In This Issue...
NIST, Maryland Researchers COMMAND a Better Class of Liposomes
Pop a bubble while washing the dishes and you're likely to release a few drops of water trapped when the soapy sphere formed. A few years ago, researchers at the National Institute of Standards and Technology (NIST) pioneered a method* using a microscopic fluidic (microfluidic) device that exploits the same principle to create liquid-filled vesicles called liposomes from phospholipids, the fat complexes that are the building blocks for animal cell membranes. These structures are valued for their potential use as agents to deliver drugs directly to cancers and other disease cells within the body.
Widespread application of liposomes as artificial drug carriers has been hindered by a number of limiting factors such as inconsistency in size, structural instability and high production costs. In a new study,** the NIST and University of Maryland (UM) researchers have detailed the operation of their liposome manufacturing technique—known as COMMAND for COntrolled Microfluidic Mixing And Nanoparticle Determination—in order to maximize its effectiveness. Their goal was to better understand how COMMAND works as it produces liposomes with diameters controlled from about 50 to 150 nanometers (billionths of a meter) that are consistently uniform in size and inexpensively produced in what might be called an "assembly-line-on-a-microchip."
The researchers fabricate the COMMAND microfluidic devices by etching tiny channels into a silicon wafer with the same techniques used for making integrated circuits. In COMMAND, phospholipid molecules dissolved in isopropyl alcohol are fed via a central inlet channel into a "mixer" channel and "focused" into a fluid jet by a water-based solution (that in production would carry a drug or other cargo for the vesicles) added through two side channels. The components blend together as they mix by diffusion across the interfaces of the flowing fluid streams, directing the phospholipid molecules to self-assemble into nanoscale vesicles of controlled size. Different microfluidic device designs and fluid flow conditions were tested to investigate their role in producing liposomes.
The research team found that their liposome manufacturing process fundamentally depends on the flow and mixing of the fluid streams. The size of the liposomes can be "tuned" by manipulating the fluid flow rates, which in combination with the dimensions of the microfluidic device, determine the resulting mixing conditions. A tightly focused stream of phospholipid-carrying alcohol flowing at a slow rate tends to mix quickly with the buffer at the beginning of the mixing channel and forms small vesicles. A loosely focused stream flowing at a fast rate travels farther down the length of the mixing channel, allowing more mixing time and yielding larger vesicles.
The geometry of the channels plays an additional role, the researchers noted, in regulating the speed of production and the quantity and concentration of liposomes manufactured. This may be important for future clinical applications of liposomes as well as the integration of COMMAND into more complicated microchip systems for health care.
* A. Jahn, W.N. Vreeland, M. Gaitan and L.E. Locascio. Controlled vesicle self-assembly in microfluidic channels with hydrodynamic focusing. Journal of the American Chemical Society. Vol. 126, 2674-2675 (Feb. 17, 2004).
** A. Jahn, S.M. Stavis, J.S. Hong, W.N. Vreeland, D.L. DeVoe and M. Gaitan. Microfluidic mixing and the formation of nanoscale lipid vesicles. ACS Nano. Published online March 31, 2010.
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NIST Develops 'Dimmer Switch' for Superconducting Quantum Computing
Scientists at the National Institute of Standards and Technology (NIST) have developed the first "dimmer switch" for a superconducting circuit linking a quantum bit (qubit) and a quantum bus—promising technologies for storing and transporting information in future quantum computers. The NIST switch is a new type of control device that can "tune" interactions between these components and potentially could speed up the development of a practical quantum computer.
Quantum computers, if they can be built, would use the curious rules of quantum mechanics to solve certain problems that are now intractable, such as breaking today’s most widely used data encryption codes, or running simulations of quantum systems that could unlock the secrets of high-temperature superconductors. Unlike many competing systems that store and transport information using the quantum properties of individual atoms, superconducting qubits use a "super flow" of oscillating electrical current to store information in the form of microwave energy. Superconducting quantum devices are fabricated like today’s silicon processor chips and may be easy to manufacture at the large scales needed for computation.
As described in a forthcoming paper in Physical Review Letters,* the new NIST switch can reliably tune the interaction strength or rate between the two types of circuits—a qubit and a bus—from 100 megahertz to nearly zero. The advance could enable researchers to flexibly control the interactions between many circuit elements in an intricate network as would be needed in a quantum computer of a practical size.
