Tag Archives: brain

Locusts inspire new aerosol-based nanoparticle drug delivery system

Getting medication directly to the brain is a worldwide medical research goal and it seems that a team of scientists at the Washington University at St. Louis (WUSTL) has taken a step forward to accomplishing the goal. From an April 12, 2017 news item on ScienceDaily,

Delivering life-saving drugs directly to the brain in a safe and effective way is a challenge for medical providers. One key reason: the blood-brain barrier, which protects the brain from tissue-specific drug delivery. Methods such as an injection or a pill aren’t as precise or immediate as doctors might prefer, and ensuring delivery right to the brain often requires invasive, risky techniques.

A team of engineers from Washington University in St. Louis has developed a new nanoparticle generation-delivery method that could someday vastly improve drug delivery to the brain, making it as simple as a sniff.

“This would be a nanoparticle nasal spray, and the delivery system could allow a therapeutic dose of medicine to reach the brain within 30 minutes to one hour,” said Ramesh Raliya, research scientist at the School of Engineering & Applied Science.

Caption: Engineers at Washington University have discovered a new technique that could change drug delivery to the brain. They were able to apply a nanoparticle aerosol spray to the antenna of locusts, then track the nanoparticles as they traveled through the olfactory nerves, crossed the blood-brain barrier and accumulated in the brain. This new, non-invasive approach could someday make drug delivery as simple as a sniff for patients with brain injuries or tumors.

Credit: Washington University in St. Louis

An April 12, 2017 WUSTL news release by Erika Ebsworth-Goold (also on EurekAlert), which originated the news item, describes the work in more detail,

“The blood-brain barrier protects the brain from foreign substances in the blood that may injure the brain,” Raliya said. “But when we need to deliver something there, getting through that barrier is difficult and invasive. Our non-invasive technique can deliver drugs via nanoparticles, so there’s less risk and better response times.”

The novel approach is based on aerosol science and engineering principles that allow the generation of monodisperse nanoparticles, which can deposit on upper regions of the nasal cavity via diffusion. Working with Assistant Vice Chancellor Pratim Biswas, chair of the Department of Energy, Environmental & Chemical Engineering and the Lucy & Stanley Lopata Professor, Raliya developed an aerosol consisting of gold nanoparticles of controlled size, shape and surface charge. The nanoparticles were tagged with fluorescent markers, allowing the researchers to track their movement.

Next, Raliya and biomedical engineering postdoctoral fellow Debajit Saha exposed locusts’ antennae to the aerosol, and observed the nanoparticles travel from the antennas up through the olfactory nerves. Due to their tiny size, the nanoparticles passed through the brain-blood barrier, reaching the brain and suffusing it in a matter of minutes.

The team tested the concept in locusts because the blood-brain barriers in the insects and humans have anatomical similarities, and the researchers consider going through the nasal regions to neural pathways as the optimal way to access the brain.

“The shortest and possibly the easiest path to the brain is through your nose,” said Barani Raman, associate professor of biomedical engineering. “Your nose, the olfactory bulb and then olfactory cortex: two relays and you’ve reached the cortex. The same is true for invertebrate olfactory circuitry, although the latter is a relatively simpler system, with supraesophageal ganglion instead of an olfactory bulb and cortex.”

To determine whether or not the foreign nanoparticles disrupted normal brain function, Saha examined the physiological response of olfactory neurons in the locusts before and after the nanoparticle delivery. Several hours after the nanoparticle uptake, no noticeable change in the electrophysiological responses was detected.

“This is only a beginning of a cool set of studies that can be performed to make nanoparticle-based drug delivery approaches more principled,” Raman said.

The next phase of research involves fusing the gold nanoparticles with various medicines, and using ultrasound to target a more precise dose to specific areas of the brain, which would be especially beneficial in brain-tumor cases.

“We want to drug target delivery within the brain using this non-invasive approach,” Raliya said.  “In the case of a brain tumor, we hope to use focused ultrasound so we can guide the particles to collect at that particular point.”

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

Non-invasive aerosol delivery and transport of gold nanoparticles to the brain by Ramesh Raliya, Debajit Saha, Tandeep S. Chadha, Baranidharan Raman, & Pratim Biswas. Scientific Reports 7, Article number: 44718 (2017) doi:10.1038/srep44718 Published online: 16 March 2017

This paper is open access.

