Nasal potential difference to detect Na+ channel dysfunction in acute lung injury

Pulmonary fluid clearance is regulated by the active transport of Na+ and Cl- through respiratory epithelial ion channels. Ion channel dysfunction contributes to the pathogenesis of various pulmonary fluid disorders including high-altitude pulmonary edema (HAPE) and neonatal respiratory distress syndrome (RDS). Nasal potential difference (NPD) measurement allows an in vivo investigation of the functionality of these channels. This technique has been used for the diagnosis of cystic fibrosis, the archetypal respiratory ion channel disorder, for over a quarter of a century. NPD measurements in HAPE and RDS suggest constitutive and acquired dysfunction of respiratory epithelial Na+ channels. Acute lung injury (ALI) is characterized by pulmonary edema due to alveolar epithelial-interstitial-endothelial injury. NPD measurement may enable identification of critically ill ALI patients with a susceptible phenotype of dysfunctional respiratory Na+ channels and allow targeted therapy toward Na+ channel function. text of link

Ion channel gates: comparative analysis of energy barriers.

The energetic profile of an ion translated along the axis of an ion channel should reveal whether the structure corresponds to a functionally open or closed state of the channel. In this study, we explore the combined use of Poisson–Boltzmann electrostatic calculations and evaluation of van der Waals interactions between ion and pore to provide an initial appraisal of the gating state of a channel. This approach is exemplified by its application to the bacterial inward rectifier potassium channel KirBac3.1, where it reveals the closed gate to be formed by a ring of leucine (L124) side chains. We have extended this analysis to a comparative survey of gating profiles, including model hydrophobic nanopores, the nicotinic acetylcholine receptor, and a number of potassium channel structures and models. This enables us to identify three gating regimes, and to show the limitation of this computationally inexpensive method. For a (closed) gate radius of 0.4 nm

Impact of gate-source/drain channel architecture on the performance of an operational transconductance amplifier (OTA)

In this work, we report on the significance of gate-source/drain extension region (also known as underlap design) optimization in double gate (DG) FETs to improve the performance of an operational transconductance amplifier (OTA). It is demonstrated that high values of intrinsic voltage gain (A(VO_OTA)) > 55 dB and unity gain frequency (f(T_OTA)) similar to 57 GHz in a folded cascode OTA can be achieved with gate-underlap channel design in 60 nm DG MOSFETs. These values correspond to 15 dB improvement in A(VO_OTA) and three fold enhancement in f(T_OTA) over a conventional non-underlap design. OTA performance based on underlap single gate SOI MOSFETs realized in ultra-thin body (UTB) and ultra-thin body BOX (UTBB) technologies is also evaluated. A(VO_OTA) values exhibited by a DG MOSFET-based OTA are 1.3-1.6 times higher as compared to a conventional UTB/UTBB single gate OTA. f(T_OTA) values for DG OTA are 10 GHz higher for UTB OTAs whereas a twofold improvement is observed with respect to UTBB OTAs. The simultaneous improvement in A(VO_OTA) and f(T_OTA) highlights the usefulness of underlap channel architecture in improving gain-bandwidth trade-off in analog circuit design. Underlap channel OTAs demonstrate high degree of tolerance to misalignment/oversize between front and back gates without compromising the performance, thus relaxing crucial process/technology-dependent parameters to achieve 'idealized' DG MOSFETs. Results show that underlap OTAs designed with a spacer-to-straggle (s/sigma) ratio of 3.2 and operated below a bias current (IBIAS) of 80 mu A demonstrate optimum performance. The present work provides new opportunities for realizing future ultra-wide band OTA design with underlap DG MOSFETs.

Characterization of Nickel Germanide Schottky Contacts for the Fabrication of Germanium p-channel MOSFETs

Nickel germanide Schottky contacts, formed by rapid thermal annealing of thin nickel films, have been characterized on n-type germanium wafers for a range of RTA temperatures. The highest Schottky barrier heights for electrons (= 0.6-0.7 eV) were obtained for RTA temperatures of approximately 300°C. For this RTA schedule, the corresponding barrier height for holes is close to zero, ideal for Schottky contacted p-channel germanium MOSFETs. When the RTA temperature was increased to 400oC, a dramatic reduction in electron barrier height (< 0.1 eV) was observed. This RTA schedule, therefore, appears ideal for ohmic source/drain contacts to n channel germanium MOSFETs. From sheet resistance measurements and XRD characterization, nickel germanide formation was found to occur at 300oC and above. The NiGe phase was dominant for RTA temperatures up to at least 435oC.