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Blocking pain by turning off specific neurons with light

Optogenetic inhibition of neurons (credit: McGovern Institute for Brain Research/MIT)

McGill University researchers have discovered an effective alternative to pain medication (such as the opiate percocet that Prince was reportedly taking): optogenetics — using light to control cells (such as neurons) in living tissue.

The scientists bred mice that were genetically engineered, causing specific peripheral neurons responsible for pain transmission to express an opsin (light-sensitive protein). (See Optogenetics switch turns neurons on and off and Controlling pain by optogenetic stimulation of the brain’s pain center.)

Shining yellow light on skin above those modified Nav 1.8+ nociceptor neurons (in the hind paw) caused them to shut off, decreasing the mouse’s sensitivity to pain (from touch and heat).* The duration of the effect could be controlled by the amount of time the light was applied.

Hope for pain relief in humans

Further advances in neuroscience are necessary to apply this method of pain relief to humans, according to professor Philippe Séguéla, a researcher at the Montreal Neurological Institute and Hospital and the article’s senior author. Séguéla says one possible way to make human neurons photosensitive would be through the use of a harmless virus that could be injected, as needed, to temporarily deliver opsins to specific neurons, without causing side effects.

Opiates are the most commonly used treatment for chronic pain today, but they are often used systemically and not directed to the specific region of the body affected by the pain. The duration of the opiate effects can also not be accurate estimated, compared to the precision with a beam of light.

It is estimated that between 26.4 million and 36 million people abuse opioids worldwide, with an estimated 2.1 million people in the U.S. suffering from substance-use disorders related to prescription opioid pain relievers in 2012 and an estimated 467,000 addicted to heroin, according to the NIH National Institute on Drug Abuse.

The research, published in an open-access paper in the journal eNeuro, was funded by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council, the Quebec Pain Research Network, and the Louise and Alan Edwards Foundation.

* Q: What is the maximum transdermal penetration depth for yellow light, and based on that, which types of peripheral neurons could potentially be treated effectively without light-induced trauma?

A: We don’t have an accurate measurement of the depth of light penetration in the skin, however, we can say that yellow light reaches the different layers of the epidermis and likely the superficial part of the dermis. Light intensity decreases exponentially as it enter the skin, but at the light intensities we used, it should be sufficient to reach the terminals of various sensory neurons. Sensory neurons (except proprioceptors) innervate the skin, and their endings terminate in the dermis/epidermis of the skin. Therefore, transdermal illumination can be efficient to modulate the activity of most of these sensory fibers. The parameters of our optical stimulations (light intensity, duration of light application) are innocuous and non-invasive, hence they don’t cause any trauma. — Ihab Daou, lead author, Department of Neurology and Neurosurgery, Montreal Neurological Institute

UPDATE 4/25/2016 Added Q&A on yellow-light penetration

Abstract of Optogenetic silencing of Nav1.8-positive afferents alleviates inflammatory and neuropathic pain

We report a novel transgenic mouse model in which the terminals of peripheral nociceptors can be silenced optogenetically with high spatio-temporal precision, leading to the alleviation of inflammatory and neuropathic pain. Inhibitory archaerhodopsin-3 (Arch) proton pumps were delivered to Nav1.8+ primary afferents using the Nav1.8-Cre driver line. Arch expression covered both peptidergic and non-peptidergic nociceptors and yellow light stimulation reliably blocked electrically-induced action potentials in DRG neurons. Acute transdermal illumination of the hind paw of Nav1.8-Arch+ mice significantly reduced mechanical allodynia under inflammatory conditions, while basal mechanical sensitivity was not affected by the optical stimulation. Arch-driven hyperpolarization of nociceptive terminals was sufficient to prevent ChR2-mediated mechanical and thermal hypersensitivity in double transgenic Nav1.8-ChR2+-Arch+ mice. Furthermore, prolonged optical silencing of peripheral afferents in anesthetized Nav1.8-Arch+ mice led to post-stimulation analgesia with a significant decrease in mechanical and thermal hypersensitivity under inflammatory and neuropathic conditions. These findings highlight the role of peripheral neuronal inputs in the onset and maintenance of pain hypersensitivity, demonstrate the plasticity of pain pathways even after sensitization has occurred, and support the involvement of Nav1.8+ afferents in both inflammatory and neuropathic pain. Taken together, we present a selective analgesic approach in which genetically-identified subsets of peripheral sensory fibers can be remotely and optically inhibited with high temporal resolution, overcoming the compensatory limitations of genetic ablations.

Significance Statement: Selective activation and/or inhibition of peripheral nociceptors allow us to control pain transmission and modulate pain perception. Here, we generated a novel transgenic mouse line in which optical activation of archaerhodopsin-3 (Arch) proton pumps efficiently silenced the activity of Nav1.8+ nociceptive afferents. Acute and prolonged transdermal illumination of the hind paws of Nav1.8-Arch+ mice reduced mechanical and thermal hypersensitivity under inflammatory and neuropathic conditions, underlining the contribution of the peripheral neuronal component, particularly Nav1.8+ fibers, in the transmission of evoked pain as well as the development and maintenance of chronic pain. This optogenetic approach can be applied to functionally investigate other subsets of sensory neurons with high temporal precision, and safe genetic delivery of inhibitory opsins may prove useful for clinical applications.

