Tag Archives: Northwestern University

Congratulations to Markus Buehler on his Foresight Institute Feynman Prize for advances in nanotechnology

A May 24, 2016 Massachusetts Institute of Technology (MIT) news release celebrates Markus Buehler’s latest award,

On May 21 [2016], Department of Civil and Environmental Engineering head and McAfee Professor of Engineering Markus J. Buehler received the 2015 Foresight Institute Feynman Prize in Theoretical Molecular Nanotechnology. Buehler’s award was one of three prizes presented by the Foresight Institute, a leading think tank and public interest organization, at its annual conference in Palo Alto, California. …

The Foresight Institute recognized Buehler for his important contributions to making nanotechnology scalable for large-scale materials applications, enabled by bottom-up multiscale computational methods, and linking new manufacturing and characterization methods.

Focusing on mechanical properties — especially deformation and failure — and translation from biological materials and structures to bio-inspired synthetic materials, his work has led to the development and application of new modeling, design, and manufacturing approaches for advanced materials that offer greater resilience and a wide range of controllable properties from the nano- to the macroscale.

Buehler’s signature achievement, according to the Institute, is the application of molecular and chemical principles in the analysis of mechanical systems, with the aim to design devices and materials that provide a defined set of functions.

“It’s an incredible honor to receive such an esteemed award. I owe this to the outstanding students and postdocs whom I had a pleasure to work with over the years, my colleagues, as well my own mentors,” Buehler said. “Richard Feynman was a revolutionary scientist of his generation. It’s a privilege to share his goals of researching molecular technology at very small scale to create new, more efficient, and better lasting materials at much larger scale that will help transform lives and industries.”

The two other award winners are Professor Michelle Y. Simmons of the University of New South Wales [Australia], who won the Feynman Prize for Experimental Molecular Nanotechnology, and Northwestern University graduate student Chuyang Cheng, who won the Distinguished Student Award.

I have featured Buehler’s work here a number of times. The most recent appearance was in  a May 29, 2015 posting about synthesizing spider’s silk.

“One minus one equals zero” has been disproved

Two mirror-image molecules can be optically active according to an April 27, 2016 news item on ScienceDaily,

In 1848, Louis Pasteur showed that molecules that are mirror images of each other had exactly opposite rotations of light. When mixed in solution, they cancel the effects of the other, and no rotation of light is observed. Now, a research team has demonstrated that a mixture of mirror-image molecules crystallized in the solid state can be optically active.

An April 26, 2016 Northwestern University news release (also on EurekAlert), which originated the news item, expands on the theme,

In the world of chemistry, one minus one almost always equals zero.

But new research from Northwestern University and the Centre National de la Recherche Scientifique (CNRS) in France shows that is not always the case. And the discovery will change scientists’ understanding of mirror-image molecules and their optical activity.

Now, Northwestern’s Kenneth R. Poeppelmeier and his research team are the first to demonstrate that a mixture of mirror-image molecules crystallized in the solid state can be optically active. The scientists first designed and made the materials and then measured their optical properties.

“In our case, one minus one does not always equal zero,” said first author Romain Gautier of CNRS. “This discovery will change scientists’ understanding of these molecules, and new applications could emerge from this observation.”

The property of rotating light, which has been known for more than two centuries to exist in many molecules, already has many applications in medicine, electronics, lasers and display devices.

“The phenomenon of optical activity can occur in a mixture of mirror-image molecules, and now we’ve measured it,” said Poeppelmeier, a Morrison Professor of Chemistry in the Weinberg College of Arts and Sciences. “This is an important experiment.”

Although this phenomenon has been predicted for a long time, no one — until now — had created such a racemic mixture (a combination of equal amounts of mirror-image molecules) and measured the optical activity.

“How do you deliberately create these materials?” Poeppelmeier said. “That’s what excites me as a chemist.” He and Gautier painstakingly designed the material, using one of four possible solid-state arrangements known to exhibit circular dichroism (the ability to absorb differently the “rotated” light).

Next, Richard P. Van Duyne, a Morrison Professor of Chemistry at Northwestern, and graduate student Jordan M. Klingsporn measured the material’s optical activity, finding that mirror-image molecules are active when arranged in specific orientations in the solid state.

Here’s a link to and a citation for the paper,

Optical activity from racemates by Romain Gautier, Jordan M. Klingsporn, Richard P. Van Duyne, & Kenneth R. Poeppelmeier. Nature Materials (2016) doi:10.1038/nmat4628 Published online 18 April 2016

This paper is behind a paywall.

Trojan horse nanoparticle for asthma

A brand new technique for dealing with asthma is being proposed by researchers at Northwestern University (US), according to an April 18, 2016 news item on ScienceDaily,

In an entirely new approach to treating asthma and allergies, a biodegradable nanoparticle acts like a Trojan horse, hiding an allergen in a friendly shell, to convince the immune system not to attack it, according to new Northwestern Medicine research. As a result, the allergic reaction in the airways is shut down long- term and an asthma attack prevented.

The technology can be applied to food allergies as well. The nanoparticle is currently being tested in a mouse model of peanut allergy, similar to food allergy in humans.

“The findings represent a novel, safe and effective long-term way to treat and potentially ‘cure’ patients with life-threatening respiratory and food allergies,” said senior author Stephen Miller, the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. “This may eliminate the need for life-long use of medications to treat lung allergy.”

An April 18, 2016 Northwestern University news release (also on EurekAlert) by Marla Paul, which originated the news item, expands on the theme,

It’s the first time this method for creating tolerance in the immune system has been used in allergic diseases. The approach has been used in autoimmune diseases including multiple sclerosis and celiac disease in previous preclinical Northwestern research.

