Low Power Compact 3D-Constructed AlScN Piezoelectric MEMS Mirrors for Various Scanning Strategies.

In this paper, the newly developed 3D-constructed AlScN piezoelectric MEMS mirror is presented. This paper describes the structure and driving mechanism of the proposed mirror device, covering its driving characteristics in both quasi-static and resonant scan modes. Particularly, this paper deals with various achievable scan patterns including 1D line scan and 2D area scan capabilities and driving methods to realize each scanning strategy. Bidirectional quasi-static actuation along horizontal, vertical, and diagonal scanning directions was experimentally characterized and even under a low voltage level of ±20 V, a total optical scan angle of 10.4° was achieved. In addition, 1D line scanning methods using both resonant and non-resonant frequencies were included and a total optical scan angle of 14° was obtained with 100 mVpp under out-of-phase actuation condition. Furthermore, 2D scan patterns including Lissajous, circular and spiral, and raster scans were realized. Diverse scan patterns were realized with the presented AlScN-based MEMS mirror device even under a low level of applied voltage. Further experiments using high voltage up to ±120 V to achieve an enhanced quasi-static scan angle of more than 20° are ongoing to ensure repeatability. This multi-functional MEMS mirror possesses the potential to implement multiple scanning strategies suitable for various application purposes.

A smartphone application of alcohol resilience treatment for behavioral self-control training.

High relapse rate is one of the most prominent problems in addiction treatment. Alcohol Resilience Treatment (ART), an alcohol addiction therapy, is based on Cue Exposure Treatment, which has shown promising results in preliminary studies. ART aims at optimizing the core area of relapse prevention, and intends to improve patients' capability to withstand craving of alcohol. This method emphasizes the interplay of resilience and resourcefulness. It contains 6 sessions with different topics according to the stage of treatment circuit, and each session consists of 6 steps. Due to the purity and structure of the treatment rationale, it is realistic, reasonable and manageable to transform the method into a smartphone application. An ART app in Android system and an accessory of bilateral tactile stimulation were developed and will be used in a study with behavioral self-control training. This paper presents the design and realization of the smartphone based ART application. The design of a pilot study, which is to examine the benefits of a smartphone application providing behavioral self-control training, is also reported in this paper.

Highly-integrated lab-on-chip system for point-of-care multiparameter analysis.

A novel innovative approach towards a marketable lab-on-chip system for point-of-care in vitro diagnostics is reported. In a consortium of seven Fraunhofer Institutes a lab-on-chip system called "Fraunhofer ivD-platform" has been established which opens up the possibility for an on-site analysis at low costs. The system features a high degree of modularity and integration. Modularity allows the adaption of common and established assay types of various formats. Integration lets the system move from the laboratory to the point-of-need. By making use of the microarray format the lab-on-chip system also addresses new trends in biomedicine. Research topics such as personalized medicine or companion diagnostics show that multiparameter analyses are an added value for diagnostics, therapy as well as therapy control. These goals are addressed with a low-cost and self-contained cartridge, since reagents, microfluidic actuators and various sensors are integrated within the cartridge. In combination with a fully automated instrumentation (read-out and processing unit) a diagnostic assay can be performed in about 15 min. Via a user-friendly interface the read-out unit itself performs the assay protocol, data acquisition and data analysis. So far, example assays for nucleic acids (detection of different pathogens) and protein markers (such as CRP and PSA) have been established using an electrochemical read-out based on redoxcycling or an optical read-out based on total internal reflectance fluorescence (TIRF). It could be shown that the assay performance within the cartridge is similar to that found for the same assay in a microtiter plate. Furthermore, recent developments are the integration of sample preparation and polymerase chain reaction (PCR) on-chip. Hence, the instrument is capable of providing heating-and-cooling cycles necessary for DNA-amplification. In addition to scientific aspects also the production of such a lab-on-chip system was part of the development since this heavily affects the success of a later market launch. In summary, the Fraunhofer ivD-platform covers the whole value chain ranging from microfluidics, material and polymer sciences, assay and sensor development to the production and assembly design. In this consortium the gap between diagnostic needs and available technologies can be closed.

Postoperative non-invasive assessment of pulmonary vascular resistance using Doppler echocardiography.

