11.15.2007

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hydroxyl

hydroxyl
hU-drokcsil  

The radical, –OH.

Hydroxyl

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This artical is about the hydroxyl functional group. For the Hydroxyl radical see Hydroxyl radical.

Hydroxyl in chemistry stands for a molecule consisting of an oxygen atom and a hydrogen atom connected by a covalent bond. The neutral form is a hydroxyl radical and the hydroxyl anion is called a hydroxide. When the oxygen atom is linked to a larger molecule the hydroxyl group is a functional group (HO– or –OH) .

[edit] Hydroxyl group

The term hydroxyl group is used to describe the functional group –OH when it is a substituent in an organic compound. Organic molecules containing a hydroxyl group are known as alcohols (the simplest of which have the formula CnH2n+1OH).

[edit] Hydroxyl radical

Main article: Hydroxyl radical

The hydroxyl radical, ·OH, is the neutral form of the hydroxide ion. Hydroxyl radicals are highly reactive and consequently short lived; however, they form an important part of radical chemistry.

 This organic chemistry article is a stub. You can help Wikipedia by expanding it.



hydroxyl group

From: The Columbia Encyclopedia, Sixth Edition  |  Date: 2007

hydroxyl group , in chemistry, functional group that consists of an oxygen atom joined by a single bond to a hydrogen atom. An alcohol is formed when a hydroxyl group is joined by a single bond to an alkyl group or aryl group . A metal hydroxide is formed when a hydroxyl group is joined to a metal (e.g., sodium hydroxide).

Author not available, HYDROXYL GROUP., The Columbia Encyclopedia, Sixth Edition 2007




Hydroxyl radical

From Wikipedia, the free encyclopedia

Jump to: navigation, search
This artical is about the Hydroxyl radical molecule. For the hydroxyl functional group see Hydroxyl

Hydroxyl in chemistry stands for a molecule consisting of an oxygen atom and a hydrogen atom connected by a covalent bond. The neutral form is a hydroxyl radical and the hydroxyl anion is called a hydroxide. When the oxygen atom is linked to a larger molecule the hydroxyl group is a functional group (HO– or –OH) .

Contents

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[edit] Hydroxyl group

Main article: Hydroxyl

The term hydroxyl group is used to describe the functional group –OH when it is a substituent in an organic compound. Organic molecules containing a hydroxyl group are known as alcohols (the simplest of which have the formula CnH2n+1OH).

[edit] Hydroxyl radical

Molecular orbital of the hydroxyl radical with unpaired electron
Molecular orbital of the hydroxyl radical with unpaired electron
Skeletal formulae of 1-hydroxy-2(1H)-pyridinethione and its tautomer
Skeletal formulae of 1-hydroxy-2(1H)-pyridinethione and its tautomer

The hydroxyl radical, ·OH, is the neutral form of the hydroxide ion. Hydroxyl radicals are highly reactive and consequently short lived; however, they form an important part of radical chemistry. Most notably hydroxyl radicals are produced from the decomposition of hydro-peroxides (ROOH) or, in atmospheric chemistry, by the reaction of excited atomic oxygen with water. It is also an important radical formed in radiation chemistry, since it leads to the formation of hydrogen peroxide and oxygen, which can enhance corrosion and SCC in coolant systems subjected to radioactive environments.

In organic synthesis hydroxyl radicals are most commonly generated by photolysis of 1-Hydroxy-2(1H)-pyridinethione.

[edit] Atmospheric importance

The Hydroxyl radical is often referred to as the "detergent" of the troposphere because it reacts with many pollutants, often acting as the first step to their removal. The first reaction with many volatile organic compounds (VOCs) is the removal of a hydrogen atom forming water and an alkyl radical (R·).

OH + RH → H2O + R·

The alkyl radical will typically react rapidly with oxygen forming a peroxy radical.

R· + O2 → RO2

The fate of this radical in the troposphere is dependent on factors such as the amount of sunlight (light from the sun), pollution in the atmosphere and the nature of the alkyl radical that formed it.

[edit] Biological significance

The hydroxyl radical has a very short in vivo half-life of approx. 10 -9 s and a high reactivity. This makes it a very dangerous compound to the organism. Unlike superoxide, which can be detoxified by superoxide dismutase, the hydroxyl radical cannot be eliminated by an enzymatic reaction, as this would require its diffusion to the enzyme's active site. As diffusion is slower than the half-life of the molecule, it will react with any oxidizable compound in its vicinity. It can damage virtually all types of macromolecules: carbohydrates, nucleic acids (mutations), lipids ( lipid peroxidation) and amino acids (e.g. conversion of Phe to m-Tyrosine and o- Tyrosine). The only means to protect important cellular structures is the use of antioxidants such as glutathione and of effective repair systems.

