In-plane Strain Analysis by Correlating Geometry and Visual Data Through a Gradient-Based Surface Reconstruction.

Abnormalities in tissue can be detected and analyzed by evaluating mechanical properties, such as strain and stiffness. While current sensor systems are effective in measuring longitudinal properties perpendicular to the measurement sensor, identifying in-plane deformation remains a significant challenge. To address this issue, this paper presents a novel method for reconstructing in-plane deformation of observed tissue surfaces using a fringe projection sensor specifically designed for measuring tissue deformations. The method employs the latest techniques from computer vision, such as differentiable rendering, to formulate the in-plane reconstruction as a differentiable optimization problem. This enables the use of gradient-based solvers for an efficient and effective optimization of the problem optimum. Depth information and image information are combined using landmark correspondences between the respective image observations of the undeformed and deformed scenes. By comparing the reconstructed pre- and post-deformation geometry, the in-plane deformation can be revealed through the analysis of relative variations between the corresponding models' geometries. The proposed reconstruction pipeline is validated on an experimental setup, and the potential for intraoperative applications is discussed.

Numerical analysis of micro-optics based single photon sources via a combined physical optics and rigorous simulations approach.

The use of 3D printed micro-optical components has enabled the miniaturization of various optical systems, including those based on single photon sources. However, in order to enhance their usability and performance, it is crucial to gain insights into the physical effects influencing these systems via computational approaches. As there is no universal numerical method which can be efficiently applied in all cases, combining different techniques becomes essential to reduce modeling and simulation effort. In this work, we investigate the integration of diverse numerical techniques to simulate and analyze optical systems consisting of single photon sources and 3D printed micro-optical components. By leveraging these tools, we primarily focus in evaluating the impact of different far-field spatial distributions and the underlying physical phenomena on the overall performance of a compound micro-optical system via the direct evaluation of a fiber in-coupling efficiency integral expression.

Fast bidirectional vector wave propagation method showcased on targeted noise reduction in imaging fiber bundles using 3D-printed micro optics.

In order to extend simulation capabilities for reflective and catadioptric 3D-printed micro optics, we present a fast bidirectional vector wave propagation method (BWPM). Contrary to established fast simulation methods like the wave propagation method (WPM), the BWPM allows for the additional consideration of reflected and backwards propagating electric fields. We study the convergence of the BWPM and investigate relevant simulation examples. Especially, the BWPM is used for evaluation of 3D-printed index matching caps (IMCs) in order to suppress back reflected light in imaging fibers, used for keyhole access endoscopy. Simulations studying the viability of IMCs are followed up with experimental investigations. We demonstrate that 3D-printed IMCs can be used to suppress noise caused by back reflected light, that otherwise would prohibit the use of imaging fibers in an epi-illumination configuration.

Injection Molding of Encapsulated Diffractive Optical Elements.

Microstructuring techniques, such as laser direct writing, enable the integration of microstructures into conventional polymer lens systems and may be used to generate advanced functionality. Hybrid polymer lenses combining multiple functions such as diffraction and refraction in a single component become possible. In this paper, a process chain to enable encapsulated and aligned optical systems with advanced functionality in a cost-efficient way is presented. Within a surface diameter of 30 mm, diffractive optical microstructures are integrated in an optical system based on two conventional polymer lenses. To ensure precise alignment between the lens surfaces and the microstructure, resist-coated ultra-precision-turned brass substrates are structured via laser direct writing, and the resulting master structures with a height of less than 0.002 mm are replicated into metallic nickel plates via electroforming. The functionality of the lens system is demonstrated through the production of a zero refractive element. This approach provides a cost-efficient and highly accurate method for producing complicated optical systems with integrated alignment and advanced functionality.

Adjustment-free two-sided 3D direct laser writing for aligned micro-optics on both substrate sides.

3D direct laser writing is a powerful and widely used tool to create complex micro-optics. The fabrication method offers two different writing modes. During the immersion mode, an immersion medium is applied between the objective and the substrate while the photoresist is exposed on its back side. Alternatively, when using the dip-in mode, the objective is in direct contact with the photoresist and the structure is fabricated on the objective facing side of the substrate. In this Letter, we demonstrate the combination of dip-in and photoresist immersion printing, by using the photoresist itself as immersion medium. This way, two parts of a doublet objective can be fabricated on the front and back sides of a substrate, using it as a spacer with a lateral registration below 1 µm and without the need of additional alignment. This approach also enables the alignment free combination of different photoresists on the back and front sides. We use this benefit by printing a black aperture on the back of the substrate, while the objective lens is printed on the front.