I featured another team working on delivering drugs directly to the brain via the olfactory system, except their nanoparticles were gelatin and they were testing stroke medication on rats, in my Sept. 24, 2014 posting.

Poetry and the brain

It seems poetry goes deep into the brain. A Feb. 17, 2017 news item on ScienceDaily describes some blended poetry/brain research,

In 1932 T.S. Eliot famously argued, “Genuine poetry can communicate before it is understood.”

In a recent article published in the journal Frontiers in Psychology, Professor Guillaume Thierry and colleagues at Bangor University [Maine, US] have demonstrated that we do indeed appear to have an unconscious appreciation of poetic construction.

A Feb. 20, 2017 Frontiers (publications) blog posting, which despite the publication date appears to have originated the news item, provides more detail,

“Poetry,” explains Professor Thierry “is a particular type of literary expression that conveys feelings, thoughts and ideas by accentuating metric constraints, rhyme and alliteration.”

However, can we appreciate the musical sound of poetry independent of its literary meaning?

To address this question the authors created sentence sample sets that either conformed or violated poetic construction rules of Cynghanedd — a traditional form of Welsh poetry. These sentences were randomly presented to study participants; all of whom were native welsh speakers but had no prior knowledge of Cynghanedd poetic form.

Initially participants were asked to rate sentences as either “good” or “not good” depending on whether or not they found them aesthetically pleasing to the ear. The study revealed that the participants’ brains implicitly categorized Cyngahanedd-orthodox sentences as sounding “good” compared to sentences violating its construction rules.

The authors also mapped Event-Related Brain Potential (ERP) in participants a fraction of a second after they heard the final word in a poetic construction. These elegant results reveal an electrophysiological response in the brain when participants were exposed to consonantal repetition and stress patterns that are characteristic of Cynghanedd, but not when such patterns were violated.

Interestingly the positive responses from the brain to Cynghanedd were present even though participants could not explicitly tell which of the sentences were correct and which featured errors of rhythm or sound repetitions.

Professor Thierry concludes, “It is the first time that we show unconscious processing of poetic constructs by the brain, and of course, it is extremely exciting to think that one can inspire the human mind without being noticed!”

So when you read a poem, if you feel something special but you cannot really pinpoint what it is, make no mistake, your brain loves it even if you don’t really know why.

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

Implicit Detection of Poetic Harmony by the Naïve Brain by Awel Vaughan-Evans, Robat Trefor, Llion Jones, Peredur Lynch, Manon W. Jones, and Guillaume Thierry. Front. Psychol., 25 November 2016 | https://doi.org/10.3389/fpsyg.2016.01859

This paper has been published in an open access. journal.

While I appreciate the enthusiasm, I think it might be better to do more research before making grand statements about poetry and the brain. For example, are they positive these native Welsh speakers had never ever encountered the poetic form being studied? Would a French or Farsi or Mandarin or Russian or … speaker respond the same way to a poem from their own poetic traditions? Is the effect cross cultural? Does a translation make a difference? Are there only certain poetic forms that create the effect?  I look forward to hearing more about this research in the years to come.

Using melanin in bioelectronic devices

Brazilian researchers are working with melanin to make biosensors and other bioelectronic devices according to a Dec. 20, 2016 news item on phys.org,

Bioelectronics, sometimes called the next medical frontier, is a research field that combines electronics and biology to develop miniaturized implantable devices capable of altering and controlling electrical signals in the human body. Large corporations are increasingly interested: a joint venture in the field has recently been announced by Alphabet, Google’s parent company, and pharmaceutical giant GlaxoSmithKline (GSK).

One of the challenges that scientists face in developing bioelectronic devices is identifying and finding ways to use materials that conduct not only electrons but also ions, as most communication and other processes in the human organism use ionic biosignals (e.g., neurotransmitters). In addition, the materials must be biocompatible.

Resolving this challenge is one of the motivations for researchers at São Paulo State University’s School of Sciences (FC-UNESP) at Bauru in Brazil. They have succeeded in developing a novel route to more rapidly synthesize and to enable the use of melanin, a polymeric compound that pigments the skin, eyes and hair of mammals and is considered one of the most promising materials for use in miniaturized implantable devices such as biosensors.