The asthma allergy study was in mice, but the technology is progressing to clinical trials in autoimmune disease. The nanoparticle technology is being developed commercially by Cour Pharmaceuticals Development Co., which is working with Miller to bring this new approach to patients. A clinical trial using the nanoparticles to treat celiac disease is in development.

“It’s a universal treatment,” Miller said. “Depending on what allergy you want to eliminate, you can load up the nanoparticle with ragweed pollen or a peanut protein.”

The nanoparticles are composed of an FDA-approved biopolymer called PLGA that includes lactic acid and glycolic acid.

Also a senior author is Lonnie Shea, adjunct professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and of obstetrics and gynecology at Feinberg, and chair of biomedical engineering at the University of Michigan.

When the allergen-loaded nanoparticle is injected into the bloodstream of mice, the immune system isn’t concerned with it because it sees the particle as innocuous debris. Then the nanoparticle and its hidden cargo are consumed by a macrophage, essentially a vacuum-cleaner cell.

“The vacuum-cleaner cell presents the allergen or antigen to the immune system in a way that says, ‘No worries, this belongs here,’” Miller said. The immune system then shuts down its attack on the allergen, and the immune system is reset to normal.

The allergen, in this case egg protein, was administered into the lungs of mice who have been pretreated to be allergic to the protein and already had antibodies in their blood against it. So when they were re-exposed to it, they responded with an allergic response like asthma. After being treated with the nanoparticle, they no longer had an allergic response to the allergen.

The approach also has a second benefit. It creates a more normal, balanced immune system by increasing the number of regulatory T cells, immune cells important for recognizing the airway allergens as normal. This method turns off the dangerous Th2 T cell that causes the allergy and expands the good, calming regulatory T cells.

If I understand this rightly, they’re rebalancing the immune system so it doesn’t treat innocuous material (dust, mould, etc.) as an allergen.

Here’s a link to and a citation for the paper,

Biodegradable antigen-associated PLG nanoparticles tolerize Th2-mediated allergic airway inflammation pre- and postsensitization by Charles B. Smarr, Woon Teck Yap, Tobias P. Neef, Ryan M. Pearson, Zoe N. Hunter, Igal Ifergan, Daniel R. Getts, Paul J. Bryce, Lonnie D. Shea, and Stephen D. Miller. PNAS 2016 doi: 10.1073/pnas.1505782113 Published ahead of print April 18, 2016,

This paper is behind a paywall.

Babies have more general physics knowledge than experts realized

A Feb. 10, 2016 news item on ScienceDaily sheds some light on babies and their knowledge of physics,

We are born with a basic grasp of physics, just enough not to be surprised when we interact with objects. Scientists discovered this in the past two decades. What they did not know yet was that, as early as five months of age, this ‘naive’ physics also extends to liquids and materials that do not behave like solids (for example, sand), as demonstrated by a new study.

A Feb. 10, 2016 SISSA (International School of Advanced Studies) press release (also on EurekAlert), which originated the news item, describes the conclusions and the research in more detail,

If we hold a ball and then let go of it and the ball remains suspended in mid-air, even a baby a few months old will be surprised. Just like an adult, the baby expects the ball to fall to the floor. Even at such a young age humans already have some rudimentary knowledge of the behaviour of solids. Now a new study extends this knowledge to add liquids and other non-solids to the “naïve physics” of infants.

“This new study developed out of previous experiments”, explains Alissa Ferry, SISSA research scientist and among the authors of the paper, “in which we observed that infants were surprised when a liquid failed to behave as a liquid (in those experiments we “cheated” by disguising solids as liquids)”. Their surprise, explains Ferry, demonstrates that their expectations for a liquid had not been met. “However, what we couldn’t establish was whether the infants knew how a liquid should behave or whether they just expected it to be different from a solid”.

Ferry and colleagues (the first author is Susan Hespos of Northwestern University in Illinois, USA, where the experiments were conducted) therefore devised a new set of tests with a greater range of materials and “interactions”. In a first “habituation” phase, the infants were shown the contents of a glass by tilting the glass in front of them. The glass either contained a solid (which, when not moving, had identical appearance to water) or some water. When the glass was tilted back and forth, the two materials behaved differently: the solid remained perfectly still whereas the water moved. This phase served to teach the infants whether they were looking at a solid or a liquid.

Next, the infants were shown an identical glass to the one seen in the previous phase (making them believe that it was the same glass) which contained either the material they had already seen or the other material. At this point, the infants watched the experimenter either pour the contents (liquid or solid) of the glass into another glass containing a grid or submerge the grid in the liquid (or rest it on top of the solid) inside the glass.

“In the previous experiments we merely poured the contents of the glass. This time we added a grid to find out whether the infants really understood the loose cohesiveness of liquids, which can pass through a perforated surface and recompose in the vessel unlike solids which, being highly cohesive, cannot pass through a grid” explains Ferry.

In the habituation phase, in fact, the infants could know how liquids change shape with movement, but it was unknown if they could use this knowledge to understand other properties of liquids, like loose cohesiveness. “If infants understand the properties of liquids, then they should be surprised when, what they think is a liquid gets trapped on a grid”.

And the analysis of the infants’ behaviour shows that when they expected a liquid they were surprised to see it blocked by the grid (or see the grid unable to penetrate the material). Conversely, if they thought they were looking at a solid, then they were surprised when they saw it pass through the grid.

