Outside Washington, D.C., just a stone’s throw up the road in Gaithersburg, Md., lies the sprawling 580-acre headquarters of the National Institute of Standards and Technology (NIST), an unheralded government agency that has played a part in some of the biggest advances in science, manufacturing and communications in the last century.
To be precise, the front gate of the institute’s wooded, rural campus is exactly 20.664 miles from the center of the U.S. Capitol Building. It’s worth mentioning, because NIST is in the business of precision: everything the institute does revolves around standards, measurements and comparisons, all reliant on a meticulous attention to detail. Since it was established in 1901, the agency has worked to promote U.S. innovation and industry by developing tools that help speed up research, ensure the reliability of manufactured goods, and improve our quality of life.
Everything from the recipe for steel used in automobile production to earthquake safety standards for buildings to the nation’s official atomic clock stemmed from the efforts of NIST researchers.
The institute’s bucolic setting — complete with wildlife like deer and foxes — belies a modern core of state-of-the-art facilities like the Center for Nanoscale Science and Technology. This massive concrete, steel and glass building houses laboratories isolated as much as 40 feet underground, tightly temperature- and humitity-controlled so as not to perturb the exquisitely sensitive experiments conducted there.
It’s in this pantheon of precision that researchers Gordon Shaw and Jon Pratt are working to develop new standards for measuring extremely tiny forces, all the way down at the molecular level. The centerpiece of their Small Force Metrology Lab is the atomic force microscope, a phenomenally sensitive instrument that can create an ultra-high resolution image by dragging a silicon strip tipped with a diamond point (much like a phonograph needle) back and forth over a surface, and measuring the force exerted on the silicon strip as it bends and flexes with the contours of the surface.
What Shaw and Pratt are looking for is a new way for scientists using atomic force microscopes around the world to cheaply and efficiently calibrate their machines. Their current research is exploring the hypothesis that tiny snippets of DNA could be used as a “standard reference material” for just such a purpose.
Shaw, a stocky, enthusiastic man with a ready smile and long brown hair pulled back into a ponytail, explained the concept in the cramped atomic force microscope control room. DNA, he said, has some basic characteristics that make it appealing as a reference material: it’s cheap to produce, it can be replicated identically every time, and it appears to break when stretched with a predictable amount of force.
“Anyone can really make this DNA molecule,” Shaw said. “Our goal is to come up with a recipe that people can repeat anywhere in the world and get the same force.”
To test this idea, Shaw places under the microscope DNA that has been specially treated so one end of each strand sticks to the surface being scanned, while the other is attracted to the tip of the silicon probe. Then, he goes fishing. When the probe has snagged the loose end of a DNA molecule, the researchers gradually pull on it until it comes apart, then record the force at which it broke.
With any luck, their research will be a success, and before long yet another NIST recipe for precision will be circulating the globe, helping spur scientists and entrepreneurs to break new ground and push the boundaries of technology ever further forward.
Friday, August 20, 2010
Wednesday, August 18, 2010
At NIST, the Future of Healthcare Technology Rapidly Approaches
Imagine this: out of the blue one day, you begin to feel nauseated and achy. As your body temperature soars, you smartly head to the hospital, where you are greeted by the usual intake procedure. Once you get to the exam room, though, something unfamiliar happens. Instead of collecting a few milliliters of blood into a series of test tubes which are carefully labeled and sent off to a lab that will analyze the samples and return with a complete analysis in a matter of hours, the nurse removes a few microliters -- just a couple drops, really -- of blood and ejects them onto a thin, credit card-sized chip. Within minutes, the doctor is explaining to you the bacterial infection that is at the root of your symptoms and is handing you a prescription for antibiotics.
Thanks to researchers like Dr. Samuel Stavis, this sci-fi-sounding scenario may one day be a reality. Stavis is a physical scientist in the Semiconductor Electronics Division of the National Institutes of Standards and Technology (NIST), which sounds like a field pretty far removed from making bedside lab test equipment. But Stavis' expertise in nanofluidics, the study of fluids on a tiny, tiny, scale (think fractions of a drop of liquid), and nanofabrication make him aptly positioned for developing this kind of technology. His lab at NIST's Gaithersburg, MD, headquarters looks similar to the kind he may one day make obsolete: a large Zeiss microscope setup takes center stage, surrounded by various computers and intimidating apparatuses of chrome and every color of wire. Stavis himself appears equally sophisticated; his gelled blond hair, thin metal eyeglasses, and sharp dress make him appear more like a Scandanavian businessman than a scientist, but once he begins to energetically describe his work, his engineering prowess becomes clear.
He explains that the current process of sorting nanoparticles of different sizes is a lengthy and expensive one, as it relies on costly machines like electron microscopes and laborious techniques like chromatography. "The methods we have now for separating and characterizing nanoparticles are slowing down the whole field," he says.
His solution: integrate the separation process into a single nanofluidic device. His idea came to fruition in early 2009, when he published an article describing the successful creation of a nanofluidic device with a complex 3-D structure, the first of its kind in the world. The device is a chamber with a stair-step structure, a significant departure from the traditional flat channels of this equipment, and it is this unique structure that enables the device to separate nanoparticles ranging from 10 to 620 nanometers (approximately 1% the thickness of a strand of human hair, which is around 60,000 nanometers in diameter). Like a coin sorter on a scale a million times smaller, the device traps particles at certain points along the chamber based on their size. Once particles are separated, identifying and characterizing them becomes a much simpler process.
