Soft ray looks to save lives by developing rapid, low-cost system for detection of bacteria in blood platelets

Johnson, a University of Wyoming professor of physics since 1981, is venturing from the classroom to the boardroom with his biotechnology company SoftRay Inc., where he has created a lab instrument that can be used in hospitals and health clinics to detect bacteria in blood platelets or fungus in blood much earlier than current methodologies allow. And he is receiving assistance and expertise from the Wyoming Technology Business Center to make it happen.

"The WTBC has helped me develop a business plan. I've received feedback from venture capitalists and developed presentations to give to venture capitalists," says Johnson, who is currently in the pre-venture stage of his business idea. "They've helped me connect with a lot of people in the business community."

The WTBC is a statewide business development program (under the UW Office of Research and Economic Development) that is developing a technology business incubator and an outreach program focused on early-stage, high-growth companies. The 30,000-square-foot facility, which opened in 2006, offers laboratory, office and shared-conference room space for client companies as well as a state-of-the-art data center.

Johnson has created a technology he calls FountainFlow cytometry, which is used for measuring microorganisms in food, water and human blood. The platform technology can be used to detect environmental or drinking water contamination, fungus in the blood and bacteria in blood platelets -- and more quickly than current detection methods, Johnson says.

Platelets are the cells in human blood which cause blood to coagulate upon exposure to air. Platelets are used for transfusions for hospital patients who have undergone trauma or bled out; or for people who are immune-compromised, meaning their bodies cannot naturally produce platelets on their own.

Johnson says his technology -- which he began working on approximately six years ago because he wanted to make a significant societal impact -- can detect fungal infection in blood within a few hours compared to the current methodology, such as culturing, which takes 1-3 days to diagnose a form of fungus. That can be the difference between life and death for a patient who has gone into septic shock. A person can die from septic shock within 1-24 hours while current diagnosis typically takes 48-72 hours, Johnson says.

"A person's survival rate depends critically on quick diagnosis and treatment," Johnson says. "With our current FountainFlow platform technology, we will be able to make a diagnosis within 1-2 hours. And the physician will be able to use the appropriate drug regimen to save the person's life."

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In his technology, Johnson says a fluid, such as blood or water, is mixed with chemicals. It is then pumped through the hoses of the instrument. The fluid is illuminated, using light from an LED. A dye is added to the fluid, which allows Johnson to pinpoint the microorganisms he's specifically interested in detecting. When the microorganisms are illuminated with the ultra-bright LED light, the microorganisms glow. A camera, which is part of the instrument, captures video frames of that fluid flow. A computer can analyze those frames to count the number of glowing particles in the images. It then determines the number of particles per volume in the fluid flow. This process allows the physician to determine the level of infection.

"Camera technology and LED technology have both become cheaper and more powerful," Johnson says. "I've managed to ride both of those waves to develop an instrument that can conduct cell detection."

Johnson currently is conducting his research with Poudre Valley Hospital in Fort Collins and Bonfils Blood Center in Denver. Poudre Valley Hospital is a 241-bed regional medical center which serves northern Colorado, southern Wyoming and western Nebraska. Bonfils operates six community donor centers; serves nearly 200 health care facilities in Colorado and beyond; and collects nearly 154,000 units of blood annually, according to its website.

While Johnson conducts his research at his laboratory in UW's Physical Sciences Building and at Bonfils -- with the aid of National Institutes of Health (NIH) grants -- he stressed that the WTBC and its facilities have been invaluable to his efforts.

"There is a lot of commercialization with something as complicated as this device. It requires meeting with (people in the) business and scientific fields," Johnson says. "I've been able to meet with people very good at dye development, and those that have to work with blood and blood platelets. I'm constantly getting feedback. They (WTBC) really care about the success of their clients."

He adds, "The great thing about the WTBC is we have a group of people intimately familiar with high-tech business development. It's really great to have someone identify problems. Before, I felt isolated. They (WTBC) have a lot of experience."

Johnson said he has lived and learned with a previous Laramie-based business venture, First Magnitude Corp., he started. First Magnitude marketed electronic, high-sensitive cameras used for research. While that company proved profitable, Johnson admitted to some business mistakes.

"We were attracting the high end of the market, but we didn't have the patents" for the technology, Johnson recalls. "If you don't have the patents, you get taken over rapidly by the big boys."

When he started SoftRay, Johnson shuttered First Magnitude Corp. And he vowed to learn from that experience.

While UW owns the patent on Johnson's technology, Johnson has an exclusive license on the patent, which means he owns the rights to market the technology.

Johnson says he is still mulling whether he would want to manufacture the technology himself or provide a license to a large corporation with production and manufacturing facilities already in place.

"I would like to be a Laramie-based company for the foreseeable future. The bio-detection industry is growing and is in excess of $30 billion annually," Johnson says. "I'd like to be a major player in the bio-detection industry."

