Nanotube technology leading to new era of fast, lower-cost medical diagnostics

 Researchers at Oregon State University have tapped into the extraordinary power of carbon "nanotubes" to increase the speed of biological sensors, a technology that might one day allow a doctor to routinely perform lab tests in minutes, speeding diagnosis and treatment while reducing costs.

The new findings have almost tripled the speed of prototype nano-biosensors, and should find applications not only in medicine but in toxicology, environmental monitoring, new drug development and other fields.

The research was just reported in Lab on a Chip, a professional journal. More refinements are necessary before the systems are ready for commercial production, scientists say, but they hold great potential.

"With these types of sensors, it should be possible to do many medical lab tests in minutes, allowing the doctor to make a diagnosis during a single office visit," said Ethan Minot, an OSU assistant professor of physics. "Many existing tests take days, cost quite a bit and require trained laboratory technicians.

"This approach should accomplish the same thing with a hand-held sensor, and might cut the cost of an existing $50 lab test to about $1," he said.

The key to the new technology, the researchers say, is the unusual capability of carbon nanotubes. An outgrowth of nanotechnology, which deals with extraordinarily small particles near the molecular level, these nanotubes are long, hollow structures that have unique mechanical, optical and electronic properties, and are finding many applications.

In this case, carbon nanotubes can be used to detect a protein on the surface of a sensor. The nanotubes change their electrical resistance when a protein lands on them, and the extent of this change can be measured to determine the presence of a particular protein -- such as serum and ductal protein biomarkers that may be indicators of breast cancer.

The newest advance was the creation of a way to keep proteins from sticking to other surfaces, like fluid sticking to the wall of a pipe. By finding a way to essentially "grease the pipe," OSU researchers were able to speed the sensing process by 2.5 times.

Further work is needed to improve the selective binding of proteins, the scientists said, before it is ready to develop into commercial biosensors.

"Electronic detection of blood-borne biomarker proteins offers the exciting possibility of point-of-care medical diagnostics," the researchers wrote in their study. "Ideally such electronic biosensor devices would be low-cost and would quantify multiple biomarkers within a few minutes."

This work was a collaboration of researchers in the OSU Department of Physics, Department of Chemistry, and the University of California at Santa Barbara. A co-author was Vincent Remcho, professor and interim dean of the OSU College of Science, and a national expert in new biosensing technology.

The research was supported by the U.S. Army Research Laboratory through the Oregon Nanoscience and Microtechnologies Institute.

Story Source:

The above story is reprinted from materials provided by Oregon State University.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Matthew R. Leyden, Robert J. Messinger, Canan Schuman, Tal Sharf, Vincent T. Remcho, Todd M. Squires, Ethan D. Minot. Increasing the detection speed of an all-electronic real-time biosensor. Lab on a Chip, 2012; 12 (5): 954 DOI: 10.1039/C2LC21020G

Researchers discover the processes leading to acute myeloid leukemia

The UCSB research team described how a certain mutation in DNA disrupts cellular function in patients with acute myeloid leukemia (AML). The researchers were prompted to study this process by another research team's discovery that AML patients have a mutation in a certain enzyme, which was reported in the New England Journal of Medicine. The enzyme is a protein called DNMT3A, which leads to changes in how the DNA of AML patients is methylated, or "tagged." Norbert Reich, professor in the Department of Chemistry and Biochemistry at UCSB, was already studying that particular enzyme with his research group, so they began to study the disease process of AML at the cellular level.

Reich explained that tagging is a way of reading DNA at the cellular level. This falls within an area of study called epigenetics, a process that occurs "on top" of genetics. Each person has approximately 200 types of cells, all with the same DNA, and these must be controlled in different ways. "There is an enzyme –– a protein –– that tags DNA and controls which of the genes in your cells, your DNA, gets turned on and off," said Reich. "So you have 20,000 genes, and you have to control them differently in your brain than in your liver."

Reich explained that there is current interest in this broader field of epigenetics as a direction for the treatment of cancer. "There's definitely the idea that this may be a new way of developing therapeutics, because you don't have to kill the cancer cell," said Reich. "Almost every cancer therapy that's out there works on the principle that a cancer cell needs to be killed."

In this artist's conception, the four-protein complex called DNMT3A is shown in its normal configuration (top left). The complex reads or "tags" the cell's DNA. In the upper right side of the image, several of these tags are shown on top of the double helix of DNA. The tags control which genes in a cell get turned on and off. In the bottom left image, the complex of four proteins is disrupted. This disruption is caused by the mutation found in patients with acute myeloid leukemia. In the right side of the bottom image, the protein leaves only one tag on the DNA and then moves on. Credit: Norbert Reich, UCSB

With epigenetics, instead of only having DNA sequence coding for certain genes, there is an epigenetic process, with another layer of information on top of the genetic process. In this case, that information is the tagging by the methyl groups.

"If you really think about it, this is part of the answer as to how your cells can be so different and yet they all have the same DNA," said Reich. "You have the same genome in every one of your cells, but you do not have the same epigenome, which is basically the methylation pattern, the tagging pattern. That is different in every type of your cells. And the way this relates back to cancer, with leukemia, in those patients, the tagging is messed up. The patterns are not correct. Our big contribution to that is we've explained how the mutations in the enzyme could lead to that disruption of the tagging pattern."

The UCSB group developed a test to demonstrate that the mutant enzymes in AML can only work on DNA for short distances. As a result, the precise methylation patterns of a healthy cell are disturbed, resulting in genes being turned on at the wrong place and time, which in turn can initiate the growth of cancerous cells.