Other research groups have demonstrated switches for two or three superconducting qubits coupled together, but the NIST switch is the first to produce predictable quantum behavior over time with the controllable exchange of an individual microwave photon (particle of light) between a qubit and a resonant cavity. The resonant cavity serves as what engineers call a "bus"—a channel for moving information from one section of the computer to another. "We have three different elements all working together, coherently (in concert with each other) and without losing a lot of energy," says the CU-Boulder graduate student Michael (Shane) Allman who performed the experiments with NIST physicist Ray Simmonds, the principal investigator.
All three components (qubit, switch, and cavity) were made of aluminum in an overlapping pattern on a sapphire chip (see image). The switch is a radio-frequency SQUID (superconducting quantum interference device), a magnetic field sensor that acts like a tunable transformer. The circuit is created with a voltage pulse that places one unit of energy—a single microwave photon—in the qubit. By tuning a magnetic field applied to the SQUID, scientists can alter the coupling energy or transfer rate of the single photon between the qubit and cavity. The researchers watch this photon slosh back and forth at a rate they can now adjust with a knob.
The switch research was supported in part by the Army Research Office. Simmonds’s group previously demonstrated the first superconducting quantum bus between qubits (see "Digital Cable Goes Quantum: NIST Debuts Superconducting Quantum Computing Cable," www.nist.gov/public_affairs/releases/quantum_cable.html, which also describes how the superconducting qubits operate).
* M.S. Allman, F. Altomare, J.D. Whittaker, K. Cicak, D. Li, A. Sirois, J. Strong, J.D. Teufel, R.W. Simmonds. 2010. rf-SQUID-Mediated Coherent Tunable Coupling Between a Superconducting Phase Qubit and a Lumped Element Resonator. Physical Review Letters. Forthcoming.
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Lollipops and Ice Fishing: Molecular Rulers Used to Probe Nanopores
Using a pair of exotic techniques including a molecular-scale version of ice fishing, a team of researchers working at the National Institute of Standards and Technology (NIST) have developed methods to measure accurately the length of "nanopores," the miniscule channels found in cell membranes. The "molecular rulers" they describe in a recent paper* could serve as a way to calibrate tailor-made nanopores—whose diameters on average are nearly 10,000 times smaller than that of a human hair—for a variety of applications such as rapid DNA analysis.
Studies at NIST and other research institutions have shown that a single nanometer-scale pore in a thin membrane can be used as a "miniature analysis laboratory" to detect and characterize individual biological molecules such as DNA or toxins as they pass through or block the passage. Such a system could potentially fit on a single microchip device, for a wide variety of applications. However, making the mini-lab practical requires an accurate definition of the dimensions and structural features of the nanopore.
In new experiments, researchers from NIST and the University of Maryland first built a membrane—a bilayer sheet of lipid molecules—similar to that found in animal cells. They "drilled" a pore in it with a protein** designed specifically to penetrate cell membranes. When voltage is applied across the membrane wall, charged molecules such as single-stranded DNA are forced into the nanopore. As the molecule passes into the channel, the ionic current flow is reduced for a time that is proportional to the size of the chain, allowing its length to be easily derived.
If a chain is long enough to reach the narrowest part of the nanopore—known as the pinch point—the force of the electrical field behind it will push the molecule on through the rest of the channel. Exploiting this characteristic, the NIST/Maryland team developed a DNA probe method to measure the distances from the openings on each side of the membrane to the pinch point, and in turn, the entire length of the nanopore by adding the two measurements together. The probes consist of DNA strands of known lengths topped on one end by a polymer sphere. The sphere prevents the probe from completely moving through the nanopore while leaving the DNA chain dangling from it free to extend into the channel. If the chain reaches the pinch point, the force that would normally drive a free DNA chain past the junction instead holds the probe in place (since the polymer sphere "locks" it at the other end) and defines the distance to the pinch point. If the chain is shorter than the distance to the pinch point, it will be bounced out of the nanopore, telling researchers that a longer-length chain is needed to measure the distance to the gap.
