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We present a compact adaptive glass membrane lens for higher order wavefront correction and axial scanning, driven by integrated segmented piezoelectric actuators. The membrane can be deformed in a combination of rotational symmetry providing focus control of up to ± 6 m-1 and spherical aberration correction of up to 5 wavelengths and different discrete symmetries to correct higher order aberrations such as astigmatism, coma and trefoil by up to 10 wavelengths. Our design provides a large clear aperture of 12 mm at an outer diameter of the actuator of 18 mm, a thickness of 2 mm and a response time of less than 2 ms.
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Various techniques in microscopy are based on point-wise acquisition, which provides advantages in acquiring sectioned images, for example in confocal or two-photon microscopy. The advantages come along with the need to perform three-dimensional scanning, which is often realized by mechanical movement achieved by stage-scanning or piezo-based scanning in the axial direction. Lateral scanning often employs galvo-mirrors, leading to a reflective setup and hence to a folded beam path. In this paper, we introduce a fully refractive microscope capable of three-dimensional scanning, which employs the combination of an adaptive lens, an adaptive prism, and a tailored telecentric f-theta objective. Our results show that this microscope is capable to perform flexible three-dimensional scanning, with low scan-induced aberrations, at a uniform resolution over a large tuning range of X=Y=6300 µ m and Z=480 µ m with only transmissive components. We demonstrate the capabilities at the example of volumetric measurements on the transgenic fluorescence of the thyroid of a zebrafish embryo and mixed pollen grains. This is the first step towards flexible aberration-free volumetric smart microscopy of three-dimensional samples like embryos and organoids, which could be exploited for the demands in both lateral and axial dimensions in biomedical samples without compromising image quality.
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Microscopía , Pez Cebra , Animales , Refracción Ocular , Pruebas de Visión , CintigrafíaRESUMEN
We present a simple method to determine the refractive index of fluids that is suitable for real-time integrated measurements by imaging a collimated beam through a fluid volume and determining its diameter on a CMOS sensor. Our experimental results agree with the prediction of our analytical model, and the resulting refractive index agrees with the measurements obtained with a commercial refractometer with an RMS deviation of just ±0.003. This method requires only inexpensive components: a light source, two lenses, and a camera sensor; it is suitable for real-time monitoring, and it is essentially unlimited in the range of refractive indices.
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We compare different aspects of the robustness to environmental conditions of two different types of piezo-actuated fluid-membrane lenses: a silicone membrane lens, where the piezo actuator indirectly deforms the flexible membrane through fluid displacement, and a glass membrane lens, where the piezo actuator directly deforms the stiff membrane. While both lenses operated reliably over the temperature range of 0°-75°C, there was a significant effect on their actuation characteristics, which can be well described through a simple model. The silicone lens in particular showed a variation in focal power of up to 0.1m-1 ∘C-1. We demonstrated that integrated pressure and temperature sensors can provide feedback for focal power, however, limited by the response time of the elastomers in the lenses, with polyurethane in the support structures of the glass membrane lens being more critical than the silicone. Studying the mechanical effects, the silicone membrane lens showed a gravity-induced coma and tilt, and a reduced imaging quality with the Strehl ratio decreasing from 0.89 to 0.31 at a vibration frequency of 100 Hz and an acceleration of 3g. The glass membrane lens was unaffected by gravity, and the Strehl ratio decreased from 0.92 to 0.73 at a vibration of 100 Hz, 3g. Overall, the stiffer glass membrane lens is more robust against environmental influences.
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We demonstrate a method for self-sensing of a magnetically actuated prism that can be used, e.g., in a feedback-loop without the need of additional sensors. In order to use the impedance of the actuation coils as a measurement parameter, we first obtained the optimal measurement frequency that is well separated from the actuation frequencies and at the same time provides the best compromise between sensitivity to the position and robustness. We then developed a combined actuation and measurement driver, and correlated its output signal to the mechanical state of the prism using a defined calibration sequence. We demonstrate that we can reliably measure the state of each actuator and determine the tilt angle of the prism with an accuracy of ±0.1∘ in the polar angle over a range of ±4∘ and ±20 mrad in the azimuthal angle.
