Systems and Synthetic Biology

Editors-in-Chief: P.K. Dhar; R. Weiss

Systems and Synthetic Biology is a new biomedical journal publishing original papers and articles on all aspects of Systems and Synthetic Biology.

Systems Biology is an integrated approach to study collective behaviour of biological interactions. The grand challenge in Systems Biology is to connect molecular topography with physiological responses. Systems Biology field will realize its fullest potential once individual contributions are tied to variations in the system level behavior.

The emerging field of synthetic biology combines knowledge from various disciplines including molecular biology, engineering, mathematics, and physics to design and implement new cellular behaviors. The goal of synthetic biology is both to improve our quantitative understanding of natural phenomenon as well as to foster an engineering discipline for obtaining new complex cell behaviors in a predictable and reliable fashion. Systems and Synthetic Biology will publish research articles that either advance this field as an engineering discipline or use synthetic biology to improve our scientific knowledge of existing phenomena.

Synthetic biology: new engineering rules for an emerging discipline

I came across this very informative article...it's really long, but very good..

Synthetic biologists engineer complex artificial biological systems to investigate natural biological phenomena and for a variety of applications. We outline the basic features of synthetic biology as a new engineering discipline, covering examples from the latest literature and reflecting on the features that make it unique among all other existing engineering fields. We discuss methods for designing and constructing engineered cells with novel functions in a framework of an abstract hierarchy of biological devices, modules, cells, and multicellular systems. The classical engineering strategies of standardization, decoupling, and abstraction will have to be extended to take into account the inherent characteristics of biological devices and modules. To achieve predictability and reliability, strategies for engineering biology must include the notion of cellular context in the functional definition of devices and modules, use rational redesign and directed evolution for system optimization, and focus on accomplishing tasks using cell populations rather than individual cells. The discussion brings to light issues at the heart of designing complex living systems and provides a trajectory for future development.

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Synthetic Biology is 'Extreme Genetic Engineering' and Far More Dangerous

A new report by the ETC Group concludes that the social,
environmental and bio-weapons threats of synthetic biology surpass
the possible dangers and abuses of biotech. The full text of the 70-
page report, Extreme Genetic Engineering: An Introduction to
Synthetic Biology, is available for downloading free-of-charge on the
ETC Group website: www.etcgroup.org

"Genetic engineering is passe," said Pat Mooney, Executive Director
of ETC Group. "Today, scientists aren't just mapping genomes and
manipulating genes, they're building life from scratch - and they're
doing it in the absence of societal debate and regulatory oversight,"
said Mooney.

Synbio - dubbed "genetic engineering on steroids" - is inspired by
the convergence of nano-scale biology, computing and engineering.
Using a laptop computer, published gene sequence information and mail-
order synthetic DNA, just about anyone has the potential to construct
genes or entire genomes from scratch (including those of lethal
pathogens). Scientists predict that within 2-5 years it will be
possible to synthesise any virus; the first de novo bacterium will
likely make its debut in 2007; in 5-10 years simple bacterial genomes
will be synthesised routinely and it will become no big deal to
cobble together a designer genome, insert it into an empty bacterial
cell and - voila - give birth to a living, self-replicating organism.
Other synthetic biologists hope to reconfigure the genetic pathways
of existing organisms to perform new functions - such as
manufacturing high-value drugs or chemicals.

A clutch of entrepreneurial scientists, including the gene maverick
J. Craig Venter, is setting up synthetic biology companies backed by
government funding and venture capital. They aim to commercialise new
biological parts, devices and systems that don't exist in the natural
world - some of which are designed for environmental release.
Advocates insist that synthetic biology is the key to cheap biofuels,
a cure for malaria, and climate change remediation - media-friendly
goals that aim to mollify public concerns about a dangerous and
controversial technology. Ultimately synthetic biology means cheaper
and widely accessible tools to build bioweapons, virulent pathogens
and artificial organisms that could pose grave threats to people and
the planet. The danger is not just bio-terror, but "bio-error," warns
ETC Group.

Despite calls for open source biology, corporate and academic
scientists are winning exclusive monopoly patents on the products and
processes of synthetic genetics. Like biotech, the power to make
synthetic life could be concentrated in the hands of major
multinational firms. As gene synthesis becomes cheaper and faster, it
will become easier to synthesise a microbe than to find it in nature
or retrieve it from a gene bank. Biological samples, sequenced and
stored in digital form, will move instantaneously across the globe
and be resurrected in corporate labs thousands of miles away - a
practice that could erode future support for genetic conservation and
create new challenges for international negotiations on biodiversity.