In addition to the health care industry, Johnson sees other potential market applications -- including detection of contamination in food and water products -- for his technology.

"We're interested in licensing technology," he says. "If someone would want to use it for bottled water, that would be huge. The sky's the limit."

Provided by University of Wyoming

Finding cancer cells in blood: Chip-based method for the rapid, sensitive isolation of rare cells in blood

The detection of circulating tumor cells is a difficult challenge because it requires the detection of quantities as low as one to ten cells per milliliter of blood—in the presence of large numbers of red blood cells and other cells. Conventional methods cannot manage this, but scientists led by Daniel T. Chiu have now developed a microfluidic system that allows for the analysis of 1 mL of blood within 20 minutes. The secret of their success is to virtually divide the sample into aliquots (portions) and to search these for the presence or absence of the desired cell types.

The blood is initially marked with fluorescent markers that specifically bind to the desired tumor cells. The sample is then passed through a system of microchannels, where it passes through a zone that is irradiated by a laser. The size of this zone determines the volume of the virtual aliquot; 2 nanoliters was found to work well. The laser causes the marker to fluoresce if marked cells are present. It can thus be determined whether or not an aliquot contains one (or more) of the desired cells. If the aliquot fluoresces, it is automatically pumped into a different channel than the fractions that do not fluoresce. The positive aliquots enter a filtration chamber. Red blood cells and the majority of blood cells pass through the filter; tumor cells are larger and are trapped. They can be counted on the filter, examined by microscope, or removed by micropipette for further examination. By using a second marker, certain subpopulations, such as tumor stem cells, can be identified.

Experiments with blood containing a known number of breast cancer cells yielded a recovery rate of 93 % and a false positive rate of zero. Real blood samples from patients were also examined and the results compared with those from a clinically established system. The new microfluidic system proved to be significantly more sensitive. This new procedure has potential for monitoring treatment, aftercare, and the early detection of cancer.

More information: Daniel T. Chiu, Sensitive and High-Throughput Isolation of Rare Cells from Peripheral Blood with Ensemble-Decision Aliquot Ranking, Angewandte Chemie International Edition, http://dx.doi.org/ … ie.201108695

Provided by Wiley (news : web)

Twist-and-glow molecules aid rapid gas detection

Now, Takashi Uemura of Kyoto University and colleagues at several other Japanese institutes, including the RIKEN SPring-8 Center, have created a gas sensor that works rapidly, emits a clear fluorescent signal, and detects different gases. Most importantly, the new sensor can distinguish between gases with similar chemical and physical properties.

Uemura and colleagues’ sensor contains so-called ‘flexible porous coordination polymers’ coupled with fluorescent reporter molecules that change structure, and therefore emit signals, according to different gases present in the air. 

“We thought that the incorporation of functional polymers into flexible porous coordination matrices would show unique dynamic properties,” says Uemura. He and his colleagues therefore inserted a fluorescent reporter molecule into the coordination polymer, whereupon the whole combined structure twisted out of shape.

In this normal and twisted state, the fluorescent light from the reporter is quite dim and green. Once gas molecules are introduced, the structure begins to return to its original shape, and the fluorescence returns, brightening as the gas pressure intensifies. For example, the fluorescence changes from green to blue when the molecule adsorbs carbon dioxide.

By this method, the sensor allows regular monitoring of both the type of gas and its concentration in the air. Crucially, the fluorescent response begins within seconds upon interaction with the gas and is complete within minutes, allowing emergency responders to make decisions quickly (Fig. 1).

In addition to these attributes, this is the first such detection system shown to work for gases with almost identical physical properties, the team notes. “Physical properties, such as size, shape, and boiling points, are very similar between carbon dioxide and acetylene, for example, so it is difficult to distinguish between them,” explains Uemura. “Our material has carboxylate sites in the pore, and these sites can bind to acetylene more strongly than carbon dioxide.

“This unique cooperative change of host and guest could allow us to design new advanced materials,” he adds. By investigating different flexible host structures and other ‘guest’ reporter molecules, the researchers believe they could create gas detection systems for a variety of different gases and other applications in the future.

More information: Nature Materials 10, 787–793 (2011) doi:10.1038/nmat3104

Provided by RIKEN (news : web)

Reverse engineering materials with a rapid, non-destructive laser-based technique can aid the fight against counterfeits

In business, protecting a company’s intellectual property can mean the difference between market success and bankruptcy. As the threat of competition from illegal copies of patented technology grows, high-tech firms are themselves turning to reverse engineering to spot potential patent infringements. Effendi Widjaja and Marc Garland from the A*STAR Institute of Chemical and Engineering Sciences have now developed a technique that promises to revolutionize reverse-engineering protocols—a rapid, non-destructive approach for mapping the composition of multilayered materials.

