With the advent of Next-Generation-Sequencing (NGS) technologies, an enormous volume of DNA sequencing data - in excess of one billion short reads per instrument per day - can be generated at low cost, placing genomic science within the grasp of everyday medicine. Mired in this voluminous data, a new problem has emerged: the assembly of the genome from the short reads. De novo assembly is an NP-hard problem and repetitive segments longer than the read length are the crux of the matter. It becomes exponentially harder to assemble a genome as the number of repeats grows. We propose to develop a nanopore device for de novo sequencing of a single DNA molecule with very long (>1 kbp) reads. Nanopore sequencing has the potential for very long reads, reducing the computational burden posed by alignment and genome assembly, while at the same time eliminating logistically challenging and error-prone amplification and library formation due to its exquisite single molecule sensitivity. Nanopore sequencing relies on the electrolytic current that develops when a DNA molecule, immersed in electrolyte, is forced by an electric field to translocate through a pore. Each nucleotide in the pore presents an energy barrier to the passage of ions, which blocks the current through the pore in a characteristic way. However, long, high fidelity reads demand stringent control over both the DNA configuration in the pore and the translocation kinetics. The configuration determines how the ions passing - read more >

Quorum sensing (QS) is a prime example of paracrine signaling in which a cell affects gene expression in a neighboring cell. According to the classic QS hypothesis, bacteria communicate and count their numbers by producing, releasing, and detecting small, diffusible, signaling molecules called autoinducers (AI). Quorum-sensing has also been implicated in the regulation of processes such as bioluminescence, swarming, swimming, and virulence. But despite its appeal, the QS hypothesis may not be an accurate description of all these phenomenon. To elucidate how cell-to-cell signaling works in bacteria, it is vital to control signal transmission between cells, yet most of the experiments used to test QS are done in a shaken culture flask, where the signal accumulates to a threshold concentration along a growth curve. It is difficult to emulate the diffusion, mixing and flow of signalsfound in vivo using a flask. In particular, bacteria naturally co-exist in sessile communities called biofilms. A biofilm is comprised of microcolonies of bacteria encapsulated in a hydrated matrix of polysaccharides, proteins and exopolymeric substances. The mass transport in a biofilm may exhibit gross deviations from Brownian diffusion - in some cases the diffusion coefficient is 50x smaller than in aqueous solutions - and so the chemistry can vary drastically over a short (100nm) distance and have a profound effect on signal transmission, production rate, and half-life. We have been exploring the physical parameters governing - read more >

Mobile/(broadband) wireless communications is changing everything. Portable communication devices like the cell phone, along with 3G, WLAN, Bluetooth are spurring the demand for high frequency, mixed signal integrated circuits that are inexpensive, reliable and have a long battery life. CMOS technology can satisfy these demands. The relentless scaling of CMOS toward nanometer-scale gate lengths has produced MOSFETs with digital and RF performance that is suitable for mixed-signal applications. The merit of a transistor depends on the circuit design. While large signal digital integrated circuits often use gate delay as a metric, the same loading conditions don't generally apply to RF circuits. Along with the RF performance, another prerequisite for the implementation of mixed circuits in CMOS is accurate, high frequency models for the MOSFET and passives. Specifically, the MOSFET model must accurately represent the power gain, input and output impedance and phase delay between the gate voltage and the drain current. A microwave table-based approach to modeling can be very accurate, but requires a large database obtained from numerous measurements and computationally intensive simulations - it becomes intractable for designing highly integrated CMOS communications circuits. Instead, a compact physics-based model is preferred, but a physics-based model has to be valid over a range of bias conditions, temperatures, and frequencies. Consequently, it has - read more >