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Diabetic kidney disease (DKD) is a common diabetes complication mainly caused by lipid toxicity characterized by oxidative stress. Studies have shown that adropin (Ad) regulates energy metabolism and may be an effective target to improve DKD. This study investigated the effect of exogenous Ad encapsulated in reactive oxygen species (ROS)-responsive nanocapsules (Ad@Gel) on DKD. HK2 cells were induced with high glucose (HG) and intervened with Ad@Gel. A diabetes mouse model was established using HG and high-fat diet combined with streptozotocin and treated with Ad@Gel to observe its effects on renal function, pathological damage, lipid metabolism, and oxidative stress. Results showed that Ad@Gel could protect HK2 from HG stimulation

Optical interference microscopes are widespread in topography and roughness measurement on the micro- and nanoscale. In spite of a wide range of scientific and industrial applications, systematic d...

Increasing evidence suggests that activation of microglia-induced neuroinflammation plays a crucial role in the pathophysiology of depression. Consequently, targeting the central nervous system to reduce neuroinflammation holds great promise for the treatment of depression. However, few drugs can enter the brain via a circulatory route through the blood-brain barrier (BBB) to reach the central nervous system efficiently, which limits the pharmacological treatment for neuropsychiatric diseases. Herein, a light-responsive system named UZPM, consisting of blue-emitting NaYF

Depression medication is still facing challenges, where the key issue is to explore a desirable delivery platform to assist drugs in penetrating blood-brain barrier (BBB). Herein, we prepared beard nanoscale particles (BNPs) from the beard of young Asian males, which were mainly composed by keratin and melanin. BNPs were able to load antidepressants (Fluoxetine) and exhibited therapeutic effect on depression. Moreover, in vitro and in vivo studies showed that BNPs held favorable photothermal conversion capability, prominent BBB permeability under near-infrared (NIR) irradiation and reliable biocompatibility. Deserved to be mentioned, BNPs also performed a pivotal role in redox equilibrium, which was thus capable of scavenging ROS induced by depression. Subsequently, behavioral and biochemical experiments also demonstrated significant depression-ameliorating effects in vivo. In summary, our data for the first time suggested that biological organism derived beard could serve as ideal low-cost nanovectors for depression therapy.

A new material measure for characterising two-dimensional (2D) instrument transfer functions (ITF) of areal surface topography measuring instruments has been designed, manufactured, calibrated and applied. Several innovative ideas are implemented in its design. Firstly, the material measure is designed with circular structure patterns. Such rotational symmetric patterns are advantageous for characterising the ITF in different angular directions, thus for characterising angular-dependent asymmetries of instruments. Secondly, different types of patterns are designed: circular chirp (CC) pattern and circular discreate grating (CDG) pattern. They represent different kinds of spatial signals applicable for characterising ITFs. A material measure consists of 25 different circular patterns with radii from 30 μm to 300 μm, and wavelengths from 0.1 μm to 150 μm. These patterns can be applied complementary and combinedly, offering high application flexibility for calibrating a variety of instruments, e.g. with different optical objectives from 5× to 100× and with different sizes of field of view (FOV). Material measures with heights of 8 nm, 16 nm and 32 nm, respectively, have been manufactured using state-of-the-art e-beam lithography technique. The feature heights are far less than λ/4, thus they are suitable for characterising the ITF of optical tools which can be approximated as linear systems. A metrological large range atomic force microscope (AFM) has been applied in the calibration of the developed material measure, showing good feature quality. The calibrated material measure has been successfully applied in research and industry.

