Biocompatible materials (or “Biomaterials”) are substances that are intended to mimic and interact with biological systems. For the safe and reliable function of implants, composition and materials are as important as form. Surfaces may require appropriate coatings or functionalization. Therefore the last two decades have seen strong advancements in biomaterials and related science, with capital investments and research efforts into the development of new products in several fields of applications. Biomaterials science embraces several disciplines such as materials science, tissue engineering, chemistry, biology, and medicine.

When a new material is designed and created or optimized and adopted, application specific characterization is of paramount importance. The need of imaging and metrological tools is very important in defining and measuring properties of the materials from different points of view: morphological properties and their spatio-temporal changes, mechanical properties (stress and strain analysis), surface characterization, reaction to stimulus, degradation, assembling, and many more.

Innovative aspects
Optical techniques have some advantageous features: they are largely non-invasive, non-contact, possibly have a large field of view and high spatial resolution and very high sensitivity for measuring and evaluating most of physical and material parameters. This gives them a prominent role among diagnostic tools. The requirements depend on the situation, varying substantially from single cell and tissue engineering to complex biological systems or components. In analogy to what occurred in „Photomechanics“ which furnished many decisive answers in the past 40 years, in a variety of engineering problems (in materials engineering, testing and characterization of components and structures for aerospace, automobile industry, optics and micromechanics industries), optical metrology can provide answers for emerging problems and key issues in biomaterials research.

Intention
The intention of this conference is to bring together researchers working in the emerging fields of biomaterials, either at microscopic or at macroscopic scale. The conference will provide a rare platform for detailed exchange between groups working on the development of “biomaterials” and experts in “optical metrology”, in order to promote and stimulate stronger interaction between these topics. We invite experts from very different areas, who are usually not attending the same conferences, and we expect new collaborations to come into being from these encounters. The emphasis of the conference lies on the development of new and smart diagnostic metrological tools of biomaterials, to furnish quantitative data to optimize engineering design, fabrication and characterization of biomaterials.

Expected topics among contributions include:
  • characterization of implantable devices and materials
  • visualization and evaluation of self-assembly processes at the nanoscale/microscale of biological/polymeric matter
  • biodegradable and/or biocompatible polymers and their characterization
  • mechanical strength, viscoelastic, optical and other properties of bone, cartilage, and other soft tissues
  • measurements polymer scaffold characterization for tissue engineering
  • single cell mechanics, cell motility, cell adhesion and morphological evolution and correlation to biomechanisms and cell fate
  • collagen and other tissue investigation
  • optics of the eye and vision correction (i.e. characterization of intraocular lenses)
  • materials for dental applications
  • diagnostic systems on innovative phase-contrast imaging and optical tomography
  • innovative approaches for biomarker sensing
  • optical micro-manipulation for materials characterization
  • study of liquid-solid interfaces by optical/imaging methods
  • bioinspired biomimetic and nanobiomaterials
  • investigation and characterization of biological nano-diffractive materials/surfaces
  • characterization of soft-like biomaterials
  • optical method for study fluids at micro and nanoscale.


  • Contributions are expected but not limited to the following approaches and multimodal methods:
  • quantitative phase contrast imaging
  • digital differential image contrast imaging
  • interference microscopy
  • holographic interferometry
  • deep learning in microscopy
  • SLM-based microscopy
  • lensless imaging
  • photoacoustic imaging
  • ultrasound imaging
  • spectroscopy, microscopy, and endoscope optics
  • optical absorption, reflection, transmission and scattering techniques
  • 3D modeling and profiling
  • speckle interferometry and imaging
  • optical methods for biomechanics of materials and evaluation of its functionalities
  • fluorescence microscopy techniques
  • optical coherence tomography and microscopy
  • wavefront sensing
  • fringe projection accurate shape measurement
  • topography and 3D shape measurements
  • optical elastography methods.

  • Special session:

    FET (Future and Emerging Technologies) Open on Disruptive Ideas and Optical Technologies for Health


    The conference will feature a FET Open session where projects of excellence, funded by the European Commission within the FET-Open program of Horizon 2020, will be discussed. The session will consist of short presentations from researchers working in FET-Open projects, followed by a general Q&A panel, and will be chaired by Pietro Ferraro and Simonetta Grilli, ISASI-CNR (Italy);
    In progress – view active session
    Conference 11786

