In science, sometimes the best discoveries come when you’re exploring something else entirely.
That’s the case with recent findings from the National Institute of Standards and Technology (NIST), where a research team has come up with a way to build safe, nontoxic gold wires onto flexible, thin plastic film. Their demonstration potentially clears the path for a host of wearable electronic devices that monitor our health.
The finding might overcome a basic issue confronting medical engineers: How to create electronics that are flexible enough to be worn comfortably on or even inside the human body—without exposing a person to harmful chemicals in the process—and will last long enough to be useful and convenient.
“Overall this could be a major step in wearable sensor research,” said NIST biomedical engineer Darwin Reyes-Hernandez.
Wearable electronics, as envisioned in this brief animation, would permit the wearer to monitor not only familiar vital signs, but a host of other biomarkers in the body – potentially catching the signs of disease well before symptoms appear.
Wearable health monitors are already commonplace; bracelet-style fitness trackers have escaped mere utility to become a full-on fashion trend. But the medical field has its eye on something more profound, known as personalized medicine. The long-term goal is to keep track of hundreds of real-time changes in our bodies—from fluctuations in the amount of potassium in sweat to the level of particular sugars or proteins in the bloodstream. These changes manifest themselves a bit differently in each person, and some of them could mark the onset of disease in ways not yet apparent to a doctor’s eye. Wearable electronics might help spot those problems early.
First, though, engineers need a way to build them so that they work dependably and safely—a tall order for the metals that make up their circuits and the flexible surfaces or “substrates” on which they are built.
Gold is a good option because it does not corrode, unlike most metals, and it has the added value of being nontoxic. But it’s also brittle. If you bend it, it tends to crack, potentially breaking completely— meaning thin gold wires might stop conducting electricity after a few twists of the body.
“Gold has been used to make wires that run across plastic surfaces, but until now the plastic has needed to be fairly rigid,” said Reyes-Hernandez. “You wouldn’t want it attached to you; it would be uncomfortable.”
Reyes-Hernandez doesn’t work on wearable electronics. His field is microfluidics, the study of tiny quantities of liquid and their flow, typically through narrow, thin channels. One day he was exploring a commercially available porous polyester membrane—it feels like ordinary plastic wrap, only a lot lighter and thinner—to see if its tiny holes could make it useful for separating different fluid components. He patterned some gold electrodes onto the membrane to create a simple device that would help with separations. While sitting at his desk, he twisted the plastic a few times and noticed the electrodes, which covered numerous pores as they crisscrossed the surface, still conducted electricity. This wasn’t the case with nonporous membranes.
“Apparently the pores keep the gold from cracking as dramatically as usual,” he said. “The cracks are so tiny that the gold still conducts well after bending.”
Reyes-Hernandez said the porous membrane’s electrodes show even higher conductivity than their counterparts on rigid surfaces, an unexpected benefit that he cannot explain as yet. The next steps, he said, will be to test changes in conductivity over the long term after many bends and twists, and also to build some sort of sensor out of the electrode-coated membrane to explore its real-world usability.
“This thin membrane could fit into very small places,” he said, “and its flexibility and high conductivity make it a very special material, almost one of a kind.”
The institute’s official mission is to:
- Promote U.S. innovation and industrial competitiveness by advancing measurement science, standards, and technology in ways that enhance economic security and improve our quality of life.
NIST had an operating budget for fiscal year 2007 (October 1, 2006-September 30, 2007) of about $843.3 million. NIST’s 2009 budget was $992 million, and it also received $610 million as part of the American Recovery and Reinvestment Act. NIST employs about 2,900 scientists, engineers, technicians, and support and administrative personnel. About 1,800 NIST associates (guest researchers and engineers from American companies and foreign countries) complement the staff.
In addition, NIST partners with 1,400 manufacturing specialists and staff at nearly 350 affiliated centers around the country. NIST publishes the Handbook 44 that provides the “Specifications, tolerances, and other technical requirements for weighing and measuring devices”.
