|
Research Interests
Prof. Schneider's work focuses on the development of novel colloidal and biomolecular materials for bioanalytical devices, pharmaceutical processing, and drug delivery. We are also developing methods to better characterize these biologically inspired materials using atomic force microscopy (AFM) and other aspects of nanotechnology.
DNA Purification using Peptide Nucleic Acid Amphiphiles
Peptide nucleic acids (PNAs) are synthetic materials that hybridize with complementary DNA and RNA with great sequence selectivity. We have developed a series of PNA amphiphiles that self-assemble in solution and bind tightly to nonpolar chromatographic media while retaining their unique DNA binding properties. We have demonstrated that both single-stranded and double-stranded DNA targets can be easily separated from non- target DNA by this tag-and-separate approach. Current efforts include scaling up the process for the large-scale purification of plasmid DNA, and using capillary electrophoresis to separate and concentrate target DNA or RNA in microfluidic, lab-on-a- chip analysis systems.
Intermolecular Force Measurement by Dynamic AFM
Tapping-mode AFM is a well established method for the imaging of soft surfaces. We have developed a methodology to interpret the attenuation of the AFM tip oscillation as the tip approaches soft surfaces. By accounting for and removing the effect of hydrodynamic forces and other viscous effects, we obtain the interaction force between tip and sample during a tapping mode experiment. By using this method, we can probe polymer chain dynamics and receptor-ligand interactions at very fast time scales. Currently, we are applying this method to investigate receptor-ligand interactions in polymer thin films similar to those used in biosensors.
Improved Mass Transfer in Bioanalytical Devices
Many biosensing modalities require that probes be immobilized on surfaces for detection using waveguides, acoustic vibrations, or fluorescence. Here, detection can be slow in highly dilute solutions due to the long (average) distances analytes must traverse to bind immobilized probes. We are working to accelerate the transport of these analytes to surface-bound probes by approaches that encourage surface diffusion or employ responsive polymers. Surface diffusion and binding kinetics are measured using fluorescence recovery after photobleaching (FRAP) and total-internal-reflection fluorescence (TIRF), respectively.
Highly Sensitive DNA Detection Using Functionalized Liposomes
Liposomes can serve as high-gain amplifiers for biomolecule detection by gravimetry, or when filled with dyes, fluorescence. We have developed chemistries that rigidly attach PNAs to liposomes for DNA detection with great sequence selectivity and high resolution. Currently we are implementing DNA-binding liposomes in capillary electrophoresis with laser-induced fluorescence (LIF) detection with an eye toward incorporation in microfluidic systems.
Representative Publications
"Characterization of Distance-Dependent Damping in Tapping-Mode AFM Force Measurements in Liquid," I. Nnebe and J.W. Schneider, Langmuir 20:3195-3201 (2004).
"Sequence-Specific Purification of Oligonucleotides using Peptide Nucleic Acid Amphiphiles in Hydrophobic Interaction Chromatography," J.P. Vernille and J.W. Schneider, in press for Biotech. Progress (2004).
"Direct Force Measurement of the Stability of Poly(ethylene glycol)- Poly(ethylenimine) Graft Films," I. Nnebe, R.D. Tilton, and J.W. Schneider, 276:306-316 J. Coll. Int. Sci. (2004).
"Peptide Nucleic Acid (PNA) Amphiphiles: Synthesis, Self-Assembly, and Duplex Stability," J.P. Vernille, B.F. Marques, and J.W. Schneider, submitted to Bioconj. Chem. (2004).
"Nanometer Scale Surface Properties of Supported Lipid Bilayers Measured with Hydrophobic and Hydrophilic Atomic Force Microscope Probes," J. Schneider, W. Barger, and G.U. Lee, Langmuir 19: 1899-1907 (2003).
"Surface Force Measurements of Electrostatic and Hydrogen Bonding Interactions between Bilayers of Glycine Amphiphiles," J. Schneider, P. Berndt, K. Haverstick, S. Kumar, S. Chiruvolu, and M. Tirrell, Langmuir 18: 3923-3931 (2002).
|