Functionalized nanoparticles hold great promise in realizing highly sensitive and selective biodetection. We report a single disposable chip which is capable of carrying out a multi-step process that employs nanoparticles--a bio-barcode assay (BCA) for single protein marker detection. To illustrate the capability of the system, we tested for the presence of prostate specific antigen (PSA) in buffer solution and goat serum. Detection was accomplished at PSA concentrations as low as 500 aM. This corresponds to only 300 copies of protein analytes using 1 microL total sample volume. We established that the on-chip BCA for PSA detection offers four orders of magnitude higher sensitivity compared to commercially available ELISA-based PSA tests.

Microfluidic laboratory-on-a-chip (LOC) systems based on a modular architecture are presented. The architecture is conceptualized on two levels: a single-chip level and a multiple-chip module (MCM) system level. At the individual chip level, a multilayer approach segregates components belonging to two fundamental categories: passive fluidic components (channels and reaction chambers) and active electromechanical control structures (sensors and actuators). This distinction is explicitly made to simplify the development process and minimize cost. Components belonging to these two categories are built separately on different physical layers and can communicate fluidically via cross-layer interconnects. The chip that hosts the electromechanical control structures is called the microfluidic breadboard (FBB). A single LOC module is constructed by attaching a chip comprised of a custom arrangement of fluid routing channels and reactors (passive chip) to the FBB. Many different LOC functions can be achieved by using different passive chips on an FBB with a standard resource configuration. Multiple modules can be interconnected to form a larger LOC system (MCM level). We demonstrated the utility of this architecture by developing systems for two separate biochemical applications: one for detection of protein markers of cancer and another for detection of metal ions. In the first case, free prostate-specific antigen was detected at 500 aM concentration by using a nanoparticle-based bio-bar-code protocol on a parallel MCM system. In the second case, we used a DNAzyme-based biosensor to identify the presence of Pb 2؉ (lead) at a sensitivity of 500 nM in <1 nl of solution.laboratory-on-a-chip ͉ microfluidic breadboard ͉ polydimethylsiloxane

Previously, we reported a micro magnetic stir-bar mixer driven by an external rotating magnetic field and its rapid mixing performance in polydimethyl-siloxane (PDMS) channels. The PDMS piece with embedded fluid channels were manually aligned to a glass substrate and assembled. In this paper, we report the fabrication and testing results of a micro magnetic stir-bar monolithically integrated in parylene surface-micromachined channels with improved design features, including small tolerance of the stir-bar to channel wall (10 microm). Using of parylene based microchannels with improved design not only provides improved mixing, but also eliminates certain problems associated with PDMS-based channels. For example, porosity of PDMS causes evaporation and absorption of chemicals and thus channels made of PDMS are prone to cross-contamination. We have also demonstrated that the magnetic stir-bar can be used to pump liquid in micro channels.

We report on the development of a nanoplotter that consists of an array of microfabricated probes for parallel dip-pen nanolithography. Two types of device have been developed by using microelectromechanical systems micromachining technology. The first consists of 32 silicon nitride cantilevers separated by 100 µm, while the second consists of eight boron-doped silicon tips separated by 310 µm. The former offers writing and imaging capabilities, but is challenged with respect to tip sharpness. The latter offers smaller linewidths and increased imaging capabilities at the expense of probe density. Parallel generation of nanoscopic monolayer patterns with a minimum linewidth of 60 nm has been demonstrated using an eight-pen microfabricated probe array.

This paper reports a scanning probe contact printing (SP-CP) method for generating submicron patterns. It uses a novel scanning probe with an integrated elastomeric tip to transfer chemical materials onto a substrate. The SP-CP method combines the advantages of microcontact printing and dip-pen nanolithography to generate monolayer features chemisorbed on a gold surface. Arbitrary, connected features such as lines or blocks can be formed by connecting multiple dots, analogous to dot-matrix printing. We discuss the design and fabrication of the novel probes for SP-CP and how they can be used to generate sub-500-nm dots and lines of 1-octadecanethiol on a gold surface.

We report the development of a micromachined magnetic-bar micromixer for microscale fluid mixing in biological laboratory-on-a-chip applications. The mixer design is inspired by large scale magnetic bar mixers. A rotating magnetic field causes a single magnetic bar or an array of them to rotate rapidly within a fluid environment. A fabrication process of the magnetic bar mixer is developed. Results of fluid mixing in micro channels and chambers are investigated using experimental means and computer-aided fluid simulation.[729]

We report a general fabrication technology for realizing singular or arrayed probes for scanning probe microscopy (SPM) applications. This method allows SPM probes to be made of a variety of materials, including metal, polymer (e.g., polyimide, SU-8), elastomer and silicon nitride. The probe shank and tip may be made of different materials. The mould-and-transfer fabrication process can realize arrayed tips with uniform geometries across a wafer, a feature that is especially useful for the development of large arrayed SPM probes. For example, an array with 1 M probes has been made with good uniformity of tip geometries and tip-to-tip spacing of 50 µm. Several specific SPM probe applications based on this process have been demonstrated to illustrate the utility of this general fabrication method. We discuss SPM probes with tips made of metal or polymer materials (polyimide, SU-8 and elastomer), for surface characterization and nanolithography.

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