Optical profilers are mature instruments used in research and industry to study surface topography features. Although the corresponding standards are based on simple step height measurements, in practical applications these instruments are often used to study the fidelity of surface topography. In this context it is well-known that in certain situations a surface profile obtained by an optical profiler will differ from the real profile. With respect to practical applications such deviations often occur in the vicinity of steep walls and in cases of high aspect ratio. In this contribution we compare the transfer characteristics of different 3D optical profiler principles, namely white-light interferometry, focus sensing, and confocal microscopy. Experimental results demonstrate that the transfer characteristics do not only depend on the parameters of the optical measurement system (e. g. wavelength and coherence of light, numerical aperture, evaluated signal feature, polarization) but also on the properties of the measuring object such as step height, aspect ratio, material properties and homogeneity, rounding and steepness of the edges, surface roughness. As a result, typical artefacts such as batwings occur for certain parameter combinations, particularly at certain height-to-wavelength ratio (HWR) values. Understanding of the mechanisms behind these phenomena enables to reduce them by an appropriate parameter adaption. However, it is not only the edge artefacts, but also the position of an edge that may be changed due to the properties of the measuring object. In order to investigate the relevant effects theoretically, several models are introduced. These are based on either an extension of Richards-Wolf modeling or rigorous coupled wave analysis (RCWA). Although these models explain the experimental effects quite well they suffer from different limitations, so that a quantitative correspondence of theoretical modeling and experimental results is hard to achieve. Nevertheless, these models are used to study the characteristics of the measured signals occurring at edges of different step height compared to signals occurring at plateaus. Moreover, a special calibration sample with continuous step height variation was developed to reduce the impact of unknown sample properties. We analyzed the signals in both, the spatial and the spatial frequency domain, and found systematic signal changes that will be discussed. As a consequence, these simulations will help to interpret measurement results appropriately and to improve them by proper parameter settings and calibration and finally to increase the edge detection accuracy.

Besides the illumination wavelength also the numerical aperture (NA) of a microscope objective affects the fringe spacing in interference microscopy. Therefore, at high NA values an effective wavelength should be obtained by calibration. At step height structures both, the effective wavelength and the batwing effect strongly depend on the height-to-wavelength-ratio (HWR). Therefore, changes of the effective wavelength considering temporal and spatial coherence enable us to estimate the batwing effect in measurement results. For high NA systems and broadband illumination two different theoretical approaches for signal modeling are introduced to study the influence of the center wavelength, the temporal, and the spatial coherence of the illuminating light on measurement results of a rectangular grating. In both models diffraction is considered. While the first simulation model (Kirchhoff) is mostly analytical the second one (Richards-Wolf) is primarily numerical. Simulation results of both models show a good agreement with experimental measurement results.

Optical measurement techniques are widely applied in high-resolution contour, topography and roughness measurement. In this context vertical scanning white-light interferometers and confocal microscopes have become mature instruments over the last decades. The accuracy of measurement results is highly related not only to the type and physical properties of the measuring instruments, but also to the measurement object itself. This contribution focuses on measurement effects occurring at edges and height steps using white-light interferometers of different numerical apertures. If the edge is perfectly perpendicular, batwing effects appear at height steps. These batwings show maximum height if the height-to-wavelength-ratio (HWR) is about one forth or three forth, and they disappear if the HWR value is about an integer multiple of one half. The wavelength that is relevant in this context is the effective wavelength, i.e. the center wavelength of the illuminating light multiplied by a correction factor known as the numerical aperture correction. However, in practice the edges are usually not perfectly perpendicular. In this case, the measurement results depend also on the derivative of the surface height function and they may differ from theory and the prediction according to the HWR value. Measurements of such steps show systematical effects depending on the lateral resolution of the instrument. In this context, a Linnik interferometer with a magnification of 100x and NA = 0.9 is used to characterize the three dimensional topography of more or less rectangular calibration specimens and quasi-perpendicular structures produced by the nanoimprint technology. The Linnik interferometer is equipped with LED light sources emitting at different wavelengths, so that the HWR value can be changed. This is possible since the high NA objective lenses show a rather limited depth of focus such that the temporal coherence gating may be replaced by focal gating in this particular instrument. In addition, measurement results are compared with those achieved by a Mirau interferometer of NA = 0.55. A commercial confocal microscope with NA of 0.95 serves as a reference instrument for further comparison. Numerical simulations considering diffraction effects are carried out in order to explain the experimental results obtained by the different white and colored light interferometers