A Dec. 14, 2016 FAPESP (São Paulo Research Foundation) press release, which originated the news item, further describes both the research and a recent meeting where the research was shared (Note: A link has been removed),

Some of the group’s research findings were presented at FAPESP Week Montevideo during a round-table session on materials science and engineering.

The symposium was organized by the Montevideo Group Association of Universities (AUGM), Uruguay’s University of the Republic (UdelaR) and FAPESP and took place on November 17-18 at UdelaR’s campus in Montevideo. Its purpose was to strengthen existing collaborations and establish new partnerships among South American scientists in a range of knowledge areas. Researchers and leaders of institutions in Uruguay, Brazil, Argentina, Chile and Paraguay attended the meeting.

“All the materials that have been tested to date for applications in bioelectronics are entirely synthetic,” said Carlos Frederico de Oliveira Graeff, a professor at UNESP Bauru and principal investigator for the project, in an interview given to Agência FAPESP.

“One of the great advantages of melanin is that it’s a totally natural compound and biocompatible with the human body: hence its potential use in electronic devices that interface with brain neurons, for example.”

Application challenges

According to Graeff, the challenges of using melanin as a material for the development of bioelectronic devices include the fact that like other carbon-based materials, such as graphene, melanin is not easily dispersible in an aqueous medium, a characteristic that hinders its application in thin-film production.

Furthermore, the conventional process for synthesizing melanin is complex: several steps are hard to control, it can last up to 56 days, and it can result in disorderly structures.

In a series of studies performed in recent years at the Center for Research and Development of Functional Materials (CDFM), where Graeff is a leading researcher and which is one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP, he and his collaborators managed to obtain biosynthetic melanin with good dispersion in water and a strong resemblance to natural melanin using a novel synthesis route.

The process developed by the group at CDMF takes only a few hours and is based on changes in parameters such as temperature and the application of oxygen pressure to promote oxidation of the material.

By applying oxygen pressure, the researchers were able to increase the density of carboxyl groups, which are organic functional groups consisting of a carbon atom double bonded to an oxygen atom and single bonded to a hydroxyl group (oxygen + hydrogen). This enhances solubility and facilitates the suspension of biosynthetic melanin in water.

“The production of thin films of melanin with high homogeneity and quality is made far easier by these characteristics,” Graeff said.

By increasing the density of carboxyl groups, the researchers were also able to make biosynthetic melanin more similar to the biological compound.

In living organisms, an enzyme that participates in the synthesis of melanin facilitates the production of carboxylic acids. The new melanin synthesis route enabled the researchers to mimic the role of this enzyme chemically while increasing carboxyl group density.

“We’ve succeeded in obtaining a material that’s very close to biological melanin by chemical synthesis and in producing high-quality film for use in bioelectronic devices,” Graeff said.

Through collaboration with colleagues at research institutions in Canada [emphasis mine], the Brazilian researchers have begun using the material in a series of applications, including electrical contacts, pH sensors and photovoltaic cells.

More recently, they have embarked on an attempt to develop a transistor, a semiconductor device used to amplify or switch electronic signals and electrical power.

“Above all, we aim to produce transistors precisely in order to enhance this coupling of electronics with biological systems,” Graeff said.

I’m glad to have gotten some information about the work in South America. It’s one of FrogHeart’s shortcomings that I have so little about the research in that area of the world. I believe this is largely due to my lack of Spanish language skills. Perhaps one day there’ll be a universal translator that works well. In the meantime, it was a surprise to see Canada mentioned in this piece. I wonder which Canadian research institutions are involved with this research in South America.

Electrochemical measurements of biomolecules

This work comes from Finland and features some new nano shapes. From a Nov. 10, 2016 news item on phys.org,

Tomi Laurila’s research topic has many quirky names.

“Nanodiamond, nanohorn, nano-onion…,” lists off the Aalto University Professor, recounting the many nano-shapes of carbon. Laurila is using these shapes to build new materials: tiny sensors, only a few hundred nanometres across, that can achieve great things due to their special characteristics.