Numerical optimization of single-mode fiber-coupled single-photon sources based on semiconductor quantum dots.

We perform extended numerical studies to maximize the overall photon coupling efficiency of fiber-coupled quantum dot single-photon sources emitting in the near-infrared and O-band and C-band. Using the finite element method, we optimize the photon extraction and fiber-coupling efficiency of quantum dot single-photon sources based on micromesas, microlenses, circular Bragg grating cavities and micropillars. The numerical simulations which consider the entire system consisting of the quantum dot source itself, the coupling lens, and the single-mode fiber, yield overall photon coupling efficiencies of up to 83%. Our work provides objectified comparability of different fiber-coupled single-photon sources and proposes optimized geometries for the realization of practical and highly efficient quantum dot single-photon sources.

Coupling light emission of single-photon sources into single-mode fibers: mode matching, coupling efficiencies, and thermo-optical effects.

We discuss the coupling efficiency of single-photon sources into single-mode fibers using 3D printed micro-optical lens designs. Using the wave propagation method, we optimize lens systems for two different quantum light sources and assess the results in terms of maximum coupling efficiencies, misalignment effects, and thermo-optical influences. Thereby, we compare singlet lens designs with one lens printed onto the fiber with doublet lens designs with an additional lens printed onto the semiconductor substrate. The single-photon sources are quantum dots based on microlenses and circular Bragg grating cavities at 930 nm and 1550 nm, respectively.

Fast algorithm for the simulation of 3D-printed microoptics based on the vector wave propagation method.

In this work, we propose the Fast Polarized Wave Propagation Method (FPWPM), which is an efficient method for vector wave optical simulations of microoptics. The FPWPM is capable of handling comparably large simulation volumes while maintaining quick runtime. This allows for real-world application of this method for the rapid development process of 3D-printed microoptics. By comparison to established routines like the rigorous coupled wave analysis (RCWA) or the Richards-Wolf-Integral, accuracy and superior runtime efficiency of the FPWPM are demonstrated by simulation of interfaces, gratings, and lenses. By considering polarization in simulations, the FPWPM facilitates the analysis of optical elements which employ this property of electromagnetic waves as a feature in their optical design, e.g., diffractive elements, gratings, or optics with high angle of incidence like high numerical aperture lenses.

Data-Driven Identification of Biomarkers for In Situ Monitoring of Drug Treatment in Bladder Cancer Organoids.

Three-dimensional (3D) organoid culture recapitulating patient-specific histopathological and molecular diversity offers great promise for precision medicine in cancer. In this study, we established label-free imaging procedures, including Raman microspectroscopy (RMS) and fluorescence lifetime imaging microscopy (FLIM), for in situ cellular analysis and metabolic monitoring of drug treatment efficacy. Primary tumor and urine specimens were utilized to generate bladder cancer organoids, which were further treated with various concentrations of pharmaceutical agents relevant for the treatment of bladder cancer (i.e., cisplatin, venetoclax). Direct cellular response upon drug treatment was monitored by RMS. Raman spectra of treated and untreated bladder cancer organoids were compared using multivariate data analysis to monitor the impact of drugs on subcellular structures such as nuclei and mitochondria based on shifts and intensity changes of specific molecular vibrations. The effects of different drugs on cell metabolism were assessed by the local autofluorophore environment of NADH and FAD, determined by multiexponential fitting of lifetime decays. Data-driven neural network and data validation analyses (k-means clustering) were performed to retrieve additional and non-biased biomarkers for the classification of drug-specific responsiveness. Together, FLIM and RMS allowed for non-invasive and molecular-sensitive monitoring of tumor-drug interactions, providing the potential to determine and optimize patient-specific treatment efficacy.

3D-Printed Micro Lens-in-Lens for In Vivo Multimodal Microendoscopy.