    Optical Methods for Inspection, Characterization, and Imaging of Biomaterials V

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    View Session ∨
    • DIgital Optical Technologies Plenary Session
    • Special Focus: Keynote Session I
    • Special Focus: Keynote Session II
    • FET-Open on Disruptive Ideas and Optical Technologies for Health I
    • Special Focus: Keynote Session III
    • Optical Metrology Plenary Session
    • FET-Open on Disruptive Ideas and Optical Technologies for Health II
    • 1: Imaging in Microfluidics
    • 2: Digital Holographic Microscopy I
    • 3: Digital Holographic Microscopy II
    • 4: Micromanipulation
    • 5: Biomaterial Fabrication
    • 6: Phase Microscopy and Tomography
    • 7: Tissue Imaging
    • 8: Imaging
    • 9: Biophotonics and Additive Manufacturing Technologies for 3D Health Monitoring
    • 10: Scaffolds and Advanced Materials
    • Poster Session
    Session LIVE: DIgital Optical Technologies Plenary Session
    Livestream: 21 June 2021 • 12:30 - 13:30 CEST | Zoom
    11788-600
    Author(s): Hiroki Kikuchi, Sony Corp. (Japan)
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    Sony is leveraging its "3R Technology" - Reality, Real-time, and Remote - to inspire Kando (emotion) value creation. Immersive, large-screen displays give us a sense of reality as if we are traveling around the world while we're at home. Sensors for automotive provide real-time feedback to the drivers to provide safety and comfort. AR/MR/VR technology connects people who are separated remotely and enriches their communication. Photonics is one of the core technologies of Sony and is the foundation of the core devices which create the values of Reality, Realtime and Remote. In this talk, Sony's unique photonic device technologies are introduced, including micro-display, AR/MR/VR, light field displays and laser devices. The prospects for the evolution of these technologies will also be presented.
    Session LIVE: Special Focus: Keynote Session I
    Livestream: 21 June 2021 • 14:15 - 15:45 CEST | Zoom
    11786-33
    Author(s): Adam P. Wax, Duke Univ. (United States)
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    OCT adoption is somewhat limited by the lack of an effective means for obtaining adequate image penetration in highly scattering tissue. For example, the ability to observe subtle changes in the layers of skin tissue where microcirculation occurs, generally anywhere between 1-4 mm deep, a depth currently beyond the penetration of traditional OCT systems. DA-OCT presents an attractive potential to image deeper into tissues exposing morphology that otherwise may go undetected. The approach is based on an off-axis scanning approach which uses distinct illumination and collection apertures to accept a larger proportion of quasiballistic signal. Here we present transliation ofDA-OCT to image large tissue volumes using a broadband SLD centered about 1.3 μm paired with a dynamic focus-tracking method to create an enhanced depth of focus.
    11788-1
    Author(s): Frederik Bachhuber, Olaf Claussen, Zhengyang Lu, Clemens Ottermann, Simone Ritter, Bianca Schreder, Ruediger Sprengard, Stefan Weidlich, Ute Woelfel, SCHOTT AG (Germany)
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    Waveguide technology is widely believed to constitute the most promising approach to realize affordable and fully immersive Augmented Reality (AR) / Mixed Reality (MR) devices. For all major technology platforms (diffractive, reflective, or holographic), specialty grade high index optical glass is the central component to achieve some of the key features of AR devices, such as field of view, MTF, or weight. We will provide insights into SCHOTT’s roadmap for dedicated glass development for the AR sector and discuss the latest achievement with high relevance for the industry. It is a game of trade-offs between the desired properties to produce an optical glass which enables the entry of AR devices into the consumer market.
    Session LIVE: Special Focus: Keynote Session II
    Livestream: 22 June 2021 • 08:30 - 10:15 CEST | Zoom
    11782-14
    Author(s): Saoucene Hassad, Lab. d'Acoustique de l'Univ. du Maine, CNRS (France); Kouider Ferria, Larbi Bouamama, Univ. Ferhat Abbas Sétif 1 (Algeria); Pascal Picart, Lab. d'Acoustique de l'Univ. du Maine (France)
    On demand
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    Data acquisition and processing is a critical issue for high-speed applications especially for three-dimensional imaging and analysis. Digital holographic tomography is a potential approach that can quantitatively measure the three-dimensional distribution of the refractive index of any phase object or transparent specimen. Generally, tomography is operated by acquiring projections of the sample and numerically mapping those projections onto a 3D representation using an inverse problem, such as the filtered back projection algorithm. From the practical point of view, there are mainly two ways for recording the data. First, the set of data can be acquired when varying the illumination angle. Last, the data can be acquired by the sample rotation. In both approaches, the sample and the optical set-up must be highly stationary whereas the illumination beam or the object is rotated. Another option is to simultaneously acquire the necessary set of data with a single shot acquisition and then to process them. This would have for advantage of permitting 3D imaging of non-stationary targets or transient time-varying object. The use of multiple camera sensors is complicated and not cost efficient. So, this paper presents the proof of concept for a novel approach based on three color digital holography and the use of a single monochromatic sensor. The principle is based on off-axis holography and spatial multiplexing of multi-wavelength holograms. Three wavelengths from three different laser lines are used to illuminate the target at different incidence angles. The reference beams from the lasers are combined into a single three color beam and the spatial frequencies of the reference waves are adjusted so as to allow for the spatial multiplexing of digital holograms with the monochromatic sensor. After de-multiplexing and processing the color holograms, the amplitude and phase of the target along the views are obtained. Further processing in order to compensate for aberrations of the set-up are proposed and discussed. As proof of concept, we provide results for 3D shape of a 3D ball reconstructed using the inverse Radon transform. These first results are adequate to be exploited in the study of the acoustic field of an ultrasound transducer, for a frequency of 40Khz.
    11785-34
    Author(s): Byoungho Lee, Youngjin Jo, Dongheon Yoo, Juhyun Lee, Seoul National University (Korea, Republic of)
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    Near-eye displays (NEDs) for augmented and virtual reality (AR/VR) are spotlighted because they have a possibility to provide much more immersive experiences never possible before. With the virtue of recent progress in sensors, optics, and computer science, several commercial products are already available, and the consumer market is expanding rapidly. However, there are several challenging issues for AR and VR NEDs to become closer to our lives. Here, we will explore these issues and important topics for AR and VR, and introduce some of the ideas to overcome them: diffractive optical elements (DOEs), retinal projection displays, and 3D display with focus cues. First, unlike VR with a simple optical system, AR that needs to merge an artificial image with an outer scene requires additional optics. The diffractive elements have the merit of being thin and transparent, suitable for the image combiner. Among them, holographic optical elements (HOEs) have great potential as they can record the desired volume grating from the simple lens to the complex wavefront using light interference. Second, in order to wear the NEDs for a long time, it must deal with the visual fatigue as well as the form factor. Retinal projection display can effectively prevent the vergence-accommodation conflict problem even with a simple optical design. In the retinal projection display, the light rays from the display are adjusted to converge into a small point using a lens. It ensures a wide depth range in which the images are clearly visible. Furthermore, it is possible to provide observers with accurate focus cues for the alleviation of visual fatigue via multi-layer displays and holographic displays. Recently, we conceived tomographic NED that can reproduce dense focal planes. We confirm that this system provides quasi-continuous focus cues, semi-original contrast, and considerable depth of field. The experimental results of our prototypes are explained. We also explain the recent activities of using deep learning in holographic NED system.
    11784-7
    Author(s): Claudia Conti, CNR-Istituto di Scienze del Patrimonio Culturale (Italy); Alessandra Botteon, Istituto di Fisica del Plasma "Piero Caldirola", Consiglio Nazionale delle Ricerche (Italy); Christopher Corden, Ioan Notingher, The Univ. of Nottingham (United Kingdom); Pavel Matousek, STFC Rutherford Appleton Lab. (United Kingdom)
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    Recent advances on micro Spatially Offset Raman Spectroscopy (micro-SORS), an optical spectroscopy method able to non-invasively investigate at the microscale the molecular composition of the subsurface of turbid materials, will be presented. The recent research topics include the application of micro-SORS to non-invasively reconstruct the diffusion profiles of conservation treatments applied in calcium-based matrices, the first in-situ surveys of prestigious panel paintings with a portable micro-SORS prototype derived modifying a commercial portable Raman spectrometer, and proof-of-concept experiments performed coupling micro-SORS with Time-Gated Raman Spectral Multiplexing method for the non-invasive suppression of the fluorescence originated by the subsurface.
    Session LIVE: FET-Open on Disruptive Ideas and Optical Technologies for Health I
    Livestream: 22 June 2021 • 11:00 - 12:50 CEST | Zoom
    11786-57
    From FET to EIC-Pathfinder (Invited Paper)
    Author(s): Ioannis Fiamegkos, European Innovation Council and SMEs Executive Agency (EISMEA) (Belgium)
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    The European Innovation Council (EIC) is Europe's flagship innovation programme aiming to identify, develop and scale up breakthrough technologies and game changing innovations. EIC has been established under the EU Horizon Europe programme and It has a budget of €10.1 billion. The aim is to support game changing innovations from early stage research, to proof of concept, technology transfer, and the financing and scale up of start-ups and SMEs. The EIC takes a pro-active approach to managing funding by developing the visions for innovation and technology breakthroughs and by steering the portfolios of projects to achieve these goals. In this new environment the well-known FET is transformed to EIC Pathfinder (with the Pathfinder Open and Pathfinder Challenges calls) aiming to develop a diverse portfolio of targeted projects that explore wide-ranging technological potential, inspired by cutting-edge science, unconventional collaboration and innovative practices. Grants of up to 3 to 4 million euros support early stage development of future technologies (e.g. various activities at low Technology Readiness Levels 1-3), up to proof of concept. Pathfinder projects can also receive additional funding for testing the innovation potential of their research outputs.
    11786-58
    Author(s): Romina Rega, Martina Mugnano, Danila del Giudice, Simona Itri, Volodymyr Tkachenko, Veronica Vespini, Sara Coppola, Pietro Ferraro, Istituto di Scienze Applicate e Sistemi Intelligenti (Italy); Heidi Ottevaere, Yunfeng Nie, Vrije Universiteit Brussel (Belgium); Sanna Uusitalo, VTT Technical Research Centre of Finland (Finland); Reinhard Schwoediauer, Martin Kaltenbrunner, University of Linz (Austria); Markku Känsäkoski, Ginolis (Finland); Emanuela Mazzon, IRCCS Bonino Pulejo (Italy); Pier Luca Maffettone, Gaetano D'Avino, University of Naples (Italy); Simonetta Grilli, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy)
