Surface Bioanalytical/Physical Chemistry: Particle-Based Biosensors

We have been developing barcoded metallic nanowires as encoded supports for multiplexed bioanalysis. The nanowires are encoded during electrochemical synthesis with stripes of different metals. Barcode readout is accomplished by brightfield reflectance imaging, typically using blue illumination to enhance contrast between Au and Ag stripes. A different bioassay can be performed on each different nanowire pattern; we have demonstrated both multiplexed DNA hybridization assays and sandwich immunoassays. In these experiments, a fluorescence image is acquired to provide assay response, followed by a reflectance image to enable assay identification. Importantly, such experiments can be performed using a conventional fluorescence optical microscopes, which are available in laboratories, hospitals, and many clinics.

For some biosensing applications, such as small clinics or in the field, fluorescence microscopy is unwieldy, and chip-based sensor arrays with electrical readout are preferable. We have two such sensing approaches under development.

For all of these sensors, the surface physical chemistry of the biomolecule/particle interface is critically important to sensor performance, and is one focus of our research.

Representative publications:

• “Striped metal nanowires as building blocks and optical tags,” Keating, C. D.; Natan, M. J. Advanced Materials 2003, 15, 451-454.

• “Submicrometer metallic barcodes,” Nicewarner-Peña, S. R.; Freeman, G. P.; Reiss, B. D.; He, L.; Peña, D. J.; Walton, I. D.; Cromer, R.; Keating, C. D., Natan, M. J. Science, 2001, 294, 137-141.

• “Stabilization of silver metal in citrate buffer: Barcoded nanowires and their bioconjugates,” Stoermer, R. L.; Sioss, J. A.; Keating, C. D. Chemistry of Materials 2005, 17, 4356-4361.

• “Barcoded metal nanowires: Optical reflectivity and patterned fluorescence,” Nicewarner-Peña, S. R.; Carado, A. J.; Shale, K. E.; Keating, C. D. Journal of Physical Chemistry B 2003, 107, 7360-7367.

• “Electrochemical synthesis and optical readout of striped metal rods with submicron features,” Reiss, B. D.; Freeman, R. G.; Walton, I. D.; Norton, S. M.; Smith, P. C.; Stonas, W. G.; Keating, C. D.; Natan, M. J. Journal of Electroanalytical Chemistry 2002, 522, 95-103.

• “Distance-dependent emission from dye-labeled oligonucleotides and striped Au/Ag nanowires: effect of secondary structure and hybridization efficiency,” Stoermer, R. L.; Keating, C. D. Journal of the American Chemical Society 2006, in press.