Mayo Clinic researchers have used electrical stimulation of the spinal cord and intense physical therapy to help Jared Chinnock intentionally move his paralyzed legs, stand, and make steplike motions for the first time in three years. The chronic traumatic paraplegia case marks the first time a patient has intentionally controlled previously paralyzed functions within the first two weeks of stimulation.
The case was documented April 3, 2017 in an open-access paper in Mayo Clinic Proceedings. The researchers say these results offer further evidence that a combination of this technology and rehabilitation may help patients with spinal cord injuries regain control over previously paralyzed movements, such as steplike actions, balance control, and standing.
“We’re really excited, because our results went beyond our expectations,” says neurosurgeon Kendall Lee, M.D., Ph.D., principal investigator and director of Mayo Clinic’s Neural Engineering Laboratory. “These are initial findings, but the patient is continuing to make progress.”
Chinnock injured his spinal cord at the sixth thoracic vertebrae in the middle of his back three years earlier. He was diagnosed with a “motor complete spinal cord injury,” meaning he could not move or feel anything below the middle of his torso.
The study started with the patient going through 22 weeks of physical therapy. He had three training sessions a week to prepare his muscles for attempting tasks during spinal cord stimulation, and was tested for changes regularly. Some results led researchers to characterize his injury further as “discomplete,” suggesting dormant connections across his injury may remain.
Following physical therapy, he underwent surgery to implant an electrode in the epidural space near the spinal cord below the injured area. The electrode is connected to a computer-controlled device under the skin in the patient’s abdomen that which sends electrical current to the spinal cord, enabling the patient to create movement.*
The data suggest that people with discomplete spinal cord injuries may be candidates for epidural stimulation therapy, but more research is needed into how a discomplete injury contributes to recovering function, the researchers note.
* The Mayo Clinic received permission from the FDA for off-label use. The Mayo researchers worked closely with the team of V. Reggie Edgerton, Ph.D., at UCLA on this study, which replicates earlier research done at the University of Louisville. Teams from Mayo Clinic’s departments of Neurosurgery and Physical Medicine and Rehabilitation, and the Division of Engineering collaborated on this project. The research was funded by Craig H. Neilsen Foundation, Jack Jablonski BEL13VE in Miracles Foundation, Mayo Clinic Center for Clinical and Translational Sciences, Mayo Clinic Rehabilitation Medicine Research Center, Mayo Clinic Transform the Practice, and The Grainger Foundation.
Mayo Clinic | Researchers Strive to Help Paralyzed Man Make Strides – Mayo Clinic
Abstract of Enabling Task-Specific Volitional Motor Functions via Spinal Cord Neuromodulation in a Human With Paraplegia
Mayo Clinic |Epidural Stimulation Enables Motor Function After Chronic Paraplegia
We report a case of chronic traumatic paraplegia in which epidural electrical stimulation (EES) of the lumbosacral spinal cord enabled (1) volitional control of task-specific muscle activity, (2) volitional control of rhythmic muscle activity to produce steplike movements while side-lying, (3) independent standing, and (4) while in a vertical position with body weight partially supported, voluntary control of steplike movements and rhythmic muscle activity. This is the first time that the application of EES enabled all of these tasks in the same patient within the first 2 weeks (8 stimulation sessions total) of EES therapy.
A research team led by MIT scientists has developed rubbery fibers for neural probes that can flex and stretch and be implanted into the mouse spinal cord.
The goal is to study spinal cord neurons and ultimately develop treatments to alleviate spinal cord injuries in humans. That requires matching the stretchiness, softness, and flexibility of the spinal cord. In addition, the fibers have to deliver optical impulses (for optoelectronic stimulation of neurons with blue or yellow laser light) and have electrical connections (for electrical stimulation and monitoring of neurons).
Implantable fibers have allowed brain researchers to stimulate specific targets in the brain and monitor electrical responses. But similar studies in the nerves of the spinal cord have been more difficult to carry out. That’s because the spine flexes and stretches as the body moves, and the relatively stiff, brittle fibers used today could damage the delicate spinal cord tissue.
The scientists used a newly developed elastomer (a tough elastic polymer material that can flow and be stretched) that is transparent (like a fiber optic cable) for transmitting optical signals, and formed an external mesh coating of silver nanowires as a conductive layer for electrical signals. Think of it as tough, transparent, silver spaghetti.
The fibers are “so floppy, you could use them to do sutures and deliver light at the same time,” says MIT Professor Polina Anikeeva. The fiber can stretch by at least 20 to 30 percent without affecting its properties, she says. “Eventually, we’d like to be able to use something like this to combat spinal cord injury. But first, we have to have biocompatibility and to be able to withstand the stresses in the spinal cord without causing any damage.”
Scientists doing research on spinal cord injuries or disease usually must use larger animals in their studies, because the larger nerve fibers can withstand the more rigid wires used for stimulus and recording. While mice are generally much easier to study and available in many genetically modified strains, there was previously no technology that allowed them to be used for this type of research.
The team included researchers at the University of Washington and Oxford University. The research was supported by the National Science Foundation, the National Institute of Neurological Disorders and Stroke, the U.S. Army Research Laboratory, and the U.S. Army Research Office through the Institute for Soldier Nanotechnologies at MIT.Abstract of Flexible and stretchable nanowire-coated fibers for optoelectronic probing of spinal cord circuits
Studies of neural pathways that contribute to loss and recovery of function following paralyzing spinal cord injury require devices for modulating and recording electrophysiological activity in specific neurons. These devices must be sufficiently flexible to match the low elastic modulus of neural tissue and to withstand repeated strains experienced by the spinal cord during normal movement. We report flexible, stretchable probes consisting of thermally drawn polymer fibers coated with micrometer-thick conductive meshes of silver nanowires. These hybrid probes maintain low optical transmission losses in the visible range and impedance suitable for extracellular recording under strains exceeding those occurring in mammalian spinal cords. Evaluation in freely moving mice confirms the ability of these probes to record endogenous electrophysiological activity in the spinal cord. Simultaneous stimulation and recording is demonstrated in transgenic mice expressing channelrhodopsin 2, where optical excitation evokes electromyographic activity and hindlimb movement correlated to local field potentials measured in the spinal cord.
Astronomers have detected an atmosphere around an Earth-like planet beyond our solar system for the first time: the super-Earth planet GJ 1132b in the Southern constellation Vela, at a distance of 39 light-years from Earth.
The team, led by Keele University’s John Southworth, PhD, used the 2.2 m ESO/MPG telescope in Chile to take images of the planet’s host star GJ 1132. The astronomers made the detection by measuring the slight decrease in brightness, finding that its atmosphere absorbed some of the starlight while transiting (passing in front of) the host star. Previous detections of exoplanet atmospheres all involved gas giants reminiscent of a high-temperature Jupiter.
Possible “water world”
“With this research, we have taken the first tentative step into studying the atmospheres of smaller, Earth-like, planets,” said Southworth. “We simulated a range of possible atmospheres for this planet, finding that those rich in water and/or methane would explain the observations of GJ 1132b. The planet is significantly hotter and a bit larger than Earth, so one possibility is that it is a ‘water world’ with an atmosphere of hot steam.”
Very low-mass stars are extremely common (much more so than Sun-like stars), and are known to host lots of small planets. But they also show a lot of magnetic activity, causing high levels of X-rays and ultraviolet light to be produced, which might completely evaporate the planets’ atmospheres. The properties of GJ 1132b show that an atmosphere can endure for a billion years without being destroyed, the astronomers say.
Given the huge number of very low-mass stars and planets, this could mean the conditions suitable for life are common in the Universe, the astronomers suggest.
The discovery, reported March 31 in Astronomical Journal, makes GJ 1132b one of the highest-priority targets for further study by current top facilities, such as the Hubble Space Telescope and ESO’s Very Large Telescope, as well as the James Webb Space Telescope, slated for launch in 2018.
The team also included astronomers at Luigi Mancini Max Planck Institute for Astronomy (MPIA), University of Rome, University of Cambridge, and Stockholm University.
Transparent biosensors embedded into contact lenses could soon allow doctors and patients to monitor blood glucose levels and many other telltale signs of disease from teardops without invasive tests, according to Oregon State University chemical engineering professor Gregory S. Herman, Ph.D. who presented his work Tuesday April 4, 2017 at the American Chemical Society (ACS) National Meeting & Exposition.