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We present two versions of tunable achromatic doublets based on each two piezoelectrically actuated glass membranes that create the surface of fluid volumes with different dispersions: a straightforward back-to-back and a more intricate stack of the fluid volumes. In both cases, we can control the chromatic focal shift and focal power independently by a suitable combination of actuation voltages on both active membranes. The doublets have a large aperture of 12 mm at an outer diameter of the actuator of 18 mm, an overall thickness of 3 mm and a short response time of around 0.5 ms and, in addition, provide spherical aberration correction. The two designs have an achromatic focal power range of ±2.2 m-1 and ±3.2 m-1 or, for the purpose of actively correcting chromatic errors, a chromatic focal shift at vanishing combined focal power of up to ±0.08 m-1 and ±0.12 m-1.
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We present a highly compact and fast varifocal lens with aspherical tunability based on an active piezo-glass-piezo sandwich membrane. Using an optimized geometry, improved fabrication and compliant elastomer structures together with an index-matched optical fluid, we achieved an outer diameter of just 9 mm (10 mm packaged) for a clear aperture of 7.6 mm. The range of the focal power was -7 m-1 to +6 m-1, with a wavefront error around 100 nm and a response time between 0.1 and 0.15 ms.
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We present a new and accurate method to determine the Poisson's ratio of PDMS, using thermal expansion and an optical surface profilometer. The Poisson's ratio of Sylgard 184 was found to be ν = 0.4950 ± 0.0010 and for Sylgard 182, ν = 0.4974 ± 0.0006. Furthermore, we found that for both PDMS types, the coefficient of thermal expansion depends approximately linearly on the curing temperature. This method can be used for almost any kind of soft polymer that can be cured from a liquid at elevated temperatures.
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OBJECTIVE: The applicability of the balanced steady-state free precession (bSSFP) sequence to the field of MR microscopy was investigated, since the potentially high SNR makes bSSFP attractive. However, particularly at ultra-high magnetic fields, a number of constraints emerge: the frequency sensitivity of the bSSFP signal, the duty cycle of the imaging gradients, and the intrinsic diffusion attenuation of the steady state due to the imaging gradients. MATERIALS AND METHODS: Optimization of the bSSFP sequence was performed on three imaging systems (7 T and 9.4 T) suited for MR microscopy. Since biological samples are often imaged in the very proximity of materials from sample containers/holder or devices such as electrodes, several microscopy phantoms representing such circumstances were fabricated and examined with 3D bSSFP. RESULTS: Artifact-free microscopic bSSFP images could be obtained with voxel sizes down to 16 µm × 16 µm × 78 µm and with an SNR gain of 25% over standard gradient echo images. CONCLUSION: With appropriate choice of phantom materials, optimization of the flip angle to the diffusion-attenuated steady state and protocols considering duty-cycle limitations, bSSFP can be a valuable tool in MR microscopy.
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Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Microscopía/métodos , Algoritmos , Artefactos , Simulación por Computador , Aumento de la Imagen , Procesamiento de Imagen Asistido por Computador/métodos , Campos Magnéticos , Fantasmas de Imagen , Reproducibilidad de los Resultados , Relación Señal-Ruido , AguaRESUMEN
We present a varifocal mirror based on a piezo-actuated glass membrane that can be used as a secondary mirror in miniature Cassegrain-type mirror- or catadioptric objectives. The mirror section has a diameter of 10 mm on a clear membrane diameter of 23 mm, with a focal range of ±8 m-1 and a response time on the millisecond-scale. The two piezo layers enable an aspherical tuning range that covers the elliptic, parabolic and hyperbolic regime over most of the focal range. We demonstrate the application of the mirror in a simple catadioptric telefocus objective with a focal length of 68 mm at an aperture of 22 mm and a thickness of 16.6 mm.