"Last year, 38 civil society organizations rejected proposals for
self-regulation of synthetic biology put forth by a small group of
synthetic biologists," said Kathy Jo Wetter of ETC Group. "Widespread
debate on the social, economic and ethical implications of synbio
must come first - and it must not be limited to biosecurity and
biosafety issues," said Wetter.

The tools for synthesising genes and genomes are widely accessible
and advancing at break-neck pace. ETC Group's new report concludes
that it is not enough to regulate synthetic biology on the national
level. Decisions must be considered in a global context, with broad
participation from civil society and social movements. In keeping
with the Precautionary Principle, ETC Group asserts that - at a
minimum - there must be an immediate ban on environmental release of
de novo synthetic organisms until wide societal debate and strong
governance are in place.

The Dangers of Synthetic Biology

Nobel Prize winner David Baltimore explains why building smallpox from scratch is a key safety concern in synthetic biology.

The emerging field of synthetic biology -- the quest to design and build new life forms that can perform useful functions -- brings exciting promise and potentially dangerous capabilities. Scientists have the ability to synthesize entire strings of DNA and put together complicated molecular machinery. But that power has raised some troubling questions. Could terrorists recreate viruses such as smallpox? Or engineer a virus even more deadly than avian flu? (see "The Knowledge").

In the 1970s, scientists faced a similar dilemma. The advent of recombinant DNA technology meant biologists could manipulate DNA as they never could before. Concerned about the potential perils of this new tool, a prominent group of scientists held the now-famous Asilomar Conference in 1975 (formally titled the "International Congress on Recombinant DNA Molecules") to determine how to proceed safely.

Thirty years later, at the Synthetic Biology 2.0 meeting at the University of California, Berkeley this month, scientists met to discuss not only new developments in the field, but also how the community should deal with the growing safety concerns surrounding synthetic biology.

David Baltimore, a winner of the 1975 Nobel Prize in physiology or medicine, and president of the California Institute of Technology, was one of the organizers of the Asilomar Conference. At the Synthetic Biology conference last week, he reflected on changes in the field over the last 30 years. Baltimore talks here with Technology Review about what scientists have learned since 1975 and the specific dangers we should be most worried about.

Technology Review: What were you were most concerned about 30 years ago?

David Baltimore: The Asilomar Conference was convened in a very different context than we have today. We were marveling at a wholly new world of experimentation -- we literally had no experience with moving DNA around. But people were also concerned, and rightly so, about issues of intrinsic safety. They were worried, for example, that we could create organisms that we didn't know how to control.

At the conference, we decided to focus purely on safety, rather than ethics or biowarfare. We believed, somewhat naively, that there was a treaty that everyone held to prohibiting use of technology to make biological weapons. In retrospect, the U.S.S.R. had a huge clandestine program. We also didn't have the situation we have today, where terrorist organizations cross boundaries and are not held by treaties. So we clearly have an unfinished agenda from Asilomar on biowarfare.

TR: What issues are you most worried about today?

DB: The real danger today is from organisms that already exist. The idea of synthesizing something worse than that, of taking bits of Ebola and other viruses to create something more deadly, underestimates how hard it is to survive in the natural world.

Adapting to the human lifestyle is very complicated, so I would guess that we would fail if we tried to engineer a dangerous organism. Ebola, for example, is very pathogenic. It infects families and health workers, but it never spreads widely because it is too lethal -- it isn't in the community long enough to spread. Bird flu is not likely to spread widely until it mutates to become less pathogenic.

Read the full interview here

Next-Generation Retinal Implant

On Thursday, scientists at the University of Southern California (USC) announced their plans to test an improved retinal implant in blind patients. The new implant, which scientists hope will better improve patients' vision, has four times the resolution of the previous version.

"My expectation, without really knowing what is going to happen, is that this will be useful for people in allowing them to find a lit doorway or the edge of an object when going into a room," says James Weiland, a scientist at USC involved in the project.

People with retinal-degeneration diseases, such as retinitis pigmentosa and macular degeneration, lose their sight as the cells in the eye that normally sense light deteriorate. Retinal implants can take over for these lost cells, converting light into neural signals that are then interpreted by the brain. Simpler versions of these devices, developed by researchers at USC and other institutions, have already been tested in humans, giving patients rudimentary vision, such as the ability to detect light and to occasionally distinguish between simple objects. One patient, for example, wears the device to her grandson's soccer games and reports that she perceives the sensation of the players' movement as they run by, says Weiland.