Herman and two colleagues previously invented a compound composed of indium gallium zinc oxide (IGZO). This semiconductor is the same one that has revolutionized electronics, providing higher resolution displays on televisions, smartphones and tablets while saving power and improving touch-screen sensitivity.
In his research, Herman’s goal was to find a way to help people with diabetes continuously monitor their blood glucose levels more efficiently using bio-sensing contact lenses. Continuous glucose monitoring — instead of the prick-and-test approach — helps reduce the risk of diabetes-related health problems. But most continuous glucose monitoring systems require inserting electrodes in various locations under the skin. This can be painful, and the electrodes can cause skin irritation or infections.
Herman says bio-sensing contact lenses could eliminate many of these problems and improve compliance since users can easily replace them on a daily basis. And, unlike electrodes on the skin, they are invisible, which could help users feel less self-conscious about using them.
To test this idea, Herman and his colleagues first developed an inexpensive method to make IGZO electronics. Then, they used the approach to fabricate a biosensor containing a transparent sheet of IGZO field-effect transistors and glucose oxidase, an enzyme that breaks down glucose. When they added glucose to the mixture, the enzyme oxidized the blood sugar. As a result, the pH level in the mixture shifted and, in turn, triggered changes in the electrical current flowing through the IGZO transistor.
In conventional biosensors, these electrical changes would be used to measure the glucose concentrations in the interstitial fluid under a patient’s skin. But glucose concentrations are much lower in the eye. So any biosensors embedded into contact lenses will need to be far more sensitive. To address this problem, the researchers created nanostructures within the IGZO biosensor that were able to detect glucose concentrations much lower than found in tears.*
In theory, Herman says, more than 2,000 transparent biosensors — each measuring a different bodily function — could be embedded in a 1-millimeter square patch of an IGZO contact lens. Once developed, the biosensors could transmit vital health information to smartphones and other Wi-Fi or Bluetooth-enabled devices.
Herman’s team has already used the IGZO system in catheters to measure uric acid, a key indicator of kidney function, and is exploring the possibility of using it for early detection of cancer and other serious conditions. However, Herman says it could be a year or more before a prototype bio-sensing contact lens is ready for animal testing.
The concept appears similar to Goggle’s smart contact lens project, using a tiny wireless chip and miniaturized glucose sensor that are embedded between two layers of soft contact lens material, announced in 2014, but Herman says the Google design is more limited and that the research has stalled.
Herman acknowledges funding from the Juvenile Diabetes Research Foundation and the Northwest Nanotechnology Infrastructure, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the National Science Foundation.
* “We have functionalized the back-channel of IGZO-FETs with aminosilane groups that are cross-linked to glucose oxidase and have demonstrated that these devices have high sensitivity to changes in glucose concentrations. Glucose sensing occurs through the decrease in pH during glucose oxidation, which modulates the positive charge of the aminosilane groups attached to the IGZO surface. The change in charge affects the number of acceptor-like surface states which can deplete electron density in the n-type IGZO semiconductor. Increasing glucose concentrations leads to an increase in acceptor states and a decrease in drain-source conductance due to a positive shift in the turn-on voltage. The functionalized IGZO-FET devices are effective in minimizing detection of interfering compounds including acetaminophen and ascorbic acid.” — Du X, Li Y, Motley JR, Stickle WF, Herman GS, Glucose Sensing Using Functionalized Amorphous In-Ga-Zn-O Field-Effect Transistors. ACS Applied Materials & Interfaces. 2016 03 30.Abstract of Implantable indium gallium zinc oxide field effect biosensors
Amorphous indium gallium zinc oxide (IGZO) field effect transistors (FETs) are a promising technology for a wide range of electronic applications including implantable and wearable biosensors. We have recently developed novel, low-cost methods to fabricate IGZO-FETs, with a wide range of form factors. Attaching self-assembled monolayers (SAM) to the IGZO backchannel allows us to precisely control surface chemistry and improve stability of the sensors. Functionalizing the SAMs with enzymes provides excellent selectivity for the sensors, and effectively minimizes interference from acetaminophen/ascorbic acid. We have recently demonstrated that a nanostructured IGZO network can significantly improve sensitivity as a sensing transducer, compared to blanket IGZO films. In Figure (a) we show a scanning electron microscopy image of a nanostructured IGZO transducer located between two indium tin oxide source/drain electrodes. In Figure (b) we show an atomic force microscope image of the close packed hexagonal IGZO nanostructured network (3×3 mm2), and Figure (c) shows the corresponding height profile along the arrow shown in (b). We will discuss reasons for improved sensitivity for the nanostructured IGZO, and demonstrate high sensitivity for glucose sensing. Finally, fully transparent glucose sensors have been fabricated directly on catheters, and have been characterized by a range of techniques. These results suggest that IGZO-FETs may provide a means to integrate fully transparent, highly-sensitive sensors into contact lenses.
A group of researchers at Munich University of Applied Sciences in Germany and INRS-EMT in Canada is paving the way for mass-producing low-cost printable electronics by demonstrating a fully inkjet-printable flexible resistive memory.*
Additive manufacturing (commonly used in 3-D printing), allows for a streamlined process flow, replacing complex lithography (used in making chips), at the detriment of feature size, which od usually not critical for memory devices in less computationally demanding uses.
Inkjet printing allows for roll-to-roll printing, making possible mass-produced printable electronics. In an open-access paper appearing this week in Applied Physics Letters, from AIP Publishing, the group presents a proof of concept for using inkjet printing of resistive memory (ReRAM).
“We use functional inks to deposit a capacitor structure — conductor-insulator-conductor — with commercially available materials** that have already been deployed in cleanroom processes,” said Bernhard Huber, a doctoral student at INRS-EMT and working in the Laboratory for Microsystems Technology at Munich University of Applied Sciences. “This process is identical to that of an office inkjet printer, with an additional option of fine-tuning the droplet size and heating the target material.”
The process enables extremely low-cost flexible electronics and may lead to print-on-demand electronics, which shows huge potential for small, flexible lines of production and end-user products, the researchers suggest.
Examples include supermarkets printing their own smart tags, public transport providers customizing multifunctional tickets on demand, and wearables.
* Currently, computing devices use two different types of memory: a non-volatile but slow storage memory like Flash and a fast but volatile random access memory (RAM) like DRAM. Resistive RAM combines non-volatile behavior and fast read-and-write access in one device. The two memory states (0 and 1) are defined by the resistance of the memory cell.
** Silver/spin-on-glass (SOG)/poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) cells were fabricated by inkjet printing alone. The cells feature low switching voltages, low write currents, and a high ratio between high and low resistance state of 10,000.
Resistively switching memory cells (ReRAM) are strong contenders for next-generation non-volatile random access memories. In this paper, we present ReRAM cells on flexible substrates consisting of Ag/spin-on-glass/PEDOT:PSS (poly(3,4-ethylenedioxythiophene) polystyrene sulfonate).
The complete cell is fabricated using a standard inkjet printer without additional process steps. Investigations on the spin-on-glass insulating layer showed that low sintering temperatures are sufficient for good switching behavior, providing compatibility with various foils. The cells feature low switching voltages, low write currents, and a high ratio between high and low resistance state of 104. Combined with excellent switching characteristics under bending conditions, these results pave the way for low-power and low-cost memory devices for future applications in flexible electronics.
Imagine you could store a bit on a single atom or small molecule — the ultimate magnetic data-storage system. An international team of researchers led by chemists from ETH Zurich has taken a step toward that idea by depositing single magnetizable atoms onto a silica surface, with the atoms retaining their magnetism.
In theory, certain atoms can be magnetized in one of two possible directions: “spin up” or “spin down” (representing zero or one); information could then be stored and read based on the sequence of the molecules’ magnetic spin directions. But finding molecules that can store the magnetic information permanently is a challenge, and it’s even more difficult to arrange these molecules on a solid surface to build actual data storage devices.Magnetizing atoms on nanoparticles
Nonetheless, Christophe Copéret, a professor at the Laboratory of Inorganic Chemistry at ETH Zurich, and his team have developed a method using a dysprosium atom (dysprosium is a metal belonging to the rare-earth elements). The atom is surrounded by a molecular scaffold that serves as a vehicle. The scientists also developed a method for depositing such molecules on the surface of silica nanoparticles and fusing them by annealing (heating) at 400 degrees Celsius.
The scaffold molecular structure disintegrates in the process, yielding nanoparticles with dysprosium atoms well-dispersed at the surface. The scientists showed that these atoms can then be magnetized and that they maintain their magnetic information.