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We investigate segmented Bessel beams that are created by placing different ring apertures behind an axicon that is illuminated with a plane wave. We find an analytical estimate to determine the shortest possible beam segment by deriving a scale-invariant analytical model using appropriate dimensionless parameters such as the wavelength and the axicon angle. This is verified using simulations and measurements, which are in good agreement. The size of the ring apertures was varied from small aperture sizes in the Frauhofer diffraction limit to larger aperture sizes in the classical limit.
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We present a new principle for tuning the diffraction efficiency of an optical grating and its implementation in a micro-optical device. The overlap of two phase gratings is used to vary the effective phase shift and hence the diffraction efficiency. We study the working principle using Fourier Optics to simulate the diffraction pattern in the far field and design and realize a device based on integrated piezo actuation. We find good agreement between simulation and experiment and observe a suppression of the first diffraction order intensity by more than 97% and response times of less than 3 ms.
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We study the spatial intensity distribution and the self-reconstruction of quasi-Bessel beams produced from refractive axicon lenses with edge emitting laser diodes as asymmetric and astigmatic illumination sources. Comparing these to a symmetric mono-mode fiber source, we find that the asymmetry results in a transition of a quasi-Bessel beam into a bow-tie shaped pattern and eventually to a line shaped profile at a larger distance along the optical axis. Furthermore, we analytically estimate and discuss the effects of astigmatism, substrate modes and non-perfect axicons. We find a good agreement between experiment, simulation and analytic considerations. Results include the derivation of a maximal axicon angle related to astigmatism of the illuminating beam, impact of laser diode beam profile imperfections like substrate modes and a longitudinal oscillation of the core intensity and radius caused by a rounded axicon tip.
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In this Letter, we demonstrate the first high-speed piezoelectric axicon mirror. We achieve a usable aperture of 10 mm up to the maximum radius of the robust, 300 µm thick mirror substrate using a floating boundary condition. The highly aspheric, conical shape is programmed into the device by ring-shaped electrodes, for which we have developed an automated optimization strategy for their individual electrode potentials. In addition, we developed a simple control circuit, in which the conical profile can be programmed and adjusted with just one control signal. The device is fabricated by rapid prototyping to avoid cleanroom processing. The tunable mirror features a resonance frequency of 10 kHz and a static deflection of 5.8 µm at a surface deviation of 63 nm, and is thus able to generate a quasi-Bessel beam.
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Electrodos , Lentes , Sistemas Microelectromecánicos/instrumentación , Diseño de Equipo , Análisis de Falla de EquipoRESUMEN
We present the prototype and analytical model of a miniaturized impact actuation mechanism, providing a fast out-of-plane displacement to accelerate objects against gravity, allowing for freely moving objects and hence for large displacements without the need for cantilevers. To achieve the necessary high speed, we chose a piezoelectric stack actuator driven by a high-current pulse generator, connected to a rigid support and a rigid three-point contact with the object. We describe this mechanism with a spring-mass model and compare various spheres with different masses and diameters and from different materials. As expected, we found that larger flight heights are achieved by harder spheres, achieving, e.g., approx. 3 mm displacement for a 3 mm steel sphere using a 3 × 3 × 2 mm3 piezo stack.
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We present the development of a dual-mode imaging platform that combines optical microscopy with magnetic resonance microscopy. Our microscope is designed to operate inside a 9.4T small animal scanner with the option to use a 72mm bore animal RF coil or different integrated linear micro coils. With a design that minimizes the magnetic distortions near the sample, we achieved a field inhomogeneity of 19 ppb RMS. We further integrated a waveguide in the optical layout for the electromagnetic shielding of the camera, which minimizes the noise increase in the MR and optical images below practical relevance. The optical layout uses an adaptive lens for focusing, 2 × 2 modular combinations of objectives with 0.6mm to 2.3mm field of view and 4 configurable RGBW illumination channels and achieves a plano-apochromatic optical aberration correction with 0.6µm to 2.3µm resolution. We present the design, implementation and characterization of the prototype including the general optical and MR-compatible design strategies, a knife-edge optical characterization and different concurrent imaging demonstrations.