Multilayer films are used in the lamination of electronic components as well as sport equipment, providing multifunctional protection that single-layer films cannot, such as water and corrosion resistance, for example. Identifying the composition of these films, however, usually involves chopping the sample up and dissolving it in solvents, a destructive and labor-intensive process. Widjaja and Garland have developed a non-destructive reverse-engineering strategies based on vibrational spectroscopy and advanced signal processing.

Scientists have long known that when excited by light, molecules emit vibrational signals that provide detailed information on their chemical and structural environments. Raman spectroscopy is a laser-based version of such a techniques that can be used with very little sample preparation and provides high precision. The difficulty in applying such analyses to multilayer films has been the volume of data generated—particles in a multilayer films have a wide range of overlapping vibrational signals, resulting in a complex readout that is hard to assign to individual substances.

Widjaja and Garland overcame this challenge by developing an algorithm called band-target entropy minimization (BTEM), in which rigorous statistical equations are used to ascertain the simplest sets of ‘pure’ component patterns within a vibrational spectrum. The program is extraordinarily sensitive to trace components within a material: it has been show in previous studies that even substances contributing less than 1% to the total vibrational signal information can be recovered by BTEM.

The team tested their strategy by attempting to reverse engineer the multilayer structure of a commercial packaging envelope. After shining the Raman beam onto the sample, the BTEM algorithm detected seven underlying patterns in the spectra. These patterns correspond to two forms of paper fiber, three inorganic crystalline materials and two polymers. By distributing each pure signal across the sample’s dimensions, the team successfully reconstructed the spatial distributions of the components in each laminated layer.

The speed and precision of the Raman/BTEM analysis, Widjaja and Garland note, makes the technique a valuable weapon in the fight against patent infringement.

More information: Widjaja, E. & Garland, M. Reverse engineering of multi-layer films. Materials Today 14, 114–117 (2011).

Provided by Agency for Science, Technology and Research (A*STAR)

New sensor promises rapid detection of dangerous heavy metal levels in humans

 Work by University of Cincinnati researchers to create a sensor that provides fast feedback related to the presence and levels of heavy metals -- specifically manganese -- in humans is published in the August issue of the journal, Biomedical Microdevices.

Described in the article is the development of a low-cost, disposable lab-on-a-chip sensor that detects highly electronegative heavy metals more quickly than current technology generally available in health-care settings. It's envisioned that the new UC sensor technology will be used in point-of-care devices that provide needed feedback on heavy-metal levels within about ten minutes.

It's expected that the sensor will have potential for large-scale use in clinical, occupational and research settings, e.g., for nutrition testing in children.

The new sensor is environmentally friendly in that its working electrode is made of bismuth vs. the more typical mercury, and it's child friendly in that it requires only a droplet or two of blood for testing vs. the typical five-milliliter sample now required.

Explained one of the researchers, UC's Ian Papautsky, "The conventional methods for measuring manganese levels in blood currently requires about five milliliters of whole blood sent to a lab, with results back in 48 hours. For a clinician monitoring health effects by measuring these levels in a patient's blood -- where a small level of manganese is normal and necessary for metabolic functions -- you want an answer much more quickly about exposure levels, especially in a rural, high-risk area where access to a certified metals lab is limited. Our sensor will only require about two droplets of blood serum and will provide results in about ten minutes. It's portable and usable anywhere."

Papautsky, UC associate professor of electrical and computer engineering, is co-author of the Biomedical Devices-published research, "Lab-on-a-Chip Sensor for Detection of Highly Electronegative Heavy Metals by Anodic Stripping Voltammetry." Other co-authors are Erin Haynes, assistant professor of environmental engineering; William Heineman, distinguished research professor of chemistry; and just-graduated electrical and computer engineering doctoral student Preetha Jothimuthu, just-graduated chemistry doctoral student Robert Wilson, and biomedical engineering undergraduate research co-op student Josi Herren.

First Field Test of Sensor Expected in in Marietta, Ohio

One specific motivation for developing the sensor was an ongoing project by UC's Erin Haynes, who is studying air pollution and the health effects of manganese and lead in Marietta, Ohio. Manganese is emitted in that area because it is home to the only manganese refinery in the United States and Canada. Preliminary results from UC's Mid-Ohio Valley Air Pollution Study (M.A.P.S.) found elevated levels of manganese in Marietta residents when compared to those who live in other cities.

How the UC Sensor Works

The new UC sensor uses a technology called anodic stripping voltammetry that incorporates three electrodes: a working electrode, a reference electrode and an auxiliary electrode.

A critical challenge for such sensors is the detection of electronegative metals like manganese. Detection is difficult because hydrolysis, the splitting of a molecule into two parts by the addition of a water molecule, at the auxiliary electrode severely limits a sensor's ability to detect an electronegative metal.

To resolve this challenge, the UC team developed a thin-film bismuth working electrode vs. the conventional mercury or carbon electrode. The favorable performance of the bismuth working electrode combined with its environmentally friendly nature means the new sensor will be especially attractive in settings where a disposable lab-on-a-chip is wanted.