Zusammenfassung Tiefenscannende Weißlichtinterferometer haben sich in der Mikro- und Nanotechnologie als Messgeräte zur 3D-Geometrieerfassung etabliert. Während eine axiale Auflösung im Sub-Nanometerbereich erreicht werden kann, ist die laterale Auflösung durch die Beugung auf die Größenordnung der Lichtwellenlänge begrenzt. Zudem treten bei der Messung von Kantenstrukturen Abweichungen von einer korrekten Übertragung der zu messenden Topographie auf. Die Beugung führt hier zu dem Batwing-Effekt. Ein Ansatz, das Übertragungsverhalten eines optischen Profilometers zu charakterisieren, basiert auf der ITF (Instrument Transfer Function), die sich von der für Abbildungssysteme gebräuchlichen MTF (Modulation Transfer Function) ableitet. Unsere Untersuchungen zeigen, dass die ITF nicht nur von der Periodenlänge eines gemessenen Profils, sondern auch von dessen Amplitude und Form abhängt. Der Profilverlauf bei Rechteckprofilen geeigneter Amplitude kann bis zu einer Periodenlänge, die der optischen Auflösung gemäß dem Rayleigh-Kriterium entspricht, korrekt erfasst werden. Bei Messobjekten mit inhomogenem Fresnel-Koeffizienten, z. B. ein Chromgitter auf einem Glassubstrat, kann die laterale Auflösung deutlich schlechter sein. Eine Simulation für stochastisch raue Oberflächenprofile zeigt eine Überhöhung der Rauheit bei kurzer Korrelationslänge des Oberflächenprofils.

To get physical insight into the 3D transfer characteristics of interference microscopy at high numerical apertures we study reflecting rectangular grating structures. In general, the height obtained from phase information seems to be reduced, whereas height values resulting from coherence scanning sometimes seem to be systematically overestimated. Increasing the numerical aperture of an interference microscope broadens the spectra of the resulting interference signals, thus offering a broad variety of wavelength contributions to be analyzed. If phase analysis of a measured far-field interference wavefront is performed at very short wavelengths the periodical profiles obtained from coherence scanning and phase shifting analysis differ only by the measured amplitude. However, at longer wavelength there is a 180° phase shift of the measured profiles obtained from phase analysis compared to coherence peak analysis. Increasing the evaluation wavelength improves the lateral resolution since the long wavelength contributions are related to electromagnetic waves of high angles of incidence. This behavior is to the best of our knowledge not documented in literature so far. It was first observed experimentally and could be confirmed by simulation results obtained from either Kirchhoff diffraction theory or an extended Richards-Wolf model developed in our group. Compared to original input profiles used for the simulation the profiles obtained from phase evaluation correspond quite well at longer wavelength, whereas the results obtained from coherence peak analysis are typically inverted with respect to height.

Increasing capabilities in precision manufacturing and micro technology are accompanied by increasing demands for high precision industrial metrology systems. With respect to optical metrology especially the lateral resolution capabilities of an optical profiler gains in importance. If, in addition, nanometer height resolution is needed interferometers seem to be the most promising instruments. This contribution focuses on interference microscopes using objective lenses of high numerical apertures in order to reach high lateral resolution. Increasing the numerical aperture influences both, the envelope as well as the phase of interference signals obtained by a so-called depth scan, i. e. changing the distance between the measuring object and the interference microscope. The depth of focus of a high numerical aperture objective limits the width of the signal envelope simultaneously increasing the fringe spacing which results in a longer effective wavelength. We demonstrate the practical consequences of these effects using a self-assembled Linnik interferometer of 0.9 numerical aperture. Phenomena resulting from concrete measuring objects will be discussed: Step height structures may lead to a further change of the effective wavelength as a consequence of changes in the signal spectrum due to interference phenomena within a single Airy disk. This may influence the lateral resolution of an interference microscope for a specific measurement task. In addition, a strong dependence of the measurement results on either TE or TM polarization occurs if step height structures are measured. Modeling the polarization dependence requires to consider the angle dependence of Fresnel reflection coefficients and edge diffraction phenomena. Although the maximum measurable surface slope of a tilted surface can be increased by increasing the numerical aperture there is a limitation due to the fringe density compared to the optical resolution of the microscope as it will be demonstrated by measurement results obtained from a chirp-shaped surface standard.

