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Bioenergy & Defense

Jason C. Harper, Ph.D.


Research Summary - Publications - Education
Jason Harper

Senior Member of the Technical Staff
Bioenergy and Defense Technologies Department

(505) 284 - 8832
Jason.Harper@sandia.gov

Research Interests

Bio-materials

Stabilizing living cells & biomolecules

Selective patterning of biofunctional/selective surfaces

Electrochemistry

Surface chemistry

Low-cost bioanalytical platforms


Research Summary


My group focuses on development of novel biomaterials and bioanalytical platforms enabling the biodefense missions of Sandia National Labs.

We have developed, and continue to develop, biocompatible materials that can preserve long-term viability and function of biomolecules and living cells outside their natural environment. This allows us to exploit the unique properties of these biomolecules and cells to rapidly detect and identify chemical and biological threats.

Many techniques have been developed for biomolecule stabilization, especially protein and enzyme stabilization through entrapment. However, stabilization of living cells is significantly more challenging due to the more stringent requirements for the encapsulation matrix which must provide a functional bio/nano interface between the cells and the macroenvironment.

Using self-assembling biocompatible materials we have shown the first co-entrapment of eukaryotic and prokaryotic cells that remain viable and responsive, even when immobilized at intimate proximities.  This allowed us to detect multiple target molecules by mixing cell lines that would not be compatible under standard conditions.  We have also shown the first entrapment of viable cortical neuron cells that remain viable for 7+ days. Cortical neurons are arguably the most sensitive cells to maintain, and are extremely relevant to cell-based sensing as many chemical agents act on the nervous system.

    
Additionally, our group develops inexpensive, simple-to-operate, hand-held platforms for bioanalytical assay. One such device was recently featured on the front cover of the journal, Small (Harper at al. Small 2012, 8, 2743-2751). This approximately credit-card sized device houses communities of living cells, stabilized in a silica matrix, allowing the cells to survive and respond for 2+ months when stored under dry, ambient conditions. It also permitted simultaneous orthogonal detection modes – electrochemical, fluorescent, and colorimetric – increasing confidence in the sensor’s response.

This multidisciplinary work has a direct impact on areas as diverse as biocatalysis, controlled delivery of therapeutics, environmental and industrial process monitoring, early warning of warfare agents, bioelectronics, and tissue/organ replacement, and opens intriguing opportunities for integrating living cells with nanomaterials and macroscale systems.


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Publications

Journal Articles

2012 - present

Padilla, D., Pelowitz, J., Castillo, R., Epler, K., Harper, J., Brinker, C. J., Ashley, C., Carnes, E. “Encapsulation of Escherichia coli in a Phospholipid-Templated Silica Nanostructure Enables In situ Quantification of Protein Expression” 2012, submitted.

Harper, J. C., Brozik, S. M., Brinker, C. J., Kaehr, B. “Biocompatible Microfabrication of 3D Isolation Chambers for Targeted Confinement of Individual Cells and Their Progeny” 2012, Anal. Chem. 2012,84, 8985-8989.

Achyuthan, K. E., Allen, A., Arango, D. C., Harper, J. C., Whitten, D. G., Brozik, S. M. “High-throughput Screening of Transglutaminase Activity using Plasmonic Fluorescent Nanocomposites” Anal. Sci. 2012, 28, 905-910.

Harper, J. C., Edwards, T. L., Savage, T., Harbaugh, S., Kelley-Loughnane, N., Stone, M. O., Brinker, C. J., Brozik, S. M. “Orthogonal Cell-Based Biosensing: Fluorescent, Electrochemical, and Colorimetric Detection with Silica-Immobilized Cellular Communities Integrated with an ITO/Plastic Laminate Cartridge” Small, 2012, 8, 2743-2751. FRONT COVER.

