Biological chips could speed up testing for serious diseases

Protein chips, also known as protein arrays, are objects such as slides that have proteins attached to them and allow important scientific data about the behaviour of proteins to be gathered.

Functional protein arrays could give scientists the ability to run tests on tens of thousands of different proteins simultaneously, observing how they interact with cells, other proteins, DNA and drugs.

As proteins can be placed and located precisely on a chip, it would be possible to scan large numbers of them at the same time but then isolate the data relating to individual proteins. These chips would allow large amounts of data to be generated with the minimum use of materials - especially rare proteins that are only available in very small amounts.

MRSA infections

Scientists at the University of Manchester in England have developed a new and fast method for making such biological chips, technology that could lead to quick testing for serious diseases, fast detection of MRSA infections and rapid discovery of new drugs.

Researchers working at the Manchester Interdisciplinary Biocentre (MIB) and the School of Chemistry unveiled a new technique for producing functional protein chips in a paper in the 22nd August issue of the Journal of the American Chemical Society.

Protein chips

The Manchester team of Lu Shin Wong, Jenny Thirlway and Jason Micklefield say the technical challenges of attaching proteins in a reliable way have previously held back the widespread application and development of protein chips.

Existing techniques for attaching proteins often results in them becoming fixed in random orientations, which can cause them to become damaged and inactive.

Current methods also require proteins to be purified first - and this means that creating large and powerful protein arrays would be hugely costly in terms of time, manpower and money.

Now researchers at The University of Manchester say they have found a reliable new way of attaching active proteins to a chip.

Biological chemists have engineered modified proteins with a special tag, which makes the protein attach to a surface in a highly specified way and ensures it remains functional.

The attachment occurs in a single step in just a few hours - unlike with existing techniques - and requires no prior chemical modification of the protein of interest or additional chemical steps.

DNA chips

DNA chips have revolutionised biological and medical science. For many years scientists have tried to develop similar protein chips but technical difficulties associated with attaching large numbers of proteins to surfaces have prevented their widespread application.

"The method we have developed could have profound applications in the diagnosis of disease, screening of new drugs and in the detection of bacteria, pollutants, toxins and other molecules," says Micklefield.

Researchers from Manchester are currently working as part of a consortium of several universities on a £3.1million project which is aiming to develop so-called nanoarrays. These would be much smaller than existing micro arrays and would allow thousands more protein samples to be placed on a single chip, reducing cost and vastly increasing the volume of data that could be simultaneously collected.

Microsizing genetic testing

Using new lab-on-a-chip technology, James Landers hopes to create a hand-held device that may eventually allow physicians, crime scene investigators, pharmacists, even the general public to quickly and inexpensively conduct DNA tests from almost anywhere, without need for a complex and expensive central laboratory.

"We are simplifying and miniaturising the analytical processes so we can do this work in the field, away from traditional laboratories, with very fast analysis times, and at a greatly reduced cost," said Landers, a University of Virginia professor of chemistry and mechanical engineering and associate professor of pathology.

Landers published a review in October of his research and the emerging field of lab-on-a-chip technology in the journal Analytical Chemistry.

"This area of research has matured enough during the last five years to allow us to seriously consider future possibilities for devices that would allow sample-in, answer-out capabilities from almost anywhere," he said.

Landers and a team of researchers, including mechanical and electrical engineers, with input from pathologists and physicians, are designing a hand-held device - based on a unit the size of a microscope slide - that houses many of the analytical tools of an entire laboratory, in extreme miniature. The unit can test, for example, a pin-prick-size droplet of blood, and within an hour provide a DNA analysis.

"In creating these automated micro-fluidic devices, we can now begin to do macro-chemistry at the microscale," Landers said.

Such a device could be used in a doctor's office, for example, to quickly test for an array of infectious diseases, such as anthrax, avian flu or HIV, as well as for cancer or genetic defects.

Because of the quick turn-around time, a patient would be able to wait only a short time on-site for a diagnosis. Appropriate treatment, if needed, could begin immediately.

Currently, test tube-size fluid samples are sent to external labs for analysis, usually requiring a 24- to 48-hour wait for a result.

"Time is of the essence when dealing with an infectious disease such as meningitis," Landers said. "We can greatly reduce that test time, and reduce the anxiety a patient experiences while waiting."

A lab-on-a-bead

Researchers at Wake Forest University in North Carolina, USA are using nanotechnology to search for new cancer-fighting drugs through a process that could be up to 10000 times faster than current methods.

The Lab-on-Bead process will screen millions of chemicals simultaneously using tiny plastic beads so small that 1000 of them would fit across a human hair. Each bead carries a separate chemical, which can be identified later if it displays the properties needed to treat cancer cells. One batch of nanoscopic beads can replace the work of thousands of conventional, repetitive laboratory tests.

"This process allows the beads to do the work for you," explains Jed Macosko, project director and assistant professor of physics at Wake Forest. "By working at this scale, we will be able to screen more than a billion possible drug candidates per day as opposed to the current limit of hundreds of thousands per day."

Other members of the research team at Wake Forest include co-principal investigator Martin Guthold, an associate professor of physics, and Keith Bonin, department chair and professor of physics.

Parallel processing

Macosko said the team and their collaborators at the University of Waterloo in Ontario, Canada, are developing a device that will automate the Lab-on-Bead process and permit parallel processing to attain faster screening results.

The Wake Forest researchers are also working with biotechnologists at Harvard University in Boston and Université Louis Pasteur in Strasbourg, France, which are providing the chemicals being screened for drug candidates.

Biotech company NanoMedica has already shown interest in commercialising the process

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