Category Archives: medicine

Detecting peanut allergies with nanoparticles

Researchers at Notre Dame University are designing a platform that will make allergy detection easier and more precise according to a June 26, 2017 news item on phys.org,

Researchers have developed a novel platform to more accurately detect and identify the presence and severity of peanut allergies, without directly exposing patients to the allergen, according to a new study published in the journal Scientific Reports.

A team of chemical and biomolecular engineers at the University of Notre Dame designed nanoparticles that mimic natural allergens by displaying each allergic component one at a time on their surfaces. The researchers named the nanoparticles “nanoallergens” and used them to dissect the critical components of major peanut allergy proteins and evaluate the potency of the allergic response using the antibodies present in a blood sample from a patient.

“The goal of this study was to show how nanoallergen technology could be used to provide a clearer and more accurate assessment of the severity of an allergic condition,” said Basar Bilgicer, associate professor of chemical and biomolecular engineering and a member of the Advanced Diagnostics and Therapeutics initiative at Notre Dame. “We are currently working with allergy specialist clinicians for further testing and verification of the diagnostic tool using a larger patient population. Ultimately, our vision is to take this technology and make it available to all people who suffer from food allergies.”

A June 26, 2017 University of Notre Dame news release, which originated the news item, explains the need for better allergy detection,

Food allergies are a growing problem in developing countries and are of particular concern to parents. According to the study, 8 percent of children under the age of 4 have a food allergy. Bilgicer said a need exists for more accurate testing, improved diagnostics and better treatment options.

Current food allergy testing methods carry risks or fail to provide detailed information on the severity of the allergic response. For instance, a test known as the oral food challenge requires exposing a patient to increasing amounts of a suspected allergen. Patients must remain under close observation in clinics with highly trained specialists. The test is stopped only when the patient exhibits an extreme allergic response, such as anaphylactic shock. Doctors then treat the reaction with epinephrine injections, antihistamines and steroids.

The skin prick test, another common diagnostic tool, can indicate whether a patient is allergic to a particular food. However, it provides no detail on the severity of those allergies.

During skin prick testing, doctors place a drop of liquid containing the allergen on the patient’s skin, typically on their back, and then scratch the skin to expose the patient. Skin irritations, such as redness, itching and white bumps, are indications that the patient has an allergy.

“Most of the time, parents of children with food allergies are not inclined to have their child go through such excruciating experiences of a food challenge,” Bilgicer said. “Rather than investigate the severity of the allergy, they respond to it with most extreme caution and complete avoidance of the allergen. Meanwhile, there are cases where the skin prick test might have yielded a positive result for a child, and yet the child can consume a handful of the allergen and demonstrate no signs of any allergic response.”

While the study focused on peanut allergens, Bilgicer said he and his team are working on testing the platform on additional allergens and allergic conditions.

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

Determination of Crucial Immunogenic Epitopes in Major Peanut Allergy Protein, Ara h2, via Novel Nanoallergen Platform by Peter E. Deak, Maura R. Vrabel, Tanyel Kiziltepe & Basar Bilgicer. Scientific Reports 7, Article number: 3981 (2017) doi:10.1038/s41598-017-04268-6 Published online: 21 June 2017

This paper is open access.

Carbon nanotubes to repair nerve fibres (cyborg brains?)

Can cyborg brains be far behind now that researchers are looking at ways to repair nerve fibers with carbon nanotubes (CNTs)? A June 26, 2017 news item on ScienceDaily describes the scheme using carbon nanotubes as a material for repairing nerve fibers,

Carbon nanotubes exhibit interesting characteristics rendering them particularly suited to the construction of special hybrid devices — consisting of biological issue and synthetic material — planned to re-establish connections between nerve cells, for instance at spinal level, lost on account of lesions or trauma. This is the result of a piece of research published on the scientific journal Nanomedicine: Nanotechnology, Biology, and Medicine conducted by a multi-disciplinary team comprising SISSA (International School for Advanced Studies), the University of Trieste, ELETTRA Sincrotrone and two Spanish institutions, Basque Foundation for Science and CIC BiomaGUNE. More specifically, researchers have investigated the possible effects on neurons of the interaction with carbon nanotubes. Scientists have proven that these nanomaterials may regulate the formation of synapses, specialized structures through which the nerve cells communicate, and modulate biological mechanisms, such as the growth of neurons, as part of a self-regulating process. This result, which shows the extent to which the integration between nerve cells and these synthetic structures is stable and efficient, highlights the great potentialities of carbon nanotubes as innovative materials capable of facilitating neuronal regeneration or in order to create a kind of artificial bridge between groups of neurons whose connection has been interrupted. In vivo testing has actually already begun.

The researchers have included a gorgeous image to illustrate their work,

Caption: Scientists have proven that these nanomaterials may regulate the formation of synapses, specialized structures through which the nerve cells communicate, and modulate biological mechanisms, such as the growth of neurons, as part of a self-regulating process. Credit: Pixabay

A June 26, 2017 SISSA press release (also on EurekAlert), which originated the news item, describes the work in more detail while explaining future research needs,

“Interface systems, or, more in general, neuronal prostheses, that enable an effective re-establishment of these connections are under active investigation” explain Laura Ballerini (SISSA) and Maurizio Prato (UniTS-CIC BiomaGUNE), coordinating the research project. “The perfect material to build these neural interfaces does not exist, yet the carbon nanotubes we are working on have already proved to have great potentialities. After all, nanomaterials currently represent our best hope for developing innovative strategies in the treatment of spinal cord injuries”. These nanomaterials are used both as scaffolds, a supportive framework for nerve cells, and as means of interfaces releasing those signals that empower nerve cells to communicate with each other.