One advantage of their new method is its simplicity. Nanoparticles bonded with dysprosium can be made in any chemical laboratory. No cleanroom and complex equipment required. And the magnetizable nanoparticles can be stored at room temperature and re-utilized.
Their magnetization process currently only works at around minus 270 degrees Celsius (near absolute zero), and the magnetization can only be maintained for up to one and a half minutes. So the scientists are now looking for methods that will allow the magnetization to be stabilized at higher temperatures and for longer periods of time. They are also looking for ways to fuse atoms to a flat surface instead of to spherical nanoparticles.
Other preparation methods also involve direct deposition of individual atoms onto a surface, but the materials are only stable at very low temperatures, mainly due to the agglomeration of these individual atoms. Alternatively, molecules with ideal magnetic properties can be deposited onto a surface, but this immobilization often negatively affects the structure and the magnetic properties of the final object.
Scientists from the Universities of Lyon and Rennes, Collège de France in Paris, Paul Scherrer Institute in Switzerland, and Berkeley National Laboratory were involved in the research.Abstract of Magnetic Memory from Site Isolated Dy(III) on Silica Materials
Achieving magnetic remanence at single isolated metal sites dispersed at the surface of a solid matrix has been envisioned as a key step toward information storage and processing in the smallest unit of matter. Here, we show that isolated Dy(III) sites distributed at the surface of silica nanoparticles, prepared with a simple and scalable two-step process, show magnetic remanence and display a hysteresis loop open at liquid 4He temperature, in contrast to the molecular precursor which does not display any magnetic memory. This singular behavior is achieved through the controlled grafting of a tailored Dy(III) siloxide complex on partially dehydroxylated silica nanoparticles followed by thermal annealing. This approach allows control of the density and the structure of isolated, “bare” Dy(III) sites bound to the silica surface. During the process, all organic fragments are removed, leaving the surface as the sole ligand, promoting magnetic remanence.
Harvard University chemists have invented a new kind of “bionic” leaf that uses bacteria, sunlight, water, and air to make fertilizer right in the soil where crops are grown. It could make possible a future low-cost commercial fertilizer for poorer countries in the emerging world.
The invention deals with the renewed challenge of feeding the world as the population continues to balloon.* “When you have a large centralized process and a massive infrastructure, you can easily make and deliver fertilizer,” Daniel Nocera, Ph.D., says. “But if I said that now you’ve got to do it in a village in India onsite with dirty water — forget it. Poorer countries in the emerging world don’t always have the resources to do this. We should be thinking of a distributed system because that’s where it’s really needed.”
The research was presented at the national meeting of the American Chemical Society (ACS) today (April 3, 2017). The new bionic leaf builds on a previous Nocera-team invention: the “artificial leaf” — a device that mimics photosynthesis: When exposed to sunlight, it mimics a natural leaf by splitting water into hydrogen and oxygen. These two gases would be stored in a fuel cell, which can use those two materials to produce electricity from inexpensive materials.
That was followed by “bionic leaf 2.0,” a water-splitting system that carbon dioxide out of the air and uses solar energy plus hydrogen-eating Ralstonia eutropha bacteria to produce liquid fuel with 10 percent efficiency, compared to the 1 percent seen in the fastest-growing plants. It provided biomass and liquid fuel yields that greatly exceeded those from natural photosynthesis.
Fertilizer created from sunlight + water + carbon dioxide and nitrogen from the air
For the new “bionic leaf,” Nocera’s team has designed a system in which bacteria use hydrogen from the water split by the artificial leaf plus carbon dioxide from the atmosphere to make a bioplastic that the bacteria store inside themselves as fuel. “I can then put the bug [bacteria] in the soil because it has already used the sunlight to make the bioplastic,” Nocera says. “Then the bug pulls nitrogen from the air and uses the bioplastic, which is basically stored hydrogen, to drive the fixation cycle to make ammonia for fertilizing crops.”
The researchers have used their approach to grow five crop cycles of radishes. The vegetables receiving the bionic-leaf-derived fertilizer weigh 150 percent more than the control crops. The next step, Nocera says, is to boost throughput so that one day, farmers in India or sub-Saharan Africa can produce their own fertilizer with this method.
Nocera said a paper describing the new system will be submitted for publication in about six weeks.
* The first “green revolution” in the 1960s saw the increased use of fertilizer on new varieties of rice and wheat, which helped double agricultural production. Although the transformation resulted in some serious environmental damage, it potentially saved millions of lives, particularly in Asia, according to the United Nations (U.N.) Food and Agriculture Organization. But the world’s population continues to grow and is expected to swell by more than 2 billion people by 2050, with much of this growth occurring in some of the poorest countries, according to the U.N. Providing food for everyone will require a multi-pronged approach, but experts generally agree that one of the tactics will have to involve boosting crop yields to avoid clearing even more land for farming.
American Chemical Society | A ‘bionic leaf’ could help feed the world
Graphene has attractive properties, such as extremely high conductivity, meaning it conducts the flow of electrical current really well (compared to copper, for example), but it’s not a semiconductor, so it can’t work in a transistor (aside from providing great connections). A form of graphene called “graphene oxide” is a semiconductor, but it does not conduct well.
However, a form of graphene oxide called “reduced graphene oxide” (rGO) does conduct well*. Despite that, rGO still can’t function in a transistor. That’s because the design of a transistor is based on creating a junction between two materials: one that is positively charged (p-type) and one that is negatively charged (n-type), and native rGO is only a p-type.
The NC State researchers’ solution was to use high-powered laser pulses to disrupt chemical groups on an rGO thin film. This disruption moved electrons from one group to another, effectively converting p-type rGO to n-type rGO. They then used the two forms of rGO as two layers (a layer of n-type rGO on the surface and a layer of p-type rGO underneath) — creating a layered thin-film material that could be used to develop rGO-based transistors for use in future semiconductor chips.
The researchers were also able to integrate the rGO-based transistors onto sapphire and silicon wafers across the entire wafer.
The paper was published in the Journal of Applied Physics. The work was done with support from the National Science Foundation.
* Reduction is a chemical reaction that involves the gaining of electrons.Abstract of Conversion of p to n-type reduced graphene oxide by laser annealing at room temperature and pressure
Physical properties of reduced graphene oxide (rGO) are strongly dependent on the ratio of sp2 to sp3hybridized carbon atoms and the presence of different functional groups in its structural framework. This research for the very first time illustrates successful wafer scale integration of graphene-related materials by a pulsed laser deposition technique, and controlled conversion of p to n-type 2D rGO by pulsed laser annealing using a nanosecond ArF excimer laser. Reduced graphene oxide is grown onto c-sapphire by employing pulsed laser deposition in a laser MBE chamber and is intrinsically p-type in nature. Subsequent laser annealing converts p into n-type rGO. The XRD, SEM, and Raman spectroscopy indicate the presence of large-area rGO onto c-sapphire having Raman-active vibrational modes: D, G, and 2D. High-resolution SEM and AFM reveal the morphology due to interfacial instability and formation of n-type rGO. Temperature-dependent resistance data of rGO thin films follow the Efros-Shklovskii variable-range-hopping model in the low-temperature region and Arrhenius conduction in the high-temperature regime. The photoluminescence spectra also reveal less intense and broader blue fluorescence spectra, indicating the presence of miniature sized sp2 domains in the vicinity of π* electronic states, which favor the VRH transport phenomena. The XPS results reveal a reduction of the rGO network after laser annealing with the C/O ratio measuring as high as 23% after laser-assisted reduction. The p to n-type conversion is due to the reduction of the rGO framework which also decreases the ratio of the intensity of the D peak to that of the G peak as it is evident from the Raman spectra. This wafer scale integration of rGO with c-sapphire and p to n-type conversion employing a laser annealing technique at room temperature and pressure will be useful for large-area electronic devices and will open a new frontier for further extensive research in graphene-based functionalized 2D materials.
A research team headed by Worcester Polytechnic Institute (WPI) scientists* has solved a major tissue engineering problem holding back the regeneration of damaged human tissues and organs: how to grow small, delicate blood vessels, which are beyond the capabilities of 3D printing.**
The researchers used plant leaves as scaffolds (structures) in an attempt to create the branching network of blood vessels — down to the capillary scale — required to deliver the oxygen, nutrients, and essential molecules required for proper tissue growth.
