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[Sandia Lab News]

Vol. 54, No. 15        July 26, 2002
[Sandia National Laboratories]

Albuquerque, New Mexico 87185-0165    ||   Livermore, California 94550-0969
Tonopah, Nevada; Nevada Test Site; Amarillo, Texas

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DOE annouces 'Genome to Life' grants Sandia and Air Force test arsenic removal technologies Labs pursues Molecular Integrated Micosystems Microchannels and protein sorting 'Smart' materials modeled on living systems

Sandia to lead one of five 'Genomes to Life' programs

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By Neal Singer

Sandia will lead one of five major research awards -- and participate in two others -- announced this week by the Department of Energy for what it terms "post-genomic" research.

Secretary of Energy Spencer Abraham announced the new projects, entitled "Genomes to Life," in Washington Tuesday. They will total $103 million over the next five years. Research will be conducted at six national laboratories, including Sandia; 16 universities and research hospitals; and four private research institutes. The work is headed by DOE's Office of Science.

Said Abraham, "One could hardly imagine when the Energy Department began the human genome project in the '80s that the resulting information and technologies could yield such diverse benefits."

He said the new research program is expected to provide "biotechnology solutions to help produce clean energy, clean up the environment, and contribute to the President's policy on climate change."

The Sandia-led effort is headed by Grant Heffelfinger (1802) and involves $19.1 million over three years to understand the sequestration of carbon in a seaborne bacteria called Synechococcus. The grant -- subtitled "From Molecular Machines to Hierarchical Modeling" -- brings together a formidable collection of research institutions, including Sandia, Oak Ridge National Laboratory, Lawrence Berkeley National Laboratory, Los Alamos National Laboratory, National Center for Genome Resources in Santa Fe, N.M., the University of California at San Diego, the University of Tennessee at Knoxville, the University of Michigan at Ann Arbor, The Molecular Science Institute in Berkeley, Calif., the University of California at Santa Barbara, and the University of Illinois at Urbana-Champaign.

Of the total for this project, $2.35 million comes to Sandia, with internal distribution of approximately $1 million going to Computation, Computers, and Mathematics Center 9200; $650,000 to Exploratory Systems and Development Center 8100, with the remaining $500,000 to Materials and Process Sciences Center 1800. Other research monies will be distributed among the ten partners.

The reason that Sandia -- not particularly known for biological expertise -- was awarded its leadership role, says Grant, is that "the Genomes to Life program is jointly sponsored by the Office of Science's Office of Biological and Environmental Research and the Office of Advanced Scientific Computing Research.

"The Genomes to Life project has four goals," he says: "to understand the molecular machines of life, regulatory networks, and how microbial communities work together. The final goal is to develop computational capabilities to address the first three.

"So our proposal, though it has a biological title, is based on our world-class computing and experiment-analysis expertise -- abilities we've proven time and time again. So it makes sense for Sandia to lead what I think of as the Genomes to Life program's lead effort in goal 4."

By the end of the project, Grant's intent is to have "developed and prototyped a set of computational capabilities to enable the advancement of life science research for DOE's missions, particularly in sequestration of carbon by Synechococcus.

Other projects in which Sandia is formally involved are led by:

Further information on these projects will appear in later Lab News issues.

The awards are, without exception, for multi-institutional, multidisciplinary projects that involve both biological and computational sciences. Their purpose is to go beyond the workings of small groups of genes and instead focus on entire networks of genes and even entire biological systems. Single-celled organisms are first; later, more complex creatures -- including humans -- will be studied.

The human genome and those of other organisms -- microbes, plants, worms, and mice -- are expected to provide new perspectives on the inner workings of biological systems.

The program will use advanced computation, genomic information, and other resources to "take advantage of solutions that nature has already devised to help solve problems in energy production, environmental cleanup, and carbon cycling," according to a DOE news release. "Through a systems approach to biology at the interface of the biological, physical, and computational sciences, the program seeks to understand entire living organisms and their interactions with the environment."

One goal of the Genomes to Life program is to understand molecular machines and their controls so well that they can be used and even redesigned to address national needs. (The concept is widespread that nature creates arrays of molecular machines with precise and efficient functions that include motion, molecular detection, chemical synthesis and degradation, and light emission and detection.)