The investigators also used other materials like sand and small glass spheres. “Even in these cases the infants showed that they knew the behaviour of substances”, concludes Ferry. “This is especially interesting because, while we can imagine that 5-month-old infants already have had extensive direct experience with liquids and especially water through meals, baths and 9 months in the amniotic liquid, it’s unlikely that they’ve had many encounters with sand or glass balls, suggesting that infants have a naïve understanding of the physics of nonsolid substances”.

Here’s a link to and a citation for the paper,

Five-Month-Old Infants Have General Knowledge of How Nonsolid Substances Behave and Interact by Susan J. Hespos, Alissa L. Ferry, Erin M. Anderson, Emily N. Hollenbeck, anb Lance J. Rips. Psychological Science February 2016 vol. 27 no. 2 244-256 doi: 10.1177/0956797615617897 Published online: January 7, 2016

This paper is behind a paywall.

A view to controversies about nanoparticle drug delivery, sticky-flares, and a PNAS surprise

Despite all the excitement and claims for nanoparticles as vehicles for drug delivery to ‘sick’ cells there is at least one substantive problem, the drug-laden nanoparticles don’t actually enter the interior of the cell. They are held in a kind of cellular ‘waiting room’.

Leonid Schneider in a Nov. 20, 2015 posting on his For Better Science blog describes the process in more detail,

A large body of scientific nanotechnology literature is dedicated to the biomedical aspect of nanoparticle delivery into cells and tissues. The functionalization of the nanoparticle surface is designed to insure their specificity at targeting only a certain type of cells, such as cancers cells. Other technological approaches aim at the cargo design, in order to ensure the targeted release of various biologically active agents: small pharmacological substances, peptides or entire enzymes, or nucleotides such as regulatory small RNAs or even genes. There is however a main limitation to this approach: though cells do readily take up nanoparticles through specific membrane-bound receptor interaction (endocytosis) or randomly (pinocytosis), these nanoparticles hardly ever truly reach the inside of the cell, namely its nucleocytoplasmic space. Solid nanoparticles are namely continuously surrounded by the very same membrane barrier they first interacted with when entering the cell. These outer-cell membrane compartments mature into endosomal and then lysosomal vesicles, where their cargo is subjected to low pH and enzymatic digestion. The nanoparticles, though seemingly inside the cell, remain actually outside. …

What follows is a stellar piece featuring counterclaims about and including Schneider’s own journalistic research into scientific claims that the problem of gaining entry to a cell’s true interior has been addressed by technologies developed in two different labs.

Having featured one of the technologies here in a July 24, 2015 posting titled: Sticky-flares nanotechnology to track and observe RNA (ribonucleic acid) regulation and having been contacted a couple of times by one of the scientists, Raphaël Lévy from the University of Liverpool (UK), challenging the claims made (Lévy’s responses can be found in the comments section of the July 2015 posting), I thought a followup of sorts was in order.

Scientific debates (then and now)

Scientific debates and controversies are part and parcel of the scientific process and what most outsiders, such as myself, don’t realize is how fraught it is. For a good example from the past, there’s Leviathan and the Air-Pump: Hobbes, Boyle, and the Experimental Life (from its Wikipedia entry), Note: Links have been removed),

Leviathan and the Air-Pump: Hobbes, Boyle, and the Experimental Life (published 1985) is a book by Steven Shapin and Simon Schaffer. It examines the debate between Robert Boyle and Thomas Hobbes over Boyle’s air-pump experiments in the 1660s.

The style seems more genteel than what a contemporary Canadian or US audience is accustomed to but Hobbes and Boyle (and proponents of both sides) engaged in bruising communication.

There was a lot at stake then and now. It’s not just the power, prestige, and money, as powerfully motivating as they are, it’s the research itself. Scientists work for years to achieve breakthroughs or to add more to our common store of knowledge. It’s painstaking and if you work at something for a long time, you tend to be invested in it. Saying you’ve wasted ten years of your life looking at the problem the wrong way or have misunderstood your data is not easy.

As for the current debate, Schneider’s description gives no indication that there is rancour between any of the parties but it does provide a fascinating view of two scientists challenging one of the US’s nanomedicine rockstars, Chad Mirkin. The following excerpt follows the latest technical breakthroughs to the interior portion of the cell through three phases of the naming conventions (Nano-Flares, also known by its trade name, SmartFlares, which is a precursor technology to Sticky-Flares), Note: Links have been removed,

The next family of allegedly nucleocytoplasmic nanoparticles which Lévy turned his attention to, was that of the so called “spherical nucleic acids”, developed in the lab of Chad Mirkin, multiple professor and director of the International Institute for Nanotechnology at the Northwestern University, USA. These so called “Nano-Flares” are gold nanoparticles, functionalized with fluorophore-coupled oligonucleotides matching the messenger RNA (mRNA) of interest (Prigodich et al., ACS Nano 3:2147-2152, 2009; Seferos et al., J Am. Chem.Soc. 129:15477-15479, 2007). The mRNA detection method is such that the fluorescence is initially quenched by the gold nanoparticle proximity. Yet when the oligonucleotide is displaced by the specific binding of the mRNA molecules present inside the cell, the fluorescence becomes detectable and serves thus as quantitative read-out for the intracellular mRNA abundance. Exactly this is where concerns arise. To find and bind mRNA, spherical nucleic acids must leave the endosomal compartments. Is there any evidence that Nano-Flares ever achieve this and reach intact the nucleocytoplasmatic space, where their target mRNA is?