[edit] See also

11.14.2007

Lung-on-a-Chip Replicates the Tiny Explosions Inside Diseased Lungs

Lung-on-a-Chip Replicates the Tiny Explosions Inside Diseased Lungs: "

Lung-on-a-Chip Replicates the Tiny Explosions Inside Diseased Lungs

By Alexis Madrigal Email 11.12.07 | 5:30 PM
The channels on the surface of the University of Michigan's microfluidics device allow scientists to carefully regulate the flow of liquids to the cells that are cultured on it.
Image: Courtesy of Shuichi Takayama

Scientists have modeled the lungs' tiniest airways on a microchip device a little larger than a quarter, providing new insight into lung diseases like pneumonia and cystic fibrosis.

By scientifically reproducing the real crackling sound diseased lungs make when clogged with fluid, the lung-on-a-chip showed that the crackles aren't just a symptom of trouble, they're also a cause.

"The crackles are the sound of liquid plugs rupturing," said Shuichi Takayama, associate professor of biomedical engineering at the University of Michigan. "When the plugs rupture, they damage and even kill the surrounding cells."

It's one of a number of new tissue-engineering methods that more realistically model conditions inside the body. In another example, scientists found that cancer cells act more like cancer in the body growing on a 3-D scaffold than they do smeared on a flat petri dish.

More-realistic cell action improves pharmaceutical research, making drug discovery faster and more likely to make it through human trials. BCC Research predicts the so-called lab-on-a-chip market will grow from $566 million in 2006 to $1.25 billion in 2013.

The lung-on-a-chip is made by culturing actual human lung-tissue cells on a plastic chip laced with microscopic channels. The microfluidics device allows scientists to act like micro-plumbers, selectively exposing cells to various liquids and air.

The research appears in the Nov. 12 edition of the Proceedings of the National Academy of Sciences.

The chip mimics the fluid dynamics in the body's respiratory system. Takayama's tiny plumbing unit models the alveolar ducts, the smallest of the bronchial tubes, which carry air from the environment to the alveolar sacs that exchange carbon dioxide for oxygen.

In the video, an hourglass-shaped "liquid plug" forms on the lung-on-a-chip device. As it's pushed to the center of the air channel, it ruptures.

Video: Courtesy of Shuichi Takayama

To make the cells recognize they should behave like airway cells, the scientists provided liquid nutrients (simulating pulmonary fluid) on one end of the cell and exposed the other to air, Takayama said.

The Michigan team modeled an unhealthy lung by using liquid that was missing lung surfactant, which normally reduces surface tension in the bronchial tubes. Without the substance, the fluid sticks in the airways, causing liquid plugs to form. They prevent air from moving along the airway: In other words, the plugs prevent the lung-on-a-chip from breathing.

"Basically, the microfluidic airway tries to clear itself. In so doing, it causes the liquid plug to rupture," he said.

That rupture acts as a tiny explosion in the alveolar duct. Small numbers of pops, which might happen in healthy lungs, didn't damage the cells much. But in conditions that mimicked seriously diseased lungs (100 events in 10 minutes), the mini-explosions damaged the large majority of cells. Takayama noted the ruptures could be a major contributor to lung impairment.

The miniaturization through microfluidic devices will allow us to better understand the microscopic infrastructure that allows complex organisms to function, said Abraham Stroock, an assistant professor in Cornell's School of Chemical and Biomolecular Engineering.

"The lung, as a gas exchanger, is luckily serving our entire body," Stroock said. "We have one pump and then a network of vascular structures that pervade our entire body. Microfluidics help us understand microphysiological details, like the structure inside the lung."

The University of Michigan researchers plan to use the lung-on-a-chip to examine many lung conditions.

"Now that we have a lung-on-a-chip, what would happen if we make the chip smoke?" asked Takayama. Or the chip could be deliberately infected with bacteria, he added. "We can study how we can make lungs better with pharmaceuticals."