The program is also expected to lead to an understanding of the complex regulatory networks that control the assembly and coordinate the operations of these machines.

Another goal is to better understand the complex workings of microbial communities that could help solve energy and environmental challenges. These organisms normally do their work as part of communities made up of many different microbes. Eight types of microbes will be studied in these research projects because of their potential for bioremediation of metals and radionuclides, degradation of organic pollutants, production of hydrogen or sequestration of carbon, or because of their importance in ocean carbon cycling. All of these individual microbes have had their genetic sequence determined under DOE's Microbial Genome program.

The project's 10-year goal is to advance systems biology, computation, and technology to increase sources of biological-based energy; help understand the earth's carbon cycle, design ways to enhance carbon capture, and lead to cost-effective ways to clean up the environment.

Because these projects require sophisticated computational tools, new computational techniques to predict the functions and behaviors of complex biological systems are expected to be developed.

More information on the Genomes to Life program is available at http://DOEGenomesToLife.org - - Will Keener

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Sandia and Kirtland Air Force Base test existing and new arsenic removal technologies at existing well

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By John German

By 2006, according to a recently finalized EPA regulation, US drinking water shall contain less than 10 parts per billion of arsenic, a naturally occurring element that is thought to cause cancer when ingested at higher concentrations over long periods of time.

Arsenic levels in water from thousands of municipal groundwater supplies in the US, particularly in the western US, exceed the new limit by tens of ppb. (The current limit is 50 ppb.)

Communities are looking for treatment technologies that might reduce the cost of complying with the new regulation.

This summer Sandia and Kirtland Air Force Base are operating one of a growing number of arsenic-removal test facilities in the country.

The results of field tests conducted here should have national implications. Data from the tests will be shared widely to help communities and other water suppliers in their search for cost-effective arsenic-treatment technologies.

At a KAFB well station just inside the base's Truman Gate, Sandia has designed and Kirtland has installed a filtration unit that allows the team to test a variety of existing and emerging technologies for extracting arsenic from drinking water, including several approaches recently developed at Sandia.

The well supplies some one million gallons per day, which is about one-fourth of the base's average daily water needs. The arsenic content of Well 15 averages about 15 ppb.

"This is going to be an issue for us, so we thought it would be good to help Sandia with its field tests so they can have a look at the data from a real well," says Pat Montano, KAFB Water Quality Program Manager.

The field tests began May 24. Portions of Well 15 water are being flowed periodically through columns of activated alumina, a commercially available sorbent the EPA has designated as one of the Best Available Technologies for removing arsenic from drinking water down to the sub 10 ppb range.

Sandia project leader Nadim Khandaker (6118) says it will take several weeks to determine how thoroughly the activated alumina strips arsenic from the water and how long before the alumina granules are too saturated to filter out arsenic below the 10 ppb limit.

Then, with the activated alumina performance data as a baseline, the team will begin putting other treatment technologies to the test.

Among the Sandia-developed approaches to be tested are Specific Anion Nanoengineered Sorbents (SANS) -- a family of proprietary formulations of mixed metal oxides that remove arsenic from water by trapping it permanently within the SANS' chemical structures. SANS developers include Dave Teter, Pat Brady, Jim Krumhansl (all 6118), and Nadim (Lab News, March 9, 2001).

In small-scale laboratory batch and column tests with water containing 300 ppb arsenic, the SANS material outperformed activated alumina by about a factor of ten.

"We need to try SANS at a real well with real arsenic concentrations using real valves, pumps, etc.," says Nadim.

Well 15 water will be flowed through columns of granular SANS to verify whether the materials' performance scales up to real-world situations.

Two other sorbents developed by Bob Moore (6849) also will be tested -- a stabilized metal hyroxide and a doped activated carbon, both of which trap arsenic on their surfaces.

Following the sorbent trials the team will test an improved approach to coagulation/microfiltration, a common method of removing arsenic from drinking water. (Essentially, coagulant materials dissolved in the water bond with arsenic, then clump together into larger particles that are filtered out.)

