Scott Gilbert, left, and Todd Miller collaborated in developing this industrial micromixer. (Photo: Karl Maasdam)

Dime-sized mixers perform a critical step in high-value chemical operations including nanoparticle synthesis, precision blending and laboratory automation, but they can also add value to the broader chemical industry. Microflow CVO’s microfluidics architecture leverages integrated-circuit design concepts to create devices that can be scaled and designed to manufacturer specifications, said Todd Miller, prototyping manager at the MBI and president of the new firm. Miller said the company has licensed rights to patent applications he has made over the past five years while at OSU.

A market analysis by the OSU College of Business estimates the global micromixer (also called “microreactors”) market in the life sciences at $2 billion. “It’s a rapidly changing and growing market,” said John Turner, OSU instructor and CEO of Microflow CVO. He and OSU MBA student Ken True identified more than 1,000 researchers at 270 institutions in 30 countries using microreactors in pharmaceutical research. “We expect the market to exceed $3 billion by 2014. And that’s only in the life sciences. Other chemical manufacturing markets raise the potential for these products,” added Turner.

The problem that Microflow CVO has addressed seems simple: how to efficiently mix two liquids with consistently high-quality results. Manufacturers commonly perform this step in large vats where batches of liquids are stirred and then processed.

In contrast, microfluidic technologies push liquids through channels slightly larger than a human hair where mixing occurs under precisely controlled conditions. While the results can meet manufacturer specifications, existing micromixer designs tend to be fragile, expensive and hard to adapt to specific circumstances.

This micromixer made by OSU-spinoff company Microflow CVO combines liquids in the pharmaceutical, petrochemical and consumer products industries. (Photo: Karl Maasdam)

Compared to existing designs, Microflow CVO’s stainless steel microreactors, perform better, cost less and can be customized easily for existing processing operations, said Miller. “Currently, most users of micromixers are forced to adapt their processes to a discrete number of available designs,” added Norm Galvin, vice president of sales. “Microflow CVO’s mixers can be built to customer specifications. We adapt to our customer’s needs; they don’t have to adapt to ours.”

The company currently offers two products for sale and will expand its offerings to more than 15 by the end of the calendar year. The additional offerings will provide options in flow rates, fluid inputs and operational scale.

Microflow CVO began with a chance encounter at a Portland, Ore., meeting hosted by the Oregon Nanoscience and Microtechnologies Institute (ONAMI). Miller met Scott Gilbert, an expert in microfluidics then affiliated with the University of Washington. Gilbert was looking for a microfluidics device that could provide precision blending of modestly viscous fluids (such as anti-freeze) at a high flow rate but a low pressure drop. His target was the petrochemicals industry.

Years before, Miller had made prototypes of such devices, but further development was slowed as other duties and projects required his attention.  Gilbert’s question sent him back to the drawing board — in this case, computer modeling software — where he worked out the details. The prototype Miller built at the MBI exceeded mixture specifications without additional processing.

Since then, Miller has developed and tested other micromixers to produce copper nanoparticles, a collaborative effort with Gilbert, OSU chemistry professor Vincent Remcho and the Department of Energy’s Pacific Northwest National Laboratory. With proof-of-concept in hand, he applied for and received “gap funding” assistance through ONAMI, which supports efforts to commercialize technology originating from the Oregon University System. “ONAMI has been critical to this whole process,” said Miller. “Without ONAMI, we wouldn’t be here.”

Gilbert now serves as chemical safety officer and research associate at the MBI and is chief technology officer of Microflow CVO. Ormond “Norm” Galvin is vice president of sales for the company.

More information is available at http://www.microflowcvo.com.

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Based in Corvallis, Oregon, Microflow CVO designs innovative high-performance micromixers and microfluidic components that improve industrial processes, reduce waste and lower capital costs. The company maintains close ties to the Oregon State University Microproducts Breakthrough Institute and the Oregon Nanoscience and Microtechnologies Institute.