The device, developed by Mark Humayun and colleagues at USC, consists of a tiny chip dotted with hair-thin electrodes. When implanted in the retina, the electrodes transmit electrical signals from the chip to neural cells in the eye, which then send the message to the brain. A wireless camera mounted on glasses and a video processing unit worn on the belt capture and process visual information from the wearer's surroundings and wirelessly transmit those signals to the chip.

The new version of the implant, which the researchers have been working on for the past eight years, has nearly quadrupled the number of electrodes--from 16 to 60--and is about half the size of the previous model. The researchers recently received permission from the Food and Drug Administration to start human tests, which they plan to begin in the next few months.

Once the device is implanted, researchers will need to do extensive tests to figure out how to optimize it. "A camera gets at least tens of thousands of pixel information, and we need to transmit that to just 60 stimulating channels," says Weiland. "We have to figure out what is the most important information to keep."

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New DNA test in Anna Nicole Smith case

i know.. i know... but it's still about what genetics can do!!

A judge ordered another DNA sample be taken fromAnna Nicole Smith's body Thursday as he heard often fiery arguments in the fight over the former Playboy Playmate's remains and custody of her infant daughter.

The swab of Smith's cheek was to be taken in the afternoon, despite the objections of attorneys for her longtime companion, Howard K. Stern, and her estranged mother, Vergie Arthur, and testimony from the medical examiner and DNA experts that such an additional sample was likely not necessary.

Circuit Judge Larry Seidlin said he wanted to make sure all samples were taken before Smith was buried, so her body wouldn't have to be exhumed.

"When we bury her, I want it to be forever," he said in the second day of an emergency hearing.

Smith, 39, died Feb. 8 after collapsing at a Florida hotel.

As the proceedings dragged on, investigators in the Bahamas went into a mansion that Stern and Smith shared, though the officers declined to say why they were there. Stern filed a burglary report claiming a computer, home videos and other items were taken from the house after Smith's death.

Stern claims he is executor of Smith's will and wants to have her buried next to her son in the Bahamas. Arthur wants her daughter buried in her home state of Texas.

"She sits here today to take her to Texas and put her in the ground all alone ... and it's sad and it's sick," Stern's lawyer, Krista Barth, told the judge in attacking Smith's mother.

Arthur's attorney, Stephen Tunstall, said his client "wants to take her home to Texas to bury her with the rest of her family." Arthur wiped tears away outside an elevator during a break in the proceedings.

Photographer Larry Birkhead hopes DNA taken from Smith will help prove he fathered the former centerfold's 5-month-old daughter, Dannielynn, who could inherit millions.

The judge has said the dispute could be lengthy. The hearing, which began Wednesday, stretched into the afternoon Thursday and was to continue Friday.

Debra Opri, an attorney for Birkhead, said earlier in a news release that she was satisfied DNA samples would be provided by Florida authorities. Opri has said Smith's DNA is needed to connect her with Dannielynn, and to help prove there was no baby switch.

Prince Frederic von Anhalt, the husband of the actress
Zsa Zsa Gabor, has said he had a decade-long affair with Smith and may also be the father. He filed legal documents Thursday in California seeking a DNA test to determine if he is the father of the baby.

Smith's body remained at the medical examiner's office, and Seidlin said it would stay there. "This body's not leaving Broward County till I make the ruling."

Smith was the widow of Texas oil tycoon J. Howard Marshall II, whom she married in 1994 when he was 89 and she was 26. She had been fighting his family over his fortune since his death in 1995.

A judge in the Bahamas issued an injunction Tuesday preventing the baby from being taken out of the country until the custody case is resolved.

Arthur wants to be named guardian of her granddaughter and sought the order because she feared Stern would take the child from the Bahamas, her lawyer said.

Your Genetic Destiny for Sale

I found this article while browsing around... it's a very old one.. almost 6 years old..2001 i think.. but totally fascinating. I'm not publishing the whole article here, it's about 6 pages long.

Large extended families have traditionally been the mother lode of genetic research. From them came a precious commodity: links between the presence of a disease and the errant genes responsible for it. When medical researcher Nancy Wexler, for instance, went looking for the genetic cause of Huntington's disease in 1979, it was a 9,000-member Venezuelan family that enabled her to trace the telltale patterns of disease inheritance.