"

Lab on a chip : Insight : Nature

Lab on a chip : Insight : Nature: "

Supplements

Insight: Lab on a chip

Vol. 442, No. 7101 pp367-418

Lab on a chip

The ability to perform laboratory operations on small scales using miniaturized (lab-on-a-chip) devices has many benefits. Designing and fabricating such systems is extremely challenging, but physicists and engineers are beginning to construct highly integrated and compact labs on chips with exciting functionality as outlined in this Insight. The collection also highlights recent advances in the application of microfluidic-chip-based technologies such as chemical synthesis, the study of complex cellular processes and medical diagnostics.

Top

Editorial

Lab on a chip

Rosamund Daw and Joshua Finkelstein

doi:10.1038/442367a


Top

Overview

The origins and the future of microfluidics

George M. Whitesides

doi:10.1038/nature05058


Top

Reviews

Scaling and the design of miniaturized chemical-analysis systems

Dirk Janasek, Joachim Franzke and Andreas Manz

doi:10.1038/nature05059


Developing optofluidic technology through the fusion of microfluidics and optics

Demetri Psaltis, Stephen R. Quake and Changhuei Yang

doi:10.1038/nature05060


Future lab-on-a-chip technologies for interrogating individual molecules

Harold Craighead

doi:10.1038/nature05061


Control and detection of chemical reactions in microfluidic systems

Andrew J. deMello

doi:10.1038/nature05062


Cells on chips

Jamil El-Ali, Peter K. Sorger and Klavs F. Jensen

doi:10.1038/nature05063


Microfluidic diagnostic technologies for global public health

Paul Yager, Thayne Edwards, Elain Fu, Kristen Helton, Kjell Nelson, Milton R. Tam and Bernhard H. Weigl

doi:10.1038/nature05064

"

Microfluidic diagnostic technologies for global public health : Abstract : Nature

Microfluidic diagnostic technologies for global public health : Abstract : Nature: "

Insight

Nature 442, 412-418 (27 July 2006) | doi:10.1038/nature05064; Published online 26 July 2006

Microfluidic diagnostic technologies for global public health

Paul Yager1, Thayne Edwards1, Elain Fu1, Kristen Helton1, Kjell Nelson1, Milton R. Tam2 and Bernhard H. Weigl3

The developing world does not have access to many of the best medical diagnostic technologies; they were designed for air-conditioned laboratories, refrigerated storage of chemicals, a constant supply of calibrators and reagents, stable electrical power, highly trained personnel and rapid transportation of samples. Microfluidic systems allow miniaturization and integration of complex functions, which could move sophisticated diagnostic tools out of the developed-world laboratory. These systems must be inexpensive, but also accurate, reliable, rugged and well suited to the medical and social contexts of the developing world.

"

Cells on chips : Abstract : Nature

Cells on chips : Abstract : Nature: "

Insight

Nature 442, 403-411 (27 July 2006) | doi:10.1038/nature05063; Published online 26 July 2006

Cells on chips

Jamil El-Ali1, Peter K. Sorger2 and Klavs F. Jensen1

Microsystems create new opportunities for the spatial and temporal control of cell growth and stimuli by combining surfaces that mimic complex biochemistries and geometries of the extracellular matrix with microfluidic channels that regulate transport of fluids and soluble factors. Further integration with bioanalytic microsystems results in multifunctional platforms for basic biological insights into cells and tissues, as well as for cell-based sensors with biochemical, biomedical and environmental functions. Highly integrated microdevices show great promise for basic biomedical and pharmaceutical research, and robust and portable point-of-care devices could be used in clinical settings, in both the developed and the developing world.

"

Control and detection of chemical reactions in microfluidic systems : Abstract : Nature

Control and detection of chemical reactions in microfluidic systems : Abstract : Nature: "

Insight

Nature 442, 394-402 (27 July 2006) | doi:10.1038/nature05062; Published online 26 July 2006

Control and detection of chemical reactions in microfluidic systems

Andrew J. deMello1

Recent years have seen considerable progress in the development of microfabricated systems for use in the chemical and biological sciences. Much development has been driven by a need to perform rapid measurements on small sample volumes. However, at a more primary level, interest in miniaturized analytical systems has been stimulated by the fact that physical processes can be more easily controlled and harnessed when instrumental dimensions are reduced to the micrometre scale. Such systems define new operational paradigms and provide predictions about how molecular synthesis might be revolutionized in the fields of high-throughput synthesis and chemical production.

