Feb 3 2009
Scientists at the Naval Research Laboratory (NRL) are partnering with industry to develop a sensor system for biomolecules that could make a significant contribution to a variety of fields such as healthcare, veterinary diagnostics, food safety, environmental testing, and national security. NRL has developed a highly sensitive, portable biosensor system called the compact Bead Array Sensor System (cBASS®).
This portable magnetoresistive biosensor system utilizes an IC chip with an embedded giant magnetoresistance sensor array called the Bead ARray Counter (BARC). BARC detects paramagnetic microparticles that are used to label protein or DNA molecules of interest in a sandwich-based assay. The BARC chip is housed in an assay cartridge which contains an integrated fluid cell, microfludics bus and a PCMCIA connector to quickly interface with the compact Bead Array Sensor System (cBASS). cBASS includes a low power electromagnet, an automated fluidic system, and supporting electronics, all of which is controlled by a computer through a USB interface. Credit: NRL photograph
This innovative instrument utilizes a special integrated sensor chip, called the Bead ARray Counter (BARC®), which contains an embedded array of giant magnetoresistive sensors. With 64, 200 µm diameter sensors on the chip, BARC® has the potential to detect 64 different target analytes. Through the efforts of Dr. Lloyd Whitman, former head of the Surface Nanoscience and Sensor Technology Section at NRL, the NRL-developed technology has been licensed to Seahawk Biosystems Corporation in Rockville, Maryland, for further development in veterinary diagnostic, clinical diagnostic, and environmental applications.
Researchers at NRL began working on the magnetoelectronic biosensor concept more than a decade ago, under the leadership of Dr. Richard Colton and former NRL researcher Dr. David Baselt. Dr. Baselt used a quantum-mechanical effect called giant magnetoresistance (GMR). In simplistic terms, GMR materials are magnetic field-dependent resistors, i.e. their resistance changes when subjected to an externally applied magnetic field. GMR devices are typically constructed of alternating magnetic and non-magnetic metal thin-film multilayers that are only nanometers in thickness. Dr. Baselt looked specifically at a type of GMR called multilayer GMR in which the resistance of two thin antiferromagnetically exchange-coupled layers, separated by a thin non-magnetic conducting layer, can be altered by changing the moments of the ferromagnetic layers from anti-parallel to parallel. This change decreases the spin-dependent interfacial scattering of charge carriers resulting in a decrease in the resistance of the GMR material. Dr. Baselt realized this very sensitive phenomenon could have potential in the development of sensors for biological materials which are naturally biochemically specific, but are not usually magnetic. By attaching tiny paramagnetic particles to biomolecules, such as proteins or single-stranded DNA, scientists could then perform standard sandwich-type immuno or nucleic acid hybridization assays over the GMR sensors. The GMR sensors, each covered with complementary protein or single-stranded DNA (the "probe"), could then detect the magnetically labeled biomolecules (the "target") the assays were designed to identify.
A decade in the making, the instrumentation that reads the BARC® chip is called the "compact Bead Array Sensor System" (cBASS®). NRL's current engineering team is led by Dr. Cy Tamanaha, working with Dr. Jack Rife, Mr. Matthew Kniller, and Mr. Michael Malito. The engineering team has worked to make many improvements to cBASS®, including:
- a new quick assembly assay cartridge with an integrated microfluidic cell, PCMCIA interface and kinematic microfluidics bus;
- an onboard fully automated fluidic valve and pumping system;
- a new electromagnet design with lower power requirements;
- a faster data exchange via USB with the controlling computer; and
- a rechargeable battery unit for enhanced portability (they have shrunk cBASS® down to approximately the size of a shoebox).
Ultimately, the success of the NRL's magnetoelectronic biosensor depends on the performance of the microbead label assays whose continued development is currently spearheaded by Dr. Shawn Mulvaney with the assistance of Ms. Kristina Myers. Over the past several years, NRL has made significant strides in surface biofunctionalization and assay development. With these advances, they have achieved high sensitivity and speed; low, non-specific binding with femtomolar DNA and attomolar protein detection, typically in less than 10 minutes. One important characteristic of the NRL-developed assays is that the size of the microbead labels allows for either magnetoelectronic detection with GMR sensors, or optical enumeration with image processing software via a standard low-power microscope. The detection sensitivity under each method is nearly identical. However, there are differences in the two methods related to the size of the detection system and the cost of the consumables used.