National Institute of Standards and Technology (NIST) research articles from Innovation Toronto
- New Experimental Test Detects Signs of Lyme Disease Near Time of Infection – February 17, 2016
- Nanoworld Snow Blowers: a New Method for Self-Assembly – January 2, 2016
- NIST Team Proves Spooky Action at a Distance is Really Real – November 13, 2015
- NIST Team Breaks Distance Record for Quantum Teleportation – September 30, 2015
- NIST Physicists Show ‘Molecules’ Made of Light May Be Possible – September 14, 2015
- Ultra-stable Microscopy Technique Tracks Tiny Objects for Hours – July 6, 2015
- Shape-Shifting Sensor Can Report Conditions from Deep in the Body – April 7, 2015
- Hybrid Memory Device for Superconducting Computing – February 1, 2015
- Ultrasonically propelled nanorods spin at 150,000 rpm! – July 28, 2014
- New NIST Metamaterial Gives Light a One-Way Ticket – July 5, 2014
- Net-zero energy test house exceeds goal and ends year with energy to spare – July 4, 2014
- A development that could have profound implications for the future of electronics, sensors, energy conversion and energy storage. | metal-organic framework
- Getting 3-D Printing and Next-Generation Manufacturing to the Factory Floor
- Quantum Refrigerator Offers Extreme Cooling and Convenience
- KAIST develops wireless power transfer technology for high capacity transit
- Internet security: Besieged
- These new materials work well up to 100 GHz, opening the door for the next generation of devices for advanced communications.
- NIST Study Advances Use of Iris Images as a Long-Term Form of Identification
- New Filtration Material Could Make Petroleum Refining Cheaper, More Efficient
- Scientists Build Record-Setting Metamaterial Flat Lens
- UBC engineer helps pioneer flat spray-on optical lens
- NIST Demonstrates Significant Improvement in the Performance of Solar-Powered Hydrogen Generation
- A New Delivery for Cancer Drugs
- Prototype Generators Emit Much Less Carbon Monoxide, NIST Finds
- Quantum Teleportation in Space Explored as Message Encryption Solution
- Breakthrough offers new route to large-scale quantum computing
- Tiny new sensor could simplify brain wave research
- Ultrasound Idea
- Chemical-etching technique could lead to diamond micro-machines
- Iron ‘Veins’ Are Secret of Promising New Hydrogen Storage Material
- Reliability Issues for Carbon Nanotubes in Future Electronics Uncovered
- Perception Challenge has next-generation robots in its sights
- ‘Breathalyzers’ May Be Useful for Medical Diagnostics
- Language Translation Devices for US Troops Tested
- Electrical potential
- Home Energy Savings Are Made In The Shade
- Sympathy for the Luddites
- The Patent Wars Begin Over Graphene, A Material That’s About To Change Our Lives
- Net-Zero Energy Buildings Take Hold in U.S.
- Toga, toga, toga
- Energy-efficiency measures could save consumers $41 billion
For the first time, a team including scientists from the National Institute of Standards and Technology (NIST) have used neutron beams to create holograms of large solid objects, revealing details about their interiors in ways that ordinary laser light-based visual holograms cannot.
Holograms—flat images that change depending on the viewer’s perspective, giving the sense that they are three-dimensional objects—owe their striking capability to what’s called an interference pattern. All matter, such as neutrons and photons of light, has the ability to act like rippling waves with peaks and valleys. Like a water wave hitting a gap between the two rocks, a wave can split up and then re-combine to create information-rich interference patterns(link is external).
An optical hologram is made by shining a laser at an object. Instead of merely photographing the light reflected from the object, a hologram is formed by recording how the reflected laser light waves interfere with each other. The resulting patterns, based on the waves’ phase differences(link is external), or relative positions of their peaks and valleys, contain far more information about an object’s appearance than a simple photo does, though they don’t generally tell us much about its hidden interior.
Hidden interiors, however, are just what neutron scientists explore. Neutrons are great at penetrating metals and many other solid things, making neutron beams useful for scientists who create a new substance and want to investigate its properties. But neutrons have limitations, too. They aren’t very good for creating visual images; neutron experiment data is usually expressed as graphs that would look at home in a high school algebra textbook. And this data typically tells them about how a substance is made on average—fine if they want to know broadly about an object built from a bunch of repeating structures like a crystal(link is external), but not so good if they want to know the details about one specific bit of it.
But what if we could have the best of both worlds? The research team has found a way.
The team’s previous work, performed at the NIST Center for Neutron Research (NCNR), involved passing neutrons through a cylinder of aluminum that had a tiny “spiral staircase” carved into one of its circular faces. The cylinder’s shape imparted a twist to the neutron beam, but the team also noticed that the beam’s individual neutrons changed phase depending on what section of the cylinder they passed through: the thicker the section, the greater the phase shift. Eventually they realized this was essentially the information they needed to create holograms of objects’ innards, and they detail their method in their new paper.
The discovery won’t change anything about interstellar chess games, but it adds to the palette of techniques scientists have to explore solid materials. The team has shown that all it takes is a beam of neutrons and an interferometer—a detector that measures interference patterns—to create direct visual representations of an object and reveal details about specific points within it.