Stavis hopes that this device will put scientists closer to achieving the so-called lab-on-a-chip technology, a method by which processes and analyses that used to depend on entire labs' worth of equipment can be performed on a chip the size of a stick of gum.
The applications of this lab-on-a-chip technology are extensive, like in criminology where it could be used for instant DNA-matching analysis (which would be particularly helpful in light of recent revelations about the massive FBI backlog of DNA cases), but the field where it could make the biggest difference is healthcare. Doctors will be able to detect bacteria, viruses, and even cancer almost instantly. Besides making analyses much faster and cheaper to perform, the mobility of this technology makes it ideal for responding to large-scale medical disasters like the recent earthquake in Haiti. It could also be especially helpful in countries with poor healthcare infrastructure, where clinics often have the proper drugs to treat infectious diseases, but lack the diagnostic tools to determine who needs treatment.
For now, these bedside lab tests remain in the realm of fiction. But with groundbreaking work and innovative thinking like Stavis's, this future may be closer than it appears.
Tuesday, August 17, 2010
Researchers Create Measurement Standards from Nature
The doors on the oversized freight elevator slam shut. We slowly descend until we are forty feet below the surface of the earth. The doors open and we file out of the elevator into a long, artificially lit stretch of hall. We have reached the depths of Building 219 on the National Institute of Standards and Technology (NIST) campus in Gaithersburg, Maryland, where every aspect of the local environment – temperature, humidity, lighting, etc. – is strictly controlled.
“The researchers fight to work here,” mechanical engineer Jon Pratt remarks as we walk down the pristine hallway. Pratt and research chemist Gordon Shaw are creating reliable and accurate intrinsic (based on nature) reference standards as part of the Mass and Force Group of NIST’s Manufacturing Engineering Laboratory.
Shaw leads us to a room housing an atomic force microscope (AFM). We pass through one door, walk a few feet, and then pass through another door. This double isolation system helps keep the vibrations in the microscope room to a minimum and the temperature at 20 degrees Celsius plus or minus two-hundredths of a degree. Humidity is maintained at 30 percent plus or minus 1 percent. Not a bad place to work, especially during one of the hottest summers on record in the Washington, DC area.
Light is piped into the room along the ceiling so that no one light bulb creates a hot spot. “Thermogradients are the enemy,” Shaw says. “Even small temperature changes can cause the measurement system to be unstable enough that it won’t be able to measure what you’re interested in.”
With an AFM, you can view objects over 1,000 times smaller than with conventional light microscopy. The AFM uses a cantilever system to characterize materials at the atomic and molecular levels. A cantilever resembles a miniature diving board with a sharp silicone tip.
“As you bring the tip close to the surface, it may start to bend toward the surface because of the electrostatic force interactions with the surface,” Shaw notes.
The cantilever tip moves slowly back and forth across the surface of the sample. We look in amazement as the monitor starts to display a pattern that resembles an intertwined assortment of twigs. Shaw notes that the AFM is imaging collagen fibers. Collagen – the most abundant protein in mammals – is found in tendons, ligaments, skin, cartilage, and bone, among other tissues.
Shaw tells us that he would have preferred to image DNA this evening, but he acknowledges that it is rather “tricky” to do so.
Tricky, but not impossible. Actually, Shaw and Pratt have successfully used the AFM to measure the mechanical properties of a single DNA molecule so that it can serve as an intrinsic reference standard for force.
DNA normally forms random coils in solution. In a typical experiment, Shaw and Pratt would move the cantilever around, hunting for the DNA in a solution. They would coat the tip of the cantilever with a chemical that specifically binds to a substance found at one end of a DNA molecule. Eventually, they would get a molecule of DNA attached to the tip of the cantilever. The researchers would then begin to stretch the DNA molecule. At a certain point, typically at a force of approximately 65 piconewtons, the DNA molecule would stretch for a long distance with very little extra applied force.
“Some of the base pairs in the DNA are starting to come apart,” Shaw says. “You have a partial melting of the double helix at that point. That happens as far as we can tell at a fairly well-defined force.”
As Shaw and Pratt and another NIST colleague, Douglas Smith, note in a recent article published in the Proceedings of the SEM Annual Conference, a DNA molecule can therefore be used as a “force reference that will allow the calibration of a wide variety of force measuring instruments such as optical, magnetic, and dielectrophoretic tweezers.”
And thanks to modern polymerase chain reaction (PCR) methods, the same DNA molecule can be made over and over again. “In an afternoon’s work you can make enough to give everyone on the planet 5,000 force references,” Shaw notes as we exit through the double-door climate and vibration control system.
The freight elevator slowly rises to ground level. The doors open and natural light filters in through the first-floor windows. We have returned to a “normal” hallway, where a simple thermostat keeps the temperature at a comfortable level and rooms have just one door.
Still, I tread lightly as I walk down the hall.
“The researchers fight to work here,” mechanical engineer Jon Pratt remarks as we walk down the pristine hallway. Pratt and research chemist Gordon Shaw are creating reliable and accurate intrinsic (based on nature) reference standards as part of the Mass and Force Group of NIST’s Manufacturing Engineering Laboratory.