Non-invasive monitoring of pulmonary vascular resistance (PVR) in postoperative cardiac surgery patients might be useful, particularly for management of pulmonary hypertension. For this purpose, we sought to assess Doppler echocardiography in the intensive care setting. In 73 patients, hemodynamics was measured using both, invasive gold standard (pulmonary artery catheter), and non-invasively by Doppler echocardiography. Four Doppler parameters: (1) tricuspid regurgitant velocity/time-velocity-integral of right ventricular outflow tract (TRV/VTI(RVOT)), (2) tricuspid annular systolic velocity (S'), (3) tricuspid annular strain, and (4) tricuspid annular strain rate, were compared with invasive PVR, using linear regression analysis and receiver-operating-characteristics. Patients without (n = 25, group 1) and patients with elevated left ventricular filling pressure (wedge pressure ≥ 15 mmHg, group 2, n = 48) were compared. Correlations were (1) R = 0.874, P < 0.0001, (2) R = -0.765, P < 0.0001, (3) R = 0.279, P = 0.009, (4) R = 0.378, P = 0.001. TRV/VTI(RVOT) showed prediction of PVR >300 dyn*s*/cm(5) (area-under-curve 0.975, cut-off 0.245, sensitivity 100%, specificity 91%). Strain correlated with PVR in group 2 patients only. TRV/VTI(RVOT) and tricuspid annular systolic velocity (S'), are useful for non-invasive monitoring of PVR in postoperative cardiac surgery patients with or without elevated left ventricular filling pressure. Strain may be used in patients with elevated filling pressure.

Quantitative measurement of human anti-HCV Core immunoglobulins on an electrical biochip platform.

The importance of early diagnosis devices increased continuously in the last two decades and plays an important role in medical care. Early stage diagnosis of e.g. ovarian cancer, HCV-infection or HIV-infection increased the survival rate of patients significantly. In parallel there is a trend leaving centralized diagnostic laboratories in order to get closer to the patient to perform analysis of even complex parameters in the field. This often saves time, increases the prognosis of the patient significantly and is cheaper in many cases. In this study we employ a rapid and cost-effective detection system based on electrical biochip technology for decentralized detection of anti-HCV Core immunoglobulins (HCV antibodies). In this system the qualitative and quantitative detection of virus-specific antibodies is done by an ELISA directly on a gold electrode array utilizing HCV Core as capture antigen. The biochip allows antibody detection within 20 min. Signal amplification was done by enzyme labelling and by "Single Electrode Redox Cycling". This method enhances current signals up to 40-fold in comparison to simple oxidation. The sensitivity of this approach is therefore comparable to a standard microtiter plate based ELISA with a 9-fold saving of assay time. This biochip system allows serum or whole blood analysis with no signal loss or increasing background caused by the red blood cells. Fields of application can be hospital emergency units where only single detections have to be conducted in a quick manner or by the general practitioner.

Evidence for a negative inotropic effect of obesity in human myocardium?

OBJECTIVE: The present study was performed as an attempt to analyze the relationship between body weight and human myocardial performance. As overweight is frequently associated with hypertension, stenosis of epimyocardial coronary arteries and other factors that influence myocardial performance, the experimental model of isolated human atrial myocardium was selected. Atrial contractile performance does neither depend on the extent of stenosis of epicardial coronary arteries nor on the degree of hypertension and its secondary pathology. METHODS: Right atrial muscle preparations (0.5 x 6 mm) of 183 patients undergoing coronary artery bypass surgery were electrically stimulated at optimal length. Active tension (stimulation) and passive resting tension (relaxation) were measured (measurement conditions: 37 degrees C, Krebs-Henseleit solution, optimal length and supramaximal electrical stimulation). The relationship of body weight with the measured parameters was analyzed statistically by using linear regression model and Student's t-test. RESULTS: Active tension (mN/mm2) and passive resting tension (mN/mm(2)) declined significantly with increasing body weight (p < 0.0001). The ratio passive resting tension/active tension correlated significantly with body weight (p < 0.0001). The negative association between body weight and active tension amplitude was more pronounced in women (p < 0.05). The following linear regression was calculated: for men: force = -0.04 x body weight + 8.74 (R = 0.505, p < 0.0001, n = 106); for women: force = -0.08 x body weight + 12.03 (R = 0.717, p < 0.0001, n = 77). CONCLUSION: The experimental data are in accordance with the hypothesis, that obese tissue may exert a direct cardio-depressant effect on electromechanical coupling.

Electrical microarrays for highly sensitive detection of multiplex PCR products from biological agents.