“Other techniques measure small features as well, only they are limited to measuring surface properties,” said team member Michael Huber of NIST’s Physical Measurement Laboratory. “This might be a more prudent technique for measuring small, 10-micron size structures and buried interfaces inside the bulk of the material.”
The research was a multi-institutional collaboration that included scientists from NIST and the Joint Quantum Institute(link is external), a research partnership of NIST and the University of Maryland, as well as North Carolina State University and Canada’s University of Waterloo.
Paper: D. Sarenac, M.G. Huber, B. Heacock, M. Arif, C.W. Clark, D.G. Cory, C.B. Shahi and D.A. Pushin. Holography with a neutron interferometer. Optics Express. DOI: 10.1364/OE.24.022528(link is external).
Neutron Holography Video
Though they aren’t holograms themselves, these animations demonstrate data that proved that neutron beams—rather than the usual laser light—can be used to create holograms of solid objects, in this case a tiny aluminum plate with a spiral carved into one of its faces.
The first animation illustrates what happens as you slowly move back from the plate, which dominates as the bright circle in the center. Near the end, fainter circles appear at top and bottom (created by interference patterns in the neutron beams) that usefully show the outlines of the plate’s spiral surface.
Animation of neutron scanning data, demonstrating that scientists can use neutron beams to create holograms instead of the usual laser light.
Passing the neutron beam through successively thicker portions of the spiral plate produces the interference data used to create the second animation below, whose “fork” grows greater numbers of tines at right as the plate’s thickness increases. Combining these data with other neutron measurements can produce 3-D holograms, which could make neutron scan results easier for scientists to interpret visually.
Animation of neutron scanning data, demonstrating that scientists can use neutron beams to create holograms instead of the usual laser light.
Multiferroics – materials that exhibit both magnetic and electric order – are of interest for next-generation computing but difficult to create because the conditions conducive to each of those states are usually mutually exclusive. And in most multiferroics found to date, their respective properties emerge only at extremely low temperatures.
Two years ago, researchers in the labs of Darrell Schlom, the Herbert Fisk Johnson Professor of Industrial Chemistry in the Department of Materials Science and Engineering, and Dan Ralph, the F.R. Newman Professor in the College of Arts and Sciences, in collaboration with professor Ramamoorthy Ramesh at UC Berkeley, published a paper announcing a breakthrough in multiferroics involving the only known material in which magnetism can be controlled by applying an electric field at room temperature: the multiferroic bismuth ferrite.
Schlom’s group has partnered with David Muller and Craig Fennie, professors of applied and engineering physics, to take that research a step further: The researchers have combined two non-multiferroic materials, using the best attributes of both to create a new room-temperature multiferroic.
Their paper, “Atomically engineered ferroic layers yield a room-temperature magnetoelectric multiferroic,” was published – along with a companion News & Views piece – Sept. 22 in Nature. The lead authors are Julia Mundy, Ph.D. ’14, a former doctoral student working jointly with Muller and Schlom who’s now a postdoctoral researcher at the University of California, Berkeley; Charles Brooks, Ph.D., a visiting scientist in the Schlom group; and Megan Holtz, a doctoral student in the Muller group.
The group engineered thin films of hexagonal lutetium iron oxide (LuFeO3), a material known to be a robust ferroelectric but not strongly magnetic. The LuFeO3 consists of alternating single monolayers of lutetium oxide and iron oxide, and differs from a strong ferrimagnetic oxide (LuFe2O4), which consists of alternating monolayers of lutetium oxide with double monolayers of iron oxide.
The researchers found, however, that they could combine these two materials at the atomic-scale to create a new compound that was not only multiferroic but had better properties that either of the individual constituents. In particular, they found they need to add just one extra monolayer of iron oxide to every 10 atomic repeats of the LuFeO3 to dramatically change the properties of the system.
That precision engineering was done via molecular-beam epitaxy (MBE), a specialty of the Schlom lab. A technique Schlom likens to “atomic spray painting,” MBE let the researchers design and assemble the two different materials in layers, a single atom at a time.
The combination of the two materials produced a strongly ferrimagnetic layer near room temperature. They then tested the new material at the Lawrence Berkeley National Laboratory (LBNL) Advanced Light Source in collaboration with co-author Ramesh to show that the ferrimagnetic atoms followed the alignment of their ferroelectric neighbors when switched by an electric field.
“It was when our collaborators at LBNL demonstrated electrical control of magnetism in the material that we made that things got super exciting,” Schlom said. “Room-temperature multiferroics are exceedingly rare and only multiferroics that enable electrical control of magnetism are relevant to applications.”