Multimodal microendoscopes enable co-located structural and molecular measurements in vivo, thus providing useful insights into the pathological changes associated with disease. However, different optical imaging modalities often have conflicting optical requirements for optimal lens design. For example, a high numerical aperture (NA) lens is needed to realize high-sensitivity fluorescence measurements. In contrast, optical coherence tomography (OCT) demands a low NA to achieve a large depth of focus. These competing requirements present a significant challenge in the design and fabrication of miniaturized imaging probes that are capable of supporting high-quality multiple modalities simultaneously. An optical design is demonstrated which uses two-photon 3D printing to create a miniaturized lens that is simultaneously optimized for these conflicting imaging modalities. The lens-in-lens design contains distinct but connected optical surfaces that separately address the needs of both fluorescence and OCT imaging within a lens of 330 µm diameter. This design shows an improvement in fluorescence sensitivity of >10x in contrast to more conventional fiber-optic design approaches. This lens-in-lens is then integrated into an intravascular catheter probe with a diameter of 520 µm. The first simultaneous intravascular OCT and fluorescence imaging of a mouse artery in vivo is reported.

Ultra-compact 3D-printed wide-angle cameras realized by multi-aperture freeform optical design.

Simultaneous realization of ultra-large field of view (FOV), large lateral image size, and a small form factor is one of the challenges in imaging lens design and fabrication. All combined this yields an extensive flow of information while conserving ease of integration where space is limited. Here, we present concepts, correction methods and realizations towards freeform multi-aperture wide-angle cameras fabricated by femtosecond direct laser writing (fsDLW). The 3D printing process gives us the design freedom to create 180° × 360° cameras with a flat form factor in the micrometer range by splitting the FOV into several apertures. Highly tilted and decentered non-rotational lens shapes as well as catadioptric elements are used in the optical design to map the FOV onto a flat surface in a Scheimpflug manner. We present methods to measure and correct freeform surfaces with up to 180° surface normals by confocal measurements, and iterative fabrication via fsDLW. Finally, approaches for digital distortion correction and image stitching are demonstrated and two realizations of freeform multi-aperture wide-angle cameras are presented.

Misalignment of spheres, aspheres and freeforms in optical measurement systems.

When measuring surfaces it is always a challenge to differentiate whether differences to the expected form originate from positioning errors or from surface errors. In interferometry it is common to subtract tilt and power terms from the measurement result to remove misalignment contributions. This is a suitable approximation for spherical surfaces with small NA. For high NAs and increasing deviations from a spherical shape, which applies to aspheres and freeforms, additional terms show increasing magnitudes. A residual error remains after subtraction of tilt and power. Its form depends on the surface's nominal shape and oftentimes has a non-negligible magnitude, therefore imposing the risk of being misinterpreted as topography error.

Event based coherence scanning interferometry.

Coherence scanning interferometry enables high precision measurements in manifold research and industry applications. In most modern systems, a digital camera (CCD/CMOS) is used to record the interference signals for each pixel. When measuring steep surfaces or using light sources with a broad wavelength spectrum, only a small area of the sensor captures useable interference signals in one frame, so a large fraction of pixels is unused. To overcome this problem and enable measurements with high dynamic range and high scan speeds, we propose the use of an event based image sensor. In these sensors, each pixel independently registers only changes in the signal, which leads to a continuous asynchronous pixel stream of information not based on fixed frame capturing. In this Letter, we show the signal generation, an implementation in a coherence scanning microscope in combination with the nanopositioning and nanometrology machine NPMM-200, and first measurements as promising results for event based interferometry.

3D printed hybrid refractive/diffractive achromat and apochromat for the visible wavelength range.

Three-dimensional (3D) direct laser writing is a powerful technology to create nano- and microscopic optical devices. While the design freedom of this technology offers the possibility to reduce different monochromatic aberrations, reducing chromatic aberrations is often neglected. In this Letter, we successfully demonstrate the combination of refractive and diffractive surfaces to create a refractive/diffractive achromat and show, to the best of our knowledge, the first refractive/diffractive apochromat by using DOEs and simultaneously combining two different photoresists, namely IP-S and IP-n162. These combinations drastically reduce chromatic aberrations in 3D printed micro-optics for the visible wavelength range. The optical properties, as well as the substantial reduction of chromatic aberrations, are characterized, and we outline the benefits of 3D direct laser written achromats and apochromats for micro-optics.

Ultrathin monolithic 3D printed optical coherence tomography endoscopy for preclinical and clinical use.

