Nanoscale transport devices made of quantum dots have been studied a lot over the past decades. In solid state setups, a quantum dot, e.g. made from a two-dimensional electron gas, is connected to two metallic contacts and a current is driven through the system. One reason for the great experimental as well as theoretical interest is the hope to make the next step in the miniaturization of informational technology devices. This is why molecular quantum dots, i.e. quantum dots built on the basis of singlemolecules, have attracted more and more interest recently, since they are truly only a few nanometers long. Besides the aspect of size reduction, molecules exhibit various quantized degrees of freedom such as charge, vibrations and spin which can be useful. For instance, switching behavior due to conformational changes of the shape of the molecule influences the current and can therefore be used to manipulate the charge flow. Practically, however, transport junctions made of molecules still have a limited degree of controllability. For example, the orientation of the molecule in the junction cannot always be controlled as desired. Solid state quantum dots, on the other hand, can be designed and their properties can be tuned very precisely. However, they do not exhibit the same richness of degrees of freedom and their interplay as molecules do. Many experiments and theories have addressed the crossover between molecules and solid state quantum dots in carbon-based mate- rials, such as carbon nano-tubes (CNT), graphene and recently even singlemolecules enclosed in CNTs ("peapods"). These exhibit molecular-like degrees of freedom, e.g., they function as nano electro-mechanical systems (NEMS), while also allowing for control.
photo-multiplier tubes or more sensitive avalanche photo diodes (APDs). In order to excite the molecules within and detect the signal from the diffraction limited confo- cal volume, the collimated excitation laser beam is focussed onto the sample plane, and the emitted fluorescence is then re-collected and re-collimated by the same micro- scope objective. Residual laser light is filtered with high quality interference filters, like in wide-field imaging. A pinhole in the detection pathway, as shown in Figure 3.3b, blocks out of focus light in the detection pathway to increase the resolution along the optical z-axis. The diameter of the pinhole determines the absolute depth of field for the confocal image, so that the overall size of the focal spot is in the range of 300 nm in diameter in the observation plane and about 900 nm along the optical axis. It has a volume of about one femtoliter. In order to obtain images of larger areas on the sample, the excitation focus or the sample have to be scanned point by point. Therefore confo- cal techniques are also referred to as scanning methods. In addition to the molecules’ position, confocal microscopy can provide further useful information about the single emitters. By introducing a polarizer into the excitation and detection pathway the ori- entation of the molecule in the observation plane can be determined. 94, 112, 113 The point signal from immobile single-molecules can be split into the spectral components by a prism or grating and imaged onto a CCD camera. 112 In this way the spectral dynamics of a dye can be followed at video rate, i.e. 24 frames per second. However, even though one point can be observed with high temporal resolution, the scanning time per point is the limiting factor for fast accumulation of larger images. In a conventional laser scanning microscope like the Zeiss LSM 410 used for the confocal measurements in Chapter 7, the fastest scanning time for a 256 px × 256 px region of the sample is about one second. To obtain high resolution images with a signal-to-noise ratio suitable for tracking with high positioning accuracy, much slower scanning times have to be cho- sen (e.g. 64 s for one 256 px × 256 px image). Therefore, real-time observation of the molecular motion is only possible for very slowly diffusing species.
In literature, reflective light-sheet microscopy was employed to combine the beneficial at- tributes of free 3D imaging and the sensitivity to detect singlemolecules. The technique employs a mirror that reflects the light sheet onto the focal plane of the detection objective in order to selectively excite the sample. In this work, a fixed micro prism with reflective surface allowed to employ high numerical aperture objectives while keeping the optical alignment procedure at a minimum. Together, single 10 kDa Dextran-Alexa647 molecules were recorded deep in the late-stage Drosophila embryo roughly 80 µm above the cover slip surface. The detection and tracking on the multi-cellular scale revealed different behaviors that strongly correlated with the respective location. While Brownian motion was detected in the periv- itelline space, active transportation was observed in individual cells of the epidermis. With complementary experiments using Rab5-GFP, the active transportation of vesicles was at- tributed to endosomal trafficking. The detection of singlemolecules on the multi-cellular scale at different sample depths enables and fosters to study their role such as transcription factor binding to DNA.
occur due to the unique properties of singlemolecules. In this thesis we develop min- imal, microscopic transport models that account for the intrinsic molecular properties (different redox centers, magnetic anisotropies, high spin, etc.). On the one hand the introduced parameters may be fixed by input from ab-initio calculations when a com- parison to experimental data is needed. On the other hand the models under discus- sion describe large classes of molecules and therefore the results are generic for these molecules and may apply to various experiments. These models are analyzed in the regimes of weak and strong coupling between electrode and molecule by appropriate methods: In the weak coupling regime a master equation approach captures the non- equilibrium imposed by the applied bias voltages correctly, while in the strong coupling regime the numerical renormalization group is the method of choice.