In addition, the UC team also optimized the sensor layout and working-electrode surface to further reduce the effects of hydrolysis and to boost the reliability and sensitivity in detecting heavy metals. The new sensor layout better allowed for its functioning, which consists of taking of a blood serum sample, stripping out the heavy metal and then measuring that heavy metal.

The end result is the first lab-on-a-chip able to consistently pinpoint levels of highly electronegative manganese in humans. The new sensor also exhibits high reliability over multiple days of use, with hours of continuous operation. With further developments, the chip may even be converted into a self-check mechanism, such as with glucose screening for diabetics.

Funding for this research has been provided by the National Institute of Environmental Health Sciences, the National Institute of Occupational Safety and Health Pilot Research Project Training Program and the University of Cincinnati.

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by University of Cincinnati.

Journal Reference:

Preetha Jothimuthu, Robert A. Wilson, Josi Herren, Erin N. Haynes, William R. Heineman, Ian Papautsky. Lab-on-a-chip sensor for detection of highly electronegative heavy metals by anodic stripping voltammetry. Biomedical Microdevices, 2011; 13 (4): 695 DOI: 10.1007/s10544-011-9539-1

Extremely rapid water: Scientists decipher a protein-bound water chain

Researchers from the RUB-Department of Biophysics of Prof. Dr. Klaus Gerwert have succeeded in providing evidence that a protein is capable of creating a water molecule chain for a few milliseconds for the directed proton transfer. The combination of vibrational spectroscopy and biomolecular simulations enabled the elucidation of the proton pump mechanism of a cell-membrane protein in atomic detail. The researchers demonstrated that protein-bound water molecules play a decisive role in the function. Their results were selected for the Early Edition of PNAS.

Specific proteins can transport protons from one side (uptake side) of the cell membrane to the other side (release side). This is a central process in biological energy conversion. In past editions of Nature and Angewandte Chemie the researchers from the Department of Biophysics had already published their observations that in the ground state the protein-bound water molecules at the release side are optimally arranged for the release of protons. "As with dominos, the protein initiates movement of the protons which finally leads to their release", explains Prof. Gerwert. Just how the protein re-attains its initial state in order to start another pumping cycle remained to be clarified. New protons must be acquired at the uptake side of the protein to substitute the released protons. The researchers in Bochum discovered that a chain of only three water molecules is formed for just a few thousandths of a second to transfer the protons into the interior of the protein.

The protein kills two birds with one stone. The water molecules are disordered during the release phase, which prevents the protons from being transported in the false direction. Only during the uptake phase, they are correctly aligned and can conduct protons. These results are the solution to the riddle as to why proton transfer only functions in one direction at the uptake side and why the protein is capable of effective and directional pumping. "This paper, together with the two preceding publications, now constitutes a trilogy which supplies a full explanation for the proton pumping cycle at an atomic level", summarizes Prof. Gerwert.

The researchers combined experimental physics with theoretical chemistry to be able to observe the processes with a high spatial and temporal resolution at a nano-level. Steffen Wolf simulated the structural changes within the protein using biomolecular computer simulations (molecular dynamics simulations). Erik Freier subsequently verified the effects experimentally using a special kind of vibrational spectroscopy developed by Prof. Gerwert (time-resolved step-scan FTIR spectroscopy). "This interdisciplinary interplay, which showed that the individual components of the protein are as precisely synchronized as the gears of a machine, was the key to success", says Prof. Gerwert.

The protein arranges the three water molecules so skillfully that they transport the protons using the physico-chemical Grotthuss mechanism. In the 1950s, the Nobel Prize winner Manfred Eigen elucidated this mechanism to explain extremely rapid, non-directional proton transport in water. Surprisingly enough, the publications of the RUB researchers now reveal that amino acids coupled with protein-bound water molecules can give this extremely rapid transportation a direction of movement. Prof. Gerwert's team was thus able to augment Manfred Eigen's results and apply them to protein research.

The group of research scientists in Bochum primarily works with the membrane protein bacteriorhodopsin, which is used by certain bacteria to carry out an archaic form of photosynthesis. Bacteriorhodopsin creates a proton concentration gradient by transporting protons from the interior to the exterior of a cell. Other proteins use this gradient to produce ATP, the universal cellular fuel. It is important that the proton transport has a specific direction and that spontaneous backflow of protons is prevented to ensure that light energy can be effectively used.

