Researchers design placenta-on-a-chip to better understand pregnancy

National Institutes of Health (NIH) researchers and their colleagues have developed a "placenta-on-a-chip" to study the inner workings of the human placenta and its role in pregnancy. The device was designed to imitate, on a micro-level, the structure and function of the placenta and model the transfer of nutrients from mother to fetus. This prototype is one of the latest in a series of organ-on-a-chip technologies developed to accelerate biomedical advances. The study, published online in the ("Placenta-on-a-chip: a novel platform to study the biology of the human placenta"), was conducted by an interdisciplinary team of researchers from the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the University of Pennsylvania, Wayne State University/Detroit Medical Center, Seoul National University and Asan Medical Center in South Korea. "We believe that this technology may be used to address questions that are difficult to answer with current placenta model systems and help enable research on pregnancy and its complications," said Roberto Romero, M.D., chief of the NICHD's Perinatology Research Branch and one of the study authors. The placenta is a temporary organ that develops in pregnancy and is the major interface between mother and fetus. Among its many functions is to serve as a "crossing guard" for substances traveling between mother and fetus. The placenta helps nutrients and oxygen move to the fetus and helps waste products move away. At the same time, the placenta tries to stop harmful environmental exposures, like bacteria, viruses and certain medications, from reaching the fetus. When the placenta doesn't function correctly, the health of both mom and baby suffers. Researchers are trying to learn how the placenta manages all this traffic, transporting some substances and blocking others. This knowledge may one day help clinicians better assess placental health and ultimately improve pregnancy outcomes. However, studying the placenta in humans is challenging: it is time-consuming, subject to a great deal of variability and potentially risky for the fetus. For those reasons, previous studies on placental transport have relied largely on animal models and on laboratory-grown human cells. These methods have yielded helpful information, but are limited as to how well they can mimic physiological processes in humans. The researchers created the placenta-on-a-chip technology to address these challenges, using human cells in a structure that more closely resembles the placenta's maternal-fetal barrier. The device consists of a semi-permeable membrane between two tiny chambers, one filled with maternal cells derived from a delivered placenta and the other filled with fetal cells derived from an umbilical cord. After designing the structure of the model, the researchers tested its function by evaluating the transfer of glucose (a substance made by the body when converting carbohydrates to energy) from the maternal compartment to the fetal compartment. The successful transfer of glucose in the device mirrored what occurs in the body. "The chip may allow us to do experiments more efficiently and at a lower cost than animal studies," said Dr. Romero. "With further improvements, we hope this technology may lead to better understanding of normal placental processes and placental disorders."
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Structural origin of glass transition

A University of Tokyo research group has demonstrated through computer simulations that the enhancement of fluctuations in a liquid’s structure plays an important role as a liquid becomes a solid near the glass-transition point, a temperature below the melting point ("Assessing the role of static length scales behind glassy dynamics in polydisperse hard disks"). This result increases our understanding of the origin of the glass transition and is expected to shed new light on the structure of liquids, thought until now to have been uniform and random. Snapshot of correlation of particle structure and dynamics at density of 0.97 Snapshot of correlation of particle structure and dynamics at density of 0.97. Disks are colored according to the following criteria: white, low mobility and high order; black, high mobility and low order; cyan, low mobility and low order; and magenta, high mobility and high order. (Image: John Russo, Hajime Tanaka) Normally, a liquid changes to a solid when its temperature becomes lower than the melting point. However, some materials remain liquid even below the melting point, finally solidifying with further cooling (supercooling) at what is called the glass-transition point. Despite intensive research over the years, its physical mechanism has remained elusive. One possibility is that increasing structural order develops in a supercooled liquid upon cooling, increasing the size of that structure and thus slowing down the dynamics and leading to the glass transition. Because the structure of liquids that undergo a glass transition is disordered, it was difficult to detect fluctuations of such a structure, but a new method has been proposed recently. This method does not depend on the type of liquid structure and has attracted much attention as it may enable extraction of structure size, which is key to understanding slow dynamics, for all liquids. The research group of Professor Hajime Tanaka and Project Research Associate John Russo at the Institute of Industrial Science, the University of Tokyo, were only able to retrieve the separation distance of two particles using this method, finding instead that this method fails at extracting the correlation between more than two particles (many-body correlations) which are key for understanding the glass transition. In a liquid composed of disk-shaped particles that do not deform no matter how much force is applied (a hard disc liquid), it is apparent that the dynamics of the liquid are dominated by a hexagonal lattice structure that is impossible to extract using this method. “These findings not only support the physical mechanism proposed by this group that slow glassy dynamics is a consequence of the development of structural fluctuations in a supercooled liquid, but also provides a new insight into the liquid phase, which was believed to be uniform and random, and leads to a deeper understanding of the very nature of the supercooled liquid state,” says Professor Tanaka.
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Graphene wrappings could boost chip speeds by up to 30 percent

