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BioMEMS Devices for Patterning and Sensing Biomolecules Stephan Koev, Peter Dykstra, Mariana Meyer    Collaborators - Dr. Gregory F. Payne, Univ. of Maryland Biotechnology Institute - Dr. William E. Bentley, Dept. of Chemical Eng., Univ. of Maryland - Dr. Gary W. Rubloff, Dept. of Materials and Nuclear Eng., Univ. of Maryland - Dr. Mariano Anderle, Istituto Trentino di Cultura - Dr. Liangli Yu, Dept. of Nutrition & Food Science, Univ. of Maryland    Research Overview Microfabrication enables patterned surfaces and three-dimensional structures to be constructed with precise spatial selectivity. Biomolecules (proteins and nucleic acids) offer exquisite capabilities for molecular recognition and sensing. Together, microfabrication and biotechnology offer the potential for the creation of miniaturized devices with enhanced abilities to sense contaminants, diagnose diseases, and screen drugs (e.g. MEMS Bio-Sensor). A current limitation is the integration of the biological system with the inorganic surface of typical devices. Through a collaborative project we are exploring an amine-rich biopolymer - the polysaccharide chitosan as an interface material that can be templated onto patterned surfaces and can be covalently coupled with sensing Biomolecules. Our Project group has developed a means to spatially localize biofunctional surfaces in specific locations by chitosan electrodeposition. Specifically, spatial control of the deposition is based on where electrodes are patterned on the surface while temporal control of deposition is achieved according to when the voltage is applied. This approach was combined with conventional MEMS fabrication to create photonic and micromechanical biosensors. The photonic sensors analyze localized biomolecules by optical excitation and collecting the emitted light. The micromechanical sensors detect the attachment of biomolecules to specific locations by means of their physical interaction with microfabricated structures. These demonstrations have shown that chitosan is a novel biomaterial that can serve to marry microfabrication with biotechnology. We hope this interface material will provide new opportunities for the creation of robust and reusable biosensors.    Thesis S. T. Koev, "Microcantilever Biosensors with Chitosan for the Detection of Nucleic Acids and Dopamine," Master's Thesis, University of Maryland, College Park, MD, October 2006. M. Powers, "Design, Fabrication and Testing of a Chitosan Based Optical Biosensor," Master's Thesis, University of Maryland, College Park, MD, July 2006.    Journal Papers S. T. Koev and R. Ghodssi, "Advanced Interferometric Profile Measurements through Refractive Media," Review of Scientific Instruments (RSI), Vol. 79, No. 9, pp. 093702, 2008. A. T. Lewandowski, H. Yi, G. F. Payne, R. Ghodssi, G. W. Rubloff, and W. E. Bentley, "Programmable Assembly of Active Pfs Enzyme onto Patterned Areas of Microfabricated Chips," Langmuir, Submitted March 2007. A. T. Lewandowski, H. Yi, X. Luo, G. F. Payne, R. Ghodssi, G. W. Rubloff, and W. E. Bentley, "Protein Assembly onto Microfabricated Devices through Enzymatic Activation of Fusion Pro-tag," Biotechnology and Bioengineering, Vol. 99, No. 3, pp. 499-507, 2008. X. W. Shi, A. T. Lewandowski, L. Q. Wu, H. C. Wu, R. Ghodssi, G. W. Rbuloff, W. E. Bentley, and G. F. Payne, " Chitosan Biotinylation and Electrodeposition for Selective Protein Assembly," Macromolecular Bioscience, Vol. 8, pp. 451-457, 2008. X. Luo, A. T. Lewandowski, H. Yi, G. F. Payne, R. Ghodssi, W. E. Bentley, G. W. Rubloff, "Programmable Assembly of a Metabolic Pathway Enzyme in a Pre-packaged Reusable BioMEMS Device," Lab on a Chip (LOC), Vol. 8, pp. 420-430, 2008. S. T. Koev, M. A. Powers, H. Yi, L-Q. Wu, W. E. Bentley, G. W. Rubloff, G. F. Payne, and R. Ghodssi, "Mechano-transduction of DNA Hybridization and Dopamine Oxidation through Electrodeposited Chitosan Network," Lab on a Chip (LOC), Vol. 7, pp. 103-111, 2007. C. Zhu, L.