More information: References:

Freier, E., Wolf, S., Gerwert, K. Proton transfer via a transient linear water-molecule chain in a membrane protein. PNAS, early edition, doi: 10.1073/pnas.1104735108 (2011)

Wolf, S., Freier, E., Potschies, M., Hofmann, E., Gerwert, K. Directional Proton Transfer in Membrane Proteins Achieved through Protonated Protein-Bound Water Molecules: A Proton Diode. Angew. Chem. Int. Ed., 49, 6889-6893 (2010)

Garczarek, F., Gerwert, K.: „Functional waters in intraprotein proton transfer monitored by FTIR difference spectroscopy". Nature, 439, 109-112 (2006)

Provided by Ruhr-University Bochum

Extremely rapid water: Scientists decipher a protein-bound water chain

Researchers from the RUB-Department of Biophysics of Prof. Dr. Klaus Gerwert have succeeded in providing evidence that a protein is capable of creating a water molecule chain for a few milliseconds for the directed proton transfer. The combination of vibrational spectroscopy and biomolecular simulations enabled the elucidation of the proton pump mechanism of a cell-membrane protein in atomic detail. The researchers demonstrated that protein-bound water molecules play a decisive role in the function.

Their results were selected for the Early Edition of Proceedings of the National Academy of Sciences.

Protein-bound water is decisive

Specific proteins can transport protons from one side (uptake side) of the cell membrane to the other side (release side). This is a central process in biological energy conversion. In past editions of Nature and Angewandte Chemie the researchers from the Department of Biophysics had already published their observations that in the ground state the protein-bound water molecules at the release side are optimally arranged for the release of protons. "As with dominos, the protein initiates movement of the protons which finally leads to their release," explains Prof. Gerwert. Just how the protein re-attains its initial state in order to start another pumping cycle remained to be clarified. New protons must be acquired at the uptake side of the protein to substitute the released protons. The researchers in Bochum discovered that a chain of only three water molecules is formed for just a few thousandths of a second to transfer the protons into the interior of the protein.

Water molecules lead the way

The protein kills two birds with one stone. The water molecules are disordered during the release phase, which prevents the protons from being transported in the false direction. Only during the uptake phase, they are correctly aligned and can conduct protons. These results are the solution to the riddle as to why proton transfer only functions in one direction at the uptake side and why the protein is capable of effective and directional pumping. "This paper, together with the two preceding publications, now constitutes a trilogy which supplies a full explanation for the proton pumping cycle at an atomic level," summarizes Prof. Gerwert.

Experimental physics and theoretical chemistry combined

The researchers combined experimental physics with theoretical chemistry to be able to observe the processes with a high spatial and temporal resolution at a nano-level. Steffen Wolf simulated the structural changes within the protein using biomolecular computer simulations (molecular dynamics simulations). Erik Freier subsequently verified the effects experimentally using a special kind of vibrational spectroscopy developed by Prof. Gerwert (time-resolved step-scan FTIR spectroscopy). "This interdisciplinary interplay, which showed that the individual components of the protein are as precisely synchronized as the gears of a machine, was the key to success," says Prof. Gerwert.

As in water, so in the protein

The protein arranges the three water molecules so skillfully that they transport the protons using the physico-chemical Grotthuss mechanism. In the 1950s, the Nobel Prize winner Manfred Eigen elucidated this mechanism to explain extremely rapid, non-directional proton transport in water. Surprisingly enough, the publications of the RUB researchers now reveal that amino acids coupled with protein-bound water molecules can give this extremely rapid transportation a direction of movement. Prof. Gerwert's team was thus able to augment Manfred Eigen's results and apply them to protein research.

Effective conversion of light energy into chemical energy

The group of research scientists in Bochum primarily works with the membrane protein bacteriorhodopsin, which is used by certain bacteria to carry out an archaic form of photosynthesis. Bacteriorhodopsin creates a proton concentration gradient by transporting protons from the interior to the exterior of a cell. Other proteins use this gradient to produce ATP, the universal cellular fuel. It is important that the proton transport has a specific direction and that spontaneous backflow of protons is prevented to ensure that light energy can be effectively used.

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by Ruhr-Universitaet-Bochum, via AlphaGalileo.

Journal Reference:

E. Freier, S. Wolf, K. Gerwert. Proton transfer via a transient linear water-molecule chain in a membrane protein. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1104735108

New rapid test tells difference between bacterial and viral infections

 Scientists are reporting development and successful testing of a rapid and accurate test to tell the difference between bacterial and viral infections. Those common afflictions often have similar symptoms but vastly different treatments — antibiotics work for bacterial infections but not for viruses. The report appears in ACS' journal Analytical Chemistry.

Robert Marks, Daria Prilutsky, and colleagues cite the importance of determining the source of an infection in order to quickly start the right treatment. If left untreated until results of a throat culture, for instance, are in, bacterial infections can get worse. But needlessly giving antibiotics to patients with a viral infection could contribute to the growing problem of antibiotic-resistant bacteria. Since current diagnostic methods to sort out the two kinds of infection are time-consuming and may not be completely accurate, the researchers sought to develop a new test that would enable doctors to rapidly make the right diagnosis.

They found that the immune systems of patients with bacterial infections behaved differently than the immune systems of patients with viral infections, and developed a test based on those differences. "The method is time-saving, easy to perform and can be commercially available, thus, having predictive diagnostic value and could be implemented in various medical institutions as an adjunct to clinical decision making," say the researchers.