Wayne Gulliver's family is not nearly so large, but it is impressive nonetheless. Until two years ago, when his great-great-aunt passed away, six generations of Gullivers were alive in Newfoundland. His grandmother, who died last October, had some hundred descendants, while his parents, only in their 60s, already have 26 grandchildren to go with their 10 children. All of this would be professionally irrelevant if Gulliver's family were not typical of Newfoundland, and if Gulliver himself, a dermatologist who studies the genetics of psoriasis, were not involved in a rapidly emerging discipline called population genomics, the goal of which is to identify the underlying genes responsible for common chronic diseases, such as cancer and heart disease.

Two years ago Gulliver met Paul Kelly, CEO of the British company Gemini Genomics, which had already assembled a huge international network of twins to use in searching for gene-disease associations. Gulliver pitched Kelly the idea of supplementing Gemini's database with population statistics from Newfoundland and Labrador. His selling points were simple: a population of 550,000, of which almost 90 percent are descended from the original Irish, Scottish and English immigrants who arrived before the mid-19th century. It is, Gulliver says, a population in which the locals often know their family lineages back to the original immigrants. "Not like the States," he says, "where you have three kids, send them off to college, and you might be lucky if you see each other every fifth Thanksgiving."

And many of those families, like Gulliver's own, are large. In such a tightly knit population consisting of large extended families, common diseases might run in recognizable patterns-shared by siblings, for instance, or passing through paternal or maternal lines, or linked to other distinctive physical characteristics. All it would take to mine this rich vein of medical history for valuable clues to disease-causing genes would be a sufficient effort, some very advanced biotechnology tools and some startup capital.

Gulliver's pitch prompted Gemini to launch Newfound Genomics in February 2000. In the near term, Newfound Genomics aims to concentrate on diseases endemic to the local population-psoriasis, diabetes, obesity, inflammatory bowel disease, osteoporosis and rheumatoid arthritis-with the hope, considering the Irish/English/Scottish ancestry, that any relevant genes or gene variants that might be uncovered would play significant roles in other populations. The expectations behind the company are anything but modest, at least judging by the inaugural press release. "We have the potential here to develop a major international powerhouse of clinical genetics," said Kelly, "that will provide benefit not only for the Newfoundland and Labrador community but also patients suffering from these diseases worldwide."

To read the entire article click here

Can RNA Turn Genes On?

Researchers at the University of Texas Southwestern Medical Center have found that RNA may be a potential tool in activating dormant genes.

RNA--a tiny cousin of DNA that may be the key to developing genetic therapies for a huge range of diseases, including cancer, neurological and respiratory diseases, and HIV. Nearly eight years ago, researchers Craig Mello, of the University of Massachusetts Medical School, and Andrew Fire, of Stanford University's School of Medicine, discovered that RNA plays a crucial role in regulating gene expression: the ability to turn genes off. They won a Nobel Prize for their work in 2006 identifying the mechanism for a process called RNA interference, or RNAi. They found that RNA blocks a gene from delivering its message to proteins, essentially shutting down that gene. Since then, scientists around the world have run with the idea, finding ways for RNAi to turn off a variety of genes--in particular, those that cause disease. It's RNA's role in switching off genes that dominates the talks at this week's conference, titled "RNAi for Target Validation and as a Therapeutic."

read the rest of the story here

Human Model Completed

Researchers at the University of California, San Diego, have constructed the first complete computer model of human metabolism. Available free on the Web, the model is a major step forward in the fledging field of systems biology, and it will help researchers uncover new drug pathways and understand the molecular basis of cancer and other diseases.

Metabolism is the sum of all chemical reactions involved in breaking down the nutrients in food into energy and using them as the raw materials for making everything the body needs, from hormones like insulin to the lipids that make up cell membranes. The computer model of metabolism, constructed by researchers in the lab of Bernhard Palsson, professor of bioengineering, connects all such known chemical reactions in the body to every human gene.

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Sea Urchin Genome Is Sequenced

When scientists sequenced the sea urchin genome, they found surprising similarities to that of human beings AND are putting it to good use...

Who would have guessed that the lowly sea urchin, that brain-less, limb-less porcupine of the sea, would be the star of a multi-million dollar, worldwide effort to map out every letter of its genetic code? Or that the information gathered in that effort may eventually lead to new treatments for cancer, infertility, blindness, and diseases like muscular dystrophy and Huntington's Disease?

James Coffman, Ph.D., of the Mount Desert Island Biological Laboratory in Bar Harbor was one of the scientists who helped decode the 814 million pairs of nucleotide bases in the sea urchin's chromosomes. The Human Genome Sequencing Center at Baylor College of Medicine in Texas led the project and announced the completion of the three-year project today. Having the complete genome, Coffman says, "makes doing research on urchins so much easier."