Many aspects, however, still need to be addressed. Among them, the impact on neuronal physiology of the integration of these nanometric structures with the cell membrane. “Studying the interaction between these two elements is crucial, as it might also lead to some undesired effects, which we ought to exclude”. Laura Ballerini explains: “If, for example, the mere contact provoked a vertiginous rise in the number of synapses, these materials would be essentially unusable”. “This”, Maurizio Prato adds, “is precisely what we have investigated in this study where we used pure carbon nanotubes”.

The results of the research are extremely encouraging: “First of all we have proved that nanotubes do not interfere with the composition of lipids, of cholesterol in particular, which make up the cellular membrane in neurons. Membrane lipids play a very important role in the transmission of signals through the synapses. Nanotubes do not seem to influence this process, which is very important”.

There is more, however. The research has also highlighted the fact that the nerve cells growing on the substratum of nanotubes, thanks to this interaction, develop and reach maturity very quickly, eventually reaching a condition of biological homeostasis. “Nanotubes facilitate the full growth of neurons and the formation of new synapses. This growth, however, is not indiscriminate and unlimited since, as we proved, after a few weeks a physiological balance is attained. Having established the fact that this interaction is stable and efficient is an aspect of fundamental importance”. Maurizio Prato and Laura Ballerini conclude as follows: “We are proving that carbon nanotubes perform excellently in terms of duration, adaptability and mechanical compatibility with the tissue. Now we know that their interaction with the biological material, too, is efficient. Based on this evidence, we are already studying the in vivo application, and preliminary results appear to be quite promising also in terms of recovery of the lost neurological functions”.

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

Sculpting neurotransmission during synaptic development by 2D nanostructured interfaces by Niccolò Paolo Pampaloni, Denis Scaini, Fabio Perissinotto, Susanna Bosi, Maurizio Prato, Laura Ballerini. Nanomedicine: Nanotechnology, Biology and Medicine, DOI: http://dx.doi.org/10.1016/j.nano.2017.01.020 Published online: May 25, 2017

This paper is open access.

Brain stuff: quantum entanglement and a multi-dimensional universe

I have two brain news bits, one about neural networks and quantum entanglement and another about how the brain operates on more than three dimensions.

Quantum entanglement and neural networks

A June 13, 2017 news item on phys.org describes how machine learning can be used to solve problems in physics (Note: Links have been removed),

Machine learning, the field that’s driving a revolution in artificial intelligence, has cemented its role in modern technology. Its tools and techniques have led to rapid improvements in everything from self-driving cars and speech recognition to the digital mastery of an ancient board game.

Now, physicists are beginning to use machine learning tools to tackle a different kind of problem, one at the heart of quantum physics. In a paper published recently in Physical Review X, researchers from JQI [Joint Quantum Institute] and the Condensed Matter Theory Center (CMTC) at the University of Maryland showed that certain neural networks—abstract webs that pass information from node to node like neurons in the brain—can succinctly describe wide swathes of quantum systems.

An artist’s rendering of a neural network with two layers. At the top is a real quantum system, like atoms in an optical lattice. Below is a network of hidden neurons that capture their interactions (Credit: E. Edwards/JQI)

A June 12, 2017 JQI news release by Chris Cesare, which originated the news item, describes how neural networks can represent quantum entanglement,

Dongling Deng, a JQI Postdoctoral Fellow who is a member of CMTC and the paper’s first author, says that researchers who use computers to study quantum systems might benefit from the simple descriptions that neural networks provide. “If we want to numerically tackle some quantum problem,” Deng says, “we first need to find an efficient representation.”

On paper and, more importantly, on computers, physicists have many ways of representing quantum systems. Typically these representations comprise lists of numbers describing the likelihood that a system will be found in different quantum states. But it becomes difficult to extract properties or predictions from a digital description as the number of quantum particles grows, and the prevailing wisdom has been that entanglement—an exotic quantum connection between particles—plays a key role in thwarting simple representations.

The neural networks used by Deng and his collaborators—CMTC Director and JQI Fellow Sankar Das Sarma and Fudan University physicist and former JQI Postdoctoral Fellow Xiaopeng Li—can efficiently represent quantum systems that harbor lots of entanglement, a surprising improvement over prior methods.

What’s more, the new results go beyond mere representation. “This research is unique in that it does not just provide an efficient representation of highly entangled quantum states,” Das Sarma says. “It is a new way of solving intractable, interacting quantum many-body problems that uses machine learning tools to find exact solutions.”

Neural networks and their accompanying learning techniques powered AlphaGo, the computer program that beat some of the world’s best Go players last year (link is external) (and the top player this year (link is external)). The news excited Deng, an avid fan of the board game. Last year, around the same time as AlphaGo’s triumphs, a paper appeared that introduced the idea of using neural networks to represent quantum states (link is external), although it gave no indication of exactly how wide the tool’s reach might be. “We immediately recognized that this should be a very important paper,” Deng says, “so we put all our energy and time into studying the problem more.”

The result was a more complete account of the capabilities of certain neural networks to represent quantum states. In particular, the team studied neural networks that use two distinct groups of neurons. The first group, called the visible neurons, represents real quantum particles, like atoms in an optical lattice or ions in a chain. To account for interactions between particles, the researchers employed a second group of neurons—the hidden neurons—which link up with visible neurons. These links capture the physical interactions between real particles, and as long as the number of connections stays relatively small, the neural network description remains simple.