Preclinical and clinical diagnostics increasingly rely on techniques to visualize internal organs at high resolution via endoscopes. Miniaturized endoscopic probes are necessary for imaging small luminal or delicate organs without causing trauma to tissue. However, current fabrication methods limit the imaging performance of highly miniaturized probes, restricting their widespread application. To overcome this limitation, we developed a novel ultrathin probe fabrication technique that utilizes 3D microprinting to reliably create side-facing freeform micro-optics (<130 µm diameter) on single-mode fibers. Using this technique, we built a fully functional ultrathin aberration-corrected optical coherence tomography probe. This is the smallest freeform 3D imaging probe yet reported, with a diameter of 0.457 mm, including the catheter sheath. We demonstrated image quality and mechanical flexibility by imaging atherosclerotic human and mouse arteries. The ability to provide microstructural information with the smallest optical coherence tomography catheter opens a gateway for novel minimally invasive applications in disease.

Distortion-free multi-element Hypergon wide-angle micro-objective obtained by femtosecond 3D printing.

In this Letter, we present a 3D-printed complex wide-angle multi-element Hypergon micro-objective, composed of aspherical lenses smaller than 1 mm, which exhibits distortion-free imaging performance. The objective is fabricated by a multi-step femtosecond two-photon lithography process. To realize the design, we apply a novel (to the best of our knowledge) approach using shadow evaporation to create highly non-transparent aperture stops, which are crucial components in many optical systems. We achieve a field-of-view (FOV) of 70°, at a resolution of 12.4 µm, and distortion-free imaging over the entire FOV. In the future, such objectives can be directly printed onto complementary metal-oxide-semiconductor (CMOS) imaging chips to produce extremely compact, high-quality image sensors to yield integrated sensor devices used in industry.

Mass-producible micro-optical elements by injection compression molding and focused ion beam structured titanium molding tools.

We demonstrate mass production compatible fabrication of polymer-based micro Fresnel lenses by injection compression molding. The extremely robust titanium-molding tool is structured with high precision by focused ion beam milling. In order to achieve optimal shape accuracy in the titanium we use an iterative design optimization. The inverse Fresnel lens structured into the titanium is transferred to polymers by injection compression molding, enabling rapid mass replication. We show that the optical performance of the molded diffractive Fresnel lenses is in good agreement with simulations, rendering our approach suitable for applications that require compact and high-quality optical elements in large numbers.

3D printed stacked diffractive microlenses.

Planar lenses such as metalenses and diffractive lenses exhibit severe field-dependent aberrations when imaging extended objects with high numerical aperture. This problem can be overcome by stacking at least two of such devices on top of each other. In this work, we present such stacked imaging systems, namely doublets and triplets of diffractive optical elements. They are fabricated by femtosecond direct laser writing in one single step without the need for alignment in sizes of below 200 µm in diameter and 100 µm in height. The lenses allow for efficient sub µm resolution imaging at visible wavelengths combined with a full field-of-view of up to 60°. As additional benefit, our approach dramatically reduces the writing times of 3D printed lens systems to below 15 minutes.

Optimum Wavelengths in the Near Infrared for Imaging Photoplethysmography.

OBJECTIVE: The purpose of this contribution is to determine the ideal near infrared wavelength bands for monochromatic and dual-band remote heartbeat detection using imaging photoplethysmography (iPPG) of the forehead. METHODS: Experimental data of 38 healthy volunteers has been recorded and analyzed. For the data acquisition, a fast hyperspectral imager has been used. A new combination approach has been implemented that computes the quotient of the bands and, therefore, reduces motion artifacts. RESULTS: With this dual-band method excellent results (1.67 beats per minute mean deviation from electrocardiogram measurements for 73 recordings) have been obtained using a simple algorithm to analyze images at 799 and 861 nm. CONCLUSION: It can be concluded that excellent imaging photoplethysmography measurements can be performed at low cost using conventional silicon-based image sensors with invisible light in the near infrared region. SIGNIFICANCE: This approach is a contribution to the development of non-contact heart rate measurement systems that can be used for medical diagnosis or other applications.

Three-dimensional direct laser written achromatic axicons and multi-component microlenses.

Femtosecond 3D printing is an important technology for manufacturing nano- and microscopic optical devices and elements. However, most structures in the past have been created using only one photoresist at a time, thus limiting potential applications. In this Letter, we successfully demonstrate the combination of two different photoresists, namely, IP-S and IP-Dip, to realize multi-component three-dimensional direct laser written optics. We use the combination of IP-S and IP-Dip to correct chromatic aberrations and to realize an achromatic axicon. In a second step, we demonstrate, to the best of our knowledge, the first three-dimensional direct laser written Fraunhofer doublet. We characterize their optical properties and measure the substantial reduction in chromatic aberrations. We outline the possibilities and benefits of creating three-dimensional direct laser written multi-component structures for micro-optics.