Development of Micro-Valves actuated by polypyrrole/gold bilayers

Many American women suffer from urinary incontinence that decreases their quality of life. To treat urinary incontinence without surgery, we are developing micro-valves that can be used in the bladder to open and close the flow of urine. A process was developed to microfabricate the valves on a Kapton substrate. The micro-valves are actuated by polypyrrole(PPy)/gold bilayers, and the open and closed states of the valve are controlled by application of a small voltage (< 1V). In order to show the feasibility of operating the micro-valves in the human bladder, the valves were tested under various pH (4 9), body temperature (30 42 oC), and pressure (10 110 cm of water) ranges. The power consumption of the valve was determined; a small silver oxide battery that provides 110 mA-hr of power can be used to power the valve for 30 days. Also, the lifetime of the valves, which was initially tens of cycles due to delamination of gold and polypyrrole from the substrate, was increased to 1,000 cycles. An adhesion layer of Cr between the Kapton and Au, as well as an electroplated layer of Au between the evaporated Au and electrochemically deposited PPy, were used to prevent the early delamination. Lastly, in order to optimize the performance of the bilayer, we wanted to determine the relationships among PPy thickness and bilayer hinge length, force, and bending angle. A new actuator was designed to collect bending angle and force. Larger bending angles were observed with longer hinges, and smaller bending angles with thicker PPy. Preliminary force measurements were made by stacking weights on the actuators. The thicker the PPy was, the heavier the weight it could lift

Fabrication and Sub-Assembly of Electrostatically Actuated Silicon Nitride Microshutter Arrays

We have developed a new microshutter array (MSA) subassembly. The MSA and a silicon substrate are flip-bonded together. The MSA has a new back side fabrication process to actuate the microshutters electrostatically, and the new silicon substrate has light shields. The microshutters with a pixel size of 100 x 200 sq micrometers are fabricated on silicon with thin silicon nitride membranes. The microshutters rotate 90 deg on torsion bars. The selected microshutters are actuated, held, and addressed electrostatically by applying voltages on the electrodes the front and back sides of the microshutters. The substrate has the light shield to block lights around the microshutters. Also, electrical connections are made from the MSA to a controller board via the substrate

2D Electrostatic Actuation of Microshutter Arrays

An electrostatically actuated microshutter array consisting of rotational microshutters (shutters that rotate about a torsion bar) were designed and fabricated through the use of models and experiments. Design iterations focused on minimizing the torsional stiffness of the microshutters, while maintaining their structural integrity. Mechanical and electromechanical test systems were constructed to measure the static and dynamic behavior of the microshutters. The torsional stiffness was reduced by a factor of four over initial designs without sacrificing durability. Analysis of the resonant behavior of the microshutter arrays demonstrates that the first resonant mode is a torsional mode occurring around 3000 Hz. At low vacuum pressures, this resonant mode can be used to significantly reduce the drive voltage necessary for actuation requiring as little as 25V. 2D electrostatic latching and addressing was demonstrated using both a resonant and pulsed addressing scheme