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How to make the world’s fastest flexible silicon transistor

World’s fastest silicon-based flexible transistors, shown here on a plastic substrate (credit: Jung-Hun Seo/UW–Madison)

A team headed by University of Wisconsin—Madison engineers has fabricated a flexible transistor that operates at a record 38 gigahertz, but may be able to operate at 110 gigahertz.

The process could allow manufacturers to easily and cheaply fabricate high-performance transistors with wireless capabilities, using a radical fabrication method based on huge rolls of flexible plastic.

The new transistor can also transmit data or transfer power wirelessly, which could unlock advances in a whole host of applications ranging from wearable electronics to sensors.

Low-cost radical method uses less energy, achieves higher transistor density

The researchers’ nanoscale fabrication method (based on a simple, low-cost process called nanoimprint lithography) replaces conventional lithographic approaches — which use light and chemicals to pattern flexible transistors — overcoming such limitations as light diffraction, imprecision that leads to short circuits of different contacts, and the need to fabricate the circuitry in multiple passes.

The researchers — led by Zhenqiang (Jack) Ma, the Lynn H. Matthias Professor in Engineering and Vilas Distinguished Achievement Professor in electrical and computer engineering, and research scientist Jung-Hun Seo —  published details of the advance Wednesday April 20 in an open-access paper in the journal Scientific Reports.

With a unique, three-dimensional current-flow pattern, the high-performance transistor consumes less energy and operates more efficiently. And because the researchers’ method enables them to slice much narrower trenches than conventional fabrication processes can, it also could enable semiconductor manufacturers to squeeze an even greater number of transistors onto an electronic device.

Ultimately, says Ma, because the mold can be reused, the method could easily scale for use in a technology called roll-to-roll processing (think of a giant, patterned rolling pin moving across sheets of plastic the size of a tabletop), and that would allow semiconductor manufacturers to repeat their pattern and mass-fabricate many devices on a roll of flexible plastic.

“Nanoimprint lithography addresses future applications for flexible electronics,” says Ma, whose work was supported by the Air Force Office of Scientific Research. “We don’t want to make them the way the semiconductor industry does now. Our step, which is most critical for roll-to-roll printing, is ready.”

The process

  1. Using low-temperature processes, the researchers patterned the transistor circuitry using nanoimprint lithography.
  2. Using selective doping, the researchers introduced impurities into materials in precise locations to enhance their properties — in this case, electrical conductivity. Currently, the dopant sometimes merges into areas of the material it shouldn’t, causing what is known as the “short channel” effect. The researchers took an unconventional approach: They blanketed their single crystalline silicon with a dopant, rather than selectively doping it.
  3. They added a light-sensitive material, or photoresist layer, and used a technique called electron-beam lithography — which uses a focused beam of electrons to create shapes as narrow as 10 nanometers wide — on the photoresist to create a reusable mold of the nanoscale patterns they desired. They applied the mold to an ultrathin, very flexible silicon membrane to create a photoresist pattern.
  4. They finished with a dry-etching process — essentially, a nanoscale knife — that cut precise, nanometer-scale trenches in the silicon following the patterns in the mold, and added wide gates, which function as switches, atop the trenches.

Additional authors are at UW–Madison, the University of Michigan, the University of Texas at Arlington, and the University of California, Berkeley.

Abstract of Fast Flexible Transistors with a Nanotrench Structure

The simplification of fabrication processes that can define very fine patterns for large-area flexible radio-frequency (RF) applications is very desirable because it is generally very challenging to realize submicron scale patterns on flexible substrates. Conventional nanoscale patterning methods, such as e-beam lithography, cannot be easily applied to such applications. On the other hand, recent advances in nanoimprinting lithography (NIL) may enable the fabrication of large-area nanoelectronics, especially flexible RF electronics with finely defined patterns, thereby significantly broadening RF applications. Here we report a generic strategy for fabricating high-performance flexible Si nanomembrane (NM)-based RF thin-film transistors (TFTs), capable of over 100 GHz operation in theory, with NIL patterned deep-submicron-scale channel lengths. A unique 3-dimensional etched-trench-channel configuration was used to allow for TFT fabrication compatible with flexible substrates. Optimal device parameters were obtained through device simulation to understand the underlying device physics and to enhance device controllability. Experimentally, a record-breaking 38 GHz maximum oscillation frequency fmax value has been successfully demonstrated from TFTs with a 2 μm gate length built with flexible Si NM on plastic substrates.

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A battery you never have to replace

Top: Schematic diagram of all-nanowire-based capacitor (similar to a battery), using gold-manganese dioxide conductors and PMMA gel layer. Bottom: photograph of the capacitor containing 750 parallel nanowire loops patterned onto a glass microscope slide. (credit: Mya Le Thai/ACS Energy Lett.)

