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Treating cardiac arrhythmia with light: a graphene tattoo

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An April 17, 2023 news item on Nanowerk announced research into a graphene cardiac implant/tattoo,

Researchers led by Northwestern University and the University of Texas at Austin (UT) have developed the first cardiac implant made from graphene, a two-dimensional super material with ultra-strong, lightweight and conductive properties.

Similar in appearance to a child’s temporary tattoo, the new graphene “tattoo” implant is thinner than a single strand of hair yet still functions like a classical pacemaker. But unlike current pacemakers and implanted defibrillators, which require hard, rigid materials that are mechanically incompatible with the body, the new device softly melds to the heart to simultaneously sense and treat irregular heartbeats. The implant is thin and flexible enough to conform to the heart’s delicate contours as well as stretchy and strong enough to withstand the dynamic motions of a beating heart.

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Caption: Graphene implant on tattoo paper. Credit: Ning Liu/University of Texas at Austin

An April 17, 2023 Northwestern University news release (also on EurekAlert), which originated the news item, provides more detail about the research, graphene, and the difficulties of monitoring a beating heart, Note: Links have been removed,

After implanting the device into a rat model, the researchers demonstrated that the graphene tattoo could successfully sense irregular heart rhythms and then deliver electrical stimulation through a series of pulses without constraining or altering the heart’s natural motions. Even better: The technology also is optically transparent, allowing the researchers to use an external source of optical light to record and stimulate the heart through the device.

The study will be published on Thursday (April 20 [2023]) in the journal Advanced Materials. It marks the thinnest known cardiac implant to date.

“One of the challenges for current pacemakers and defibrillators is that they are difficult to affix onto the surface of the heart,” said Northwestern’s Igor Efimov, the study’s senior author. “Defibrillator electrodes, for example, are essentially coils made of very thick wires. These wires are not flexible, and they break. Rigid interfaces with soft tissues, like the heart, can cause various complications. By contrast, our soft, flexible device is not only unobtrusive but also intimately and seamlessly conforms directly onto the heart to deliver more precise measurements.”

An experimental cardiologist, Efimov is a professor of biomedical engineering at Northwestern’s McCormick School of Engineering and professor of medicine at Northwestern University Feinberg School of Medicine. He co-led the study with Dmitry Kireev, a research associate at UT. Zexu Lin, a Ph.D. candidate in Efimov’s laboratory, is the paper’s first author.

Miracle material

Known as cardiac arrhythmias, heart rhythm disorders occur when the heart beats either too quickly or too slowly. While some cases of arrhythmia are not serious, many cases can lead to heart failure, stroke and even sudden death. In fact, complications related to arrythmia claim about 300,000 lives annually in the United States. Physicians commonly treat arrhythmia with implantable pacemakers and defibrillators that detect abnormal heartbeats and then correct rhythm with electrical stimulation. While these devices are lifesaving, their rigid nature may constrain the heart’s natural motions, injure soft tissues, cause temporary discomfort and induce complications, such as painful swelling, perforations, blood clots, infection and more.

With these challenges in mind, Efimov and his team sought to develop a bio-compatible device ideal for conforming to soft, dynamic tissues. After reviewing multiple materials, the researchers settled on graphene, an atomically thin form of carbon. With its ultra-strong, lightweight structure and superior conductivity, graphene has potential for many applications in high-performance electronics, high-strength materials and energy devices.

“For bio-compatibility reasons, graphene is particularly attractive,” Efimov said. “Carbon is the basis of life, so it’s a safe material that is already used in different clinical applications. It also is flexible and soft, which works well as an interface between electronics and a soft, mechanically active organ.”

Hitting a beating target

At UT, study co-authors Dimitry Kireev and Deji Akinwande were already developing graphene electronic tattoos (GETs) with sensing capabilities. Flexible and weightless, their team’s e-tattoos adhere to the skin to continuously monitor the body’s vital signs, including blood pressure and the electrical activity of the brain, heart and muscles.

But, while the e-tattoos work well on the skin’s surface, Efimov’s team needed to investigate new methods to use these devices inside the body — directly onto the surface of the heart.

“It’s a completely different application scheme,” Efimov said. “Skin is relatively dry and easily accessible. Obviously, the heart is inside the chest, so it’s difficult to access and in a wet environment.”

The researchers developed an entirely new technique to encase the graphene tattoo and adhere it to the surface of a beating heart. First, they encapsulated the graphene inside a flexible, elastic silicone membrane — with a hole punched in it to give access to the interior graphene electrode. Then, they gently placed gold tape (with a thickness of 10 microns) onto the encapsulating layer to serve as an electrical interconnect between the graphene and the external electronics used to measure and stimulate the heart. Finally, they placed it onto the heart. The entire thickness of all layers together measures about 100 microns in total.

The resulting device was stable for 60 days on an actively beating heart at body temperature, which is comparable to the duration of temporary pacemakers used as bridges to permanent pacemakers or rhythm management after surgery or other therapies.

Optical opportunities

Leveraging the device’s transparent nature, Efimov and his team performed optocardiography — using light to track and modulate heart rhythm — in the animal study. Not only does this offer a new way to diagnose and treat heart ailments, the approach also opens new possibilities for optogenetics, a method to control and monitor single cells with light. 

While electrical stimulation can correct a heart’s abnormal rhythm, optical stimulation is more precise. With light, researchers can track specific enzymes as well as interrogate specific heart, muscle or nerve cells.

“We can essentially combine electrical and optical functions into one biointerface,” Efimov said. “Because graphene is optically transparent, we can actually read through it, which gives us a much higher density of readout.”

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The University of Texas at Austin issued an April 18, 2023 news release and as you would expect the focus is on their researchers, Note 1: I’ve removed many but not all of the redundancies between the two news releases; Note 2: A link has been removed,

A new cardiac implant made from graphene, a two-dimensional super material with ultra-strong, lightweight and conductive properties, functions like a classic pacemaker with some major improvements.

A team led by researchers from The University of Texas at Austin and Northwestern University developed the implantable derivative from wearable graphene-based electronic tattoo, or e-tattoo – graphene biointerface. The device, detailed in the journal Advanced Materials, marks the thinnest known cardiac implant to date.

“It’s very exciting to take our e-tattoo technology and use it as an implantable device inside the body,” said Dmitry Kireev, a postdoctoral research associate in the lab of professor Deji Akinwande’s lab at UT Austin who co-led the research. “The fact that is much more compatible with the human body, lightweight, and transparent, makes this a more natural solution for people dealing with heart problems.”

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Hitting a beating target

At UT Austin, Akinwande and his team had been developing e-tattoos using graphene for several years, with a variety of functions, including monitoring body signals. Flexible and weightless, their team’s e-tattoos adhere to the skin to continuously monitor the body’s vital signs, including blood pressure and the electrical activity of the brain, heart and muscles.

But, while the e-tattoos work well on the skin’s surface, the researchers needed to find new ways to deploy these devices inside the body — directly onto the surface of the heart.

“The conditions inside the body are very different compared to affixing a device to the skin, so we had to re-imagine how we package our e-tattoo technology,” said Akinwande, a professor in the Chandra Family Department of Electrical and Computer Engineering.  