In electronics devices, the advantages of multiferroics include their reversible polarization in response to low-power electric fields – as opposed to heat-generating and power-sapping electrical currents – and their ability to hold their polarized state without the need for continuous power. High-performance memory chips make use of ferroelectric or ferromagnetic materials.
“Our work shows that an entirely different mechanism is active in this new material,” Schlom said, “giving us hope for even better – higher-temperature and stronger – multiferroics for the future.”
Precision time signals sent through the Global Positioning System (GPS) synchronize cellphone calls, time-stamp financial transactions, and support safe travel by aircraft, ship, train and car.
What if GPS goes down? The National Institute of Standards and Technology (NIST) and the U.S. Naval Observatory (USNO), which operate U.S. civilian and military time standards, respectively, have worked with two companies—Monroe, Louisiana-based CenturyLink, and Aliso Viejo, California-based Microsemi—to identify a practical backup possibility: Commercial fiber-optic telecommunications networks.
In GPS systems, transmissions can be disrupted unintentionally by radio interference or the weather in space, for instance. Various types of intentional interference are possible also. Federal agencies have long recognized the need to back up GPS, a collection of several dozen satellites that has provided users with time and position information since the 1970s.
To explore the possibility of using commercial telecom networks as a backup for time services, an ongoing experiment connects the NIST time scales in Boulder, Colorado, with the USNO alternate time scale at Schriever Air Force Base in Colorado Springs by means of CenturyLink’s fiber-optic cables. The two federal time scales, 150 kilometers apart, are ensembles of clocks that generate versions of the international standard for time, Coordinated Universal Time (known as UTC), in real time.
In this experiment, time signals were sent at regular intervals in both directions between the two locations. Researchers measured the differences between the remote (transmitted) and local time.
The results, just presented at a conference(link is external), showed UTC could be transferred with a stability of under 100 nanoseconds (ns, or billionths of a second)—thus meeting the project’s original goal for this metric—as long as the connection remained unbroken. Stability refers to how well the remote and local clocks remain synchronized. Because the signals were forwarded by various pieces of equipment along each path, they experienced significant unequal delays in the two different directions. This reduced overall performance, resulting in an accuracy that did not meet the stated goal of 1 microsecond (millionths of a second).* With the GPS available to calibrate (and thus correct for) the unequal delays, time transfer could be accomplished maintaining that calibration within 100 ns if GPS were to “disappear,” the study suggests.
“The 100 ns stability level is good enough to meet a new telecommunications standard,” said lead author Marc Weiss, a mathematical physicist at NIST. “We’ll continue trying to meet the 1 microsecond accuracy level, which is needed by critical infrastructure such as the power industry.”
The conference paper notes that if the fiber-optic network or its power source went down and had to be re-established, then GPS or some other alternative time reference would be needed to recalibrate the fiber-optic circuit. The authors suggest the fiber network could serve as a partial backup to the GPS, and the GPS could be used for calibration to correct timing delays. Or, to provide a more reliable backup for the GPS, two independent telecom network paths could be used.
In the experiment, fiber-optic cables run from NIST and USNO to their respective nearby CenturyLink offices, where the signals are multiplexed into the network on a dedicated wavelength not shared with any other customers. The experiment began in April 2014 and will run through the end of 2016.
“It appears that there is at least one commercial transport mechanism that could serve to back up GPS for time transfer at the 100 ns level,” the paper concludes. “We have some certainty that similar results will apply if this technique were used as a service across the country.”
The need for precision timing backup has grown along with the importance of GPS. According to a 2013 study by the Government Accountability Office, “GPS is essential to U.S. national security and is a key component in economic growth, safety, and national critical infrastructure sectors.” An inability to mitigate GPS disruptions could result in billions of dollars in economic losses, the study found.
The NIST research is being carried out under a Cooperative Research and Development Agreement among NIST, CenturyLink, and Microsemi, which, in addition to collaborating on the research, is providing equipment that transmits and receives timing signals. The project has been extended to January 2017, with the possibility of testing the technique in a time transfer experiment spanning the nation.
Laser applications may benefit from crystal research by scientists at the National Institute of Standards and Technology (NIST) and China’s Shandong University. They have discovered a potential way to sidestep longstanding difficulties with making the crystals that are a crucial part of laser technology. But the science behind their discovery has experts scratching their heads.
The findings, published today in Science Advances, suggest that the relatively large crystals used to change several properties of light in lasers – changes that are crucial for making lasers into practical tools – might be created by stacking up far smaller, rod-shaped microcrystals that can be grown easily and cheaply.
