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We developed a novel 512 x 320 tip-tilt micro mirror array (MMA) together with the entire related technology platform, including mirror fabrication process, integrated CMOS address circuitry and external drive electronics. The MMA itself consists of 2axis-tip-tilt actuators at 48μm pixel size, allowing a continuous pure tip-tilt motion up to 3.5° in arbitrary directions, fully calibratable at standard deviations of better than 0.025°. The mirrors are realized within a 2-level architecture defined by three structural layers, two for hinge and reinforcement suspension and one for the overlying mirror. They are fabricated by surface-micromachining within a fully CMOS compatible process. MMA programming is accomplished by an underlying CMOS backplane supporting drive voltages up to 27V and frame rates up to 3.6kHz.

We have developed a novel $\mathbf{512\ x\ 320}$ micro mirror array consisting of 2axis-tip-tilt actuators with $\mathbf{48}\mu\mathbf{m}$ pixel size, allowing a continuous, pure tip-tilt motion up to 3.5° in arbitrary directions, fully calibratable with standard deviations of better than 0.025°. The device is realized in a fully CMOS compatible process with an underlying integrated address circuitry.

Mechanical load is an important regulator of cardiac force. Stretching human atrial and ventricular trabeculae elicited a biphasic force increase: an immediate increase (Frank-Starling mechanism) followed by a further slow increase (slow force response, SFR). In ventricle, the SFR was unaffected by AT- and ET-receptor antagonism, by inhibition of protein-kinase-C, PI-3-kinase, and NO-synthase, but attenuated by inhibition of Na+/H+- (NHE) and Na+/Ca2+-exchange (NCX). In atrium, however, neither NHE- nor NCX-inhibition affected the SFR. Stretch elicited a large NHE-dependent [Na+]i increase in ventricle but only a small, NHE-independent [Na+]i increase in atrium. Stretch-activated non-selective cation channels contributed to basal force development in atrium but not ventricle and were not involved in the SFR in either tissue. Interestingly, inhibition of AT-receptors or pre-application of angiotensin II or endothelin-1 reduced the atrial SFR. Furthermore, stretch increased phosphorylation of atrial myosin light chain 2 (MLC2) and inhibition of myosin light chain kinase (MLCK) attenuated the SFR in atrium and ventricle. Thus, in human heart both atrial and ventricular myocardium exhibit a stretch-dependent SFR that might serve to adjust cardiac output to increased workload. In ventricle, there is a robust NHE-dependent (but angiotensin II- and endothelin-1-independent) [Na+]i increase that is translated into a [Ca2+]i and force increase via NCX. In atrium, on the other hand, there is an angiotensin II- and endothelin-dependent (but NHE- and NCX-independent) force increase. Increased myofilament Ca2+ sensitivity through MLCK-induced phosphorylation of MLC2 is a novel mechanism contributing to the SFR in both atrium and ventricle.

Background Cardiac glycosides are characterized by a narrow therapeutic range with Ca2+-overload and arrhythmias occurring at higher concentrations. Data on cardiac glycosides in isolated failing human myocardium are scarce and the frequency-dependent actions and toxicity of Strophanthidin have not yet been characterized. Aims To determine inotropic responses and toxicity of Strophanthidin in failing human myocardium. Methods and results Experiments were performed in trabeculae from 64 end-stage failing hearts. Developed force, and intracellular [Ca2+]i and [Na+]i were recorded with Strophanthidin (0.01 to 1 μmol/L; 37°C, 1 Hz) and compared to interventions with distinct mechanisms of action (elevated [Ca2+]o, Isoproterenol, and EMD57033). The effects of Strophanthidin on force–frequency behaviour were also assessed. Strophanthidin exerted concentration-dependent positive inotropic effects. These were paralleled by increases in intracellular [Na+] as well as increasing [Ca2+]i-transients and SR-Ca2+-load. At high concentrations (>0.5 μmol/L), Strophanthidin caused afterglimmers and aftercontractions, with declining developed force despite further increasing [Ca2+]i-transients. The force–frequency-relationship and diastolic function at higher pacing rates was worsened by Strophanthidin in a concentration-dependent manner. Conclusions Strophanthidin toxicity was dependent on concentration, calcium load, beating rate and β-adrenergic receptor activation. Our data support the view that low doses, heart rate control and additional β-adrenergic receptor blockade are essential in the use of cardiac glycosides in heart failure.