Lévy’s lab has focused its research on the commercially available analogue of the Nano-Flares, based on the patent to Mirkin and Northwestern University and sold by Merck Millipore under the trade name of SmartFlares. These were described by Mirkin as “a powerful and prolific tool in biology and medical diagnostics, with ∼ 1,600 unique forms commercially available today”. The work, led by Lévy’s postdoctoral scientist David Mason, now available in post-publication process at ScienceOpen and on Figshare, found no experimental evidence for SmartFlares to be ever found outside the endosomal membrane vesicles. On the contrary, the analysis by several complementary approaches, i.e., electron, fluorescence and photothermal microscopy, revealed that the probes are retained exclusively within the endosomal compartments.

In fact, even Merck Millipore was apparently well aware of this problem when the product was developed for the market. As I learned, Merck performed a number of assays to address the specificity issue. Multiple hundred-fold induction of mRNA by biological cell stimulation (confirmed by quantitative RT-PCR) led to no significant changes in the corresponding SmartFlare signal. Similarly, biological gene downregulation or experimental siRNA knock-down had no effect on the corresponding SmartFlare fluorescence. Cell lines confirmed as negative for a certain biomarker proved highly positive in a SmartFlare assay.  Live cell imaging showed the SmartFlare signal to be almost entirely mitochondrial, inconsistent with reported patterns of the respective mRNA distributions.  Elsewhere however, cyanine dye-labelled oligonucleotides were found to unspecifically localise to mitochondria   (Orio et al., J. RNAi Gene Silencing 9:479-485, 2013), which might account to the often observed punctate Smart Flare signal.

More recently, Mirkin lab has developed a novel version of spherical nucleic acids, named Sticky-Flares (Briley et al., PNAS 112:9591-9595, 2015), which has also been patented for commercial use. The claim is that “the Sticky-flare is capable of entering live cells without the need for transfection agents and recognizing target RNA transcripts in a sequence-specific manner”. To confirm this, Lévy used the same approach as for the striped nanoparticles [not excerpted here]: he approached Mirkin by email and in person, requesting the original microscopy data from this publication. As Mirkin appeared reluctant, Lévy invoked the rules for data sharing by the journal PNAS, the funder NSF as well as the Northwestern University. After finally receiving Mirkin’s thin-optical microscopy data by air mail, Lévy and Mason re-analyzed it and determined the absence of any evidence for endosomal escape, while all Sticky-Flare particles appeared to be localized exclusively inside vesicular membrane compartments, i.e., endosomes (Mason & Levy, bioRxiv 2015).

I encourage you to read Schneider’s Nov. 20, 2015 posting in its entirety as these excerpts can’t do justice to it.

The PNAS surprise

PNAS (Proceedings of the National Academy of Science) published one of Mirkin’s papers on ‘Sticky-flares’ and is where scientists, Raphaël Lévy and David Mason, submitted a letter outlining their concerns with the ‘Sticky-flares’ research. Here’s the response as reproduced in Lévy’s Nov. 16, 2015 posting on his Rapha-Z-Lab blog

Dear Dr. Levy,

I regret to inform you that the PNAS Editorial Board has declined to publish your Letter to the Editor. After careful consideration, the Board has decided that your letter does not contribute significantly to the discussion of this paper.

Thank you for submitting your comments to PNAS.

Sincerely yours,
Inder Verma
Editor-in-Chief

Judge for yourself, Lévy’s and Mason’s letter can be found here (pdf) and here.

Conclusions

My primary interest in this story is in the view it provides of the scientific process and the importance of and difficulty associated with the debates.

I can’t venture an opinion about the research or the counterarguments other than to say that Lévy’s and Mason’s thoughtful challenge bears more examination than PNAS is inclined to accord. If their conclusions or Chad Mirkin’s are wrong, let that be determined in an open process.

I’ll leave the very last comment to Schneider who is both writer and cartoonist, from his Nov. 20, 2015 posting,

LeonidSchneiderImagination

A perovskite memristor with three stable resistive states

Thanks to Dexter Johnson’s Oct. 22, 2015 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers]) website, I’ve found information about a second memristor with three terminals, aka, three stable resistive states,  (the first is mentioned in my April 10, 2015 posting). From Dexter’s posting (Note: Links have been removed),

Now researchers at ETH Zurich have designed a memristor device out of perovskite just 5 nanometres thick that has three stable resistive states, which means it can encode data as 0,1 and 2, or a “trit” as opposed to a “bit.”

The research, which was published in the journal ACS Nano, developed model devices that have two competing nonvolatile resistive switching processes. These switching processes can be alternatively triggered by the effective switching voltage and time applied to the device.

“Our component could therefore also be useful for a new type of IT (Information Technology) that is not based on binary logic, but on a logic that provides for information located ‘between’ the 0 and 1,” said Jennifer Rupp, professor in the Department of Materials at ETH Zurich, in a press release. “This has interesting implications for what is referred to as fuzzy logic, which seeks to incorporate a form of uncertainty into the processing of digital information. You could describe it as less rigid computing.”

An Oct. 19, 2015 Swiss National Science Foundation press release provides context for the research,

Two IT giants, Intel and HP, have entered a race to produce a commercial version of memristors, a new electronics component that could one day replace flash memory (DRAM) used in USB memory sticks, SD cards and SSD hard drives. “Basically, memristors require less energy since they work at lower voltages,” explains Jennifer Rupp, professor in the Department of Materials at ETH Zurich and holder of a SNSF professorship grant. “They can be made much smaller than today’s memory modules, and therefore offer much greater density. This means they can store more megabytes of information per square millimetre.” But currently memristors are only at the prototype stage. [emphasis mine]

There is a memristor-based product on the market as I noted in a Sept. 10, 2015 posting, although that may not be the type of memristive device that Rupp seems to be discussing. (Should you have problems accessing the Swiss National Science Foundation press release, you can find a lightly edited version (a brief [two sentences] history of the memristor has been left out) here on Azonano.

