Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Penn Researchers attach Lyme disease antibodies to nanotubes, paving way for diagnostic device

27.03.2013
Early diagnosis is critical in treating Lyme disease. However, nearly one quarter of Lyme disease patients are initially misdiagnosed because currently available serological tests have poor sensitivity and specificity during the early stages of infection. Misdiagnosed patients may go untreated and thus progress to late-stage Lyme disease, where they face longer and more invasive treatments, as well as persistent symptoms.

Existing tests assess the presence of antibodies against bacterial proteins, which take weeks to form after the initial infection and persist after the infection is gone. Now, a nanotechnology-inspired technique developed by researchers at the University of Pennsylvania may lead to diagnostics that can detect the organism itself.

The study was led by professor A. T. Charlie Johnson of the Department of Physics and Astronomy in Penn's School of Arts and Sciences along with graduate student Mitchell Lerner, undergraduate researcher Jennifer Dailey and postdoctoral fellow Brett R. Goldsmith, all of Physics. They collaborated with Dustin Brisson, an assistant professor of biology who provided the team with expertise on the bacterium.

Their research was published in the journal Biosensors and Bioelectronics.

"When you're initially infected with the Lyme disease bacterium, you don't develop antibodies for many days to a few weeks," Johnson said. "Many people see their physician before antibodies develop, leading to negative serological test results. And after an initial infection, you're still going to have these antibodies, so using these serological diagnostics won't make it clear if you're still infected or not after you've been treated with antibiotics."

The research team's idea was to flip the process around, using laboratory-produced antibodies to detect the presence of proteins from the organism. This is an extension of previous work Johnson's lab has done connecting other biological structures, such as olfactory receptors and DNA, to carbon nanotube-based devices.

Carbon nanotubes, rolled-up lattices of carbon atoms, are highly conductive and sensitive to electrical charge, making them promising components of nanoscale electronic devices. By attaching different biological structures to the exteriors of the nanotubes, they can function as highly specific biosensors. When the attached structure binds to a molecule, that molecule's charge can affect the electrical conduction of the nanotube, which can be part of an electrical circuit like a wire. Such a device can therefore provide an electronic read-out of the presence, or even concentration, of a particular molecule.

To get the electrical signal out of these nanotubes, the team first turned them into transistor devices.

"We first grow these nanotubes on what amounts to a large chip using a vapor deposition method, then make electrical connections essentially at random," Johnson said. "We then break up the chip and test all of the individual nanotube transistors to see which work the best."

In their recent experiment, Johnson's team attached antibodies that naturally develop in most animals that are infected with the Lyme disease bacterium to these nanotube transistors. These antibodies naturally bind to an antigen, in this case, a protein in the Lyme bacterium, as part of the body's immune response.

"We have a chemical process that lets us connect any protein to carbon nanotubes. Nanotubes are very stable, so we have a very reactive compound that binds to the nanotube and also has a carboxylic acid group on the other end. For biochemists, getting any kind of protein to bind to a carboxylic acid group is just child's play at this point, and we have worked with them to learn how to perform this chemistry on the side wall of nanotubes. "

After using atomic-force microscopy to show that antibodies had indeed bound to the exteriors of their nanotube transistors, the researchers tested them electrically to get a baseline reading. They then put the nanotubes in solutions that contained different concentrations of the target Lyme bacteria protein.

"When we wash away the solution and test the nanotube transistors again, the change in what we measure tells us that how much of the antigen has bound," Johnson said. "And we see the relationship we expect to see, in that the more antigen there was in the solution, the bigger the change in the signal."

The smallest concentration the nanotube devices could detect was four nanograms of protein per milliliter of solution.

"This sensitivity is more than sufficient to detect the Lyme disease bacterium in the blood of recently-infected patients and may be sufficient to detect the bacterium in fluids of patients that have received inadequate treatment," Brisson said.

"We really want the protein we are looking to detect to bind as close to the nanotube as possible, as that is what increases the strength of the electrical signal," Johnson said. "Developing a smaller, minimal version of the antibody — what we call a single chain variable fragment — would be a next step.

"Based on our previous work with single chain variable fragments of other antibodies, this would probably make such a device about a thousand times more sensitive."

The researchers suggested that, given the flexibility of their technique for attaching different biological structure, eventual diagnostic tools could incorporate multiple antibodies, each detecting a different protein from the Lyme bacterium. Such a setup would improve accuracy and cut down on the possibility of false-positive diagnoses.

"If we were to do this type of test on a person's blood now, however, we would say the person has the disease," Johnson said. "The first thought is that if you detect any protein coming from the Lyme organism in your blood, you are infected and should get treatment right away."

This research was supported by the Department of Defense U.S. Army Medical Research and Materiel Command, the National Institutes of Health, Penn's Nano/Bio Interface Center, the National Science Foundation and Penn's Laboratory for Research on the Structure of Matter.

Evan Lerner | EurekAlert!
Further information:
http://www.upenn.edu

More articles from Health and Medicine:

nachricht Satellites, airport visibility readings shed light on troops' exposure to air pollution
09.12.2016 | Veterans Affairs Research Communications

nachricht Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>