In a series of unconventional experiments, the team cultured beating human heart cells on spinach leaves that were stripped of plant cells.*** The researchers first decellularized spinach leaves (removed cells, leaving only the veins) by perfusing (flowing) a detergent solution through the leaves’ veins. What remained was a framework made up primarily of biocompatible cellulose, which is already used in a wide variety of regenerative medicine applications, such as cartilage tissue engineering, bone tissue engineering, and wound healing.
After testing the spinach vascular (leaf vessel structure) system mechanically by flowing fluids and microbeads similar in size to human blood cells through it, the researchers seeded the vasculature with human umbilical vein endothelial cells (HUVECs) to grow endothelial cells (which line blood vessels).
Human mesenchymal stem cells (hMSC) and human pluripotent stem-cell-derived cardiomyocytes (cardiac muscle cells) (hPS-CM) were then seeded to the outer surfaces of the plant scaffolds. The cardiomyocytes spontaneously demonstrated cardiac contractile function (beating) and calcium-handling capabilities over the course of 21 days.
The future of ”crossing kingdoms”
These proof-of-concept studies may open the door to using multiple spinach leaves to grow layers of healthy heart muscle, and a potential tissue engineered graft based upon the plant scaffolds could use multiple leaves, where some act as arterial support and some act as venous return of blood and fluids from human tissue, say the researchers.
“Our goal is always to develop new therapies that can treat myocardial infarction, or heart attacks,” said Glenn Gaudette, PhD, professor of biomedical engineering at WPI and corresponding author of an open-access paper in the journal Biomaterials, published online in advance of the May 2017 issue.
“Unfortunately, we are not doing a very good job of treating them today. We need to improve that. We have a lot more work to do, but so far this is very promising.”
Currently, it’s not clear how the plant vasculature would be integrated into the native human vasculature and whether there would be an immune response, the authors advise.
The researchers are also now optimizing the decellularization process and seeing how well various human cell types grow while they are attached to (and potentially nourished by) various plant-based scaffolds that could be adapted for specialized tissue regeneration studies. “The cylindrical hollow structure of the stem of Impatiens capensis might better suit an arterial graft,” the authors note. “Conversely, the vascular columns of wood might be useful in bone engineering due to their relative strength and geometries.”
Other types of plants could also provide the framework for a wide range of other tissue engineering technologies, the authors suggest.****
The authors conclude that “development of decellularized plants for scaffolding opens up the potential for a new branch of science that investigates the mimicry between kingdoms, e.g., between plant and animal. Although further investigation is needed to understand future applications of this new technology, we believe it has the potential to develop into a ‘green’ solution pertinent to a myriad of regenerative medicine applications.”
* The research team also includes human stem cell and plant biology researchers at the University of Wisconsin-Madison, and Arkansas State University-Jonesboro.
** The research is driven by the pressing need for organs and tissues available for transplantation, which far exceeds their availability. More than 100,000 patients are on the donor waiting list at any given time and an average of 22 people die each day while waiting for a donor organ or tissue to become available, according to a 2016 paper in the American Journal of Transplantation
*** In addition to spinach leaves, the team successfully removed cells from parsley, Artemesia annua (sweet wormwood), and peanut hairy roots.
**** “Tissue engineered scaffolds are typically produced either from animal-derived or synthetic biomaterials, both of which have a large cost and large environmental impact. Animal-derived biomaterials used extensively as scaffold materials for tissue engineering include native [extracellular matrix] proteins such as collagen I or fibronectin and whole animal tissues and organs. Annually, 115 million animals are estimated to be used in research. Due to this large number, a lot of energy is necessary for the upkeep and feeding of such animals as well as to dispose of the large amount of waste that is generated. Along with this environmental impact, animal research also has a plethora of ethical considerations, which could be alleviated by forgoing animal models in favor of more biologically relevant in vitro human tissue models,” the authors advise.
Worcester Polytechnic Institute | Spinach leaves can carry blood to grow human tissues
Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Environmental Defense Fund (EDF) have developed an online tool that incorporates 21 years of night-time lights data to understand and compare changes in human activities in countries around the world.
The research is published in PLOS One.
The tool compares the brightness of a country’s night-time lights with the corresponding electricity consumption, GDP, population, poverty, and emissions of CO2, CH4, N2O, and F-gases since 1992, without relying on national statistics with often differing methodologies and motivations by those collecting them.
Consistent with previous research, the team found the highest correlations between night-time lights and GDP, electricity consumption, and CO2 emissions. Correlations with population, N2O, and CH4 emissions were still slightly less pronounced and, as expected, there was an inverse correlation between the brightness of lights and of poverty.
“This is the most comprehensive tool to date to look at the relationship between night-time lights and a series of socio-economic indicators,” said Gernot Wagner, a research associate at SEAS and coauthor of the paper.
The data source is the Defense Meteorological Satellite Program (DMSP) dataset, providing 21 years worth of night-time data. The researchers also use Google Earth Engine (GEE), a platform recently made available to researchers that allows them to explore more comprehensive global aggregate relationships at national scales between DMSP and a series of economic and environmental variables.Abstract of Night-time lights: A global, long term look at links to socio-economic trends
We use a parallelized spatial analytics platform to process the twenty-one year totality of the longest-running time series of night-time lights data—the Defense Meteorological Satellite Program (DMSP) dataset—surpassing the narrower scope of prior studies to assess changes in area lit of countries globally. Doing so allows a retrospective look at the global, long-term relationships between night-time lights and a series of socio-economic indicators. We find the strongest correlations with electricity consumption, CO2 emissions, and GDP, followed by population, CH4 emissions, N2O emissions, poverty (inverse) and F-gas emissions. Relating area lit to electricity consumption shows that while a basic linear model provides a good statistical fit, regional and temporal trends are found to have a significant impact.
Researchers from the European Graphene Flagship* have developed a new microelectrode array neural probe based on graphene field-effect transistors (FETs) for recording brain activity at high resolution while maintaining excellent signal-to-noise ratio (quality).
The new neural probe could lay the foundation for a future generation of in vivo neural recording implants, for patients with epilepsy, for example, and for disorders that affect brain function and motor control, the researchers suggest. It could possibly play a role in Elon Musk’s just-announced Neuralink “neural lace” research project.
Measuring neural activity with high precision
Neural activity is measured by detecting the electric fields generated when neurons fire. These fields are highly localized, so ultra-small measuring devices that can be densely packed are required for accurate brain readings.
The new device has an microelectrode array of 16 graphene-based transistors arranged on a flexible substrate that can conform to the brain’s surface. Graphene provides biocompatibility, chemical stability, flexibility, and excellent electrical properties, which make it attractive for use in medical devices, especially for brain activity, the researchers suggest.**
(For a state-of-the-art example of microelectrode array use in the brain, see “Brain-computer interface advance allows paralyzed people to type almost as fast as some smartphone users.”)
In an experiment with rats, the researchers used the new devices to record brain activity during sleep and in response to visual light stimulation.
The graphene transistor probes showed good spatial discrimination (identifying specific locations) of the brain activity and outperformed state-of-the-art platinum electrode arrays, with higher signal amplification and a better signal-to-noise performance when scaled down to very small sizes.
That means the graphene transistor probes can be more densely packed and at higher resolution, features that are vital for precision mapping of brain activity. And since the probes have transistor amplifiers built in, they remove the need for the separate pre-amplification required with metal electrodes.
Neural probes are placed directly on the surface of the brain, so safety is important. The researchers determined that the flexible graphene-based probes are non-toxic, did not induce any significant inflammation, and are long-lasting.
“Graphene neural interfaces have shown already a great potential, but we have to improve on the yield and homogeneity of the device production in order to advance towards a real technology,” said Jose Antonio Garrido, who led the research at the Catalan Institute of Nanoscience and Nanotechnology in Spain.
“Once we have demonstrated the proof of concept in animal studies, the next goal will be to work towards the first human clinical trial with graphene devices during intraoperative mapping of the brain. This means addressing all regulatory issues associated to medical devices such as safety, biocompatibility, etc.”
The research was published in the journal 2D Materials.
* With a budget of €1 billion, the Graphene Flagship consortium consists of more than 150 academic and industrial research groups in 23 countries. Launched in 2013, the goal is to take graphene from the realm of academic laboratories into European society within 10 years. The research was a collaborative effort involving Flagship partners Technical University of Munich (TU Munich. Germany), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS, Spain), Spanish National Research Council (CSIC, Spain), The Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN, Spain) and the Catalan Institute of Nanoscience and Nanotechnology (ICN2, Spain).