The researchers developed an entirely new technique to encase the graphene tattoo and adhere it to the surface of a beating heart. …

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

Graphene Biointerface for Cardiac Arrhythmia Diagnosis and Treatment by Zexu Lin, Dmitry Kireev, Ning Liu, Shubham Gupta, Jessica LaPiano, Sofian N. Obaid, Zhiyuan Chen, Deji Akinwande, Igor R. Efimov. Advanced Materials Volume 35, Issue 22 June 1, 2023 2212190 DOI: https://doi.org/10.1002/adma.202212190 First published online: 25 March 2023

This paper is open access.

Powered by light: a battery-free pacemaker

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I think it looks more like a potato than a heart but it does illustrate how this new battery-free pacemaker would wrap around a heart,

Caption: An artist’s rendering shows how a new pacemaker, designed by a UArizona-led team of researchers, is able to envelop the heart. The wireless, battery-free pacemaker could be implanted with a less invasive procedure than currently possible and would cause patients less pain. Credit: Philipp Gutruff

An October 27, 2022 news item on ScienceDaily announces a technology that could make life much easier for people with pacemakers (Comment: In the image, that looks more like a potato than a heart, to me),

University of Arizona engineers lead a research team that is developing a new kind of pacemaker, which envelops the heart and uses precise targeting capabilities to bypass pain receptors and reduce patient discomfort.

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An October 27, 2022 University of Arizona news release (also on EurekAlert) by Emily Dieckman, which originated the news item, explains the reasons for the research and provides some technical details (Note: Links have been removed),

Pacemakers are lifesaving devices that regulate the heartbeats of people with chronic heart diseases like atrial fibrillation and other forms of arrhythmia. However, pacemaker implantation is an invasive procedure, and the lifesaving pacing the devices provide can be extremely painful. Additionally, pacemakers can only be used to treat a few specific types of disease.

In a paper published Wednesday [October 26, 2022] in Science Advances, a University of Arizona-led team of researchers detail the workings of a wireless, battery-free pacemaker they designed that could be implanted with a less invasive procedure than currently possible and would cause patients less pain. The study was helmed by researchers in the Gutruf Lab, led by biomedical engineering assistant professor and Craig M. Berge Faculty Fellow Philipp Gutruf.

Currently available pacemakers work by implanting one or two leads, or points of contact, into the heart with hooks or screws. If the sensors on these leads detect a dangerous irregularity, they send an electrical shock through the heart to reset the beat.

“All of the cells inside the heart get hit at one time, including the pain receptors, and that’s what makes pacing or defibrillation painful,” Gutruf said. “It affects the heart muscle as a whole.”

The device Gutruf’s team has developed, which has not yet been tested in humans, would allow pacemakers to send much more targeted signals using a new digitally manufactured mesh design that encompasses the entire heart. The device uses light and a technique called optogenetics.

Optogenetics modifies cells, usually neurons, sensitive to light, then uses light to affect the behavior of those cells. This technique only targets cardiomyocytes, the cells of the muscle that trigger contraction and make up the beat of the heart. This precision will not only reduce pain for pacemaker patients by bypassing the heart’s pain receptors, it will also allow the pacemaker to respond to different kinds of irregularities in more appropriate ways. For example, during atrial fibrillation, the upper and lower chambers of the heart beat asynchronously, and a pacemaker’s role is to get the two parts back in line.

“Whereas right now, we have to shock the whole heart to do this, these new devices can do much more precise targeting, making defibrillation both more effective and less painful,” said Igor Efimov, professor of biomedical engineering and medicine at Northwestern University, where the devices were lab-tested. “This technology could make life easier for patients all over the world, while also helping scientists and physicians learn more about how to monitor and treat the disease.”

Flexible mesh encompasses the heart

To ensure the light signals can reach many different parts of the heart, the team created a design that involves encompassing the organ, rather than implanting leads that provide limited points of contact.

The new pacemaker model consists of four petallike structures made of thin, flexible film, which contain light sources and a recording electrode. The petals, specially designed to accommodate the way the heart changes shape as it beats, fold up around the sides of the organ to envelop it, like a flower closing up at night.

“Current pacemakers record basically a simple threshold, and they will tell you, ‘This is going into arrhythmia, now shock!'” Gutruf said. “But this device has a computer on board where you can input different algorithms that allow you to pace in a more sophisticated way. It’s made for research.”

Because the system uses light to affect the heart, rather than electrical signals, the device can continue recording information even when the pacemaker needs to defibrillate. In current pacemakers, the electrical signal from the defibrillation can interfere with recording capabilities, leaving physicians with an incomplete picture of cardiac episodes. Additionally, the device does not require a battery, which could save pacemaker patients from needing to replace the battery in their device every five to seven years, as is currently the norm.

Gutruf’s team collaborated with researchers at Northwestern University on the project. While the current version of the device has been successfully demonstrated in animal models, the researchers look forward to furthering their work, which could improve the quality of life for millions of people.

The prototype looks like this,

Caption: The device uses light and a technique called optogenetics, which modifies cells that are sensitive to light, then uses light to affect the behavior of those cells.. Credit: Philipp Gutruff

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

Wireless, fully implantable cardiac stimulation and recording with on-device computation for closed-loop pacing and defibrillation by Jokubas Ausra, Micah Madrid, Rose T. Yin, Jessica Hanna, Suzanne Arnott, Jaclyn A. Brennan, Roberto Peralta, David Clausen, Jakob A. Bakall, Igor R. Efimov, and Philipp Gutruf. Science Advances 26 Oct 2022 Vol 8, Issue 43 DOI: 10.1126/sciadv.abq7469

This paper is open access.

Living optical fibers

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The word ‘living’ isn’t usually associated with optical fibers and the addition had me thinking that this October 11, 2021 Nanowerk Spotlight story by Michael Berger would be a synthetic biology story. Well, not exactly. Do read on for a good introduction describing glass, fiber optics, and optogenetics,

Glass is one of the oldest manufactured materials used by humans and glass making dates back at least 6000 years, long before humans had discovered how to smelt iron. Glasses have been based on the chemical compound silica – silicon dioxide, or quartz – the primary constituent of sand. Soda-lime glass, containing around 70% silica, accounts for around 90% of manufactured glass.

Historically, we are familiar with glasses’ decorative use or as window panes, household items, and in optics such as eyeglasses, microscopes and telescopes. More recently, starting in the 1950s, glass has been used in the manufacture of fiber optic cables, a technology that has revolutionized the communications industry and helped ring in the digital revolution.

Fiber optic cables propagate a signal as a pulse of light along a transparent medium, usually glass. This is not only used to transmit information but, for instance in many healthcare and biomedical applications, scientists use optical fibers for sensing applications by shining light into a sample and evaluating the absorbed or transmitted light.

A recent development in this field is optogenetics, a neuromodulation method that uses activation or deactivation of brain cells by illumination with different colors of light in order to treat brain disorders.

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Berger goes on to explain the latest work and reveals what ‘living’ means where this work is concerned,

This work represents a simple and low-cost approach to fabricating optical fibers made from biological materials. These fibers can be easily modified for specific applications and don’t require sophisticated equipment to generate relevant information. This method could be used for many practical sensing and biological modeling applications.