So far, the team’s microcrystals outperform conventional crystals in some ways, suggesting that harnessing them could signal the end of a long search for a fast, economical way to develop large crystals that would otherwise be prohibitively expensive and time-consuming to create. But the microcrystals also challenge conventional scientific theory as to why they perform as they do.
The color you see in a laser’s light is often different than the one it initially generates. Many lasers create infrared light, which then passes through a crystal converting its energy – and therefore its wavelength – to light of a visible color like green or blue.
Frequently, that crystal is made of potassium diphosphate (KDP), a common material that has properties that make it invaluable: Not only can a KDP crystal alter the light’s color, but it also can act as a switch that changes the light’s polarization (the direction in which its electric field vibrates) or prevent it from passing through the crystal until just the right moment. The data carried by laser light through fiber-optic cables depends on the light’s polarization, and many applications depend on a laser pulse’s timing.
Small KDP crystals are easy to make, and these find use in pocket laser pointers and telecommunications systems alike. But for higher-energy applications, scientists have searched for decades for a way to make large, high-quality crystals that can survive repeated exposure to intense laser pulses, but a solution has remained elusive.
The team has found useful results by growing KDP crystals in solution. These crystals take the form of hexagonal-shaped hollow tubes and long rods just a few micrometers wide. Individually, these KDP microcrystals have an energy-conversion efficiency surpassing even the best KDP crystals under the same conditions, raising the possibility of directly growing crystals for use in telecommunications.
The team also suggests the rods could be stacked up like firewood, building a larger piece out of billions of the tiny filaments. Before they are stacked together they could be coated by a thin layer of conductive material that carries heat away, rendering them capable of handling repeated pulses of high-intensity laser light – potentially broadening their application range if a way can be found to stack them.
The mystery is why the microcrystals perform as they do. Basic physics says they shouldn’t. Conventional physics models indicate that an optical medium like a crystal must not be symmetric about its center if it is to convert energy efficiently, yet these microcrystals appear to break this rule.
“We’ve spoken to a number of experts in different fields worldwide, and none of them can explain it,” says NIST physicist Lu Deng. “Currently no theory can explain the initial growth mechanism of this exotic crystal. It’s challenging our current understanding in fields from crystallography to condensed matter physics.”
While theory catches up with data, Deng said the team is concentrating on the engineering challenges of growing stackable microcrystal rods.
“We can grow more than 1,000 microstructures every 10 minutes or so on a single glass slide, so growing a large amount is not a problem,” he said. “What we need to figure out is how to grow a large fraction of them with nearly uniform cross-sections since that will be important in the final assembly stage.”
Visible lasers offer exquisite control of x-ray light in a tabletop apparatus, potentially providing access to new insights to chemical reactions, proteins, and even atoms’ inner workings.
By crossing two counter-rotating ultrafast laser beams in a gas target, scientists controlled the direction and polarization of laser-like beams in the extreme ultraviolet and soft x-ray portions of the spectrum. This represents a new ability to manipulate x-ray light using visible light, and obviates the need for inefficient and expensive optics that other approaches must use to filter and steer such beams.
This source enables, for example, tabletop measurements of dynamics in novel magnetic materials occurring on the fastest time scales. It also allows scientists to study chiral molecules, such as proteins or DNA, that come in left- and right-handed versions. Furthermore, the method used to generate the beams provides a path to generating isolated attosecond (one quintillionth of a second) pulses of light with circular polarization.
Researchers at JILA, a joint research institute of the University of Colorado and the National Institute of Standards and Technology, have developed a method to produce ultrafast pulses of circularly polarized extreme ultraviolet (EUV) light in a tabletop setup. The approach uses high-harmonic generation (HHG) driven by ultrafast laser pulses. In this process, laser pulses rip electrons from atoms, accelerate the electrons to high energy, and smash them back into the parent ion to generate pulses of extreme ultraviolet light at harmonics of the driving laser frequency. Specifically, the researchers developed a new experimental configuration in collaboration with the Colorado School of Mines, in which the HHG process is driven by two ultrafast laser beams of opposite circular polarization that are crossed in a gas sample. This novel HHG geometry simultaneously generates left- and right-circularly polarized EUV beams at each of the emitted harmonic wavelengths. This approach can be implemented on a laboratory tabletop, and the EUV beams of different helicity and harmonic order are physically separated from each other as well as from the driving lasers. The angular separation of the EUV beams eliminates the need for expensive filters, mirrors, or gratings that otherwise would attenuate and temporally broaden the pulse. This flexible arrangement allows researchers to make measurements at a particular wavelength and polarization by simply placing a sample into the isolated beam path. The researchers demonstrated the practical use of this new light source by measuring the magnetic circular dichroism of a 20-nm iron film. Furthermore, numerical simulations demonstrate that this phase-matching configuration makes possible the generation of isolated attosecond pulses with circular polarization. Before this discovery, there were no experimentally realized methods for generating isolated circularly polarized high harmonics.