-Q. Wu, X. Wang, J.-H. Lee, D. S. English, R. Ghodssi, S. R. Raghavan, and G. F. Payne, "Reversible Vesicle Restraint in Response to Spatiotemporally-Controlled Electrical Signals: A Bridge Between Electrical and Chemical Signaling Modes," Langmuir, Vol. 23, 286-291, 2007. J. J. Park, X. Luo, H. Yi, T. M. Valentine, G. F. Payne, W. E. Bentley, R. Ghodssi, and G. W. Rubloff, "In situ Biomolecule Assembly in Completely Packaged Microfluidic Devices," Lab on a Chip (LOC), Vol. 6, pp. 1315-1321, 2006. L-Q Wu, M. K. McDermott, R. Ghodssi, and G. F. Payne, " Mimicking Biological Phenol Reaction Cascades to Confer Mechanical Function," Advanced Functional Materials, vol. 16, no. 15, pp.1967-1974, 2006. H. Yi, S. Nisar, S-Y Lee, M. A. Powers, W. E. Bently, G. F. Payne, R. Ghodssi, G. W. Rubloff, M. T. Harris, and J. N. Culver, "Patterened Assembly of Genetically Modified Viral Nanotemplates via Nucleic Acid Hybridization," Nano Letters, Vol. 5, No. 10, pp. 1931-1936, 2005. H. Yi, L-Q Wu, W. E. Bentley, R. Ghodssi, G. W. Rubloff, J. N. Culver, and G. F. Payne, "Biofabrication with Chitosan," Journal of Biomacromolecules, Vol. 6, No. 6, pp. 2881-2894, 2005. M. A. Powers, S. T. Koev, A. Schleunitz, H. Yi, V. Hodzic, W. E. Bentley, G. F. Payne, G. W. Rubloff, and R. Ghodssi, "A Fabrication Platform for Electrically Mediated Optically Active Biofunctionalized Sites in BioMEMS", Lab on a Chip (LOC), Vol. 5, pp. 583-586, 2005. H. Yi, L-Q. Wu, R. Ghodssi, G. F. Payne and W. E. Bentley, "Signal-Directed Sequential Assembly of Biomolecules onto Patterned Surfaces," Langmuir, Vol. 21, pp. 2104-2107, 2005. L-Q. Wu, R. Ghodssi, Y. A. Elabd and G. Payne, "Biomimetic Pattern Transfer," Advanced Functional Materials, Vol. 15, pp. 189-195, 2005. R. Fernandes, H. Yi, L-Q. Wu, G. W. Rubloff, R. Ghodssi, W. E. Bentley and G. F. Payne, "Thermo-Biolithography: A Technique for Patterning Nucleic Acids and Proteins," Langmuir, Vol. 20, pp. 906-913, 2004. H. Yi, L-Q. Wu, R. Ghodssi, G. W. Rubolff, G. F. Payne and W. E. Bentley, "A Robust Technique for Assembly of Nucleic Acid Hybridization Chips based on Electrochemically Templated Chitosan," Analytical Chemistry, Vol. 76, pp. 365-372, 2004. T. Chen, D.  A. Small, L-Q. Wu, G. W. Rubloff, R. Ghodssi, R. Vazquez-Duhalt, W. E. Bentley and G. F. Payne, "Nature-inspired Creation of Protein-Polysaccharide Conjugate and its Subsequent Assembly onto a Patterned Surface,"Langmuir Vol. 19, pp. 9382-9386, 2003. M. J. Kastantin, S. Li, A. P. Gadre, L-Q. Wu, G. W. Rubloff, W. E. Bentley, G. F. Payne and R. Ghodssi, "Integrated Fabrication of Polymeric Devices for Biological Applications," Sensors and Materials, Vol. 15, pp. 295-311, 2003 (Invited). R. Fernandes, L-Q. Wu, T. Chen, H. Yi, S. Li, G. W. Rubloff, R. Ghodssi, W. E. Bentley and G. F. Payne, "Electrochemically-Induced Deposition of a Polysaccharide Hydrogel onto a Patterned Surface," Langmuir, Vol. 19, pp. 4058-62, 2003. L-Q. Wu, H. Yi, S. Li, G. W. Rubloff, W. E. Bentley, R. Ghodssi and G. F. Payne, "Spatially-Selective Deposition of a Reactive Polysaccharide Layer onto a Patterned Template," Langmuir, Vol. 19, pp. 519-524, 2003. L-Q. Wu, A. P. Gadre, H. Yi, M. J. Kastantin, G. W. Rubloff, W. E. Bentley, G. F. Payne and R. Ghodssi, "Voltage-Dependent Assembly of the Polysaccharide Chitosan onto an Electrode Surface," Langmuir, Vol. 18, pp. 8620-25, 2002.    