Specifying a number for each connection and mathematically forgetting the hidden neurons can produce a compact representation of many interesting quantum states, including states with topological characteristics and some with surprising amounts of entanglement.

Beyond its potential as a tool in numerical simulations, the new framework allowed Deng and collaborators to prove some mathematical facts about the families of quantum states represented by neural networks. For instance, neural networks with only short-range interactions—those in which each hidden neuron is only connected to a small cluster of visible neurons—have a strict limit on their total entanglement. This technical result, known as an area law, is a research pursuit of many condensed matter physicists.

These neural networks can’t capture everything, though. “They are a very restricted regime,” Deng says, adding that they don’t offer an efficient universal representation. If they did, they could be used to simulate a quantum computer with an ordinary computer, something physicists and computer scientists think is very unlikely. Still, the collection of states that they do represent efficiently, and the overlap of that collection with other representation methods, is an open problem that Deng says is ripe for further exploration.

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

Quantum Entanglement in Neural Network States by Dong-Ling Deng, Xiaopeng Li, and S. Das Sarma. Phys. Rev. X 7, 021021 – Published 11 May 2017

This paper is open access.

Blue Brain and the multidimensional universe

Blue Brain is a Swiss government brain research initiative which officially came to life in 2006 although the initial agreement between the École Politechnique Fédérale de Lausanne (EPFL) and IBM was signed in 2005 (according to the project’s Timeline page). Moving on, the project’s latest research reveals something astounding (from a June 12, 2017 Frontiers Publishing press release on EurekAlert),

For most people, it is a stretch of the imagination to understand the world in four dimensions but a new study has discovered structures in the brain with up to eleven dimensions – ground-breaking work that is beginning to reveal the brain’s deepest architectural secrets.

Using algebraic topology in a way that it has never been used before in neuroscience, a team from the Blue Brain Project has uncovered a universe of multi-dimensional geometrical structures and spaces within the networks of the brain.

The research, published today in Frontiers in Computational Neuroscience, shows that these structures arise when a group of neurons forms a clique: each neuron connects to every other neuron in the group in a very specific way that generates a precise geometric object. The more neurons there are in a clique, the higher the dimension of the geometric object.

“We found a world that we had never imagined,” says neuroscientist Henry Markram, director of Blue Brain Project and professor at the EPFL in Lausanne, Switzerland, “there are tens of millions of these objects even in a small speck of the brain, up through seven dimensions. In some networks, we even found structures with up to eleven dimensions.”

Markram suggests this may explain why it has been so hard to understand the brain. “The mathematics usually applied to study networks cannot detect the high-dimensional structures and spaces that we now see clearly.”

If 4D worlds stretch our imagination, worlds with 5, 6 or more dimensions are too complex for most of us to comprehend. This is where algebraic topology comes in: a branch of mathematics that can describe systems with any number of dimensions. The mathematicians who brought algebraic topology to the study of brain networks in the Blue Brain Project were Kathryn Hess from EPFL and Ran Levi from Aberdeen University.

“Algebraic topology is like a telescope and microscope at the same time. It can zoom into networks to find hidden structures – the trees in the forest – and see the empty spaces – the clearings – all at the same time,” explains Hess.

In 2015, Blue Brain published the first digital copy of a piece of the neocortex – the most evolved part of the brain and the seat of our sensations, actions, and consciousness. In this latest research, using algebraic topology, multiple tests were performed on the virtual brain tissue to show that the multi-dimensional brain structures discovered could never be produced by chance. Experiments were then performed on real brain tissue in the Blue Brain’s wet lab in Lausanne confirming that the earlier discoveries in the virtual tissue are biologically relevant and also suggesting that the brain constantly rewires during development to build a network with as many high-dimensional structures as possible.

When the researchers presented the virtual brain tissue with a stimulus, cliques of progressively higher dimensions assembled momentarily to enclose high-dimensional holes, that the researchers refer to as cavities. “The appearance of high-dimensional cavities when the brain is processing information means that the neurons in the network react to stimuli in an extremely organized manner,” says Levi. “It is as if the brain reacts to a stimulus by building then razing a tower of multi-dimensional blocks, starting with rods (1D), then planks (2D), then cubes (3D), and then more complex geometries with 4D, 5D, etc. The progression of activity through the brain resembles a multi-dimensional sandcastle that materializes out of the sand and then disintegrates.”

The big question these researchers are asking now is whether the intricacy of tasks we can perform depends on the complexity of the multi-dimensional “sandcastles” the brain can build. Neuroscience has also been struggling to find where the brain stores its memories. “They may be ‘hiding’ in high-dimensional cavities,” Markram speculates.

###

About Blue Brain

The aim of the Blue Brain Project, a Swiss brain initiative founded and directed by Professor Henry Markram, is to build accurate, biologically detailed digital reconstructions and simulations of the rodent brain, and ultimately, the human brain. The supercomputer-based reconstructions and simulations built by Blue Brain offer a radically new approach for understanding the multilevel structure and function of the brain. http://bluebrain.epfl.ch

About Frontiers

Frontiers is a leading community-driven open-access publisher. By taking publishing entirely online, we drive innovation with new technologies to make peer review more efficient and transparent. We provide impact metrics for articles and researchers, and merge open access publishing with a research network platform – Loop – to catalyse research dissemination, and popularize research to the public, including children. Our goal is to increase the reach and impact of research articles and their authors. Frontiers has received the ALPSP Gold Award for Innovation in Publishing in 2014. http://www.frontiersin.org.

