Technique enables development of viable diagnostic tests and instruments in fight against cancer
Cancer is the second leading cause of death in the U.S., making early, reliable diagnosis and treatment a priority for researchers. Genomic biomarkers offer great potential for diagnostics and new forms of treatment, such as immunotherapy. Miniaturized lab-on-chip approaches are prime candidates for developing viable diagnostic tests and instruments because they are small, need only limited test volumes, and can be cost-effective.
A team of scientists and engineers from the University of California, Santa Cruz and Brigham Young University have developed just such an approach capable of processing biomolecular samples from blood. Their method can analyze and identify multiple targets on a silicon-based molecular detection platform and is described this week in Biomicrofluidics, from AIP Publishing.
Laboratory–on-a-chip describes the miniaturization of laboratory functions such as blood testing on a chip. Instead of transferring relatively large (micro- to milliliters) samples between test tubes or using bulky analytical equipment, samples and reagents are handled on chip-scale devices with fluidic microchannels. This requires much smaller test volumes, and multiple functions can be integrated on a single device, improving speed, reliability and portability of these lab processes.
“Our approach uses optofluidic chips where both fluid processing and optical sensing are done on a chip, allowing for further miniaturization and performance enhancements of the chip system,” said Holger Schmidt, a Narinder Kapany professor of electrical engineering at the University of California, Santa Cruz.
The entire process of testing was a challenge for the team, led by Schmidt and Aaron Hawkins, a physics professor at Brigham Young University. Each of the chips had to be developed and tested for multiple functions, from filtering of blood cells without clogging the filter to reliably analyzing optical data to create the right excitation patterns on the silicon chip. However, the process worked as envisioned, and the team was pleasantly surprised to see just how powerful the multi-spot optical excitation method actually was.
The next step to realizing the potential of this research is to move toward real clinical samples and to detect individual DNA biomarkers.
“We have shown single nucleic acid analysis in the context of on-chip Ebola detection and would like to transfer that to this application,” said Schmidt.
Other goals for the team include increasing the speed of the analysis process, and integrating more optical elements on the chip. They also want to expand their capabilities to analyzing protein biomarkers in addition to nucleic acids and whole virus particles already demonstrated.
This research is expected to have a wide range of applications because the underlying principle of this kind of on-chip optical analysis and manipulation is very general.
“In the near term, we hope to build new diagnostic instruments for molecular diagnostics with applications in oncology and infectious disease detection, both viruses and (drug-resistant) bacteria,” Schmidt said. “In addition, these chips could be very useful for fundamental research in molecular biology and other life sciences since they can provide analysis of single nano- and microparticles without the need for expensive equipment. And they require a relatively low amount of experimental skills.”
The AIP is made up of various member societies. Its corporate headquarters are at the American Center for Physics in College Park, Maryland, but the institute also has an office in Melville, New York and Beijing, China.
The focus of the AIP appears to be organized around a set of core activities. The first delineated activity is to support member societies regarding essential society functions. This is accomplished by annually convening the various society officers to discuss common areas of concern. A range of topics is discussed which includes scientific publishing, public policy issues, membership-base issues, philanthropic giving, science education, science careers for a diverse population, and a forum for sharing ideas.
Another core activity is publishing the science of physics in research journals, magazines, and conference proceedings. Other core activities are tracking employment and education trends with six decades of coverage, being a liaison between research science and industry, historical collections and outreach programs, and supporting science education initiatives and supporting undergraduate physics. One other core activity is as an advocate for science policy to the U.S. Congress and the general public.
American Institute of Physics research articles from Innovation Toronto
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Interdisciplinary approach makes linking biological materials and electronic devices possible
One of the biggest challenges in cognitive or rehabilitation neurosciences is the ability to design a functional hybrid system that can connect and exchange information between biological systems, like neurons in the brain, and human-made electronic devices. A large multidisciplinary effort of researchers in Italy brought together physicists, chemists, biochemists, engineers, molecular biologists and physiologists to analyze the biocompatibility of the substrate used to connect these biological and human-made components, and investigate the functionality of the adhering cells, creating a living biohybrid system.
