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Published Mon, Jul 26, 2010 05:43 AM
Modified Mon, Jul 26, 2010 06:40 AM

Tiny beads speed drug development

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- Staff Writer
Tags: scitech

Wake Forest University physicists are ramping up drug development - by scaling down size.

Their new invention, called Lab-on-Bead, screens millions of chemical candidates at once to zero in on the few that could become disease-fighting drugs, using beads so tiny that 1,000 can fit across a human hair.

The findings, which were published this month online in the Journal of Molecular Recognition, can dramatically speed the process of developing effective treatments against diseases ranging from cancer to HIV.

The scientists are working with the bioscience startup NanoMedica Inc., which moved to Winston-Salem from New Jersey last month for the project.

With a promise that technology can reduce costs and speed development of new drugs, the group aims to market to pharmaceutical companies.

"Our slogan is 'discovering more with less' - and by 'less,' we mean both time and money," said physicist Jed Macosko, associate professor of physics at Wake Forest University and co-author of the report.

Pharmaceutical companies cook up millions of chemicals that might work as drugs in a process known as combinatorial chemistry, in which different molecular parts are mixed and matched in a kind of scientific equivalent to Mr. Potato Head.

The problem is that the vast majority of the products won't work, meaning that extensive testing of each one is required.

Currently, pharmaceutical and biotechnology companies test the smorgasbord of drugs in a type of assembly line that monitors how well each drug candidate interacts with each disease target.

These methods, which have dominated the market for the past decade, consume large amounts of material and use expensive robotic systems.

Wake Forest's development is unique because it miniaturizes in order to maximize - using fewer materials to screen more drugs in one fell swoop.

How the beads work

The key to the Lab-on-Bead technology is its nanoscopic beads, which help scientists filter a vast number of possibilities and find the few that may work.

Each bead is loaded with thousands of clones of DNA whose codes match molecular barcodes labeling each potential drug. When a cocktail of drug candidates is squirted onto the beads, each drug finds its way to its own bead.

With the drugs neatly collected on the beads, the next step is easy. The bead-drug mixture is added to a glass slide that has been previously coated with disease targets to form a kind of sticky spread. When a drug matches a disease target, it gets stuck to that point on the spread. The beads then get slurped up so the researchers can identify the drugs by their barcodes, allowing them to zoom in on the effective ones.

Macosko calls it the Goldilocks solution.

"A whole test tube full of molecules would be too big, but one molecule would be too small. The bead size is just right."

The researchers say the simple bead-based design may eventually allow the tool to be used to help diagnose as well as treat diseases. .

Market competitors

Nanotechnology is a competitive field, with laboratories across the countries scrambling to achieve similar aims.

"Everyone wants to detect molecules with higher sensitivity," said Robert Linhardt, a professor of chemistry and biological engineering at the Rensselaer Polytechnic Institute in New York. "People like to shrink analytical devices and shrink samples. This [Wake Forest] isn't theonly game in town."

NanoMedica Inc. has a timeline of one year to bring Lab-on-Bead to the market before it loses its rights over the patent. Because of the newness of the technology, it has no customers yet.

"We are pursuing business developments and potential partners to get a sense of its commercial viability," said Roger Cubicciotti, president and CEO of the company.

ilanay@nando.com or 919-829-4881

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Match made between barcodes

Lab-on-Bead technology depends on four parts so small that its developers can't even see what they're working on without the help of powerful microscopes.

First, there's the bead itself. Second, dangling off the bead are thousands of DNA clones that act as bait for the third ingredient: the molecular barcode. This is a special segment made of DNA or PNA (a chemical sister of DNA) that acts as the bead's molecular nametag. Last come the drug candidates themselves - millions of chemical combinations, created by pharmaceutical companies or research labs.

Like all would-be drugs, these candidates need to be tested for their ability to stick to disease targets. In Lab-on-Bead, each drug candidate has its own barcode tightly attached, and if the drug gets stuck on a disease target, its barcode allows researchers to determine which drug it is. Lining up millions of beads on a single glass slide enables researchers to test millions of chemicals at once, homing in on the few that can stick to medically important targets.


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