More information: “Differentiation between viral and bacterial acute infections using chemiluminescent signatures of circulating phagocytes” Anal. Chem., 2011, 83 (11), pp 4258–4265 DOI: 10.1021/ac200596f

Abstract
Oftentimes the etiological diagnostic differentiation between viral and bacterial infections is problematic, while clinical management decisions need to be made promptly upon admission. Thus, alternative rapid and sensitive diagnostic approaches need to be developed. Polymorphonuclear leukocytes (PMNs) or phagocytes act as major players in the defense response of the host during an episode of infection, and thereby undergo functional changes that differ according to the infections. PMNs functional activity can be characterized by quantification and localization of respiratory burst production and assessed by chemiluminescent (CL) byproduct reaction. We have assessed the functional states of PMNs of patients with acute infections in a luminol-amplified whole blood system using the component CL approach. In this study, blood was drawn from 69 patients with fever (>38 °C), and diagnosed as mainly viral or bacterial infections in origin. Data mining algorithms (C4.5, Support Vector Machines (SVM) and Nave Bayes) were used to induce classification models to distinguish between clinical groups. The model with the best predictive accuracy was induced using C4.5 algorithm, resulting in 94.7% accuracy on the training set and 88.9% accuracy on the testing set. The method demonstrated a high predictive diagnostic value and may assist the clinician one day in the distinction between viral and bacterial infections and the choice of proper medication.

Provided by American Chemical Society (news : web)

CAS REGISTRY Keeps Pace with Rapid Growth of Chemical Research, Registers 60 Millionth Substance

 Chemical Abstracts Service (CAS) announced that a patent application claiming compounds with potential therapeutic activity submitted to the State Intellectual Property Office of the People’s Republic of China (SIPO) included the 60 millionth substance recorded in CAS REGISTRY.

CAS observed in 2009 that China surpassed all other nations as the top producer of chemical patent applications. China still maintains the lead today, and finding that the 60 millionth substance registered is from a SIPO application reconfirms that observation.

Coming less than two years after CAS REGISTRY crossed the 50 million mark, this second major milestone shows the continued acceleration of chemical and scientific output across the globe. CAS scientists keep up with this growth daily, by analyzing, organizing, and curating the output of worldwide research in their native languages to maintain the completeness and quality of CAS’ premier substance collection.

The 60 millionth substance, a potential antiviral compound, was assigned the CAS Registry Number® 1298016-92-8. The substance was discovered by the Institute of Materia Medica, Chinese Academy of Medical Sciences, which is one of the key drug research institutions in China. In the patent application, a team of inventors prepared derivatives of 2-amino-1,3,4-thiadiazine.

“Our organization relies on CAS’ research tool, SciFinder®, as a critical asset to our research team, helping to educate our R&D teams along every step of the research process,” said Pei Cheng Zhang, a professor at Materia Medica. “Its database’s rapid growth demonstrates its leadership within the industry and breadth of coverage, making it paramount to our success.”

“It seems fitting that the 60 millionth substance in CAS REGISTRY would originate from within an Asian country, given the region’s growing and significant impact on scientific discovery in recent years,” said Christine McCue, Vice President of Marketing at CAS. “This growth is illustrated not only in the patent arena, but also with respect to journal literature, and led CAS to expand coverage of Asian chemistry through the analysis of more than 300 additional journal titles in the past three years from China, Japan, and Korea alone.”

 

Did Rapid DNA Analysis Verify Osama Bin Laden's Death?

A few years ago, I worked as a Writing Department Intern for C.S.I. Crime Scene Investigation and C.S.I. New York. Seeing producers, writers and real C.S.I.s collaboratively bring a story from pitch to beatsheat was intoxicating. Research was meticulous. Science served as mascot, foundation and muse.

Despite the show's dedication to rigorous research, its ultimate success had a lot to do with the fact that the creators didn't try to replicate a day in the life of a C.S.I. Team or a forensic DNA lab. The actual C.S.I. Investigators don't go from the crime scene to the lab. The forensic analysis is done by trained lab techs. What would those award-winning "C.S.I. Shots" be without charismatic stars in starch white lab jackets peering through microscopes, though?

A photo of the real and considerably less glamorous Las Vegas C.S.I. Team taped to the refrigerator was one of many many testaments to the team's awareness of the conscious discrepancy between factual and actual. Another was the timing. Turnaround time for DNA analysis is not instantaneous. Enter the episodic Hollywood procedural fiat clause. Two beats later the DNA is verified.

The evening of May 1, 2011, American audiences were riveted to their computers and television screens watching the most expensive criminal investigations in history unfold. As would be expected, scientists, journalists and laypeople are now scrutinizing the verification details with the fundamental question, "How do we know it was Bin Laden?"

Real forensic science labs may not incorporate the Hollywood fiat into their practices. A European Community–funded portable rapid DNA test, developed at University of Arizona Phoenix, however, might.