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“We use a natural, ionic, and biologically compatible crosslinking approach, which enables us to produce flexible hydrogel fibers in continuous multi-layered architectures, meaning they are easy to produce and can be modified after fabrication,” explains Guimarães [Carlos Guimarães, the paper’s first author]. “Similarly to silica fibers, the core hydrogel of our structures can be exposed, fused to another fiber or reassembled if they break, and efficiently guide light through the established connection.”

These flexible hydrogel fibers are made from sugars and work just like solid-state optical fibers used to transmit data. However, they are biocompatible so they can be easily integrated with biological systems.

“We could even consider them to be alive [emphasis mine] since we can use them to grow living cells inside the fiber,” says Guimarães. “As these embedded cells grow over time, we can then use light to inform on living dynamic events, for example to track cancer invasive proliferation into optical information.” [emphasis mine]

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As to what constitutes optical information in this context,

Another intriguing aspect of these hydrogel fibers is that their permeable mesh enables the inclusion of biological targets of interest for detection. For example, the scientists observed that fibers were able to soak SARS-CoV-2 viruses, and by integrating nanoparticles for their binding and detection, shifts in visible light could be observed for detecting the accumulation of viral particles within the fiber.

“When light moving through the fiber encounters living cells, it changes its characteristics depending on cellular density, invasive proliferation, expression of molecules, etc.” Guimarães notes. “This light-cell interaction can digitize complex biological events, converting responses such as cancer cell progression in 3D environments and susceptibility to drugs into numbers and data, very fast and without the need for sample destruction.”

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

Engineering Polysaccharide-Based Hydrogel Photonic Constructs: From Multiscale Detection to the Biofabrication of Living Optical Fibers by Carlos F. Guimarães, Rajib Ahmed, Amideddin Mataji-Kojouri, Fernando Soto, Jie Wang, Shiqin Liu, Tanya Stoyanova, Alexandra P. Marques, Rui L. Reis, Utkan Demirci. Advanced Materials DOI: https://doi.org/10.1002/adma.202105361 First published: 07 October 2021

This paper is behind a paywall.

Will you be my friend? Yes, after we activate our ultraminiature, wireless, battery-free, fully implantable devices

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Perhaps I’m the only one who’s disconcerted?

Here’s the research (in text form) as to why we’re watching these scampering, momentary mouse friends, from a May 10, 2021 Northwestern University news release (also on EurekAlert) by Amanda Morris,

Northwestern University researchers are building social bonds with beams of light.

For the first time ever, Northwestern engineers and neurobiologists have wirelessly programmed — and then deprogrammed — mice to socially interact with one another in real time. The advancement is thanks to a first-of-its-kind ultraminiature, wireless, battery-free and fully implantable device that uses light to activate neurons.

This study is the first optogenetics (a method for controlling neurons with light) paper exploring social interactions within groups of animals, which was previously impossible with current technologies.

The research was published May 10 [2021] in the journal Nature Neuroscience.

The thin, flexible, wireless nature of the implant allows the mice to look normal and behave normally in realistic environments, enabling researchers to observe them under natural conditions. Previous research using optogenetics required fiberoptic wires, which restrained mouse movements and caused them to become entangled during social interactions or in complex environments.

“With previous technologies, we were unable to observe multiple animals socially interacting in complex environments because they were tethered,” said Northwestern neurobiologist Yevgenia Kozorovitskiy, who designed the experiment. “The fibers would break or the animals would become entangled. In order to ask more complex questions about animal behavior in realistic environments, we needed this innovative wireless technology. It’s tremendous to get away from the tethers.”

“This paper represents the first time we’ve been able to achieve wireless, battery-free implants for optogenetics with full, independent digital control over multiple devices simultaneously in a given environment,” said Northwestern bioelectronics pioneer John A. Rogers, who led the technology development. “Brain activity in an isolated animal is interesting, but going beyond research on individuals to studies of complex, socially interacting groups is one of the most important and exciting frontiers in neuroscience. We now have the technology to investigate how bonds form and break between individuals in these groups and to examine how social hierarchies arise from these interactions.”

Kozorovitskiy is the Soretta and Henry Shapiro Research Professor of Molecular Biology and associate professor of neurobiology in Northwestern’s Weinberg College of Arts and Sciences. She also is a member of the Chemistry of Life Processes Institute. Rogers is the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery in the McCormick School of Engineering and Northwestern University Feinberg School of Medicine and the director of the Querrey Simpson Institute for Bioelectronics.

Kozorovitskiy and Rogers led the work with Yonggang Huang, the Jan and Marcia Achenbach Professor in Mechanical Engineering at McCormick, and Zhaoqian Xie, a professor of engineering mechanics at Dalian University of Technology in China. The paper’s co-first authors are Yiyuan Yang, Mingzheng Wu and Abraham Vázquez-Guardado — all at Northwestern.

Promise and problems of optogenetics

Because the human brain is a system of nearly 100 billion intertwined neurons, it’s extremely difficult to probe single — or even groups of — neurons. Introduced in animal models around 2005, optogenetics offers control of specific, genetically targeted neurons in order to probe them in unprecedented detail to study their connectivity or neurotransmitter release. Researchers first modify neurons in living mice to express a modified gene from light-sensitive algae. Then they can use external light to specifically control and monitor brain activity. Because of the genetic engineering involved, the method is not yet approved in humans.

“It sounds like sci-fi, but it’s an incredibly useful technique,” Kozorovitskiy said. “Optogenetics could someday soon be used to fix blindness or reverse paralysis.”

Previous optogenetics studies, however, were limited by the available technology to deliver light. Although researchers could easily probe one animal in isolation, it was challenging to simultaneously control neural activity in flexible patterns within groups of animals interacting socially. Fiberoptic wires typically emerged from an animal’s head, connecting to an external light source. Then a software program could be used to turn the light off and on, while monitoring the animal’s behavior.

“As they move around, the fibers tugged in different ways,” Rogers said. “As expected, these effects changed the animal’s patterns of motion. One, therefore, has to wonder: What behavior are you actually studying? Are you studying natural behaviors or behaviors associated with a physical constraint?”

Wireless control in real time

A world-renowned leader in wireless, wearable technology, Rogers and his team developed a tiny, wireless device that gently rests on the skull’s outer surface but beneath the skin and fur of a small animal. The half-millimeter-thick device connects to a fine, flexible filamentary probe with LEDs on the tip, which extend down into the brain through a tiny cranial defect.

The miniature device leverages near-field communication protocols, the same technology used in smartphones for electronic payments. Researchers wirelessly operate the light in real time with a user interface on a computer. An antenna surrounding the animals’ enclosure delivers power to the wireless device, thereby eliminating the need for a bulky, heavy battery.

Activating social connections

To establish proof of principle for Rogers’ technology, Kozorovitskiy and colleagues designed an experiment to explore an optogenetics approach to remote-control social interactions among pairs or groups of mice.

When mice were physically near one another in an enclosed environment, Kozorovitskiy’s team wirelessly synchronously activated a set of neurons in a brain region related to higher order executive function, causing them to increase the frequency and duration of social interactions. Desynchronizing the stimulation promptly decreased social interactions in the same pair of mice. In a group setting, researchers could bias an arbitrarily chosen pair to interact more than others.

“We didn’t actually think this would work,” Kozorovitskiy said. “To our knowledge, this is the first direct evaluation of a major long-standing hypothesis about neural synchrony in social behavior.”