** “Using multielectrode arrays for high-density recordings presents important drawbacks. Since the electrode impedance and noise are inversely proportional to the electrode size, a trade-off between spatial resolution and signal-to-noise ratio has to be made. Further, the very small voltages of the recorded signals are highly susceptible to noise in the standard electrode configuration. [That requires preamplification, which means] the fabrication complexity is significantly increased and the additional electrical components required for the voltage-to-current conversion limit the integration density. … Metal-oxide-semiconductor field-effect transistors (MOSFETs) where the gate metal is replaced with an electrolyte and an electrode, referred to as “solution-gated field-effect transistors (SGFETs) or electrolyte-gated field-effect transistors, can be exposed directly to neurons and be used to record action potentials with high fidelity. … Although the potential of graphene-based SGFET technology has been suggested in in vitro studies, so far no in vivo confirmation has been demonstrated. Here we present the fabrication of flexible arrays of graphene SGFETs and demonstrate in vivo mapping of spontaneous slow waves, as well as visually evoked and pre-epileptic activity in the rat.” — Benno M. Blaschke et al./2D Mater.Abstract of Mapping brain activity with flexible graphene micro-transistors
Establishing a reliable communication interface between the brain and electronic devices is of paramount importance for exploiting the full potential of neural prostheses. Current microelectrode technologies for recording electrical activity, however, evidence important shortcomings, e.g. challenging high density integration. Solution-gated field-effect transistors (SGFETs), on the other hand, could overcome these shortcomings if a suitable transistor material were available. Graphene is particularly attractive due to its biocompatibility, chemical stability, flexibility, low intrinsic electronic noise and high charge carrier mobilities. Here, we report on the use of an array of flexible graphene SGFETs for recording spontaneous slow waves, as well as visually evoked and also pre-epileptic activity in vivo in rats. The flexible array of graphene SGFETs allows mapping brain electrical activity with excellent signal-to-noise ratio (SNR), suggesting that this technology could lay the foundation for a future generation of in vivo recording implants.
Elon Musk has launched a California-based company called Neuralink Corp., The Wall Street Journal reported today (Monday, March 27, 2017), citing people familiar with the matter, to pursue “neural lace” brain-interface technology.
Neural lace would help prevent humans from becoming “house cats” to AI, he suggests. “I think one of the solutions that seems maybe the best is to add an AI layer,” Musk hinted at the Code Conference last year. It would be a “digital layer above the cortex that could work well and symbiotically with you.
“We are already a cyborg,” he added. “You have a digital version of yourself online in form of emails and social media. … But the constraint is input/output — we’re I/O bound … particularly output. … Merging with digital intelligence revolves around … some sort of interface with your cortical neurons.”
Reflecting concepts that have been proposed by Ray Kurzweil, “over time I think we will probably see a closer merger of biological intelligence and digital intelligence,” Musk said at the recent World Government Summit in Dubai.
Musk suggested the neural lace interface could be inserted via veins and arteries.
KurzweilAI reported on one approach to a neural-lace-like brain interface in 2015. A “syringe-injectable electronics” concept was invented by researchers in Charles Lieber’s lab at Harvard University and the National Center for Nanoscience and Technology in Beijing. It would involve injecting a biocompatible polymer scaffold mesh with attached microelectronic devices into the brain via syringe.
The process for fabricating the scaffold is similar to that used to etch microchips, and begins with a dissolvable layer deposited on a biocompatible nanoscale polymer mesh substrate, with embedded nanowires, transistors, and other microelectronic devices attached. The mesh is then tightly rolled up, allowing it to be sucked up into a syringe via a thin (100 micrometers internal diameter) glass needle. The mesh can then be injected into brain tissue by the syringe.
The input-output connection of the mesh electronics can be connected to standard electronics devices (for voltage insertion or measurement, for example), allowing the mesh-embedded devices to be individually addressed and used to precisely stimulate or record individual neural activity.
Lieber’s team has demonstrated this in live mice and verified continuous monitoring and recordings of brain signals on 16 channels. “We have shown that mesh electronics with widths more than 30 times the needle ID can be injected and maintain a high yield of active electronic devices … little chronic immunoreactivity,” the researchers said in a June 8, 2015 paper in Nature Nanotechnology. “In the future, our new approach and results could be extended in several directions, including the incorporation of multifunctional electronic devices and/or wireless interfaces to further increase the complexity of the injected electronics.”
This technology would require surgery, but would not have the accessibility limitation of the blood-brain barrier with Musk’s preliminary concept. For direct delivery via the bloodstream, it’s possible that the nanorobots conceived by Robert A. Freitas, Jr. (and extended to interface with the cloud, as Ray Kurzweil has suggested) might be appropriate at some point in the future.
“Neuralink has reportedly already hired several high profile academics in the field of neuroscience: flexible electrodes and nano technology expert Venessa Tolosa, PhD; UCSF professor Philip Sabes, PhD, who also participated in the Musk-sponsored Beneficial AI conference; and Boston University professor Timothy Gardner, PhD, who studies neural pathways in the brains of songbirds,” Engadget reports.
UPDATE Mar. 28, 2017:
Recode | We are already cyborgs | Elon Musk | Code Conference 2016
Travelers to Mars risk leukemia cancer, weakened immune function from radiation, NASA-funded study finds
Radiation encountered in deep space travel may increase the risk of leukemia cancer in humans traveling to Mars, NASA-funded researchers at the Wake Forest Institute for Regenerative Medicine and colleagues have found, using mice transplanted with human stem cells.
“Our results are troubling because they show radiation exposure could potentially increase the risk of leukemia,” said Christopher Porada, Ph.D., associate professor of regenerative medicine and senior researcher on the project.
Radiation exposure is believed to be one of the most dangerous aspects of traveling to Mars, according to NASA. The average distance to Mars is 140 million miles, and a round trip could take three years.
The goal of the study, published in the journal Leukemia, was to assess the direct effects of simulated solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation on human hematopoietic stem cells (HSCs). These stem cells comprise less than 0.1% of the bone marrow of adults, but produce the many types of blood cells that circulate through the body and work to transport oxygen, fight infection, and eliminate any malignant cells that arise.
For the study, human HSCs from healthy donors of typical astronaut age (30–55 years) were exposed to Mars mission-relevant doses of protons and iron ions — the same types of radiation that astronauts would be exposed to in deep space, followed by laboratory and animal studies to define the impact of the exposure.
“Radiation exposure at these levels was highly deleterious to HSC function, reducing their ability to produce almost all types of blood cells, often by 60–80 percent,” said Porada. “This could translate into a severely weakened immune system and anemia during prolonged missions in deep space.”
The radiation also caused mutations in genes involved in the hematopoietic process and dramatically reduced the ability of HSCs to give rise to mature blood cells.
Previous studies had already demonstrated that exposure to high doses of radiation, such as from X-rays, can have harmful (even life-threatening) effects on the body’s ability to make blood cells, and can significantly increase the likelihood of cancers, especially leukemias. However, the current study was the first to show a damaging effect of lower, mission-relevant doses of space radiation.
Mice develop T-cell acute lymphoblastic leukemia, weakened immune function
The next step was to assess how the cells would function in the human body. For that purpose, mice were transplanted with GCR-irradiated human HSCs, essentially “humanizing” the animals. The mice developed what appeared to be T-cell acute lymphoblastic leukemia — the first demonstration that exposure to space radiation may increase the risk of leukemia in humans.
“Our results show radiation exposure could potentially increase the risk of leukemia in two ways,” said Porada. “We found that genetic damage to HSCs directly led to leukemia. Secondly, radiation also altered the ability of HSCs to generate T and B cells, types of white blood cells involved in fighting foreign ‘invaders’ like infections or tumor cells. This may reduce the ability of the astronaut’s immune system to eliminate malignant cells that arise as a result of radiation-induced mutations.”
Porada said the findings are particularly troubling given previous work showing that conditions of weightlessness/microgravity present during spaceflight can also cause marked alterations in astronaut’s immune function, even after short duration missions in low-earth orbit, where they are largely protected from cosmic radiation.
Taken together, the results indicate that the combined exposure to microgravity and SEP/GCR radiation that would occur during extended deep space missions, such as to Mars, could potentially exacerbate the risk of immune-dysfunction and cancer,
NASA’s Human Research Program is also exploring conditions of microgravity, isolation and confinement, hostile and closed environments, and distance from Earth. The ultimate goal of the research is to make space missions as safe as possible.