The NIST/Maryland researchers also developed a second means of measuring the length of the nanopore to confirm the results of the "single lollipop" method. In this system, polymer molecules are allowed to circulate freely in the solution found on the inner side of the membrane. Polymer-capped DNA probes of different lengths are forced one at a time into the nanopore from the opposite side. If the end of a probe’s chain is long enough to completely transverse the channel, it will grab hold of a free polymer molecule in solution. This defines the length of the channel.
Additionally, this "ice fishing" method provides insight into the structure of the nanopore. As the DNA chain winds its way through, changes in electrical voltage correspond to the changing shape of the channel. This information can be used to effectively map the passageway.
* S.E. Henrickson, E.A. DiMarzio, Q. Wang, V.M. Stanford and J.J. Kasianowicz. Probing single nanometer-scale pores with polymeric molecular rulers. The Journal of Chemical Physics 132, 135101 (published online April 2, 2010).
** Alpha-hemolysin, produced by the Staphylococcus aureus bacteria
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To Improve Lung Cancer Diagnosis, Good Medicine Is a Polymer Pill
Doctors may soon be able to diagnose lung cancer more effectively thanks to research performed at the National Institute of Standards and Technology (NIST), where scientists have found ways both to increase the accuracy of computed tomography (CT) scans and to lessen the amount of time necessary to perceive telltale changes in lung tissue.*
For years, radiologists have determined the size of potentially cancerous lung nodules by measuring the largest distance across them as displayed on a computer screen in two dimensions. A method called RECIST is widely used for this purpose, but some members of the research community have suggested that three-dimensional analysis, or volumetrics, may provide a better way to determine the size of the nodules. Recently, a NIST team quantified this improvement: Volumetrics could allow physicians to notice volume changes that are up to 10 times smaller than RECIST can, potentially cutting diagnosis time from six months to four weeks—a critical difference in terms of a patient’s chance of survival.
CT scans combine a series of X-ray views taken from many different angles to produce cross-sectional images of the body, but there are several approaches to interpreting scan data, so NIST’s Zachary Levine set out to determine which was best by creating a set of reference objects that could mimic potential lung tumors. His team measured 283 polymer-silicate ellipsoids of precise volume that resemble pills ranging from four to 11 mm in diameter.
“For diagnosis in the earliest stage of cancer, other studies have shown this is the size of nodule you want to be looking at,” says Levine.
The team encased the mimics in foam rubber and put them into layered racks of a box akin to one that holds fishing tackle. Because foam appears transparent to the CT reconstruction, in a scan the denser mimics look very much like tumors. The team was then able to compare their ellipsoids’ known volumes with what the volumetrics and RECIST methods indicated from the scan data.
“We found that volumetrics allows you to notice volume changes that are a factor of 10 smaller than RECIST can with a similar level of confidence,” Levine says. “This implies that you could notice life-threatening changes from a follow-up scan performed only weeks after the first, instead of months.”
Levine cautions that cancers often grow in strange shapes not resembling elliptical pills which can make a diagnosis more difficult, but that the study was a good start toward improving data interpretation.
“Our work only applies to the simplest of cases, but it’s still a large class of lung cancers,” he says.
* Z.H. Levine, B.R. Borchardt, N.J. Brandenburg, C.W. Clark, B. Muralikrishnan, C.M. Shakarji, J.J. Chen, and E.L. Siegel. RECIST vs. Volume Measurement in Medical CT Using Ellipsoids of Known Size. Optics Express, Vol. 18, Issue 8, pp. 8151–8159, 2010.
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New Study Helps Explain the Surprising Behavior of Tiny 'Artificial Muscles'
Using neutron beams and atomic-force microscopes, a team of university researchers working with the National Institute of Standards and Technology (NIST) may have resolved a 10-year-old question about an exotic class of "artificial muscles"—how do they work? Their results* could influence the design of future specialized robotic tools.
These "artificial muscles," first demonstrated in the early 1990s, are "ionic polymer metal composite" (IPMC) actuators, a thin polymer strip plated on both surfaces with conducting metal. The basic unit of the polymer molecule has a charged component attached to it (hence, "ionic"), and it forms a sort of open, permeable structure that can be soaked with water molecules and oppositely charged ions. A modest electric charge across the metalized surfaces will cause the strip to flex in one direction; an alternating charge will make it wiggle like a fish's tail. But why?