Increasing capabilities in precision manufacturing and micro technology are accompanied by increasing demands of high precision industrial metrology systems. Especially for measuring functional surfaces, areal optical principles are widely used. If, in addition, nanometer height resolution is needed interferometers seem to be the most promising instruments. First, this contribution focuses on the transfer characteristics of white-light interferometers with microscopic field of view. In general, microscopic instruments suffer from their limited lateral resolution capabilities. Hence, the transfer function of these instruments is typically assumed to show a linear low-pass characteristic. We studied the transfer characteristics of white-light interferometers by theoretical simulations and experimental investigations. Our results show that in most practical cases these instruments behave nonlinear, i.e. the output surface profile cannot be obtained from the input profile by a simple linear filter operation. Although they are well-established, there are some further limitations of white-light interferometers if they are used to measure micro or even sub-microstructures. If edges, steeper slopes or abrupt slope changes are present on a measuring object characteristic errors such as batwings occur. Furthermore, a high effort concerning the correction of chromatic aberration is necessary in order to avoid dispersion effects. Otherwise, there will be systematic discrepancies between profiles obtained from evaluation of the coherence peak and those resulting from the phase of the interference signals. These may lead to 2π phase jumps if the fringe order is obtained from the position of the coherence peak. Finally, measurement artifacts may also result if the measured micro-structure shows discontinuities of the surface slope. This contribution analyses the different phenomena and discusses approaches to overcome existing limitations.

Scanning white-light interferometry (SWLI) provides the capability of fast and high-precision three-dimensional measurement of surface topography. Nevertheless, it is well-known that white-light interferometers more than imaging microscopes suffer from chromatic aberration caused by the influence of dispersion. In this paper several interferometric measurement systems are used for surface topography measurement. A Linnik interferometer and two Michelson interferometers of different aberration correction are compared. A correction system designed using the ray tracing software “Zemax” aims at an optimization the modulation transfer function (MTF). Although the MTF is optimized the resulting spot diagrams are blurred due to chromatic aberration. Finally, a doubly corrected Michelson interferometer will be presented. For this interferometer a nearly optimal MTF as well as minimized spot diagrams are achieved.

We discuss the height and lateral resolution that can be achieved in vertical scanning white-light interferometry (SWLI). With respect to interferometric height resolution, phase-shifting interferometry (PSI) is assumed to provide the highest accuracy. However, if the noise dependence of SWLI phase evaluation and PSI algorithms is considered, SWLI measurements can be shown to be more precise. With respect to lateral resolution, the determination of the coherence peak position of SWLI signals seems to lead to better results compared to phase based-interferometric measurements. This can be attributed to the well-known batwing effect. Since batwing is a nonlinear effect applying nonlinear filters, e.g. a median filter, it reduces them significantly. If filtering is applied prior to the fringe order determination and phase evaluation, the number of artefacts known as ghost steps can be eliminated without changing the modulus of the phase. Finally, we discuss the dependence of measured height values on surface slope. We show that in interference microscopy there are additional limitations which are more rigid compared to the maximum surface slope angle resulting from the numerical aperture of the objective lens. As a consequence, the measurement precision breaks down at slope changes of steeper flanks even if the modulation depth of the interference signals is still good enough for signal analysis.

Due to its outstanding depth resolution capabilities vertical scanning low-coherence or white-light interferometry is one of the most used optical techniques in the field of 3D micro-metrology. Unfortunately, step height structures often lead to disturbing effects known as batwings in SWLI measurement that overlay the real profile heights of a rectangular structure. As a consequence, the lateral resolution capabilities and the transfer characteristics of white-light interference microscopes are difficult to characterize. In general, the lateral resolution of such instruments is assumed to agree with the lateral resolution of a conventional light microscope for 2D imaging and the measurement process of an optical profiler is assumed to be linear similar to a microscopic imaging process. Our results show that there are significant discrepancies between the instrument transfer function of a white-light interferometer and the optical transfer function of a conventional microscope. In this paper we analyze the transfer characteristics of current white-light interferometers based on theoretical considerations, simulation studies, and experimental investigations. It turns out that under certain conditions a correct measurement of a rectangular profile is possible even if only the first order diffraction component is captured by an objective lens with a given numerical aperture. In addition to the discussion of current instruments new approaches to overcome existing limits will be introduced: In order to reduce the batwing effect we combine a Mirau white-light interferometer with a confocal illumination system. Furthermore, it is shown that proper adaption of the evaluation wavelength of the low-coherent light can improve the measurement accuracy significantly if rectangular profiles are obtained from the phase information inherent in WLI signals.