A SANS-like nanoengineered enhancing agent developed at Sandia will be added to conventional coagulants. In previous laboratory tests, small amounts of these SANS enhancers significantly improved the effectiveness of standard ferric chloride coagulants.

The approach could reduce the cost of arsenic removal, says Nadim.

Other Sandia approaches to be tested include nanoengineered calcium oxide and magnesium oxide enhancers that could reduce the cost of lime-softening water treatment approaches.

The plumbing equipment used for the field tests incorporates a modular design so many different technologies and approaches can be tested, says Nadim. The equipment will remain at the well station following this summer's test series for possible tests of future technologies.

The SANS and other Labs-developed treatment technologies have never been field tested before, says Nadim, so it's too early to predict the possible outcomes.

"Our small-scale experimentation and models tell us the SANS will significantly outperform other approaches, but any engineer knows to wait for the data," he says. "The field tests will tell us how long a column of these is going to last in real water."

The data also will provide scientifically objective information about the performance of the Sandia technologies relative to commercial systems and might also help the team design future water-treatment systems, he says.

The field tests should have national and international implications, depending on how well the Sandia approaches perform, says Henry Westrich, Manager of Geochemistry Dept. 6118.

"This technology has the potential for dramatic reductions in water-treatment costs, especially for rural and small water utilities in the US and the world," he says.

Other project team members include Capt. Mike Dunlop and Mark Dalzell (both KAFB); Prof. Bruce Thompson and Greg Gartland (both University of New Mexico); Howard Anderson (6118), and Paul Baca (6245).

The field tests are funded through the Laboratory Directed Research and Development program and sponsored by Sandia's Water Initiative, which supports the development of technologies that make water supplies safe, secure, and sustainable. - - John German

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Molecular Integrated Microsystems grand challenge pursues revolutionary approach to microsystems

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By Chris Burroughs

The next generation of microsystems may be like nothing anyone has ever seen.

Sandia researchers are pursuing a revolutionary approach to building microsystems in which functions found in biological and nanoscale systems are combined with manufacturable materials. The ultimate result may be the first-ever programmable Molecular Integrated Microsystems (MIMS) devices that can be used for rapid chemical and biochemical analysis in sensors and encoded optical interconnects that can route optical energy on demand.

The research, funded as an internal Laboratory Directed Research and Development (LDRD) Grand Challenge, is led by Terry Michalske (1040) and Len Napolitano (8130).

"A programmable system is a new vision for microsystems," Terry says. "Our goal is to be able to reconfigure the architecture and tune the functions of microsystems, on-the-fly. This approach combines new developments in biotechnology and materials science to provide the methods needed to control materials and manipulate molecules at the nanometer scale. The ability to manipulate nanoscale structures is at the heart of the next revolution in programmable microsystems."

Over the past decade Sandia has taken a pioneering role in the movement from traditional macroscale components and devices to fully miniaturized engineering systems. However, Terry says that "we are now taking advantage of microscale addressability to locally control materials properties and molecular interactions within the microsystem itself."

The MIMS grand challenge was initiated two-and-one-half years ago with the goal of developing the technical basis for the next generation of biochemical analysis and integrated optical microsystems. The biochemical analysis portion of the project is focused on new approaches to sort and separate small quantities of proteins in complex biochemical mixtures using the µProLab -- Sandia's on-chip protein lab (see "Microchannels in chips speed protein sorting" below). The µProLab will preconcentrate dilute protein samples and do on-chip biochemical separations, similar to what Sandia's "chem-lab-on-a-chip, " formally called µChemlab, does with deadly chemicals.

"The ability to rapidly analyze protein signatures is a critical component of Sandia's approach for detecting and mitigating bio-threats," Len says. "Traditional methods for analyzing the protein signatures involve labor-intensive and time-consuming techniques such as multidimensional chemical separations. Using the technologies developed in the MIMS, the team has already demonstrated that key components of protein analyses can be completed in a matter of minutes."

The programmable optical interconnect objective of MIMS is to write new optical paths, "on demand." The MIMS team has already demonstrated the ability to route on-chip optical signals in a programmable fashion. This new capability to create optical connections has important implications for spectroscopic analysis in chip-based chemical and biological analysis and may lead to new ways to control the access of information in weapons systems or secure data networks.