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

Wireless multilateral devices for optogenetic studies of individual and social behaviors by Yiyuan Yang, Mingzheng Wu, Amy J. Wegener, Jose G. Grajales-Reyes, Yujun Deng, Taoyi Wang, Raudel Avila, Justin A. Moreno, Samuel Minkowicz, Vasin Dumrongprechachan, Jungyup Lee, Shuangyang Zhang, Alex A. Legaria, Yuhang Ma, Sunita Mehta, Daniel Franklin, Layne Hartman, Wubin Bai, Mengdi Han, Hangbo Zhao, Wei Lu, Yongjoon Yu, Xing Sheng, Anthony Banks, Xinge Yu, Zoe R. Donaldson, Robert W. Gereau IV, Cameron H. Good, Zhaoqian Xie, Yonggang Huang, Yevgenia Kozorovitskiy and John A. Rogers. Nature Neuroscience (2021)
DOI: https://doi.org/10.1038/s41593-021-00849-x Published 10 May 2021

This paper is behind a paywall.

This latest research seems to be the continuation of research featured here in a July 16, 2019 posting: “Controlling neurons with light: no batteries or wires needed.”

Optical fibers made from marine algae

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Apparently after you’ve finished imaging with your marine algae-based optical fibers, you can eat them. A July 24, 2020 news item on Nanowerk announces the new research,

An optical fiber made of agar has been produced at the University of Campinas (UNICAMP) in the state of São Paulo, Brazil. This device is edible, biocompatible and biodegradable. It can be used in vivo for body structure imaging, localized light delivery in phototherapy or optogenetics (e.g., stimulating neurons with light to study neural circuits in a living brain), and localized drug delivery.

Another possible application is the detection of microorganisms in specific organs, in which case the probe would be completely absorbed by the body after performing its function.

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Caption: Edible, biocompatible and biodegradable, these fibers have potential for various medical applications. Credit: Eric Fujiwara

A July 24, 2020 Fundação de Amparo à Pesquisa dFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) do Estado de São Paulo press release on EurekAlert, which originated the news item, provides a few more details about the researches and the work,

The research project, which was supported by São Paulo Research Foundation – FAPESP, was led by Eric Fujiwara, a professor in UNICAMP’s School of Mechanical Engineering, and Cristiano Cordeiro, a professor in UNICAMP’s Gleb Wataghin Institute of Physics, in collaboration with Hiromasa Oku, a professor at Gunma University in Japan.

An article on the study is published) in Scientific Reports, an online journal owned by Springer Nature.

Agar, also called agar-agar, is a natural gelatin obtained from marine algae. Its composition consists of a mixture of two polysaccharides, agarose and agaropectin. “Our optical fiber is an agar cylinder with an external diameter of 2.5 millimeters [mm] and a regular inner arrangement of six 0.5 mm cylindrical airholes around a solid core. Light is confined owing to the difference between the refraction indices of the agar core and the airholes,” Fujiwara told.

“To produce the fiber, we poured food-grade agar into a mold with six internal rods placed lengthwise around the main axis,” he continued. “The gel distributes itself to fill the available space. After cooling, the rods are removed to form airholes, and the solidified waveguide is released from the mold. The refraction index and geometry of the fiber can be adapted by varying the composition of the agar solution and mold design, respectively.”

The researchers tested the fiber in different media, from air and water to ethanol and acetone, concluding that it is context-sensitive. “The fact that the gel undergoes structural changes in response to variations in temperature, humidity and pH makes the fiber suitable for optical sensing,” Fujiwara said.

Another promising application is its simultaneous use as an optical sensor and a growth medium for microorganisms. “In this case, the waveguide can be designed as a disposable sample unit containing the necessary nutrients. The immobilized cells in the device would be optically sensed, and the signal would be analyzed using a camera or spectrometer,” he said.

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About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at http://www.fapesp.br/en and visit FAPESP news agency at http://www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

As per my usual practice, here’s a link to and a citation for the paper,

Agarose-based structured optical fibre by Eric Fujiwara, Thiago D. Cabral, Miko Sato, Hiromasa Oku & Cristiano M. B. Cordeiro. Scientific Reports volume 10, Article number: 7035 (2020) DOI: https://doi.org/10.1038/s41598-020-64103-3 Published: 27 April 2020

This paper is open access.

Should you have a problem accessing the English language version of the FAPESP website, the Portuguese language version of the site seems more accessible (assuming you have the language skills).

Using light to manipulate neurons

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There are three (or more?) possible applications including neuromorphic computing for this new optoelectronic technology which is based on black phophorus. A July 16, 2019 news item on Nanowerk announces the research,

Researchers from RMIT University [Australia] drew inspiration from an emerging tool in biotechnology – optogenetics – to develop a device that replicates the way the brain stores and loses information.

Optogenetics allows scientists to delve into the body’s electrical system with incredible precision, using light to manipulate neurons so that they can be turned on or off.

The new chip is based on an ultra-thin material that changes electrical resistance in response to different wavelengths of light, enabling it to mimic the way that neurons work to store and delete information in the brain.

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Caption: The new chip is based on an ultra-thin material that changes electrical resistance in response to different wavelengths of light. Credit: RMIT University

A July 17, 2019 RMIT University press release (also on EurekAlert but published on July 16, 2019), which originated the news item, expands on the theme,

Research team leader Dr Sumeet Walia said the technology moves us closer towards artificial intelligence (AI) that can harness the brain’s full sophisticated functionality.

“Our optogenetically-inspired chip imitates the fundamental biology of nature’s best computer – the human brain,” Walia said.

“Being able to store, delete and process information is critical for computing, and the brain does this extremely efficiently.

“We’re able to simulate the brain’s neural approach simply by shining different colours onto our chip.

“This technology takes us further on the path towards fast, efficient and secure light-based computing.

“It also brings us an important step closer to the realisation of a bionic brain – a brain-on-a-chip that can learn from its environment just like humans do.”

Dr Taimur Ahmed, lead author of the study published in Advanced Functional Materials, said being able to replicate neural behavior on an artificial chip offered exciting avenues for research across sectors.

“This technology creates tremendous opportunities for researchers to better understand the brain and how it’s affected by disorders that disrupt neural connections, like Alzheimer’s disease and dementia,” Ahmed said.

The researchers, from the Functional Materials and Microsystems Research Group at RMIT, have also demonstrated the chip can perform logic operations – information processing – ticking another box for brain-like functionality.

Developed at RMIT’s MicroNano Research Facility, the technology is compatible with existing electronics and has also been demonstrated on a flexible platform, for integration into wearable electronics.

How the chip works:

Neural connections happen in the brain through electrical impulses. When tiny energy spikes reach a certain threshold of voltage, the neurons bind together – and you’ve started creating a memory.

On the chip, light is used to generate a photocurrent. Switching between colors causes the current to reverse direction from positive to negative.

This direction switch, or polarity shift, is equivalent to the binding and breaking of neural connections, a mechanism that enables neurons to connect (and induce learning) or inhibit (and induce forgetting).

This is akin to optogenetics, where light-induced modification of neurons causes them to either turn on or off, enabling or inhibiting connections to the next neuron in the chain.

To develop the technology, the researchers used a material called black phosphorus (BP) that can be inherently defective in nature.