White-light interferometers are widely used for high-accuracy topography measurement in industrial and scientific applications. A common way to characterize a white-light interferometer is to assume small surface amplitudes resulting in linear transfer characteristics described by the instrument transfer function (ITF). However, the well-known batwing effect gives rise to systematic errors, causing extra nonlinearity to the ITF. In this paper a model to simulate an interference pattern in the image plane as it is obtained by a vertical scanning white-light interferometer is introduced in order to overcome the limitation of small surface amplitudes. Repeating the simulation procedure for different height positions of the object results in an image stack that can be analyzed by the same algorithms as real measurement data. The simulation results agree with experimental observations: the batwing effect occurs in certain situations and the correct amplitude of a rectangular grating structure can be obtained as long as the structure is optically resolved. Both simulation, as well as experimental results, provide transfer characteristics of broader bandwidth than predicted by theoretical approaches based on linear system behavior.

In this Letter, the transfer characteristics of rectangular periodic phase objects are studied. It turns out that there are significant differences compared to amplitude objects. The imaging of an amplitude object can be understood as a linear process, whereas phase objects behave nonlinearly. It is shown that under certain conditions the correct shape of a rectangular phase grating can be obtained by an interference microscope as long as the first order diffraction component passes the optical imaging system. This result is in a good agreement with experimental observations and computer simulation results.

Vertical scanning white-light interferometry (SWLI) is a well-established method that is widely used in high precision surface topography measurement. However, SWLI results show characteristic slope-dependent errors due to dispersion effects and lateral chromatic aberrations of the optical imaging system. In this paper, we present methods to characterize these systematic errors related to dispersion and lateral colour. Lateral colour leads to field-dependent systematic discrepancies of the topography data obtained from the envelope position of a low-coherence interference signal and the data resulting from its interference phase. Hence, an erroneous fringe order obtained from the envelope position leads to a 2π phase jump and thus to a so-called ghost step in the measured topography. Our first approach to solve this problem is based on the measurement of a surface standard of well-known geometry. By comparison of measurement results related to the envelope position and the phase of SWLI signals, the systematic error is estimated and a numerical error compensation method is proposed. Both experimental and simulation results confirm the validity of this numerical method. In addition, using an improved design of a white-light Michelson interferometer we demonstrate experimentally that lateral chromatic aberrations and dispersion influences can be reduced also in a physical way. In this context, a conventional long working distance microscope objective is used which was not originally designed for a Michelson interference microscope.

The precise acquisition of three-dimensional geometrical data in micro- and nanotechnologies plays a crucial role in advanced fabrication processes. Scanning white-light interferometry achieves nanometer resolution in the axial direction, but the lateral resolution is far more critical. The requirements for an area-based optical sensor in a nano-measuring machine are very high. The resolution in every dimension and the working distance have to be as high as possible. In contrast to a Mirau interferometer, a Linnik interferometer does not need any optical components in front of the objective lens. This benefit permits both a long working distance and a high lateral resolution. In the EC-funded project 'NanoCMM' we developed a Linnik interferometer providing a working distance of more than 5 mm and a lateral resolution of 0.44 µm. This is achieved by near-UV illumination. The interferometer measures the full modulation depth and the rectangular shape of a pitch standard with 0.6 µm pitch length.

We report on the fabrication of miniaturized NIR spectrometers based on arrays of multiple Fabry-Perot (FP) filters. The various cavities of different height are fabricated via a single patterning step using high resolution 3D nanoimprint technology. Today, low-cost patterning of extended cavity heights for NIR filters using the conventional spin-coated nanoimprint methodology is not available because of insufficient coating layers and low mobility of the resist materials to fill extended cavity structures. Our investigation focuses on reducing the technological effort for fabrication of homogeneous extended cavities. We study alternative cavity designs, including a new resist and apply large-area 3D nanoimprint based on hybrid mold and UV Substrate Conformal Imprint Lithography (UV-SCIL) to overcome these limitations. We compare three different solutions, i.e. (1) applying multiple spin coating of the resist to obtain thicker initial resist layers, (2) introducing a hybrid cavity (combination of a thin oxide layer and the organic cavity) to compensate the height differences, and (3) optimizing the imprint process with a novel resist material. The imprint results based on these methods demonstrate the implementation of NIR FP filters with high transmission intensity (best single filter transmission >90 %) and small line widths (