Holland, T. D., Harper, J. C., Dolan, P. L., Manginell, M. M., Arango, D. C., Rawlings, J. A., Apblett, C. A., Brozik, S. M. “Rational Redesign of Glucose Oxidase for Improved Function in Biological Fuel Cells” 2012, PLoS ONE, 2012, 7, e37924.

Achyuthan, K. E., Achyuthan, A. M., Brozik, S. M., Dirk, S. M., Lujan, T., Romero, J., Whitten, D. G., Harper, J. C. “Plasmonic Fluorescent Nanocomposites of Cyanines Self-Assembled upon Gold Nanoparticle Scaffolds” Anal. Sci. 2012, 28, 433-438.

Zarzar, L. D., Swartzentruber, B. S., Harper, J. C., Dunphy, D. R., Brinker, C. J., Aizenberg, J., Kaehr, B. “Multiphoton Lithography of Nanocrystalline Platinum and Palladium for Site-Specific Catalysis in 3D Microenvironments” J. Am. Chem. Soc. 2012, 134, 4007-4010.

2009 – 2011

Edwards, T. L., Harper, J. C., Polsky, R., Lopez, D. M., Wheeler, D. R, Allen, A. C, Brozik, S. M. “A Parallel Microfluidic Channel Fixture Fabricated using Laser Ablated Plastic Laminates for Biodetection” Biomicrofluidics 2011, 5, 044115.

Harper, J. C., Lopez, D. M., Larkin, E., Economides, M. K., McIntyre, S. K., Alan, T. M., Tartis, M. S., Werner-Washburne, M., Brinker, C. J., Brozik, S. M., Wheeler, D. R. “Encapsulation of S. cerevisiae in Poly(glycerol) Silicate Derived Matrices: Effect of Matrix Additives and Cell Metabolic Phase on Long-Term Viability and Rate of Gene Expression” Chem. Mater. 2011, 23, 2555-2564.

Achyuthan, K. E., Achyuthan, A. M., Adams, P. D., Dirk, S. M., Harper, J. C., Simmons, B. A., Singh, A. K. “Supramolecular Self-Assembled Chaos: Polyphenolic Lignin’s Barrier to Cost-Effective Biofuels” Molecules 2010, 15, 8641-8688.

Harper, J. C., Khirpin,C. Y. Carnes, E. C., Ashley, C. E, Lopez, D. M., Savage, T., Jones, H. D. T., Davis, R. W., Nunez, D. E.; Brinker, L. M., Kaehr, B., Brozik, S. M., Brinker, C. J. “Cell-Directed Integration into 3D Lipid-Silica Nanostructured Matrices” ACN Nano 2010, 4, 5539-5550.

Carnes, E. C., Harper, J. C., Ashley, C. E., Lopez, D. M., Brinker, L. M., Liu, J., Singh, S., Brozik, S. M., Brinker, C. J. “Cell-Directed Localization and Orientation of a Functional Foreign Transmembrane Protein with a Silica Nanostructure” J. Am. Chem. Soc. 2009, 131, 14255-14257.

Polsky, R., Washburn, C. M., Montano, G., Liu, H., Edwards, T. L., Lopez, D. M., Harper, J. C., Brozik, S. M., Wheeler, D. R. “Reactive Ion Etching of Gold Nanoparticle-Modified Pyrolyzed Photoresist Films” Small 2009, 5, 2510-2513.

Harper, J. C., Brozik, S. M., Flemming, J. H., McClain, J. L., Polsky, R., Raj, D., Ten Eyck, G. A., Wheeler, D. R., Achyuthan, K. E. “Fabrication and Testing of a Microneedles Sensor Array for p-Cresol Detection with Potential Biofuel Applications” ACS App. Mater. Interfaces 2009, 1, 1591-1598.

Harper, J. C., Polsky, R., Wheeler, D. R., Arango, D. C., Brozik, S. M. “A Multi-Functional Thin Film Au Electrode Surface Formed by Consecutive Electrochemical Reduction of Aryl Diazonium Salts” Langmuir 2009, 25, 3282-3288.