For one, the sensors can be used to enhance the treatment of neurological conditions. That is why Laurila, University of Helsinki Professor Tomi Taira and experts from HUS (the Hospital District of Helsinki and Uusimaa) are looking for ways to use the sensors for taking electrochemical measurements of biomolecules. Biomolecules are e.g. neurotransmitters such as glutamate, dopamine and opioids, which are used by nerve cells to communicate with each other.

A Nov. 10, 2016 Aalto University press release, which originated the news item, expands on the theme,

Most of the drugs meant for treating neurological diseases change the communication between nerve cells that is based on neurotransmitters. If we had real time and individual information on the operation of the neurotransmitter system, it would make it much easier to for example plan precise treatments’, explains Taira.

Due to their small size, carbon sensors can be taken directly next to a nerve cell, where the sensors will report what kind of neurotransmitter the cell is emitting and what kind of reaction it is inducing in other cells.

‘In practice, we are measuring the electrons that are moving in oxidation and reduction reactions’, Laurila explains the operating principle of the sensors.

‘The advantage of the sensors developed by Tomi and the others is their speed and small size. The probes used in current measurement methods can be compared to logs on a cellular scale – it’s impossible to use them and get an idea of the brain’s dynamic’, summarizes Taira.

Feedback system and memory traces

For the sensors, the journey from in vitro tests conducted in glass dishes and test tubes to in vivo tests and clinical use is long. However, the researchers are highly motivated.

‘About 165 million people are suffering from various neurological diseases in Europe alone. And because they are so expensive to treat, neurological diseases make up as much as 80 per cent of health care costs’, tells Taira.

Tomi Laurila believes that carbon sensors will have applications in fields such as optogenetics. Optogenetics is a recently developed method where a light-sensitive molecule is brought into a nerve cell so that the cell’s electric operation can then be turned on or off by stimulating it with light. A few years ago, a group of scientists proved in the scientific journal Nature that they had managed to use optogenetics to activate a memory trace that had been created previously due to learning. Using the same technique, researchers were able to demonstrate that with a certain type of Alzheimer’s, the problem is not that there are no memory traces being created, but that the brain cannot read the traces.

‘So the traces exist, and they can be activated by boosting them with light stimuli’, explains Taira but stresses that a clinical application is not yet a reality. However, clinical applications for other conditions may be closer by. One example is Parkinson’s disease. In Parkinson’s disease, the amount of dopamine starts to decrease in the cells of a particular brain section, which causes the typical symptoms such as tremors, rigidity and slowness of movement. With the sensors, the level of dopamine could be monitored in real time.

‘A sort of feedback system could be connected to it, so that it would react by giving an electric or optical stimulus to the cells, which would in turn release more dopamine’, envisions Taira.

‘Another application that would have an immediate clinical use is monitoring unconscious and comatose patients. With these patients, the level of glutamate fluctuates very much, and too much glutamate damages the nerve cell – online monitoring would therefore improve their treatment significantly.

Atom by atom

Manufacturing carbon sensors is definitely not a mass production process; it is slow and meticulous handiwork.

‘At this stage, the sensors are practically being built atom by atom’, summarises Tomi Laurila.

‘Luckily, we have many experts on carbon materials of our own. For example, the nanobuds of Professor Esko Kauppinen and the carbon films of Professor Jari Koskinen help with the manufacturing of the sensors. Carbon-based materials are mainly very compatible with the human body, but there is still little information about them. That’s why a big part of the work is to go through the electrochemical characterisation that has been done on different forms of carbon.’

The sensors are being developed and tested by experts from various fields, such as chemistry, materials science, modelling, medicine and imaging. Twenty or so articles have been published on the basic properties of the materials. Now, the challenge is to build them into geometries that are functional in a physiological environment. And taking measurements is not simple, either.

‘Brain tissue is delicate and doesn’t appreciate having objects being inserted in it. But if this were easy, someone would’ve already done it’, conclude the two.

I wish the researchers good luck.

Getting your brain cells to glow in the dark

The extraordinary effort to colonize our brains continues apace with a new sensor from Vanderbilt University. From an Oct. 27, 2016 news item on ScienceDaily,

A new kind of bioluminescent sensor causes individual brain cells to imitate fireflies and glow in the dark.

The probe, which was developed by a team of Vanderbilt scientists, is a genetically modified form of luciferase, the enzyme that a number of other species including fireflies use to produce light. …

The scientists created the technique as a new and improved method for tracking the interactions within large neural networks in the brain.

