a thin plastic foil. As a result, it is now possible to print thousands of transistors on a flexible substrate and use them to develop artificial nerve cells.

In the newly developed artificial neuron, ions are used to control the flow of electronic current through an n-type conducting polymer, leading to spikes in the device’s voltage. This process is similar to that which occurs in biological nerve cells. The unique material in the artificial nerve cell also allows the current to be increased and decreased in an almost perfect bell-shaped curve that resembles the activation and inactivation of sodium ion channels found in biology.

“Several other polymers show this behaviour, but only rigid polymers are resilient to disorder, enabling stable device operation”, says Simone Fabiano

In experiments carried out in collaboration with Karolinska Institute (KI), the new c-OECN neurons were connected to the vagus nerve of mice. The results show that the artificial neuron could stimulate the mice’s nerves, causing a 4.5% change in their heart rate.

The fact that the artificial neuron can stimulate the vagus nerve itself could, in the long run, pave the way for essential applications in various forms of medical treatment. In general, organic semiconductors have the advantage of being biocompatible, soft, and malleable, while the vagus nerve plays a key role, for example, in the body’s immune system and metabolism.

The next step for the researchers will be to reduce the energy consumption of the artificial neurons, which is still much higher than that of human nerve cells. Much work remains to be done to replicate nature artificially.

“There is much we still don’t fully understand about the human brain and nerve cells. In fact, we don’t know how the nerve cell makes use of many of these 15 demonstrated features. Mimicking the nerve cells can enable us to understand the brain better and build circuits capable of performing intelligent tasks. We’ve got a long road ahead, but this study is a good start,” says Padinhare Cholakkal Harikesh, postdoc and main author of the scientific paper.

Here’s a link to and a citation for the paper,

Ion-tunable antiambipolarity in mixed ion–electron conducting polymers enables biorealistic organic electrochemical neurons by Padinhare Cholakkal Harikesh, Chi-Yuan Yang, Han-Yan Wu, Silan Zhang, Mary J. Donahue, April S. Caravaca, Jun-Da Huang, Peder S. Olofsson, Magnus Berggren, Deyu Tu & Simone Fabiano. Nature Materials volume 22, pages 242–248 (2023) DOI: https://doi.org/10.1038/s41563-022-01450-8 Published online: 12 January 2023 Issue Date: February 2023

This paper is open access.