"

Future lab-on-a-chip technologies for interrogating individual molecules : Abstract : Nature

Future lab-on-a-chip technologies for interrogating individual molecules : Abstract : Nature: "

Insight

Nature 442, 387-393 (27 July 2006) | doi:10.1038/nature05061; Published online 26 July 2006

Future lab-on-a-chip technologies for interrogating individual molecules

Harold Craighead1

Advances in technology have allowed chemical sampling with high spatial resolution and the manipulation and measurement of individual molecules. Adaptation of these approaches to lab-on-a-chip formats is providing a new class of research tools for the investigation of biochemistry and life processes.

"

Developing optofluidic technology through the fusion of microfluidics and optics : Abstract : Nature

Developing optofluidic technology through the fusion of microfluidics and optics : Abstract : Nature: "

Insight

Nature 442, 381-386 (27 July 2006) | doi:10.1038/nature05060; Published online 26 July 2006

Developing optofluidic technology through the fusion of microfluidics and optics

Demetri Psaltis1, Stephen R. Quake2 and Changhuei Yang1

We describe devices in which optics and fluidics are used synergistically to synthesize novel functionalities. Fluidic replacement or modification leads to reconfigurable optical systems, whereas the implementation of optics through the microfluidic toolkit gives highly compact and integrated devices. We categorize optofluidics according to three broad categories of interactions: fluid–solid interfaces, purely fluidic interfaces and colloidal suspensions. We describe examples of optofluidic devices in each category.

"

Scaling and the design of miniaturized chemical-analysis systems : Abstract : Nature

Scaling and the design of miniaturized chemical-analysis systems : Abstract : Nature: "

Insight

Nature 442, 374-380 (27 July 2006) | doi:10.1038/nature05059; Published online 26 July 2006

Scaling and the design of miniaturized chemical-analysis systems

Dirk Janasek1, Joachim Franzke1 and Andreas Manz1

Micrometre-scale analytical devices are more attractive than their macroscale counterparts for various reasons. For example, they use smaller volumes of reagents and are therefore cheaper, quicker and less hazardous to use, and more environmentally appealing. Scaling laws compare the relative performance of a system as the dimensions of the system change, and can predict the operational success of miniaturized chemical separation, reaction and detection devices before they are fabricated. Some devices designed using basic principles of scaling are now commercially available, and opportunities for miniaturizing new and challenging analytical systems continue to arise.

"

The origins and the future of microfluidics : Abstract : Nature

The origins and the future of microfluidics : Abstract : Nature: "

Insight

Nature 442, 368-373 (27 July 2006) | doi:10.1038/nature05058; Published online 26 July 2006

The origins and the future of microfluidics

George M. Whitesides1

The manipulation of fluids in channels with dimensions of tens of micrometres — microfluidics — has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology. But the field is still at an early stage of development. Even as the basic science and technological demonstrations develop, other problems must be addressed: choosing and focusing on initial applications, and developing strategies to complete the cycle of development, including commercialization. The solutions to these problems will require imagination and ingenuity.

"

Lab on a chip : Article : Nature

Lab on a chip : Article : Nature: "

Insight

Nature 442, 367 (27 July 2006) | doi:10.1038/442367a; Published online 26 July 2006

Introduction Lab on a chip

Rosamund Daw1 & Joshua Finkelstein2

The ability to perform laboratory operations on a small scale using miniaturized (lab-on-a-chip) devices is very appealing. Small volumes reduce the time taken to synthesize and analyse a product; the unique behaviour of liquids at the microscale allows greater control of molecular concentrations and interactions; and reagent costs and the amount of chemical waste can be much reduced.

"

NASA - Lab on a Chip Works!

NASA - Lab on a Chip Works!: "

No Foolin' -- 'Lab on a Chip' Works!

04.06.2007

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April 6, 2007: "What a huge relief," says Norman Wainwright of the Charles River Laboratories in Charleston, SC. "The whole technical team was delighted that it worked so well."

see captionHe's talking about a miniature biological laboratory just tested for the first time onboard the International Space Station. Called LOCAD-PTS (short for Lab-On-a-Chip Application Development–Portable Test System), the mini-lab detects the presence of bacteria or fungi on the surfaces of a spacecraft far more rapidly than standard methods of culturing.

Right: LOCAD-PTS, a handheld biological laboratory for space travel. [More]

"The ability to monitor microorganisms would be especially important on long space voyages, not only to check the health of astronauts but also to monitor electronics and structural materials, which can be corroded or otherwise damaged by certain fungi and bacteria," says Wainwright, the experiment's principal investigator. LOCAD-PTS is designed so that "astronauts can do the analysis onboard with no need to return samples to laboratories on Earth."