Len notes that the MIMS project has already had several successes. The researchers can reconfigure a microfluid channel in real-time and can use electrical signals to manipulate proteins within those channels. In fact, some MIMS technologies are already licensed for commercial use while others are in various stages of negotiation.

"Our work over the past couple of years has brought us closer to our goal of building workable MIMS," Len says.

This fiscal year the goal is to build and demonstrate complete architectures and use science understanding to extend and increase programmable capabilities.

The MIMS grand challenge project received high praise from its external advisory panel that is made up of members representing universities, National Institutes of Health, Department of Defense, National Science Foundation, and DOE. The panel noted that, "At this stage of the project you have a terrific technology. What you are doing with this program is important science and promising technology."

"We believe there have been some very significant accomplishments thus far," the panel said in a report. "Further, we were impressed with the talent of the technical people that presented to us, as well as your breadth of understanding of what others are doing in this field. We feel that you have the promise here to wow biologists." -- Chris Burroughs

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George Bachand explores ways to develop 'smart' materials that behave like living systems

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By Chris Burroughs

Imagine a new "smart" material that can "heal" itself like a living system.

It may sound like science fiction, but to Sandia molecular biologist George Bachand (1141), such materials may be just around the research corner.

George is working with Jun Liu and Bruce Bunker (all 1141) and a team on a project called "Active Assembly of Dynamic and Adaptable Materials." Its goal is to identify and learn how to exploit key strategies used by living systems to develop materials that can be programmed to assemble and disassemble in controlled environments.

The project is funded by the Nanoscale Science, Engineering, and Technology Initiative through the DOE Office of Basic Energy Sciences.

"With this project we are attempting to break the walls between living and nonliving systems at the nano-scale," George says. "We are looking at designing materials that have properties of living cells."

Synthetic materials tend to have static structures and are not capable of adapting to a changing environment. In contrast, living systems have the ability to create, heal, reconfigure, and dismantle.

As part of the project, George, Bruce, Jun and the rest of the team are studying how to mimic the dynamic assembly and active transport of living systems in new materials.

"The research moves material sciences from static structures to a regime in which materials can be assembled and reconfigured in response to an external stimuli," George says.

With this understanding, a new generation of "smart," dynamic, and adaptable materials may emerge.

As a first step, the researchers plan to use or modify key components from living systems and integrate and control those components in artificial microfluidic environments.

Specifically, they will be looking at motor proteins -- considered to be nature's means for transporting cargo within living cells -- as the active components in the new dynamic nanomaterials. The species George is studying is kinesin, a linear motor protein that walks along fibers in a "hand-over-hand" fashion for hundreds of steps. Kinesin motor proteins are among the fastest and most efficient of motor proteins.

The motor proteins are grown in a Petri dish. Using a DNA sequence for a target protein, the specific gene that encodes the motor protein is isolated. The gene is placed into a nonpathogenic Escherichia coli strain where the motor protein is expressed and purified by liquid chromatography.

George became particularly familiar with motor proteins while working as a research professor at Cornell University. There, he as part of a team used motor proteins derived from adenosine triphosphate synthase (ATPase) enzymes to power a nano-nickel propeller in a solution. The entire device, including the motor and propeller on a nickel post, was comparable in size to some virus particles.

George joined Sandia last year, becoming the Labs' first molecular biologist. Besides working on the Active Assembly of Dynamic and Adaptable Materials project, he plans to continue his efforts in using living motor proteins to power nanoelectromechanical (NEMS) systems.

"Both research efforts will give us valuable understanding of motor proteins and how they work and a means for controlling the activity of proteins in synthetic systems," George says.

While George has cloned kinesin motor proteins in his lab, he still needs to characterize them to better understand how they bind and move. Over the next couple of years, he will perform biochemical and biophysical analyses of the motor proteins, which should provide him insight into the structural and mechanical features of the motor protein enzymes that are critical for conversion of chemical energy into mechanical motion.

He will also genetically engineer these proteins to survive in synthetic systems, as well as provide mechanisms to control motor functions such as starting/stopping and cargo pick-up/delivery.