The team found that the mutation AML patients have causes a certain complex of four proteins to be disrupted. "The surprise was that the disruption doesn't stop the enzyme from being active; it doesn't stop the enzyme from tagging the DNA," said Reich. "Instead, it stops the way it can do it. Instead of going to your DNA and tagging an entire region of chromosome, it goes there, does one thing, and leaves. That process, that change, is what we see in the AML patients. So we think we have a molecular explanation for this disease."

Reich said that the currently prescribed drug Vidaza works by affecting the same enzyme that is mutated in AML. There is interest in the pharmaceutical industry in developing other therapeutics to target the enzymes responsible for tagging the DNA. These epigenetic inhibitors would reprogram rather than kill the cell.

Traditional cancer therapies use radiation and chemotherapy to remove or kill cancer cells. "The problem with that is that cancer cells are often very subtly different from normal cells," said Reich. "So you have one of the most difficult therapeutic challenges known to man, which is to distinguish between two human cells –– one that's cancerous and one that's not. Instead of killing the cell, the notion is that if you could just reprogram the cell, then it goes back to being normal. You intercept the cancer development. This is still an aspiration; it hasn't been achieved really, but that's what attracts people to the field of epigenetic-based therapies, because of the prospect of not having to kill cells."

Provided by University of California - Santa Barbara (news : web)

Graphene cloak protects bacteria, leading to better images

It's a cloak that surpasses all others: a microscopic carbon cloak made of graphene that could change the way bacteria and other cells are imaged.

Vikas Berry, assistant professor of chemical engineering at Kansas State University, and his research team are wrapping bacteria with graphene to address current challenges with imaging bacteria under electron microscopes. Berry's method creates a carbon cloak that protects the bacteria, allowing them to be imaged at their natural size and increasing the image's resolution.

Graphene is a form of carbon that is only one atom thick, giving it several important properties: it's impermeable, it's the strongest nanomaterial, it's optically transparent and it has high thermal conductance.

"Graphene is the next-generation material," Berry said. "Although only an atom thick, graphene does not allow even the smallest of molecules to pass through. Furthermore, it's strong and highly flexible so it can conform to any shape."

Berry's team has been researching graphene for three years, and Berry recently saw a connection between graphene and cell imaging research. Because graphene is impermeable, he decided to use the material to preserve the size of bacterial cells imaged under high-vacuum electron microscopes.

The research results appear in the paper "Impermeable Graphenic Encasement of Bacteria," which was published in a recent issue of Nano Letters, a monthly scientific journal published by the American Chemical Society. The team's preliminary research appeared in Nature News in 2010.

The current challenge with cell imaging occurs when scientists use electron microscopes to image bacterial cells. Because these microscopes require a high vacuum, they remove water from the cells. Biological cells contain 70 to 80 percent water, and the result is a severely shrunk cell. As a result, it is challenging to obtain an accurate image of the cells and their components in their natural state.

But Berry and his team created a solution to the imaging challenge by applying graphene. The graphene acts as an impermeable cloak around the bacteria so that the cells retain water and don't shrink under the high vacuum of electron microscopes. This provides a microscopic image of the cell at its natural size.

The carbon cloaks can be wrapped around the bacteria using two methods. The first method involves putting a sheet of graphene on top of the bacteria, much like covering up with a bed sheet. The other method involves wrapping the bacteria with a graphene solution, where the graphene sheets swaddle the bacteria. In both cases the graphene sheets were functionalized with a protein to enhance binding with the bacterial cell wall.

Under the high vacuum of an electron microscope, the wrapped bacteria did not change in size for 30 minutes, giving scientists enough time to observe them. This is a direct result of the high strength and impermeability of the graphene cloak, Berry said.

Graphene's other extraordinary properties enhance the imaging resolution in microscopy. Its electron-transparency enables a clean imaging of the cells. Since graphene is a good conductor of heat and electricity, the local electronic-charging and heating is conducted off the graphene cloak, giving a clear view of the bacterial cell well. Unwrapped bacterial cells appear dark with an indistinguishable cell wall.

"Uniquely, graphene has all the properties needed to image bacteria at high resolutions," Berry said. "The project provides a very simple route to image samples in their native wet state."

The process has potential to influence future research. Scientists have always had trouble observing liquid samples under electron microscopes, but using carbon cloaks could allow them to image wet samples in a vacuum. Graphene's strong and impermeable characteristics ensure that wrapped cells can be easily imaged without degrading them. Berry said it might be possible in the future to use graphene to keep bacterium alive in a vacuum while observing its biochemistry under a microscope.

The research also paves the way for enhanced protein microscopy. Proteins act differently when they are dry and when they are in an aqueous solution. So far most protein studies have been conducted in dry phases, but Berry's research may allow proteins to be observed more in aqueous environments.

"This research could be the point of evolution for processing of sensitive samples with graphene to achieve enhanced imaging," Berry said.

Other researchers involved in the project include Daniel Boyle, research assistant professor in biology; Nihar Mohanty, doctoral student in chemical engineering, India; Ashvin Nagaraja, former master's student in electrical engineering; and Monica Fahrenholtz, a May 2010 chemical engineering graduate from Clearwater.

Story Source:

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

Journal Reference:

Nihar Mohanty, Monica Fahrenholtz, Ashvin Nagaraja, Daniel Boyle, Vikas Berry. Impermeable Graphenic Encasement of Bacteria. Nano Letters, 2011; 11 (3): 1270 DOI: 10.1021/nl104292k