The device was launched last December 9th on board the space shuttle Discovery, and then stowed aboard ISS until its scheduled experiment time—which happened to be Saturday night, March 31, Marshall Space Flight Center time. (Remember that time!)

Astronaut Sunita "Suni" Williams opened the instrument kit bag, assembled LOCAD-PTS, and then took six readings. "The first two readings were controls to show that the instrument was operating correctly," explains Jake Maule, LOCAD-PTS project scientist at the Carnegie Institution of Washington. "First she swabbed her palm, which she had first pressed to handrails and other often-handled surfaces that should have had lots of bacteria—and indeed, we got a strong positive reading," he continues. "Then she sampled some ultraclean water in the instrument that is used to moisten samples, to check that the water was truly clean—and indeed, we got a great negative reading."

see caption
Above: The International Space Station. [Larger image]

Next, Williams chose a wall panel in ISS Node 1 to test using both LOCAD-PTS and, for comparison, a standard culturing method.

For the standard method, she pressed a layer of solid gel growth medium (rather like agar) to the panel for a few seconds, replaced it securely in its packaging, and then set it aside to incubate for a few days.

Then she took a dry swab, rather like a high-tech Q-tip, from LOCAD-PTS and rubbed it on the panel next to the same area. Flushing ultraclean water through the swab converted the sample to liquid form, and a few drops were dispensed into the hand-held LOCAD-PTS instrument.

"The cleaner the sample, the longer the analysis takes," Wainwright says. "Because this site was pretty clean, it took about 12 minutes, but dirty samples can take as little as a couple of minutes."

It was during the wait that Williams must have noted the time. Although it was 10:20 PM Central Daylight Time at Marshall in Huntsville, Alabama, where all the LOCAD-PTS scientists were anxiously watching television monitors, it was actually past midnight on April 1, Greenwich Mean Time, the time zone used by ISS.

see caption"Suni said, 'Ah, this last set of readings for LOCAD-PTS looks a bit strange,'" Maule recalls. "After a pause of about five seconds, she exclaimed, 'Happy April Fools' Day! The numbers are just fine!'"

"She definitely got me!" he laughs.

Right: Researchers in the control room at MSFC celebrate when they hear that LOCAD-PTS has worked. From left to right: Dr. Lisa Monaco, Tony Lyons, Dr. Jake Maule, Dan Gunter. [Larger image]

Over the next few months, LOCAD-PTS and standard culture methods will be used to investigate different parts of ISS. "A second-generation of LOCAD-PTS cartridges for the specific detection of fungi are scheduled to launch to ISS on Space Shuttle STS-123," says Anthony T. Lyons, LOCAD-PTS project manager at Marshall, the NASA center that has overseen the project since its inception and supervised getting the equipment spaceflight-ready. "With each generation of cartridges, we are getting more and more specific in what we detect. Our ultimate aim is to provide the crew with a selection of cartridges for the detection of a wide variety of target compounds, biological and chemical both inside and outside the spacecraft—something that would be especially important for long-duration missions to the Moon or to Mars."

"Right now, we're very happy with the first tests."

"

Lab-On-A-Chip Devices Set To Advance With Miniature Microwave Technology

Lab-On-A-Chip Devices Set To Advance With Miniature Microwave Technology: "

Lab-On-A-Chip Devices Set To Advance With Miniature Microwave Technology

Main Category: Medical Devices News
Article Date: 09 Nov 2007 - 2:00 PST

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Researchers at the National Institute of Standards of Technology (NIST) and George Mason University have demonstrated what is probably the world's smallest microwave oven, a tiny mechanism that can heat a pinhead-sized drop of liquid inside a container slightly shorter than an ant and half as wide as a single hair. The micro microwave is intended for lab-on-a-chip devices that perform rapid, complex chemical analyses on tiny samples.

In a paper in the November 2007 Journal of Micromechanics and Microengineering*, the research team led by NIST engineer Michael Gaitan describes for the first time how a tiny dielectric microwave heater can be successfully integrated with a microfluidic channel to control selectively and precisely the temperature of fluid volumes ranging from a few microliters (millionth of a liter) to sub-nanoliters (less than a billionth of a liter). Sample heating is an essential step in a wide range of analytic techniques that could be built into microfluidic devices, including the high-efficiency polymerase chain reaction (PCR) process that rapidly amplifies tiny samples of DNA for forensic work, and and methods to break cells open to release their contents for study.

