Tag Archives: Stéphanie P. Lacour

Imprinting fibres at the nanometric scale

Switzerland’s École Polytechnique Fédérale de Lausanne (EPFL) announces a discovery in a Jan. 24, 2017 press release (also on EurkeAlert),

Researchers at EPFL have come up with a way of imprinting nanometric patterns on the inside and outside of polymer fibers. These fibers could prove useful in guiding nerve regeneration and producing optical effects, for example, as well as in eventually creating artificial tissue and smart bandages.

Researchers at EPFL’s Laboratory of Photonic Materials and Fibre Devices, which is run by Fabien Sorin, have come up with a simple and innovative technique for drawing or imprinting complex, nanometric patterns on hollow polymer fibers. Their work has been published in Advanced Functional Materials.

The potential applications of this breakthrough are numerous. The imprinted designs could be used to impart certain optical effects on a fiber or make it water-resistant. They could also guide stem-cell growth in textured fiber channels or be used to break down the fiber at a specific location and point in time in order to release drugs as part of a smart bandage.

Stretching the fiber like molten plastic

To make their nanometric imprints, the researchers began with a technique called thermal drawing, which is the technique used to fabricate optical fibers. Thermal drawing involves engraving or imprinting millimeter-sized patterns on a preform, which is a macroscopic version of the target fiber. The imprinted preform is heated to change its viscosity, stretched like molten plastic into a long, thin fiber and then allowed to harden again. Stretching causes the pattern to shrink while maintaining its proportions and position. Yet this method has a major shortcoming: the pattern does not remain intact below the micrometer scale. “When the fiber is stretched, the surface tension of the structured polymer causes the pattern to deform and even disappear below a certain size, around several microns,” said Sorin.

To avoid this problem, the EPFL researchers came up with the idea of sandwiching the imprinted preform in a sacrificial polymer [emphasis mine]. This polymer protects the pattern during stretching by reducing the surface tension. It is discarded once the stretching is complete. Thanks to this trick, the researchers are able to apply tiny and highly complex patterns to various types of fibers. “We have achieved 300-nanometer patterns, but we could easily make them as small as several tens of nanometers,” said Sorin. This is the first time that such minute and highly complex patterns have been imprinted on flexible fiber on a very large scale. “This technique enables to achieve textures with feature sizes two order of magnitude smaller than previously reported,” said Sorin. “It could be applied to kilometers of fibers at a highly reasonable cost.”

To highlight potential applications of their achievement, the researchers teamed up with the Bertarelli Foundation Chair in Neuroprosthetic Technology, led by Stéphanie Lacour. Working in vitro, they were able to use their fibers to guide neurites from a spinal ganglion (on the spinal nerve). This was an encouraging step toward using these fibers to help nerves regenerate or to create artificial tissue.

This development could have implications in many other fields besides biology. “Fibers that are rendered water-resistant by the pattern could be used to make clothes. Or we could give the fibers special optical effects for design or detection purposes. There is also much to be done with the many new microfluidic systems out there,” said Sorin. The next step for the researchers will be to join forces with other EPFL labs on initiatives such as studying in vivo nerve regeneration. All this, thanks to the wonder of imprinted polymer fibers.

I like the term “sacrificial polymer.”

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

Controlled Sub-Micrometer Hierarchical Textures Engineered in Polymeric Fibers and Microchannels via Thermal Drawing by Tung Nguyen-Dang, Alba C. de Luca, Wei Yan, Yunpeng Qu, Alexis G. Page, Marco Volpi, Tapajyoti Das Gupta, Stéphanie P. Lacour, and Fabien Sorin. Advanced Functional Materials DOI: 10.1002/adfm.201605935 Version of Record online: 24 JAN 2017

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Spinal cords, brains, implants, and remote control

I have two items about implants and brains and an item about being able to exert remote control of the brain, all of which hint at a cyborg future for at least a few of us.

e-Dura, the spinal column, and the brain

The first item concerns some research, at the École Polytechnique de Lausanne (EPFL) which features flexible electronics. From a March 24, 2015 article by Ben Schiller for Fast Company (Note: Links have been removed),

Researchers at the Swiss Federal Institute of Technology, in Lausanne, have developed the e-Dura—a tiny skinlike device that attaches directly to damaged spinal cords. By sending out small electrical pulses, it stimulates the cord as if it were receiving signals from the brain, thus allowing movement.