Editors note: Photos of the new Microflow CVO™ device and of Scott Gilbert and Todd Miller are available on Flickr:

http://www.flickr.com/photos/oregonstateuniversity/7158821648/

http://www.flickr.com/photos/oregonstateuniversity/7158820442/

Kate Saili videos zebrafish in the act of regenerating their tails (Contributed photo)

Saili, who grew up in Kalispell, Montana, studies the effect of nanomaterials on inflammation. She uses transgenic zebrafish whose white blood cells fluoresce under ultraviolet light. White blood cells are foot soldiers in the inflammation process, and in her experiments, Saili observes that process as it proceeds in the presence of nanomaterials.

First, Saili immerses a zebrafish in an anesthetic. Then she removes the tip of the tailfin. As the fish’s immune system kicks in, Saili places the animal in a solution containing nanomaterials that have been designed by a scientist at Tennessee State University potentially to treat inflammation. Through a microscope, she captures images of the white blood cells rushing to the injured fin.

“I’m really interested in how the immune system works,” says Saili, who has a bachelor’s degree in biology from Carroll College in Helena, Montana. Her studies show that fewer white blood cells migrate to the site of the injured fin when certain gold- or silver-based nanomaterials are present. “All we can say for sure is that nanoparticles are reducing the number of white bloods cells that migrate to or remain at the site of an injury. We don’t know why,” she adds.

Before coming to OSU, Saili was studying wildlife in American Samoa. Someday, she would like to monitor wildlife health and apply what she learns to human health. “I think you can get a lot farther and do lot more interesting and relevant work with a molecular foundation. What I want to do is investigate a disease, look at the mechanics behind it. I came to OSU,” she says, “because I knew it has a good toxicology program.”

Saili is a Ph.D. student in the Department of Environmental and Molecular Toxicology.

Linsa Truong studies how gold nanoparticles behave in the body. (Photo: Nick Houtman)

Truong, who grew up in the Seattle area, wants to know how gold nanomaterials behave in the body. Through ONAMI’s Safer Nanomaterials and Nanomanufacturing Initiative, she is testing products from Professor Jim Hutchison’s University of Oregon lab, which has created “green” methods (highly efficient, precise and less toxic) for making gold nanomaterials.

“We actually know how they’re made every step of the way,” says Truong. Such information about manufacturing methods, chemical composition and purity is crucial for linking nanomaterial characteristics to the outcomes of tests in the OSU zebrafish lab.

Moreover, ONAMI provides Truong with direct access to information. “I can pick up the phone and ask questions about a nanomaterial I’m working with. I can ask how many ligands (a molecule that bonds with a metal) is on the surface of a nanomaterial, rather than have to look it up or wait online,” she says.

Truong’s desire for better health care is personal. As a child, she watched her grandparents struggle with heart problems. Diagnostic tests and treatments made them sick. “I didn’t want to be a doctor,” she says. “But I wanted to develop the technology that would help them.”

Lisa Truong is a Ph.D. student in the Department of Environmental and Molecular Toxicology.

OSU nanotechnology researchers are leveraging the power of molecular-scale processes to improve quality and create new products.

Nanotechnology has arrived. No longer do we just have to imagine the benefits. Advertisers tout them in cosmetics, clothing, batteries, dental adhesives, paint and golf clubs. In 2004, nanotech consultant Lux Research, Inc., estimated the worldwide sale of products containing nanomaterials at $158 billion. And new products are on the horizon: medicines, sensors, filters and more efficient solar collectors.

If you take a historical view, we’ve been driving to work on nanotechnology for the past century. About one-quarter of an automobile tire consists of nanosize-carbon black particles. Without them, our treads would lack strength and wear resistance.

“Nano” refers not just to small but to a specific kind of smallness. One nanometer is one-billionth of a meter, the width of a human hair sliced lengthwise into 100,000 strands. It takes 10 carbon atoms to span one nanometer. Lined up side by side, 152 million carbon atoms are as wide as a penny.