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    The goal of SensApp FET-Open project is to develop an innovative super-sensor that will be able to detect Alzheimer’s disease (AD) biomarkers (β-amyloid, Tau and pTAU) in peripheral blood. Considering that nowadays an accurate diagnosis of AD requires the highly invasive withdrawal and analysis of cerebrospinal fluid, SensApp will represent a breakthrough in the field of AD diagnosis thanks to the ability to detect the early stage of the disease by a simple blood collection. We call Droplet-Spilt-and-Stack (DSS) the new technology that will emerge from SensApp. The achievement of SensApp goal will be insured by the interdisciplinary cooperation between different research institutions and one company involved in the key fields of the project, Vrije University of Brussels, VTT Technical Research Centre of Finland, University of Linz, Ginolis Ltd, IRCCS Centre “Bonino Pulejo”, under the coordination of CNR-Institute of Applied Sciences and Intelligent Systems. This communication will illustrate the progress of the activities. Acknowledgments: The authors acknowledge the EU funding within the Horizon 2020 Program, under the FET-OPEN Project “SensApp”, Grant Agreement n.829104.
    11786-59
    Author(s): Stefano Vassanelli, Univ. degli Studi di Padova (Italy)
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    Neural probes for electrical imaging and microstimulation of brain networks represent an ideal communication gateway between nanoelectronic devices emulating neuron computation and biological neurons. We show that titanium oxide microelectrodes and memristors can establish synaptic-like connections between biological and silicon spiking neurons across an elementary biohybrid network.
    Session LIVE: Special Focus: Keynote Session III
    Livestream: 23 June 2021 • 14:00 - 15:30 CEST | Zoom
    11783-1
    Author(s): Lynford L. Goddard, Univ. of Illinois (United States)
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    In this talk, I will discuss several new forms of optical microscopy that my group developed in recent years. Our goal was to recover tiny nanoscale features using a conventional microscope. This problem is challenging because of the low signal to noise ratio for such features. In the first method, we introduced the regularized pseudo-phase and used it to measure nanoscale defects, minute amounts of tilt in patterned samples, and severely noise-polluted nanostructure profiles in optical images. We also extended the method to study the dynamics of droplet condensation using environmental scanning electron microscopy. In the second method, we built upon electrodynamic principles (mechanical work and force) of the light-matter interaction and applied it to sense sub-10 nm wide perturbations. In the third method, we introduced the concepts of electromagnetic canyons and non-resonance amplification using nanowires and applied these concepts to directly view individual perturbations (25-nm radius = λ/31) in a nanoscale volume.
    11786-67
    Author(s): Donald T. Miller, Indiana Univ. (United States)
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    Vision starts when light is captured by photoreceptors, specialized cells in the retina that set fundamental limits on what we can see and are unfortunately lost in many blinding diseases. While photoreceptors carry considerable clinical and scientific importance in ophthalmology and vision science, means to assess their function and health at the level of individual cells remain limited. Recent advances in adaptive optics optical coherence tomography (AO-OCT) imaging systems have enabled photoreceptor cells to be observed and tracked with unprecedented 3D resolution and sensitivity in the living human eye. This imaging capability has allowed the dynamics of these cells to be studied in exquisite detail, in particular nanoscale transients the cells generate after being stimulated by light. These changes have been found to carry fundamental information about the photoreceptor’s physiology. Here, I will describe the capability of AO-OCT to image, track, and quantify these miniscule cell dynamics and how these measurements are being used to study vision and to assess cell dysfunction and health in disease.
    Session LIVE: Optical Metrology Plenary Session
    Livestream: 23 June 2021 • 16:30 - 17:30 CEST | Zoom
    11782-500
    Author(s): Peter J. de Groot, Zygo Corporation (United States)
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    Optical instruments have long played a role in manufacturing, and strong arguments favor accelerated adoption of fast, non-contact measurements of surfaces, shapes and positions as an enabler for industry 4.0. High-precision techniques such as optical interferometry have advanced considerably and have found applications ranging from semiconductor wafer lithography to automotive engine production. Even though there are clear benefits, there are obstacles to the more widespread adoption of optical techniques for dimensional measurements. Many of these obstacles are technical--such as vibration sensitivity and metrological traceability; but others reflect the cultural gaps between academia, makers of optical instruments, standards organizations and end users. In this talk, I propose that understanding these cultural differences can assist in advancing optical methods for the most critical needs of data-driven manufacturing.
    Session LIVE: FET-Open on Disruptive Ideas and Optical Technologies for Health II
    Livestream: 24 June 2021 • 10:00 - 12:25 CEST | Zoom
    11786-60
    Author(s): Giuseppe Chirico, Univ. degli Studi di Milano-Bicocca (Italy)
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    I will review the fundamental limiting issues in in-vivo optical imaging and discuss the proposal made by the IN2SIGHT consortium to overcome them and its impact. IN2SIGHT will foster a breakthrough in in-vivo optical imaging that will renovate the biocompatibility tests (ISO10993 EU norm) required for the development of biomaterials for clinical use. These tests are economical and ethical unsustainable for small-medium industries and for the society. The IN2SIGHT approach stands on a micro-structured chip that will recast our thinking of deep tissue in-vivo imaging. I discuss how this proposal will allow unique quantification of the immune reaction to biomaterials, thus reducing time and costs for testing with a potential huge impact on public health systems and our society. The project sees the collaboration of seven partners from five countries and will exploit from the beginning inter-sectorial approaches in an interdisciplinary environment.
    11786-61
    Author(s): Paula Marques, University of Aveiro (Portugal)
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    The goal of NeuroStimSpinal FETOPEN project is to contribute with a solution for spinal cord injury (SCI). Considering the biological complexity of SCI, a small incremental discovery in this area may represent an improvement that will translate into better clinical care and in the quality of life of these patients. Therefore, a neural tissue engineered scaffold capable of not only combining fibrous and porous topographic cues in order to mimic the morphology of the native spinal cord, but also potentiating the properties of graphenebased materials supported in a protein-rich decellularized matrix is being developed to be coupled with a wireless electrical stimulation device to promote the growth and reconnection of the ruptured nerves. This communication will cover the challenge and the progresses obtained so far.
    11786-62
    Author(s): Joost Brancart, Seppe Terryn, Guy Van Assche, Vrije Univ. Brussel (Belgium); François Tournhilhac, Ecole Supérieure de Physique et de Chimie Industrielles de la Ville de Paris (France); Frank Clemens, EMPA (Switzerland); Fumiya Iida, Univ. of Cambridge (United Kingdom); Anton W. Bosman, SupraPolix B.V. (Netherlands); Bram Vanderborght, Vrije Univ. Brussel (Belgium)
    On demand
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    Soft robotic systems benefit from improved compliance and larger degrees of freedom, allowing more complex motions and safer interaction with their environment than rigid robotic structures. Due to the inherent softness of the materials that are often used to create such soft robotic structures, these systems are highly susceptible to various damage modes, such as cuts or punctures by sharp objects, overloading during actuation, flaws originating from manufacturing process or fatigue failure, drastically limiting their service lifetimes. Various types of synthetic materials that possess the ability to repair damage are being used to create soft robotic systems that are able to recover their performance by repairing incurred damage, either autonomously or after the application of a stimulus. The breakthrough targeted in the SHERO project is the development of complete robotic systems that are able to (1) sense and locate damage and to evaluate the system performance, (2) react intelligently to alleviate the damaging event and prevent catastrophic failure, (3) take the necessary measures to heal the damage to restore all functions by facilitating an autonomous or controlled healing action of the damaged element, and (4) perform a rehabilitation by evaluating the quality of the healing process and the recovery of functional performance, and finally, (5) return to action.
    11786-66
    Author(s): Mantas Grigalavicius, Kristian Berg, Theodossis A. Theodossiou, Oslo Univ. Hospital (Norway)
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    In the course of experiments for our FET open project Lumiblast, we set off to measure the excitation of various photoactive drugs (photosensitizers, PS) by the luminescence emission of luminol. Luminol (5-Amino-2,3-dihydrophthalazine-1,4-dione) is a chemical that interacts with reactive oxygen species (ROS) in basic conditions, and in the presence of metal catalysts like Fe or Cu, gives out a characteristic blue luminescence. When dissolved in organic solvents like DMSO, however, luminol only requires the addition of bases like KOH, NaOH or potassium terbutoxide, to fulfil the conditions for luminescence emission. In the present work we employed a detection system based on a spectrograph coupled to a ccd camera to register fluorescence (Fig 1B) or luminescence (Fig 1 A, C). In the case of characteristic fluorescence registration (Fig. 1B), the PSs investigated were excited by a 532 nm laser with a variable power output. We have documented the energy transfer from chemically induced luminol luminescence to a number of PSs including rose bengal, erythrosin B, hypericin amongst others. In all cases both the luminol emission and the luminol luminescence-induced PS fluorescence were registered as shown in the example of luminol and erythrosine b in Fig. 1C. We further attempted to register the generation of singlet oxygen from luminol-excited PSs. To achieve this, we employed the near-infrared (NIR) photomultiplier tube (PMT) shown in Fig.1 E, with a cut-off filter at 900nm and a bandpass filter at 1270±30 nm. This allowed only radiation within this spectral region to reach the PMT, corresponding to the characteristic phosphorescence of singlet oxygen, spin forbidden de-excitation to ground state triplet oxygen. A characteristic steady state singlet oxygen registration can be seen in Fig. 1D, for erythrosine b which has a high singlet oxygen quantum yield. The luminol luminescence was initiated by addition of terbutoxide to the DMSO luminol solution, at which point we can see a rise of the signal at 1270 nm. Upon addition of the singlet oxygen quencher, L-histidine, the signal dropped steeply to background levels. NOTE: Figures are not available.
    Session 1: Imaging in Microfluidics