Why would anyone want to do biomedical research on sea urchins? According to Coffman, sea urchins are remarkably similar to humans in many ways, sharing most of the same gene families, and yet differ in a few critical areas besides the obvious physical ones. For one thing, sea urchins have a "extraordinarily complex innate immune system" which is not based on antibodies, like that of jawed vertebrates, but is effective enough to give sea urchins a surprisingly long life span of up to a hundred years or more.

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Regards

Genetic map offers new tool for malaria research

Did you know that the malaria Parasite's DNA has nearly 47,000 genetic variations worldwide; kills every 30 seconds??

An international research team has completed a map that charts the genetic variability of the human malaria parasite, Plasmodium falciparum. The work, published in the Dec. 10 advance online edition of Nature Genetics, has already unearthed novel genes that may underlie resistance to current drugs against the disease.

The study reveals striking variation within the pathogen's genome, including an initial catalog of nearly 47,000 specific genetic differences among parasites sampled worldwide. That's more than double the expected level of diversity in the parasite's DNA. These differences lay the foundation for dissecting the functions of important parasite genes and for tracing the global spread of malaria.

The scientists who created the map are from the Broad Institute of MIT and Harvard, the Harvard School of Public Health and Cheikh Anta Diop University in Senegal, where malaria is endemic.

"Malaria remains a significant threat to global public health, driven in part by the genetic changes in the parasite that causes the disease," said senior author Dyann Wirth, a professor at the Harvard School of Public Health and co-director of the Broad Institute's Infectious Disease Initiative. "This study gives us one of the first looks at genetic variation across the entire malaria parasite genome--a critical step toward a comprehensive genetic tool for the malaria research community."

Plasmodium falciparum--the deadliest of the four parasites that cause malaria in humans--kills one person every 30 seconds, mostly children living in Africa. Despite decades of research, the genetic changes that enable it to escape the body's natural defenses and to overcome malaria drugs remain largely unknown.

To gain a broad picture of genetic variability--worldwide and genome-wide--the scientists analyzed more than 50 different P. falciparum samples from diverse geographic locations. This includes the complete genome sequencing of two well-studied samples, as well as extensive DNA analyses of 16 additional isolates.

By comparing the DNA sequences to each other and to the P. falciparum genome sequenced in 2002, the researchers uncovered extensive differences, including 47,000 single-letter changes called single nucleotide polymorphisms (SNPs). Although there are probably many more SNPs to be found, this initial survey provides a launching point for future systematic efforts to identify parasite genes that are essential to malaria.

"The roles of most of the malaria parasite's genes are still not known," said Sarah Volkman, a research scientist at the Harvard School of Public Health. "An important application of this new tool will be in pinpointing the genes that are vital to the development and spread of malaria."

Volkman and Pardis Sabeti, a postdoctoral fellow at the Broad Institute, are first authors on the paper.

One of the map's strengths is its ability to reveal evolutionary differences among parasites. This information can shed light on the genes responsible for malaria drug resistance--a major obstacle to adequate control of the disease.

Using the map to compare parasites exposed to different anti-malarial drugs, the scientists identified a novel genome region that is strongly implicated in resistance to the drug pyrimethamine, and also confirmed a region of the genome known to be involved in chloroquine drug resistance.

"The same genetic principles used to study human evolution can provide important clues about malaria," said Sabeti. "This tool has already yielded insights into the genetic changes that correlate with different drug treatments, pointing us to genes that may contribute to drug resistance."

The map can also define the genetic landscapes of different parasite populations. Applying it to parasites from various continents, the scientists discovered greater DNA variability among P. falciparum samples from Africa relative to those from Asia and the Americas. This knowledge guides the selection of genetic markers to track the transmission of distinct parasites, particularly ones that are virulent or drug resistant. It also lays the groundwork for connecting parasite genes with traits that vary geographically and bolster malaria's foothold in many parts of the world.

"Genomic tools have largely been applied to First World diseases up to now. This project underscores the power and importance of applying them to the devastating diseases of the developing world," said Eric Lander, one of the study's authors and the director of the Broad Institute. "By joining forces among scientists in the U.S., Africa and elsewhere, it should be possible to rapidly reveal the genetic variation in malaria around the world.

"Knowing the enemy will be a crucial step in fighting it," said Lander, who is also a professor of biology at MIT and a member of the Whitehead Institute for Biomedical Research.