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

Cliques of Neurons Bound into Cavities Provide a Missing Link between Structure and Function by Michael W. Reimann, Max Nolte, Martina Scolamiero, Katharine Turner, Rodrigo Perin, Giuseppe Chindemi, Paweł Dłotko, Ran Levi, Kathryn Hess, and Henry Markram. Front. Comput. Neurosci., 12 June 2017 | https://doi.org/10.3389/fncom.2017.00048

This paper is open access.

Meet Pepper, a robot for health care clinical settings

A Canadian project to introduce robots like Pepper into clinical settings (aside: can seniors’ facilities be far behind?) is the subject of a June 23, 2017 news item on phys.org,

McMaster and Ryerson universities today announced the Smart Robots for Health Communication project, a joint research initiative designed to introduce social robotics and artificial intelligence into clinical health care.

A June 22, 2017 McMaster University news release, which originated the news item, provides more detail,

With the help of Softbank’s humanoid robot Pepper and IBM Bluemix Watson Cognitive Services, the researchers will study health information exchange through a state-of-the-art human-robot interaction system. The project is a collaboration between David Harris Smith, professor in the Department of Communication Studies and Multimedia at McMaster University, Frauke Zeller, professor in the School of Professional Communication at Ryerson University and Hermenio Lima, a dermatologist and professor of medicine at McMaster’s Michael G. DeGroote School of Medicine. His main research interests are in the area of immunodermatology and technology applied to human health.

The research project involves the development and analysis of physical and virtual human-robot interactions, and has the capability to improve healthcare outcomes by helping healthcare professionals better understand patients’ behaviour.

Zeller and Harris Smith have previously worked together on hitchBOT, the friendly hitchhiking robot that travelled across Canada and has since found its new home in the [Canada] Science and Technology Museum in Ottawa.

“Pepper will help us highlight some very important aspects and motives of human behaviour and communication,” said Zeller.

Designed to be used in professional environments, Pepper is a humanoid robot that can interact with people, ‘read’ emotions, learn, move and adapt to its environment, and even recharge on its own. Pepper is able to perform facial recognition and develop individualized relationships when it interacts with people.

Lima, the clinic director, said: “We are excited to have the opportunity to potentially transform patient engagement in a clinical setting, and ultimately improve healthcare outcomes by adapting to clients’ communications needs.”

At Ryerson, Pepper was funded by the Co-lab in the Faculty of Communication and Design. FCAD’s Co-lab provides strategic leadership, technological support and acquisitions of technologies that are shaping the future of communications.

“This partnership is a testament to the collaborative nature of innovation,” said dean of FCAD, Charles Falzon. “I’m thrilled to support this multidisciplinary project that pushes the boundaries of research, and allows our faculty and students to find uses for emerging tech inside and outside the classroom.”

“This project exemplifies the value that research in the Humanities can bring to the wider world, in this case building understanding and enhancing communications in critical settings such as health care,” says McMaster’s Dean of Humanities, Ken Cruikshank.

The integration of IBM Watson cognitive computing services with the state-of-the-art social robot Pepper, offers a rich source of research potential for the projects at Ryerson and McMaster. This integration is also supported by IBM Canada and [Southern Ontario Smart Computing Innovation Platform] SOSCIP by providing the project access to high performance research computing resources and staff in Ontario.

“We see this as the initiation of an ongoing collaborative university and industry research program to develop and test applications of embodied AI, a research program that is well-positioned to integrate and apply emerging improvements in machine learning and social robotics innovations,” said Harris Smith.

I just went to a presentation at the facility where my mother lives and it was all about delivering more individualized and better care for residents. Given that most seniors in British Columbia care facilities do not receive the number of service hours per resident recommended by the province due to funding issues, it seemed a well-meaning initiative offered in the face of daunting odds against success. Now with this news, I wonder what impact ‘Pepper’ might ultimately have on seniors and on the people who currently deliver service. Of course, this assumes that researchers will be able to tackle problems with understanding various accents and communication strategies, which are strongly influenced by culture and, over time, the aging process.

After writing that last paragraph I stumbled onto this June 27, 2017 Sage Publications press release on EurekAlert about a related matter,

Existing digital technologies must be exploited to enable a paradigm shift in current healthcare delivery which focuses on tests, treatments and targets rather than the therapeutic benefits of empathy. Writing in the Journal of the Royal Society of Medicine, Dr Jeremy Howick and Dr Sian Rees of the Oxford Empathy Programme, say a new paradigm of empathy-based medicine is needed to improve patient outcomes, reduce practitioner burnout and save money.

Empathy-based medicine, they write, re-establishes relationship as the heart of healthcare. “Time pressure, conflicting priorities and bureaucracy can make practitioners less likely to express empathy. By re-establishing the clinical encounter as the heart of healthcare, and exploiting available technologies, this can change”, said Dr Howick, a Senior Researcher in Oxford University’s Nuffield Department of Primary Care Health Sciences.

Technology is already available that could reduce the burden of practitioner paperwork by gathering basic information prior to consultation, for example via email or a mobile device in the waiting room.

During the consultation, the computer screen could be placed so that both patient and clinician can see it, a help to both if needed, for example, to show infographics on risks and treatment options to aid decision-making and the joint development of a treatment plan.

Dr Howick said: “The spread of alternatives to face-to-face consultations is still in its infancy, as is our understanding of when a machine will do and when a person-to-person relationship is needed.” However, he warned, technology can also get in the way. A computer screen can become a barrier to communication rather than an aid to decision-making. “Patients and carers need to be involved in determining the need for, and designing, new technologies”, he said.