    Presentations scheduled in this session will be live-streamed on Monday 21 June, 9:30 to 11:00 hrs CEST


    To view the presentation timing and to connect to this live session, please follow the Live Link at:
    https://spie.org/optical-metrology/event/monday-am-live-stream-presentations-optical-methods-for-inspection-characterization-and-imaging-of-biomaterials/2601560

    The link will be live 15 minutes prior to the announced start of the session.
    Note that times for the live broadcast are all Central European Summer Time, CEST (UTC+2:00 hours)
    11786-1
    Author(s): Massimiliano M. Villone, Erica Santonastaso, Univ. degli Studi di Napoli Federico II (Italy); Pasquale Memmolo, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy); Gianluca Trotta, Sistemi e Tecnologie Industriali Intelligenti per iil Manifattuiero Avanzato (Italy); Francesco Merola, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy); Pier Luca Maffettone, Univ. degli Studi di Napoli Federico II (Italy); Pietro Ferraro, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy)
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    The so-called “liquid biopsy” is a diagnostic test that can allow the early detection of tumors by identifying the presence of circulating tumor cells (CTC) in human peripheral blood. Such a technique can be also useful to guide the patient’s treatment, to evaluate efficacy of the treatment, and to validate whether cancer has relapsed [1]. The detection of CTCs is a challenging task due to their rarity (less than 5 cells/mL) and to their great variety. The most widely employed diagnostic techniques identify cell surface markers that are highly selective and, therefore, each of them can be used only in specific cases. On the contrary, we aim at the development of a new label-free and all-optical approach at the lab-on-chip scale for the detection of CTCs based on morphological biomarkers. In particular, we are working on the design, development, and implementation of a microfluidic platform combined with a phase-contrast tomography system to carry out quantitative measurements of the three-dimensional structure of each single cell in a blood sample [2,3]. In order to do that, the microchannels need to be engineered to conjugate two aspects: on the one hand, the cells need to perform at least one complete rotation within the field of view of the imaging apparatus; on the other hand, the highest possible throughput has to be achieved, yet without deforming the cells significantly, which would impede their tomographic reconstruction. In this contribution, the design of microfluidic channels that would allow the achievement of the aforementioned objectives for cells with different shape and deformability is presented, going from the preliminary phase, which is based on finite-element direct numerical simulations, to the actual realization of a prototype. [1] Miccio, L., et al.. Perspectives on liquid biopsy for label‐free detection of “circulating tumor cells” through intelligent lab‐on‐chips, View 2020; 20200034. [2] Villone, M.M., et al.. Full-angle tomographic phase microscopy of flowing quasi-spherical cells, Lab on a Chip 2018; 18(1):126-131. [3] Merola, F., et al.. Tomographic flow cytometry by digital holography, Light: Science & Applications 2017; 6.4:e16241-e16241.
    11786-2
    Author(s): Jalal Sadeghi, Univ. of Maryland (United States), National Institute of Standards and Technology (United States); Paul N. Patrone, Anthony J. Kearsley, Gregory Cooksey, National Institute of Standards and Technology (United States)
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    Performance improvements in microfluidic systems depend on accurate measurement and control of fluids on the micro- and nanoscale, and new applications are continuously moving the needle to lower volumetric flow rates. This work focuses on improving an optofluidic system for the measurement and calibration of microflows to the sub-nanoliter per minute range. The experimental measurements rely on an optofluidic system that delivers excitation light and records fluorescence in a precise interrogation region of a microfluidic channel. Using a scaling relationship between flow rate and the fluorescence emission after photobleaching, the system enables real-time determination of flow rates. Here we demonstrate improved calibration of a flow controller to 1 % uncertainty and improved resolution of the optofluidic flow meter to less than 1 nL/min using molecules with lower diffusion coefficients.
    11786-3
    Author(s): Yuval Atzitz, Itay Barnea, Natan T. Shaked, Tel Aviv Univ. (Israel)
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    We propose a label-free metrology technique that can perform analysis of live individual cells while they are growing individually in droplets. The cells first flow in a microfluidics device and imaged using interferometry. At the end of this device the droplets with the cells accumulate and then the cells can be monitored over time. The device presents the possibility for both high-throughput label-free analysis of individual biological cells and tracking their long-term development.
    11786-4
    Author(s): Mia Kvåle Løvmo, Benedikt Pressl, Gregor Thalhammer, Monika Ritsch-Marte, Medizinische Univ. Innsbruck (Austria)
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    As cells and tissues are highly dependent on their specific microenvironment, in-vitro models need to incorporate this 3D structure to yield reliable results in biomedical research. Cancer cell spheroids and organoids have become valuable tools in oncology and development studies as they are more representative of in-vivo tissues than the traditional 2D cell culture models and have the potential to improve throughput in drug-screening compared to animal-models and also to go towards personalized medicine. Platforms for both assembly and non-invasive long-term monitoring of such models and also for layered bio-engineered tissues are of great interest. We have developed a sono-optical microfluidic device with 3D acoustic trapping and optical tweezers for non-contact manipulation and imaging of biological samples in liquid suspension. 3D acoustic trapping is achieved with two orthogonal side-transducers and an optically transparent top-transducer that enables optical access for imaging and tweezers to the sample volume. We have demonstrated trapping of biological samples and cancer cell spheroids of several 100µm in size. With acoustics alone or combined with optical tweezers, we can trap samples, change their location and orientation or induce sustained rotation of them, without the sample being in contact with confining structures or embedded in gels. With 3D independent control of the transducers we can adjust the relative strength of the acoustic radiation and viscous torques which will determine whether transient reorientation or continuous rotation of a given sample takes place, and along with numerical simulations and experimental insight we can optimize our strategy to achieve a desired manipulation, within limitations depending on sample size and shape asymmetry. Our technique offers access to optical tomographic information, by rotation of samples around one chosen axis or two axes, and mechanical probing or it can be used for 3D patterning of cells and cell structures in gel precursors for tissue-engineering.
    11786-5
    Author(s): Biagio Mandracchia, Jeonghwan Son, Shu Jia, Georgia Institute of Technology (United States), Emory Univ. (United States)
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    A great interest in the integration between microfluidics and fluorescence microscopy has led to the flourishing of new flow-based imaging methods for both bench-top and portable solutions. Nonetheless, such systems still operate in a diffraction-limited regime due to the fact that super-resolution techniques are usually incompatible with a continuous sample flow. Here, we propose an optofluidic-based system that allows resolution doubling in moving samples, paving the way for the addition of sub-diffraction-limited imaging to the available tools for optofluidic devices.
    11786-6
    Author(s): Daniele Pirone, Pasquale Memmolo, Francesco Merola, Lisa Miccio, Martina Mugnano, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy); Amedeo Capozzoli, Claudio Curcio, Angelo Liseno, Univ. degli Studi di Napoli Federico II (Italy); Pietro Ferraro, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy)
    On demand
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    Holographic Tomography (HT) is an emerging label-free technique for microscopic bioimaging applications, that allows reconstructing the three-dimensional (3D) refractive index (RI) distribution of biological specimens. Recently, an in-flow HT technique has been proposed in which multiple digital holograms are recorded at different uncontrolled viewing angles around a sample while it flows and rotates within a microfluidic channel. Here we investigate a tracking-based rolling angles recovery method, in which the orientations of the flowing cell are retrieved from the computed 3D positions. The proposed method has been assessed both numerically and experimentally, by reconstructing the 3D RI tomograms of cancer cells.
    Session 2: Digital Holographic Microscopy I

    Presentations scheduled in this session will be live-streamed on Monday 21 June, 16:15 to 17:20 hrs CEST


    To view the presentation timing and to connect to this live session, please follow the Live Link at:
    https://spie.org/optical-metrology/event/monday-pm-live-stream-presentations-optical-methods-for-inspection-characterization-and-imaging-of-biomaterials/2601561

    The link will be live 15 minutes prior to the announced start of the session.
    Note that times for the live broadcast are all Central European Summer Time, CEST (UTC+2:00 hours)
    11786-7
    Author(s): Björn Kemper, Álvaro Barroso, Kai Eder, Anne Marzi, Sabrina Ritz, Angelos Ntovas, Jürgen Schnekenbürger, Steffi Ketelhut, Westfälische Wilhelms-Univ. Münster (Germany)
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    In laser based digital holographic microscopy (DHM) quantitative phase imaging (QPI) is affected by scattering and interference fringes due to internal reflections in the experimental setup. We present a concept for the reduction of such coherence induced disturbances. In our approach, the sample illumination light is modulated by an electrically focus tunable lens while series of digital off-axis holograms are recorded from which subsequently averaged QPI images are calculated. The concept is compatible with Mach-Zehnder interferometer-based off-axis DHM and capable for usage with commercial research microscopes. The performance is illustrated by results from living cells and tissues sections.
    11786-8
    Author(s): Alexander S. Machikhin, Scientific and Technological Ctr. of Unique Instrumentation (Russian Federation), Scientific and Technological Center of Unique Instrumentation (Russian Federation); Olga V. Polschikova, Alexey V. Gorevoy, Scientific and Technological Ctr. of Unique Instrumentation (Russian Federation); Elena V. Stoykova, Institute of Optical Materials and Technologies (Bulgaria)
    On demand
    11786-9
    Author(s): Yasaman Ganjkhani, Max-Planck-Institut für die Physik des Lichts (Germany); Alejandro Calabuig, Giancarlo Pedrini, Institut für Technische Optik (Germany), Univ. Stuttgart (Germany); Ali-Reza Moradi, Institute for Advanced Studies in Basic Sciences (Iran, Islamic Republic of)
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    In this paper, the application of oblique illumination towards removing overlapping object information from the field of view in self-referencing digital holographic microscopy is demonstrated. Self-referencing digital holographic microscopy is a compact and vibration-immune technique for 3D imaging of phase objects, however normally it suffers from restrictions on the sample type and field of view due to the interference of the object beam with part of itself. In this study, we show that applying oblique illumination in this technique not only improves the resolution, but also solves the problem of overlapping object information which can have various applications in different configurations. We first studied the application of this exciting capability in lateral shearing digital holographic microscopy using a glass plate. In lateral shearing with a glass plate, the object beams reflected from the front and back surfaces of the plate interfere on the camera plane. We used a USAF test target as a 2D object and a 1D phase grating to verify the capability of the technique. Furthermore, the technique was applied in the self-referencing digital holographic microscopy using a Lloyd’s mirror, in which part of the object beam reflected from the Lloyd’s mirror interferes with the part that arrives straightly at the camera plane and they form the hologram we showed that using two oblique lights simultaneously in this setup can enhance the resolution of 1D objects in single shot, having no overlapping object information. This characteristic was verified using the USAF test target as a sparse object and also with the 1D phase grating. The grating is a good candidate to demonstrate the capability of our method, as it is a continuous and non-sparse object.
    11786-10
    Author(s): Vincenzo Ferraro, Zhe Wang, Univ. degli Studi di Napoli Federico II (Italy); Lisa Miccio, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy); Pier Luca Maffettone, Univ. degli Studi di Napoli Federico II (Italy)
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    Quantitative measurement for thin-film thickness has been a widely studied issue, and, visualizing and characterizing for full-field thin-film evolution can provide effective data support for membrane science, polymer chemistry, biomaterials, applied Chemistry, etc. Interferometry was considered the most useful tool to measure film thickness in past decades. This is a strong limitation, especially in dynamic phenomena. In this paper, we proposed a fusion method to achieve full-field and quantitative analysis of the thin liquid film at nanoscale by using Digital Holography (DH) and White Light Interferometry (WLI) simultaneously. Compared with our previous holographic studies on thin film measurement, this new method can overcome the shortcomings of the holographic method related to registration and reconstruction, which are a) the entire life cycle registration is no longer required to obtain the thickness information; b) the region where the thin film thickness is less than half the wavelength is now measurable; c) the film thickness calibration can be obtained without any background subtraction, in the meantime, the background hologram becomes not essential in the holographic recording process.
    11786-11
    Author(s): Zhe Wang, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy), Univ. degli Studi di Napoli Federico II (Italy); Vittorio Bianco, Daniele Pirone, Pasquale Memmolo, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy); Massimiliano Maria Villone, Pier Luca Maffettone, Univ. degli Studi di Napoli Federico II (Italy); Pietro Ferraro, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy)
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    Visualizing the intracellular dynamics of plant cells has been an open challenge for modern botany, agronomy and pharmacy. In this paper, we proposed an approach to improve the phase contrast during plant cell holographic imaging by cells’ dehydration, and used this method to realize the observation of cytoplasmic circulation inside the living onion epithelial cell. The dehydration process can be seen as a sort of label-free contrast agent for better imaging biological processes. We have investigated live onion epidermal cells, observing their inner dynamics during long time recordings using a digital holographic microscopy system. For the experiments, an off-axis digital holography setup in transmission configuration with double spherical wave interference was used to record the digital holograms of onion cells. Then, we performed long-term time lapse holographic recordings of onion epidermal cells, and the results show that the intracellular tissue structure and the dynamic behavior of the cytoskeleton features and nuclei can be better exhibited via high-contrast phase imaging under cell dehydration conditions. In this case, the movements of intracellular filaments and the nucleus are observed via dynamical high-contrast phase imaging during the dehydration process. The experimental results clearly show the positive effect of dehydration process on intracellular imaging quality, and create the possibility to track the movement of plant organelles. In sum, thanks to the dehydration process of plant cells, holographic phase contrast enhancement imaging is realized.
    Session 3: Digital Holographic Microscopy II