In an article appearing this week in AIP Advances, from AIP Publishing, the research team used the interaction between light and matter to investigate the material properties at the molecular level using Raman spectroscopy, a technique that, until now, has been principally applied to material science. Thanks to the coupling of the Raman spectrometer with a microscope, spectroscopy becomes a useful tool for investigating micro-objects such as cells and tissues. Raman spectroscopy presents clear advantages for this type of investigation: The molecular composition and the modi?cation of subcellular compartments can be obtained in label-free conditions with non-invasive methods and under physiological conditions, allowing the investigation of a large variety of biological processes both in vitro and in vivo.
Once the biocompatibility of the substrate was analyzed and the functionality of the adhering cells investigated, the next part of this puzzle is connecting with the electronic component. In this case a memristor was used.
“Its name reveals its peculiarity (MEMory ResISTOR), it has a sort of “memory”: depending on the amount of voltage that has been applied to it in the past, it is able to vary its resistance, because of a change of its microscopic physical properties,” said Silvia Caponi, a physicist at the Italian National Research Council in Rome. By combining memristors, it is possible to create pathways within the electrical circuits that work similar to the natural synapses, which develop variable weight in their connections to reproduce the adaptive/learning mechanism. Layers of organic polymers, like polyaniline (PANI) a semiconductor polymer, also have memristive properties, allowing them to work directly with biological materials into a hybrid bio-electronic system.
“We applied the analysis on a hybrid bio-inspired device but in a prospective view, this work provides the proof of concept of an integrated study able to analyse the status of living cells in a large variety of applications that merges nanosciences, neurosciences and bioelectronics,” said Caponi. A natural long-term objective of this work would be interfacing machines and nervous systems as seamlessly as possible.
The multidisciplinary team is ready to build on this proof of principle to realize the potential of memristor networks.
“Once assured the biocompatibility of the materials on which neurons grow,” said Caponi, “we want to define the materials and their functionalization procedures to find the best configuration for the neuron-memristor interface to deliver a full working hybrid bio-memristive system.”
Learn more: Researchers Create Living Bio-Hybrid System
New method can deposit nanomaterials onto flexible surfaces and 3-D objects
Printing has come a long way since the days of Johannes Gutenberg. Now, researchers have developed a new method that uses plasma to print nanomaterials onto a 3-D object or flexible surface, such as paper or cloth. The technique could make it easier and cheaper to build devices like wearable chemical and biological sensors, flexible memory devices and batteries, and integrated circuits.
One of the most common methods to deposit nanomaterials–such as a layer of nanoparticles or nanotubes–onto a surface is with an inkjet printer similar to an ordinary printer found in an office. Although they use well-established technology and are relatively cheap, inkjet printers have limitations. They can’t print on textiles or other flexible materials, let alone 3-D objects. They also must print liquid ink, and not all materials are easily made into a liquid.
Some nanomaterials can be printed using aerosol printing techniques. But the material must be heated several hundreds of degrees to consolidate into a thin and smooth film. The extra step is impossible for printing on cloth or other materials that can burn, and means higher cost for the materials that can take the heat.
The plasma method skips this heating step and works at temperatures not much warmer than 40 degrees Celsius. “You can use it to deposit things on paper, plastic, cotton, or any kind of textile,” said Meyya Meyyappan of NASA Ames Research Center. “It’s ideal for soft substrates.” It also doesn’t require the printing material to be liquid.
The researchers, from NASA Ames and SLAC National Accelerator Laboratory, describe their work in Applied Physics Letters, from AIP Publishing>.
They demonstrated their technique by printing a layer of carbon nanotubes on paper. They mixed the nanotubes into a plasma of helium ions, which they then blasted through a nozzle and onto paper. The plasma focuses the nanoparticles onto the paper surface, forming a consolidated layer without any need for additional heating.
The team printed two simple chemical and biological sensors. The presence of certain molecules can change the electrical resistance of the carbon nanotubes. By measuring this change, the device can identify and determine the concentration of the molecule. The researchers made a chemical sensor that detects ammonia gas and a biological sensor that detects dopamine, a molecule linked to disorders like Parkinson’s disease and epilepsy.