Background— Proton pump inhibitors are used extensively for acid-related gastrointestinal diseases. Their effect on cardiac contractility has not been assessed directly. Methods and Results— Under physiological conditions (37°C, pH 7.35, 1.25 mmol/L Ca 2+ ), there was a dose-dependent decrease in contractile force in ventricular trabeculae isolated from end-stage failing human hearts superfused with pantoprazole. The concentration leading to 50% maximal response was 17.3±1.3 μg/mL. Similar observations were made in trabeculae from human atria, normal rabbit ventricles, and isolated rabbit ventricular myocytes. Real-time polymerase chain reaction demonstrated the expression of gastric H + /K + –adenosine triphosphatase in human and rabbit myocardium. However, measurements with BCECF-loaded rabbit trabeculae did not reveal any significant pantoprazole-dependent changes of pH i . Ca 2+ transients recorded from field-stimulated fluo 3–loaded myocytes (F/F 0 ) were significantly depressed by 10.4±2.1% at 40 μg/mL. Intracellular Ca 2+ fluxes were assessed in fura 2–loaded, voltage-clamped rabbit ventricular myocytes. Pantoprazole (40 μg/mL) caused an increase in diastolic [Ca 2+ ] i by 33±12%, but peak systolic [Ca 2+ ] i was unchanged, resulting in a decreased Ca 2+ transient amplitude by 25±8%. The amplitude of the L-type Ca 2+ current ( I Ca,L ) was reduced by 35±5%, and sarcoplasmic reticulum Ca 2+ content was reduced by 18±6%. Measurements of oxalate-supported sarcoplasmic reticulum Ca 2+ uptake in permeabilized cardiomyocytes indicated that pantoprazole decreased Ca 2+ sensitivity (K d ) of sarcoplasmic reticulum Ca 2+ adenosine triphosphatase: control, K d =358±15 nmol/L; 40 μg/mL pantoprazole, K d =395±12 nmol/L ( P 2+ -activated force. Conclusions— Pantoprazole depresses cardiac contractility in vitro by depression of Ca 2+ signaling and myofilament activity. In view of the extensive use of this agent, the effects should be evaluated in vivo.

Rabbit ventricular myocardium is characterized by a biphasic response to stretch with an initial, rapid increase in force followed by a delayed, slow increase in force (slow force response, SFR). The initial phase is attributed to increased myofilament Ca(2+) sensitivity, but the mechanisms of the delayed phase are only incompletely understood. We tested whether stretch-dependent stimulation of Na(+)/H(+) exchange (NHE1) and consecutive changes in pH(i) and/or [Na(+)](i) may underlie the SFR.Isometric contractions of rabbit ventricular muscles were recorded in bicarbonate-containing Tyrode's (Tyrode) or bicarbonate-free HEPES-buffered solution (HEPES). Muscles were loaded with the Ca(2+) indicator aequorin, the pH indicator BCECF, or the Na(+) indicator SBFI and rapidly stretched from 88% (L(88)) to 98% (L(98)) of optimal length. The resulting immediate and slow increases in twitch force (1st phase and SFR) as well as changes in [Ca(2+)](i), [Na(+)](i), or pH(i) were quantified before and after inhibition of NHE1 by HOE 642 (3 microM) or reverse-mode Na(+)/Ca(2+) exchange (NCX) by KB-R 7943 (5 microM).In both Tyrode (n=21) and HEPES (n=22), developed force increased to approximately 160% during the 1st phase followed by a further increase to approximately 205% during the SFR. The SFR was accompanied by a 21% increase of the aequorin light transient (n=4; normalized to the 1st phase) and a approximately 3 mM increase in [Na(+)](i) (n=4-7). The SFR was also associated with an increase in pH(i). However, this increase was delayed and was significant only after the SFR had reached its maximum. The delayed pH(i) increase was larger in HEPES than in Tyrode. HOE 642 and/or KB-R 7943 reduced the SFR by approximately 30-40%. In addition, HOE 642 diminished the stretch-mediated elevation of [Na(+)](i) by 72% and the delayed alkalinization.The data are consistent with the hypothesis that SFR results from increases in [Ca(2+)](i) secondary to altered flux via NCX in part resulting from increases in [Na(+)](i) mediated by NHE1.

