Neurotech Researchers Advance New Implant Materials

by James Cavuoto, editor

February 2024 issue

Future advances in implantable neurotechnology devices will depend heavily on developments in materials science. In particular, soft, thin, flexible materials that conform to neural tissue and conduct electricity are highly desirable for brain implants. Researchers at a number of institutions have recently reported progress with two such materials: EGNITE and PEDOT: PSS.

A study published in Nature Nanotechnology presents an innovative graphene-based neurotechnology with the potential for a transformative impact in neuroscience and medical applications. This research, spearheaded by the Catalan Institute of Nanoscience and Nanotechnology (ICN2) together with the Universitat Autònoma de Barcelona and other national and international partners, is currently being developed for therapeutic applications through the spin-off firm INBRAIN Neuroelectronics.

Following years of research under the European Graphene Flagship project, ICN2 spearheaded in collaboration with the University of Manchester the development of EGNITE (Engineered Graphene for Neural Interfaces), a novel class of flexible, high-resolution, high-precision graphene-based implantable neurotechnology. The results aim to contribute to the blooming landscape of neuroelectronics and brain-computer interfaces.

EGNITE builds on the vast experience of its inventors in fabrication and medical translation of carbon nanomaterials. This technology, based on nanoporous graphene, integrates fabrication processes standard in the semiconductor industry to assemble graphene microelectrodes a mere 25 µm in diameter. The graphene microelectrodes exhibit low impedance and high charge injection, essential attributes for flexible and efficient neural interfaces.

Preclinical studies by various neuroscience and biomedical experts that partnered with ICN2, using different models for both the central and peripheral nervous system, demonstrated the capacity of EGNITE in recording high-fidelity neural signals with exceptional clarity and precision and, more importantly, afford highly targeted nerve modulation. The unique combination of high-fidelity signal recording and precise nerve stimulation offered by EGNITE technology represents a potentially critical advancement in neuroelectronic therapeutics.

This innovative approach addresses a critical gap in neurotechnology, which has seen little advancement in materials over the last two decades. The development of EGNITE electrodes has the capacity to place graphene at the forefront of neurotechnological materials.

The collaboration includes the contribution from leading national and international institutions, such as the Institut de Microelectrònica de Barcelona, the National Graphene Institute in Manchester, in the U.K., the Grenoble Institut des Neurosciences in France and the University of Barcelona in Spain.

The EGNITE technology described in the Nature Nanotechnology article has been patented and licensed to INBRAIN Neuroelectronics. The company, also a partner in the Graphene Flagship project, is leading the translation of the technology into clinical applications and products. Under the direction of CEO Carolina Aguilar, INBRAIN Neuroelectronics is gearing up for the first-in-human clinical trials of this innovative graphene technology.

The Nature Nanotechnology article describes an innovative graphene-based neurotechnology that can be upscaled using established semiconductor fabrication processes, holding the potential for a transformative impact. ICN2 and its partners continue to advance and mature the technology with the aim to translate it into a real efficacious and innovative therapeutic neurotechnology.

While graphene certainly shows promise for neurotechnology, another team from North Carolina State University reported significant advances using a different material. The scientific community has long been enamored of the potential for soft bioelectronic devices, but has faced hurdles in identifying materials that are biocompatible and have all of the necessary characteristics to operate effectively. The NC State team has now taken a step in the right direction, modifying an existing biocompatible material so that it conducts electricity efficiently in wet environments and can send and receive ionic signals from biological media.

“We’re talking about an order-of-magnitude improvement in the ability of soft bioelectronic materials to function efficiently in biological environments,” says Aram Amassian, co-corresponding author of a paper on the work and a professor of materials science and engineering at North Carolina State University. “This is not an incremental advance.”

There is tremendous interest in creating organic bioelectronics and organic electrochemical transistors (OECTs), with a wide range of biomedical applications. However, one limiting factor is identifying nontoxic materials that can conduct electricity, interacting with ions—which is critical to functioning in biological environments, and operating efficiently in the aqueous, water-based environments of biological systems.

One material of interest has been PEDOT:PSS, which is a nontoxic polymer that is able to conduct electricity. PEDOT:PSS is used to create thin films which are effectively fiber networks that are only nanometers wide. Electrical current can run through the fibers, which are also sensitive to ions in their environment.

“The idea is that, because ions interact with the fibers—and affect their conductivity—PEDOT:PSS can be used to sense what is happening around the fibers,” said Laine Taussig, co-first author of the paper and a recent Ph.D. graduate of NC State who now works at the Air Force Research laboratory.

“Essentially, PEDOT:PSS would be able to monitor its biological environment. But we could also use the electric current to influence the ions surrounding the PEDOT:PSS, sending signals to that biological environment,” said Masoud Ghasemi, co-first author and a former postdoctoral fellow at NC State who is now a postdoctoral fellow at Penn State.

However, PEDOT:PSS’s structural stability declines significantly when placed in aqueous environments—like biological systems. That’s because PEDOT:PSS is a single material made from two components: the PEDOT, which conducts electricity and is not soluble in water; and PSS, which responds to ions, but is water soluble. In other words, the PSS makes the material start to fall apart when it comes into contact with water.

Previous efforts to stabilize the structure of PEDOT:PSS have been able to help the material withstand aqueous environments, but have both hurt PEDOT:PSS’s performance as a conductor and made it more difficult for ions to interact with the material’s PSS components.

“Our work here is important, because we’ve found a new way to make a PEDOT:PSS that is structurally stable in wet environments and able to both interact with ions and conduct electricity very efficiently,” said George Malliaras, co-corresponding author and Prince Philip Professor of Technology at Cambridge University.

Specifically, the researchers start with PEDOT:PSS in solution and then add ionic salts. Given time, the ionic salts interact with the PEDOT:PSS, causing it to self-assemble into fibers with a unique structure that remains stable in wet environments. This modified PEDOT:PSS is then dried and the ionic salts rinsed off.

“We already knew that ionic salts could affect PEDOT:PSS,” Amassian said. “What’s new here is that by giving the ionic salts more time to see the full extent of those effects, we modified the crystalline structures of the PEDOT and the PSS to essentially lace themselves together at the molecular scale. This makes the PSS impervious to the water in the environment, allowing the PEDOT:PSS to maintain its structural stability at the molecular level.”

“The change is also hierarchical, meaning that there are shifts at the molecular level all the way up to macroscale,” says Yaroslava Yingling, co-author of the paper and Kobe Steel Distinguished Professor of materials science and engineering at NC State. “The ionic salts cause the PEDOT:PSS to essentially reorganize itself into a phase that resembles a web-like gel that is preserved in both dry and wet environments.”

In addition to being stable in aqueous environments, the resulting films retain their conductivity. What’s more, because the PEDOT and PSS are tightly interwoven, it’s easy for ions to reach and interact with the PSS component of the material.

“This new phase of PEDOT:PSS was used to create OECTs by our collaborators at Cambridge,” Amassian said. “And those OECTs set a new state-of-the-art standard in both volumetric capacitance and electronic carrier mobility. In other words, it’s the new gold standard in both conductivity and ion responsiveness in bio-friendly electronics.

The paper, “Electrostatic Self-Assembly Yields a Structurally-Stabilized PEDOT:PSS With Efficient Mixed Transport and High Performance OECTs,” was published in the journal Matter.