University of California, Irvine researchers have invented a new nanowire-based battery material that can be recharged hundreds of thousands of times, moving us closer to a battery that would never require replacement.

It could lead to commercial batteries with greatly lengthened lifespans for computers, smartphones, appliances, cars, and spacecraft.

The design is based on nanowires, which are highly conductive and feature a large surface area for the storage and transfer of electrons.

Currently, nanowires are extremely fragile and don’t hold up well to repeated discharging and recharging (cycling). In a typical lithium-ion battery, they expand and grow brittle, which leads to cracking.

UCI researchers have solved this problem by coating a gold nanowire in a manganese dioxide shell and encasing the assembly in an electrolyte made of a Plexiglas-like gel. The liquid electrolyte is replaced with a poly(methyl methacrylate) (PMMA) gel electrolyte. The combination is reliable and resistant to failure.

The study leader, UCI doctoral candidate Mya Le Thai, cycled the testing electrode up to 200,000 times over three months without detecting any loss of capacity or power and without fracturing any nanowires. The findings were published Wednesday Apr. 20 in an open-access paper in the American Chemical Society’s Energy Letters.

“Mya was playing around, and she coated this whole thing with a very thin gel layer and started to cycle it,” said senior author Reginald Penner, chair of UCI’s chemistry department. “She discovered that just by using this gel, she could cycle it hundreds of thousands of times without losing any capacity. That was crazy, because these things typically die in dramatic fashion after 5,000 or 6,000 or 7,000 cycles at most.”

The researchers think the gel plasticizes the metal oxide in the battery and gives it flexibility, preventing cracking.

“The coated electrode holds its shape much better, making it a more reliable option,” Thai said. “This research proves that a nanowire-based battery electrode can have a long lifetime and that we can make these kinds of batteries a reality.”

Abstract of 100k Cycles and Beyond: Extraordinary Cycle Stability for MnO2 Nanowires Imparted by a Gel Electrolyte

We demonstrate reversible cycle stability for up to 200 000 cycles with 94–96% average Coulombic efficiency for symmetrical δ-MnO2 nanowire capacitors operating across a 1.2 V voltage window in a poly(methyl methacrylate) (PMMA) gel electrolyte. The nanowires investigated here have a Au@δ-MnO2 core@shell architecture in which a central gold nanowire current collector is surrounded by an electrodeposited layer of δ-MnO2 that has a thickness of between 143 and 300 nm. Identical capacitors operating in the absence of PMMA (propylene carbonate (PC), 1.0 M LiClO4) show dramatically reduced cycle stabilities ranging from 2000 to 8000 cycles. In the liquid PC electrolyte, the δ-MnO2 shell fractures, delaminates, and separates from the gold nanowire current collector. These deleterious processes are not observed in the PMMA electrolyte.

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You can now be identified by your ‘brainprint’ with 100% accuracy

(credit: Jonathan Cohen/Binghamton University)

Binghamton University researchers have developed a biometric identification method called Cognitive Event-RElated Biometric REcognition (CEREBRE) for identifying an individual’s unique “brainprint.” They recorded the brain activity of 50 subjects wearing an electroencephalograph (EEG) headset while looking at selected images from a set of 500 images.

The researchers found that participants’ brains reacted uniquely to each image — enough so that a computer system that analyzed the different reactions was able to identify each volunteer’s “brainprint” with 100 percent accuracy.

In their original brainprint study in 2015, published in Neurocomputing (see ‘Brainprints’ could replace passwords), the research team was able to identify one person out of a group of 32 by that person’s responses, with 97 percent accuracy. That study only used words. Switching to images made a huge difference.

High-security sites

It’s only a three-point difference, but going from 97 to 100 percent makes possible a reliable system for high-security situations, such as “ensuring the person going into the Pentagon or the nuclear launch bay is the right person,” said Assistant Professor of Psychology Sarah Laszlo. “You don’t want to be 97 percent accurate for that, you want to be 100 percent accurate.”

Laszlo says brain biometrics are appealing because they can be cancelled (meaning the person can simple do another EEG session) and cannot be imitated or stolen by malicious means, the way a finger or retina can (as in the movie Minority Report).

“If someone’s fingerprint is stolen, that person can’t just grow a new finger to replace the compromised fingerprint — the fingerprint for that person is compromised forever. Fingerprints are ‘non-cancellable.’ Brainprints, on the other hand, are potentially cancellable. So, in the unlikely event that attackers were actually able to steal a brainprint from an authorized user, the authorized user could then ‘reset’ their brainprint,” Laszlo explained.

Analyzing “event-related potential” brain signals 

Reference ERPs (originally recorded from the subject) and challenge ERPs (the ERP response detected from the subject being tested, which must match the reference ERP to verify it’s the same person) from two representative participants in the experiment, in response to viewing a “black and white foods” image, measured over the middle occipital (Oz) channel in the brain. Notice that even by eye, it is possible to determine which challenge ERP corresponds to which reference ERP. (credit: Maria V. Ruiz-Blondet et al./IEEE Trans. Inf. Forensics Security)

The researchers found in their original study that the key to detecting differences in brain signals was to look at and analyze “event-related potential (ERP) brain signals recorded from each subject. ERPs are brain signals that are triggered by specific events (such as seeing a photo). Unlike EEG signals, ERPs are unique and happen over a period of a few milliseconds.