The team embedded a thin-film microwave transmission line between a glass substrate and a polymer block to create its micro microwave oven. A trapezoidal-shaped cut in the polymer block only 7 micrometers across at its narrowest -- the diameter of a red blood cell -- and nearly 4 millimeters long (approximately the length of an ant) serves as the chamber for the fluid to be heated.

Based on classical theory of how microwave energy is absorbed by fluids, the research team developed a model to explain how their minature oven would work. They predicted that electromagnetic fields localized in the gap would directly heat the fluid in a selected portion of the micro channel while leaving the surrounding area unaffected. Measurements of the microwaves produced by the system and their effect on the fluid temperature in the micro channel validated the model by showing that the increase in temperature of the fluid was predominantly due to the absorbed microwave power.

Once the new technology is more refined, the researchers hope to use it to design a microfluidic microwave heater that can cycle temperatures rapidly and efficiently for a host of applications.

----------------------------
Article adapted by Medical News Today from original press release.
----------------------------

The work is supported by the Office of Science and Technology at the Department of Justice's National Institute of Justice.

* J.J. Shah, S.G. Sundaresan, J. Geist, D.R. Reyes, J.C. Booth, M.V. Rao and M. Gaitan. Microwave dielectric heating of fluids in an integrated microfluidic device. Journal of Micromechanics and Microengineering, 17: 2224-2230 (2007)

Source: Michael E. Newman
National Institute of Standards and Technology (NIST) "

Research News: Lab-on-a-Chip Device from Berkeley Lab to Speed Proteomics Research

Research News: Lab-on-a-Chip Device from Berkeley Lab to Speed Proteomics Research: "

Lab-on-a-Chip Device from Berkeley Lab to Speed Proteomics Research


BERKELEY, CA —In recent years, the science of biology has been dominated by genomics – the study of genes and their functions. The genomics era is now making way for the era of proteomics – the study of the proteins that genes encode.



Science image spacer image
This zoom-in Scanning Electron Microscope image shows a five-nozzle M3 emitter, where each nozzle measures 10x12 microns.


Future proteomics research should see a substantial acceleration with the development of a new device that provides the first monolithic interface between mass spectrometry and silicon/silica-based microfluidic “lab-on-a-chip” technologies. This new device, called a multinozzle nanoelectrospray emitter array, was developed by scientists with the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab).

“Proteomics has become an indispensable tool in biological research, be it diagnostics, therapeutics, bioenergy or stem cell research, and mass spectrometry is proteomics’ enabling technology,” said Daojing Wang, a scientist with Berkeley Lab’s Life Sciences Division who leads the proteomics research group and was the principal investigator behind the development of the multinozzle nanoelectrospray emitter.

“Lab-on-a-chip technology has enormous potential for proteomics research,” Wang said, “but for this potential to be fully realized, a major advance in interfacing microfluidics with mass spectrometry is needed. Our device provides that interface.”

Wang and Peidong Yang, a leading nanoscience authority with Berkeley Lab’s Molecular Foundry and Materials Sciences Division, and also a chemistry professor with the University of California’s Berkeley campus, co-authored a paper on this work which is being published by the American Chemical Society (ACS). The paper, which is now available in the on-line version. is entitled: “Microfabricated Monolithic Multinozzle Emitters for Nanoelectrospray Mass Spectrometry.”

Other authors of the ACS paper were Woong Kim, a postdoctoral fellow in the Molecular Foundry, and Mingquan Guo, a postdoctoral fellow in the Life Sciences Division.

When the Human Genome Project was completed in 2003, giving scientists a complete catalogue of human DNA, the next big effort focused on genomics, identifying DNA sequences that code for proteins, aka, genes. With the identification of each and every new gene, the emphasis shifts to determining the biochemical function of its associated proteins.

All biological cells are constructed from aggregations of proteins that interact with other protein aggregations like an elaborate, finely choreographed network of interdependent machines. This biomolecular machinery also controls nearly every chemical process inside a cell, and forms much of the connectivity that enable cells to come together into tissues and organs. One of the first steps in proteomics research is to determine the identity and modifications of individual proteins that make up a cell or tissue sample. The principal means of doing this is through mass spectrometry.

Mass spectrometers use a combination of ionization and magnets to separate a protein’s constituent peptides. Detection and analysis of this mass spectrum can then be used to identify the protein and quantify its presence in a sample. The most popular technique today for ionizing a protein’s constituents for mass spectrometry is to liquefy the protein and send it through electrically charged capillaries – a technique known as electrospray ionization. One of the best candidates for high throughput integration of the detection and analysis processes is to interface the mass spectrometers with lab-on-a-chip technology, where biological fluids are introduced onto a microprocessor chip. However, microfluidic analysis of proteins has been a separate process from mass spectrometry - until now.

