Biosensors Provide Near-Single-Molecule Sensitivity

In a Division of Chemical Physics session at the March Meeting, scientists at the Naval Research Laboratory reported developments of a novel, high-sensitivity biosensor for potential applications including environmental monitoring of airborne or waterborne contaminants, and clinical tests where ultra-sensitive detection is needed. Employed in a working device, an array of such biosensors would be able to perform immunoassays — the process by which the presence of antigens is detected — in about 10 minutes, much faster that other methods at these small concentrations.

Atomic force microscopes (AFMs) can directly measure the forces at the nanoscopic level, and the NRL researchers have used them to measure the force between two complementary strands of DNA. According to team member Gil Lee, they now hope to use a device based on AFM technology to detect biomolecules. They have developed a "force amplified biological sensor" (FABS), which uses the ultra-sensitive force transducers originally developed for AFMs to detect molecular recognition forces between DNA molecules, metal ions-chelators, -antibodies-antigens, or other ligand--receptor molecules. This gives FABS near-single-molecule sensitivity, an improvement of six to eight orders of magnitude over competitive techniques.

According to Lee, the device will soon be capable of detecting atto-molar amounts of various biological species such as cells, proteins, viruses and bacteria. The increased sensitivity of the device greatly reduces sampling requirements, requires no washing or amplification steps, and can be fully automated. The transducers are also micromachined, so FABS devices could eventually be miniaturized into portable units with low power requirements.

Currently, the prototype device works with an immunobead assay, consisting of an antibody attached to a sensitive cantilever beam. Next, an antigen in solution binds to the antibody. A second antibody, mounted on a micron-sized magnetic bead, also binds to the antigen, forming an antibody-antigen-antibody-bead sandwich. After washing away excess particles, a magnetic field is applied, which pulls out the particles, causing the cantilever to bend. The deflection of the cantilever is then measured, and by counting the beads one arrives at the antigen concentration in the solution.