But these were just simple proofs-of-principle, Meyyappan said. “There’s a wide range of biosensing applications.” For example, you can make sensors that monitor health biomarkers like cholesterol, or food-borne pathogens like E. coli and Salmonella.
Because the method uses a simple nozzle, it’s versatile and can be easily scaled up. For example, a system could have many nozzles like a showerhead, allowing it to print on large areas. Or, the nozzle could act like a hose, free to spray nanomaterials on the surfaces of 3-D objects.
“It can do things inkjet printing cannot do,” Meyyappan said. “But anything inkjet printing can do, it can be pretty competitive.”
The method is ready for commercialization, Meyyappan said, and should be relatively inexpensive and straightforward to develop. Right now, the researchers are designing the technique to print other kinds of materials such as copper. They can then print materials used for batteries onto thin sheets of metal such as aluminum. The sheet can then be rolled into tiny batteries for cellphones or other devices.
Learn more: Printing nanomaterials with plasma
Hall thrusters are advanced electric rocket engines primarily used for station-keeping and attitude control of geosynchronous communication satellites and space probes.
Recently, the launch of two satellites based on an all-electric bus has marked the debut of a new era – one in which Hall thrusters could be used not just to adjust orbits, but to power the voyage as well. Consuming 100 million times less propellant or fuels than conventional chemical rockets, a Hall thruster is an attractive candidate for exploring Mars, asteroids and the edge of the solar system. By saving fuel the thruster could leave room for spacecraft and send a large amount of cargo in support of space missions. However, the current lifespan of Hall thrusters, which is around 10,000 operation hours, is too short for most space explorations, which require at least 50,000 operation hours.
To prolong the lifespan of Hall thrusters, a team of researchers from the French National Center for Scientific Research have experimentally optimized the operation of a novel, wall-less thruster prototype developed a year ago by the same team. The preliminary performance results were satisfactory, the team said, and pave the way toward developing a high-efficiency wall-less Hall thruster suitable for long-duration, deep space missions. The researchers present their work in a paper published this week in the journal Applied Physics Letters, from AIP Publishing.
Hall thrusters are electric rocket engines using a super high speed (on the order of 45,000 mph) stream of plasma to push spacecraft forward. Their operating principle relies on the creation of a low-pressure quasi-neutral plasma discharge in a crossed magnetic and electric field configuration. The propellant gas, typically xenon, is ionized by electrons trapped in the magnetic field.
In the conventional Hall thruster configuration, the magnetized discharge is confined to an annular dielectric cavity with the anode at one end, where the gas is injected, and an external cathode injecting electrons. Ionization of the propellant gas occurs inside the cavity, with ions accelerated by the electric field that stretches from the interior to the exterior of the cavity.
“The major drawback of Hall thrusters is that the discharge channel wall materials largely determine the discharge properties, and consequently, the performance level and the operational time,” said Julien Vaudolon, the primary researcher in the Electric Propulsion team led by Professor Stéphane Mazouffre in the ICARE-CNRS Laboratory, France.
Vaudolon explained that the wall materials play a role in the plasma properties mainly through secondary electron emission, a phenomenon where high-energy ions hit the channel wall surface and induce the emission of secondary electrons. Additionally, the erosion of the discharge cavity walls due to bombardment of high-energy ions shortens the thruster’s lifetime.
“Thus, an effective approach to avoid the interaction between the plasma and the discharge channel wall is to move the ionization and acceleration regions outside the cavity, which is an unconventional design named a Wall-Less Hall Thruster,” Vaudolon said.
Last year, the team developed a small-scale, wall-less thruster prototype based on a classical Hall thruster. At first the researchers simply moved the anode to the channel exhaust plane. However, this first wall-less thruster turned out to be a low-performance device, as the magnetic field lines are perpendicular to the thruster axis, which cross the anode placed at the channel exhaust plane.
“Magnetic fields are used to trap hot electrons injected from the external cathode and prevent them from reaching the anode,” Vaudolon said. “Basically an electron travels along the magnetic field line. If the magnetic field lines cross the anode, a large portion of hot electrons will be collected at the anode and won’t take part in the ionization of the xenon atoms, resulting in high discharge current, low ionization degree, and consequently, low performance level.”