Standard antibody is important addition to the toolkits of biological drug manufacturers, regulators
The National Institute of Standards and Technology (NIST) has issued one of the world’s most intricate measurement standards: an exhaustively analyzed antibody protein that the biopharmaceutical industry will use to help ensure the quality of treatments across a widening range of health conditions, including cancers, autoimmune disorders and infectious diseases.
The standard is an antibody protein–consisting of more than 20,000 atoms–analyzed so thoroughly that the material can be used by organizations around the globe to verify and improve their analytical methods for quality control.
Donated by MedImmune, the global biologics research and development arm of AstraZeneca, and then characterized by NIST and collaborators, the new reference material (RM)–NIST RM 8671–is a monoclonal antibody, or mAb. This class of therapeutic compounds is produced in the lab by living cells, usually from mouse or hamster cell lines.
Uniform in composition and structure, mAbs account for five of the 10 top-selling drugs and over $75 billion in annual sales worldwide. According to one estimate, about 300 monoclonal-antibody-based therapeutics are being evaluated for safety and effectiveness in clinical trials.
Antibodies work by binding to and inactivating proteins involved in disease pathways. mAbs also can act like guided missiles that precisely deliver therapeutic payloads of chemicals or radiation.
Chosen for development in consultation with industry, NIST RM 8671 is an important addition to the toolkits of biological drug manufacturers and their suppliers and regulators. It serves as a representative molecule that can be used to determine that methods for assessing product quality are working properly and to evaluate new methods or technologies.
It also provides an industry very mindful of intellectual property concerns with a standard benchmark for everyone, from aspiring startup to multinational firm to regulator.
As such, “it can serve as a common benchmark for future innovation,” explained NIST research chemist John Schiel, who led an international effort that explored and demonstrated uses of the reference mAb. “The material has many anticipated applications–in establishing industry-recognized best practices, for example–and we are hoping that there will be many future uses that we can’t predict from the current state of practice in biopharmaceutical research and production.”
A Useful Tool
Industry experts have indicated that a universally available ‘public’ mAb, characterized and distributed by NIST, will allow better assessment of existing analytical methods and potentially faster adoption of new technologies.
In fact, the utility of the reference material already has been demonstrated by more than 100 collaborators from companies, regulatory agencies and universities around the world. As documented in a three-volume book set published by the American Chemical Society (ACS), the partners engaged in a “crowdsourcing” exercise. Research teams used current and emerging analytical methods to, in effect, take measure of the mAb from many different vantage points before NIST formally released it as a standard.
“NISTmAb, will act as a shared catalyst for developing, troubleshooting, adapting and bridging analytical technologies,” explained Oleg Borisov, director of analytical development at Novavax. “The book from ACS demonstrates this. It presents extensive information and data on a single monoclonal antibody, and describes the methodologies that enabled this state-of-the-art characterization. The result is a comprehensive characterization dossier that should serve as a valuable reference to researchers.”
Schiel, Borisov and Darryl Davis, associate director of biologics research at Janssen R&D, LLC, Pharmaceutical Companies of Johnson & Johnson, are editors of the set, State-of-the-Art and Emerging Technologies for Therapeutic Monoclonal Antibody Characterization.
Each vial of NIST RM 8671 will contain 800 microliters of the NISTmAb at a concentration of 10 milligrams per milliliter. The standard comes with the results of NIST measurements that provide a thorough profile of the standard protein, Schiel said, providing details on size, concentration, composition, structure, purity, stability and other attributes.
Kurt Brorson, a research biologist in the Office of Biotechnology Products at the Food and Drug Administration (FDA), said the new standard can be used as a “universal system suitability test” for many of the assays and test methods used to assure the quality of mAbs. “The biotech industry can more efficiently cross-validate (measurement) methods at different sites or more efficiently develop platform analytics for related molecules,” he explained.
“The NISTmAb should help in answering a simple, yet critical, question that can consume a disproportionate amount of time when deviations arise with testing; is it the sample or the method that is varying?” said Michael Tarlov, chief of NIST’s Biomolecular Measurement Division and leader of the NIST-wide Biomanufacturing Program.