Researchers at Wake Forest Baptist Medical Center, Brookhaven National Laboratory, and the University of California Davis Comprehensive Cancer Center were also involved in the study.
Abstract of In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells
Future deep space missions to Mars and near-Earth asteroids will expose astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation, and likely one or more solar particle events (SPEs). Given the inherent radiosensitivity of hematopoietic cells and short latency period of leukemias, space radiation-induced hematopoietic damage poses a particular threat to astronauts on extended missions. We show that exposing human hematopoietic stem/progenitor cells (HSC) to extended mission-relevant doses of accelerated high-energy protons and iron ions leads to the following: (1) introduces mutations that are frequently located within genes involved in hematopoiesis and are distinct from those induced by γ-radiation; (2) markedly reduces in vitro colony formation; (3) markedly alters engraftment and lineage commitment in vivo; and (4) leads to the development, in vivo, of what appears to be T-ALL. Sequential exposure to protons and iron ions (as typically occurs in deep space) proved far more deleterious to HSC genome integrity and function than either particle species alone. Our results represent a critical step for more accurately estimating risks to the human hematopoietic system from space radiation, identifying and better defining molecular mechanisms by which space radiation impairs hematopoiesis and induces leukemogenesis, as well as for developing appropriately targeted countermeasures.
A research team led by Harvard Medical School professor of genetics David Sinclair, PhD, has made a discovery that could lead to a revolutionary new drug that allows cells to repair DNA damaged by aging, cancer, and radiation.
In a paper published in the journal Science on Friday (March 24), the scientists identified a critical step in the molecular process related to DNA damage.
The researchers found that a compound known as NAD (nicotinamide adenine dinucleotide), which is naturally present in every cell of our body, has a key role as a regulator in protein-to-protein interactions that control DNA repair. In an experiment, they found that treating mice with a NAD+ precursor called NMN (nicotinamide mononucleotide) improved their cells’ ability to repair DNA damage.
“The cells of the old mice were indistinguishable from the young mice, after just one week of treatment,” said senior author Sinclair.
Human trials of NMN therapy will begin within the next few months to “see if these results translate to people,” he said. A safe and effective anti-aging drug is “perhaps only three to five years away from being on the market if the trials go well.”
What it means for astronauts, childhood cancer survivors, and the rest of us
The researchers say that in addition to reversing aging, the DNA-repair research has attracted the attention of NASA. The treatment could help deal with radiation damage to astronauts in its Mars mission, which could cause muscle weakness, memory loss, and other symptoms (see “Mars-bound astronauts face brain damage from galactic cosmic ray exposure, says NASA-funded study“), and more seriously, leukemia cancer and weakened immune function (see “Travelers to Mars risk leukemia cancer, weakend immune function from radiation, NASA-funded study finds“).
The treatment could also help travelers aboard aircraft flying across the poles. A 2011 NASA study showed that passengers on polar flights receive about 12 percent of the annual radiation limit recommended by the International Committee on Radiological Protection.
The other group that could benefit from this work is survivors of childhood cancers, who are likely to suffer a chronic illness by age 45, leading to accelerated aging, including cardiovascular disease, Type 2 diabetes, Alzheimer’s disease, and cancers unrelated to the original cancer, the researchers noted.
For the past four years, Sinclair’s team has been working with spinoff MetroBiotech on developing NMN as a drug. Sinclair previously made a link between the anti-aging enzyme SIRT1 and resveratrol. “While resveratrol activates SIRT1 alone, NAD boosters [like NMN] activate all seven sirtuins, SIRT1-7, and should have an even greater impact on health and longevity,” he says.
Sinclair is also a professor at the University of New South Wales School of Medicine in Sydney, Australia.
Abstract of A conserved NAD+ binding pocket that regulates protein-protein interactions during aging
DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD+ (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD+ to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate–ribose) polymerase], a critical DNA repair protein. As mice age and NAD+ concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD+. Thus, NAD+ directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging.
MIT researchers have designed a radical new method of creating flexible, printable electronics that combine sensors and processing circuitry.
Covering a robot — or an airplane or a bridge, for example — with sensors will require a technology that is both flexible and cost-effective to manufacture in bulk. To demonstrate the feasibility of their new method, the researchers at MIT’s Computer Science and Artificial Intelligence Laboratory have designed and built a 3D-printed device that responds to mechanical stresses by changing the color of a spot on its surface.
“In nature, networks of sensors and interconnects [such as the human nervous system] are called sensorimotor pathways,” says Subramanian Sundaram, an MIT graduate student in electrical engineering and computer science (EECS), who led the project. “We were trying to see whether we could replicate sensorimotor pathways inside a 3-D-printed object. So we considered the simplest organism we could find” — the golden tortoise beetle, or “goldbug,” an insect whose exterior usually appears golden but turns reddish orange if the insect is poked or prodded, that is, mechanically stressed.
The researchers present their new design in the latest issue of the journal Advanced Materials Technologies.
The key innovation was to 3D-print directly on the plastic substrate (support structure) instead of placing components on top. That greatly increases the range of devices that can be created; a printed substrate could consist of many materials, interlocked in intricate but regular patterns, which broadens the range of functional materials that printable electronics can use.*
Printed substrates also open the possibility of devices that, although printed as flat sheets, can fold themselves up into more complex, three-dimensional shapes. Printable robots that spontaneously self-assemble when heated, for instance (see “Self-assembling printable robotic components“), are a topic of ongoing research at the CSAIL Distributed Robotics Laboratory, led by Daniela Rus, the Andrew and Erna Viterbi Professor of Electrical Engineering and Computer Science at MIT.
3D-printed sensory composite
The MIT researchers’ new device is approximately T-shaped, but with a wide, squat base and an elongated crossbar. The crossbar is made from an elastic plastic, with a strip of silver running its length; in the researchers’ experiments, electrodes were connected to the crossbar’s ends. The base of the T is made from a more rigid plastic. It includes two printed transistors and what the researchers call a “pixel,” a circle of semiconducting polymer whose color changes when the crossbars stretch, modifying the electrical resistance of the silver strip.**
A transistor consists of semiconductor channel on top of which sits a “gate,” a metal wire that, when charged, generates an electric field that switches the semiconductor between its electrically conductive and nonconductive states. In a standard transistor, there’s an insulator between the gate and the semiconductor, to prevent the gate current from leaking into the semiconductor channel.
The transistors in the MIT researchers’ device instead separate the gate and the semiconductor with an electrolyte — a layer of water containing potassium chloride mixed with glycerol. Charging the gate drives potassium ions into the semiconductor, changing its conductivity.***
“I am very impressed with both the concept and the realization of the system,” says Hagen Klauk, who leads the Organic Electronic Research Group at the Max Planck Institute for Solid State Research, in Stuttgart, Germany. “The approach of printing an entire optoelectronic system — including the substrate and all the components — by depositing all the materials, including solids and liquids, by 3-D printing is certainly novel, interesting, and useful, and the demonstration of the functional system confirms that the approach is also doable. By fabricating the substrate on the fly, the approach is particularly useful for improvised manufacturing environments where dedicated substrate materials may not be available.”
The work was supported by the DARPA SIMPLEX program through SPAWAR.
* To build the device, the researchers used the MultiFab, a custom 3-D printer developed MIT. The MultiFab already included two different “print heads,” one for emitting hot materials and one for cool, and an array of ultraviolet light-emitting diodes. Using ultraviolet radiation to “cure” fluids deposited by the print heads produces the device’s substrate.
** Sundaram added a copper-and-ceramic heater, which was necessary to deposit the semiconducting plastic: The plastic is suspended in a fluid that’s sprayed onto the device surface, and the heater evaporates the fluid, leaving behind a layer of plastic only 200 nanometers thick. The layer of saltwater lowers the device’s operational voltage, so that it can be powered with an ordinary 1.5-volt battery.
*** But it does render the device less durable. “I think we can probably get it to work stably for two months, maybe,” Sundaram says. “One option is to replace that liquid with something between a solid and a liquid, like a hydrogel, perhaps. But that’s something we would work on later. This is an initial demonstration.”Abstract of 3D-Printed Autonomous Sensory Composites
A method for 3D-printing autonomous sensory composites requiring no external processing is presented. The composite operates at 1.5 V, locally performs active signal transduction with embedded electrical gain, and responds to stimuli, reversibly transducing mechanical strain into a transparency change. Digital assembly of spatially tailored solids and thin films, with encapsulated liquids, provides a route for realizing complex autonomous systems.