The first step was to optimize all assays by testing different enzyme and compound concen- trations without hydrolases, with HCl or ethanol as signal inducing molecules, mostly for the luminescence assay. For comparison of the three HTS assays, endpoint measurements were done. The two step oxidative luminescence assay was optimized by design of experiments (DoE) to maximize the duration of luminescence and the sensitivity for endpoint measure- ments. The isochronic induction of luminescence in all wells was very important for the reliable quantification of ethanol. The assay mixtures were automatically pipetted by the Tecan evo pipetting robot that can simultaneously pipette 96 wells. It turned out that a pre-incubation time of 15 min without peroxidase was necessary. Without pre-incubation, the resulting lumi- nescence signal was too weak for the quantification of ethanol. Luminescence enhancers like 4-iodophenol [ 76 ], were added in order to maximize the luminescence output, however no suf- ficient signal amplification was observed so that these additives were omitted. Due to the rela- tively weak signal the luminescence assay was only suitable for endpoint determinations. For quantification, we calculated both the numeric integral and the mean of luminescence over the measured time. A clear luminescence signal was detectable for about 50 min.
Mesostructured silica fibers inside the channels of AAMs were produced according to the method described in Chapter II, Section 1. Flat films were prepared via spin-coating of similar precursor solutions on glass slides resulting in thin silica layers with a thickness of about 200 nm (Chapter II, Section 2). Strongly fluorescent terrylenediimide molecules  (TDI, Figure 8.1), acting as molecular beacons, were added at very low concentrations to the synthesis solutions (10 -8 mol/l). The dimension of the TDI molecule is about 1 x 1 x 3.2 nm 3 . During evaporation-induced self-assembly the dye molecules are located in the non polar environment of the surfactant micelle centers and thus are incorporated into the pores of the mesostructured silica. Single molecule fluorescence microscopy was carried out on the as- synthesized films without further sample preparation. Here the term “pore” that classically defines the empty space in porous materials after removal of the organic template is used to describe the template-filled space where the dye molecules are moving.
Prolonged illuminating and exciting the fluorescence molecules by an epifluorescence microcopy can induce damages on the molecules. In addition, the noise as a result of thermal drift and the molecule diffusion in imaging by an optical microscope can limit a good signal- to-noise ratio, especially in imaging of the single-molecules. By real time read out measurements of the elongated DNA molecules under a focused laser spot, a photoluminescence intensity signal is achieved along the time, instead of imaging the molecules with a microscope. This improves the resolution as instead of a 1-µm light spot, the focused laser spot is confined in a 100-µm diameter pinhole before striking on the APD. Furthermore, a laser light is monochromatic and, thus, provides a single wavelength in spectral region, whereas the lamps are polychromatic, so that only a small fraction of the light is emitted in the required spectral region. Moreover, this method allows the rapid analysis of a large number of the molecules, for instance, counting the molecules. In this technique, the ultrasensitive detection of the individual molecules is also not limited by the length of the molecule. The PL signal is recorded along the time, as the molecules are dynamically transported in the nanochannels. On-chip detection in real time is a new technology which is possible, due to the improvements in the photon-counting system. This technique has a greater sensitivity to collect more emitted photons from the single-molecules. For fluorescence dyes with nanosecond excited state lifetimes, a single-molecule will need to stay in a laser beam for approximately 10 to 50 μs to generate about 20 photon counts (at 5% overall photon detection efficiency).
With methods such as scanning tunneling microscopy (STM) or atomic force microscopy (AFM) it is possible to study chirality at the molecular level 19 – 21 . In particular, the reduction of the degrees of freedom, which results from analyzing adsorbed 2D molecular layers or small 2D clusters can facilitate differentiation between enantiomers. Following this strategy, along with choos- ing a substrate where surface reconstruction can take place, it is sometimes possible to identify the chirality of molecular dimers even without submolecular resolution 21 . However, to assign the absolute conﬁguration at the level of individual molecules sub- molecular resolution is essential. For example, Ernst et al. recently demonstrated the concept of stereochemical assignment for helical molecules on a metal surface using the submolecular resolution capabilities of standard STM 10 . Furthermore, high- resolution AFM was also used to identify products of on-surface chirality transfer reactions from helicene substrates by deter- mining the handedness of mostly planar singlemolecules 22 . In these two exemplary cases, however, the unique structure of the studied types of helical molecules facilitates their identiﬁcation. Additionally, since such helicenes are non-natural aromatic hydrocarbons that typically have large optical rotations and intense CD spectra, their assignment by conventional means is straightforward. Extending the assignment of absolute conﬁg- uration by direct visual inspection to single sp 3 systems would therefore represent a signiﬁcant advance.
