Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New device can help defend against novel biological agents

12.01.2004


Close-up of four-channel microphysiometer; Photo by Daniel Dubois, Vanderbilt University


Dale Taylor, Sven Eklund and David Cliffel, left to right, posed next to the four-channel microphysiometer; Photo by Daniel Dubois, Vanderbilt University.


The ability to analyze and defend against novel biological agents has been strengthened by the development of a new device that can monitor the metabolism of living cells in near real time.

"So far we have been lucky that terrorists have used well-known biological agents like anthrax and sarin gas," says David Cliffel, assistant professor of chemistry at Vanderbilt University, who led the development group working under the auspices of the Vanderbilt Institute for Integrative Biosystems Research and Education. "But how will we respond if one of these groups uses recent advances in genetic engineering to produce an agent that is new and unknown?"

Part of the answer, Cliffel says, is the device he and his colleagues have developed, called a four-channel microphysiometer. It is a modification of a 10-year-old commercial device called the Cytosensor made by the company Molecular Devices that measures changes in acidity in a small chamber holding between 100,000 to 1,000,000 individual cells. Cliffel’s research team has added three additional sensors so that the machine can simultaneously chart minute-by-minute variations in the concentrations of oxygen, glucose, and lactic acid, in addition to pH.



The added capability – reported in the Feb. 1 issue of the journal Analytical Chemistry and now available online – is important because the basic metabolism of a cell involves consuming oxygen and glucose and producing lactic and carbonic acid. As a result, monitoring variations in these four chemicals allows researchers to quickly assess the impact that exposure to different chemicals have on the activity and health of relatively small groups of cells.

"I envision having a microphysiometer with an array of chambers," says Cliffel. "One of them contains heart cells, another contains kidney cells, another nerve cells and so on. Then, when an unknown agent is pumped into all these chambers, we quickly will be able to determine exactly which part of the body it attacks and the response of the affected cells will provide us with important clues about the manner of its attack."

Because of its potential application for bioterrorism and chemical and biological warfare, the development of the device has been funded by the Defense Advance Research Projects Agency. But the microphysiometer also has important potential applications in detecting and assessing the toxicity of environmental pollutants. It also has many possible uses in basic biological research, its developers point out. The microphysiometer consists of a series of reservoirs, switches, rotary pumps and tiny chambers made from two thin membrane sheets that contain the cell colonies. The original unit also included a single sensor that measured changes in acidity (pH) in the extracellular liquid.

"Over the years, the Cytosensor has been used in a number of studies involving changes in pH," says Cliffel. "But its usefulness was limited because it could only measure a single variable. We realized that analytical chemists had recently developed new techniques that would allow us to simultaneously measure variations in several different key compounds."

Using these techniques, Cliffel’s interdisciplinary research team – chemistry post-doctoral assistants Sven Eklund and Dale Taylor working with senior research associate Eugene Kozlov and research professor Ales Prokop from chemical engineering – developed the three additional sensors out of specially coated electrodes. They attached these to another commercial device that has recently come on the market, called a multipotentiostat, that allowed them to take simultaneous readings from the sensors.

One of the biggest problems they had with these modifications was due to the fact that one of the devices was designed to be controlled by a Windows computer and the other by a Macintosh. "In the beginning, there was a tremendous amount of cross talk between the two computers that we had to eliminate," Eklund says.

The researchers tested the modified device with several different toxic agents and two cell types.

In one test they added fluoride to Chinese hamster ovary cells. Fluoride blocks cells’ ability to convert glucose into ATP, the chemical that cells use as an energy source. Their measurements showed that the lactate concentration and acidification rate dropped rapidly as the cell slowed its production while oxygen and glucose concentrations rose as the cell consumption slowed.

"We could see the cells basically go into hibernation," says Cliffel. "Then, when we flushed out the fluoride, we could see them start up again."

They ran similar tests with two other known metabolic poisons, antimycin A and 2,4-dinitrophenol, and a type of cell that produces connective tissue called a fibroblast and got similar results.

Last year, the Vanderbilt researchers upgraded a Cytosensor at the Edgewood Chemical Biological Center at the Aberdeen Proving Ground in Maryland. Since then their ECBC collaborators have been using the device to study cell response to a number of different chemical and biological agents.

Since submitting the recent paper, Cliffel’s group has also successfully tested the device with two pesticides, parathion and paraoxon, and two common pollutants, the gas additive MTBE and hexachromium, the pollutant that Erin Brochovich made famous.

A paper that provides detailed instructions on how to modify the Cytosensor and multipotentiostat to make a four-channel microphysiometer has been accepted for publication by Humana Press and is scheduled to appear later in the year.

David F. Salisbury | EurekAlert!
Further information:
http://www.exploration.vanderbilt.edu

More articles from Life Sciences:

nachricht New mechanisms uncovered explaining frost tolerance in plants
26.09.2016 | Technische Universität München

nachricht Chains of nanogold – forged with atomic precision
23.09.2016 | Suomen Akatemia (Academy of Finland)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

Im Focus: New laser joining technologies at ‘K 2016’ trade fair

Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.

K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

Using mathematical models to understand our brain

16.09.2016 | Event News

 
Latest News

Stronger turbine blades with molybdenum silicides

26.09.2016 | Materials Sciences

Scientists Find Twisting 3-D Raceway for Electrons in Nanoscale Crystal Slices

26.09.2016 | Materials Sciences

Lowering the Heat Makes New Materials Possible While Saving Energy

26.09.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>