A sensor being developed by a Sandia National Laboratories research team is claimed to be able to simultaneously detect thousands of biomolecules on a single platform. By integrating antibodies, DNA and other biomolecules on a single device, the number of laboratory instruments, volume of reagents required, time for analysis and the cost of performing effectively thousands of tests will all be reduced.
Sensor technology has been developing rapidly for some time. Many functions traditionally performed in quality control and process laboratories are now done online. The results are available in real time and any system or process adjustments are automated. This is great for industry. There is no backup of product waiting for lab results and out of spec product is eliminated or minimised.
Sandia's sensor technology will simplify online testing even more. The electrochemical sensor will use a unique surface chemistry to reliably and accurately detect thousands of differing biomolecules on a single platform.
The platform, a microfabricated chip, is just 2.5 cm2 in size. Several technological advances in microfabrication processes have increased the numbers of electrodes that can be produced on a sensor platform. A major challenge is how to pattern different biomolecules onto closely spaced micrometre-sized electrodes. The research team believes the answer lies in the electrodeposition of aryl diazonium salts.
The surface chemistry, produced by team members David Wheeler and Shawn Dirk, possesses several advantages over currently-used chemistry, Wheeler says.
"This diazonium-based surface chemistry can be selectively deposited onto several types of substrates by controlling the charge of the substrate in the diazonium solution," Wheeler says. "Because the deposition of the diazonium molecules is based on the application of an electrical potential, the selective patterning of individually addressable electrodes is possible. Upon deposition, covalent bonds are formed with the substrate, producing a highly stable film."
The chemistry is also compatible with a wide variety of biomolecules. DNA, antibodies, enzymes and peptides all have been patterned onto arrays at Sandia using this chemistry.
After treating the sensor with the target solution, the array is washed and treated with a different solution containing molecules that bind to the other end of the target biomolecule, forming a 'sandwich'. These secondary labels form an electroactive product that is detected by the electrode.
"A problem with the majority of existing biosensors is that they only look for one type of biomolecule at a time," says Jason Harper, research team member. "This can often lead to inaccurate or inconclusive results and limits the use of the sensor. Where our sensor differs is that multiple characteristics of several bioagent targets can be tested on a single chip."
For example, instead of using only an antibody that binds to the surface of an anthrax spore, the new Sandia sensor could test for several DNA sequences and internal and external proteins unique to anthrax. This provides numerous positive readings for the target agent or agents, significantly increasing confidence in the sensor results.
"Identification of several DNA sequences and protein markers will allow for detection of multiple targets and accurate discrimination between similar bioagent threats," Harper says.
Currently, the sensor arrays in the project allow for selective identification of nine biomolecules, Harper says. However, the work has kindled the interest of commercial sensor companies. The Sandia team recently travelled to Seattle to test their surface chemistry on a commercial array produced by CombiMatrix, a company that specialises in producing semiconductor arrays with more than 12,000 individually addressable electrodes in an area less than 2.5 cm square.
Because of the initial success, Sandia and CombiMatrix are pursuing a cooperative research and development agreement (CRADA) for further development of a sensor using Sandia's surface chemistry and CombiMatrix's electrode array, to ultimately test for thousands of biomolecules simultaneously.
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