George notes that if he and the other researchers can understand key design criteria used by living systems, they will be able to identify basic concepts that will allow them to develop artificial materials and systems that may ultimately surpass the survivability and functionality constraints of existing biological systems.

"This work holds the promise of opening up a completely new branch of material science in which the nanostructures that can be produced will only be limited by our imagination," George says. -- Chris Burroughs

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Microchannels in chips speed protein sorting

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By Nancy Garcia

If a cell typically contains up to 10,000 to 100,000 proteins or subcomponent peptides, then just finding one, or discerning distinct identities of a few, can seem like looking for a proverbial needle in a haystack.

The task's all the harder if your starting material is hardly more than a few cells. Then, provided the target has been sorted out, how do you manipulate that bit to analyze it further? Standard screening currently requires cumbersome and lengthy processing steps using equipment the size of kitchen appliances.

Anup Singh (8130) and colleagues are developing microfabricated devices for protein and peptide analysis (dubbed a µProLab) through the Molecular Integrated Microsystems (MIMS) grand challenge Laboratory Directed Research and Development project.

They've found, Anup says, that "by miniaturizing, we can actually do better." Using microchannels a few centimeters long, and in some cases just a few millimeters long, on glass chips, they've demonstrated separation of six proteins and peptides in 45 seconds -- one-tenth the time it would take if performed in longer capillaries, and with 1/1,000th the starting sample needed for laboratory-bench-top-scale separations using porous-matrix-filled tubes called chromatography columns.

Chromatography works by selectively delaying different groups of proteins for different lengths of time in the matrix as the sample, applied to the top like pouring a liquid into a funnel, is rinsed through the material with a buffered solution and collected in a row of vials at the bottom. Different types of proteins drip out at different times, forming isolated "peaks" in the collection vials.

Separations can be tailored to proteins' different physical properties, based on the material used for the spongelike sieving matrix and the liquid used to rinse it.

MIMS aims to integrate steps needed to sort and identify small amounts of proteins or peptides by "addressing" smart materials on chip assemblies to "do certain things at certain times in a certain place," Anup says. In addition to running chromatography and other separations at microscale, the chips will include components such as valves to control and manipulate movement of fluids and concentrators to permit pre- and postanalysis concentration of dilute samples.

Anup hit upon his patent-applied preconcentrator invention by serendipity. He was working determinedly to get ready for a conference presentation. A minuscule, pico-liter-sized protein sample he'd injected onto a microchannel that had been carefully packed with porous beads should have emerged, based on theory, after an electric field was applied. Anup suspected the initial sample injection didn't work. He used a hand-held syringe to push the fluid out of the channel. The detector happened to still be on, and to his surprise it registered a huge peak of concentrated protein.

"If not for that conference, I might not have discovered it," he says. "I was just working day and night."

He and collaborators termed the technique electrokinetic trapping. Sharp, concentrated peaks form by using an electric field to focus charged analytes into a small spot in the separation channel. The preconcentration technique is addressable and reversible; proteins can be trapped and concentrated at specific locations by turning the voltage on and released by turning the voltage off.

The investigators, including Tim Shepodd (8722), have created a new method of creating in place sieving gels by using ultraviolet light to polymerize a porous matrix whose composition can be fine-tuned for various separations. Select locations can be polymerized by using a mask.

For controlling flow through a branching array of intersecting channels, Brian Kirby (8358) has used a moving plug of polymerized material to shuttle flow through a bypass, thus creating a sort of nonreturn, or check, valve.

The team intends to combine separation techniques to "fingerprint" proteins, as is currently done in bench-top processes, separating by both charge and size dimensions. Already, Anup and coworkers, including Jongyoon Han and Dan Throckmorton (8130), have seen separation efficiencies in a single dimension two to three times greater than the larger techniques allow.

"We hope to cut the time, overall, 10- to 100-fold," he says, "and work with a small sample -- possibly a few cells." The ultimate goal is that, once sorted by charge and size, a spot of protein can be microfluidically transported to a mass spectrometer for analysis of its constituent elements -- ideally through a completely automatic transfer when the device integration is complete. -- Nancy Garcia

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Last modified: July 24, 2002

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