Jacopo Prisco wrote for CNN online in a March 2, 2015 article about memristors and Rupp’s work (Note: A link has been removed),

Simply put, the memristor could mean the end of electronics as we know it and the beginning of a new era called “ionics”.

The transistor, developed in 1947, is the main component of computer chips. It functions using a flow of electrons, whereas the memristor couples the electrons with ions, or electrically charged atoms.

In a transistor, once the flow of electrons is interrupted by, say, cutting the power, all information is lost. But a memristor can remember the amount of charge that was flowing through it, and much like a memory stick it will retain the data even when the power is turned off.

This can pave the way for computers that will instantly turn on and off like a light bulb and never lose data: the RAM, or memory, will no longer be erased when the machine is turned off, without the need to save anything to hard drives as with current technology.

Jennifer Rupp is a Professor of electrochemical materials at ETH Zurich, and she’s working with IBM to build a memristor-based machine.

Memristors, she points out, function in a way that is similar to a human brain: “Unlike a transistor, which is based on binary codes, a memristor can have multi-levels. You could have several states, let’s say zero, one half, one quarter, one third, and so on, and that gives us a very powerful new perspective on how our computers may develop in the future,” she told CNN’s Nick Glass.

This is the CNN interview with Rupp,

Prisco also provides an update about HP’s memristor-based product,

After manufacturing the first ever memristor, Hewlett Packard has been working for years on a new type of computer based on the technology. According to plans, it will launch by 2020.

Simply called “The Machine”, it uses “electrons for processing, photons for communication, and ions for storage.”

I first wrote about HP’s The Machine in a June 25, 2014 posting (scroll down about 40% of the way).

There are many academic teams researching memristors including a team at Northwestern University. I highlighted their announcement of a three-terminal version in an April 10, 2015 posting. While Rupp’s team achieved its effect with a perovskite substrate, the Northwestern team used a molybdenum disulfide (MoS2) substrate.

For anyone wanting to read the latest research from ETH, here’s a link to and a citation for the paper,

Uncovering Two Competing Switching Mechanisms for Epitaxial and Ultrathin Strontium Titanate-Based Resistive Switching Bits by Markus Kubicek, Rafael Schmitt, Felix Messerschmitt, and Jennifer L. M. Rupp. ACS Nano, Article ASAP DOI: 10.1021/acsnano.5b02752 Publication Date (Web): October 8, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

Finally, should you find the commercialization aspects of the memristor story interesting, there’s a June 6, 2015 posting by Knowm CEO (chief executive officer) Alex Nugent waxes eloquent on HP Labs’ ‘memristor problem’ (Note: A link has been removed),

Today I read something that did not surprise me. HP has said that their memristor technology will be replaced by traditional DRAM memory for use in “The Machine”. This is not surprising for those of us who have been in the field since before HP’s memristor marketing engine first revved up in 2008. While I have to admit the miscommunication between HP’s research and business development departments is starting to get really old, I do understand the problem, or at least part of it.

There are two ways to develop memristors. The first way is to force them to behave as you want them to behave. Most memristors that I have seen do not behave like fast, binary, non-volatile, deterministic switches. This is a problem because this is how HP wants them to behave. Consequently a perception has been created that memristors are for non-volatile fast memory. HP wants a drop-in replacement for standard memory because this is a large and established market. Makes sense of course, but its not the whole story on memristors.

Memristors exhibit a huge range of amazing phenomena. Some are very fast to switch but operate probabilistically. Others can be changed a little bit at a time and are ideal for learning. Still others have capacitance (with memory), or act as batteries. I’ve even seen some devices that can be programmed to be a capacitor or a resistor or a memristor. (Seriously).

Nugent, whether you agree with him or not provides, some fascinating insight. In the excerpt I’ve included here, he seems to provide confirmation that it’s possible to state ‘there are no memristors on the market’ and ‘there are memristors on the market’ because different devices are being called memristors.

$81M for US National Nanotechnology Coordinated Infrastructure (NNCI)

Academics, small business, and industry researchers are the big winners in a US National Science Foundation bonanza according to a Sept. 16, 2015 news item on Nanowerk,

To advance research in nanoscale science, engineering and technology, the National Science Foundation (NSF) will provide a total of $81 million over five years to support 16 sites and a coordinating office as part of a new National Nanotechnology Coordinated Infrastructure (NNCI).

The NNCI sites will provide researchers from academia, government, and companies large and small with access to university user facilities with leading-edge fabrication and characterization tools, instrumentation, and expertise within all disciplines of nanoscale science, engineering and technology.

A Sept. 16, 2015 NSF news release provides a brief history of US nanotechnology infrastructures and describes this latest effort in slightly more detail (Note: Links have been removed),

The NNCI framework builds on the National Nanotechnology Infrastructure Network (NNIN), which enabled major discoveries, innovations, and contributions to education and commerce for more than 10 years.

“NSF’s long-standing investments in nanotechnology infrastructure have helped the research community to make great progress by making research facilities available,” said Pramod Khargonekar, assistant director for engineering. “NNCI will serve as a nationwide backbone for nanoscale research, which will lead to continuing innovations and economic and societal benefits.”

The awards are up to five years and range from $500,000 to $1.6 million each per year. Nine of the sites have at least one regional partner institution. These 16 sites are located in 15 states and involve 27 universities across the nation.