I sincerely hope that the Canadian project has taken into account some of the issues described in the ’empathy’ press release and in the article, which can be found here,

Overthrowing barriers to empathy in healthcare: empathy in the age of the Internet
by J Howick and S Rees. Journaly= of the Royal Society of Medicine Article first published online: June 27, 2017 DOI: https://doi.org/10.1177/0141076817714443

This article is open access.

Mussels to muscles for biocompatible fibres

Mussels and barnacles in the intertidal near Newquay, Cornwall, England.
Wilson44691 at English Wikipedia – Photograph taken by Mark A. Wilson (Department of Geology, The College of Wooster

I love puns and word play so I was happy to see this in a June 9, 2017 news item on ScienceDaily,

Rice University chemists can thank the mussel for putting the muscle into their new macroscale scaffold fibers.

A June 9, 2017 Rice University news release (also on EurekAlert), which originated the news item, provides more details about the research,

The Rice lab of chemist Jeffrey Hartgerink had already figured out how to make biocompatible nanofibers out of synthetic peptides. In new work, the lab is using an amino acid found in the sticky feet of mussels to make those fibers line up into strong hydrogel strings.

Hartgerink and Rice graduate student I-Che Li introduced their room-temperature method this month in an open-access paper in the Journal of the American Chemical Society.

The hydrogel strings can be picked up and moved with tweezers, and Li said he expects they will help labs gain better control over the growth of cell cultures.

“Usually when cells grow on a surface, they spread randomly,” he said. “There are a lot of biomaterials we want to grow in a specific direction. With the hydrogel scaffold aligned, we can expect cells to grow the way we want them to. One example would be neuron cells, which we want to grow head-to-tail to aid nerve regeneration.

“Basically, this could allow us to direct cell growth from here to there,” he said. “That’s why this material is so exciting.”

In previous research Hartgerink’s lab had developed synthetic hydrogels that could be injected into the body to serve as scaffolds for tissue growth. The hydrogels contained hydrophobic peptides that self-assembled into fibers about 6 nanometers wide and up to several microns long. However, because the fibers did not interact with one other, they generally appeared in microscope images as a tangled mass.

Experiments showed the fibers could be coaxed into alignment with the application of shear forces, in the same way that playing cards are aligned during shuffling by pushing on both the top and bottom of the deck.

Hartgerink and Li decided to try pushing the fibers through a needle to force them into alignment, a process that would be easier if the material was water soluble. So they added a chain of amino acids known as DOPA to the sides of the fibers to allow them to remain water-soluble in the syringe, Li said.

DOPA — short for 3,4-dihydroxyphenylalanine — is the compound that lets mussels stick to just about anything. Hartgerink and Li found that the combination of DOPA and shear stress from passing through the needle prompted the fibers to form visible, rope-like bundles.

They also found that DOPA promoted chemical cross-linking reactions that helped the bundles hold their shape. “DOPA is really sensitive to oxidizing agents,” Li said. “Even exposing DOPA to air oxidizes it, and that aids in cross-linking the fibers.”

As a bonus, the aligned fibers also proved to have a curious and useful optical property called “uniform birefringence,” or double-refraction. Li said this could allow researchers to use polarized light to see exactly where the aligned fibers are, even if they’re covered by cells.

“This will be an important technique for us to make sure of the long-range order of fiber alignment when we are testing directed cell growth,” he said.

The researchers expect the aligned fibers can be used for macroscale medical applications but with nanoscale control over the structures.

“Self-assembly is basically the ability of a molecule to make ordered structure from chaos, and what I-Che has done is push this organization to a new level with his aligned strings,” said Hartgerink, a professor of chemistry and of bioengineering. “With this material, we are excited to see if we can impose this organization onto the growth of cells that interact with it.”

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

Covalent Capture of Aligned Self-Assembling Nanofibers by I-Che Li and Jeffrey D. Hartgerink. J. Am. Chem. Soc., Article ASAP DOI: 10.1021/jacs.7b04655 Publication Date (Web): June 5, 2017

Copyright © 2017 American Chemical Society

This paper is open access.

Scientists claim off-the-shelf, power-generating clothes almost here

PEDOT-coated yarns act as “normal” wires to transmit electricity from a wall outlet to an incandescent lightbulb. Materials scientist Trisha Andrew at UMass Amherst and colleagues outline in a new paper how they have invented a way to apply breathable, pliable, metal-free electrodes to fabric and off-the-shelf clothing so it feels good to the touch and also transports electricity to power small electronics. Harvesting body motion energy generates the power. Courtesy: UMass Amherst

I’m not quite as optimistic (it’s a long way from the lab to the marketplace) as the scientists do eventually note but this does seem promising (from a May 23, 2017 news item on Nanowerk),

A lightweight, comfortable jacket that can generate the power to light up a jogger at night may sound futuristic, but materials scientist Trisha Andrew at the University of Massachusetts Amherst could make one today.

In a new paper this month, she and colleagues outline how they have invented a way to apply breathable, pliable, metal-free electrodes to fabric and off-the-shelf clothing so it feels good to the touch and also transports enough electricity to power small electronics.

A May 23, 2017 University of Massachusetts Amherst news release (also on EurekAlert), which originated the news item,

She says, “Our lab works on textile electronics. We aim to build up the materials science so you can give us any garment you want, any fabric, any weave type, and turn it into a conductor. Such conducting textiles can then be built up into sophisticated electronics. One such application is to harvest body motion energy and convert it into electricity in such a way that every time you move, it generates power.” Powering advanced fabrics that can monitor health data remotely are important to the military and increasingly valued by the health care industry, she notes.