A Mayo Clinic study says the best training for adults is high-intensity aerobic exercise, which they believe can reverse some cellular aspects of aging.
Mayo researchers compared 12 weeks of high-intensity interval training (workouts in which you alternate periods of high-intensity exercise with low-intensity recovery periods), resistance training, and combined training. While all three enhanced insulin sensitivity and lean mass, only high-intensity interval training and combined training improved aerobic capacity and skeletal muscle mitochondrial respiration. (Decline in mitochondrial content and function are common in older adults.)
High-intensity intervals also improved muscle protein content, which enhanced energetic functions and also caused muscle enlargement, especially in older adults. The researchers said exercise training significantly enhanced the cellular machinery responsible for making new proteins. That contributes to protein synthesis, thus reversing a major adverse effect of aging.
“We encourage everyone to exercise regularly, but the take-home message for aging adults is that supervised high-intensity training is probably best, because, both metabolically and at the molecular level, it confers the most benefits,” says K. Sreekumaran Nair, M.D., Ph.D., a Mayo Clinic endocrinologist and senior researcher on the study.
He says the high-intensity training reversed some manifestations of aging in the body’s protein function, but noted that increasing muscle strength requires resistance training a couple of days a week.
In the study, researchers tracked metabolic and molecular changes in a group of young and older adults over 12 weeks, gathering data 72 hours after individuals in randomized groups completed each type of exercise. General findings showed:
- Cardio respiratory health, muscle mass, and insulin sensitivity improved with all training.
- Mitochondrial cellular function declined with age but improved with training.
- Increase in muscle strength occurred only modestly with high-intensity interval training, but occurred with resistance training alone or when added to the aerobic training.
- Exercise improves skeletal muscle gene expression independent of age.
- Exercise substantially enhanced the ribosomal proteins responsible for synthesizing new proteins, which is mainly responsible for enhanced mitochondrial function.
- Training has no significant effect on skeletal muscle DNA epigenetic changes but promotes skeletal muscle protein expression with maximum effect in older adults.
The research findings appear in Cell Metabolism. The research was supported by the National Institutes of Health, Mayo Clinic, the Robert and Arlene Kogod Center on Aging, and the Murdock-Dole Professorship.Abstract of Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans
The molecular transducers of benefits from different exercise modalities remain incompletely defined. Here we report that 12 weeks of high-intensity aerobic interval (HIIT), resistance (RT), and combined exercise training enhanced insulin sensitivity and lean mass, but only HIIT and combined training improved aerobic capacity and skeletal muscle mitochondrial respiration. HIIT revealed a more robust increase in gene transcripts than other exercise modalities, particularly in older adults, although little overlap with corresponding individual protein abundance was noted. HIIT reversed many age-related differences in the proteome, particularly of mitochondrial proteins in concert with increased mitochondrial protein synthesis. Both RT and HIIT enhanced proteins involved in translational machinery irrespective of age. Only small changes of methylation of DNA promoter regions were observed. We provide evidence for predominant exercise regulation at the translational level, enhancing translational capacity and proteome abundance to explain phenotypic gains in muscle mitochondrial function and hypertrophy in all ages.
A new infrared-light WiFi network can provide more than 40 gigabits per second (Gbps) for each user* — about 100 times faster than current WiFi systems — say researchers at Eindhoven University of Technology (TU/e) in the Netherlands.
The TU/e WiFi design was inspired by experimental systems using ceiling LED lights (such as Oregon State University’s experimental WiFiFO, or WiFi Free space Optic, system), which can increase the total per-user speed of WiFi systems and extend the range to multiple rooms, while avoiding interference from neighboring WiFi systems. (However, WiFiFo is limited to 100 Mbps.)
Instead of visible light, the TU/e system uses invisible near-infrared light.** Supplied by a fiber optic cable, a few central “light antennas” (mounted on the ceiling, for instance) each use a pair of ”passive diffraction gratings” that radiate light rays of different wavelengths at different angles.
That allows for directing the light beams to specific users. The network tracks the precise location of every wireless device, using a radio signal transmitted in the return direction.***
The TU/e system uses infrared light with a wavelength of 1500 nanometers (a frequency of 200 terahertz, or 40,000 times higher than 5GHz), allowing for significantly increased capacity. The system has so far used the light rays only for downloading; uploads are still done using WiFi radio signals, since much less capacity is usually needed for uploading.
The researchers expect it will take five years or more for the new technology to be commercially available. The first devices to be connected will likely be high-data devices like video monitors, laptops, and tablets.
* That speed is 67 times higher than the current 802.11n WiFi system’s max theoretical speed of 600Mbps capacity — which has to be shared between users, so the ratio is actually about 100 times, according to TU/e researchers. That speed is also 16 times higher than the 2.5 Gbps performance with the best (802.11ac) Wi-Fi system — which also has to be shared (so actually lower) — and in addition, uses the 5GHz wireless band, which has limited range. “The theoretical max speed of 802.11ac is eight 160MHz 256-QAM channels, each of which are capable of 866.7Mbps, for a total of 6,933Mbps, or just shy of 7Gbps,” notes Extreme Tech. “In the real world, thanks to channel contention, you probably won’t get more than two or three 160MHz channels, so the max speed comes down to somewhere between 1.7Gbps and 2.5Gbps. Compare this with 802.11n’s max theoretical speed, which is 600Mbps.”
** The TU/e system was designed by Joanne Oh as a doctoral thesis and part of the wider BROWSE project headed up by professor of broadband communication technology Ton Koonen, with funding from the European Research Council, under the auspices of the noted TU/e Institute for Photonic Integration.
*** According to TU/e researchers, a few other groups are investigating network concepts in which infrared-light rays are directed using movable mirrors. The disadvantage here is that this requires active control of the mirrors and therefore energy, and each mirror is only capable of handling one ray of light at a time. The grating used the and Oh can cope with many rays of light and, therefore, devices at the same time.
Do-it-yourself robotics kit gives science, tech, engineering, math students tools to automate biology and chemistry experiments
Stanford bioengineers have developed liquid-handling robots to allow students to modify and create their own robotic systems that can transfer precise amounts of fluids between flasks, test tubes, and experimental dishes.
The bioengineers combined a Lego Mindstorms robotics kit with a cheap and easy-to-find plastic syringe to create robots that approach the performance of the far more costly automation systems found at universities and biotech labs.
Step-by-step DIY plans
The idea is to enable students to learn the basics of robotics and the wet sciences in an integrated way. Students learn STEM skills like mechanical engineering, computer programming, and collaboration while gaining a deeper appreciation of the value of robots in life-sciences experiments.
“We really want kids to learn by doing,” said Ingmar Riedel-Kruse, assistant professor of bioengineering and a member of Stanford Bio-X, who led the team. “We show that with a few relatively inexpensive parts, a little training and some imagination, students can create their own liquid-handling robots and then run experiments on it — so they learn about engineering, coding, and the wet sciences at the same time.”
In an open-access paper in the journal PLoS Biology and on Riedel-Kruse’s lab website, the team offers step-by-step building plans and several fundamental experiments targeted to elementary, middle and high school students. They also offer experiments that students can conduct using common household consumables like food coloring, yeast or sugar.
In one experiment, colored liquids with distinct salt concentrations are layered atop one another to teach about liquid density. Other tests measure whether liquids are acids like vinegar or bases like baking soda, or which sugar concentration is best for yeast.
Funding was provided by grants from the National Science Foundation (Cyberlearning and National Robotics Initiative).
Stanford University School of Engineering | SFENG Robots Riedel Kruse v4
Abstract of Liquid-handling Lego robots and experiments for STEM education and research
Liquid-handling robots have many applications for biotechnology and the life sciences, with increasing impact on everyday life. While playful robotics such as Lego Mindstorms significantly support education initiatives in mechatronics and programming, equivalent connections to the life sciences do not currently exist. To close this gap, we developed Lego-based pipetting robots that reliably handle liquid volumes from 1 ml down to the sub-μl range and that operate on standard laboratory plasticware, such as cuvettes and multiwell plates. These robots can support a range of science and chemistry experiments for education and even research. Using standard, low-cost household consumables, programming pipetting routines, and modifying robot designs, we enabled a rich activity space. We successfully tested these activities in afterschool settings with elementary, middle, and high school students. The simplest robot can be directly built from the widely used Lego Education EV3 core set alone, and this publication includes building and experiment instructions to set the stage for dissemination and further development in education and research.