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Diseño de Equipo/instrumentación , Imagen por Resonancia Magnética/métodos , Microscopía/métodos , Imagen Óptica/métodos , Animales , Imagen por Resonancia Magnética/instrumentación , Microscopía/instrumentación , Imagen Óptica/instrumentación , Fantasmas de Imagen , Ondas de RadioRESUMEN
Diffraction-limited deep focusing into biological tissue is challenging due to aberrations that lead to a broadening of the focal spot. The diffraction limit can be restored by employing aberration correction for example with a deformable mirror. However, this results in a bulky setup due to the required beam folding. We propose a bi-actuator adaptive lens that simultaneously enables axial scanning and the correction of specimen-induced spherical aberrations with a compact setup. Using the bi-actuator lens in a confocal microscope, we show diffraction-limited axial scanning up to 340 µm deep inside a phantom specimen. The application of this technique to in vivo measurements of zebrafish embryos with reporter-gene-driven fluorescence in a thyroid gland reveals substructures of the thyroid follicles, indicating that the bi-actuator adaptive lens is a meaningful supplement to the existing adaptive optics toolset.
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Patients suffering from neuronal degenerative diseases are increasingly being equipped with neural implants to treat symptoms or restore functions and increase their quality of life. Magnetic resonance imaging (MRI) would be the modality of choice for the diagnosis and compulsory postoperative monitoring of such patients. However, interactions between the magnetic resonance (MR) environment and implants pose severe health risks to the patient. Nevertheless, neural implant recipients regularly undergo MRI examinations, and adverse events are rarely reported. However, this should not imply that the procedures are safe. More than 300 000 cochlear implant recipients are excluded from MRI, unless the indication outweighs the excruciating pain. For 75 000 deep brain stimulation (DBS) recipients quite the opposite holds true: MRI is considered an essential part of the implantation procedure and some medical centres deliberately exceed safety regulations, which they refer to as crucially impractical. Permanent MRI-related neurological dysfunctions in DBS recipients have occurred in the past when manufacturer recommendations were exceeded. Within the last few decades, extensive effort has been invested to identify, characterise and quantify the occurring interactions. Yet today we are still far from a satisfying solution concerning a safe and beneficial MR procedure for all implant recipients. To contribute, we intend to raise awareness of the growing concern, summon the community to stop absurdities and instead improve the situation for the increasing number of patients. Therefore, we review implant safety in the MRI literature from an engineering point of view, with a focus on cochlear and DBS implants as success stories of neural implants in clinical practice. We briefly explain fundamental phenomena which can lead to patient harm, and point out breakthroughs and errors made. Then, we end with conclusions and strategies to avoid future implants from being contraindicated in MR examinations. We believe that implant recipients should enter MRI, but before doing so, it should be made sure that the procedure is reasonable.
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Implantes Cocleares/normas , Estimulación Encefálica Profunda/normas , Electrodos Implantados/normas , Imagen por Resonancia Magnética/normas , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiología , Implantación Coclear/efectos adversos , Implantación Coclear/normas , Implantación Coclear/tendencias , Implantes Cocleares/efectos adversos , Implantes Cocleares/tendencias , Estimulación Encefálica Profunda/efectos adversos , Estimulación Encefálica Profunda/tendencias , Electrodos Implantados/efectos adversos , Electrodos Implantados/tendencias , Humanos , Imagen por Resonancia Magnética/efectos adversos , Imagen por Resonancia Magnética/tendencias , Dolor/diagnóstico , Dolor/etiología , Falla de Prótesis/etiologíaRESUMEN
We present the results of a systematic measurement of the magnetic susceptibility of small material samples in a 9.4 T MRI scanner. We measured many of the most widely used materials in MR engineering and MR micro technology, including various polymers, optical and substrate glasses, resins, glues, photoresists, PCB substrates and some fluids. Based on our data, we identify particularly suitable materials with susceptibilities close to water. For polyurethane resins and elastomers, we also show the MR spectra, as they may be a good substitute for silicone elastomers and good casting resins.