Generating small electric currents through relative movement of layers is called triboelectric charging, explains Andrew, who trained as a polymer chemist and electrical engineer. Materials can become electrically charged as they create friction by moving against a different material, like rubbing a comb on a sweater. “By sandwiching layers of differently materials between two conducting electrodes, a few microwatts of power can be generated when we move,” she adds.

In the current early online edition of Advanced Functional Materials, she and postdoctoral researcher Lu Shuai Zhang in her lab describe the vapor deposition method they use to coat fabrics with a conducting polymer, poly(3,4-ethylenedioxytiophene) also known as PEDOT, to make plain-woven, conducting fabrics that are resistant to stretching and wear and remain stable after washing and ironing. The thickest coating they put down is about 500 nanometers, or about 1/10 the diameter of a human hair, which retains a fabric’s hand feel.

The authors report results of testing electrical conductivity, fabric stability, chemical and mechanical stability of PEDOT films and textile parameter effects on conductivity for 14 fabrics, including five cottons with different weaves, linen and silk from a craft store.

“Our article describes the materials science needed to make these robust conductors,” Andrew says. “We show them to be stable to washing, rubbing, human sweat and a lot of wear and tear.” PEDOT coating did not change the feel of any fabric as determined by touch with bare hands before and after coating. Coating did not increase fabric weight by more than 2 percent. The work was supported by the Air Force Office of Scientific Research.

Until recently, she and Zhang point out, textile scientists have tended not to use vapor deposition because of technical difficulties and high cost of scaling up from the laboratory. But over the last 10 years, industries such as carpet manufacturers and mechanical component makers have shown that the technology can be scaled up and remain cost-effective. The researchers say their invention also overcomes the obstacle of power-generating electronics mounted on plastic or cladded, veneer-like fibers that make garments heavier and/or less flexible than off-the-shelf clothing “no matter how thin or flexible these device arrays are.”

“There is strong motivation to use something that is already familiar, such as cotton/silk thread, fabrics and clothes, and imperceptibly adapting it to a new technological application.” Andrew adds, “This is a huge leap for consumer products, if you don’t have to convince people to wear something different than what they are already wearing.”

Test results were sometimes a surprise, Andrew notes. “You’d be amazed how much stress your clothes go through until you try to make a coating that will survive a shirt being pulled over the head. The stress can be huge, up to a thousand newtons of force. For comparison, one footstep is equal to about 10 newtons, so it’s yanking hard. If your coating is not stable, a single pull like that will flake it all off. That’s why we had to show that we could bend it, rub it and torture it. That is a very powerful requirement to move forward.”

Andrew is director of wearable electronics at the Center for Personalized Health Monitoring in UMass Amherst’s Institute of Applied Life Sciences (IALS). Since the basic work reported this month was completed, her lab has also made a wearable heart rate monitor with an off-the-shelf fitness bra to which they added eight monitoring electrodes. They will soon test it with volunteers on a treadmill at the IALS human movement facility.

She explains that a hospital heart rate monitor has 12 electrodes, while the wrist-worn fitness devices popular today have one, which makes them prone to false positives. They will be testing a bra with eight electrodes, alone and worn with leggings that add four more, against a control to see if sensors can match the accuracy and sensitivity of what a hospital can do. As the authors note in their paper, flexible, body-worn electronics represent a frontier of human interface devices that make advanced physiological and performance monitoring possible.

For the future, Andrew says, “We’re working on taking any garment you give us and turning it into a solar cell so that as you are walking around the sunlight that hits your clothes can be stored in a battery or be plugged in to power a small electronic device.”

Zhang and Andrew believe their vapor coating is able to stick to fabrics by a process called surface grafting, which takes advantage of free bonds dangling on the surface chemically bonding to one end of the polymer coating, but they have yet to investigate this fully.

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

Rugged Textile Electrodes for Wearable Devices Obtained by Vapor Coating Off-the-Shelf, Plain-Woven Fabrics by Lushuai Zhang, Marianne Fairbanks, and Trisha L. Andrew. Advanced Functional Materials DOI: 10.1002/adfm.201700415 Version of Record online: 2 MAY 2017

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

This paper is behind a paywall.

A t-shirt that monitors your breathing in real time

This May 18, 2017 news item on Nanowerk features research at the Université Laval (Québec, Canada), Note: A link has been removed,

Researchers at Université Laval’s Faculty of Science and Engineering and its Center for Optics, Photonics, and Lasers have created a smart T-shirt that monitors the wearer’s respiratory rate in real time.

This innovation, the details of which are published in the latest edition of Sensors (“Wearable Contactless Respiration Sensor Based on Multi-Material Fibers Integrated into Textile”), paves the way for manufacturing clothing that could be used to diagnose respiratory illnesses or monitor people suffering from asthma, sleep apnea, or chronic obstructive pulmonary disease.

A May 18, 2017 Université Laval press release, which originated the news item, provides a little more detail about the work,

Unlike other methods of measuring respiratory rate, the smart T-shirt works without any wires, electrodes, or sensors attached to the user’s body, explains Younès Messaddeq, the professor who led the team that developed the technology. “The T-shirt is really comfortable and doesn’t inhibit the subject’s natural movements. Our tests show that the data captured by the shirt is reliable, whether the user is lying down, sitting, standing, or moving around.”

The key to the smart T-shirt is an antenna sewn in at chest level that’s made of a hollow optical fiber coated with a thin layer of silver on its inner surface. The fiber’s exterior surface is covered in a polymer that protects it against the environment. “The antenna does double?duty, sensing and transmitting the signals created by respiratory movements,” adds Professor Messaddeq, who also holds the Canada Excellence Research Chair in Photonic Innovations. “The data can be sent to the user’s smartphone or a nearby computer.”

