Design and characterization of a current sensing platform for silicon-based nanopores with integrated tunneling nanoelectrodes

Solid-state nanopores have been gaining popularity in nano-biotechnology for single molecule detection, in particular for label-free high-throughput DNA sequencing. In order to address the improvement of the resolution/speed trade-off critical in this application, here we present a new two-channel current amplifier tailored for solid-state nanopore devices with integrated tunneling electrodes. The simultaneous detection of ion and tunneling currents provides enhanced molecule tracking capability. We describe the system design starting from a detailed noise analysis and device modeling, highlighting the detrimental role of the conductive silicon substrate and of all the stray capacitive couplings between the electrodes. Given the high input capacitance (0.1–1 nF), the input voltage noise has been carefully minimized choosing a discrete couple of matched low-noise JFETs as input stage, thus achieving an equivalent input noise of 1.5 nV/√Hz (corresponding to a current noise floor of 15 fA/√Hz at 10 kHz). Low-noise performance (11 pA rms noise integrated over a 75 kHz bandwidth) is preserved at a wide bandwidth (300 kHz) and high gain (100 MΩ) thanks to the adoption of an improved integrator/differentiator cascade topology. Furthermore, along with biasing networks and selectable low-pass filters, an AC-coupled channel providing additional gain has been introduced in order to “zoom” in the current signature during pore blockade events. Together with an experimental characterization of the system (and comparison with the noise performance of other instruments), the platform is validated by demonstrating the detection of λ-DNA with 20 nm pores.     

有限元方法计算J积分

本文讨论了有限元方法计算Ｊ积分，并依据能量区域积分方法编制了计算机程序，通 过对ＣＣＴ试块的计算表明程序可靠准确。     

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Book reviews

     

Ambient media for peripheral information display

In our everyday lives, we use surrounding living and working environments to arrange physical information artefacts such as books, pictures and calendars. However, when it comes to consumption of computer-based information, this is almost entirely based on attending to screens that separate us from our surroundings. In this paper, we explore the augmentative use of non-computer artefacts in our surroundings for peripheral display of digital information. We discuss system integration of such ambient media, the mapping of information to ambient media, and issues of flexibility and user control. Ambient media have been in everyday use in our work environment, and we report observations from which we conclude their utility as extensions to our digital information spaces.     

Responses of Human Cells to PAH-Induced DNA Damage

Benzo[ a ]pyrene (B[ a ]P) and dibenzo[ a,l ]pyrene (DB[ a,l ]P) induce cytochrome P450 (CYP) CYP1A1 and CYP1B1, which metabolize these polycyclic aromatic hydrocarbons (PAHs) into DNA-binding species. In order to detail roles of CYP1A1 and CYP1B1 in activation of DB[ a,l ]P to the diol epoxide, we here report the inhibition of CYP1A1 in human MCF-7 cells with phosphorodiamidate morpholino antisense oligomers (morpholinos). PAH-DNA adduct formation was also determined after treatment with morpholinos and B[ a ]P or DB[ a,l ]P. p53 is involved in DNA repair, cell cycle arrest, and apoptosis. Cells with normal p53 protein arrest in the G1 phase of the cell cycle on exposure to DNA-damaging agents (presumably allowing the cell sufficient time to repair damaged DNA prior to replication). Previous studies in human MCF-7 cells indicate that cells with PAH-DNA adducts escape cell cycle arrest and accumulate in the S phase. In the present study the effect of PAH-DNA adducts on the cell cycle were observed in human diploid fibroblasts (HDF). We found that treatment of HDF with the diol epoxide of DB[ a,l ]P causes cell cycle arrest in G 1 . An increase in DNA adduct formation with increase in concentration of dibenzo[ a,l ]pyrene diol epoxide {( m )- anti -DB[ a,l ]PDE} was also observed.     

Extensible Prototyping for pragmatic engineering of knowledge-based systems

Knowledge-based systems (KBSs) have been built and practically applied in various contexts for decades. Yet, they still challenge developers by their complexity: Apart from a sound knowledge base they likewise require comprehensive user interface (UI) and interaction design for supporting the task at hand optimally. However, current KBS-Engineering methodologies still mostly focus on knowledge base development, regarding UI/interaction design a more incidental, low priority task. Thus, the UI often is developed in a rather ad hoc manner, thereby neglecting the potential of experimental design and creating reusable solutions. The integration of (rapid) evolutionary prototyping activities with KBS Engineering offers the chance for incorporating UI/interaction design more prominently into the process while at the same time leveraging the overall development task; specifically, we propose Extensible Prototyping as a tailored prototyping approach and we suggest its integration with the Agile Process Model for knowledge-based systems in this paper. For practical support, we further introduce the customized prototyping and knowledge systems engineering tool ProKEt, and we report on practical experiences with applying both the approach and the tool.     

Styrene-Butadiene Polytelomers for Pressure-Sensitive Applications

Novel styrene-butadiene polymer latex compositions and their utility for pressure-sensitive and other adhesive applications are described. These compositions, termed polytelomers, are based on the concept of synthesising sequentially a low glass transition temperature, high molecular weight (polymeric) fraction, followed by a high glass transition, low molecular weight (telomeric) fraction, in an attempt to simulate the compounding of elastomeric adhesives. Some of the described compositions can exhibit multiphase morphology, having discrete styrene-rich domains surrounded by butadiene rich phase, both of these phases being embedded in a “honeycomb” carboxyl-rich phase. The compositions were characterized by dynamic mechanical spectroscopy and by electron transmission microscopy, as well as by molecular weight distribution and glass transition temperature range data. Examples of adhesive applications are also given.