Polsky, R., Stork, C. L., Wheeler, D. R., Steen, W. A., Harper, J. C., Washburn, C. M., Brozik, S. M.  “Multivariate Analysis for the Electrochemical Discrimination and Quantitation of Nitroaromatic Explosives” Electroanalysis 2009, 21, 550-556.

2007 – 2008

Polsky, R., Harper, J. C., Wheeler, D. R., Arango, D. C., Brozik, S. M. “Electrically Addressable Cell Immobilization Using Phenyl Boronic Acid Diazonium Salts” Angew. Chem., Int. Ed. 2008, 47, 2631-2634.

Polsky, R., Harper, J. C., Wheeler, D. R., Brozik, S. M. “Multi-Functional Electrode Arrays: Towards a Universal Detection Platform” Electroanalysis 2008, 20, 671-679.

Harper, J. C., Polsky, R., Wheeler, D. R., Brozik, S. M. “Maleimide-Activated Arly Diazonium Salts for Electrode Surface Functionalization with Biological and Redox Active Molecules” Langmuir 2008, 24, 2206-2211.

Polsky, R., Harper, J. C., Wheeler, D. R., Dirk, S. M., Arango, D. C., Brozik, S. M. “Electrically Addressable Diazonium Modified Antibodies for Multianalyte Electrochemical Sensor Applications” Biosens. Bioelectron. 2008, 23, 757-764.

Harper, J. C., Polsky, R., Wheeler, D. R., Dirk, S. M., Brozik, S. M. “Selective Immobilization of DNA and Antibody Probes on Electrode Arrays: Simultaneous Electrochemical Detection of DNA and Protein on a Single Platform” Langmuir 2007, 23, 8285-8287.

Harper, J. C., Polsky, R., Dirk, S. M., Wheeler, D. R., Brozik, S. M. “Electro-Addressable Selective Functionalization in Electrode Arrays: Catalytic NADH Detection Using Aryl Diazonium Modified Gold Electrodes” Electroanalysis 2007, 19, 1268-1274.

Polsky, R., Harper, J. C., Wheeler, D. R., Dirk, S. M., Rawlings, J. A., Brozik, S. M. “Reagentless Electrochemical Immunoassay Using Electrocatalytic Nanoparticle-Modified Antibodies” Chem. Commun.  2007, 2741-2743.

Polsky, R., Harper, J. C., Dirk, S. M., Arango, D. C., Wheeler, D. R., Brozik, S. M. “Diazonium Functionalized Horseradish Peroxidase Immobilized via Addressable Electrodeposition: Direct Electron Transfer and Electrochemical Detection” Langmuir 2007, 23, 364-366.

 

Book Chapters

Polsky, R., Harper, J. C., Brozik, S. M.  (2012). “Nanomaterial-Based Electrochemical DNA Detection” in Electrochemical DNA Biosensors. pp. 427-480.  City, Singapore: Pan Stanford Publishing.

Polsky, R., Harper, J. C., Brozik, S. M.  (2010). “Electrochemical Signaling with Modified Surfaces and Nanoparticles” in The Supramolecular Chemistry of Organic-Inorganic Hybrid Materials. pp. 273-296.  Hoboken, New Jersey: John Wiley & Sons, Inc.

Dolan, P. L., Harper, J. C., Brozik, S. M.  (2006). “Microbial Detection Systems” in Encyclopedia of Medical Devices and Instrumentation.  2nd ed. Vol. 4, pp. 373-383.  Hoboken, New Jersey: John Wiley & Sons, Inc.


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Education

2011 PhD, Chemical Engineering, University of New Mexico, Albuquerque, NM

2004 MS, Chemical Engineering, Purdue University, West Lafayette, IN

2002 BS, Chemical Engineering, New Mexico Institute of Mining and Technology, Socorro, NM

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