Electron-Beam Directed Layer-by-Layer Assembly of Dendrimer Scaffold for Biomolecule Patterning
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0921-T04-08
Electron-Beam Directed Layer-by-Layer Assembly of Dendrimer Scaffold for Biomolecule Patterning Parijat Bhatnagar1, Sonny S Mark2, Il Kim3, Hongyu Chen3, Brad Schmidt4, Michal Lipson4, and Carl A Batt5 1 Department of Biomedical Engineering, Cornell University, Ithaca, NY, 14853 2 Department of Microbiology, Cornell University, Ithaca, NY, 14853 3 Department of Food Science, Cornell University, Ithaca, NY, 14853 4 Department of Electrical and Computer Engineering, Cornell University, Ithaca, NY, 14853 5 Department of Biomedical Engineering, Microbiology, and Food Science, Cornell University, Ithaca, NY, 14853
ABSTRACT A method for patterning biomolecules using electron beam (e-beam) lithography has been developed. A non-biofouling poly(ethylene glycol) terminated self-assembled monolayer (SAM) was ablated by e-beam to create patterns aligned with the pre-existing features on the wafer. Aldehyde-terminated polyamidoamine dendrimers were assembled in a layer-by-layer fashion in the ablated patterns to allow the covalent immobilization of oligonucleotide probes. The functionality of the attached oligonucleotides was demonstrated by the hybridization of fluorescently labeled complementary target oligonucleotides. The hybridized target oligonucleotides could be stripped and the regenerated surface bound probe oligonucleotides could be rehybridized with complementary target oligonucleotide. INTRODUCTION The demand for improved sensitivity and throughput of biomolecular assays[1,2] has led to a considerable research effort to integrate nanofabricated sensors[3-5] on the microarray chips for early detection of disease biomarkers,[5,6] discovering cell-signal transduction pathways,[7] drug-discovery,[1,8] and low reagent consumption.[9] Patterning of biomolecules in functional state is an important requirement for the successful integration of nanofabrication with biosensors. Here, we have demonstrated an e-beam based approach for patterning biological macromolecules that does not expose them to the harsh nanofabrication processes and organic solvents.[10,11] Currently used poly (dimethylsiloxane) (PDMS) based soft lithographic techniques[12] cannot be used to create high resolution patterns as aligning the PDMS stamp with submicron features is non-trivial.[13] Polymer lift-off[14] and patterned gold[15] based biomolecule patterning involves extra microfabrication steps. Also, gold cannot be integrated in some sensors[3-5] due to interference with optical signal or conductivity of the sensor. Dip-Pen Nanolithography[16] and nanografting[17] approaches provide resolution at atomic scale but the process is slow.
EXPERIMENT Patterning reactive aldehyde functionalized PAMAM on inert PEG-SAM surface: A silicon wafer with 20 nm thermal SiO2 was plasma cleaned and PEG-SAM was assembled in vapor phase at the chamber pressure of 0.5 Torr using short chain (single PEG unit) 2-[methoxy(polyethylenoxy)propyl] trichlorosilane (MPEGTCS) (MVD-100, Applied Microstructures, Inc., San Jose, CA). The process was repeated four t
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