In 1959, Caltech physicist Richard Feynman issued a call to arms for research at this scale. He explained to a conference of his colleagues how all 24 volumes of the Encyclopaedia Britannica could fit on the head of a pin. Not only is there enough room among the atoms to encode that much information, he argued, “there is plenty of room,” enough for all the world’s books to be copied onto a mote of dust.

Among Feynman’s nanotech dreams were room-sized computers shrunk to the size of a briefcase (check that one off), ingestible surgical devices that could repair a damaged heart and factories that make flawless products, atom by atom.

Today, OSU researchers in engineering, chemistry, physics and wood science are among those putting Feynman’s ideas into practice. Through the Oregon Nanoscience and Microtechnologies Institute (ONAMI), they are working with colleagues at the University of Oregon, Portland State University, the Pacific Northwest National Laboratory and the private sector (HP, FEI, Intel, IBM and others) on projects designed to address manufacturing and safety issues as well as to develop new materials and products. Funding support comes from the State of Oregon and the federal government’s National Nanotechnology Initiative.

The Joke Among Chemists

Among scientists, this investment is both a welcome source of support and validation of existing ideas. “The joke among the chemists is, ‘have you heard about nanotechnology? It’s the new name for chemistry,’” says OSU physicist Janet Tate. “We’ve been doing nanotechnology for a long time in physics and chemistry. A lot of what we talk about when we teach quantum mechanics is inherently nano in scale.”

Tate grew up in South Africa, received her Ph.D. at Stanford and has won awards for her teaching and research since coming to OSU in 1989. A major focus has been OSU’s transparent electronics initiative, nanoscale research that demonstrated the world’s first transparent thin-film transistor in 2003 and integrated circuit in 2006.

“Transparent electronics is a new field, but it exploits old ideas,” says Tate. It all starts with semiconductors in which the flow of electricity can be easily manipulated. Most semiconductors, such as silicon-based materials in computers, cell phones and other electronic devices, are visible because they absorb light. However, some semiconductors let particles of visible light (photons) sail right through them untouched. Thus, they are as clear as glass.

The trick with invisible semiconductors (indium oxide, zinc oxide, tin oxide and others), adds Tate, is to find ways to make them conduct electricity without making them visible. In her research, she collaborates with Doug Keszler (Chemistry), John Wager (Electrical Engineering and Computer Science) and a team of technicians and students to make transparent semiconductor films that are tens of nanometers thick. By placing other molecules into the films, they hope to achieve the kind of control over the flow of electricity that is now possible with silicon-based semiconductors.

“You inevitably shift off into the fringes where things are not quite as transparent, and you discover that maybe it’s useful for something else like solar cells,” Tate adds.

Common as Wood

That kind of opportunity strikes a chord with John Simonsen, a chemist in OSU’s Wood Science and Engineering Department. After receiving his Ph.D. from the University of Colorado, he worked in the private sector before coming to OSU in 1990. He specialized in wood-plastic composites and wood preservatives. Strength is a problem with composites, he says, especially the bond between wood and synthetic polymers. “They just don’t have the mechanical properties at the cost that we expect for building materials. You have to go to exotic polymers to get strength. You’re talking dollars a pound. Wood costs a dime a pound.”

So he became intrigued when he began learning about the ability of nanosize-cellulose crystals to increase strength in composites. “Cellulose crystals are stronger than steel and stiffer than aluminum. And they’re renewable. That’s probably why nature uses them for trees,” he says.

Just as important for researchers, cellulose chemistry is well known, and, compared to many other nanoparticles, easy to work with. In his lab, Simonsen makes cellulose nanocrystals by grinding standard filter paper, then hydrolyzing it with acid. A simplified version of the process goes like this: Add acid, spin the solution in a centrifuge, then pass it through an ultrafilter to concentrate the cellulose and remove the impurities. The resulting liquid looks like watered-down milk. For show-and-tell, he keeps a vial of the cloudy liquid on his desk, telling visitors that the cellulose has remained suspended in solution for more than a year.