Professor Frederic Zenhausern at the Center for Applied Nanobioscience and Medicine said that the technology he is developing through the UK Forensic Science Service "is currently under validation by several crime labs in the UK, Germany, Austria and the Netherlands."

Could those dots connect all the way to Pakistan? Not likely.

Zenhausern reiterated that "there is no rapid DNA system available for a portable deployment in such a mission yet." The system his team is developing is the "only one reported to be close to such requirements," however, it is "not validated yet."

Exciting as it may be to speculate, "it is unlikely USG (U.S. Government) used such a system at the site. More likely they transported the samples (and/or body) to a command center" equipped with the "instrumentation and bench space to accommodate the lab equipment."

Whereas a low profile DNA case would be "processed with the conventional lab-bench techniques" that could "take up to 10-14 days," an extraordinary case, such as the most expensive manhunt in history, "could be performed in less than 24 hours" through an integrated system that has a "turnaround time of less than 2 hours."

Zenhausern speculates that "Osama Bin Laden’s DNA analysis may have been performed through cross-validation of processing at different USG labs...possibly located at some strategic and local command centers equipped with conventional and high quality STR (Short Tandem Repeat) profiling platform technologies."

Given the highly orchestrated nature of the operation, surrounding military bases—already prepared with on-site facilities for identifying soldiers—could have been alerted ahead of time, but they still needed to travel there. This explains the gap between the 3:50 pm EST ID confirmation and The White House's 10:30 pm DNA verified announcement.

"In a near future, rapid DNA testing using a single piece of portable equipment will improve the cycle time, mobility and possibly reduce some of the cost of the analysis while providing a much simpler user interface." Zenhausern said, positing that "comparative matches may have been done from previously collected samples from skin, hair, fingerprint or any other object Bin Laden may have been touching (e.g. cup) and/or from samples collected from family members."

It won't be long before the rapid technology being developed will be a legitimate DNA verification process. Right now, however, it's still a Hollywood thing.

Photo credit: picture of Dr. Zenhausern with the machine at his lab in Chandler, Ariz., taken by Keven Siegert, University of Arizona College of Medicine – Phoenix.

Related at Scientific American: How do you ID a dead Osama?

Related, elsewhere on the Web:

Univ. of Arizona scientists have been working with FBI to develop 2-hour DNA fingerprint device. Could it have ID'd bin Laden?

Experts Say DNA Match Is Likely a Parent or Child

It's a Match: How Officials Used DNA to Identify bin Laden

UA Scientists Develop Quick DNA Test Device

Did DNA Finger bin Laden?

Rapid DNA testing being developed at University of Arizona

Center for Applied NanoBioscience and Medicine [video]

Integrated microfluidic system for rapid forensic DNA analysis: sample collection to DNA profile.

About the Author: Although Susanna Speier was never able to formally pursue her passion for science, her "ear" for layman-friendly science explanations—deemed "excellent" by The New York Times—has enabled her to enter through the back door on many occasions. She talks to scientists whenever she can. Conversations often turn into collaborations. Five of her plays have been produced; over 100 of her articles have been published and one of her screenplays remains in liminal purgatory. She dayjobs as a multiplatform social media specialist and digital journalist.

The views expressed are those of the author and are not necessarily those of Scientific American.

 

Rapid etching X-rayed: Physicists unveil processes during fast chemical dissolution

A breakthrough in the study of chemical reactions during etching and coating of materials was achieved by a research group headed by Kiel physicist, Professor Olaf Magnussen. The team from the Christian-Albrechts-Universität zu Kiel (CAU), Germany, in collaboration with staff from the European Synchrotron Radiation Facility (ESRF) in Grenoble, France, have uncovered for the first time just what happens in manufacturing processes, used for the formation of metal contacts thinner than a human hair in modern consumer electronics, such as flat-screen television.

The results appear in the Journal of the American Chemical Society.

For their research the scientists used the intense X-ray radiation of the experimental station ID32, one of the ESRF's instruments. The X-ray beam was directed onto a gold surface while it dissolved in diluted hydrochloric acid. Because the reflected X-rays are sensitive to tiny changes in the atomic arrangement at the material's surface, the metal removal during the reaction can be precisely measured.

"Such studies were only possible during very slow changes of the material so far," Olaf Magnussen explains. To gain insight into the fast reactions going on in industrially employed processes the speed of the measurements had to be increased more than a hundredfold. Even during very fast etching the removal of the metal proceeded very uniformly. "The material dissolves quasi atomic layer by atomic layer, without formation of deeper holes," Magnussen remarks. In a similar way, the team could follow the attachment of atoms during the chemical coating of materials.

Among the diverse industrial applications of chemical etching and coating are high-tech manufacturing processes, for example in the production of electronic devices. These require precisely controlled reactions. In order to optimize such etching and coating processes they are intensely studied worldwide. Until now it was only possible to analyse the finished product. With the method developed by the scientists, changes within a few thousandth seconds may be detected so that the reactions at the material's surface can be tracked on the atomic scale under realistic conditions.

