A high-sensitivity micromachined biosensor

The Force Amplified Biological Sensor (FABS) is a desktop or portable instrument currently under development at the Naval Research Laboratory. FABS will use a rapid, automated immunoassay to detect analytes such as proteins, viruses, and bacteria. The assay uses forces produced by micron-sized magnetic particles to pull on antibody-antigen bonds. Microfabricated piezoresistive cantilevers measure the resulting piconewton-level forces with sufficient sensitivity to detect single antibody-antigen bonds. These forces also serve to characterize the bonds, allowing FABS to distinguish specific antibody-antigen bonds from nonspecific interactions.

[1]  J. Calvert Lithographically Patterned Self-Assembled Films , 1995 .

[2]  Thomas Thundat,et al.  Vapor detection using resonating microcantilevers , 1995 .

[3]  H. Gaub,et al.  Adhesion forces between individual ligand-receptor pairs. , 1994, Science.

[4]  C. Dulcey,et al.  Fabrication of patterned DNA surfaces. , 1996, Nucleic acids research.

[5]  Matthias Rief,et al.  Sensing specific molecular interactions with the atomic force microscope , 1995 .

[6]  M. Ohta,et al.  Atomic resolution imaging of InP(110) surface observed with ultrahigh vacuum atomic force microscope in noncontact mode , 1996 .

[7]  C. Quate,et al.  Atomic resolution with an atomic force microscope using piezoresistive detection , 1993 .

[8]  B Manning,et al.  Immunosensors in medical diagnostics--major hurdles to commercial success. , 1992, Biosensors & bioelectronics.

[9]  Gerber,et al.  Atomic force microscope. , 1986, Physical review letters.

[10]  James K. Gimzewski,et al.  Observation of a chemical reaction using a micromechanical sensor , 1994 .

[11]  K. Hempel,et al.  Improvement of sensitivity of the vibrating reed magnetometer , 1988 .

[12]  V. Hlady,et al.  Effects of Discrete Protein-Surface Interactions in Scanning Force Microscopy Adhesion Force Measurements. , 1995, Langmuir : the ACS journal of surfaces and colloids.

[13]  W. Dressick,et al.  Selective Attachment of Synthetic DNA to Self-Assembled-Monolayer Functionalized Surfaces , 1993 .

[14]  Richard J. Colton,et al.  Biosensor based on force microscope technology , 1996 .

[15]  M. Hegner,et al.  Measuring Molecular Adhesion with Force Microscopy , 1995 .

[16]  C P Price,et al.  Immunosensors: technology and opportunities in laboratory medicine. , 1996, Clinical chemistry.

[17]  Gil U. Lee,et al.  Chemically‐Specific Probes for the Atomic Force Microscope , 1996 .

[18]  B D Ratner,et al.  Direct measurement of hydrogen bonding in DNA nucleotide bases by atomic force microscopy. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Paul K. Hansma,et al.  Quantized adhesion detected with the atomic force microscope , 1992 .

[20]  M. Hegner,et al.  Specific antigen/antibody interactions measured by force microscopy. , 1996, Biophysical journal.

[21]  Thomas W. Kenny,et al.  Low‐stiffness silicon cantilevers for thermal writing and piezoresistive readback with the atomic force microscope , 1996 .

[22]  J M Calvert,et al.  Use of thiol-terminal silanes and heterobifunctional crosslinkers for immobilization of antibodies on silica surfaces. , 1989, Analytical biochemistry.

[23]  Jeffrey M. Calvert,et al.  Lithographic patterning of self‐assembled films , 1993 .

[24]  F. Ligler,et al.  New approach to producing patterned biomolecular assemblies , 1992 .

[25]  B D Ratner,et al.  The relationship between ligand-binding thermodynamics and protein-ligand interaction forces measured by atomic force microscopy. , 1995, Biophysical journal.

[26]  G. Hubler,et al.  The pitting behavior of silicon nitride ion beam assisted deposited coatings on aluminum , 1992 .

[27]  L. Kricka Selected strategies for improving sensitivity and reliability of immunoassays. , 1994, Clinical chemistry.

[28]  H. Nygren,et al.  Kinetics of antigen-antibody reactions at solid-liquid interfaces. , 1988, Journal of immunological methods.

[29]  Calvin F. Quate,et al.  Microfabrication of cantilever styli for the atomic force microscope , 1990 .

[30]  H. Gaub,et al.  Intermolecular forces and energies between ligands and receptors. , 1994, Science.

[31]  Gil U. Lee,et al.  Direct measurement of the forces between complementary strands of DNA. , 1994, Science.

[32]  T. Kuji,et al.  Microstructural studies of NdFeB powders produced by gas atomization , 1994 .

[33]  David A. Kidwell,et al.  Sensing Discrete Streptavidin-Biotin Interactions with Atomic Force Microscopy , 1994 .

[34]  Mark E. Welland,et al.  Atomic force microscopy stress sensors for studies in liquids , 1996 .

[35]  F. Ligler,et al.  Fabrication of surfaces resistant to protein adsorption and application to two-dimensional protein patterning. , 1993, Analytical biochemistry.

[36]  N. Amer,et al.  Novel optical approach to atomic force microscopy , 1988 .

[37]  H Schindler,et al.  Detection and localization of individual antibody-antigen recognition events by atomic force microscopy. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Walter J. Dressick,et al.  Deep UV Photochemistry of Chemisorbed Monolayers : Patterned Coplanar Molecular Assemblies " , .

[39]  D. Anselmetti,et al.  Binding strength between cell adhesion proteoglycans measured by atomic force microscopy , 1995, Science.