A typical computer chip includes millions of transistors connected with an extensive network of copper wires. Although chip wires are unimaginably short and thin compared to household wires both have one thing in common: in each case the copper is wrapped within a protective sheath. For years a material called tantalum nitride has formed protective layer in chip wires. Now Stanford-led experiments demonstrate that a different sheathing material, graphene, can help electrons scoot through tiny copper wires in chips more quickly. graphene
Graphene is a single layer of carbon atoms arranged in a strong yet thin lattice. Stanford electrical engineer H.-S. Philip Wong says this modest fix, using graphene to wrap wires, could allow transistors to exchange data faster than is currently possible. And the advantages of using graphene would become greater in the future as transistors continue to shrink.

"Researchers have made tremendous advances on all of the other components in chips but recently, there hasn't been much progress on improving the performance of the wires," he said.

Wong led a team of six researchers, including two from the University of Wisconsin-Madison, who will present their findings at the Symposia of VLSI Technology and Circuits in Kyoto, a leading venue for the electronics industry.

Ling Li, a graduate student in electrical engineering at Stanford and first author of the research paper, explained why changing the exterior wrapper on connecting wires can have such a big impact on chip performance.

It begins with understanding the dual role of this protective layer: it isolates the copper from the silicon on the chip and also serve to conduct electricity. On silicon chips, the transistors act like tiny gates to switch electrons on or off. That switching function is how transistors process data. The copper wires between the transistors transport this data once it is processed. The isolating material--currently tantalum nitride--keeps the copper from migrating into the silicon transistors and rendering them non-functional. Why switch to graphene? Two reasons, starting with the ceaseless desire to keep making electronic components smaller. When the Stanford team used the thinnest possible layer of tantalum nitride needed to perform this isolating function, they found that the industry-standard was eight times thicker than the graphene layer that did the same work. Graphene had a second advantage as a protective sheathing and here it's important to differentiate how this outer layer functions in chip wires versus a household wires. In house wires the outer layer insulates the copper to prevent electrocution or fires. In a chip the layer around the wires is a barrier to prevent copper atoms from infiltrating the silicon. Were that to happen the transistors would cease to function. So the protective layer isolates the copper from the silicon The Stanford experiment showed that graphene could perform this isolating role while also serving as an auxiliary conductor of electrons. Its lattice structure allows electrons to leap from carbon atom to carbon atom straight down the wire, while effectively containing the copper atoms within the copper wire. These benefits--the thinness of the graphene layer and its dual role as isolator and auxiliary conductor--allow this new wire technology to carry more data between transistors, speeding up overall chip performance in the process. In today's chips the benefits are modest; a graphene isolator would boost wire speeds from four percent to 17 percent, depending on the length of the wire. But as transistors and wires continue to shrink in size, the benefits of the ultrathin yet conductive graphene isolator become greater. The Stanford engineers estimate that their technology could increase wire speeds by 30 percent in the next two generations. The Stanford researchers think the promise of faster computing will induce other researchers to get interested in wires, and help to overcome some of the hurdles needed to take this proof of principle into common practice. This would include techniques to grow graphene, especially growing it directly onto wires while chips are being mass-produced. In addition to his University of Wisconsin collaborator Professor Michael Arnold, Wong cited Purdue University Professor Zhihong Chen. Wong noted that the idea of using graphene as an isolator was inspired by Cornell University Professor Paul McEuen and his pioneering research on the basic properties of this marvelous material. Alexander Balandin of the University of California-Riverside has also made contributions to using graphene in chips. "Graphene has been promised to benefit the electronics industry for a long time, and using it as a copper barrier is perhaps the first realization of this promise," Wong said.
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