How ERPs are identified

The researchers used six types of stimuli in the CEREBRE protocol: sine gratings, low frequency words, color versions of black and white images, black and white foods, black and white celebrity faces, and color foods. For the foods and celebrity faces, they used ten tokens of each stimulus type (e.g., 10 different foods).

As the authors note in a new paper in The IEEE Transactions on Information Forensics and Security, “We … predict that, while ERPs elicited in response to single categories of stimulation (e.g., foods) will be somewhat identifiable, combinations of ERPs elicited in response to multiple categories of stimulation will be even more identifiable.

“This prediction is supported by the likelihood that each category of stimulation will draw upon differing (though overlapping) brain systems. For example, if the sine gratings call primarily upon the primary visual cortex, and the foods call primarily on the ventral midbrain, then considering both responses together for biometric identification provides multiple, independent, pieces of information about the user’s functional brain organization — each of which can contribute unique variability to the overall biometric solution.”

Andrew Hatling/Binghamton University | The New Biometric — Brainprint

Abstract of CEREBRE: A Novel Method for Very High Accuracy Event-Related Potential Biometric Identification

The vast majority of existing work on brain biometrics has been conducted on the ongoing electroencephalogram. Here, we argue that the averaged event-related potential (ERP) may provide the potential for more accurate biometric identification, as its elicitation allows for some control over the cognitive state of the user to be obtained through the design of the challenge protocol. We describe the Cognitive Event-RElated Biometric REcognition (CEREBRE) protocol, an ERP biometric protocol designed to elicit individually unique responses from multiple functional brain systems (e.g., the primary visual, facial recognition, and gustatory/appetitive systems). Results indicate that there are multiple configurations of data collected with the CEREBRE protocol that all allow 100% identification accuracy in a pool of 50 users. We take this result as the evidence that ERP biometrics are a feasible method of user identification and worthy of further research.

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Scientists shoot anticancer drugs deep into tumors

Schematic of a magnetic microbubble used in the study, containing gas core (blue) and shell of magnetic iron-oxide nanoparticles (red) that form a dense shell (center) around drug-containing nanoparticles. When stimulated by ultrasound at resonant frequencies, the microbubbles explode, releasing the nanoparticles, which can travel hundreds of micrometers into tumor tissue to deliver anticancer drugs and can also be imaged on an MRI machine. (credit: Yu Gao et al./NPG Asia Materials)

Scientists at Nanyang Technological University (NTU Singapore) have invented a new way to deliver cancer drugs deep into tumor cells.

They created micro-sized gas bubbles coated with anticancer drug particles embedded in iron oxide nanoparticles and used MRI or other magnetic sources to direct these microbubbles to gather around a specific tumor. Then they used ultrasound to vibrate the microbubbles, providing the energy to direct the drug particles into a targeted kill zone in the tumor. The magnetic nanoparticles also allow for imaging in an MRI machine.

The microbubbles were successfully tested in mice and the study has been published by the Nature Publishing Group in Asia Materials.

Overcoming limitations of chemotherapy

This innovative technique was developed by a multidisciplinary team of scientists led by Asst Prof C. J. Xu from the School of Chemical and Biomedical Engineering and Assoc. Prof Claus-Dieter Ohl from the School of Physical and Mathematical Sciences.

Xu, who is also a researcher at the NTU-Northwestern Institute for Nanomedicine, said their new method may solve some of the most pressing problems faced in chemotherapy used to treat cancer.

The main problem is that current chemotherapy drugs cannot be easily targeted. The drug particles flow in the bloodstream, damaging both healthy and cancerous cells. Typically, these drugs are flushed away quickly in organs such as the lungs and liver, limiting their effectiveness.

The remaining drugs are also unable to penetrate deep into the core of the tumor, leaving some cancer cells alive, which could lead to a resurgence in tumor growth.

Delivering anticancer drugs deep into tumors

Schematic of the apparatus used to investigate magnetic microbubble oscillation and nanoparticle release (credit: Yu Gao et al./NPG Asia Materials)

The microbubbles are magnetic, so after injecting them into the bloodstream, they can be clustered around the tumor using magnets to ensure that they don’t kill the healthy cells, explains Xu, who has been working on cancer diagnosis and drug delivery systems since 2004.

“More importantly, our invention is the first of its kind that allows drug particles to be directed deep into a tumor in a few milliseconds. They can penetrate a depth of 50 cell layers or more (about 200 micrometers) — twice the width of a human hair. This helps to ensure that the drugs can reach the cancer cells on the surface and also inside the core of the tumor.”