• Family preservation services with an emphasis on keeping together families that would have been separated in the past. Services include maintaining and strengthening family bonds, stabilizing a crisis situation that precipitated any need for outside placement, and increasing family’s coping skills, competencies, and use of appropriate and informal helping resources. Among the services-oriented on children in single-parent families are the following; • School-established support groups for students coping with family problems such as divorce
The sensitivity and specificity of the ISAC microarray testing in our study (Table 1 ) was overall comparable to previous studies [ 28 ], and showed a strong correlation with single plex tests including IgE and SPT [ 13 , 36 ], specifically for respiratory allergens [ 30 , 31 ], but in fact varied slightly from allergen to allergen. This was also observed in a recent study, suggesting to ultimately ap- prove diagnosis by more sensitive single plex tests, for instance, in cases of anaphylaxis [ 11 ]. In our study the highest sensitivities were achieved with the PR10 family molecules Cor a 1 and Bet v 1, followed by Phl p 1. These sensitivities were complemented by good specific- ities, like in the case of Bet v 1 which showed a 97.8% sensitivity and a 77.4% specificity to birch, followed by a 65.3% specificity to hazel. This could also be observed for Phl p 1 with a sensitivity of 92.3% and a specificity of 75.9%. The mugwort allergen Art v 1, a good predictor for ragweed, showed 90% specificity, and 61.5% sensitiv- ity. Indeed, Art v 1 has a homology to the so called “rag- weed homologue of Art v 1 precursor ”, varying between 64 to 50% amino acid homologies (from BLAST), with- out significant similarity with major Ambrosia allergen Amb a 1. We therefore hypothesize that the mugwort al- lergen extract used for SPT contained cross-reacting com- ponents that do not seem to be significant for the identification of a genuine sensitization. For Alternaria only the genuine allergen Alt a 1 was a predictor of sensitization, with 80% specificity and 100% sensitivity. As expected, Ole e 1 was a good predictor of ash tree (86.2% sensitivity, 81.8% specificity).
Auf das Phänomen “Älterwerden als Single” angewandt, müsste daher gefragt werden, worin die problematische Betroffenheit besteht, ob soziale Verursachungszusammenhänge dabei eine Rolle spielen und ob daraus benachteiligende Verhaltenskonsequenzen für eine relevante Anzahl von Betroffenen resultieren, die in der Öffentlichkeit als problematisch angesehen und thematisiert werden. Dabei können wir davon ausgehen, dass das Singledasein als eine Form individueller Lebensführung in unserer Gesellschaft inzwischen zu einer akzeptierten, ja kulturell legitimierten Option der Lebensgestaltung geworden ist. Aus der Tatsache, dass jemand als Single lebt, resultieren keine eklatanten Benachteiligungen z.B. in Form von Vorurteilen oder rechtlichen Diskriminierungen. Benachteiligend wäre das Singledasein auch, wenn z.B. diese Lebensform für bestimmte Mitglieder der Gesellschaft gesellschaftlich erzwungen wäre. Dies ist aber nicht (mehr) der Fall. Singledasein ist zu einer wählbaren Option der individuellen Lebensführung geworden. Dies bedeutet allerdings nicht, dass diese Lebensform immer freiwillig gewählt wird. Das Alleinleben kann durch verschiedene Lebensumstände bedingt sein (z.B. wenn jemand keine/keinen geeignete Partnerin/Partner findet um eine Familie zu gründen). In diesem Zusammenhang spielen sozial strukturelle Bedingungen jedoch keine wesentliche Rolle. Im Gegenteil: Eine Entscheidung für die Lebensform “Single” z.B. aus Gründen der erfolgreichen Berufskarriere kann für Singles erhebliche Vorteile Z.B. in materieller Hinsicht bringen; aber auch Vorteile hinsichtlich der erforderlichen, berufsbedingten geographischen Mobilität, Möglichkeiten der Einübung der selbständigen Lebensführung, Freizeitgestaltung usw.
Services for single parents may be coordinated through resource centers where families can receive thorough assessments, so they can be referred to appropriate agencies and databases that contain information about the services available to single parents run by social groups and networks. Services should be adapted to the cultural diversity of the single-parent family.