"There has been a lot of debate as to the mechanism of actuation in these kinds of systems," says NIST materials scientist Kirt Page. One possibility was that the electric charge on the metalized faces causes the polymer and the free ions to reorient themselves next to the metal, stretching one side and contracting the other. But using a neutron beam at the NIST Center for Neutron Research (NCNR) to watch an IPMC in action as it wiggled back and forth, the team found something very different. Neutrons are particularly good for mapping the locations of water molecules, and they showed that a major force in the actuator is hydraulics. "The water and ions move to one electrode swelling one side and dehydrating the other, causing that to contract, and it bends in that direction," explains Virginia Tech professor Robert Moore, who directed the research. "Then you flip the potential, the ions come screaming back—positive ions again moving towards the new negative electrode—and you can go back and forth."
It happens surprisingly fast, according to Page. "People weren't quite convinced that water could actually move over these distances that quickly," he says, "This paper is the first to show that in fact, this gradient in the water concentration is established almost instantaneously."
A better understanding of just how IPMC actuators work could allow researchers to engineer better materials of this type with improved performance. Current actuators can be small and light-weight, and they can flex over relatively large distances, but the force they can generate is low so these "muscles" are not very strong, according to Moore. They could be used in microfluidic systems as pumps or valves, as tiny robotic grippers in applications where other actuators are impractical or even, says Moore, "as actual artificial muscles in living tissues. I think we're still in the infancy stage of using these. There are still quite a number of details about the mechanism that we need to unlock."
* J.K. Park, P.J. Jones, C. Sahagun, K.A. Page, D.S. Hussey, D.L. Jacobson, S.E. Morgan and R.B. Moore. Electrically stimulated gradients in water and counterion concentrations within electroactive polymer actuators Soft Matter. 2010. 6. 1444–1452. DOI: 10.1039/b922828d.
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Seeing Moiré in Graphene
Researchers at the National Institute of Standards and Technology (NIST) and the Georgia Institute of Technology have demonstrated* that atomic scale moiré patterns, an interference pattern that appears when two or more grids are overlaid slightly askew, can be used to measure how sheets of graphene are stacked and reveal areas of strain. The ability to determine the rotational orientation of graphene sheets and map strain is useful for understanding the electronic and transport properties of multiple layers of graphene, a one-atom thick form of carbon with potentially revolutionary semiconducting properties.
In digital photography, moiré (pronounced mwar-ray) patterns occur because of errors in the rendering process, which causes grid patterns to look wavy or distorted. Materials scientists have been using microscopic moiré patterns to detect stresses such as wrinkles or bulges in a variety of materials.
Researchers created graphene on the surface of a silicon carbide substrate at the Georgia Institute of Technology by heating one side so that only carbon, in the form of multilayer sheets of graphene, was left. Using a custom-built scanning tunneling microscope at NIST, the researchers were able to peer through the topmost layers of graphene to the layers beneath. This process, which the group dubbed “atomic moiré interferometry,” enabled them to image the patterns created by the stacked graphene layers, which in turn allowed the group to model how the hexagonal lattices of the individual graphene layers were stacked in relation to one another.
Unlike other materials that tend to stretch out when they cool, graphene bunches up like a wrinkled bed sheet. The researchers were able to map these stress fields by comparing the relative distortion of the hexagons of carbon atoms that comprise the individual graphene layers. Their technique is so sensitive that it is able to detect strains in the graphene layers causing as little as a 0.1 percent change in atom spacing.
This collaboration between NIST and the Georgia Institute of Technology is part of a series of experiments aimed at gaining a fundamental understanding of the properties of graphene. Other examples of the group’s work can been seen at www.mrs.org/s_mrs/bin.asp?CID=8684&DID=320520&DOC=FILE.PDF and www.mrs.org/s_mrs/bin.asp?CID=26616&DID=320529&DOC=FILE.PDF.
Their article, “Structural analysis of multilayer graphene via atomic moiré interferometry” was selected as an Editor’s Highlight in Physical Review B for the month of March, 2010.