    Presentations scheduled in this session will be live-streamed on Tuesday 22 June, 13:30 to 14:25 hrs CEST


    To view the presentation timing and to connect to this live session, please follow the Live Link at:
    https://spie.org/optical-metrology/event/tuesday-live-stream-presentations-optical-methods-for-inspection-characterization-and-imaging-of-biomaterials/2601582

    The link will be live 15 minutes prior to the announced start of the session.
    Note that times for the live broadcast are all Central European Summer Time, CEST (UTC+2:00 hours)
    11786-12
    Author(s): Martina Mugnano, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy); Giuseppe Cesare Lama, Rachele Castaldo, Istituto per i Polimeri, Compositi e Biomateriali (Italy); Francesco Merola, Danila del Giudice, Simonetta Grilli, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy); Gennaro Gentile, Istituto per i Polimeri, Compositi e Biomateriali (Italy); Veronica Ambrogi, Univ. degli Studi di Napoli Federico II (Italy); Piero Cerruti, Istituto per i Polimeri, Compositi e Biomateriali (Italy); Pasquale Memmolo, Vito Pagliarulo, Daniele Pirone, Pietro Ferraro, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy)
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    Nano graphene-based materials offer interesting physicochemical and biological properties for biotechnological applications due to their small size, large surface area and ability to interact with cells/tissues. Among carbon-based nanomaterials, graphene oxide is one of the most used in biological field. There is an increasing interest in shedding light on the interaction mechanisms of nanographene oxide (nGO) with cells. In fact, the effects on human health of GO, and its toxicological profile, are still largely unknown. Here we show that, by minimizing the oxidation degree of GO, its toxicity is significantly reduced in NIH 3T3 cells. Moreover, we show that mild oxidation of graphene nanoplatelets produces nGO particles, which are massively internalized into the cell cytoplasm. MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was performed to analyze cell viability. Transmission electron microscopy (TEM) analysis was performed to evaluate nGO internalization mechanism into the cytoplasm under different oxidation degree and concentrations. For the first time, we evaluated quantitatively, the cell volume variation after nGO internalization in live fibroblasts through a label-free digital holography (DH) imaging technique and in quasi-real-time modality, thus avoiding the time-consuming and detrimental procedures usually employed by electron-based microscopy. In conclusion, here we have demonstrated that DH can be a viable tool to visualize and display 3D distributions of nano graphene oxide (nGO) uptake by fibroblast cells. DH opens the route for high-throughput investigation at single cell level for understanding how in different conditions nanoparticles aggregates distribute inside the cells.
    11786-13
    Author(s): Lu Xin, Wen Xiao, Runyu Cao, Xintong Wu, Beihang Univ. (China); Pietro Ferraro, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy); Feng Pan, Beihang Univ. (China)
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    In bone tissue, osteocytes are embedded within a microfluid-filled network which expose them to high levels of fluid shear stress (FSS). The osteocytes’ sensitivity to different levels of FSS has demonstrated. However, there are few attempts to image 3D cellular deformation under FSS by label-free and quantitative microscopy. Digital holographic (DH) microscopy is a powerful imaging technique that can provide rich intracellular information based on the refractive index (RI) contrast, without exogenous contrast agents. However, in DH image recording process, the recorded wave-front contains not only the object’s information but also the aberrations caused by the microscope objective (MO) and the imperfections of optical components of the system. The fitting-based numerical method removes total aberrations by detecting object-free background as reference surfaces. In this paper, we proposed a convolutional neural network (CNN) for multivariate regression to cope with the phase aberration compensation problem automatically thus allows performing long-term monitoring of bone cells morphological response under FSS. We transformed the problem of estimating the coefficients for fitting a phase aberration map to a regression problem. The aberrated phase images are put into this model which can automatically learns the internal features of phase aberrations. Then the optimal coefficients are estimated as an output of the network. Based on these coefficients, the phase aberration map is built by the polynomial fitting, and the phase aberrations are removed by subtracting the aberration phase image with the phase map. The trainning and validation set contain thousands of phase image of cells. The mean square error (MSE) is used as the loss function. Then, the trained model was used for aberrations compensation in the FFS experiment of osteocytes. The results show that the proposed approach can predict the optimal coefficients and automatically compensating the phase aberrations without detecting background regions and knowing any physical parameters.
    11786-14
    Author(s): Leiping Che, Wen Xiao, Beihang Univ. (China); Pietro Ferraro, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy); Feng Pan, Beihang Univ. (China)
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    We proposed a rapid autofocusing method exploiting holographic polarization microscope, which could determine the refocusing distance without multiple reconstructions and complex network training. The defocus distance of the object is calculated rapidly by identifying the separation distance of the two defocus images of the object and using the linear relation between the defocus distance of the object and the separation distance of the two defocus images of the object. The linear relationship is obtained by numerical propagation and linear fitting. Last, we have demonstrated the effectiveness of the proposed method by reconstructing the in-focus images of flowing cells. We believe that our proposed method could be a powerful tool for dynamic observation and extend the application of holographic polarization microscope.
    11786-15
    Author(s): Zhengzhong Huang, Liangcai Cao, Tsinghua Univ. (China)
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    Digital holographic imaging has the characteristics of fast and flexible with simple set up, and it can quantitatively obtain the intensity and phase of objects. The resolution of the reconstructed image is greatly limited by the pixelated imaging detectors during the digitization processing of holograms. Due to the limited diffraction bandwidth, the diffracted beam of each object point can be viewed as a diffractive cone. The lack of diffraction components causes the reconstructed quality to decrease when the detector cannot collect a complete diffracted wave field in the inline holography. In this work, we studied the reconstructed quality of holograms under different sampling forms. The losing diffraction components can be reconstructed by using an iterative algorithm based on energy attenuation and support constraints. We propose three iterative methods. The first is the bicubic interpolation and extrapolation iterative method based on a single small detector. The second is multi-plane extrapolation iterative method. The third is a faithful iterative reconstruction based on a sparse sensor array. When the diffraction component recorded by the hologram is missing, the losing diffraction components can be reconstructed by using the principle of the holographic redundancy. The reduction of reconstruction quality caused by the loss of sampling in the small-sized detector and sparse sensor array in the digital holography can be compensated.
    11786-16
    Author(s): Lisa Miccio, Pasquale Memmolo, Jaromir Behal, Martina Mugnano, Francesco Merola, Pietro Ferraro, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy)
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    Light manipulation through living sample is one of the most challenging insight of the last ten years. Actually, in nature live matter interacts with light to manage biochemical activities and such capability inspired scientist to couple light into biological system in order to achieve well defined optical and photonic operations. In this framework, we will present the lensing effect of living cells that opens new possible routes in diagnostics and, also, in optics and photonics technologies as BioLithography.
    Session 4: Micromanipulation

    Presentations scheduled in this session will be live-streamed on Tuesday 22 June, 14:45 to 15:35 hrs CEST


    To view the presentation timing and to connect to this live session, please follow the Live Link at:
    https://spie.org/optical-metrology/event/tuesday-live-stream-presentations-optical-methods-for-inspection-characterization-and-imaging-of-biomaterials/2601582