During the NISTmAb’s meticulously recorded audition, NIST and its collaborators developed data comparable to that found in a Biologics License Application submitted to the FDA when a company seeks approval for a new mAb-based therapeutic. These data are available online, along with results of analyses done with still-experimental tools, providing a historical record of NIST RM 8671 that will be updated as more analyses are done and as questions arise and spawn new studies.
Combined with the three-volume book set, the reference material and data repository provide a comprehensive–yet updateable–picture of the state-of-practice in the fastest-growing area of biopharmaceuticals.
“We hope that this compilation serves as a baseline for many years of future collaboration, continued development and ultimately a routine analytical pipeline for rapid time-to-market for mAb therapeutics,” Schiel, Davis and Borisov state in the preface of their book set.
Researchers achieve real-time single molecule electronic DNA sequencing at single-base resolution using a protein nanopore array–a future platform for precision medicine and enabling it to be used in routine medical diagnoses
Researchers from Columbia University, with colleagues at Genia Technologies (Roche), Harvard University and the National Institute of Standards and Technology (NIST) report achieving real-time single molecule electronic DNA sequencing at single-base resolution using a protein nanopore array.
DNA sequencing is the key technology for personalized and precision medicine initiatives, enabling rapid discoveries in biomedical science. An individual’s complete genome sequence provides important markers and guidelines for medical diagnostics, healthcare, and maintaining a healthy life. To date, the cost and speed involved in obtaining highly accurate DNA sequences has been a major challenge. While various advancements have been made over the past decade, the high-throughput sequencing instruments widely used today depend on optics for the detection of four DNA building blocks: A, C, G and T. To explore alternative measurement capabilities, electronic sequencing of an ensemble of DNA templates has been developed for genetic analysis. Nanopore strand sequencing, wherein a single strand DNA is threaded through the nanoscale pores under an applied electrical voltage to produce electronic signals for sequence determination at single molecule level, has recently been developed; however, because the four nucleotides are very similar in their chemical structures, they cannot easily be distinguished using this method. Researchers are therefore actively pursing the research and development of an accurate single-molecule electronic DNA sequencing platform as it has the potential to produce a miniaturized DNA sequencer capable of deciphering the genome to facilitate personalized precision medicine.
A team of researchers at Columbia Engineering, headed by Jingyue Ju (Samuel Ruben-Peter G. Viele Professor of Engineering, Professor of Chemical Engineering and Pharmacology, Director of the Center for Genome Technology & Biomolecular Engineering), with colleagues at Harvard Medical School, led by George Church (Professor of Genetics); Genia Technologies, led by Stefan Roever (CEO of Genia); and John Kasianowicz, the Principal Investigator at NIST, have developed a complete system to sequence DNA in nanopores electronically at single molecule level with single-base resolution. This work, entitled, “Real-Time Single Molecule Electronic DNA Sequencing by Synthesis Using Polymer Tagged Nucleotides on a Nanopore Array,” is published in the journal, Proceedings of the National Academy of Sciences (PNAS) Early Edition: http://www.
Previously, researchers from the laboratories of Ju at Columbia and Kasianowicz at NIST reported the general principle of nanopore sequencing by synthesis (SBS), the feasibility of design and synthesis of polymer-tagged nucleotides as substrates for DNA polymerase, the detection and the differentiation of the polymer tags by nanopore at the single molecule level [Scientific Reports 2, 684 (2012) doi: 10.1038/srep00684; http://www.
As Carl Fuller, lead author, Adjunct Senior Research Scientist in the Ju Laboratory of the Chemical Engineering Department at Columbia and Director of Chemistry at Genia, points out, “The novelty of our nanopore SBS approach begins with the design, synthesis, and selection of four different polymer-tagged nucleotides. We use a DNA polymerase covalently attached to the nanopore and the tagged nucleotides to perform SBS. During replication of the DNA bound to the polymerase, the tag of each complementary nucleotide is captured in the pore to produce a unique electrical signal. Four distinct polymer tags yielding distinct signatures that are recognized by the electronic detector in the nanopore array chip are used for sequence determination. Thus, DNA sequences are obtained for many single molecules in parallel and in real time. The four polymer tags are designed to offer much better distinctions among themselves, in contrast to the small differences among the four native DNA nucleotides, thereby overcoming the major challenge faced by other direct nanopore sequencing methods.” Moreover, the tags can be further optimized with respect to size, charge, and structure to provide optimal resolution in the nanopore SBS system.