This is usually a problem for optoelectronics, but with precision engineering the researchers were able to harness the defects to create new functionality.

“Defects are usually looked on as something to be avoided, but here we’re using them to create something novel and useful,” Ahmed said.

“It’s a creative approach to finding solutions for the technical challenges we face.”

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

Multifunctional Optoelectronics via Harnessing Defects in Layered Black Phosphorus by Taimur Ahmed, Sruthi Kuriakose, Sherif Abbas,, Michelle J. S. Spencer, Md. Ataur Rahman, Muhammad Tahir, Yuerui Lu, Prashant Sonar, Vipul Bansal, Madhu Bhaskaran, Sharath Sriram, Sumeet Walia. Advanced Functional Materials DOI: https://doi.org/10.1002/adfm.201901991 First published (online): 17 July 2019

This paper is behind a paywall.

Transparent graphene electrode technology and complex brain imaging

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Michael Berger has written a May 24, 2018 Nanowerk Spotlight article about some of the latest research on transparent graphene electrode technology and the brain (Note: A link has been removed),

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In new work, scientists from the labs of Kuzum [Duygu Kuzum, an Assistant Professor of Electrical and Computer Engineering at the University of California, San Diego {UCSD}] and Anna Devor report a transparent graphene microelectrode neural implant that eliminates light-induced artifacts to enable crosstalk-free integration of 2-photon microscopy, optogenetic stimulation, and cortical recordings in the same in vivo experiment. The new class of transparent brain implant is based on monolayer graphene. It offers a practical pathway to investigate neuronal activity over multiple spatial scales extending from single neurons to large neuronal populations.

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Conventional metal-based microelectrodes cannot be used for simultaneous measurements of multiple optical and electrical parameters, which are essential for comprehensive investigation of brain function across spatio-temporal scales. Since they are opaque, they block the field of view of the microscopes and generate optical shadows impeding imaging.

More importantly, they cause light induced artifacts in electrical recordings, which can significantly interfere with neural signals. Transparent graphene electrode technology presented in this paper addresses these problems and allow seamless and crosstalk-free integration of optical and electrical sensing and manipulation technologies.

In their work, the scientists demonstrate that by careful design of key steps in the fabrication process for transparent graphene electrodes, the light-induced artifact problem can be mitigated and virtually artifact-free local field potential (LFP) recordings can be achieved within operating light intensities.

“Optical transparency of graphene enables seamless integration of imaging, optogenetic stimulation and electrical recording of brain activity in the same experiment with animal models,” Kuzum explains. “Different from conventional implants based on metal electrodes, graphene-based electrodes do not generate any electrical artifacts upon interacting with light used for imaging or optogenetics. That enables crosstalk free integration of three modalities: imaging, stimulation and recording to investigate brain activity over multiple spatial scales extending from single neurons to large populations of neurons in the same experiment.”

The team’s new fabrication process avoids any crack formation in the transfer process, resulting in a 95-100% yield for the electrode arrays. This fabrication quality is important for expanding this technology to high-density large area transparent arrays to monitor brain-scale cortical activity in large animal models or humans.

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“Our technology is also well-suited for neurovascular and neurometabolic studies, providing a ‘gold standard’ neuronal correlate for optical measurements of vascular, hemodynamic, and metabolic activity,” Kuzum points out. “It will find application in multiple areas, advancing our understanding of how microscopic neural activity at the cellular scale translates into macroscopic activity of large neuron populations.”

“Combining optical techniques with electrical recordings using graphene electrodes will allow to connect the large body of neuroscience knowledge obtained from animal models to human studies mainly relying on electrophysiological recordings of brain-scale activity,” she adds.

Next steps for the team involve employing this technology to investigate coupling and information transfer between different brain regions.

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This work is part of the US BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative and there’s more than one team working with transparent graphene electrodes. John Hewitt in an Oct. 21, 2014 posting on ExtremeTech describes two other teams’ work (Note: Links have been removed),

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The solution [to the problems with metal electrodes], now emerging from multiple labs throughout the universe is to build flexible, transparent electrode arrays from graphene. Two studies in the latest issue of Nature Communications, one from the University of Wisconsin-Madison and the other from Penn [University of Pennsylvania], describe how to build these devices.

The University of Wisconsin researchers are either a little bit smarter or just a little bit richer, because they published their work open access. It’s a no-brainer then that we will focus on their methods first, and also in more detail. To make the arrays, these guys first deposited the parylene (polymer) substrate on a silicon wafer, metalized it with gold, and then patterned it with an electron beam to create small contact pads. The magic was to then apply four stacked single-atom-thick graphene layers using a wet transfer technique. These layers were then protected with a silicon dioxide layer, another parylene layer, and finally molded into brain signal recording goodness with reactive ion etching.

PennTransparentelectrodeThe researchers went with four graphene layers because that provided optimal mechanical integrity and conductivity while maintaining sufficient transparency. They tested the device in opto-enhanced mice whose neurons expressed proteins that react to blue light. When they hit the neurons with a laser fired in through the implant, the protein channels opened and fired the cell beneath. The masterstroke that remained was then to successfully record the electrical signals from this firing, sit back, and wait for the Nobel prize office to call.

The Penn State group [Note: Every reearcher mentioned in the paper Hewitt linked to is from the University of Pennsylvania] in the  used a similar 16-spot electrode array (pictured above right), and proceeded — we presume — in much the same fashion. Their angle was to perform high-resolution optical imaging, in particular calcium imaging, right out through the transparent electrode arrays which simultaneously recorded in high-temporal-resolution signals. They did this in slices of the hippocampus where they could bring to bear the complex and multifarious hardware needed to perform confocal and two-photon microscopy. These latter techniques provide a boost in spatial resolution by zeroing in over narrow planes inside the specimen, and limiting the background by the requirement of two photons to generate an optical signal. We should mention that there are voltage sensitive dyes available, in addition to standard calcium dyes, which can almost record the fastest single spikes, but electrical recording still reigns supreme for speed.

What a mouse looks like with an optogenetics system plugged in

What a mouse looks like with an optogenetics system plugged in

One concern of both groups in making these kinds of simultaneous electro-optic measurements was the generation of light-induced artifacts in the electrical recordings. This potential complication, called the Becqueral photovoltaic effect, has been known to exist since it was first demonstrated back in 1839. When light hits a conventional metal electrode, a photoelectrochemical (or more simply, a photovoltaic) effect occurs. If present in these recordings, the different signals could be highly disambiguatable. The Penn researchers reported that they saw no significant artifact, while the Wisconsin researchers saw some small effects with their device. In particular, when compared with platinum electrodes put into the opposite side cortical hemisphere, the Wisconsin researchers found that the artifact from graphene was similar to that obtained from platinum electrodes.

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Here’s a link to and a citation for the latest research from UCSD,

Deep 2-photon imaging and artifact-free optogenetics through transparent graphene microelectrode arrays by Martin Thunemann, Yichen Lu, Xin Liu, Kıvılcım Kılıç, Michèle Desjardins, Matthieu Vandenberghe, Sanaz Sadegh, Payam A. Saisan, Qun Cheng, Kimberly L. Weldy, Hongming Lyu, Srdjan Djurovic, Ole A. Andreassen, Anders M. Dale, Anna Devor, & Duygu Kuzum. Nature Communicationsvolume 9, Article number: 2035 (2018) doi:10.1038/s41467-018-04457-5 Published: 23 May 2018

This paper is open access.

