We report a simple, reliable high-throughput method for patterning passivated silicon with reactive organic monolayers and demonstrate selective functionalization of the patterned substrates with both small molecules and proteins. The approach completely protects silicon from chemical oxidation, provides precise control over the shape and size of the patterned features in the 100 nm domain, and gives rapid, ready access to chemically discriminated patterns that can be further functionalized with both organic and biological molecules.

I f microfluidic devices capable of rapid genetic analysis are to affect clinical diagnostics, they ultimately must be capable of carrying out more than ultra-rapid electrophoretic separations. The last half decade has seen a groundswell of activity in defining miniaturized DNA sample preparation methodologies that can be integrated with chip-based electrophoretic separations. Successfull integration of PCR-based DNA amplification and solid-phase DNA sets the stage for integrated microminiaturized analytical systems with sample in-answer out capabilities. Here we provide a brief review of the state of the art on the microfluidic integration of sample preparation processes with discussion of several systems with highly integrated capabilities, including one capable of detection of infectious agents present in complex biofluids in less than 30 min. This overview is used as a launch point to discuss the design and functionality of similar devices capable of accepting a whole blood or fine-needle aspirate sample, purifying the DNA, amplifying target sequences of the T-cell receptor-g gene, and eletrophoretically resolving the products for detection of a signature consistent with monoclonality. We describe the details of the early experimental success in defining the individual chip-based processes required for an integrated T-cell lymphoma chip, with a vision to a device that provide sample in-answer out capabilities for diagnosing certain blood cancers in roughly 1 h.

Here we report a simple, robust approach to patterning functional SAMs on germanium. The protocol relies on catalytic soft-lithographic pattern transfer from an elastomeric stamp bearing pendant immobilized sulfonic acid moieties to an NHS-functionalized bilayer molecular system comprising a primary ordered alkyl monolayer and a reactive ester secondary overlayer. The catalytic polyurethane-acrylate stamp was used to form micrometer-scale features of chemically distinct SAMs on germanium. The methodology represents the first example of patterned SAMs on germanium, a semiconductor material.

In atomic force microscope based force spectroscopy, it is often necessary to minimize the tip-sample contact force. While it is possible to control the contact force using force feedback, this method is susceptible to sensor drift and is often under-utilized due to the noise associated with the feedback process. Here we present a method to control the tip-sample contact force for repeated pulling cycles without relying on force feedback or tedious user-controlled z-stage step increments. The custom pulling program uses the data recorded during the previous retraction cycle to automatically reposition the sample surface to account for changes in topography and system drift. Using this method we were able to complete 250 automated pulling cycles, 76% of which had evidence of tip-sample contact. Of those pulling cycles with tip-sample contact, the average contact force was 83 pN, with the maximum contact force not exceeding 292 pN.

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