Conference Papers P. Dykstra, J. Hao, S. T. Koev, G. Payne, L. Yu, and R. Ghodssi, "An Optical MEMS Sensor for On-Chip Catechol Detection," IEEE Biomedical Circuits and Systems Conference (Biocas), Baltimore, MD, November 20-22, 2008. S. T. Koev, R. Fernandes, W. E. Bentley, and R. Ghodssi, "Optical Microcantilever Sensor for Liquid Samples," IEEE Biomedical Circuits and Systems Conference (Biocas), Baltimore, MD, November 20-22, 2008. S. Buckhout-White, X. Luo, D. Berlin, G. F. Payne, W. E. Bentley, R. Ghodssi and G. W. Rubloff, "A platform for in-situ sensing of biomolecules using a chitosan mediated SERS substrate fabricated inmicrofluidics," Proceedings of the 10th International Conference on Miniaturized Chemical and Biochemical Analysis Systems (MicroTAS), San Diego, CA, October 12-16, 2008. X. Luo, D. Berlin, S. Buckhout-White, W. E. Bentley, G. F. Payne, R. Ghodssi and G. W. Rubloff, "Minimizing parasitic reactions for enzyme-controlled metabolic pathways investigated in BIOMEMS," Proceedings of the 10th International Conference on Miniaturized Chemical and Biochemical Analysis Systems (MicroTAS), San Diego, CA, October 12-16, 2008. X. Luo, A. T. Lewandowski, D. Berlin, G. F. Payne, R. Ghodssi, W. E. Bentley, and G. W. Rubloff, "Applications and Improvements of BioMEMS for Chitosan-mediated Enzyme Assembly and Catalytic Activity," Proceedings of the First Shenyang International Colloquium on Microfluidics (SICOM I), pp. 204-207, Shenyang, China. October 21-24, 2007. X. Luo, A. T. Lewandowski, G. F. Payne, R. Ghodssi, W. E. Bentley, and G. W. Rubloff, "Enzyme Assembly and Catalytic Activity in a Reusable BioMEMS Plateform for Metabolic Engineering," Proceedings of the 11th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS), pp. 1616-1618, Paris, France, October 7-11, 2007. X. Luo, A. T. Lewandowski, H. Yi, G. F. Payne, R. Ghodssi, W. E. Bentley, and G. W. Rubloff, "Signal-Guided Sequential Assembly of Nano-Bio-Components in a Completely Packaged Microfluidic Environment," Proceedings of the 11th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS), pp. 784-786, Paris, France, October 7-11, 2007. A. T. Lewandowski, X. Luo, H. Yi, G. F. Payne, R. Ghodssi, G. W. Rubloff, and W. E. Bentley, "Programmable assembly of metabolic pathway enzymes onto patterned microfabricated devices," BMES 2007 Annual Fall Meeting, Los Angeles, CA, September 26-29, 2007. V. Badilita, I. Shamim, H. Yi, S.T. Koev, K. Gerasopoulos, and R. Ghodssi, "Chitosan-Mediated BioMEMS Platform for Optical Sensing," The 14th International Conference on Solid-State Sensors, Actuators, and Microsystems (Transducers '07), Lyon, France, June 10-14, 2007. S. T. Koev, V. Badilita, H. Yi, W. E. Bentley, G. F. Payne, G. W. Rubloff, and R. Ghodssi, "Chitosan for Selective Biofunctionalization of Microsystems," Materials Research Society 2007 Spring Meeting, San Francisco, CA, April 9-13, 2007. X. Luo, J. J. Park, H. Yi, A. T. Lewandowski, W. E. Bentley, G. F. Payne, R. Ghodssi, and G. W. Rubloff, "Chitosan-mediated Enzyme Assembly toward Rebuilding a Metabolic Pathway in the Microfluidic Environment," Materials Research Society 2007 Spring Meeting, San Francisco, CA, April 9-13, 2007. V. Badilita, M. A. Powers, S. T. Koev, H. Yi, and R. Ghodssi, "Integrated Biophotonic Hybridization Sensor Based on Chitosan-mediated Assembly," Photonics West 2007, San Jose, CA, January 20-25, 2007. X. Luo, J. J. Park, H. Yi, R. Ghodssi, G. W. Rubloff, "Biomolecule Assembly and Functionality in Completely Packaged Microfluidic Devices," American Vacuum Society 53rd International Symposium, San Francisco, CA, November 12-17, 2006. S. T. Koev, L-Q. Wu, G. F. Payne, and R. Ghodssi, "A Biomimetic MEMS Neurotransmitter Detector," Proceedings of the 10th International Conference on Miniaturized Chemical and Biochemical Analysis Systems (MicroTAS), pp. 1250-1252, Tokyo, Japan, November 5-9, 2006. R. Ghodssi, S. T. Koev, M. A. Powers, V. Badilita, H. Yi, L.