Shaw leads us to a room housing an atomic force microscope (AFM). We pass through one door, walk a few feet, and then pass through another door. This double isolation system helps keep the vibrations in the microscope room to a minimum and the temperature at 20 degrees Celsius plus or minus two-hundredths of a degree. Humidity is maintained at 30 percent plus or minus 1 percent. Not a bad place to work, especially during one of the hottest summers on record in the Washington, DC area.
Light is piped into the room along the ceiling so that no one light bulb creates a hot spot. “Thermogradients are the enemy,” Shaw says. “Even small temperature changes can cause the measurement system to be unstable enough that it won’t be able to measure what you’re interested in.”
With an AFM, you can view objects over 1,000 times smaller than with conventional light microscopy. The AFM uses a cantilever system to characterize materials at the atomic and molecular levels. A cantilever resembles a miniature diving board with a sharp silicone tip.
“As you bring the tip close to the surface, it may start to bend toward the surface because of the electrostatic force interactions with the surface,” Shaw notes.
The cantilever tip moves slowly back and forth across the surface of the sample. We look in amazement as the monitor starts to display a pattern that resembles an intertwined assortment of twigs. Shaw notes that the AFM is imaging collagen fibers. Collagen – the most abundant protein in mammals – is found in tendons, ligaments, skin, cartilage, and bone, among other tissues.
Shaw tells us that he would have preferred to image DNA this evening, but he acknowledges that it is rather “tricky” to do so.
Tricky, but not impossible. Actually, Shaw and Pratt have successfully used the AFM to measure the mechanical properties of a single DNA molecule so that it can serve as an intrinsic reference standard for force.
DNA normally forms random coils in solution. In a typical experiment, Shaw and Pratt would move the cantilever around, hunting for the DNA in a solution. They would coat the tip of the cantilever with a chemical that specifically binds to a substance found at one end of a DNA molecule. Eventually, they would get a molecule of DNA attached to the tip of the cantilever. The researchers would then begin to stretch the DNA molecule. At a certain point, typically at a force of approximately 65 piconewtons, the DNA molecule would stretch for a long distance with very little extra applied force.
“Some of the base pairs in the DNA are starting to come apart,” Shaw says. “You have a partial melting of the double helix at that point. That happens as far as we can tell at a fairly well-defined force.”
As Shaw and Pratt and another NIST colleague, Douglas Smith, note in a recent article published in the Proceedings of the SEM Annual Conference, a DNA molecule can therefore be used as a “force reference that will allow the calibration of a wide variety of force measuring instruments such as optical, magnetic, and dielectrophoretic tweezers.”
And thanks to modern polymerase chain reaction (PCR) methods, the same DNA molecule can be made over and over again. “In an afternoon’s work you can make enough to give everyone on the planet 5,000 force references,” Shaw notes as we exit through the double-door climate and vibration control system.
The freight elevator slowly rises to ground level. The doors open and natural light filters in through the first-floor windows. We have returned to a “normal” hallway, where a simple thermostat keeps the temperature at a comfortable level and rooms have just one door.
Still, I tread lightly as I walk down the hall.
Nano-sized Lab Sorts Particles On the Run
The sunglasses you are wear, the vitamin you took with your breakfast, the cell phone in your pocket may all have one thing in common--a component or part built with nanotechnology. The science of materials produced from the atom up at the nanoscale has exploded over the past two decades. But the pace of this infusion may get even faster thanks to a new measurement concept developed by the National Institute of Standards and Technology (NIST) and Cornell University.
Nanotechnology is being used to make all kinds of new and improved products, fortify manufacturing processes and even change long standing medical procedures. The list of applications for the science that builds on the unique qualities of nanoparticles is growing every day. You might not think from the way nanotechnology has infiltrated our lives that there is a challenge to living lives full of nano. But in fact, the complex and expensive processes needed to measure and describe particles – the building blocks of the technology – is slowing down the rate at which new applications can land in hands of consumers, patients and users.
The size of the nanoparticle matters significantly. For every one, its size and shape determines its properties, utility and even perhaps its safety. The conventional methods for measuring these particles can be slow. But that may change in the next few years because of a new concept just proved by a team led by Sam Stavis, Ph.D. from NIST. The technique integrates the process on a “lab on a chip.” It has potential to accelerate advances in biology, medicine, engineering, physics and materials science, all fields that use nanotechnology.
The foundation for the Dr. Stavis’s new nanoscale lab is a 4-inch wafer of glass. Using similar techniques to the ones used by the semiconductor industry to “paint on” circuitry, Stavis uses a process called grayscale photolithography to build a 3-D structure on the chip. First a layer of light sensitive chemical called “photoresist” is spread across the chip. With a a precisely calibrated “stencil”, light hits the photoresist and channels of varying widths are created across the wafer. The whole structure of 20 channels is shaped like a staircase and the channels range in size form 10 nanometers to 650 nanometers.
With another wafer placed on top, the channels-on-a-chip have become a chamber-on-a -chip. Stavis injects a solution with different size nanoparticles. Inside the chamber, the particles are pushed across the channel by an electric charge. As each particle hits a stair that matches it in diameter it falls into the corresponding channel. One after the other, nanoparticles drop into the right channel like coins in a change-sorting machine. The particles have been dyed with fluorescent paint so the team can photograph them with an electron microscope. The photo arrays the particles along a scale the channel rows are set to collect the particles that can only be seen under an electron microscope.