“The purpose of the neuro-prosthesis is to excite the neurons that are on the spinal cord below the site of the injury and activate them, just like if they were receiving information from the brain,” says Stéphanie Lacour, a professor at the institute.

A January 8, 2015 (?) EPFL press release provides more information about the research,

EPFL scientists have managed to get rats walking on their own again using a combination of electrical and chemical stimulation. But applying this method to humans would require multifunctional implants that could be installed for long periods of time on the spinal cord without causing any tissue damage. This is precisely what the teams of professors Stéphanie Lacour and Grégoire Courtine have developed. Their e-Dura implant is designed specifically for implantation on the surface of the brain or spinal cord. The small device closely imitates the mechanical properties of living tissue, and can simultaneously deliver electric impulses and pharmacological substances. The risks of rejection and/or damage to the spinal cord have been drastically reduced. An article about the implant will appear in early January [2015] in Science Magazine.

So-called “surface implants” have reached a roadblock; they cannot be applied long term to the spinal cord or brain, beneath the nervous system’s protective envelope, otherwise known as the “dura mater,” because when nerve tissues move or stretch, they rub against these rigid devices. After a while, this repeated friction causes inflammation, scar tissue buildup, and rejection.

Here’s what the implant looks like,

Courtesy: EPFL

Courtesy: EPFL

The press release describes how the implant is placed (Note: A link has been removed),

Flexible and stretchy, the implant developed at EPFL is placed beneath the dura mater, directly onto the spinal cord. Its elasticity and its potential for deformation are almost identical to the living tissue surrounding it. This reduces friction and inflammation to a minimum. When implanted into rats, the e-Dura prototype caused neither damage nor rejection, even after two months. More rigid traditional implants would have caused significant nerve tissue damage during this period of time.

The researchers tested the device prototype by applying their rehabilitation protocol — which combines electrical and chemical stimulation – to paralyzed rats. Not only did the implant prove its biocompatibility, but it also did its job perfectly, allowing the rats to regain the ability to walk on their own again after a few weeks of training.

“Our e-Dura implant can remain for a long period of time on the spinal cord or the cortex, precisely because it has the same mechanical properties as the dura mater itself. This opens up new therapeutic possibilities for patients suffering from neurological trauma or disorders, particularly individuals who have become paralyzed following spinal cord injury,” explains Lacour, co-author of the paper, and holder of EPFL’s Bertarelli Chair in Neuroprosthetic Technology.

The press release goes on to describe the engineering achievements,

Developing the e-Dura implant was quite a feat of engineering. As flexible and stretchable as living tissue, it nonetheless includes electronic elements that stimulate the spinal cord at the point of injury. The silicon substrate is covered with cracked gold electric conducting tracks that can be pulled and stretched. The electrodes are made of an innovative composite of silicon and platinum microbeads. They can be deformed in any direction, while still ensuring optimal electrical conductivity. Finally, a fluidic microchannel enables the delivery of pharmacological substances – neurotransmitters in this case – that will reanimate the nerve cells beneath the injured tissue.

The implant can also be used to monitor electrical impulses from the brain in real time. When they did this, the scientists were able to extract with precision the animal’s motor intention before it was translated into movement.

“It’s the first neuronal surface implant designed from the start for long-term application. In order to build it, we had to combine expertise from a considerable number of areas,” explains Courtine, co-author and holder of EPFL’s IRP Chair in Spinal Cord Repair. “These include materials science, electronics, neuroscience, medicine, and algorithm programming. I don’t think there are many places in the world where one finds the level of interdisciplinary cooperation that exists in our Center for Neuroprosthetics.”