Through a fiscal year 2016 competition, one of the newly awarded sites will be chosen to coordinate the facilities. This coordinating office will enhance the sites’ impact as a national nanotechnology infrastructure and establish a web portal to link the individual facilities’ websites to provide a unified entry point to the user community of overall capabilities, tools and instrumentation. The office will also help to coordinate and disseminate best practices for national-level education and outreach programs across sites.

New NNCI awards:

Mid-Atlantic Nanotechnology Hub for Research, Education and Innovation, University of Pennsylvania with partner Community College of Philadelphia, principal investigator (PI): Mark Allen
Texas Nanofabrication Facility, University of Texas at Austin, PI: Sanjay Banerjee

Northwest Nanotechnology Infrastructure, University of Washington with partner Oregon State University, PI: Karl Bohringer

Southeastern Nanotechnology Infrastructure Corridor, Georgia Institute of Technology with partners North Carolina A&T State University and University of North Carolina-Greensboro, PI: Oliver Brand

Midwest Nano Infrastructure Corridor, University of  Minnesota Twin Cities with partner North Dakota State University, PI: Stephen Campbell

Montana Nanotechnology Facility, Montana State University with partner Carlton College, PI: David Dickensheets
Soft and Hybrid Nanotechnology Experimental Resource,

Northwestern University with partner University of Chicago, PI: Vinayak Dravid

The Virginia Tech National Center for Earth and Environmental Nanotechnology Infrastructure, Virginia Polytechnic Institute and State University, PI: Michael Hochella

North Carolina Research Triangle Nanotechnology Network, North Carolina State University with partners Duke University and University of North Carolina-Chapel Hill, PI: Jacob Jones

San Diego Nanotechnology Infrastructure, University of California, San Diego, PI: Yu-Hwa Lo

Stanford Site, Stanford University, PI: Kathryn Moler

Cornell Nanoscale Science and Technology Facility, Cornell University, PI: Daniel Ralph

Nebraska Nanoscale Facility, University of Nebraska-Lincoln, PI: David Sellmyer

Nanotechnology Collaborative Infrastructure Southwest, Arizona State University with partners Maricopa County Community College District and Science Foundation Arizona, PI: Trevor Thornton

The Kentucky Multi-scale Manufacturing and Nano Integration Node, University of Louisville with partner University of Kentucky, PI: Kevin Walsh

The Center for Nanoscale Systems at Harvard University, Harvard University, PI: Robert Westervelt

The universities are trumpeting this latest nanotechnology funding,

NSF-funded network set to help businesses, educators pursue nanotechnology innovation (North Carolina State University, Duke University, and University of North Carolina at Chapel Hill)

Nanotech expertise earns Virginia Tech a spot in National Science Foundation network

ASU [Arizona State University] chosen to lead national nanotechnology site

UChicago, Northwestern awarded $5 million nanotechnology infrastructure grant

That is a lot of excitement.

Center for Sustainable Nanotechnology or how not to poison and make the planet uninhabitable

I received notice of the Center for Sustainable Nanotechnology’s newest deal with the US National Science Foundation in an August 31, 2015 email University of Wisconsin-Madison (UWM) news release,

The Center for Sustainable Nanotechnology, a multi-institutional research center based at the University of Wisconsin-Madison, has inked a new contract with the National Science Foundation (NSF) that will provide nearly $20 million in support over the next five years.

Directed by UW-Madison chemistry Professor Robert Hamers, the center focuses on the molecular mechanisms by which nanoparticles interact with biological systems.

Nanotechnology involves the use of materials at the smallest scale, including the manipulation of individual atoms and molecules. Products that use nanoscale materials range from beer bottles and car wax to solar cells and electric and hybrid car batteries. If you read your books on a Kindle, a semiconducting material manufactured at the nanoscale underpins the high-resolution screen.

While there are already hundreds of products that use nanomaterials in various ways, much remains unknown about how these modern materials and the tiny particles they are composed of interact with the environment and living things.

“The purpose of the center is to explore how we can make sure these nanotechnologies come to fruition with little or no environmental impact,” explains Hamers. “We’re looking at nanoparticles in emerging technologies.”

In addition to UW-Madison, scientists from UW-Milwaukee, the University of Minnesota, the University of Illinois, Northwestern University and the Pacific Northwest National Laboratory have been involved in the center’s first phase of research. Joining the center for the next five-year phase are Tuskegee University, Johns Hopkins University, the University of Iowa, Augsburg College, Georgia Tech and the University of Maryland, Baltimore County.

At UW-Madison, Hamers leads efforts in synthesis and molecular characterization of nanomaterials. soil science Professor Joel Pedersen and chemistry Professor Qiang Cui lead groups exploring the biological and computational aspects of how nanomaterials affect life.

Much remains to be learned about how nanoparticles affect the environment and the multitude of organisms – from bacteria to plants, animals and people – that may be exposed to them.

“Some of the big questions we’re asking are: How is this going to impact bacteria and other organisms in the environment? What do these particles do? How do they interact with organisms?” says Hamers.

For instance, bacteria, the vast majority of which are beneficial or benign organisms, tend to be “sticky” and nanoparticles might cling to the microorganisms and have unintended biological effects.

“There are many different mechanisms by which these particles can do things,” Hamers adds. “The challenge is we don’t know what these nanoparticles do if they’re released into the environment.”

To get at the challenge, Hamers and his UW-Madison colleagues are drilling down to investigate the molecular-level chemical and physical principles that dictate how nanoparticles interact with living things.
Pedersen’s group, for example, is studying the complexities of how nanoparticles interact with cells and, in particular, their surface membranes.

“To enter a cell, a nanoparticle has to interact with a membrane,” notes Pedersen. “The simplest thing that can happen is the particle sticks to the cell. But it might cause toxicity or make a hole in the membrane.”