“For a long time neuroscientists relied on electrical techniques for recording the activity of neurons. These are very good at monitoring individual neurons but are limited to small numbers of neurons. The new wave is to use optical techniques to record the activity of hundreds of neurons at the same time,” said Carl Johnson, Stevenson Professor of Biological Sciences, who headed the effort.

Individual neuron glowing with bioluminescent light produced by a new genetically engineered sensor. (Johnson Lab / Vanderbilt University)

Individual neuron glowing with bioluminescent light produced by a new genetically engineered sensor. (Johnson Lab / Vanderbilt University)

An Oct. 27, 2016 Vanderbilt University news release (also on EurekAlert) by David Salisbury, which originated the news item, explains the work in more detail,

“Most of the efforts in optical recording use fluorescence, but this requires a strong external light source which can cause the tissue to heat up and can interfere with some biological processes, particularly those that are light sensitive,” he [Carl Johnson] said.

Based on their research on bioluminescence in “a scummy little organism, the green alga Chlamydomonas, that nobody cares much about” Johnson and his colleagues realized that if they could combine luminescence with optogenetics – a new biological technique that uses light to control cells, particularly neurons, in living tissue – they could create a powerful new tool for studying brain activity.

“There is an inherent conflict between fluorescent techniques and optogenetics. The light required to produce the fluorescence interferes with the light required to control the cells,” said Johnson. “Luminescence, on the other hand, works in the dark!”

Johnson and his collaborators – Associate Professor Donna Webb, Research Assistant Professor Shuqun Shi, post-doctoral student Jie Yang and doctoral student Derrick Cumberbatch in biological sciences and Professor Danny Winder and postdoctoral student Samuel Centanni in molecular physiology and biophysics – genetically modified a type of luciferase obtained from a luminescent species of shrimp so that it would light up when exposed to calcium ions. Then they hijacked a virus that infects neurons and attached it to their sensor molecule so that the sensors are inserted into the cell interior.

The researchers picked calcium ions because they are involved in neuron activation. Although calcium levels are high in the surrounding area, normally they are very low inside the neurons. However, the internal calcium level spikes briefly when a neuron receives an impulse from one of its neighbors.

They tested their new calcium sensor with one of the optogenetic probes (channelrhodopsin) that causes the calcium ion channels in the neuron’s outer membrane to open, flooding the cell with calcium. Using neurons grown in culture they found that the luminescent enzyme reacted visibly to the influx of calcium produced when the probe was stimulated by brief light flashes of visible light.

To determine how well their sensor works with larger numbers of neurons, they inserted it into brain slices from the mouse hippocampus that contain thousands of neurons. In this case they flooded the slices with an increased concentration of potassium ions, which causes the cell’s ion channels to open. Again, they found that the sensor responded to the variations in calcium concentrations by brightening and dimming.

“We’ve shown that the approach works,” Johnson said. “Now we have to determine how sensitive it is. We have some indications that it is sensitive enough to detect the firing of individual neurons, but we have to run more tests to determine if it actually has this capability.”

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

Coupling optogenetic stimulation with NanoLuc-based luminescence (BRET) Ca++ sensing by Jie Yang, Derrick Cumberbatch, Samuel Centanni, Shu-qun Shi, Danny Winder, Donna Webb, & Carl Hirschie Johnson. Nature Communications 7, Article number: 13268 (2016)  doi:10.1038/ncomms13268 Published online: 27 October 2016

This paper is open access.

Stretchy optical materials for implants that could pulse light

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.

A guide to producing transparent electronics

A blue light shines through a clear, implantable medical sensor onto a brain model. See-through sensors, which have been developed by a team of UW–Madison engineers, should help neural researchers better view brain activity. Credit: Justin Williams research group

A blue light shines through a clear, implantable medical sensor onto a brain model. See-through sensors, which have been developed by a team of UW–Madison engineers, should help neural researchers better view brain activity. Credit: Justin Williams research group

Read this Oct. 13, 2016 news item on ScienceDaily if you want to find out how to make your own transparent electronics,

When University of Wisconsin-Madison engineers announced in the journal Nature Communications that they had developed transparent sensors for use in imaging the brain, researchers around the world took notice.