You can find out more about the US BRAIN initiative here and if you’re curious, you can find out more about the project at UCSD here. Duygu Kuzum (now at UCSD) was at  the University of Pennsylvania in 2014 and participated in the work mentioned in Hewitt’s 2014 posting.

Stretchy optical materials for implants that could pulse light

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An Oct. 17, 2016 Massachusetts Institute of Technology (MIT) news release (also on EurekAlert) by Emily Chu describes research that could lead to long-lasting implants offering preventive health strategies,

Researchers from MIT and Harvard Medical School have developed a biocompatible and highly stretchable optical fiber made from hydrogel — an elastic, rubbery material composed mostly of water. The fiber, which is as bendable as a rope of licorice, may one day be implanted in the body to deliver therapeutic pulses of light or light up at the first sign of disease. [emphasis mine]

The researchers say the fiber may serve as a long-lasting implant that would bend and twist with the body without breaking down. The team has published its results online in the journal Advanced Materials.

Using light to activate cells, and particularly neurons in the brain, is a highly active field known as optogenetics, in which researchers deliver short pulses of light to targeted tissues using needle-like fibers, through which they shine light from an LED source.

“But the brain is like a bowl of Jell-O, whereas these fibers are like glass — very rigid, which can possibly damage brain tissues,” says Xuanhe Zhao, the Robert N. Noyce Career Development Associate Professor in MIT’s Department of Mechanical Engineering. “If these fibers could match the flexibility and softness of the brain, they could provide long-term more effective stimulation and therapy.”

Getting to the core of it

Zhao’s group at MIT, including graduate students Xinyue Liu and Hyunwoo Yuk, specializes in tuning the mechanical properties of hydrogels. The researchers have devised multiple recipes for making tough yet pliable hydrogels out of various biopolymers. The team has also come up with ways to bond hydrogels with various surfaces such as metallic sensors and LEDs, to create stretchable electronics.

The researchers only thought to explore hydrogel’s use in optical fibers after conversations with the bio-optics group at Harvard Medical School, led by Associate Professor Seok-Hyun (Andy) Yun. Yun’s group had previously fabricated an optical fiber from hydrogel material that successfully transmitted light through the fiber. However, the material broke apart when bent or slightly stretched. Zhao’s hydrogels, in contrast, could stretch and bend like taffy. The two groups joined efforts and looked for ways to incorporate Zhao’s hydrogel into Yun’s optical fiber design.

Yun’s design consists of a core material encased in an outer cladding. To transmit the maximum amount of light through the core of the fiber, the core and the cladding should be made of materials with very different refractive indices, or degrees to which they can bend light.

“If these two things are too similar, whatever light source flows through the fiber will just fade away,” Yuk explains. “In optical fibers, people want to have a much higher refractive index in the core, versus cladding, so that when light goes through the core, it bounces off the interface of the cladding and stays within the core.”

Happily, they found that Zhao’s hydrogel material was highly transparent and possessed a refractive index that was ideal as a core material. But when they tried to coat the hydrogel with a cladding polymer solution, the two materials tended to peel apart when the fiber was stretched or bent.

To bond the two materials together, the researchers added conjugation chemicals to the cladding solution, which, when coated over the hydrogel core, generated chemical links between the outer surfaces of both materials.

“It clicks together the carboxyl groups in the cladding, and the amine groups in the core material, like molecular-level glue,” Yuk says.

Sensing strain

The researchers tested the optical fibers’ ability to propagate light by shining a laser through fibers of various lengths. Each fiber transmitted light without significant attenuation, or fading. They also found that fibers could be stretched over seven times their original length without breaking.

Now that they had developed a highly flexible and robust optical fiber, made from a hydrogel material that was also biocompatible, the researchers began to play with the fiber’s optical properties, to see if they could design a fiber that could sense when and where it was being stretched.

They first loaded a fiber with red, green, and blue organic dyes, placed at specific spots along the fiber’s length. Next, they shone a laser through the fiber and stretched, for instance, the red region. They measured the spectrum of light that made it all the way through the fiber, and noted the intensity of the red light. They reasoned that this intensity relates directly to the amount of light absorbed by the red dye, as a result of that region being stretched.

In other words, by measuring the amount of light at the far end of the fiber, the researchers can quantitatively determine where and by how much a fiber was stretched.

“When you stretch a certain portion of the fiber, the dimensions of that part of the fiber changes, along with the amount of light that region absorbs and scatters, so in this way, the fiber can serve as a sensor of strain,” Liu explains.

“This is like a multistrain sensor through a single fiber,” Yuk adds. “So it can be an implantable or wearable strain gauge.”

The researchers imagine that such stretchable, strain-sensing optical fibers could be implanted or fitted along the length of a patient’s arm or leg, to monitor for signs of improving mobility.

Zhao envisions the fibers may also serve as sensors, lighting up in response to signs of disease.

“We may be able to use optical fibers for long-term diagnostics, to optically monitor tumors or inflammation,” he says. “The applications can be impactful.”

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

Highly Stretchable, Strain Sensing Hydrogel Optical Fibers by Jingjing Guo, Xinyue Liu, Nan Jiang, Ali K. Yetisen, Hyunwoo Yuk, Changxi Yang, Ali Khademhosseini, Xuanhe Zhao, and Seok-Hyun Yun. Advanced Materials DOI: 10.1002/adma.201603160 Version of Record online: 7 OCT 2016

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

The sense of touch via artificial skin

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Scientists have been working for years to allow artificial skin to transmit what the brain would recognize as the sense of touch. For anyone who has lost a limb and gotten a prosthetic replacement, the loss of touch is reputedly one of the more difficult losses to accept. The sense of touch is also vital in robotics if the field is to expand and include activities reliant on the sense of touch, e.g., how much pressure do you use to grasp a cup; how much strength  do you apply when moving an object from one place to another?

For anyone interested in the ‘electronic skin and pursuit of touch’ story, I have a Nov. 15, 2013 posting which highlights the evolution of the research into e-skin and what was then some of the latest work.

This posting is a 2015 update of sorts featuring the latest e-skin research from Stanford University and Xerox PARC. (Dexter Johnson in an Oct. 15, 2015 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineering] site) provides a good research summary.) For anyone with an appetite for more, there’s this from an Oct. 15, 2015 American Association for the Advancement of Science (AAAS) news release on EurekAlert,

Using flexible organic circuits and specialized pressure sensors, researchers have created an artificial “skin” that can sense the force of static objects. Furthermore, they were able to transfer these sensory signals to the brain cells of mice in vitro using optogenetics. For the many people around the world living with prosthetics, such a system could one day allow them to feel sensation in their artificial limbs. To create the artificial skin, Benjamin Tee et al. developed a specialized circuit out of flexible, organic materials. It translates static pressure into digital signals that depend on how much mechanical force is applied. A particular challenge was creating sensors that can “feel” the same range of pressure that humans can. Thus, on the sensors, the team used carbon nanotubes molded into pyramidal microstructures, which are particularly effective at tunneling the signals from the electric field of nearby objects to the receiving electrode in a way that maximizes sensitivity. Transferring the digital signal from the artificial skin system to the cortical neurons of mice proved to be another challenge, since conventional light-sensitive proteins used in optogenetics do not stimulate neural spikes for sufficient durations for these digital signals to be sensed. Tee et al. therefore engineered new optogenetic proteins able to accommodate longer intervals of stimulation. Applying these newly engineered optogenic proteins to fast-spiking interneurons of the somatosensory cortex of mice in vitro sufficiently prolonged the stimulation interval, allowing the neurons to fire in accordance with the digital stimulation pulse. These results indicate that the system may be compatible with other fast-spiking neurons, including peripheral nerves.