Pedersen’s group can make model cell membranes in the lab using the same lipids and proteins that are the building blocks of nature’s cells. By exposing the lab-made membranes to nanomaterials now used commercially, Pedersen and his colleagues can see how the membrane-particle interaction unfolds at the molecular level – the scale necessary to begin to understand the biological effects of the particles.

Such studies, Hamers argues, promise a science-based understanding that can help ensure the technology leaves a minimal environmental footprint by identifying issues before they manifest themselves in the manufacturing, use or recycling of products that contain nanotechnology-inspired materials.

To help fulfill that part of the mission, the center has established working relationships with several companies to conduct research on materials in the very early stages of development.

“We’re taking a look-ahead view. We’re trying to get into the technological design cycle,” Hamers says. “The idea is to use scientific understanding to develop a predictive ability to guide technology and guide people who are designing and using these materials.”

What with this initiative and the LCnano Network at Arizona State University (my April 8, 2014 posting; scroll down about 50% of the way), it seems that environmental and health and safety studies of nanomaterials are kicking into a higher gear as commercialization efforts intensify.

Sticky-flares nanotechnology to track and observe RNA (ribonucleic acid) regulation

I like the name ‘sticky-flares’ and had hoped there was an amusing story about its origins. Ah well, perhaps I’ll have better luck next time.

This work comes out of Chad Mirkin’s lab at Northwestern University (Chicago, US) according to a July 21, 2015 news item on Azonano,

RNA [ribonucleic acid] is a fundamental ingredient in all known forms of life — so when RNA goes awry, a lot can go wrong. RNA misregulation plays a critical role in the development of many disorders, such as mental disability, autism and cancer.

A new technology — called “Sticky-flares” — developed by nanomedicine experts at Northwestern University offers the first real-time method to track and observe the dynamics of RNA distribution as it is transported inside living cells.

A July 20, 2015 Northwestern University news release by Erin Spain, which originated the news item, describes the research in a little more detail also including information about predecessor technology,

Sticky-flares have the potential to help scientists understand the complexities of RNA better than any analytical technique to date and observe and study the biological and medical significance of RNA misregulation.

Previous technologies made it possible to attain static snapshots of RNA location, but that isn’t enough to understand the complexities of RNA transport and localization within a cell. Instead of analyzing snapshots of RNA to try to understand functioning, Sticky-flares help create an experience that is more like watching live-streaming video.

“This is very exciting because much of the RNA in cells has very specific quantities and localization, and both are critical to the cell’s function, but until this development it has been very difficult, and often impossible, to probe both attributes of RNA in a live cell,” said Chad A. Mirkin, a nanomedicine expert and corresponding author of the study. “We hope that many more researchers will be able to use this platform to increase our understanding of RNA function inside cells.”

Sticky-flares are tiny spherical nucleic acid gold nanoparticle conjugates that can enter living cells and target and transfer a fluorescent reporter or “tracking device” to RNA transcripts. This fluorescent labeling can be tracked via fluorescence microscopy as it is transported throughout the cell, including the nucleus.

In the … paper, the scientists explain how they used Sticky-flares to quantify β–actin mRNA in HeLa cells (the oldest and most commonly used human cell line) as well as to follow the real-time transport of β–actin mRNA in mouse embryonic fibroblasts.

Sticky-flares are built upon another technology from Mirkin’s group called NanoFlares, which was the first genetic-based approach that is able to detect live circulating tumor cells out of the complex matrix that is human blood.

NanoFlares have been very useful for researchers that operate in the arena of quantifying gene expression. AuraSense, Inc., a biotechnology company that licensed the NanoFlare technology from Northwestern University, and EMD-Millipore, another biotech company, have commercialized NanoFlares. There are now more than 1,700 commercial forms of NanoFlares sold under the SmartFlareä name in more than 230 countries.

The Sticky-flare is designed to address limitations of SmartFlares, most notably their inability to track RNA location and enter the nucleus. The Northwestern team believes Sticky-flares are poised to become a valuable tool for researchers who desire to understand the function of RNA in live cells.

Based on the paragraph about the precursor technology’s commercial success , I gather they are excited about similar possibilities for sticky-flares.

Here’s a link to and a citation for the paper,

Quantification and real-time tracking of RNA in live cells using Sticky-flares by William E. Briley, Madison H. Bondy, Pratik S. Randeria, Torin J. Dupper, and Chad A. Mirkin. Published online before print July 20, 2015, doi: 10.1073/pnas.1510581112 PNAS July 20, 2015

This paper is behind a paywall.

Northwestern University’s (US) International Institute for Nanotechnology (IIN) rakes in some cash

Within less than a month Northwestern University’s International Institute for Nanotechnology (IIN) has been granted awarded two grants by the US Department of Defense.

4D printing

The first grant, for 4D printing, was announced in a June 11, 2015 Northwestern news release by Megan Fellman (Note: A link has been removed),

Northwestern University’s International Institute for Nanotechnology (IIN) has received a five-year, $8.5 million grant from the U.S. Department of Defense’s competitive Multidisciplinary University Research Initiative (MURI) program to develop a “4-dimensional printer” — the next generation of printing technology for the scientific world.

Once developed, the 4-D printer, operating on the nanoscale, will be used to construct new devices for research in chemistry, materials sciences and U.S. defense-related areas that could lead to new chemical and biological sensors, catalysts, microchip designs and materials designed to respond to specific materials or signals.

“This research promises to bring transformative advancement to the development of biosensors, adaptive optics, artificially engineered tissues and more by utilizing nanotechnology,” said IIN director and chemist Chad A. Mirkin, who is leading the multi-institution project. Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences.