* D. Miller, K. Kubista, G. Rutter, M. Ruan, W. de Heer, P. First and J. Stroscio. Structural analysis of multilayer graphene via atomic moiré interferometry. Physical Review B. 81. 125427. Published March 24, 2010. http://prb.aps.org/abstract/PRB/v81/i12/e125427
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USGv6 Stakeholders Meet to Discuss Testing Program and Updated Protocol
The National Institute of Standards and Technology (NIST) is hosting a public meeting on May 20, 2010 at the NIST site in Gaithersburg, Md., to review a compliance testing program and upcoming revisions to the standards profile for USGv6, the United States government implementation of the new Internet protocol, IPv6. The USGv6 Program provides a technical infrastructure to assist federal agencies in the acquisition of IPv6 technologies.
Recent modifications to Federal Acquisition Regulations require agencies to begin using the USGv6 Profile and Test Program beginning in July 2010.
The USGv6 Test Program presently has two participating accreditors and two accredited laboratories, with more test labs in consideration. (See “First Test Labs for Next-Generation Internet Protocol (IPv6) Are Accredited,” NIST Tech Beat, March 2, 2010, at www.nist.gov/public_affairs/techbeat/tb2010_0302.htm#ipv6 for more about the test labs.)
NIST is holding the meeting to review the test program and to acquire feedback from stakeholders from agencies, IPv6 product vendors and test laboratories. Issues to be discussed include USGv6 capabilities and requirements, testing operations and interlaboratory comparisons and reporting of test results.
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Teams Gearing Up for Two NIST Robotic Competitions in Alaska
The recruitment period is over. The competitors have been selected. Let the games begin!
The National Institute of Standards and Technology (NIST) has announced that 11 university teams will square off next week in two contests designed to prove the viability of advanced technologies for robotic manufacturing automation and microrobotics. The Virtual Manufacturing Automation Competition (VMAC) and the Mobile Microrobotics Challenge (MMC) are both part of the IEEE International Conference on Robotics and Automation in Anchorage, Alaska, from May 2-6, 2010.
Vying for top honors in the VMAC will be two teams from Georgia Tech, Atlanta, Ga.; one group from the University of New Mexico, Albuquerque, N.M.; and an international squad from the University of Zagreb, Croatia. They will use off-the-shelf computer gaming engines to run simulations of a robot picking up boxes of various sizes and weights from a conveyor belt and then arranging them on a pallet for shipping. There will be several rounds in the virtual reality competition, beginning with basic scenarios and adding complexity to the tasks as the rounds progress. Successful simulations will then be run for real using Automated Guided Vehicles (AGVs) to deliver packages in a one-third scale factory environment.
Seven teams will compete in the MMC: Carnegie-Mellon University, Pittsburgh, Pa.; ETH, a science and technology university in Zürich, Switzerland; the French Team (a group consisting of researchers from the FEMTO-ST Institute and the Institut des Systèmes Intelligents et de Robotique, or ISIR), Paris, France; Stevens Institute of Technology, Hoboken, N.J.; the University of Maryland, College Park, Md.; the University of Waterloo, Ontario, Canada; and the U.S. Naval Academy, Annapolis, Md. Their tiny robots—whose dimensions are measured in micrometers (millionths of a meter)—will be pitted against each other in three tests: a two-millimeter dash in which the microbots sprint across a distance equal to the diameter of a pin head; a microassembly task where pegs must be inserted into designated holes; and a freestyle competition where each team chooses a task for its robot that emphasizes one or more abilities from among system reliability, level of autonomy, power management and task complexity.
NIST is conducting the VMAC in cooperation with IEEE and Georgia Tech, and collaborating on the MMC with the IEEE Robotics and Automation Society. The partners are hosting these two competitions to “road test” many of the skills that future industrial robots—both full-size and miniature—will need to carry out their functions.
For more information, see “Manufacturing Competition Challenges University Teams to Stack a Better Pallet,” NIST Tech Beat, Jan. 26, 2010, at www.nist.gov/public_affairs/techbeat/tb2010_0126.htm#robots and “Is Your Microrobot Up for the (NIST) Challenge?” NIST Tech Beat, Oct. 20, 2009, at www.nist.gov/public_affairs/techbeat/tb2009_1020.htm#micro.
For more details on the Mobile Microrobotics Challenge, including profiles of the seven miniscule contestants, a closer look at the world’s smallest sports arena and descriptions of the three competitions, go to 2010 NIST Mobile Microrobotics Challenge.
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