“This exciting project brings together scientists and engineers from both academia and industry with combined expertise in molecular engineering, nanotechnology, genomics, electronics and data science to produce revolutionary, cost-effective genetic diagnostic platforms with unprecedented potential for precision medicine,” says Ju. “We are extremely grateful for the generous support from the NIH that enabled us to make rapid progress in the research and development of the nanopore SBS technology, and the outstanding contributions from all the members of our research consortium.”
According to Ju, the researchers have already pushed beyond what was demonstrated in thePNAS study where the sequencing data was obtained on an early prototype sequencer based on nanopore SBS. The throughput and performance of the current sequencer has progressed beyond what was reported in the PNAS paper. The feasibility of reaching read-lengths of over 1000 bases of DNA has recently been achieved. Going forward, the collaborative research team will continue to optimize the tags by tweaking the linkers, structure, and charge at the molecular level, and fine tuning the polymerase and the electronics for the nanopore SBS system with an aim to accurately sequence an entire human genome rapidly and at low cost, thereby enabling it to be used in routine medical diagnoses.
Converting a single photon from one color, or frequency, to another is an essential tool in quantum communication, which harnesses the subtle correlations between the subatomic properties of photons (particles of light) to securely store and transmit information. Scientists at the National Institute of Standards and Technology (NIST) have now developed a miniaturized version of a frequency converter, using technology similar to that used to make computer chips.
The tiny device, which promises to help improve the security and increase the distance over which next-generation quantum communication systems operate, can be tailored for a wide variety of uses, enables easy integration with other information-processing elements and can be mass produced.
The new nanoscale optical frequency converter efficiently converts photons from one frequency to the other while consuming only a small amount of power and adding a very low level of noise, namely background light not associated with the incoming signal.
Frequency converters are essential for addressing two problems. The frequencies at which quantum systems optimally generate and store information are typically much higher than the frequencies required to transmit that information over kilometer-scale distances in optical fibers. Converting the photons between these frequencies requires a shift of hundreds of terahertz (one terahertz is a trillion wave cycles per second).
By chemically modifying and pulverizing a promising group of compounds, scientists at the National Institute of Standards and Technology (NIST) have potentially brought safer, solid-state rechargeable batteries two steps closer to reality.
These compounds are stable solid materials that would not pose the risks of leaking or catching fire typical of traditional liquid battery ingredients and are made from commonly available substances.
Since discovering their properties in 2014, a team led by NIST scientists has sought to enhance the compounds’ performance further in two key ways: Increasing their current-carrying capacity and ensuring that they can operate in a sufficiently wide temperature range to be useful in real-world environments.
Considerable advances have now been made on both fronts, according to Terrence Udovic of the NIST Center for Neutron Research, whose team has published a pair of scientific papers that detail each improvement.
The first advance came when the team found that the original compounds — made primarily of hydrogen, boron and either lithium or sodium — were even better at carrying current with a slight change to their chemical makeup. Replacing one of the boron atoms with carbon improved their ability to conduct charged particles, or ions, which are what carry electricity inside a battery. As the team reported in February in their first paper, the switch made the compounds about 10 times better at conducting.
But perhaps more important was clearing the temperature hurdle. The compounds conducted ions well enough to operate in a battery — as long as it was in an environment typically hotter than boiling water. Unfortunately, there’s not much of a market for such high-temperature batteries, and by the time they cooled to room temperature, the materials’ favorable chemical structure often changed to a less conductive form, decreasing their performance substantially.
One solution turned out to be crushing the compounds’ particles into a fine powder. The team had been exploring particles that are measured in micrometers, but as nanotechnology research has demonstrated time and again, the properties of a material can change dramatically at the nanoscale. The team found that pulverizing the compounds into nanometer-scale particles resulted in materials that could still perform well at room temperature and far below.
“This approach can remove worries about whether batteries incorporating these types of materials will perform as expected even on the coldest winter day,” said Udovic, whose collaborators on the most recent paper include scientists from Japan’s Tohoku University, the University of Maryland and Sandia National Laboratories. “We are currently exploring their use in next-generation batteries, and in the process we hope to convince people of their great potential.”
New language lets researchers design novel biological circuits
MIT biological engineers have devised a programming language that can be used to give new functions to E. coli bacteria. Using this language, anyone can write a program for the function they want, such as detecting and responding to certain environmental conditions. They can then generate a DNA sequence that will achieve it.
Another advantage of this technique is its speed. Until now, “it would take years to build these types of circuits. Now you just hit the button and immediately get a DNA sequence to test,” Voigt says.