For the time being, the e-Dura implant has been primarily tested in cases of spinal cord injury in paralyzed rats. But the potential for applying these surface implants is huge – for example in epilepsy, Parkinson’s disease and pain management. The scientists are planning to move towards clinical trials in humans, and to develop their prototype in preparation for commercialization.

EPFL has provided a video of researcher Stéphanie Lacour describing e-Dura and expressing hopes for its commercialization,

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

Electronic dura mater for long-term multimodal neural interfaces by Ivan R. Minev, Pavel Musienko, Arthur Hirsch, Quentin Barraud, Nikolaus Wenger, Eduardo Martin Moraud, Jérôme Gandar, Marco Capogrosso, Tomislav Milekovic, Léonie Asboth, Rafael Fajardo Torres, Nicolas Vachicouras, Qihan Liu, Natalia Pavlova, Simone Duis, Alexandre Larmagnac, Janos Vörös, Silvestro Micera, Zhigang Suo, Grégoire Courtine, Stéphanie P. Lacour. Science 9 January 2015: Vol. 347 no. 6218 pp. 159-163 DOI: 10.1126/science.1260318

This paper is behind a paywall.

Carbon nanotube fibres could connect to the brain

Researchers at Rice University (Texas, US) are excited about the possibilities that carbon nanotube fibres offer in the field of implantable electronics for the brain. From a March 25, 2015 news item on Nanowerk,

Carbon nanotube fibers invented at Rice University may provide the best way to communicate directly with the brain.

The fibers have proven superior to metal electrodes for deep brain stimulation and to read signals from a neuronal network. Because they provide a two-way connection, they show promise for treating patients with neurological disorders while monitoring the real-time response of neural circuits in areas that control movement, mood and bodily functions.

New experiments at Rice demonstrated the biocompatible fibers are ideal candidates for small, safe electrodes that interact with the brain’s neuronal system, according to the researchers. They could replace much larger electrodes currently used in devices for deep brain stimulation therapies in Parkinson’s disease patients.

They may also advance technologies to restore sensory or motor functions and brain-machine interfaces as well as deep brain stimulation therapies for other neurological disorders, including dystonia and depression, the researchers wrote.

A March 25, 2015 Rice University news release (also on EurekAlert*), which originated the news item, provides more details,

The fibers created by the Rice lab of chemist and chemical engineer Matteo Pasquali consist of bundles of long nanotubes originally intended for aerospace applications where strength, weight and conductivity are paramount.

The individual nanotubes measure only a few nanometers across, but when millions are bundled in a process called wet spinning, they become thread-like fibers about a quarter the width of a human hair.

“We developed these fibers as high-strength, high-conductivity materials,” Pasquali said. “Yet, once we had them in our hand, we realized that they had an unexpected property: They are really soft, much like a thread of silk. Their unique combination of strength, conductivity and softness makes them ideal for interfacing with the electrical function of the human body.”

The simultaneous arrival in 2012 of Caleb Kemere, a Rice assistant professor who brought expertise in animal models of Parkinson’s disease, and lead author Flavia Vitale, a research scientist in Pasquali’s lab with degrees in chemical and biomedical engineering, prompted the investigation.

“The brain is basically the consistency of pudding and doesn’t interact well with stiff metal electrodes,” Kemere said. “The dream is to have electrodes with the same consistency, and that’s why we’re really excited about these flexible carbon nanotube fibers and their long-term biocompatibility.”

Weeks-long tests on cells and then in rats with Parkinson’s symptoms proved the fibers are stable and as efficient as commercial platinum electrodes at only a fraction of the size. The soft fibers caused little inflammation, which helped maintain strong electrical connections to neurons by preventing the body’s defenses from scarring and encapsulating the site of the injury.

The highly conductive carbon nanotube fibers also show much more favorable impedance – the quality of the electrical connection — than state-of-the-art metal electrodes, making for better contact at lower voltages over long periods, Kemere said.

The working end of the fiber is the exposed tip, which is about the width of a neuron. The rest is encased with a three-micron layer of a flexible, biocompatible polymer with excellent insulating properties.