    The link will be live 15 minutes prior to the announced start of the session.
    Note that times for the live broadcast are all Central European Summer Time, CEST (UTC+2:00 hours)
    11786-17
    Author(s): Yuchao Li, Yao Zhang, Baojun Li, Jinan Univ. (China)
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    With observation of small objects, a precisely manipulation is also highly desirable, especially for a three-dimensional manipulation of nanoparticles or biomolecules with a size of less than 100 nm. Although optical tweezers have become powerful tools to manipulate microparticles and cells, they have limits when extended to the nanoscale because of the fundamental diffraction limit of light. The emergence of near-field methods, such as plasmonic tweezers and photonic crystal resonators, have enabled surpassing of the diffraction limit. However, these methods are usually used for two-dimensional manipulation and may lead to local heating effects that will damage the biological specimens. Therefore, we propose a near-field technique that uses a photonic nanojet to perform the three-dimensional optical manipulation of sub-100-nm objects. With the photonic nanojet generated by a dielectric microlens bound to an optical fiber probe, three-dimensional manipulations were achieved for fluorescent nanoparticles as well as for plasmid DNA molecules. Backscattering and fluorescent signals from the trapped targets were detected in real time with a strong enhancement. The demonstrated approach provides a potentially powerful tool for nanostructure assembly, biosensing and single-biomolecule studies.
    11786-20
    Author(s): Andrés Puerto Vivar, Elena Torres, Mercedes Carrascosa Rico, Jose Luis Bella, Carmen López_Fernández, Ángel García-Cabañes, Univ. Autónoma de Madrid (Spain)
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    Ferroelectric crystals generate electric fields under optical and thermal excitation. Recently, these fields have been applied to act on liquid droplets, either to dispense tiny droplets or to manipulate them. In this work, we investigate bio-droplet manipulation by light-induced electric fields in ferroelectric platforms based on LiNbO3:Fe. Water, sperm, and DNA aqueous droplets have been manipulated in the experiments. The analysis of the droplet motion combined with numerical simulations allow distinguishing between neutral and charged droplets, and among different concentrations of the bio-elements inside the droplet. The results show the potential of this technique for analysis and applications in biotechnology.
    Session 5: Biomaterial Fabrication

    Presentations scheduled in this session will be live-streamed on Tuesday 22 June, 15:50 to 16:35 hrs CEST


    To view the presentation timing and to connect to this live session, please follow the Live Link at:
    https://spie.org/optical-metrology/event/tuesday-live-stream-presentations-optical-methods-for-inspection-characterization-and-imaging-of-biomaterials/2601582

    The link will be live 15 minutes prior to the announced start of the session.
    Note that times for the live broadcast are all Central European Summer Time, CEST (UTC+2:00 hours)
    11786-22
    Author(s): Mikhail S. Savelyev, National Research Univ. of Electronic Technology (Russian Federation), I.M. Sechenov First Moscow State Medical Univ. (Russian Federation); Pavel N. Vasilevsky, National Research Univ. of Electronic Technology (Russian Federation); Olga S. Kolcheva, I.M. Sechenov First Moscow State Medical Univ. (Russian Federation); Uliana E. Kurilova, Denis T. Murashko, National Research Univ. of Electronic Technology (Russian Federation); Alexander Y. Gerasimenko, National Research Univ. of Electronic Technology (Russian Federation), I.M. Sechenov First Moscow State Medical Univ. (Russian Federation)
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    The parameters of ultrashort duration laser radiation for the process of biomaterial formation based on dispersed media of bovine serum albumin and carbon nanotubes were studied. In contrast to the use of continuous laser radiation of comparable power, the composite nanomaterial is formed when lower temperature values are reached, which provides additional advantages and less change in the structure of the protein. This effect can be related to the pulse repetition frequency of 80 MHz, in the interval of about 12.5 ns, partial cooling of the material can occur, and such an effect is sufficient for the formation of biomaterial. The hardness of this material is comparable to native tissue. A strong change in the elasticity of such a material twice compared to air-drying indicates the formation of an internal framework of carbon nanotubes. The possibility of such an effect is also confirmed by spectral studies, according to which, at the used wavelength of 810 nm, absorption of radiation occurs mainly by carbon nanotubes. Subsequently, the absorbed energy is spent on the formation of a framework of carbon nanotubes and the transfer of heat to albumin. Also, this process is accompanied by the evaporation of water. In vitro studies of cell growth in the presence of biomaterial by quantitative (MTT test) and qualitative (microscopy) methods were performed. The number of cells grown on the biomaterial exceeds the number of cells in the control after 72 hours of incubation. The cells on the composites formed a monolayer; their morphology did not differ from the morphology of the cells in the control. In vitro studies indicate a positive effect of the biomaterial on cell adhesion and proliferation and, therefore, on the possibility of their use for tissue regeneration.
    11786-23
    Author(s): Alejandro Madrid Sánchez, Vrije Univ. Brussel (Belgium); Jasper Van Hoorick, Univ. Gent (Belgium); Yunfeng Nie, Fabian Duerr, Vrije Univ. Brussel (Belgium); Sandra Van Vlierberghe, Peter Dubruel, Univ. Gent (Belgium); Hugo Thienpont, Heidi Ottevaere, Vrije Univ. Brussel (Belgium)
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    Biomaterials play a key role in tissue engineering for the 3D construction of organs and scaffolds. In particular, 3D scaffolds have been used as a support to provide cells the proper environment and mechanical structure to mimic tissues functionalities. One of the widely used techniques for its fabrication is micro-stereolithography, an optical 3D additive manufacturing technique that has the required accuracy and resolution to build porous scaffolds by a layer-by-layer approach. However, the nominal printing performance of this approach is difficult to achieve when used with current bioresins due to the photochemical properties of the available materials and the formulations used in the construction process, e.g. hydrogel, photoinitiator and photoabsorber concentrations. To improve the resolution, accuracy and reduce the printing times of the scaffolds, bioresins need to be optimized prior to be considered for medical applications. Therefore, the characterization of the photo-curing properties of bioresins becomes important to estimate the accuracy of the printing process and for its optimization, increasing the resolution, sensitivity and mechanical stability. In this work, we study the material and optical specifications needed to control the printing process and optimize the photo-curing properties of the resins. As an additional requirement, biomaterials need to be biocompatible and biodegradable for use in medical applications, which reduces the number of materials that can be efficiently used in microlithographic processes. Thus, we perform a benchmark of the biomaterials suitable for microlithographic processes and compare their synthesis and photochemical properties. Finally, we propose a set of tools and materials that help to develop large-scale scaffolds with micro-sized features to use for example as a burn wound dressing for skin regeneration. This research was supported by Research Foundation – Flanders FWO (G044516N), the EU through the Horizon 2020 Program under the FET-OPEN Project “SensApp” (Grant Agreement n.829104), the Methusalem and Hercules foundations and the OZR of the Vrije Universiteit Brussel (VUB).
    Session 6: Phase Microscopy and Tomography

    Presentations scheduled in this session will be live-streamed on Wednesday 23 June, 10:10 to 11:20 hrs CEST


    To view the presentation timing and to connect to this live session, please follow the Live Link at:
    https://spie.org/optical-metrology/event/wednesday-live-stream-presentations-optical-methods-for-inspection-characterization-and-imaging-of-biomaterials/2601595

