The use of microarrays for parallel screening of nucleic acid profiles has become an industry standard. Similar efforts for screening protein-protein interactions are gaining momentum, however, they remain limited by the requirement for relatively large sample volumes. One strategy for overcoming this problem is to significantly decrease the size and consequently the sample volume of the protein interaction assay. We report here on our progress over the last two years in the construction of ultraminiaturized, functional protein capture assays. Each one micron spot in these array-based assays covers less than 1/1000(th) of the surface area of a conventional microarray spot while still maintaining enough antibodies to provide a useful dynamic range. These nanoarray assays can be read by conventional optical fluorescence microscopy as well as by novel label-free methods such as atomic force microscopy. The size reduction realized by functional protein nanoarrays also creates opportunities for novel applications including highly multiplexed single cell analysis and integration with microfluidics and other "lab-on-a-chip" technologies.

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Chemical reactions at ultrasmall volumes are becoming increasingly necessary to study biological processes, to synthesize homogenous nanostructures and to perform high-throughput assays and combinatorial screening. Here we show that a femtolitre reaction can be realized on a surface by handling and mixing femtolitre volumes of reagents using a microfluidic stylus. This method, named microfluidic pen lithography, allows mixing reagents in isolated femtolitre droplets that can be used as reactors to conduct independent reactions and crystallization processes. This strategy overcomes the high-throughput limitations of vesicles and micelles and obviates the usually costly step of fabricating microdevices and wells. We anticipate that this process enables performing distinct reactions (acid-base, enzymatic recognition and metal-organic framework synthesis), creating multiplexed nanoscale metal-organic framework arrays, and screening combinatorial reactions to evaluate the crystallization of novel peptide-based materials.

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