A new method developed at MIT and National Chiao Tung University, based on specially treated sheets of graphene oxide, could make it possible to capture and analyze individual cells from a small sample of blood. It could potentially lead to very-low-cost diagnostic devices (less than $5 a piece) that are mass-producible and could be used almost anywhere for point-of-care testing, especially in resource-constrained settings.
A single cell can contain a wealth of information about the health of an individual. The new system could ultimately lead to a variety of simple devices that could perform a variety of sensitive diagnostic tests, even in places far from typical medical facilities, for cancer screening or treatment follow-up, for example.
How to capture DNA, proteins, or even whole cells for analysis
The material (graphene oxide, or GO) used in this research is an oxidized version of the two-dimensional form of pure carbon known as graphene. The key to the new process is heating the graphene oxide at relatively mild temperatures.
This low-temperature annealing, as it is known, makes it possible to bond particular compounds to the material’s surface that can be used to capture molecules of diagnostic interest.
The heating process changes the material’s surface properties, causing oxygen atoms to cluster together, leaving spaces of bare graphene between them. This leaves room to attach other chemicals to the surface, which can be used to select and bond with specific molecules of interest, including DNA and proteins, or even whole cells. Once captured, those molecules or cells can then be subjected to a variety of tests.*
The new research demonstrates how that basic process could potentially enable a suite of low-cost diagnostic systems.
For this proof-of-concept test, the team used molecules that can quickly and efficiently capture specific immune cells that are markers for certain cancers. They were able to demonstrate that their treated graphene oxide surfaces were almost twice as effective at capturing such cells from whole blood, compared to devices fabricated using ordinary, untreated graphene oxide.
They did this by enzymatically coating the treated graphene oxide surface with peptides called “nanobodies” — subunits of antibodies, which can be cheaply and easily produced in large quantities in bioreactors and are highly selective for particular biomolecules.**
The new process allows for rapid capture and assessment of cells or biomolecules within about 10 minutes and without the need for refrigeration of samples or incubators for precise temperature control. And the whole system is compatible with existing large-scale manufacturing methods.
The researchers believe many different tests could be incorporated on a single device, all of which could be placed on a small glass slide like those used for microscopy. The basic processing method could also make possible a wide variety of other applications, including solar cells and light-emitting devices.
The findings are reported in the journal ACS Nano. Authors include Angela Belcher, the James Mason Crafts Professor in biological engineering and materials science and engineering at MIT and a member of the Koch Institute for Integrative Cancer Research; Jeffrey Grossman, the Morton and Claire Goulder and Family Professor in Environmental Systems at MIT; Hidde L. Ploegh, a professor of biology and member of the Whitehead Institute for Biomedical Research; Guan-Yu Chen, an assistant professor in biomedical engineering at National Chiao Tung University in Taiwan; and Zeyang Li, a doctoral student at the Whitehead Institute.
“Efficiency is especially important if you’re trying to detect a rare event,” Belcher says. “The goal of this was to show a high efficiency of capture.” The next step after this basic proof of concept, she says, is to try to make a working detector for a specific disease model.
The work was supported by the Army Research Office Institute for Collaborative Biotechnologies and MIT’s Tata Center and Solar Frontiers Center.
* Other researchers have been trying to develop diagnostic systems using a graphene oxide substrate to capture specific cells or molecules, but these approaches used just the raw, untreated material. Despite a decade of research, other attempts to improve such devices’ efficiency have relied on external modifications, such as surface patterning through lithographic fabrication techniques, or adding microfluidic channels, which add to the cost and complexity. Those methods for treating graphene oxide for this purpose require high-temperature treatments or the use of harsh chemicals; the new system, which the group has patented, requires no chemical pretreatment and an annealing temperature of just 50 to 80 degrees Celsius (122 to 176 F).
** The researchers found that increasing the annealing time steadily increased the efficiency of cell capture: After nine days of annealing, the efficiency of capturing cells from whole blood went from 54 percent, for untreated graphene oxide, to 92 percent for the treated material. The team then performed molecular dynamics simulations to understand the fundamental changes in the reactivity of the graphene oxide base material. The simulation results, which the team also verified experimentally, suggested that upon annealing, the relative fraction of one type of oxygen (carbonyl) increases at the expense of the other types of oxygen functional groups (epoxy and hydroxyl) as a result of the oxygen clustering. This change makes the material more reactive, which explains the higher density of cell capture agents and increased efficiency of cell capture.
Abstract of Enhanced Cell Capture on Functionalized Graphene Oxide Nanosheets through Oxygen Clustering
With the global rise in incidence of cancer and infectious diseases, there is a need for the development of techniques to diagnose, treat, and monitor these conditions. The ability to efficiently capture and isolate cells and other biomolecules from peripheral whole blood for downstream analyses is a necessary requirement. Graphene oxide (GO) is an attractive template nanomaterial for such biosensing applications. Favorable properties include its two-dimensional architecture and wide range of functionalization chemistries, offering significant potential to tailor affinity toward aromatic functional groups expressed in biomolecules of interest. However, a limitation of current techniques is that as-synthesized GO nanosheets are used directly in sensing applications, and the benefits of their structural modification on the device performance have remained unexplored. Here, we report a microfluidic-free, sensitive, planar device on treated GO substrates to enable quick and efficient capture of Class-II MHC-positive cells from murine whole blood. We achieve this by using a mild thermal annealing treatment on the GO substrates, which drives a phase transformation through oxygen clustering. Using a combination of experimental observations and MD simulations, we demonstrate that this process leads to improved reactivity and density of functionalization of cell capture agents, resulting in an enhanced cell capture efficiency of 92 ± 7% at room temperature, almost double the efficiency afforded by devices made using as-synthesized GO (54 ± 3%). Our work highlights a scalable, cost-effective, general approach to improve the functionalization of GO, which creates diverse opportunities for various next-generation device applications.
Using just a simple inexpensive micro-thin glass surgical needle and laser light, University of Utah engineers have developed an inexpensive way to take high-resolution pictures of a mouse brain, minimizing tissue damage — a process they believe could lead to a much less invasive method for humans.
Typically, researchers must either surgically take a sample of the animal’s brain to examine the cells under a microscope or use an endoscope, which can be 10 to 100 times thicker than a needle.
With the new “computational-cannula microscopy” process, the small (220 micrometers) width of the cannula allows for minimally invasive imaging, while the long length (>2 mm*) allows for deep-brain imaging of features of about 3.5 micrometers in size. Since no (slow) scanning is involved, video at the native frame rate of the camera can be achieved, allowing for capturing near-real-time live videos (currently, it takes less than one fifth of a second to compute each frame on a desktop computer).
In the case of mice, researchers use optogenetics (genetically modify the animals so that only the cells they want to see glow under this laser light), but Utah electrical and computer engineering associate professor Rajesh Menon, who led the research, believes the new process can potentially be developed for human patients. That would create a simpler, less invasive, and less expensive method than endoscopes, and it could be used for other organs.
Menon and his team have been working with the U. of U.’s renowned Nobel-winning researcher, Distinguished Professor of Biology and Human Genetics Mario Capecchi, and Jason Shepherd, assistant professor of neurobiology and anatomy.
The research is documented in the latest issue of open-access Scientific Reports.
* “With three-photon microscopy, penetration depth of up to 1.2 mm was recently reported. However, three- or multi-photon excitation is extremely inefficient due to the low absorption cross-section, which requires large excitation intensities leading to potential for photo-toxicity. Furthermore, many interesting biological features lie at depths greater than 1.2 mm from the surface of the brain such as the basal ganglia, hippocampus, and the hypothalamus.” — Ganghun Kim et al./Scientific ReportsAbstract of Deep-brain imaging via epi-fluorescence Computational Cannula Microscopy
Here we demonstrate widefield (field diameter = 200 μm) fluorescence microscopy and video imaging inside the rodent brain at a depth of 2 mm using a simple surgical glass needle (cannula) of diameter 0.22 mm as the primary optical element. The cannula guides excitation light into the brain and the fluorescence signal out of the brain. Concomitant image-processing algorithms are utilized to convert the spatially scrambled images into fluorescent images and video. The small size of the cannula enables minimally invasive imaging, while the long length (>2 mm) allow for deep-brain imaging with no additional complexity in the optical system. Since no scanning is involved, widefield fluorescence video at the native frame rate of the camera can be achieved.