    The link will be live 15 minutes prior to the announced start of the session.
    Note that times for the live broadcast are all Central European Summer Time, CEST (UTC+2:00 hours)
    11786-25
    Author(s): Lei Tian, Alex C. Matlock, Boston Univ. (United States)
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    Intensity Diffraction Tomography (IDT) is a new computational microscopy technique providing quantitative, volumetric phase imaging of biological samples over a large field-of-view. This approach uses computationally efficient inverse scattering models to recover the 3D phase objects from a set of intensity measurements taken under diverse illumination at a single focal plane. IDT is easily implemented in a standard microscope equipped with an LED array source and requires no exogeneous contrast agents, making the technology easily accessible to the biological research community. Here, I will discuss physics-embedded deep learning-based strategies for improving the imaging capabilities of IDT for handling highly scattering 3D objects.
    11786-26
    Author(s): Hao F. Zhang, Northwestern Univ. (United States)
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    While traditional optical coherence tomography (OCT) uses near-infrared light, visible-light OCT or vis-OCT takes advantage of the much higher tissue contrast within visible light spectral range to extract physiological and pathological information in addition to ultra-high (1.3 µm) resolution anatomical imaging. Using vis-OCT, for example, we detected retinal ischemia well before the onset of angiogenesis in diabetic mouse models; produced the first three-dimensional imaging of the entire Schlemm’s canal and limbal vascular network noninvasively; and detected ganglion cell damage when clinical biomarkers were normal in glaucoma mouse models. Working with collaborators, we are also aggressively developing human vis-OCT systems and clinical protocols to improve clinical management of diabetic retinopathy and glaucoma.
    11786-27
    Author(s): Thomas Juffmann, Univ. Wien (Austria); Dorian Bouchet, Univ. Grenoble Alpes (France); Dante Maestre, Univ. Wien (Austria); Jonathan Dong, Ecole Polytechnique Fédérale de Lausanne (Switzerland)
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    Phase imaging is a widely used tool in biology with clinical applications. Various phase sensitive imaging techniques exist, ranging from phase contrast microscopy to quantitative schemes such as spatial light interference microscopy and off-axis holography. Here, we discuss these techniques in terms of the Fisher information content they provide, and the resulting Cramer Rao bounds of phase measurement accuracy [1]. We introduce the theoretical framework assuming that shot-noise is the dominant source of noise, and deduce the necessary conditions required to perform optimal phase estimations. This approach brings insights to design maximally sensitive microscopes for photon-limited applications, such as high-speed measurements, or the imaging of ultra-cold atoms or fragile biostructures. We further discuss how local wavefront shaping, adapted to the sample under study, can maximize Fisher information and enable optimal phase estimations [1,2]. We observe the largest improvement when imaging thick samples and demonstrate it experimentally. [1] Fundamental bounds on the precision of classical phase microscopes, D. Bouchet, D. Maestre, J. Dong, and T. Juffmann, https://arxiv.org/abs/2011.04799 [2] Local Optimization of Wave-fronts for optimal sensitivity PHase Imaging (LowPhi), T. Juffmann, A. de los Ríos Sommer & S. Gigan, Opt. Commun., 454, 124484 (2020), DOI: 10.1016/j.optcom.2019.124484
    11786-28
    Author(s): Vittorio Bianco, Biagio Mandracchia, Jaromir Behal, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy); Dario Barone, Univ. degli Studi di Napoli Federico II (Italy); Pasquale Memmolo, Pietro Ferraro, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy)
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    Fourier Ptychographic Microscopy (FPM) probes biological samples from multiple directions and provides amplitude and quantitative phase-contrast imaging in label-free modality with large space-bandwidth product. FPM is suitable to analyze tissues in hospitals and analysis labs by unskilled users. Whenever the FPM setup is misaligned, phase artifacts can prevent a correct retrieval of the sample complex amplitude. Here we show a blind method, named Multi-Look FPM, which eliminates the unwanted artifacts and allows non-expert users skipping the recalibration process. Multi-Look FPM is proved effective in the case of neural tissue slides, cell layers, and marine microalgae with complex inner structures.
    11786-29
    Author(s): Maciej Trusiak, Warsaw Univ. of Technology (Poland); Jose Angel Picazo-Bueno, Univ. de València (Spain); Mikołaj Rogalski, Maria Cywinska, Piotr Zdankowski, Warsaw Univ. of Technology (Poland); Vicente Micó, Univ. de València (Spain)
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    Quantitative phase imaging, employing the refractive index as endogenous contrast agent, opens wide possibilities to perform high-contrast cell measurements enabling reliable diagnostics and assessable examination. This capability can be rather easily obtained in a common-path total-shear regime after introducing a grating or beam-splitter into a regular microscope layout with a (partially-)coherent light source. Although these solutions are attractive due to straightforward implementation, overall good stability (thanks to common-path configuration) and high contrast, they are limited in time-space-bandwidth product (TSBP) as multi-frame phase reconstruction is needed to ensure sufficient accuracy and robustness. Alternative single-shot Fourier transform based approaches do allow for dynamic imaging; however they need off-axis recording and thus limit detector bandwidth and can severely truncate object spectrum (phase lateral resolution), which stays virtually intact in the multi-frame approach. Additionally, low signal-to-noise ratio of recorded fringe pattern significantly adds to the error budget via low contrast, high noise and strong incoherent background. In this contribution we study an interesting way to bypass mentioned shortcomings by recording two out-of-phase interferograms simultaneously to subtract them and thus experimentally increase the signal-to-noise ratio of otherwise low-quality dimmed fringe patterns. Ideal subtraction should yield background-rejected and modulation-doubled π-hologram, however in reality additional processing is needed. We will investigate three algorithms for such processing. Filtered interferogram is then analyzed employing Hilbert spiral transform, which is not sensitive to the carrier frequency like the Fourier transform and preserves object spectrum also in quasi on-axis configurations. Finally, sacrificing the field of view to record two interferograms at once, we gain unique feature of significantly increased TSBP enabling real-time investigation of broad-spectrum (highly detailed) transparent objects with enhanced phase resolution and signal-to-noise ratio. We corroborate the claims successfully analyzing prostate cancer cells and flowing microbeads otherwise measurable only in static regime using time-consuming phase-shifting. The technique has been validated utilizing 20x/0.46NA objective in a regular Olympus BX-60 upright microscope.
    11786-30
    Author(s): Natan Tzvi Shaked, Tel Aviv Univ. (Israel)
    On demand
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    One in six couples suffer from infertility problems. I will present our recent advances in the development of acquisition methods that enable high-resolution, fine-detail full reconstruction of the 3D movement and structure of individual human sperm cells swimming freely, in thousands of frames per second. We achieved the retrieval of the 3D refractive-index profile of the sperm head, revealing its fine internal organelles and orientation, and the detailed 4D localization of the thin and highly-dynamic sperm tail. We have also achieved virtual staining of individual sperm cells using deep learning. These stain-free imaging methods have great potential for both biological assays and clinical use of intact sperm cells during in-vitro fertilization procedures.
    Session 7: Tissue Imaging

    Presentations scheduled in this session will be live-streamed on Tuesday 22 June, 16:50 to 17:30 hrs CEST


    To view the presentation timing and to connect to this live session, please follow the Live Link at:
    https://spie.org/optical-metrology/event/tuesday-live-stream-presentations-optical-methods-for-inspection-characterization-and-imaging-of-biomaterials/2601582

    The link will be live 15 minutes prior to the announced start of the session.
    Note that times for the live broadcast are all Central European Summer Time, CEST (UTC+2:00 hours)
    11786-32
    Author(s): Kishan Dholakia, Univ of St Andrews (United Kingdom)
    On demand
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    Light is incredible. For imaging, the field of biophotonics has made astonishing advances in the last few decades due to the fact we can extract intricate knowledge of the sample, namely its morphology, molecular composition and metabolism. A prominent outcome is the 2014 Nobel Prize in Chemistry that acknowledged one of the most momentous physics developments for imaging – surpassing the spatial resolution barrier. Whilst today an impressive array of optical modalities exist and are used extensively, it is also recognised that a key barrier to optical imaging is the limited penetration depth maintaining high resolution Current all optical imaging may fail to capture high spatial resolution at significant depth. The depth of penetration for light in biological tissues and materials is limited by attenuation due to scattering and absorption. Depth may be a challenging parameter to quantify as it is highly dependent on the characteristic of the cell/tissue type and level of scattering that is present. As such quoting a distance may not always be helpful and one should also consider scattering lengths. In this talk I will describe approaches that push the use of light further in depth and allow us to gain wide fields of view with high resolution. In particular I will describe the use of shaped light in the form of propagation invariant light beams as well as the use of temporal focusing with single pixel detection. Finally progress in using more advance computational approaches such as deep learning to recover faithful images will be discussed
    11786-34
    Author(s): Almog Taieb, Tel Aviv Univ. (Israel); Garry Berkovic, Soreq Nuclear Research Ctr. (Israel); Miki Haifler, Sheba Medical Ctr. (Israel); Natan T. Shaked, Tel Aviv Univ. (Israel)
    On demand
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    We propose a multimodal quantitative, label-free and nondestructive diagnostic metrology technique by integrating off-axis interferometric phase microscopy (IPM) and Raman spectroscopy (RS), for analyzing normal and malignant bladder tissue samples. We built a Mach–Zehnder interferometer connected to a commercial confocal microscope for imaging a large area of tissue slices, up to a few millimeters, by semi-automatic scanning of the tissue. Bright-field image of hematoxylin and eosin stained tissue slice of the same area was also acquired. Measurements of Raman spectra were acquired using our RS system with excitation wavelength of 561 nm. Using the quantitative phase information, we obtained various spatial and morphological parameters of the tissues such as the anisotropy factor, which demonstrated their direct correlation with tumor presence. This method is expected to be useful for stain-free cancer diagnosis, while obtaining both quantitative information about tissue morphological modifications and changes in tissue Raman scattering properties induced by cancer.
    Session 8: Imaging

    Presentations scheduled in this session will be live-streamed on Thursday 24 June, 14:00 to 17:20 hrs CEST


    To view the presentation timing and to connect to this live session, please follow the Live Link at:
    https://spie.org/optical-metrology/event/thursday-live-stream-presentations-optical-methods-for-inspection-characterization-and-imaging-of-biomaterials/2601601