As the wearer breathes in, the smart fiber senses the increase in both thorax circumference and the volume of air in the lungs, explains Messaddeq. “These changes modify some of the resonant frequency of the antenna. That’s why the T-shirt doesn’t need to be tight or in direct contact with the wearer’s skin. The oscillations that occur with each breath are enough for the fiber to sense the user’s respiratory rate.”

To assess the durability of their invention, the researchers put a T-shirt equipped with an antenna through the wash—literally. “After 20 washes, the antenna had withstood the water and detergent and was still in good working condition,” says Messaddeq.

Protoype of the spiral antenna integrated into a cotton shirt. Inset: SEM images of the multi-material fiber structure. (© MDPI) (click on image to enlarge) Courtesy: Université Laval

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

Wearable Contactless Respiration Sensor Based on Multi-Material Fibers Integrated into Textile by Philippe Guay, Stepan Gorgutsa, Sophie LaRochelle, and Younes Messaddeq. Sensors 2017, 17(5), 1050; doi:10.3390/s17051050 (This article belongs to the Special Issue Biomedical Sensors and Systems 2017) Published: 6 May 2017

This article is open access.

A nano fabrication technique used to create next generation heart valve

I am going to have take the researchers’ word that these somehow lead to healthy heart valve tissue,

In rotary jet spinning technology, a rotating nozzle extrudes a solution of extracellular matrix (ECM) into nanofibers that wrap themselves around heart valve-shaped mandrels. By using a series of mandrels with different sizes, the manufacturing process becomes fully scalable and is able to provide JetValves for all age groups and heart sizes. Credit: Wyss Institute at Harvard University

From a May 18, 2017 news item on ScienceDaily,

The human heart beats approximately 35 million times every year, effectively pumping blood into the circulation via four different heart valves. Unfortunately, in over four million people each year, these delicate tissues malfunction due to birth defects, age-related deteriorations, and infections, causing cardiac valve disease.

Today, clinicians use either artificial prostheses or fixed animal and cadaver-sourced tissues to replace defective valves. While these prostheses can restore the function of the heart for a while, they are associated with adverse comorbidity and wear down and need to be replaced during invasive and expensive surgeries. Moreover, in children, implanted heart valve prostheses need to be replaced even more often as they cannot grow with the child.

A team lead by Kevin Kit Parker, Ph.D. at Harvard University’s Wyss Institute for Biologically Inspired Engineering recently developed a nanofiber fabrication technique to rapidly manufacture heart valves with regenerative and growth potential. In a paper published in Biomaterials, Andrew Capulli, Ph.D. and colleagues fabricated a valve-shaped nanofiber network that mimics the mechanical and chemical properties of the native valve extracellular matrix (ECM). To achieve this, the team used the Parker lab’s proprietary rotary jet spinning technology — in which a rotating nozzle extrudes an ECM solution into nanofibers that wrap themselves around heart valve-shaped mandrels. “Our setup is like a very fast cotton candy machine that can spin a range of synthetic and natural occurring materials. In this study, we used a combination of synthetic polymers and ECM proteins to fabricate biocompatible JetValves that are hemodynamically competent upon implantation and support cell migration and re-population in vitro. Importantly, we can make human-sized JetValves in minutes — much faster than possible for other regenerative prostheses,” said Parker.

A May 18,2017 Wyss Institute for Biologically Inspired Engineering news release (also on EurekAlert), which originated the news item, expands on the theme of Jetvalves,

To further develop and test the clinical potential of JetValves, Parker’s team collaborated with the translational team of Simon P. Hoerstrup, M.D., Ph.D., at the University of Zurich in Switzerland, which is a partner institution with the Wyss Institute. As a leader in regenerative heart prostheses, Hoerstrup and his team in Zurich have previously developed regenerative, tissue-engineered heart valves to replace mechanical and fixed-tissue heart valves. In Hoerstrup’s approach, human cells directly deposit a regenerative layer of complex ECM on biodegradable scaffolds shaped as heart valves and vessels. The living cells are then eliminated from the scaffolds resulting in an “off-the-shelf” human matrix-based prostheses ready for implantation.

In the paper, the cross-disciplinary team successfully implanted JetValves in sheep using a minimally invasive technique and demonstrated that the valves functioned properly in the circulation and regenerated new tissue. “In our previous studies, the cell-derived ECM-coated scaffolds could recruit cells from the receiving animal’s heart and support cell proliferation, matrix remodeling, tissue regeneration, and even animal growth. While these valves are safe and effective, their manufacturing remains complex and expensive as human cells must be cultured for a long time under heavily regulated conditions. The JetValve’s much faster manufacturing process can be a game-changer in this respect. If we can replicate these results in humans, this technology could have invaluable benefits in minimizing the number of pediatric re-operations,” said Hoerstrup.

In support of these translational efforts, the Wyss Institute for Biologically Inspired Engineering and the University of Zurich announced today a cross-institutional team effort to generate a functional heart valve replacement with the capacity for repair, regeneration, and growth. The team is also working towards a GMP-grade version of their customizable, scalable, and cost-effective manufacturing process that would enable deployment to a large patient population. In addition, the new heart valve would be compatible with minimally invasive procedures to serve both pediatric and adult patients.