And, there’s an Oct. 15, 2015 Stanford University news release on EurkeAlert describing this work from another perspective,

The heart of the technique is a two-ply plastic construct: the top layer creates a sensing mechanism and the bottom layer acts as the circuit to transport electrical signals and translate them into biochemical stimuli compatible with nerve cells. The top layer in the new work featured a sensor that can detect pressure over the same range as human skin, from a light finger tap to a firm handshake.

Five years ago, Bao’s [Zhenan Bao, a professor of chemical engineering at Stanford,] team members first described how to use plastics and rubbers as pressure sensors by measuring the natural springiness of their molecular structures. They then increased this natural pressure sensitivity by indenting a waffle pattern into the thin plastic, which further compresses the plastic’s molecular springs.

To exploit this pressure-sensing capability electronically, the team scattered billions of carbon nanotubes through the waffled plastic. Putting pressure on the plastic squeezes the nanotubes closer together and enables them to conduct electricity.

This allowed the plastic sensor to mimic human skin, which transmits pressure information as short pulses of electricity, similar to Morse code, to the brain. Increasing pressure on the waffled nanotubes squeezes them even closer together, allowing more electricity to flow through the sensor, and those varied impulses are sent as short pulses to the sensing mechanism. Remove pressure, and the flow of pulses relaxes, indicating light touch. Remove all pressure and the pulses cease entirely.

The team then hooked this pressure-sensing mechanism to the second ply of their artificial skin, a flexible electronic circuit that could carry pulses of electricity to nerve cells.

Importing the signal

Bao’s team has been developing flexible electronics that can bend without breaking. For this project, team members worked with researchers from PARC, a Xerox company, which has a technology that uses an inkjet printer to deposit flexible circuits onto plastic. Covering a large surface is important to making artificial skin practical, and the PARC collaboration offered that prospect.

Finally the team had to prove that the electronic signal could be recognized by a biological neuron. It did this by adapting a technique developed by Karl Deisseroth, a fellow professor of bioengineering at Stanford who pioneered a field that combines genetics and optics, called optogenetics. Researchers bioengineer cells to make them sensitive to specific frequencies of light, then use light pulses to switch cells, or the processes being carried on inside them, on and off.

For this experiment the team members engineered a line of neurons to simulate a portion of the human nervous system. They translated the electronic pressure signals from the artificial skin into light pulses, which activated the neurons, proving that the artificial skin could generate a sensory output compatible with nerve cells.

Optogenetics was only used as an experimental proof of concept, Bao said, and other methods of stimulating nerves are likely to be used in real prosthetic devices. Bao’s team has already worked with Bianxiao Cui, an associate professor of chemistry at Stanford, to show that direct stimulation of neurons with electrical pulses is possible.

Bao’s team envisions developing different sensors to replicate, for instance, the ability to distinguish corduroy versus silk, or a cold glass of water from a hot cup of coffee. This will take time. There are six types of biological sensing mechanisms in the human hand, and the experiment described in Science reports success in just one of them.

But the current two-ply approach means the team can add sensations as it develops new mechanisms. And the inkjet printing fabrication process suggests how a network of sensors could be deposited over a flexible layer and folded over a prosthetic hand.

“We have a lot of work to take this from experimental to practical applications,” Bao said. “But after spending many years in this work, I now see a clear path where we can take our artificial skin.”

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

A skin-inspired organic digital mechanoreceptor by Benjamin C.-K. Tee, Alex Chortos, Andre Berndt, Amanda Kim Nguyen, Ariane Tom, Allister McGuire, Ziliang Carter Lin, Kevin Tien, Won-Gyu Bae, Huiliang Wang, Ping Mei, Ho-Hsiu Chou, Bianxiao Cui, Karl Deisseroth, Tse Nga Ng, & Zhenan Bao. Science 16 October 2015 Vol. 350 no. 6258 pp. 313-316 DOI: 10.1126/science.aaa9306

This paper is behind a paywall.

‘Touching’ infrared light, if you’re a rat followed by announcement of US FDA approval of first commercial artificial retina (bionic eye)

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Researcher Miguel Nicolelis and his colleagues at Duke University have implanted a neuroprosthetic device in the portion of a rat’s brain related to touch that allows the rats to see infrared light. From the Feb. 12, 2013 news release on EurekAlert,

Researchers have given rats the ability to “touch” infrared light, normally invisible to them, by fitting them with an infrared detector wired to microscopic electrodes implanted in the part of the mammalian brain that processes tactile information. The achievement represents the first time a brain-machine interface has augmented a sense in adult animals, said Duke University neurobiologist Miguel Nicolelis, who led the research team.

The experiment also demonstrated for the first time that a novel sensory input could be processed by a cortical region specialized in another sense without “hijacking” the function of this brain area said Nicolelis. This discovery suggests, for example, that a person whose visual cortex was damaged could regain sight through a neuroprosthesis implanted in another cortical region, he said.

Although the initial experiments tested only whether rats could detect infrared light, there seems no reason that these animals in the future could not be given full-fledged infrared vision, said Nicolelis. For that matter, cortical neuroprostheses could be developed to give animals or humans the ability to see in any region of the electromagnetic spectrum, or even magnetic fields. “We could create devices sensitive to any physical energy,” he said. “It could be magnetic fields, radio waves, or ultrasound. We chose infrared initially because it didn’t interfere with our electrophysiological recordings.”

Interestingly, the research was supported by the US National Institute of Mental Health (as per the news release).

The researchers have more to say about what they’re doing,

“The philosophy of the field of brain-machine interfaces has until now been to attempt to restore a motor function lost to lesion or damage of the central nervous system,” said Thomson, [Eric Thomson] first author of the study. “This is the first paper in which a neuroprosthetic device was used to augment function—literally enabling a normal animal to acquire a sixth sense.”

Here’s how they conducted the research,

The mammalian retina is blind to infrared light, and mammals cannot detect any heat generated by the weak infrared light used in the studies. In their experiments, the researchers used a test chamber that contained three light sources that could be switched on randomly. Using visible LED lights, they first taught each rat to choose the active light source by poking its nose into an attached port to receive a reward of a sip of water.

After training the rats, the researchers implanted in their brains an array of stimulating microelectrodes, each roughly a tenth the diameter of a human hair. The microelectrodes were implanted in the cortical region that processes touch information from the animals’ facial whiskers.

Attached to the microelectrodes was an infrared detector affixed to the animals’ foreheads. The system was programmed so that orientation toward an infrared light would trigger an electrical signal to the brain. The signal pulses increased in frequency with the intensity and proximity of the light.