“Ours is the first report of a silicon/silica microfluidic channel that is integrated monolithically with a multinozzle nanoelectrospray emitter,” said Wang. “This paves the way for the large scale integration of mass spectrometry and lab-on-a-chip analysis in proteomics research.”



spacer image Science image

(From left) Peidong Yang, Mingquan Guo, Woong Kim and Daojing Wang have developed multinozzle nanoelectrospray emitter arrays that enable mass spectrometry to be fully integrated with microfluidic technology for proteomics research.


Each emitter consists of a parallel array of silica nozzles protruding out from a hollow silicon sliver with a conduit size of 100 x 10 microns. Multiple nozzles (100 nozzles per millimeter was a typical density) were used rather than single nozzles in order to reduce the pressure and clogging problems that arise as the microfluidic channels on a chip downsize to a nanometer scale. The emitters and their nozzles were produced from a silicon wafer, with the dimension and number of nozzles systematically and precisely controlled during the fabrication process. Fabrication required the use of only a single mask and involved photolithographic patterning and various etching processes.

Said Peidong Yang, “Once integrated with a mass spectrometer, our microfabricated monolithic multinozzle emitters achieved a sensitivity and stability in peptide and protein detection comparable to commercial silica-based capillary nanoelectrospray tips. This indicates that our emitters could serve as a critical component in a fully integrated silicon/silica-based micro total analysis system for proteomics.”

Added Daojing Wang, “This is also the first report of a multinozzle emitter that can be fabricated through standard microfabrication processes. In addition to having lower back pressure and higher sensitivity, multinozzle emitters also provide a means to systematically study the electrospray ionization processes because the size of each nozzle and density of nozzles on the emitters can be adjusted.”

According to Wang and Yang, the fabrication and application of the microfabricated monolithic multinozzle emitters, called “M3 emitters” for short, could be commercialized immediately and should be highly competitive with current silica capillary emitters in terms of cost and mass production.

“We are now in the process of creating a chip that integrates sample processing and preparation as well as detection and analysis,” said Wang. “The ability to perform the full process on a single chip has enormous commercial potential.”

Berkeley lab has filed for a patent on this technology. The research was supported by a grant from the National Institutes of Health, with some of the work done at Berkeley Lab’s Molecular Foundry, which is supported by the Office of Science in the U.S. Department of Energy.

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit our Website at www.lbl.gov.

Additional information

"

Lab-on-a-chip - Wikipedia, the free encyclopedia

Lab-on-a-chip - Wikipedia, the free encyclopedia: "

Lab-on-a-chip

From Wikipedia, the free encyclopedia

Jump to: navigation, search

Lab-on-a-chip (LOC) is a term for devices that integrate (multiple) laboratory functions on a single chip of only millimeters to a few square centimeters in size and that are capable of handling extremely small fluid volumes down to less than pico liters. Lab-on-a-chip devices are a subset of MEMS devices and often indicated by "Micro Total Analysis Systems" (µTAS) as well. Microfluidics is a broader term that describes also mechanical flow control devices like pumps and valves or sensors like flowmeters and viscometers. However, strictly regarded "Lab-on-a-Chip" indicates generally the scaling of single or multiple lab processes down to chip-format, whereas "µTAS" is dedicated to the integration of the total sequence of lab processes to perform chemical analysis. The term "Lab-on-a-Chip" was introduced later on when it turned out that µTAS technologies were more widely applicable than only for analysis purposes.

Contents

[hide]

[edit] History

After the discovery of microtechnology (~1958) for realizing integrated semiconductor structures for microelectronic chips, these lithography-based technologies were soon applied in pressure sensor manufacturing (1966) as well. Due to further development of these usually CMOS-compatibility limited processes, a tool box became available to create micrometre or sub-micrometre sized mechanical structures in silicon wafers as well: the Micro Electro Mechanical Systems (MEMS) era (also indicated with Micro System Technology - MST) had started.