“You can mass produce and give people references better than the electron microscope and chromatography,” said Stavis. While the new lab-on-a-chip won’t replace these tools, this nanoscale tool for nanoparticles has potential for speed, flexibility, and portability without sacrificing accuracy achieved with the conventional tools.
Nanotechnology is being used to make all kinds of new and improved products, fortify manufacturing processes and even change long standing medical procedures. The list of applications for the science that builds on the unique qualities of nanoparticles is growing every day. You might not think from the way nanotechnology has infiltrated our lives that there is a challenge to living lives full of nano. But in fact, the complex and expensive processes needed to measure and describe particles – the building blocks of the technology – is slowing down the rate at which new applications can land in hands of consumers, patients and users.
The size of the nanoparticle matters significantly. For every one, its size and shape determines its properties, utility and even perhaps its safety. The conventional methods for measuring these particles can be slow. But that may change in the next few years because of a new concept just proved by a team led by Sam Stavis, Ph.D. from NIST. The technique integrates the process on a “lab on a chip.” It has potential to accelerate advances in biology, medicine, engineering, physics and materials science, all fields that use nanotechnology.
The foundation for the Dr. Stavis’s new nanoscale lab is a 4-inch wafer of glass. Using similar techniques to the ones used by the semiconductor industry to “paint on” circuitry, Stavis uses a process called grayscale photolithography to build a 3-D structure on the chip. First a layer of light sensitive chemical called “photoresist” is spread across the chip. With a a precisely calibrated “stencil”, light hits the photoresist and channels of varying widths are created across the wafer. The whole structure of 20 channels is shaped like a staircase and the channels range in size form 10 nanometers to 650 nanometers.
With another wafer placed on top, the channels-on-a-chip have become a chamber-on-a -chip. Stavis injects a solution with different size nanoparticles. Inside the chamber, the particles are pushed across the channel by an electric charge. As each particle hits a stair that matches it in diameter it falls into the corresponding channel. One after the other, nanoparticles drop into the right channel like coins in a change-sorting machine. The particles have been dyed with fluorescent paint so the team can photograph them with an electron microscope. The photo arrays the particles along a scale the channel rows are set to collect the particles that can only be seen under an electron microscope.
“You can mass produce and give people references better than the electron microscope and chromatography,” said Stavis. While the new lab-on-a-chip won’t replace these tools, this nanoscale tool for nanoparticles has potential for speed, flexibility, and portability without sacrificing accuracy achieved with the conventional tools.
The Secret in the Suburbs
These folks know all about you. They know how much your Fruit-of-the-Looms weigh and how much vitamin C is really in your Centrum. They know the size of your Michelins and how much air they’d better hold to keep you rolling, and they know that a .38 slug will leave a dent the size of an orange in your Kevlar vest. They know whether your dentist’s autoclave reaches the temperature needed to sterilize the drill, and whether her latex gloves will tear as she’s stretching her fingers toward your molars. If it’s your business, it’s their business.
They are the people who labor at the National Institutes of Standards and Technology. Their business is metrology, the science of measurement. According to Gail Porter it’s a business as old as, well, business. And you haven’t heard of it, because NIST, like any enterprise, keeps its valuables under lock and key, deep in unassuming Gaithersburg, Maryland, a dozen miles north of Washington DC.
Porter is NIST’s Public Affairs Director, which means she’s in charge of leading tours through the facility. We are eight adult writing students, tired after a humid summer workday. Porter is an energetic woman, dressed head to toe in business brown. She greets us at dusk, with a van in a parking lot outside the facility. After we pile in, she drives us past the guarded gatehouse and winds through a five hundred acre parkland.
The forests and lawns are home to deer, foxes—and laboratories buried forty feet below ground. “To minimize vibration,” Porter explains. And there are to be no perturbations in our schedule, either. She has arranged for us to tour the museum, visit three labs, and listen to three lectures, all in exactly 90 minutes.
We disembark at an exhibit hall and Porter herds us inside. She strides down the waxed linoleum with elbows pumping, while we struggle to follow. We think we have come to learn about nanotechnology, but we gape at smashed cars and lists of peanut butter ingredients. Porter is careful to point out that NIST developed expressly to serve commerce. It’s because of NIST that buying peanut butter is something shoppers can do with confidence. A jar of Skippy’s weighs a pound and holds a pint of a standardized mixture of peanuts, salt, fat and sweetener that can be called peanut butter. But how do you measure—and sell—something as small as a molecule? That question is what made NIST scientists turn their attention to nanotechnology.
Our next stop is “Building 216.” There, in an underground laboratory, Jon Pratt has assembled an instrument he calls “an electrostatic force balance.” Pratt has close-cropped silver hair, but looks boyish in skinny jeans. Porter reminds him that we have two lectures after his, so he speaks quickly, explaining that mass is not the same as weight, but more fundamental. Weight depends on gravity, but gravity is not constant throughout the universe. For example, we weigh more on earth than we would on the moon, but we still have the same mass. Pratt moves on to his electrostatic force balance—a scale—used to measure the mass of extremely tiny objects, say strands of DNA. Instead of using gravity to measure mass, Pratt’s scale uses the intrinsic electrostatic forces surrounding an object, even one as small as a molecule.
Nested in a ceiling-high cylinder of gleaming brushed steel, Pratt’s instrument is actually a probe shaped like a diving board, with a point one atom in diameter. The object to be “weighed” is moved toward the probe, and as it approaches, the object’s electrostatic field bends the probe up or down. The more massive the object, the bigger the deflection.