Then the requests came flooding in. “So many research groups started asking us for these devices that we couldn’t keep up,” says Zhenqiang (Jack) Ma, the Lynn H. Matthias Professor and Vilas Distinguished Achievement Professor in electrical and computer engineering at UW-Madison.

As a result, in a paper published in the journal Nature Protocols, the researchers have described in great detail how to fabricate and use transparent graphene neural electrode arrays in applications in electrophysiology, fluorescent microscopy, optical coherence tomography, and optogenetics. “We described how to do these things so we can start working on the next generation,” says Ma.

Although he and collaborator Justin Williams, the Vilas Distinguished Achievement Professor in biomedical engineering and neurological surgery at UW-Madison, patented the technology through the Wisconsin Alumni Research Foundation, they saw its potential for advancements in research. “That little step has already resulted in an explosion of research in this field,” says Williams. “We didn’t want to keep this technology in our lab. We wanted to share it and expand the boundaries of its applications.”

An Oct. 13, 2016 University of Wisconsin-Madison news release, which originated the news item, provides more detail about the paper and the researchers,

‘This paper is a gateway for other groups to explore the huge potential from here,’ says Ma. ‘Our technology demonstrates one of the key in vivo applications of graphene. We expect more revolutionary research will follow in this interdisciplinary field.’

Ma’s group is a world leader in developing revolutionary flexible electronic devices. The see-through, implantable micro-electrode arrays were light years beyond anything ever created.

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

Fabrication and utility of a transparent graphene neural electrode array for electrophysiology, in vivo imaging, and optogenetics by Dong-Wook Park, Sarah K Brodnick, Jared P Ness, Farid Atry, Lisa Krugner-Higby, Amelia Sandberg, Solomon Mikael, Thomas J Richner, Joseph Novello, Hyungsoo Kim, Dong-Hyun Baek, Jihye Bong, Seth T Frye, Sanitta Thongpang, Kyle I Swanson, Wendell Lake, Ramin Pashaie, Justin C Williams, & Zhenqiang Ma. Nature Protocols 11, 2201–2222 (2016) doi:10.1038/nprot.2016.127 Published online 13 October 2016

Of course this paper is open access. The team’s previous paper published in 2014 was featured here in an Oct. 23, 2014 posting.

The memristor as the ‘missing link’ in bioelectronic medicine?

The last time I featured memrisors and a neuronal network it was in an April 22, 2016 posting about Russian research in that field. This latest work comes from the UK’s University of Southampton. From a Sept. 27, 2016 news item on phys.org,

New research, led by the University of Southampton, has demonstrated that a nanoscale device, called a memristor, could be the ‘missing link’ in the development of implants that use electrical signals from the brain to help treat medical conditions.

Monitoring neuronal cell activity is fundamental to neuroscience and the development of neuroprosthetics – biomedically engineered devices that are driven by neural activity. However, a persistent problem is the device being able to process the neural data in real-time, which imposes restrictive requirements on bandwidth, energy and computation capacity.

In a new study, published in Nature Communications, the researchers showed that memristors could provide real-time processing of neuronal signals (spiking events) leading to efficient data compression and the potential to develop more precise and affordable neuroprosthetics and bioelectronic medicines.

A Sept. 27, 2016 University of Southampton press release, which originated the news item, expands on the theme,

Memristors are electrical components that limit or regulate the flow of electrical current in a circuit and can remember the amount of charge that was flowing through it and retain the data, even when the power is turned off.

Lead author Isha Gupta, Postgraduate Research Student at the University of Southampton, said: “Our work can significantly contribute towards further enhancing the understanding of neuroscience, developing neuroprosthetics and bio-electronic medicines by building tools essential for interpreting the big data in a more effective way.”

The research team developed a nanoscale Memristive Integrating Sensor (MIS) into which they fed a series of voltage-time samples, which replicated neuronal electrical activity.

Acting like synapses in the brain, the metal-oxide MIS was able to encode and compress (up to 200 times) neuronal spiking activity recorded by multi-electrode arrays. Besides addressing the bandwidth constraints, this approach was also very power efficient – the power needed per recording channel was up to 100 times less when compared to current best practice.