-Q. Wu, W. E. Bentley, G. W. Rubloff,and G. F. Payne, "Chitosan: an Interface between Biology and Microsystems," 10th ICC - International Conference on Chiten & Chitosan, Montpellier, France, September 6-9, 2006, Invited Talk. S. T. Koev, M. A. Powers, V. Badilita, H. Yi, W. E. Bentley, G. F. Payne, G. W. Rubloff, and R. Ghodssi, "Chitosan for Biofunctionalization of Microsystems," Proceedings of the IEEE/NLM Life Science Systems and Applications Workshop, pp. 100-101, Bethesda, MD, July 13-14, 2006. H. Yi, R. Ghodssi, G. W. Rubloff, and J. N. Culver, "Chitosan-mediated Patterned Viral Nanotemplate Assembly onto Inorganic Substrates through Nucleic Acid Hybridization," Proceedings of the IEEE/NLM Life Science Systems and Applications Workshop, pp. 54-55, Bethesda, MD, July 13-14, 2006. J. J. Park, X. Luo, H. Yi, R. Ghodssi, and G.W. Rubloff, "In situ Biomolecule Assembly and Activity within Completely Packaged Microfluidic Devices," Proceedings of the IEEE/NLM Life Science Systems and Applications Workshop, pp. 88-89, Bethesda, MD, July 13-14, 2006. S. T. Koev, V. Badilita, M. A. Powers, H. Yi, W. E. Bentley, G. F. Payne, G. W. Rubloff, and R. Ghodssi, "Chitosan for Biofunctionalization of MEMS," 2006 Solid-State Sensor, Actuator and Microsystems Workshop (Hilton Head 2006), Open Poster Session, Hilton Head, SC, June 4-8, 2006. S. T. Koev, M. A. Powers, J. J. Park, H. Yi, L. Wu, W. E. Bentley, G. F. Payne, G. W. Rubloff, and R. Ghodssi, "Chitosan as a Functional Interface between Biology and Microsystems," 2nd ASM - IEEE EMBS Conference on Bio, Micro and Nanosystems, San Francisco, CA, January 15-18, 2006. L.-Q. Wu, H. Yi, T. Chen, W. Losert, D. English, G. W. Rubloff, R. Ghodssi, W. E. Bentley, and G. F. Payne, "Chitosan-mediated and spatially selective assembly of nanoparticles," American Chemical Society 230th Annual Meeting, Washington, DC, August 28-September 1, 2005. H. Yi, M. A. Powers, R. Ghodssi, G. W. Rubloff, G. F. Payne, J. N. Culver, W. E. Bentley, "Chitosan-Mediated Biofabrication: Interfacing Devices and Biology," AIChE Annual Meeting 2005, Cincinnati, OH, October 31 - November 4, 2005. S. T. Koev, M. A. Powers, H. Yi, and R. Ghodssi, "Toward a Chitosan-Based Micromechanical Biosensor," American Vacuum Society 52nd International Symposium, Boston, MA, October 30 - November 4, 2005. J. J. Park, T.M. Valentine, R. Ghodssi, and G. W. Rubloff, .Integrated Chip and Package Design for Surface-Controlled Bioreaction Processes with Robust, Reusable Fluidic Sealing,. The 9th International Conference on Miniaturized Chemical and Biochemical Analysis Systems (MicroTAS), Boston, MA, October 9-13, 2005. M. A. Powers, S.T. Koev, A. Scheunitz, H. Yi, V. Hodzic, W. E. Bentley, G.F. Payne, G. W. Rubloff, and R. Ghodssi, "Chitosan Based MEMS Biophotonic Sensor," The International Conference on Bio-Nano-Informatics Fusion, Marina Del Rey, CA, July 20-22, 2005. M. A. Powers, A. Schleunitz, H. Yi, C. Wu, W. E. Bentley, G. F. Payne, R. Ghodssi, "Toward a Biophotonic MEMS Cell Sensor," SPIE Microtechnologies for the New Millennium, Seville, Spain, May 9-11, 2005. J.J. Park, T. Valentine, M. Anderle, R. Ghodssi, and G. Rubloff, "Combinatorial Studies of Biopolymer Deposition and Surface Fictionalization for Bimolecular Reactions in BioMEMS Environments," IVC16, The  16th  International Vacuum Congress, Venice, Italy, June 28 - July 2, 2004. H. Yi, L.