According to Clinical Associate Professor Chia Sing Joo, a Senior Consultant at the Tan Tock Seng Hospital’s Endoscopy Centre and the Urology & Continence Clinic, “For anticancer drugs to achieve their best effectiveness, they need to penetrate into the tumor efficiently in order to reach the cytoplasm of all the cancer cells that are being targeted without affecting the normal cells.

“Currently, this can [only] be achieved by means of a direct injection into the tumor or by administering a large dosage of anticancer drugs, which can be painful, expensive, impractical and might have various side effects. If successful, I envisage [the new drug-delivery system] can be a good alternative treatment in the future, one which is low cost and yet effective for the treatment of cancers involving solid tumors, as it might minimize the side effects of drugs.” Joo is a surgeon experienced in the treatment of prostate, bladder and kidney cancer and a consultant for this study.

According to Ohl, an expert in biophysics who has published previous studies involving drug delivery systems and bubble dynamics, “most prototype drug delivery systems on the market face three main challenges before they can be commercially successful: they have to be non-invasive, patient-friendly, and yet cost-effective. We were able to come up with our solution that addresses these three challenges.”

The 12-person study team included scientists from City University of Hong Kong and Technion – Israel Institute of Technology (Technion). The team plans to use this new drug delivery system in studies on lung and liver cancer using animal models, and eventually clinical studies.

They estimate that it will take another eight to ten years before it reaches human clinical trials.

Abstract of Controlled nanoparticle release from stable magnetic microbubble oscillations

Magnetic microbubbles (MMBs) are microbubbles (MBs) coated with magnetic nanoparticles (NPs). MMBs not only maintain the acoustic properties of MBs, but also serve as an important contrast agent for magnetic resonance imaging. Such dual-modality functionality makes MMBs particularly useful for a wide range of biomedical applications, such as localized drug/gene delivery. This article reports the ability of MMBs to release their particle cargo on demand under stable oscillation. When stimulated by ultrasound at resonant frequencies, MMBs of 450 nm to 200 μm oscillate in volume and surface modes. Above an oscillation threshold, NPs are released from the MMB shell and can travel hundreds of micrometers from the surface of the bubble. The migration of NPs from MMBs can be described with a force balance model. With this technology, we deliver doxorubicin-containing poly(lactic-co-glycolic acid) particles across a physiological barrier bothin vitro and in vivo, with a 18-fold and 5-fold increase in NP delivery to the heart tissue of zebrafish and tumor tissue of mouse, respectively. The penetration of released NPs in tissues is also improved. The ability to remotely control the release of NPs from MMBs suggests opportunities for targeted drug delivery through/into tissues that are not easily diffused through or penetrated.

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Super-stretchy, self-healing material could lead to artificial muscle

This extremely stretchable polymer film can repair itself when punctured, suggesting potential applications in artificial muscle. (credit: Bao Research Group)

Stanford researchers have developed a new material that can stretch to 100 times its original length by exposing it to an electric field, and even repair itself if punctured, making it potentially useful as an artificial muscle.

Artificial muscles currently have applications in some consumer technology and robotics, but small holes or defects in the materials currently used make them less resilient, and they can’t self-repair if punctured or scratched, according to Stanford chemical engineering professor Zhenan Bao.

Self-healing

The new material (Fe-Hpdca-PDMS polymer film) has remarkable self-healing characteristics. Damaged polymers typically require a solvent or heat treatment to restore their properties, but the new material can heal itself at room temperature (even if the damaged pieces are aged for days) and at temperatures as low as negative 4 degrees Fahrenheit (-20 C).

The team attributes the extreme stretching and self-healing ability to a chemical bonding process known as crosslinking. To create it, they designed special organic molecules to attach to the short polymer strands in their crosslink to create a series of structure called ligands. These ligands joined together to form longer polymer chains (spring-like coils with inherent stretchiness).

Then they added metal ions, which have a chemical affinity for the ligands. When this combined material is strained, the knots loosen and allow the ligands to separate. But when relaxed, the affinity between the metal ions and the ligands pulls the fishnet taut. The result is a strong, stretchable and self-repairing elastomer.

The team found that they could tune the polymer to be stretchier or heal faster by varying the amount or type of metal ion included. The version that exceeded the measuring machine’s limits, for example, was created by decreasing the ratio of iron atoms to the polymers and organic molecules in the material.

Artificial skin

They have to do more work to increase the degree to which the material expands and contracts and control it more precisely.

This research dovetails with Bao’s efforts to create artificial skin that might be used to restore some sensory capabilities to people with prosthetic limbs.

This work in the development of strong, flexible, electronically active polymers could also spawn a new generation of wearable electronics, or medical implants that would last a long time without being repaired or replaced, says Bao.

The research is described in the current issue of Nature Chemistry. It was supported by the Air Force Office of Scientific Research, Samsung Electronics, and the Major State Basic Research Development Program of China.