MEMS Microshutter Array System for James Webb Space Telescope

A complex MEMS microshutter array system has been developed at NASA Goddard Space Flight Center (GSFC) for use as a multi-object aperture array for a Near-Infrared Spectrometer (NIRSpec). The NIRSpec is one of the four major instruments carried by the James Webb Space Telescope (JWST), the next generation of space telescope after the Hubble Space Telescope retires. The microshutter arrays (MSAs) are designed for the selective transmission of light with high efficiency and high contrast. It is demonstrated in Figure 1 how a MSA is used as a multiple object selector in deep space. The MSAs empower the NIRSpec instrument simultaneously collect spectra from more than 100 targets therefore increases the instrument efficiency 100 times or more. The MSA assembly is one of three major innovations on JWST and the first major MEMS devices serving observation missions in space. The MSA system developed at NASA GSFC is assembled with four quadrant fully addressable 365x171 shutter arrays that are actuated magnetically, latched and addressed electrostatically. As shown in Figure 2, each MSA is fabricated out of a 4' silicon-on-insulator (SOI) wafer using MEMS bulk-micromachining technology. Individual shutters are close-packed silicon nitride membranes with a pixel size close to 100x200 pm (Figure 3). Shutters are patterned with a torsion flexure permitting shutters to open 90 degrees with a minimized mechanical stress concentration. In order to prevent light leak, light shields are made on to the surrounding frame of each shutter to cover the gaps between the shutters and the Game (Figure 4). Micro-ribs and sub-micron bumps are tailored on hack walls and light shields, respectively, to prevent sticktion, shown in Figures 4 and 5. JWST instruments are required to operate at cryogenic temperatures as low as 35K, though they are to be subjected to various levels of ground tests at room temperature. The shutters should therefore maintain nearly flat in the entire temperature range between 35K and 300K. Through intensive numerical simulations and experimental studies, an optically opaque and electrically conductive metal-nitride thin film was selected as a coating material deposited on the shutters with the best thermal-expansion match to silicon nitride - the shutter blade thin film material. A shutter image shown in Figure 6 was taken at room temperature, presenting shutters slightly bowing down as expected. Shutters become flat when the temperature decreases to 35K. The MSAs are then bonded to silicon substrates that are fabricated out of 6" single-silicon wafers in the thickness of 2mm. The bonding is conducted using a novel single-sided indium flip-chip bonding technology. Indium bumps fabricated on a substrate are shown in Figure 7. There are 180,000 indium bumps for bonding a flight format MSA array to its substrate. Besides a MSA, each substrate houses five customer-designed ASIC (Application Specific Integrated Circuit) multiplexer/address chips for 2-dimensional addressing, twenty capacitors, two temperature sensors, numbers of resistors and all necessary interconnects, as shown in Figure 8. Complete MSA quadrant assemblies have been successfully manufactured and fully functionally tested. The assemblies have passed a series of critical reviews required by JWST in satisfying all the design specifications. The qualification tests cover programmable 2-D addressing, life tests, optical contrast tests, and environmental tests including radiation, vibration, and acoustic tests. A 2-D addressing pattern with 'ESA' letters programmed in a MSA is shown in Figure 9. The MSAs passed 1 million cycle life tests and achieved high optical contrast over 10,000. MSA teams are now making progress in final fabrication, testing and assembly (Figure 10). The delivery of flight-format MSA system is scheduled at the end of 2008 for being integrated to the focal plane of the NIRSpec detectors

Corticomotoneuronal function and hyperexcitability in acquired neuromyotonia

Acquired neuromyotonia encompasses a group of inflammatory disorders characterized by symptoms reflecting peripheral nerve hyperexcitability, which may be clinically confused in the early stages with amyotrophic lateral sclerosis. Despite a clear peripheral nerve focus, it remains unclear whether the ectopic activity in acquired neuromyotonia receives a central contribution. To clarify whether cortical hyperexcitability contributes to development of clinical features of acquired neuromyotonia, the present study investigated whether threshold tracking transcranial magnetic stimulation could detect cortical hyperexcitability in acquired neuromyotonia, and whether this technique could differentiate acquired neuromyotonia from amyotrophic lateral sclerosis. Cortical excitability studies were undertaken in 18 patients with acquired neuromyotonia and 104 patients with amyotrophic lateral sclerosis, with results compared to 62 normal controls. Short-interval intracortical inhibition in patients with acquired neuromyotonia was significantly different when compared to patients with amyotrophic lateral sclerosis (averaged short interval intracortical inhibition acquired neuromyotonia 11.3 ± 1.9%; amyotrophic lateral sclerosis 2.6 ± 0.9%, P < 0.001). In addition, the motor evoked potential amplitudes (acquired neuromyotonia 21.0 ± 3.1%; amyotrophic lateral sclerosis 38.1 ± 2.2%, P < 0.0001), intracortical facilitation (acquired neuromyotonia −0.9 ± 1.3%; amyotrophic lateral sclerosis −2.3 ± 0.6%, P < 0.0001), resting motor thresholds (acquired neuromyotonia 62.2 ± 1.6%; amyotrophic lateral sclerosis 57.2 ± 0.9%, P < 0.05) and cortical silent period durations (acquired neuromyotonia 212.8 ± 6.9 ms; amyotrophic lateral sclerosis 181.1 ± 4.3 ms, P < 0.0001) were significantly different between patients with acquired neuromyotonia and amyotrophic lateral sclerosis. Threshold tracking transcranial magnetic stimulation established corticomotoneuronal integrity in acquired neuromyotonia, arguing against a contribution of central processes to the development of nerve hyperexcitability in acquired neuromyotonia