Christian-Albrechts-Universität zu Kiel is a North German research university with proven international expertise in the field of nanoscience, including research using synchrotron radiation. In a number of research networks, funded by the German Federal Ministry of Education and Research, Kiel scientists develop new methods and instruments. In addition, the CAU competes for a Cluster of Excellence in the area of nanoscience and surface science within the ongoing round of the German Excellence Initiative.

The ESRF is a European research institution, funded by 19 nations, providing and utilizing brilliant synchrotron X-rays for advanced scientific research.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by Christian-Albrechts-Universitaet zu Kiel.

Journal Reference:

Frederik Golks, Klaus Krug, Yvonne Gru¨nder, Jo¨rg Zegenhagen, Jochim Stettner, Olaf M. Magnussen. High-Speed in situ Surface X-ray Diffraction Studies of the Electrochemical Dissolution of Au(001). Journal of the American Chemical Society, 2011; 133 (11): 3772 DOI: 10.1021/ja1115748

Rapid, high-definition chemistry with new imaging technique

With intensity a million times brighter than sunlight, a new synchrotron-based imaging technique offers high-resolution pictures of the molecular composition of tissues with unprecedented speed and quality. Carol Hirschmugl, a physicist at the University of Wisconsin-Milwaukee (UWM), led a team of researchers from UWM, the University of Illinois at Urbana-Champaign and University of Illinois at Chicago (UIC) to demonstrate these new capabilities.

Hirschmugl and UWM scientist Michael Nasse have built a facility called "Infrared Environmental Imaging (IRENI)," to perform the technique at the Synchrotron Radiation Center (SRC) at UW-Madison. The new technique employs multiple beams of synchrotron light to illuminate a state-of-the-art camera, instead of just one beam.

IRENI cuts the amount of time needed to image a sample from hours to minutes, while quadrupling the range of the sample size and producing high-resolution images of samples that do not have to be tagged or stained as they would for imaging with an optical microscope.

"Since IRENI reveals the molecular composition of a tissue sample, you can choose to look at the distribution of functional groups, such as proteins, carbohydrates and lipids," says Hirschmugl, "so you concurrently get detailed structure and chemistry."

The technique could have broad applications not only in medicine, but also in pharmaceutical drug analysis, art conservation, forensics, biofuel production, and advanced materials, such as graphene, she says.

Funded by $1 million grant from the National Science Foundation's Major Research Instrumentation Program, the development of the facility has quickly attracted other projects supported by the NSF and the National Institutes of Health. It is published online today in Nature Methods.

The work is a collaboration with the labs of Rohit Bhargava, assistant professor of bioengineering at the University of Illinois at Urbana-Champaign and pathologists Dr. Virgilia Macias and Dr. André Kajdacsy-Balla at UIC. "It has taken three years to establish IRENI as a national user facility located at the SRC," says Nasse. "It is the only facility of its kind worldwide."

Chemical fingerprints

The unique features of the synchrotron make it a highly versatile light source in spectroscopy. Streams of speeding electrons emit continuous light across the entire electromagnetic spectrum so that researchers can access whatever wavelength is best absorbed for a particular purpose.

Although not visible to the human eye, the mid-infrared range of light used by the team documents the light absorbed at thousands of locations on the sample, forming graphic "fingerprints" of biochemically important molecules.

Using 12 beams of synchrotron light in this range allows researchers to collect thousands of these chemical fingerprints simultaneously, producing an image that is 100 times less-pixelated than in conventional infrared imaging.

"We did not realize until now the improvement in detail and quality that sampling at this pixel size would bring," says Bhargava. "The quality of the chemical images is now quite similar to that of optical microscopy and the approach presents exciting new possibilities."

Testing for future applications

The team tested the technique on breast and prostate tissue samples to determine its capabilities for potential use in diagnostics for cancer and other diseases. The researchers were able to detect features that distinguished the epithelial cells, in which cancers begin, from the stromal cells, which are the type found in deeper tissues, with unprecedented detail.

Separating the two layers of cells is a "basement membrane" which prevents malignant cells from spreading from the epithelial cells into the stromal cells. Early-stage cancers are concentrated in the epithelial cells, but metastasis occurs when the basement membrane is breached. Using a prostate cancer sample, the team had encouraging results in locating spectra of the basement membrane, but more work needs to be done.

"IRENI provides us a new opportunity to study tissues and provides lessons for the development of the next generation of IR imaging instruments," says Michael Walsh, a Carle Foundation Hospital-Beckman Institute post-doctoral fellow at the University of Illinois at Urbana-Champaign and co-author on the paper.

It opens the door for development of synchrotron-based imaging that can monitor cellular processes, from simple metabolism to stem cell specialization.

Provided by University of Wisconsin - Milwaukee