Stanford University School of Engineering | Super-stretchy polymer could lead to artificial muscle

Abstract of A highly stretchable autonomous self-healing elastomer

It is a challenge to synthesize materials that possess the properties of biological muscles—strong, elastic and capable of self-healing. Herein we report a network of poly(dimethylsiloxane) polymer chains crosslinked by coordination complexes that combines high stretchability, high dielectric strength, autonomous self-healing and mechanical actuation. The healing process can take place at a temperature as low as −20 °C and is not significantly affected by surface ageing and moisture. The crosslinking complexes used consist of 2,6-pyridinedicarboxamide ligands that coordinate to Fe(III) centres through three different interactions: a strong pyridyl–iron one, and two weaker carboxamido–iron ones through both the nitrogen and oxygen atoms of the carboxamide groups. As a result, the iron–ligand bonds can readily break and re-form while the iron centres still remain attached to the ligands through the stronger interaction with the pyridyl ring, which enables reversible unfolding and refolding of the chains. We hypothesize that this behaviour supports the high stretchability and self-healing capability of the material.

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Ultrathin organic material enhances e-skin displays

Top left: System outline of a blood oxygen level monitor. Top right: Red and green polymer light-emitting diodes (PLEDs) are directed to shine into the finger. Reflected light from inside the finger is caught by an ultraflexible organic photodetector. This reflected light provides a measure of blood oxygen and pulse rate. Bottom: The output of the sensor can be shown on a PLED display. (credit: Someya Laboratory)

University of Tokyo researchers have developed technology to enable creation of electronic skin (e-skin) displays of blood oxygen level, e-skin heart rate sensors for medical, athletic uses, and other applications.

To serve as a demo, they’ve created an ultrathin, ultraflexible, protective layer and created an air-stable, organic light-emitting diode (OLED) display.

For use in electronic devices integrated into the human body, wearable electronics need to be thin and flexible to minimize impact where they attach to the body.

But most devices developed so far have required millimeter-scale-thickness glass or plastic substrates with limited flexibility, and micrometer-scale thin flexible organic devices have not been stable enough to survive in air.

The research group of Professor Takao Someya and Dr. Tomoyuki Yokota at the University of Tokyo’s Graduate School of Engineering has now developed a high-quality protective film less than two micrometers thick that enables the production of ultrathin, ultraflexible, high-performance wearable electronic displays and other devices.

The group developed the protective film by alternating layers of inorganic (Silicon Oxynitrite) and organic (Parylene) material. The protective film prevented passage of oxygen and water vapor in the air, extending device lifetimes from the few hours seen in prior research to several days. In addition, the research group was able to attach transparent indium tin oxide (ITO) electrodes to an ultrathin substrate without damaging it, making the e-skin display possible.

Using the new protective layer and ITO electrodes, the research group created polymer light-emitting diodes (PLEDs) and organic photodetectors (OPDs). These were thin enough to be attached to the skin and flexible enough to distort and crumple in response to body movement.

The PLEDs were just three micrometers thick and more than six times more efficient than previously reported ultrathin PLEDs. This reduced heat generation and power consumption, making them particularly suitable for direct attachment to the body for medical applications such as displays for blood oxygen concentration or pulse rate. The research group also combined red and green PLEDs with a photodetector to demonstrate a blood oxygen sensor.

In addition to medical uses, Someya sees this technology as a kind of ultra mood ring. “The advent of mobile phones has changed the way we communicate. While these communication tools are getting smaller and smaller, they are still discrete devices that we have to carry with us,” he says. “What would the world be like if we had displays that could adhere to our bodies and even show our emotions or level of stress or unease? They might enhance the way we interact with those around us or add a whole new dimension to how we communicate.”


Someya Laboratory | The red seven-segment PLED display in operation on the back of a hand.

Abstract of Ultraflexible organic photonic skin

Thin-film electronics intimately laminated onto the skin imperceptibly equip the human body with electronic components for health-monitoring and information technologies. When electronic devices are worn, the mechanical flexibility and/or stretchability of thin-film devices helps to minimize the stress and discomfort associated with wear because of their conformability and softness. For industrial applications, it is important to fabricate wearable devices using processing methods that maximize throughput and minimize cost. We demonstrate ultraflexible and conformable three-color, highly efficient polymer light-emitting diodes (PLEDs) and organic photodetectors (OPDs) to realize optoelectronic skins (oe-skins) that introduce multiple electronic functionalities such as sensing and displays on the surface of human skin. The total thickness of the devices, including the substrate and encapsulation layer, is only 3 μm, which is one order of magnitude thinner than the epidermal layer of human skin. By integrating green and red PLEDs with OPDs, we fabricate an ultraflexible reflective pulse oximeter. The device unobtrusively measures the oxygen concentration of blood when laminated on a finger. On-skin seven-segment digital displays and color indicators can visualize data directly on the body.

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NYU Holodeck to be model for year 2041 cyberlearning

NYU-X Holodeck (credit: Winslow Burleson and Armanda Lewis)

In an open-access paper in the Journal of Artificial Intelligence Education, Winslow Burleson, PhD, MSE, associate professor, New York University Rory Meyers College of Nursing, suggests that “advanced cyberlearning environments that involve VR and AI innovations are needed to solve society’s “wicked challenges*” — entrenched and seemingly intractable societal problems.