-Q. Wu, R. Ghodssi, G. W. Rubloff, G. F. Payne, and W. E. Bentley, "A Novel Biomolecule Assembly Technique onto Biosensor Surfaces," American Chemical Society (ACS) National meeting, San Diego, CA, March 13-17, 2005. H. Yi, L-Q. Wu, T. Chen, R. Ghodssi, G. W. Rubloff, G. F. Payne, and W. E. Bentley, "Spatially Resolved Biomolecule Assembly for Simple and Robust Biological Threat Detection," American Society for Microbiology (ASM) Biodefense 2004, Baltimore, MD, March 7-10 2004. H. Yi, L-Q. Wu, R. Ghodssi, G. W. Rubloff, G. F. Payne, and W. E. Bentley, "A Novel Platform for Assembling Biological Species onto Biosensor Surfaces," AIChE Annual Meeting, San Francisco, CA, November 16-21, 2003. L-Q. Wu, H. Yi, M. J. Kastantin, S. Li, D. A. Small, J. J. Park, G. W. Rubloff, R. Ghodssi, W. E. Bentley and G. F. Payne, "Chitosan - A Biomaterial Interface that can be Selectively Deposited onto Micropatterned Surfaces and Conjugated to Sensing Biomolecules, "American Vacuum Society 50th International Symposium, Baltimore, MD, November 2-7, 2003. C. Pederzolli, L. Lunelli, G. Speranza, R. Canteri, M. Anderle, J. J. Park, L-Q. Wu, H. Yi, R. Ghodssi, W. E. Bentley, G. F. Payne and G. W. Rubloff, "Material and Surface Characterization of Electrodeposited Polysaccharide Chitosan Film as a Platform for Biomolecular Reactions in BioMEMS Systems," American Vacuum Society 50th International Symposium, Baltimore, MD, November 2-7, 2003. G. F. Payne, T. Chen, L-Q. Wu, D. A. Small, H. Yi, R. Ghodssi, G. W. Rubloff and W. E. Bentley, "Assembly and Disassembly of Hydrogels to Entrap, Grow, and Release Cells," American Vacuum Society 50th International Symposium, Baltimore, MD, November 2-7, 2003. L-Q. Wu, R. Fernandes, H. Yi, D. A. Small, G. W. Rubloff, R. Ghodssi, W. E. Bentley and G. F. Payne, "Chitosan at the Interface of Microfabrication and Biotechnology," Advances in Chitin Science, EUCHIS.03, Montreal, Canada, August 2003. L-Q. Wu, H. Yi, S. Li, D. A. Small, J. J. Park, G. W. Rubloff, R. Ghodssi, W. E. Bentley and G. F. Payne, "Voltage-Programmable Biofunctionality in MEMS Environments Using Electrodeposition of a Reactive Polysaccharide," Transducers '03, The 12th Conference on Solid-State Sensors, Actuators, and Microsystems, Boston, MA, June 8-12, 2003. H. Yi, L-Q. Wu, R. Ghodssi, G. W. Rubloff, G. F. Payne and W. E. Bentley, "Novel Assembly Platform for Integrating Biological Species within MEMS Devices," ACS's 225th National Meeting, New Orleans, LA, March 23-27, 2003. H. Yi, L.-Q. Wu, S. Li, R. Ghodssi, G. W. Rubloff, G. F. Payne, and W. E. Bentley, "Electro-Deposited Chitosan as a Scaffold for Biomolecule Assembly," Mid-Atlantic Biochemical Engineering Consortium (MABEC) Annual Meeting, Baltimore, MD, March 14, 2003. L-Q. Wu, A. P. Gadre, H. Yi, M. J. Kastantin, S. Li, G. W. Rubloff, W. E. Bentley, G. F. Payne and R. Ghodssi, "Voltage-Dependent Assembly of the Polysaccharide Chitosan onto an Electrode Surface," American Vacuum Society 49th International Symposium, Denver, CO, November 3-8, 2002. A. Gadre, M. Kastantin, S. Li and R. Ghodssi, "An Integrated BioMEMS Fabrication Technology," Proceedings of the 2001 International Semiconductor Device Research Symposium (ISDRS), pp. 186-189, Washington D.C., December 5-7, 2001. A. Gadre, M. Kastantin, S. Li, E. Smela and R. Ghodssi, "An Integrated MEMS Fabrication Technology Using SU8 Negative Resist and Conducting Polymers," American Vacuum Society 48th International Symposium, San Francisco, CA, October 28 - November 2, 2001.