But that lecture is over, and we are handed off to Gordon Shaw. Shaw, also in jeans, is younger and stockier than Pratt. With enthusiastic hand motions, he explains that Pratt’s instrument allows him to measure the force required to rupture a strand of DNA (a standardized strand, of course).
Shaw leads us down an endless hall to his temperature-controlled laboratory. We crowd into a room slightly larger than a closet, and Shaw points to a work station. There, on a computer monitor, we see Pratt’s tiny diving board at work, dutifully deflecting before strands of protein. Shaw apologizes for not showing us strands of DNA. Someone tries to deflect the apology by saying that to us, protein or DNA, it’s all the same. Shaw’s voice drops. Not protein, he says, but DNA, will one day be the industry standard for measuring force on the molecular level.
But Porter has come to collect us and take us to our final stop, the laboratory of Samuel Stavis. Three years out of his PhD program, Stavis has neatly-cropped hair and Ivy League confidence. He ushers us into the small floor space separating his sprawling stereoscopic microscope from a counter that holds a dish labeled “Fragile.” His job, says Stavis, is to order a varied mixture of nanoparticles by size. To do this, he builds tiny tapering chutes, then forces nanoparticles into the chute. The nanoparticles travel down the narrowing chute and stop when their diameter equals that of the chute. Large particles stop sooner than small particles. It is a simple idea, and it strikes us as ingenius.
There are still some problems to work out, says Stavis, like how to separate the various particles once they’re stopped. But Stavis has published a paper on the topic, and the biomedical industry is reading it.
Tours are not available for the general public. But Nist does not consider students, industry groups, scouts, consumer groups, non-profits, and so on "the general public". So if you can talk Gail Porter into believing you’re not a member of the general public, a tour is well worth your time.
http://www.nist.gov/public_affairs/
They are the people who labor at the National Institutes of Standards and Technology. Their business is metrology, the science of measurement. According to Gail Porter it’s a business as old as, well, business. And you haven’t heard of it, because NIST, like any enterprise, keeps its valuables under lock and key, deep in unassuming Gaithersburg, Maryland, a dozen miles north of Washington DC.
Porter is NIST’s Public Affairs Director, which means she’s in charge of leading tours through the facility. We are eight adult writing students, tired after a humid summer workday. Porter is an energetic woman, dressed head to toe in business brown. She greets us at dusk, with a van in a parking lot outside the facility. After we pile in, she drives us past the guarded gatehouse and winds through a five hundred acre parkland.
The forests and lawns are home to deer, foxes—and laboratories buried forty feet below ground. “To minimize vibration,” Porter explains. And there are to be no perturbations in our schedule, either. She has arranged for us to tour the museum, visit three labs, and listen to three lectures, all in exactly 90 minutes.
We disembark at an exhibit hall and Porter herds us inside. She strides down the waxed linoleum with elbows pumping, while we struggle to follow. We think we have come to learn about nanotechnology, but we gape at smashed cars and lists of peanut butter ingredients. Porter is careful to point out that NIST developed expressly to serve commerce. It’s because of NIST that buying peanut butter is something shoppers can do with confidence. A jar of Skippy’s weighs a pound and holds a pint of a standardized mixture of peanuts, salt, fat and sweetener that can be called peanut butter. But how do you measure—and sell—something as small as a molecule? That question is what made NIST scientists turn their attention to nanotechnology.
Our next stop is “Building 216.” There, in an underground laboratory, Jon Pratt has assembled an instrument he calls “an electrostatic force balance.” Pratt has close-cropped silver hair, but looks boyish in skinny jeans. Porter reminds him that we have two lectures after his, so he speaks quickly, explaining that mass is not the same as weight, but more fundamental. Weight depends on gravity, but gravity is not constant throughout the universe. For example, we weigh more on earth than we would on the moon, but we still have the same mass. Pratt moves on to his electrostatic force balance—a scale—used to measure the mass of extremely tiny objects, say strands of DNA. Instead of using gravity to measure mass, Pratt’s scale uses the intrinsic electrostatic forces surrounding an object, even one as small as a molecule.
Nested in a ceiling-high cylinder of gleaming brushed steel, Pratt’s instrument is actually a probe shaped like a diving board, with a point one atom in diameter. The object to be “weighed” is moved toward the probe, and as it approaches, the object’s electrostatic field bends the probe up or down. The more massive the object, the bigger the deflection.
But that lecture is over, and we are handed off to Gordon Shaw. Shaw, also in jeans, is younger and stockier than Pratt. With enthusiastic hand motions, he explains that Pratt’s instrument allows him to measure the force required to rupture a strand of DNA (a standardized strand, of course).
Shaw leads us down an endless hall to his temperature-controlled laboratory. We crowd into a room slightly larger than a closet, and Shaw points to a work station. There, on a computer monitor, we see Pratt’s tiny diving board at work, dutifully deflecting before strands of protein. Shaw apologizes for not showing us strands of DNA. Someone tries to deflect the apology by saying that to us, protein or DNA, it’s all the same. Shaw’s voice drops. Not protein, he says, but DNA, will one day be the industry standard for measuring force on the molecular level.
