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 How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>