Many experimental and theoretical efforts have been undertaken to align and orient molecules using external electric fields. For instance, electrostatic hexapole fields can be used to prepare molecules in single rotational states [21, 28–30]. Due to their quantum nature, the spatial anisotropy of these states is, however, not very large. Another method utilizes strong static electric fields to induce "brute-force" orientation of the molecules [31– 33]. To achieve strong degrees of orientation (and alignment), this technique relies on rotationally cold molecules with large permanent electric-dipole moments and its applicability is thus limited. A more general way to align molecules was proposed by Friedrich and Herschbach [34–36] as well as Seideman . It makes use of strong nonresonant laser fields to confine the most polarizable axis (MPA) along the polarization axis of the optical field [38–40]. This method also entails the possibility of 3D alignment, e. g., by using elliptically polarized fields [41–46]. Depending on the duration and shape of the laser field, the temporal behavior of the alignment can be controlled in a variety of ways [47, 48]. Laser pulses with durations much larger than the molecule’s rotational period adiabatically transfer the initial quantum state to an aligned pendular state . In combination with weak static fields, the molecules can additionally be strongly oriented [49– 51]. This so-called mixed-field orientation was demonstrated experimentally [52–55], however, the adiabatic picture employed in the theoretical calculations proved to be insufficient to reproduce the observed degrees of orientation . Instead, a time- dependent description of the field-dressed dynamics is required [56, 57].
As estimated in Chap. 2, the theoretically expected lifetimes of 6 Li - 40 K ground state molecules in a three dimensional bulk gas are rather short. The reason is the occurrence of the ultracold chemical reaction 2 Li - K → Li - Li + K - K. When dipole moments are induced in the laboratory frame, and in addition to the van - der - Waals interaction the dipolar interaction is of a relevant strength, an even further increase of the reactive constants are predicted [Qu´em´ener et al., 2011]. While an experimental determination of the chemical rate constants in dependence on the strength and dominant type of interaction is an interesting subject by itself, the limited lifetime poses constraints for other investigations. However, a stabilization against chemical reactions is predicted in systems with strong dipolar interaction in reduced dimensionality [Micheli et al., 2010]. In this trap configuration and molecules with dipole moments oriented in the direction of tight confinement, the dipolar interaction is purely repulsive [Pupillo et al., 2008]. This stabilizes molecular samples against decay due to chemical reactions as it prevents molecules to enter into the short length scales needed for chemical reactions to occur. When a two dimensional trap is available in Singapore, it will be interesting to measure how well this stabilization mechanism will be functional at the temperatures of a few hundred nK that are expected for ground state molecules produced in our present experimental apparatus. Further, it will be interesting to measure the lifetimes of samples of polar molecules in dependence on the orientation of the dipole moment relative to the direction of tight confinement. In this manner the anisotropy of the dipolar interaction can be observed as interactions are switched from purely repulsive to attractive in one direction of the two dimensional trap geometry. This attractive interaction should lead to a fast decay of molecular samples. A further possibility to suppress chemical reactions is to load the particles into a sufficiently deep optical lattice. Preparations for one to three dimensional optical lattice configurations, in which ground state molecules can be trapped, are underway in Singapore.
of its electronic structure, dipole moment, etc. We have demonstrated a balanced beam splitter with a momentum separation of 14ℏk, which is to the best of our knowledge the largest equal-amplitude splitting demonstrated for molecules using optical gratings. Although with sufficient laser power similar or even greater splitting could be achieved with a thin optical grating, this would typically reduce the particle flux by a factor of 10 as only two of the many populated output beams have to be selected. The same problem applies to mechanical gratings, which addi- tionally are incompatible with polar molecules due to rotational averaging.
Spin-sensitive investigations on CoSal molecules are in the focus of this chapter. Preparation procedures of the probe tip and the investigated sample are provided in the first two sections. Next, the observation of many molecules in an external magnetic field allows for revealing their distinct behavior in different adsorption geometries on the GR/Fe moiré structure. Some of the molecules are ferromagnetically coupled to the substrate while others exhibit an antiferromagnetic alignment with the underlying substrate. Further, some of the molecules in the former case are sensitive to the external magnetic field changes, and therefore the molecule’s magnetization direction can be manipulated independent from the substrate – an effect which can be clearly seen in SP- STM data provided in the later part of the chapter. The detection and manipulation of the direction of the magnetic moment of individual CoSal molecules, based on the low level of hybridization with a GR/Fe substrate, is an important milestone towards planar, molecule based all-spin logic devices. The results have been published in the following paper 114 :