The researchers returned the animals to the test chamber, gradually replacing the visible lights with infrared lights. At first in infrared trials, when a light was switched on the animals would tend to poke randomly at the reward ports and scratch at their faces, said Nicolelis. This indicated that they were initially interpreting the brain signals as touch. However, over about a month, the animals learned to associate the brain signal with the infrared source. They began to actively “forage” for the signal, sweeping their heads back and forth to guide themselves to the active light source. Ultimately, they achieved a near-perfect score in tracking and identifying the correct location of the infrared light source.

To ensure that the animals were really using the infrared detector and not their eyes to sense the infrared light, the researchers conducted trials in which the light switched on, but the detector sent no signal to the brain. In these trials, the rats did not react to the infrared light.

Their finding could have an impact on notions of mammalian brain plasticity,

A key finding, said Nicolelis, was that enlisting the touch cortex for light detection did not reduce its ability to process touch signals. “When we recorded signals from the touch cortex of these animals, we found that although the cells had begun responding to infrared light, they continued to respond to whisker touch. It was almost like the cortex was dividing itself evenly so that the neurons could process both types of information.

This finding of brain plasticity is in contrast with the “optogenetic” approach to brain stimulation, which holds that a particular neuronal cell type should be stimulated to generate a desired neurological function. Rather, said Nicolelis, the experiments demonstrate that a broad electrical stimulation, which recruits many distinct cell types, can drive a cortical region to adapt to a new source of sensory input.

All of this work is part of Nicolelis’ larger project ‘Walk Again’ which is mentioned in my March 16, 2012 posting and includes a reference to some ethical issues raised by the work. Briefly, Nicolelis and an international team of collaborators are developing a brain-machine interface that will enable full mobility for people who are severely paralyzed. From the news release,

The Walk Again Project has recently received a $20 million grant from FINEP, a Brazilian research funding agency to allow the development of the first brain-controlled whole body exoskeleton aimed at restoring mobility in severely paralyzed patients. A first demonstration of this technology is expected to happen in the opening game of the 2014 Soccer World Cup in Brazil.

Expanding sensory abilities could also enable a new type of feedback loop to improve the speed and accuracy of such exoskeletons, said Nicolelis. For example, while researchers are now seeking to use tactile feedback to allow patients to feel the movements produced by such “robotic vests,” the feedback could also be in the form of a radio signal or infrared light that would give the person information on the exoskeleton limb’s position and encounter with objects.

There’s more information including videos about the work with infrared light and rats at the Nicolelis Lab website.  Here’s a citation for and link to the team’s research paper,

Perceiving invisible light through a somatosensory cortical prosthesis by Eric E. Thomson, Rafael Carra, & Miguel A.L. Nicolelis. Nature Communications Published 12 Feb 2013 DOI: 10.1038/ncomms2497

Meanwhile, the US Food and Drug Administraton (FDA) has approved the first commercial artificial retina, from the Feb. 14, 2013 news release,

The U.S. Food and Drug Administration (FDA) granted market approval to an artificial retina technology today, the first bionic eye to be approved for patients in the United States. The prosthetic technology was developed in part with support from the National Science Foundation (NSF).

The device, called the Argus® II Retinal Prosthesis System, transmits images from a small, eye-glass-mounted camera wirelessly to a microelectrode array implanted on a patient’s damaged retina. The array sends electrical signals via the optic nerve, and the brain interprets a visual image.

The FDA approval currently applies to individuals who have lost sight as a result of severe to profound retinitis pigmentosa (RP), an ailment that affects one in every 4,000 Americans. The implant allows some individuals with RP, who are completely blind, to locate objects, detect movement, improve orientation and mobility skills and discern shapes such as large letters.

The Argus II is manufactured by, and will be distributed by, Second Sight Medical Products of Sylmar, Calif., which is part of the team of scientists and engineers from the university, federal and private sectors who spent nearly two decades developing the system with public and private investment.

Scientists are often compelled to do research in an area inspired by family,

“Seeing my grandmother go blind motivated me to pursue ophthalmology and biomedical engineering to develop a treatment for patients for whom there was no foreseeable cure,” says the technology’s co-developer, Mark Humayun, associate director of research at the Doheny Eye Institute at the University of Southern California and director of the NSF Engineering Research Center for Biomimetic MicroElectronic Systems (BMES). …”

There’s also been considerable government investment,

The effort by Humayun and his colleagues has received early and continuing support from NSF, the National Institutes of Health and the Department of Energy, with grants totaling more than $100 million. The private sector’s support nearly matched that of the federal government.

“The retinal implant exemplifies how NSF grants for high-risk, fundamental research can directly result in ground-breaking technologies decades later,” said Acting NSF Assistant Director for Engineering Kesh Narayanan. “In collaboration with the Second Sight team and the courageous patients who volunteered to have experimental surgery to implant the first-generation devices, the researchers of NSF’s Biomimetic MicroElectronic Systems Engineering Research Center are developing technologies that may ultimately have as profound an impact on blindness as the cochlear implant has had for hearing loss.”

Leaving aside controversies about cochlear implants and the possibility of such controversies with artificial retinas (bionic eyes), it’s interesting to note that this device is dependent on an external camera,

The researchers’ efforts have bridged cellular biology–necessary for understanding how to stimulate the retinal ganglion cells without permanent damage–with microelectronics, which led to the miniaturized, low-power integrated chip for performing signal conversion, conditioning and stimulation functions. The hardware was paired with software processing and tuning algorithms that convert visual imagery to stimulation signals, and the entire system had to be incorporated within hermetically sealed packaging that allowed the electronics to operate in the vitreous fluid of the eye indefinitely. Finally, the research team had to develop new surgical techniques in order to integrate the device with the body, ensuring accurate placement of the stimulation electrodes on the retina.

“The artificial retina is a great engineering challenge under the interdisciplinary constraint of biology, enabling technology, regulatory compliance, as well as sophisticated design science,” adds Liu.  [Wentai Liu of the University of California, Los Angeles] “The artificial retina provides an interface between biotic and abiotic systems. Its unique design characteristics rely on system-level optimization, rather than the more common practice of component optimization, to achieve miniaturization and integration. Using the most advanced semiconductor technology, the engine for the artificial retina is a ‘system on a chip’ of mixed voltages and mixed analog-digital design, which provides self-contained power and data management and other functionality. This design for the artificial retina facilitates both surgical procedures and regulatory compliance.”

The Argus II design consists of an external video camera system matched to the implanted retinal stimulator, which contains a microelectrode array that spans 20 degrees of visual field. [emphasis mine] …

“The external camera system-built into a pair of glasses-streams video to a belt-worn computer, which converts the video into stimulus commands for the implant,” says Weiland [USC researcher Jim Weiland], “The belt-worn computer encodes the commands into a wireless signal that is transmitted to the implant, which has the necessary electronics to receive and decode both wireless power and data. Based on those data, the implant stimulates the retina with small electrical pulses. The electronics are hermetically packaged and the electrical stimulus is delivered to the retina via a microelectrode array.”

You can see some footage of people using artificial retinas in the context of Grégoire Cosendai’s TEDx Vienna presentation. As I noted in my Aug. 18, 2011 posting where this talk and developments in human enhancement are mentioned, the relevant material can be seen at approximately 13 mins., 25 secs. in Cosendai’s talk.

Second Sight Medical Devices can be found here.