To optimize the wall-less prototype and make the magnetic lines avoid the anode surface, the team rotated the magnetic barrier by 90 degrees, so that it injected the magnetic field lines parallel with the axial direction. The anode was still placed at the channel exhaust plane, but its shape is curved to avoid any interaction with the magnetic field lines.
Based on the PPS-Flex, a 1.5 kilowatts class thruster designed by the GREM3 Team at LAPLACE Laboratory, France and capable of modifying the magnetic field topology over a broad range of configurations, the team has validated their optimization strategies by modifying several parts and parameters of the thruster. The measurement of some operation parameters such as the thrust level, anode efficiency and far-field ion properties displayed a satisfactory performance level. However, Vaudolon said, some further optimization is still needed for the thruster’s efficient operation at high power.
“The wall-less thruster allows scientists to observe regions of the plasma previously hidden behind the channel walls. Now the plasma region can be observed and diagnosed using probes and/or laser diagnostic tools,” Vaudolon said. He also pointed out that the access to key regions of the plasma facilitates a thorough investigation of plasma instability and small-scale turbulence for a better understanding of the discharge physics and anomalous electron transport.
“Despite decades of research, the physics of Hall thrusters is still far from being understood, and the device characterization methods still rely on trials and testing, leading to expensive efforts,” Vaudolon said. “The major difficulty in developing predictive simulations lies in modeling the interaction between plasma and wall. The wall-less design would be an effective solution, potentially making future predictive simulations feasible and reliable.”
Tunable radiation source that reaches coveted THz region of spectrum could be used for medical imaging or security applications
Terahertz radiation, the no-man’s land of the electromagnetic spectrum, has long stymied researchers. Optical technologies can finagle light in the shorter-wavelength visible and infrared range, while electromagnetic techniques can manipulate longer-wavelength radiation like microwaves and radio waves. Terahertz radiation, on the other hand, lies in the gap between microwaves and infrared, whether neither traditional way to manipulate waves works effectively. As a result, creating coherent artificial sources of terahertz radiation in order to harness it for human use requires some ingenuity.
Difficulties of generating it aside, terahertz radiation has a wide variety of potential applications, particularly in medical and security fields. Because it’s a non-ionizing form of radiation, it is generally considered safe to use on the human body. For instance, it can distinguish between tissues of different water content or density, making it a potentially valuable tool for identifying tumors. It could also be used to detect explosives or hidden weapons, or to wirelessly transmit data.
In a step towards more widespread use of terahertz radiation, researchers have designed a new device that can convert a DC electric field into a tunable source of terahertz radiation. Their results are published this week in the Journal of Applied Physics, from AIP Publishing.
This device exploits the instabilities in the oscillation of conducting electrons at the device’s surface, a phenomenon known as surface plasmon resonance. To address the terahertz gap, the team created a hybrid semiconductor: a layer of thick conducting material paired with two thin, two-dimensional crystalline layers made from graphene, silicene (a graphene-like material made from silicon instead of carbon), or a two-dimensional electron gas. When a direct current is passed through the hybrid semiconductor, it creates a plasmon instability at a particular wavenumber. This instability induces the emission of terahertz radiation, which can be harnessed with the help of a surface grating that splits the radiation.
By adjusting various parameters — such as the density of conduction electrons in the material or the strength of the DC electric field — it is possible to tune the cutoff wavenumber and, consequently, the frequency of the resulting terahertz radiation.
“[Our work] demonstrates a new approach for efficient energy conversation from a dc electric field to coherent, high-power and electrically tunable terahertz emission by using hybrid semiconductors,” said Andrii Iurov, a researcher with a dual appointment at the University of New Mexico‘s Center for High Technology Materials and the City University of New York. “Additionally, our proposed approach based on hybrid semiconductors can be generalized to include other novel two-dimensional materials, such as hexagonal boron nitride, molybdenum disulfide and tungsten diselenide.”
Other labs have created artificial sources of terahertz radiation, but this design could enable better imaging capabilities than other sources can provide. “Our proposed devices can retain the terahertz frequency like other terahertz sources but with a much shorter wavelength for an improved spatial resolution in imaging application as well as a very wide frequency tuning range from a microwave to a terahertz wave,” said Iurov.