Co-author Dr Themis Prodromakis, Reader in Nanoelectronics and EPSRC Fellow in Electronics and Computer Science at the University of Southampton said: “We are thrilled that we succeeded in demonstrating that these emerging nanoscale devices, despite being rather simple in architecture, possess ultra-rich dynamics that can be harnessed beyond the obvious memory applications to address the fundamental constraints in bandwidth and power that currently prohibit scaling neural interfaces beyond 1,000 recording channels.”

The Prodromakis Group at the University of Southampton is acknowledged as world-leading in this field, collaborating among others with Leon Chua (a Diamond Jubilee Visiting Academic at the University of Southampton), who theoretically predicted the existence of memristors in 1971.

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

Real-time encoding and compression of neuronal spikes by metal-oxide memristors by Isha Gupta, Alexantrou Serb, Ali Khiat, Ralf Zeitler, Stefano Vassanelli, & Themistoklis Prodromakis. Nature Communications 7, Article number: 12805 doi:10.1038/ncomms12805 Published  26 September 2016

This is an open access paper.

For anyone who’s interested in better understanding memristors, there’s an interview with Forrest H Bennett III in my April 7, 2010 posting and you can always check Wikipedia.

A bionic hybrid neurochip from the University of Calgary (Canada)

The University of Calgary is publishing some very exciting work these days as can be seen in my Sept. 21, 2016 posting about quantum teleportation. Today, the university announced this via an Oct. 26, 2016 news item on Nanowerk (Note: A link has been removed),

Brain functions are controlled by millions of brain cells. However, in order to understand how the brain controls functions, such as simple reflexes or learning and memory, we must be able to record the activity of large networks and groups of neurons. Conventional methods have allowed scientists to record the activity of neurons for minutes, but a new technology, developed by University of Calgary researchers, known as a bionic hybrid neuro chip, is able to record activity in animal brain cells for weeks at a much higher resolution. The technological advancement was published in the journal Scientific Reports(“A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording”).

There’s more from an Oct. 26, 2016 University of Calgary news release on EurekAlert, which originated the news item,

“These chips are 15 times more sensitive than conventional neuro chips,” says Naweed Syed, PhD, scientific director of the University of Calgary, Cumming School of Medicine’s Alberta Children’s Hospital Research Institute, member of the Hotchkiss Brain Institute and senior author on the study. “This allows brain cell signals to be amplified more easily and to see real time recordings of brain cell activity at a resolution that has never been achieved before.”

The development of this technology will allow researchers to investigate and understand in greater depth, in animal models, the origins of neurological diseases and conditions such as epilepsy, as well as other cognitive functions such as learning and memory.

“Recording this activity over a long period of time allows you to see changes that occur over time, in the activity itself,” says Pierre Wijdenes, a PhD student in the Biomedical Engineering Graduate Program and the study’s first author. “This helps to understand why certain neurons form connections with each other and why others won’t.”

The cross-faculty team created the chip to mimic the natural biological contact between brain cells, essentially tricking the brain cells into believing that they are connecting with other brain cells. As a result, the cells immediately connect with the chip, thereby allowing researchers to view and record the two-way communication that would go on between two normal functioning brain cells.

“We simulated what mother-nature does in nature and provided brain cells with an environment where they feel as if they are at home,” says Syed. “This has allowed us to increase the sensitivity of our readings and help neurons build a long-term relationship with our electronic chip.”

While the chip is currently used to analyze animal brain cells, this increased resolution and the ability to make long-term recordings is bringing the technology one step closer to being effective in the recording of human brain cell activity.

“Human brain cell signals are smaller and therefore require more sensitive electronic tools to be designed to pick up the signals,” says Colin Dalton, Adjunct Professor in the Department of Electrical and Computer Engineering at the Schulich School of Engineering and a co-author on this study. Dalton is also the Facility Manager of the University of Calgary’s Advanced Micro/nanosystems Integration Facility (AMIF), where the chips were designed and fabricated.

Researchers hope the technology will one day be used as a tool to bring personalized therapeutic options to patients facing neurological disease.

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

A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording by Pierre Wijdenes, Hasan Ali, Ryden Armstrong, Wali Zaidi, Colin Dalton & Naweed I. Syed. Scientific Reports 6, Article number: 34553 (2016) doi:10.1038/srep34553
Published online: 12 October 2016

This paper is  open access.