Background— Stretch elicits an immediate, followed by a delayed, inotropic response in various animal models and failing human myocardium. This study aimed to characterize functional differences in the stretch response between failing and nonfailing human myocardium. Methods and Results— Experiments were performed in muscle tissue from 86 failing and 16 nonfailing human hearts. Muscles were stretched from 88% to 98% of optimal length. Resulting immediate (Frank-Starling mechanism [FSM]) and delayed (slow-force response [SFR]) increases in twitch force were assessed before and after blockade of nitric oxide synthase, phosphatidylinositol-3-kinase, or reverse-mode Na + /Ca 2+ exchange. Stretch-induced changes in [Na + ] i were measured using fluorescent indicator sodium-binding benzofuran isophthalate-AM. Nitric oxide synthase isoform expression was quantified by Western blot analysis. FSM was comparable between nonfailing (227�8%) and failing (222�9%) myocardium, whereas the additional increase during SFR (≈5 minutes) was larger in nonfailing myocardium (to 126�3% versus 119�2% of force of FSM, respectively; P + ] i and stretch-induced increase in [Na + ] i were lower in nonfailing myocardium. Inhibition of the Na + /H + exchange largely reduced the increase in [Na + ] i and significantly blocked the SFR. In both groups, SFR was almost completely prevented by reverse-mode Na + /Ca + -exchanger inhibition. Although neuronal and inducible nitric oxide synthase expression were significantly upregulated in failing myocardium, inhibition of nitric oxide synthase and phosphatidylinositol-3-kinase had no effect on FSM or SFR. Conclusions— These data demonstrate a Na + -independent FSM and a Na + -dependent SFR in both nonfailing and failing human myocardium. The larger stretch-dependent increase in [Na + ] i in failing myocardium was associated with a blunted functional response, indicating impaired Na + -contraction coupling in the failing human heart.

Stretch is an important regulator of atrial function. The functional effects of stretch on human atrium, however, are poorly understood. Thus, we characterized the stretch-induced force response in human atrium and evaluated the underlying cellular mechanisms.Isometric twitch force of human atrial trabeculae (n = 252) was recorded (37 degrees C, 1 Hz stimulation) following stretch from 88 (L88) to 98% (L98) of optimal length. [Na(+)](i) and pH(i) were measured using SBFI and BCECF epifluorescence, respectively. Stretch induced a biphasic force increase: an immediate increase [first-phase, Frank-Starling mechanism (FSM)] to approximately 190% of force at L88 followed by an additional slower increase [5-10 min; slow force response (SFR)] to approximately 120% of the FSM. FSM and SFR were unaffected by gender, age, ejection fraction, and pre-medication with major cardiovascular drugs. There was a positive correlation between the amplitude of the FSM and the SFR. [Na(+)](i) rose by approximately 1 mmol/L and pH(i) remained unchanged during the SFR. Inhibition of Na(+)/H(+)-exchange (3 microM HOE642), Na(+)/Ca(2+)-exchange (5 microM KB-R7943), or stretch-activated channels (0.5 microM GsMtx-4 and 80 microM streptomycin) did not reduce the SFR. Inhibition of angiotensin-II (AngII) receptors (5 microM saralasin and 0.5 microM PD123319) or pre-application of 0.5 microM AngII, however, reduced the SFR by approximately 40-60%. Moreover, stretch increased phosphorylation of myosin light chain 2 (MLC2a) and inhibition of MLC kinase (10 microM ML-7 and 5 microM wortmannin) decreased the SFR by approximately 40-85%.Stretch elicits a SFR in human atrium. The atrial SFR is mediated by stretch-induced release and autocrine/paracrine actions of AngII and increased myofilament Ca(2+) responsiveness via phosphorylation of MLC2a by MLC kinase.

Displays based on organic light-emitting diodes (OLED) have rapidly developed and are commercially available since some time. However, in order to achieve large market penetration in new segments like lighting and optoelectronic, it is generally expected that the current status of the field has to advance in terms of manufacturing cost and integration possibilities. OLED devices with electrically doped transport layers show low operating voltage, high efficiency and long lifetime. In this paper we demonstrate that the concept of p- and n-type electrical doping can be applied under manufacturing conditions on the worldwide first vertical in-line fabrication setup for large area lighting applications. An in-linemanufactured highly efficient white-OLED-system will be presented. The driving of large area lighting tiles defines the resulting OLED lifetime and efficiency. In this paper we will present first results on the driving of large area lighting panels. Beside the lighting application the integration of highly efficient OLEDs for optoelectronic applications is an opportunity for innovative new applications. Microdisplays, integrated optocoupler and light barriers are few examples for the potential of OLEDs in optoelectronic applications. We will present results regarding the integration of highly efficient top-emitting PIN OLEDsTM for optoelectronic applications.