Burleson and and co-author Armanda Lewis imagine such technology in a year 2041 Holodeck, which Burleson’s NYU-X Lab is currently developing in prototype form, in collaboration with colleagues at NYU Courant, Tandon, Steinhardt, and Tisch.

“The “Holodeck” will support a broad range of transdisciplinary collaborations, integrated education, research, and innovation by providing a networked software/hardware infrastructure that can synthesize visual, audio, physical, social, and societal components,” said Burleson.

It’s intended as a model for the future of cyberlearning experience, integrating visual, audio, and physical (haptics, objects, real-time fabrication) components, with shared computation, integrated distributed data, immersive visualization, and social interaction to make possible large-scale synthesis of learning, research, and innovation.

This reminds me of the book Education and Ecstasy, written in 1968 by George B. Leonard, a respected editor for LOOK magazine and, in many respects, a pioneer in what has become the transhumanism movement. That book laid out the justification and promise of advanced educational technology in the classroom for an entire generation. Other writers, such as Harry S. Broudy in the Real World of the Public Schools (1972) followed, arguing that we can not afford “master teachers” in every classroom, but still need to do far better, both then and now.

Today, theories and models of automated planning using computers in complex situations are advanced and “wicked” social simulations can demonstrate the “potholes” in proposed action scenarios. Virtual realties, holodecks, interactive games, robotic and/or AI assistants offer “sandboxes” for learning and for sharing that learning with others. Leonard’s vision, proposed in 1968 for the year 2000, has not yet been realized. However, by 2041, according to these authors, it just might be.

— Warren E. Lacefield, Ph.D. President/CEO Academic Software, Inc.; Associate Professor (retired), Evaluation, Measurement, and Research Program, Department of Educational Leadership, Research, and Technology, Western Michigan University (aka “Asiwel” on KurzweilAI)

Key aspects of the Holodeck: personal stories and interactive experiences that make it a rich environment; open streaming content that make it real and compelling; and contributions that personalize the learning experience. The goal is to create a networked infrastructure and communication environment where “wicked challenges” can be iteratively explored and re-solved, utilizing visual, acoustic, and physical sensory feedback, human dynamics with and social collaboration.

Burleson and Lewis envision that in 2041, learning is unlimited — each individual can create a teacher, team, community, world, galaxy or universe of their own.

* In the late 1960s, urban planners Horst Rittel and Melvin Webber began formulating the concept of “wicked problems” or “wicked challenges” –problems so vexing in the realm of social and organizational planning that they could not be successfully ameliorated with traditional linear, analytical, systems-engineering types of approaches.

These “wicked challenges” are poorly defined, abstruse, and connected to strong moral, political and professional issues.  Some examples might include: “How should we deal with crime and violence in our schools?  “How should we wage the ‘War on Terror’? or “What is good national immigration policy?”

“Wicked problems,” by their very nature, are strongly stakeholder dependent; there is often little consensus even about what the problem is, let alone how to deal with it. And, the challenges themselves are ever shifting sets of inherently complex, interacting issues evolving in a dynamic social context. Often, new forms of “wicked challenges” emerge as a result of trying to understand and treat just one challenge in isolation.

Abstract of Optimists’ Creed: Brave New Cyberlearning, Evolving Utopias (Circa 2041)

This essay imagines the role that artificial intelligence innovations play in the integrated living, learning and research environments of 2041. Here, in 2041, in the context of increasingly complex wicked challenges, whose solutions by their very nature continue to evade even the most capable experts, society and technology have co-evolved to embrace cyberlearning as an essential tool for envisioning and refining utopias–non-existent societies described in considerable detail. Our society appreciates that evolving these utopias is critical to creating and resolving wicked challenges and to better understanding how to create a world in which we are actively “learning to be” – deeply engaged in intrinsically motivating experiences that empower each of us to reach our full potential. Since 2015, Artificial Intelligence in Education (AIED) has transitioned from what was primarily a research endeavour, with educational impact involving millions of user/learners, to serving, now, as a core contributor to democratizing learning (Dewey 2004) and active citizenship for all (billions of learners throughout their lives). An expansive experiential super computing cyberlearning environment, we affectionately call the “Holodeck,” supports transdisciplinary collaboration and integrated education, research, and innovation, providing a networked software/hardware infrastructure that synthesizes visual, audio, physical, social, and societal components. The Holodeck’s large-scale integration of learning, research, and innovation, through real-world problem solving and teaching others what you have learned, effectively creates a global meritocratic network with the potential to resolve society’s wicked challenges while empowering every citizen to realize her or his full potential.

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Quadriplegic man is first to regain use of hand and fingers

Ian Burkhart, who is paralyzed, playing a guitar video game, made possible by a new neural bypass system. (credit: The Ohio State Wexner Medical Center and Battelle)

Battelle and The Ohio State University Wexner Medical Center have developed and surgically implanted the first neural bypass for spinal cord injuries that reconnects the brain to muscles, allowing voluntary and functional control of a paralyzed limb by using a patient’s thoughts — no robotic prosthetic arm required.