The challenge is in placing the tips. “That’s really just a matter of having a brain atlas, and during the experiment adjusting the electrodes very delicately and putting them into the right place,” said Kemere, whose lab studies ways to connect signal-processing systems and the brain’s memory and cognitive centers.

Doctors who implant deep brain stimulation devices start with a recording probe able to “listen” to neurons that emit characteristic signals depending on their functions, Kemere said. Once a surgeon finds the right spot, the probe is removed and the stimulating electrode gently inserted. Rice carbon nanotube fibers that send and receive signals would simplify implantation, Vitale said.

The fibers could lead to self-regulating therapeutic devices for Parkinson’s and other patients. Current devices include an implant that sends electrical signals to the brain to calm the tremors that afflict Parkinson’s patients.

“But our technology enables the ability to record while stimulating,” Vitale said. “Current electrodes can only stimulate tissue. They’re too big to detect any spiking activity, so basically the clinical devices send continuous pulses regardless of the response of the brain.”

Kemere foresees a closed-loop system that can read neuronal signals and adapt stimulation therapy in real time. He anticipates building a device with many electrodes that can be addressed individually to gain fine control over stimulation and monitoring from a small, implantable device.

“Interestingly, conductivity is not the most important electrical property of the nanotube fibers,” Pasquali said. “These fibers are intrinsically porous and extremely stable, which are both great advantages over metal electrodes for sensing electrochemical signals and maintaining performance over long periods of time.”

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

Neural Stimulation and Recording with Bidirectional, Soft Carbon Nanotube Fiber Microelectrodes by Flavia Vitale, Samantha R. Summerson, Behnaam Aazhang, Caleb Kemere, and Matteo Pasquali. ACS Nano, Just Accepted Manuscript DOI: 10.1021/acsnano.5b01060 Publication Date (Web): March 24, 2015

Copyright © 2015 American Chemical Society

The paper is open access provided you register on the website.

Remote control for stimulation of the brain

Mo Costandi, neuroscientist and freelance science writer, has written a March 24, 2015 post for the Guardian science blog network focusing on neuronal remote control,

Two teams of scientists have developed new ways of stimulating neurons with nanoparticles, allowing them to activate brain cells remotely using light or magnetic fields. The new methods are quicker and far less invasive than other hi-tech methods available, so could be more suitable for potential new treatments for human diseases.

Researchers have various methods for manipulating brain cell activity, arguably the most powerful being optogenetics, which enables them to switch specific brain cells on or off with unprecedented precision, and simultaneously record their behaviour, using pulses of light.

This is very useful for probing neural circuits and behaviour, but involves first creating genetically engineered mice with light-sensitive neurons, and then inserting the optical fibres that deliver light into the brain, so there are major technical and ethical barriers to its use in humans.

Nanomedicine could get around this. Francisco Bezanilla of the University of Chicago and his colleagues knew that gold nanoparticles can absorb light and convert it into heat, and several years ago they discovered that infrared light can make neurons fire nervous impulses by heating up their cell membranes.

Polina Anikeeva’s team at the Massachusetts Institute of Technology adopted a slightly different approach, using spherical iron oxide particles that give off heat when exposed to an alternating magnetic field.

Although still in the experimental stages, research like this may eventually allow for wireless and minimally invasive deep brain stimulation of the human brain. Bezanilla’s group aim to apply their method to develop treatments for macular degeneration and other conditions that kill off light-sensitive cells in the retina. This would involve injecting nanoparticles into the eye so that they bind to other retinal cells, allowing natural light to excite them into firing impulses to the optic nerve.

Costandi’s article is intended for an audience that either understands the science or can deal with the uncertainty of not understanding absolutely everything. Provided you fall into either of those categories, the article is well written and it provides links and citations to the papers for both research teams being featured.

Taken together, the research at EPFL, Rice University, University of Chicago, and Massachusetts Institute of Technology provides a clue as to how much money and intellectual power is being directed at the brain.

* EurekAlert link added on March 26, 2015.