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Development of Bioprobe Integrated with Microneedle for Cellular Function Analysis
Keywords: microneedles, atomic force microscope (AFM), BioMEMS
Atomic force microscope (AFM) is an extremely powerful tool, not only for imaging biological molecules (DNA, proteins, etc.) and living cells, but also for characterizing localized mechanical properties such as hardness and elasticity. In addition, it allows the manipulation of single biological molecules and the measurement of biomolecular interactions with pico newton sensitivity. Therefore, it is being increasingly used as active tools in life sciences and medicine, particularly in structural biology and molecular cellular biology. In order to open up novel AFM applications in biological sciences, we have been developing a newly designed probe for AFM, named gbioprobeh, in which a conventional sharp tip is superseded by a hollow silicon dioxide (SiO2) microneedle connecting the root to a fluidic microchannel embedded into a silicon (Si) cantilever beam structure. The probe will be capable not only of performing AFM measurements but also of introducing desired biomolecules into living cells and extracting biomolecules expressed in the cells. The micromachining technique of a hollow SiO2 microneedle involves an anisotropic deep reactive ion etching (DRIE) process for producing thorough holes into a Si substrate as a needle mold followed by wet oxidation and an isotropic TMAH etching process for leaving a SiO2 microneedle structure. A typical microneedle fabricated here had an inner diameter of 3 m, an outer diameter of 5 m, and a length of 50 m with sharp tip shape (<100 nm). Furthermore, a circular-shaped microchannel (typically 5 m in diameter) was also successfully fabricated into Si by a combination of anisotropic DRIE and isotropic XeF2 etching together with wet oxidation. In addition, a direct bonding technique of Si substrates with a silicon dioxide insulating layer to be structured cantilever patterns was examined. By employing the developed techniques, the prototype bioprobes were successfully fabricated.
Norihisa Kato, Student
Toyohashi University of Technology
Toyohashi, Aichi 441-8580,

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