Simonsen uses the material in several areas of research: improving the performance of membranes, such as those in kidney dialysis filters; improving the properties of barrier films to keep out toxic industrial chemicals; and making novel materials by combining the nanocrystalline cellulose with other polymers.

Initial findings from a dialysis membrane study by Simonsen, Sundar Atre (Industrial and Manufacturing Engineering) and Sweda Noorani, a graduate student, showed that by adding only 2 percent cellulose to the membrane, they increased both stiffness and water vapor transport, a property that should foster the ability of the filter to cleanse the blood.

In addition to his research, Simonsen is working with OSU faculty members on a nanotechnology curriculum in the Materials Science Program. A Nanotechnology Processes Option is also available in Chemical Engineering.

Nanofactories

While new materials are driving product development, Brian Paul is putting his money on “nanomanufacturing,” the ability to economically structure matter on the nanometer scale. Paul received his Ph.D. from Penn State and is a professor in the OSU Department of Industrial and Manufacturing Engineering. He specializes in bulk microfluidics, a technology that uses channels no wider than a human hair to improve the quality of chemical reactions and heat transfer.

With this technology, close proximity is key; forced into tight quarters, chemicals react quickly and uniformly. Paul and his colleagues in OSU’s Microproducts Breakthrough Institute (MBI) have found ways to sequence systems of chemical mixers, separators and heat exchangers within microchannels. In MBI research, bulk microfluidic technology has already shown promise in making biodiesel and hydrogen and in filtering blood for kidney dialysis. These microsystems are tested in labs on campus and fabricated at the ONAMI Nano/Micro Fabrication Facility on the Hewlett-Packard campus.

But what makes Paul’s eyes really light up is the microchannel synthesis of nanomaterials, such as nanoparticles called “dendrimers.” Named for their tree-like branching structure, these spherical molecules have spacious interiors and functional exteriors that can be tailored to selectively attach to surfaces. They can carry an anti-cancer drug to a tumor or lock onto the HIV virus, thus making it incapable of infecting a human cell.

Trouble is, dendrimers may take weeks to months to manufacture, and they are priced accordingly, from hundreds to hundreds of thousands of dollars per gram. Using bulk microfluidics, Paul says his OSU colleagues Chih-hung Chang (Chemical Engineering) and Vince Remcho (Chemistry) are continuously producing multiple pounds per hour of dendrimer molecules using much less expensive capital equipment, significantly lowering the chemical cost. Moreover, the team can achieve a level of purity unmatched by industrial batch processing.

Arrays of microchannels can also address another concern that is not so nano, says Paul: safety. “Many nanoparticles are readily absorbed through the skin, and their health affects are not yet well understood. Do we really want a supply chain that is transporting them on the highways and rails? Better to transport reagents and produce the particles at the point of use to minimize exposure,” he says.

That would mean manufacturing nanoparticles in distributed reactors instead of centralized chemical plants. “What we’re talking about is distributed and portable production. We’re talking about a new paradigm, manufacturing models that blow away existing industrial scale models of production,” he adds. The challenge is finding ways to build cheap distributed systems to replace expensive centralized facilities.

With a $650,000 grant from the W. M. Keck Foundation, Paul, Chang and Remcho are studying microsystem-enabled dendrimer production, hoping to find new and efficient ways to apply it to a commercial scale.

“I come from a manufacturing mindset. You can’t wait months tying up expensive capital equipment and expect to make a difference. The objective is to deploy,” says Paul.

Other OSU researchers working on nanoscale projects include Greg Rorrer, Goran Jovanovic and Christine Kelly in chemical engineering. And ONAMI is bringing them together with counterparts at the University of Oregon’s Center for Advanced Materials Characterization in Oregon and Portland State University’s Center for Nanoscience and Nanotechnology. Their private-sector colleagues include Oregon-based FEI, Inc., a world leader in electron microscopy, which enables researchers to see at the nanometer scale and even below, into the spaces between subatomic particles.

Together, they are contributing to an economic sector that could be valued at between $1.4 trillion and $2.6 trillion by 2015, according to recent estimates by Lux Research and the National Science Foundation.