The project will be led jointly by Parker and Hoerstrup. Parker is a Core Faculty member of the Wyss Institute and the Tarr Family Professor of Bioengineering and Applied Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). Hoerstrup is Chair and Director of the University of Zurich’s Institute for Regenerative Medicine (IREM), Co-Director of the recently founded Wyss Translational Center Zurich and a Wyss Institute Associate Faculty member.

Since JetValves can be manufactured in all desired shapes and sizes, and take seconds to minutes to produce, the team’s goal is to provide customized, ready-to-use, regenerative heart valves much faster and at much lower cost than currently possible.

“Achieving the goal of minimally invasive, low-cost regenerating heart valves could have tremendous impact on patients’ lives across age-, social- and geographical boundaries. Once again, our collaborative team structure that combines unique and leading expertise in bioengineering, regenerative medicine, surgical innovation and business development across the Wyss Institute and our partner institutions, makes it possible for us to advance technology development in ways not possible in a conventional academic laboratory,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at SEAS.

This scanning electron microscopy image shows how extracellular matrix (ECM) nanofibers generated with JetValve technology are arranged in parallel networks with physical properties comparable to those found in native heart tissue. Credit: Wyss Institute at Harvard University

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

JetValve: Rapid manufacturing of biohybrid scaffolds for biomimetic heart valve replacement by Andrew K. Capulli, Maximillian Y. Emmert, Francesco S. Pasqualini, b, Debora Kehl, Etem Caliskan, Johan U. Lind, Sean P. Sheehy, Sung Jin Park, Seungkuk Ahn, Benedikt Webe, Josue A. Goss. Biomaterials Volume 133, July 2017, Pages 229–241  https://doi.org/10.1016/j.biomaterials.2017.04.033

This paper is behind a paywall.

Using CRISPR to reverse retinosa pigmentosa (eye disease)

Years ago I worked as a publicist for the BC (British Columbia) Motorcycle Federation’s Ride for Sight; they were raising funds for research into retinitis pigmentosa (RP). I hadn’t thought about that in years but it all came back when I saw this April 21, 2017 news item on ScienceDaily,

Using the gene-editing tool CRISPR/Cas9, researchers at University of California San Diego [UCSD] School of Medicine and Shiley Eye Institute at UC San Diego Health, with colleagues in China, have reprogrammed mutated rod photoreceptors to become functioning cone photoreceptors, reversing cellular degeneration and restoring visual function in two mouse models of retinitis pigmentosa.

Caption: This is a confocal micrograph of mouse retina depicting optic fiber layer. Credit: Image courtesy of National Center for Microscopy and Imaging Research, UC San Diego.

An April 21, 2017 UCSD news release by Scott LaFee (also on EurekAlert), which originated the news item, delves further into retinitis pigmentosa and this CRISPR research,

Retinitis pigmentosa (RP) is a group of inherited vision disorders caused by numerous mutations in more than 60 genes. The mutations affect the eyes’ photoreceptors, specialized cells in the retina that sense and convert light images into electrical signals sent to the brain. There are two types: rod cells that function for night vision and peripheral vision, and cone cells that provide central vision (visual acuity) and discern color. The human retina typically contains 120 million rod cells and 6 million cone cells.

In RP, which affects approximately 100,000 Americans and 1 in 4,000 persons worldwide, rod-specific genetic mutations cause rod photoreceptor cells to dysfunction and degenerate over time. Initial symptoms are loss of peripheral and night vision, followed by diminished visual acuity and color perception as cone cells also begin to fail and die. There is no treatment for RP. The eventual result may be legal blindness.

In their published research, a team led by senior author Kang Zhang, MD, PhD, chief of ophthalmic genetics, founding director of the Institute for Genomic Medicine and co-director of biomaterials and tissue engineering at the Institute of Engineering in Medicine, both at UC San Diego School of Medicine, used CRISPR/Cas9 to deactivate a master switch gene called Nrl and a downstream transcription factor called Nr2e3.

CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, allows researchers to target specific stretches of genetic code and edit DNA at precise locations, modifying select gene functions. Deactivating either Nrl or Nr2e3 reprogrammed rod cells to become cone cells.

“Cone cells are less vulnerable to the genetic mutations that cause RP,” said Zhang. “Our strategy was to use gene therapy to make the underlying mutations irrelevant, resulting in the preservation of tissue and vision.”

The scientists tested their approach in two different mouse models of RP. In both cases, they found an abundance of reprogrammed cone cells and preserved cellular architecture in the retinas. Electroretinography testing of rod and cone receptors in live mice show improved function.

Zhang said a recent independent study led by Zhijian Wu, PhD, at National Eye Institute, part of the National Institutes of Health, also reached similar conclusions.

The researchers used adeno-associated virus (AAV) to perform the gene therapy, which they said should help advance their work to human clinical trials quicker. “AAV is a common cold virus and has been used in many successful gene therapy treatments with a relatively good safely profile,” said Zhang. “Human clinical trials could be planned soon after completion of preclinical study. There is no treatment for RP so the need is great and pressing. In addition, our approach of reprogramming mutation-sensitive cells to mutation-resistant cells may have broader application to other human diseases, including cancer.”

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

Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors by Jie Zhu, Chang Ming, Xin Fu, Yaou Duan, Duc Anh Hoang, Jeffrey Rutgard, Runze Zhang, Wenqiu Wang, Rui Hou, Daniel Zhang, Edward Zhang, Charlotte Zhang, Xiaoke Hao, Wenjun Xiong, and Kang Zhang. Cell Research advance online publication 21 April 2017; doi: 10.1038/cr.2017.57

This paper (it’s in the form of a letter to the editor) is open access.