Multimodal assessment of estrogen receptor mRNA profiles to quantify estrogen pathway activity in breast tumors

Background Molecular markers have transformed our understanding of the heterogeneity of breast cancer and have allowed the identification of genomic profiles of estrogen receptor (ER)-α signaling. However, our understanding of the transcriptional profiles of ER signaling remains inadequate. Therefore, we sought to identify the genomic indicators of ER pathway activity that could supplement traditional immunohistochemical (IHC) assessments of ER status to better understand ER signaling in the breast tumors of individual patients. Materials and Methods We reduced ESR1 (gene encoding the ER-α protein) mRNA levels using small interfering RNA in ER+ MCF7 breast cancer cells and assayed for transcriptional changes using Affymetrix HG U133 Plus 2.0 arrays. We also compared 1034 ER+ and ER− breast tumors from publicly available microarray data. The principal components of ER activity generated from these analyses and from other published estrogen signatures were compared with ESR1 expression, ER-α IHC, and patient survival. Results Genes differentially expressed in both analyses were associated with ER-α IHC and ESR1 mRNA expression. They were also significantly enriched for estrogen-driven molecular pathways associated with ESR1, cyclin D1 (CCND1), MYC (v-myc avian myelocytomatosis viral oncogene homolog), and NFKB (nuclear factor kappa B). Despite their differing constituent genes, the principal components generated from these new analyses and from previously published ER-associated gene lists were all associated with each other and with the survival of patients with breast cancer treated with endocrine therapies. Conclusion A biomarker of ER-α pathway activity, generated using ESR1-responsive mRNAs in MCF7 cells, when used alongside ER-α IHC and ESR1 mRNA expression, could provide a method for further stratification of patients and add insight into ER pathway activity in these patients

Fabrication of MEMS Microshutter Arrays for Cryogenic Applications

Two-dimensional MEMS microshutter arrays are being developed for use as a high contrast field selector for the Near Infrared Spectrograph (NIRSpec) on the James Webb Space Telescope (JWST). We present details of microshutter array fabrication and give results of work done to optimize the flatness of microshutter elements through film stress control for both room temperature and cryogenic (35K) operation

Determination of genetic structure of germplasm collections: are traditional hierarchical clustering methods appropriate for molecular marker data?

Despite the availability of newer approaches, traditional hierarchical clustering remains very popular in genetic diversity studies in plants. However, little is known about its suitability for molecular marker data. We studied the performance of traditional hierarchical clustering techniques using real and simulated molecular marker data. Our study also compared the performance of traditional hierarchical clustering with model-based clustering (STRUCTURE). We showed that the cophenetic correlation coefficient is directly related to subgroup differentiation and can thus be used as an indicator of the presence of genetically distinct subgroups in germplasm collections. Whereas UPGMA performed well in preserving distances between accessions, Ward excelled in recovering groups. Our results also showed a close similarity between clusters obtained by Ward and by STRUCTURE. Traditional cluster analysis can provide an easy and effective way of determining structure in germplasm collections using molecular marker data, and, the output can be used for sampling core collections or for association studies

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version