Ian Burkhart, a 24-year-old quadriplegic injured in a diving accident, is the first person to experience “limb reanimation,” thanks to this neural bypass system, called “NeuroLife.”

The Battelle team has been developing this technology for more than a decade. Battelle scientists first recorded neural impulses from an electrode array* implanted in a paralyzed person’s brain. They used that recorded data to illustrate and test the device’s effect on the patient and prove the concept.

How the neural bypass system works. Left: Injury to spinal cord at C7 blocks signals from the motor cortex from reaching the arm. Right: 96 implanted microelectrodes pick up motor-cortex signals and send to a computer, whose algorithms learn and decode hand and finger movement thoughts, converting them to electrical signals that then activate an electrical stimulation sleeve, which stimulates matching neurons in the patient’s wrist to trigger hand and finger movements. (credit: The Ohio State Wexner Medical Center and Battelle)

The Ohio State and Battelle teams worked together to figure out the correct sequence of electrodes to stimulate to allow Burkhart to move his fingers and hand functionally. Burkhart can now perform sophisticated movements with his hands and fingers, such as picking up a spoon, swiping a credit card, or picking up and holding a phone to his ear. For example, he uses different brain signals and muscles to rotate his hand, make a fist, or pinch his fingers together to grasp an object. (He retained some functionality in his right shoulder and bicep.)

Burkhart swiping a credit card (credit: The Ohio State Wexner Medical Center and Battelle)

“It’s amazing to see what he’s accomplished,” said Nick Annetta, electrical engineering lead for Battelle’s team on the project. “Ian can grasp a bottle, pour the contents of the bottle into a jar and put the bottle back down. Then he takes a stir bar, grips that and then stirs the contents of the jar that he just poured and puts it back down. He’s controlling it every step of the way.”

The neural bypass technology combines computer algorithms that learn and decode the user’s brain activity and a high-definition muscle stimulation sleeve that triggers neurons in the hand and finger.

Neural bypass system experimental setup and neural modulation. (a) Red regions are brain areas most active during attempts to mimic hand movements, as indicated by fMRI (functional magnetic imaging resonance) contrast. The implanted microelectrode array location from post-operation computed tomography is shown in green; The overlap of the red and green regions is shown in yellow. (b) Neuromuscular electrical stimulation sleeve. (c) Neural bypass system learning to match patient’s thoughts (about hand activity shown on computer monitor) to specific activation patterns in the electrical stimulation sleeve. (credit: Chad E. Bouton et al./Nature)

“In the 30 years I’ve been in this field, this is the first time we’ve been able to offer realistic hope to people who have very challenging lives,” said Jerry Mysiw, M.D., chair of the Department of Physical Medicine and Rehabilitation at Ohio State. “What we’re looking to do is help these people regain more control over their bodies.”

Burkhart is the first of a potential five participants in a clinical study. The researchers say this technology promises to help patients affected by various brain and spinal cord injuries such as strokes and traumatic brain injury to be more independent and functional.

Regrettably, Burkhart will not be able to take the system home when funding runs out this year, but the researchers hope to evolve the technology into a wireless system and make it readily available to be used by patients at home.

The research was published online in the journal Nature on April 13.


OSU Wexner Medical Center | Man Uses His Own Brainwaves To Retrain His Paralyzed Hand


Nature Video | The nerve bypass: how to move a paralysed hand

* Widely reported as a “computer chip” (based on an inaccurate statement in the Ohio State press release).

Abstract of Restoring cortical control of functional movement in a human with quadriplegia

Millions of people worldwide suffer from diseases that lead to paralysis through disruption of signal pathways between the brain and the muscles. Neuroprosthetic devices are designed to restore lost function and could be used to form an electronic ‘neural bypass’ to circumvent disconnected pathways in the nervous system. It has previously been shown that intracortically recorded signals can be decoded to extract information related to motion, allowing non-human primates and paralysed humans to control computers and robotic arms through imagined movements. In non-human primates, these types of signal have also been used to drive activation of chemically paralysed arm muscles. Here we show that intracortically recorded signals can be linked in real-time to muscle activation to restore movement in a paralysed human. We used a chronically implanted intracortical microelectrode array to record multiunit activity from the motor cortex in a study participant with quadriplegia from cervical spinal cord injury. We applied machine-learning algorithms to decode the neuronal activity and control activation of the participant’s forearm muscles through a custom-built high-resolution neuromuscular electrical stimulation system. The system provided isolated finger movements and the participant achieved continuous cortical control of six different wrist and hand motions. Furthermore, he was able to use the system to complete functional tasks relevant to daily living. Clinical assessment showed that, when using the system, his motor impairment improved from the fifth to the sixth cervical (C5–C6) to the seventh cervical to first thoracic (C7–T1) level unilaterally, conferring on him the critical abilities to grasp, manipulate, and release objects. This is the first demonstration to our knowledge of successful control of muscle activation using intracortically recorded signals in a paralysed human. These results have significant implications in advancing neuroprosthetic technology for people worldwide living with the effects of paralysis.