The work is one of three large-scale studies of the parasite's DNA that appear together in Nature Genetics. It was supported by the Bill and Melinda Gates Foundation, the Burroughs-Wellcome Fund, the Exxon Mobil Foundation, the National Institutes of Allergy and Infectious Disease Microbial Sequencing Center and the National Institutes of Health.

MIT improves protein sorting with a new microchip

A new MIT microchip system promises to speed up the separation and sorting of biomolecules such as proteins. The work is important because it could help scientists better detect certain molecules associated with diseases, potentially leading to earlier diagnoses or treatments.

The microchip system has an extremely tiny sieve structure built into it that can sort through continuous streams of biological fluids and separate proteins accurately by size. Conventional separation methods employ gels, which are slower and more labor-intensive to process. The new microchip system could sort proteins in minutes, as compared to the hours necessary for gel-based systems.

The MIT team's results appear in the Feb. 5 issue of Nature Nanotechnology.

The new technology is an advance from a one-dimensional sieve structure reported by the same MIT group last year. The key to this new advance, called an anisotropic nanofluidic sieving structure, is that the researchers have designed the anisotropic sieve in two orthogonal dimensions (at a right angle), which enables rapid continuous-flow separation of the biological sample. This allows continuous isolation and harvesting of subsets of biomolecules that researchers want to study. And that increases the probability of detecting even the smallest number of molecules in the sample.

"With this technology we can isolate interesting proteins faster and more efficiently. And because it can process such small biologically relevant entities, it has the potential to be used as a generic molecular sieving structure for a more complex, integrated biomolecule preparation and analysis system," said Jongyoon Han, the Karl Van Tassel Associate Professor of Electrical Engineering and associate professor of biological engineering at MIT and head of the MIT team.

Han's coauthors of the Nature Nanotechnology paper are co-lead authors Jianping Fu, a Ph.D. candidate in the Department of Mechanical Engineering, and Reto B. Schoch, a postdoctoral associate in the Research Laboratory of Electronics (RLE). Additional authors are Anna Stevens, a postdoctoral associate in the Harvard-MIT Division of Health Sciences and Technology, and Professor Steven Tannenbaum of MIT's Biological Engineering Division.

Han noted that until the late 1990s, most advances in biological laboratory equipment were aimed at the Human Genome Project and discoveries related to DNA, which are larger molecules compared to proteins. However, because of the vital role proteins play in almost all biological processes, researchers began to focus their attention on proteins. But one obstacle has been the lack of good laboratory tools with which to prepare biological samples to analyze proteins, said Han, who also has affiliations in MIT's RLE, Computational and Systems Biology Initiative, Center for Materials Science and Engineering and Microsystems Technology Laboratories.

"I shifted my attention from DNA into the area of protein separation around 2002 with the shift to proteomics (the study of proteins)," Han said. "But the field was using decades-old gel electrophoresis technology. There is a big gap in the need for technology in this area."

Han and Fu therefore devised the anisotropic sieve that is embedded into a silicon chip. A biological sample containing different proteins is placed in a sample reservoir above the chip. The sample is then run through the sieve of the chip continuously. The chip is designed with a network of microfluidic channels surrounding the sieve, and the anisotropy (directional property) in the sieve causes proteins of different sizes to follow distinct migration trajectories, leading to efficient continuous-flow separation. The current sieve has an array of nanofluidic filters of about 55 nanometers, or billionths of a meter, wide.

"The proteins to be sorted are forced to take two orthogonal paths. Each path is engineered with different sieving characters. When proteins of different sizes are injected into the sieve under applied electric fields, they will separate into different streams based on size," Han explained. At the bottom of the chip the separated proteins are collected in individual chambers. Scientists then can test the proteins.

While other scientists have used similar continuous flow techniques to separate large molecules like long DNA, the MIT team succeeded with the tinier proteins. "This is the first time physiologically relevant molecules like proteins have been separated in such a manner," said Han. "We can separate the molecules in about a minute with the current device versus hours for gels."

Another advantage of the microchip is that it can have so many different pore sizes, and unlike gels, it is possible to design an exact pore size to increase the separation accuracy. That in turn can help researchers look for so-called biomarkers, or proteins that can reveal that disease is present, and thus help researchers develop diagnostics and treatments for the disease. "Sample preparation is critical in detecting more biomarker signals," said Han.

Funding came from the National Science Foundation, the National Institutes of Health and the Singapore-MIT Alliance.