But Porter has come to collect us and take us to our final stop, the laboratory of Samuel Stavis. Three years out of his PhD program, Stavis has neatly-cropped hair and Ivy League confidence. He ushers us into the small floor space separating his sprawling stereoscopic microscope from a counter that holds a dish labeled “Fragile.” His job, says Stavis, is to order a varied mixture of nanoparticles by size. To do this, he builds tiny tapering chutes, then forces nanoparticles into the chute. The nanoparticles travel down the narrowing chute and stop when their diameter equals that of the chute. Large particles stop sooner than small particles. It is a simple idea, and it strikes us as ingenius.
There are still some problems to work out, says Stavis, like how to separate the various particles once they’re stopped. But Stavis has published a paper on the topic, and the biomedical industry is reading it.
Tours are not available for the general public. But Nist does not consider students, industry groups, scouts, consumer groups, non-profits, and so on "the general public". So if you can talk Gail Porter into believing you’re not a member of the general public, a tour is well worth your time.
http://www.nist.gov/public_affairs/
Stretching it out: Nano-force standard relies on DNA’s breaking point
Dr. Gordon Shaw squats down over the shiny linoleum floor, holding one end of a length of string in his hand. He grabs the middle of the string with his other hand and begins swirling his arms around, tracing random parabolas through the air with the string.
Shaw isn’t performing a magic trick, rather, he’s simulating how a single molecule of DNA behaves in solution. He and his colleagues have devised a way to carefully measure the force required to straighten out such a DNA molecule and stretch it beyond its breaking point, giving them the most precise standard to date for measuring forces at the nanoscale.
Shaw is a research scientist in the Advanced Measurement Lab at the National Institute for Standards and Technology in Gaithersburg, Md. For the last six years, he has been spending most of his waking hours figuring out new ways to accurately measure impossibly small masses, forces and distances.
His latest project is developing an intrinsic force measurement for things happening at the atomic scale--the individual molecules that make up everything from the cells in our bodies to the building blocks of metal alloys. Shaw’s experiments will provide a standard that could help scientists better understand, for example, the forces involved in protein folding that lead to the formation of plaques in Alzheimer’s disease or the differences in cell stiffness that distinguish healthy cells from cancerous cells.
“Proteins are like little machines,” said Shaw. “They fold and twist and perform different functions based on how they behave mechanically.”
In order to assess those differences, you need a measurement device that can distinguish between the forces that hold one protein in position versus another. You also need a way to calibrate your measurement device to make sure that what your measuring corresponds to accepted and verified scientific standards.
Shaw and his colleagues have recently developed a method of measuring nano-scale forces based on the intrinsic strength of bonds that hold DNA molecules together. In its natural state, DNA floats freely in a coiled double-helix shape like a noodle in a pot of boiling spaghetti. Using techniques developed at NIST, Shaw has found a way to grab one end of the DNA strand and gently pull it taut like a string. At first, the strand of DNA will simply straighten out with virtually no force applied at all. But eventually, with tiny, increasing amounts of force, the individual base pairs start to rip apart. Base pairs will then continue to break apart with almost no additional force applied until the double helix completely unravels. It is this point, the so called intrinsic force plateau, that serves as a reference point for future nanotechnologies. This particular strain of DNA’s breaking point happens to occur at exactly 65 piconewtons.
“It has this well defined force signature,” Shaw said. “We can calibrate it once, replicate DNA molecule trillions of time, and it will be exactly the same.”
In addition to having an extremely consistent breaking point, these specially designed DNA molecules can also be produced on the cheap. According to Shaw, just $20 of raw material can be transformed into 5000 reference samples for every person on the planet in just a few hours.
Using a synthesized DNA molecule also has the benefit of being flexible enough to work in a number of settings. A major concern with investing so much time and effort into developing a reference standard is that it will immediately become obsolete. So rather than designing a specific sensor technology, they developed a reference standard that works almost anywhere.
“That’s why we thought it would be good to calibrate to a DNA molecule,” said Shaw. “It can be used in multiple platforms and technologies.”
Shaw’s next challenge is to figure out how to reduce the uncertainty of his reference standard calibration. Currently, his measurements are picking up about a piconewton of noise--a force equal to one trillionth the weight of a small apple--which contributes to an overall uncertainty of five percent. They’d like to drive that number down by reducing the amount of noise they pick up in their measurements.
But for now, he can revel in the glory of having developed the smallest reliable measure of force known to man. Because with so many rapid advances in the field of nanotechnology, one thing is certain: the standard won’t last for long.
Shaw isn’t performing a magic trick, rather, he’s simulating how a single molecule of DNA behaves in solution. He and his colleagues have devised a way to carefully measure the force required to straighten out such a DNA molecule and stretch it beyond its breaking point, giving them the most precise standard to date for measuring forces at the nanoscale.
Shaw is a research scientist in the Advanced Measurement Lab at the National Institute for Standards and Technology in Gaithersburg, Md. For the last six years, he has been spending most of his waking hours figuring out new ways to accurately measure impossibly small masses, forces and distances.
His latest project is developing an intrinsic force measurement for things happening at the atomic scale--the individual molecules that make up everything from the cells in our bodies to the building blocks of metal alloys. Shaw’s experiments will provide a standard that could help scientists better understand, for example, the forces involved in protein folding that lead to the formation of plaques in Alzheimer’s disease or the differences in cell stiffness that distinguish healthy cells from cancerous cells.
“Proteins are like little machines,” said Shaw. “They fold and twist and perform different functions based on how they behave mechanically.”