OLED technology may be excellently suitable for lighting applications by combining high efficiency, cost effective manufacturing and the use of low cost materials. Certain issues remain to be solved so far, including OLED brightness, color, lifetime, large area uniformity and encapsulation. Another aspect, that might be capable in addressing some of the mentioned issues, is OLED lighting electrical driving. We report on the design of a driving platform for OLED lighting test panels or substrates. It is intended for being a test environment for lighting substrates as well as demonstration/presentation environment. It is based on a 128-channel passive-matrix driver/controller ASIC OC2. Its key component is an MSP430-compatible 16-bit micro-controller core including embedded Flash memory (program), EEPROM (parameter), and RAM (data memory). A significant feature of the device is an electronic approach for improving the lifetime/uniformity behavior of connected OLED. The embedded micro-controller is the key to the high versatility of OC2, since by firmware modification it can be adapted to various applications and conditions. Here its application for an OLED lighting driving platform is presented. Major features of this platform are PC-control mode (via USB interface), stand-alone mode (no external control necessary, just power supply), on-board OLED panel parameter storage, flat geometry of OLED lighting panel carrier (board), AC and DC driving regimes, adjustable reverse voltage, dedicated user SW (PC/Windows-based), sub-tile patterning and single sub-tile control, combination of multiple channels for increasing driving current. This publication contains results of the project "High Brightness OLEDs for ICT & Next Generation Lighting Applications" (OLLA), funded by the European Commission.

The MEMS Phase Former Kit developed by the Fraunhofer IPMS is a complete Spatial Light Modulator system based on a piston-type Micro Mirror Array (MMA) for the use in high-resolution, high-speed optical phase control. It has been designed for an easy system integration into an user-specific environment to offer a platform for first practical investigations to open up new applications in Adaptive Optics. The key component is a fine segmented 240 x 200 array of 40 μm piston-type mirror elements capable of 400 nm analog deflection for a 2pi phase modulation in the visible. Each mirror can be addressed and deflected independently by means of an integrated CMOS backplane address circuitry at an 8bit height resolution. Full user programmability and control is provided by a newly developed comfortable driver software for Windows XP based PCs supporting both a Graphical User Interface (GUI) for stand-alone operation with pre-defined data patterns as well as an open ActiveX programming interface for a closed-loop operation with real-time data from an external source. An IEEE1394a FireWire interface is used for high-speed data communication with an electronic driving board performing the actual MMA programming and control allowing for an overall frame rate of up to 500 Hz. Successful proof-of-concept demonstrations already have been given for eye aberration correction in ophthalmology, for error compensation of leightweight primary mirrors of future space telescopes and for ultra-short laser pulse shaping. Besides a presentation of the basic device concept and system architecture the paper will give an overview of the obtained results from these applications.

For the correction of the human eye´s higher order aberrations in vision science we developed a new micromirror device with an monolithically integrated active CMOS address matrix providing a fine segmented array of 240 × 200 mirror elements across an active area of 9.8 × 8.0 mm2. The micromirrors possess a piston-type architecture for a pure phase shifting capability and are fabricated by means of aluminum surface-micromachining. Using a basic pixel size of 40 × 40 μm2 a mechanical stroke of at least 450 nm is obtained at address voltages below 30V, which is suitable for both active matrix addressing and a modulo 2π phase correction in the visible. Furthermore, an active CMOS address matrix similar to a DRAM was developed providing one switching transistor and one storage capacitor for each mirror cell. Those devices were fabricated within a special high voltage CMOS process providing a full analog address capability of up to 30V at an 8 bit resolution defined by the external driving board. Using interferometric surface profile and laser vibrometer measurements we will present latest experimental results of the mirrors’ electromechanical properties. For the first time those micromirror devices now also have been implemented into an ophthalmic diagnosis system for the measurement and correction of the human eye’s wave aberrations. Therefore, first results of the obtained aberration reduction as well as the impact on vision enhancement will be presented.

For an enhanced wavefront correction in Adaptive Optics especially in the case of high-order aberrations we developed a new monolithic integrated micromirror device providing a dense array of 240 x 200 piston-type mirror elements on top of an active CMOS address matrix for a closer wavefront approximation. After an analytical and numerical modeling the micromirrors were designed and fabricated by means of aluminum surface-micromachining. Using a basic pixel size of 40 x 40 µm 2 a mechanical stroke of at least 450 nm could be achieved at address voltages below 30V, which is suitable for both active matrix addressing and a phase correction modulo 2 in the visible. This also includes the option of an incremental increase of the actual mirror size in units of the address grid in order to allow for an extended analog deflection range. Furthermore, we designed and fabricated an active address matrix using a special high voltage CMOS process providing a full analog capability for address voltages up to 35V. Thereby, also a special light shielding as well as chemical mechanical polishing (CMP) for a high surface planarization have been incorporated. The completed devices were experimentally characterized by surface profile measurements using white light interferometry. After determining the deflection characteristic we successfully demonstrated the analog operation capability by programming different height patterns into the matrix at an 8 bit resolution provided by the external driving board. Keywords: Adaptive optics, wavefront correction, spatial light modulator, micromirror array, piston-type mirrors, surface micromachining, active-matrix addressing, finite element analysis, MOEMS