Next to pressure sensors, airbag sensors and other mechanically movable structures, fluid handling devices were developed. Examples are: channels (capillary connections), mixers, valves, pumps and dosing devices. The first LOC analysis system was a gas chromatograph, developed in 1975 by S.C. Terry - Stanford University. However, only at the end of the 1980’s, and beginning of the 1990’s, the LOC research started to seriously grow as a few research groups in Europe developed micropumps, flowsensors and the concepts for integrated fluid treatments for analysis systems. These µTAS concepts demonstrated that integration of pre-treatment steps, usually done at lab-scale, could extend the simple sensor functionality towards a complete laboratory analysis, including e.g. additional cleaning and separation steps.

A big boost in research and commercial interest came in the mid 1990’s, when µTAS technologies turned out to provide interesting tooling for genomics applications, like capillary electrophoresis and DNA microarrays. A big boost in research support also came from the military, especially from DARPA (Defense Advanced Research Projects Agency), for their interest in portable bio/chemical warfare agent detection systems. The added value was not only limited to integration of lab processes for analysis but also the characteristic possibilities of individual components and the application to other, non-analysis, lab processes. Hence the term "Lab-on-a-Chip" was introduced.

Although the application of LOCs is still novel and modest, a growing interest of companies and applied research groups is observed in different fields such as analysis (e.g. chemical analysis, environmental monitoring, medical diagnostics and cellomics) but also in synthetic chemistry (e.g. rapid screening and microreactors for pharmaceutics). Besides further application developments, research in LOC systems is expected to extend towards downscaling of fluid handling structures as well, by using nanotechnology. Sub-micrometre and nano-sized channels, DNA labyrinths, single cell detection an analysis and nano-sensors might become feasible that allow new ways of interaction with biological species and large molecules. One commercially very successful example for LOCs in life science is the development of automated patch clamp chips, that allowed for drastically increased throughput for drug screening in the pharmaceutical industry.

[edit] Chip materials and fabrication technologies

The basis for most LOC fabrication processes is photolithography. Initially most processes were in silicon, as these well-developed technologies were directly derived from semiconductor fabrication. Because of demands for e.g. specific optical characteristics, bio- or chemical compatibility, lower production costs and faster prototyping, new processes have been developed such as glass, ceramics and metal etching, deposition and bonding, PDMS processing (e.g., soft lithography), thick-film- and stereolithography as well as fast replication methods via electroplating, injection molding and embossing. Furthermore the LOC field more and more exceeds the borders between lithography-based microsystem technology, nano technology and precision engineering.

[edit] Advantages of LOCs

LOCs may provide advantages, very specifically for their applications. Typical advantages are:

  • low fluid volumes consumption, because of the low internal chip volumes, which is beneficial for e.g. environmental pollution (less waste), lower costs of expensive reagents and less sample fluid is used for diagnostics
  • higher analysis and control speed of the chip and better efficiency due to short mixing times (short diffusion distances), fast heating (short distances, high wall surface to fluid volume ratios, small heat capacities)
  • better process control because of a faster response of the system (e.g. thermal control for exothermic chemical reactions)
  • compactness of the systems, due to large integration of functionality and small volumes
  • massive parallelization due to compactness, which allows high-throughput analysis
  • lower fabrication costs, allowing cost-effective disposable chips, fabricated in mass production
  • safer platform for chemical, radioactive or biological studies because of large integration of functionality and low stored fluid volumes and energies

[edit] Disadvantages of LOCs

  • novel technology and therefore not fully developed yet
  • physical effects like capillary forces and chemical effects of channel surfaces become more dominant and make LOC systems behave differently and sometimes more complex than conventional lab equipment
  • detection principles may not always scale down in a positive way, leading to low signal to noise ratios

[edit] Examples of what you can do with the LOC

  • Real-time PCR ;detect bacteria, viruses and cancers.
  • Immunoassay ; detect bacteria, viruses and cancers based on antigen-antibody reactions.
  • Dielectrophoresis detecting cancer cells and bacteria.
  • Blood sample preparation ; can crack cells to extract DNA.
  • Cellular lab-on-a-chip for single-cell analysis.
  • Ion channel screening


[edit] External links

[edit] Laboratories

[edit] Journals

[edit] Conferences

[edit] Books

  • (2003) Edwin Oosterbroek & A. van den Berg (eds.): Lab-on-a-Chip: Miniaturized systems for (bio)chemical analysis and synthesis, Elsevier Science, second edition, 402 pages. ISBN 0444511008.
  • (2004) Geschke, Klank & Telleman, eds.: Microsystem Engineering of Lab-on-a-chip Devices, 1st ed, John Wiley & Sons. ISBN 3-527-30733-8.

[edit] References

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