In order to assess those differences, you need a measurement device that can distinguish between the forces that hold one protein in position versus another. You also need a way to calibrate your measurement device to make sure that what your measuring corresponds to accepted and verified scientific standards.
Shaw and his colleagues have recently developed a method of measuring nano-scale forces based on the intrinsic strength of bonds that hold DNA molecules together. In its natural state, DNA floats freely in a coiled double-helix shape like a noodle in a pot of boiling spaghetti. Using techniques developed at NIST, Shaw has found a way to grab one end of the DNA strand and gently pull it taut like a string. At first, the strand of DNA will simply straighten out with virtually no force applied at all. But eventually, with tiny, increasing amounts of force, the individual base pairs start to rip apart. Base pairs will then continue to break apart with almost no additional force applied until the double helix completely unravels. It is this point, the so called intrinsic force plateau, that serves as a reference point for future nanotechnologies. This particular strain of DNA’s breaking point happens to occur at exactly 65 piconewtons.
“It has this well defined force signature,” Shaw said. “We can calibrate it once, replicate DNA molecule trillions of time, and it will be exactly the same.”
In addition to having an extremely consistent breaking point, these specially designed DNA molecules can also be produced on the cheap. According to Shaw, just $20 of raw material can be transformed into 5000 reference samples for every person on the planet in just a few hours.
Using a synthesized DNA molecule also has the benefit of being flexible enough to work in a number of settings. A major concern with investing so much time and effort into developing a reference standard is that it will immediately become obsolete. So rather than designing a specific sensor technology, they developed a reference standard that works almost anywhere.
“That’s why we thought it would be good to calibrate to a DNA molecule,” said Shaw. “It can be used in multiple platforms and technologies.”
Shaw’s next challenge is to figure out how to reduce the uncertainty of his reference standard calibration. Currently, his measurements are picking up about a piconewton of noise--a force equal to one trillionth the weight of a small apple--which contributes to an overall uncertainty of five percent. They’d like to drive that number down by reducing the amount of noise they pick up in their measurements.
But for now, he can revel in the glory of having developed the smallest reliable measure of force known to man. Because with so many rapid advances in the field of nanotechnology, one thing is certain: the standard won’t last for long.
Saturday, August 14, 2010
Setting the standard for subatomic forces
Everyday language makes plenty of references to “force” – a person with a strong personality is a ‘force of nature,’ or we worry about unseen ‘forces of evil.’ But the physics version came before all those figures of speech – force as a push or pull that changes the motion of an object. Accurate evaluation of physical force matters constantly in every day life – a car moves forward when its bulk is propelled by gas being burned in a combustion engine, or an arm thrusts a ball forward to the first baseman or wide receiver. The car only works if all its component parts, made in many different places, fit together properly, and if its chosen engine generates enough – you guessed it – force to move the assembled body.
So, how do people compare forces? Way back in high school science, you might have heard of Newton’s Second Law. The simple mathematical description of physical force boils down to a famous formula, in which Force = Mass multiplied by Acceleration. By convention, the unit of measurement of force is now the appropriately-named "Newton," which is defined as the force required to accelerate a 1 kilogram mass at a particular rate (1 square meter, to be exact). This standard definition, coupled with known reference materials like that kilogram, allows engineers in the United States to describe amounts of force in ways in the same as engineers in, say, Korea.
Interestingly, the kilogram remains the only international measurement unit that is defined by an arbitrary “artifactual” standard – a hunk of metal made in 1889 that resides outside of Paris. All the others, such as length, time, and temperature, are linked to some natural phenomenon that’s the same the world over. For example, the chief unit of time, the second, is linked to properties of cesium atoms, an “intrinsic” standard. The intrinsic approach has obvious advantages, unless you really find it convenient to travel to France every time you need to check the whether your kilogram of car parts is the same as someone else’s. That’s why researchers at the National Institute of Standards and Technology (NIST), a subdivision of the U.S. federal government’s Department of Commerce in Gaithersburg, MD, are working hard on a new definition for the kilogram (http://www.nist.gov/mel/mmd/mf/rekilo.cfm). And the problems are even harder when the objects involved are on the nanoscale, thousands of times smaller than an engine or a baseball.
Enter NIST researchers Jon Pratt and Gordon Shaw. Dr. Pratt and Dr. Gordon are developing a new and novel means of standardizing the definition of very small forces between atoms (http://www.nist.gov/mel/mmd/mf/sfmet.cfm). Their work, soon to be published in detail, was initially described during Dr. Pratt’s keynote address to the 2010 Annual Meeting of the Society for Experimental Mechanics (see http://www.nist.gov/manuscript-publication-search.cfm?pub_id=905416).
To create a new standard, they’ve studied the behavior of piece of double stranded DNA dissolved in a fluid under defined conditions of temperature and pH. Ordinarily DNA has a loose structure, rather like a woven rope that coils and flops randomly in solution. But the DNA can be anchored to a surface at one end, then picked up and pulled from the other end by a tiny lever in a large instrument designed to measure forces called an atomic force microscope (AFM). This arrangement simultaneously stretches out the DNA rope and measures the force being exerted, when the AFM lever senses resistance. When the pulling action first begins to stretch the DNA, the molecule resists the pull, and increasing force is measured via the AFM’s lever. But then at a certain point, the rope begins to unravel or fray instead of the resistance increasing – and for a fairly long period of more pulling, the force being measured doesn’t change. Eventually, when pulled hard enough and long enough, the rope puts up a last gasp of resistance and very large forces are measured, until the rope breaks apart altogether.