For the sensitive detection of amplicons derived from diagnostic PCR, a novel electrical low-density microarray is applied and compared to state-of-the-art quantitative real-time PCR. The principle of the electrochemical method and the effective use for analysis are described. Interdigitated array gold electrodes (IDA-E) embedded into a silicon chip are the core technology of the fully automated compact biosensor system, basing on enzyme coupled electrochemical detection. The biointerface is built up with thiol-modified capture oligonucleotides on gold and mediates the specific recognition of hybridised target DNA amplified with uniplex or multiplex PCR. In here we show the potential of the designed electrical microarray to function as an advanced screening method for the parallel detection of a panel of the four pathogens Bacillus anthracis, Yersinia pestis, Francisella tularensis and ortho pox viruses (genus), which are among the most relevant biowarfare agents. PCR products, generated from 10 to 50 gene equivalents, have been detected reproducibly. The experiments with varying pathogen amounts showed the good reliability and the high sensitivity of the method, equivalent to optical real-time PCR detection systems. Without PCR the total assay time amounts to 27 min. The advantage of the combination of multiplex-PCR with electrical microarray detection avoiding intensive PCR probe labelling strategies is illustrated.

Electrical detection of viral DNA using ultramicroelectrode arrays.

A fully electrical array for voltammetric detection of redox molecules produced by enzyme-labeled affinity binding complexes is shown. The electronic detection is based on ultramicroelectrode arrays manufactured in silicon technology. The 200-microm circular array positions have 800-nm-wide interdigitated gold ultramicroelectrodes embedded in silicon dioxide. Immobilization of oligonucleotide capture probes onto the gold electrodes surfaces is accomplished via thiol-gold self-assembling. Spatial separation of probes at different array positions is controlled by polymeric rings around each array position. The affinity bound complexes are labeled with alkaline phosphatase, which converts the electrochemically inactive substrate 4-aminophenyl phosphate into the active 4-hydroxyaniline (HA). The nanoscaled electrodes are used to perform a sensitive detection of enzyme activity by signal enhancing redox recycling of HA resulting in local and position-specific current signals. Multiplexing and serial readout is realized using a CMOS ASIC module and a computer-controlled multichannel potentiostat. The principle of the silicon-based electrical biochip array is shown for different experimental setups and for the detection of virus DNA in real unpurified multiplex PCR samples. The fast and quantitative electronic multicomponent analysis for all kinds of affinity assays is robust and particle tolerant.

Detection of bacteriophage infection and prophage induction in bacterial cultures by means of electric DNA chips.

Infections of bacterial cultures by bacteriophages are common and serious problems in many biotechnological laboratories and factories. A method for specific, quantitative, and quick detection of phage contamination, based on the use of electric DNA chip is described here. Different phages of Escherichia coli and Bacillus subtilis were analyzed. Phage DNA was isolated from bacterial culture samples and detected by combination of bead-based sandwich hybridization with enzyme-labeled probes and detection of the enzymatic product using silicon chips. The assay resulted in specific signals from all four tested phages without significant background. Although high sensitivity was achieved in 4h assay time, a useful level of sensitivity (10(7)-10(8) phages) is achievable within 25 min. A multiplex DNA chip technique involving a mixture of probes allows for detection of various types of phages in one sample. These analyses confirmed the specificity of the assay.

In vivo validation of cardiac spiral computed tomography using retrospective gating.

BACKGROUND: Cardiac functional assessment represents the basis for diagnostics and cardiac operation planning. Spiral computed tomography (CT) combines the advantages of three-dimensional imaging and high temporal resolution when using gating techniques. However, in vivo validation data of this novel imaging technology are lacking. The purpose of this study was to validate in vivo the new imaging method using retrospective gating and to evaluate the clinical usefulness of the achieved temporal resolution. METHODS: In domestic pigs (n = 10, weight 35 to 40 kg) a flowmeter was placed surgically on the ascending aorta. Flow velocity integrated over systole served as the gold standard for left ventricular (LV) stroke volume (LVSV-FM). CT signal, projection data, pacemaker signal, and flow velocity were recorded simultaneously at constant heart rate (pacemaker, 90 beats per minute). End-systolic and end-diastolic frames were calculated by retrospective gating. LV volumes were traced, the difference representing CT stroke volume (LVSV-CT). Image data were three-dimensionally reconstructed using ray-tracing. RESULTS: Temporal resolution was 170 ms. Correlation of stroke volumes was high (r = 0.94, mean difference 1.75 mL). Intraobserver (0.49 mL for LVEDV, 0.31 for LVESV) and interobserver variability (p = 0.21 and p = 0.06, respectively) were low. Postprocessing resulted in four-dimensional beating-heart models useful for operation planning. CONCLUSIONS: Spiral CT using retrospective gating was validated in vivo. Clinically acceptable temporal resolution and accuracy in determining cardiac stroke volumes were found. As a true volumetric imaging modality the method may now play an important role in computer-assisted diagnostics and surgery.