The award, issued by the Air Force Office of Scientific Research, supports a team of experts from Northwestern, the University of Miami, the University of California, San Diego, and the University of Maryland.

In science, “printing” encodes information at specific locations on a material’s surface, similar to how we print words on paper with ink. The 4-dimensional printer will consist of millions of tiny elastomeric “pens” that can be used individually and independently to create nanometer-size features composed of hard or soft materials.

The information encoded can be in the form of materials with a defined set of chemical and physical properties. The printing speed and resolution determine the amount and complexity of the information that can be encoded.

Progress in fields ranging from biology to chemical sensing to computing currently are limited by the lack of low-cost equipment that can perform high-resolution printing and 3-dimensional patterning on hard materials (e.g., metals and semiconductors) and soft materials (e.g., organic and biological materials) at nanometer resolution (approximately 1,000 times smaller than the width of a human hair).

“Ultimately, the 4-D printer will provide a foundation for a new generation of tools to develop novel architectures, wherein the hard materials that form the functional components of electronics can be merged with biological or soft materials,” said Milan Mrksich, a co-principal investigator on the grant.

Mrksich is the Henry Wade Rogers Professor of Biomedical Engineering, Chemistry and Cell and Molecular Biology, with appointments in the McCormick School of Engineering and Applied Science, Weinberg and Northwestern University Feinberg School of Medicine.

A July 10, 2015 article about the ‘4D printer’ grant  by Madeline Fox for the Daily Northwestern features a description of 4D printing from Milan Mrksich, a co-principal investigator on the grant,

Milan Mrksich, one of the project’s five senior participants, said that while most people are familiar with the three dimensions of length, width and depth, there are often misconceptions about the fourth property of a four-dimensional object. Mrksich used Legos as an analogy to describe 4D printing technology.

“If you take Lego blocks, you can basically build any structure you want by controlling which Lego is connected to which Lego and controlling all their dimensions in space,” Mrksich said. “Within an object made up of nanoparticles, we’re controlling the placement — as we use a printer to control the placement of every particle, our fourth dimension lets us choose which nanoparticle with which property would be at each position.”

Thank you Dr. Mrksich and Ms. Fox for that helpful analogy.

Designing advanced bioprogrammable nanomaterials

The second grant, announced in a July 6, 2015 Northwestern news release by Megan Fellman, is apparently the only one of its kind in the US (Note: A link has been removed),

Northwestern University’s International Institute for Nanotechnology (IIN) has been awarded a U.S. Air Force Center of Excellence grant to design advanced bioprogrammable nanomaterials for solutions to challenging problems in the areas of energy, the environment, security and defense, as well as for developing ways to monitor and mitigate human stress.

The five-year, $9.8 million grant establishes the Center of Excellence for Advanced Bioprogrammable Nanomaterials (C-ABN), the only one of its kind in the country. After the initial five years, the grant potentially could be renewed for an additional five years.

“Northwestern University was chosen to lead this Center of Excellence because of its investment in infrastructure development, including new facilities and instrumentation; its recruitment of high-caliber faculty members and students; and its track record in bio-nanotechnology and cognitive sciences,” said Timothy Bunning, chief scientist at the U.S. Air Force Research Laboratory (AFRL) Materials and Manufacturing Directorate.

Led by IIN director Chad A. Mirkin, C-ABN will support collaborative, discovery-based research projects aimed at developing bioprogrammable nanomaterials that will meet both military and civilian needs and facilitate the efficient transition of these new technologies from the laboratory to marketplace.

Bioprogrammable nanomaterials are structures that typically contain a biomolecular component, such as nucleic acids or proteins, which give the materials a variety of novel capabilities. [emphasis mine] Nanomaterials can be designed to assemble into large 3-D structures, to interface with biological structures inside cells or tissues, or to interface with existing macroscale devices, for example. These new bioprogrammable nanomaterials and the fundamental knowledge gained through their development will ultimately lead to the creation of wearable, portable and/or human-interactive devices with extraordinary capabilities that will significantly impact both civilian and Air Force needs.

In one research area, scientists will work to understand the molecular underpinnings of vulnerability and resilience to stress. They will use bioprogrammable nanomaterials to develop ultrasensitive sensors capable of detecting and quantifying biomarkers for human stress in biological fluids (e.g., saliva, perspiration or blood), providing means to easily monitor the soldier during times of extreme stress. Ultimately, these bioprogrammable materials may lead to methods to increase human cellular resilience to the effects of stress and/or to correct genetic mutations that decrease cellular resilience of susceptible individuals.

Other research projects, encompassing a wide variety of nanotechnology-enabled goals, include:

Developing hybrid wearable energy-storage devices;
Developing devices to identify chemical and biological targets in a field environment;
Developing flexible bio-electronic circuits;
Designing a new class of flat optics; and
Advancing understanding of design rules between 2-D and 3-D architectures.

The analysis of these nanostructures also will extend fundamental knowledge in the fields of materials science and engineering, human performance, chemistry, biology and physics.

The center will be housed under the IIN, providing researchers with access to IIN’s strong entrepreneurial community and its close ties with Northwestern’s renowned Kellogg School of Management.

This second news release provides an interesting contrast to a recent news release from Sweden’s Karolinska Intitute where the writer was careful to note that the enzymes and organic electronic ion pumps were not living as noted in my June 26, 2015 posting. It seems nucleic acids (as in RNA and DNA) can be mentioned without a proviso in the US. as there seems to be little worry about anti-GMO (genetically modified organisms) and similar backlashes affecting biotechnology research.