That intermediate zone, in which the force remains constant despite increasing pull, can be taken advantage of to use as a standard means of defining a particular amount of molecular force. “Our goal,” says Dr. Pratt, “is a recipe for people to be able to repeat anywhere in the world and get a known force.” The standard DNA can be made and used by any group anywhere in the world who has access to what are now relatively cheap and common materials and equipment. In fact, Dr. Shaw points out, “In an afternoon’s work you can make enough [DNA] to give everybody on the planet 5000 force references.” And the intrinsic property of that piece of DNA is the same whether stretched by an atomic force microscope in Montreal or in Moscow.
The technical catch is that the properties of the levers used in the atomic force microscope have to also be comparable and known, or “calibrated,” in order to get the same results everywhere. To solve that problem, Dr. Pratt built the world’s first electrostatic force balance (“Five years of my life,” jokes Dr. Pratt), a large and delicate piece of equipment that’s used to calibrate the levers used in atomic force microscopes. A calibrated set of levers can be shipped throughout the world to other reference agencies. Thus, NIST is on the forefront of furthering even more new applications for materials made on the nanoscale, which are now ubiquitous in products as varied as medicines, suntan lotion, and semi-conductors.
So, how do people compare forces? Way back in high school science, you might have heard of Newton’s Second Law. The simple mathematical description of physical force boils down to a famous formula, in which Force = Mass multiplied by Acceleration. By convention, the unit of measurement of force is now the appropriately-named "Newton," which is defined as the force required to accelerate a 1 kilogram mass at a particular rate (1 square meter, to be exact). This standard definition, coupled with known reference materials like that kilogram, allows engineers in the United States to describe amounts of force in ways in the same as engineers in, say, Korea.
Interestingly, the kilogram remains the only international measurement unit that is defined by an arbitrary “artifactual” standard – a hunk of metal made in 1889 that resides outside of Paris. All the others, such as length, time, and temperature, are linked to some natural phenomenon that’s the same the world over. For example, the chief unit of time, the second, is linked to properties of cesium atoms, an “intrinsic” standard. The intrinsic approach has obvious advantages, unless you really find it convenient to travel to France every time you need to check the whether your kilogram of car parts is the same as someone else’s. That’s why researchers at the National Institute of Standards and Technology (NIST), a subdivision of the U.S. federal government’s Department of Commerce in Gaithersburg, MD, are working hard on a new definition for the kilogram (http://www.nist.gov/mel/mmd/mf/rekilo.cfm). And the problems are even harder when the objects involved are on the nanoscale, thousands of times smaller than an engine or a baseball.
Enter NIST researchers Jon Pratt and Gordon Shaw. Dr. Pratt and Dr. Gordon are developing a new and novel means of standardizing the definition of very small forces between atoms (http://www.nist.gov/mel/mmd/mf/sfmet.cfm). Their work, soon to be published in detail, was initially described during Dr. Pratt’s keynote address to the 2010 Annual Meeting of the Society for Experimental Mechanics (see http://www.nist.gov/manuscript-publication-search.cfm?pub_id=905416).
To create a new standard, they’ve studied the behavior of piece of double stranded DNA dissolved in a fluid under defined conditions of temperature and pH. Ordinarily DNA has a loose structure, rather like a woven rope that coils and flops randomly in solution. But the DNA can be anchored to a surface at one end, then picked up and pulled from the other end by a tiny lever in a large instrument designed to measure forces called an atomic force microscope (AFM). This arrangement simultaneously stretches out the DNA rope and measures the force being exerted, when the AFM lever senses resistance. When the pulling action first begins to stretch the DNA, the molecule resists the pull, and increasing force is measured via the AFM’s lever. But then at a certain point, the rope begins to unravel or fray instead of the resistance increasing – and for a fairly long period of more pulling, the force being measured doesn’t change. Eventually, when pulled hard enough and long enough, the rope puts up a last gasp of resistance and very large forces are measured, until the rope breaks apart altogether.
That intermediate zone, in which the force remains constant despite increasing pull, can be taken advantage of to use as a standard means of defining a particular amount of molecular force. “Our goal,” says Dr. Pratt, “is a recipe for people to be able to repeat anywhere in the world and get a known force.” The standard DNA can be made and used by any group anywhere in the world who has access to what are now relatively cheap and common materials and equipment. In fact, Dr. Shaw points out, “In an afternoon’s work you can make enough [DNA] to give everybody on the planet 5000 force references.” And the intrinsic property of that piece of DNA is the same whether stretched by an atomic force microscope in Montreal or in Moscow.
The technical catch is that the properties of the levers used in the atomic force microscope have to also be comparable and known, or “calibrated,” in order to get the same results everywhere. To solve that problem, Dr. Pratt built the world’s first electrostatic force balance (“Five years of my life,” jokes Dr. Pratt), a large and delicate piece of equipment that’s used to calibrate the levers used in atomic force microscopes. A calibrated set of levers can be shipped throughout the world to other reference agencies. Thus, NIST is on the forefront of furthering even more new applications for materials made on the nanoscale, which are now ubiquitous in products as varied as medicines, suntan lotion, and semi-conductors.
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