    The link will be live 15 minutes prior to the announced start of the session.
    Note that times for the live broadcast are all Central European Summer Time, CEST (UTC+2:00 hours)
    11786-35
    Author(s): Min WAN, John J. Healy, John T. Sheridan, Univ College Dublin (Ireland)
    On demand
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    One of the most fundamental operations used when processing optical image data is a correlation. It is used to identify similarity, track movement and stitch together images. However, while the correlation technique is very useful and widely employed, it suffers from several drawbacks. It can be numerically intensive (slow) and does not work well when only low pixel number detectors are available, as is the case in the THz. I will describe a new method to deal with some of these issues and which can be used to supplement correlation and improve operation.
    11786-37
    Author(s): Jonas Pfeil, Tobias Neckernuss, Daniel Geiger, Univ. Ulm (Germany), Sensific GmbH (Germany); Othmar Marti, Univ. Ulm (Germany)
    On demand
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    Measuring the mechanical properties of living tissue is a challenging task due to the small sizes and the fragility of the living organisms. A promising method, which works best on small scales, is the passive microrheology, which observes the motion of tracing beads within the sample. The video imaging method observes this motion by imaging the tracer particles with suitable optics (e.g. a microscope). As living tissue is a complex material, the viscoelastic properties are highly frequency dependent; therefore, a fast high-speed camera is needed to resolve the important frequencies in the 100 to 1000 Hz regime. As the data rate of high-speed cameras exceed the storage speed, only short burst of measurements can be carried out. This leads to a limited dynamic range of frequencies and missed measurement opportunities. It normally is not possible to track all the particles in real time to avoid the storage requirement of the video, as the tracking needs to be very precise and thus has a high computing demand. In this presentation, a combination of a CMOS imaging sensor with an FPGA is presented, which, in combination, allows for virtually unlimited long high-speed tracking of up to eight particles at up to 10 kHz. First, the sensor and the FPGA combinations are laid out. Secondly, the used particle tracking algorithm and its implementation is explained and benchmarked with a known state-of-the-art algorithm. Finally, this integrated sensor solution is mounted on a standard microscope and hour long tracking experiments on living 3T3 fibroblasts are carried out, studying the impact of blebbistatin on the mobility of polystyrene beads within the cell.
    11786-40
    Author(s): Yunfeng Nie, Vrije Univ. Brussel (Belgium); Sanna M. Aikio, Annukka Kokkonen, Sanna Uusitalo, Teemu Sipola, VTT Technical Research Ctr. of Finland Ltd. (Finland); Simonetta Grilli, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy); Heidi Ottevaere, Vrije Univ. Brussel (Belgium)
    On demand
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    The effective detection of very low abundant biomarkers can enable fast diagnosis of many severe and disabling diseases (e.g. Alzheimer’s Disease) at an early stage. To develop a cost-efficient, super-sensitive optical fluorescence detection microscope, we have proposed an optical modelling approach to predict the signal-noise-ratio that considers various noise sources introduced by the components of the detection system. After the optimal design is identified, a tolerance analysis regarding typical perturbations is performed for further mechanical design and assembly. Finally, experiments have demonstrated a limit of detection at very low abundant concentration reaching sub pmol/ml.
    11786-41
    Author(s): Maria Mangini, Istituto di Biochimica e Biologia Cellulare, Consiglio Nazionale delle Ricerche (Italy); Maria Antonietta Ferrara, Gianluigi Zito, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy); Stefano Managò, Istituto di Biochimica e Biologia Cellulare, Consiglio Nazionale delle Ricerche (Italy); Giuseppe Coppola, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy); Anna Chiara De Luca, Istituto di Biochimica e Biologia Cellulare, Consiglio Nazionale delle Ricerche (Italy)
    On demand
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    Raman spectroscopy (RS) is a label-free, non-destructive technique able to provide information about the chemical composition of the analyzed sample. RS is particularly suitable for single- and live-cell studies as it does not require invasive sample preparations or the use of labels/dyes. However, RS do not give any morphological information and long image acquisition are required. Therefore, a great advantage would be gained by combining RS with a morphological approach such as quantitative phase imaging. Dimension, optical thickness and birefringence are additional useful parameters that may be recorded via Polarization sensitive digital holographic imaging (PSDH imaging). Here, we combine RS with PSDH imaging to set up a new strategy to identify leukemia circulating tumor cells (CTCs). Indeed, even if a patient with leukemia is in remission (no symptoms or sign of disease), there could be a small pool of leukemic cells that still circulate in the bloodstream. These cells are called minimal residual disease (MRD) and their prompt and fast detection is crucial to avoid cancer recurrence or to monitor drug response. The RS and PSDH imaging analysis indicate that the combination of the two techniques is able to provide information which correlation gives a molecular and morphological signature of each cell allowing identifying leukemia cells at different stages of differentiation.
    11786-42
    Author(s): Alessandro Verde, Maria Mangini, Stefano Managò, Diana Boraschi, Paola Italiani, Anna Chiara De Luca, Consiglio Nazionale delle Ricerche (Italy)
    On demand
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    Gold nanoparticles (AuNPs) are nanodevice widely used in medical applications but often they show toxic effects on biological systems. The origin of such nanotoxicity could be ascribed to bacterial endotoxin (or Lipopolysaccharide, LPS) presence on their surface rather than to their physicochemical properties. Here we demonstrate that Surface-enhanced Raman spectroscopy (SERS) is a powerful technique which can detect the presence of LPS molecules on NPs and quantify it. Moreover, the interaction of AuNPs with human primary macrophages is investigated, in order to distinguish the intrinsic NPs biological effects from those induced by LPS.
    11786-43
    Author(s): Cheng Liu, Zonghua Zhang, Nan Gao, Zhaozong Meng, Hebei Univ. of Technology (China)
    On demand
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    Deflectometry is an efficient measurement technology of specular surface. Due to the size and shape of the used plane screen, the traditional deflectometry has limited measuring range of height and gradient field. Curved screens can be a way to solve this problem. However, existing curved screens have a changeable radius. In this talk, we present a new method to correct the curved screen in deflectometry. This method merges point cloud of location and phase information in the curved screen. Stereo vision-based phase match technique through direct triangulation and epipolar constraint is applied to compute screen’s point cloud. The experiments have been performed to test the proposed correction method. The results show high accuracy and stability in the acquisition of point cloud containing curved screen’s location and phase.
    Session 9: Biophotonics and Additive Manufacturing Technologies for 3D Health Monitoring

    Presentations scheduled in this session will be live-streamed on Thursday 24 June, 14:00 to 17:20 hrs CEST


    To view the presentation timing and to connect to this live session, please follow the Live Link at:
    https://spie.org/optical-metrology/event/thursday-live-stream-presentations-optical-methods-for-inspection-characterization-and-imaging-of-biomaterials/2601601

    The link will be live 15 minutes prior to the announced start of the session.
    Note that times for the live broadcast are all Central European Summer Time, CEST (UTC+2:00 hours)
    11786-44
    Author(s): Jürgen Popp, Leibniz-Institut für Photonische Technologien e.V. (Germany)
    On demand
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    Multimodal nonlinear imaging techniques have proven to be a versatile tool to understand morpho-chemical properties of tissues and biomaterials. Illuminating a sample with strong laser fields gives rise to a variety of nonlinear processes. The corresponding imaging modalities are inherently label-free, non-invasive, and have intrinsic z-sectioning capabilities. By choosing appropriate wavelengths, the resulting signals can be assigned to specific molecules and structures and a combination of techniques thus provides deep insight into a samples structure and composition. Our research focuses on implementations of two-photon excited fluorescence (TPEF) arising from autofluorophores such as NADH, second harmonic generation (SHG) which can be used to specifically address non-centrosymmetric compounds like collagen/myosin, and coherent anti-Stokes Raman scattering (CARS) as a tool for imaging lipids and certain biomolecules like vitamin A. Particularly interesting is the establishment of multimodal nonlinear microscopy for medical purposes. Investigating tissues of different morpho-chemistry like human spinal disk, dura mater, liver, and colon underlines the versatility and high potential of this imaging approach, e.g. to distinguish between healthy tissue and tissue altered by mechanical stress, drugs, diseases, or tumors. Translating the knowledge gained from pathological sections and in-vitro measurements to bulk and in-vivo samples eventually helps to overcome the boundary between research and diagnostics/intraoperative application. To bring multimodal nonlinear imaging from university to clinics, setups adapted to clinical needs will be introduced within this presenation. In the past years, miniaturization and innovative optical components promoted rapid progress in custom-designed small, flexible, and sterilizable setups for fast, easy, and high-resolution imaging applicable to a broad scope of questions. Examples from our group are the compact microscope MediCARS as well as our recent developments in the field of endoscopic fiber probe designs for multimodal nonlinear microscopy such as all-optical multi-core, or piezo-tube controlled double-core-double-cladding scanning fiber probes.
    11786-45
    Author(s): Maria Farsari, Foundation for Research and Technology-Hellas (Greece)
    On demand
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    We present our latest work into the modelling and fabrication of 3D auxetic metamaterials, and their evaluation as scaffolds for cell growth. Auxetic metamaterials are materials that display a negative Poisson’s ratio; when stretched, they become thicker perpendicular to the applied force. Their properties are mainly due to their architecture, rather than their chemical composition. Natural biological tissues display auxetic characteristics in organs such as skin, artery, tendon, and cancellous bone. Auxetic porous materials facilitate mass transport and, therefore, there is potential for optimal flow or delivery of nutrients, metabolic wastes and therapeutic agents. Some of their potential application are as scaffolds for blood vessels, esophageal stents, skin grafts, scaffolds for artificial lungs and cardiac patches. To make these metamaterials scaffolds, we employ 3D multiphoton polymerisation (MPP) of photopolymers. This is a technique which allows the fabrication of 3D microstructures with sub-100 nm resolution. It is based on the phenomenon of multiphoton absorption (MPA). When the beam of an ultrafast laser tightly focused inside the volume of a transparent photopolymer, it can initiate polymerisation via MPA. Moving the beam in a three-dimensional manner will result in the direct writing of 3D structures inside the volume of the photopolymer. The material employed for the fabrication of the 3D metamaterial is a homemade zirconium silicate, known to be biocompatible. Finally, we investigate the suitability of these metamaterials as scaffolds for cell growth.
    11786-46
    Author(s): Ruben Foresti, Nicola Delmonte, Stefano Rossi, Univ. degli Studi di Parma (Italy); Lorenzo Bergonzi, MaCh3D Srl (Italy); Vincenzo Vincenti, Univ. degli Studi di Parma (Italy); Guido Maria Macaluso, Univ. degli Studi di Parma (Italy), Istituto dei Materiali per l'Elettronica ed il Magnetismo, CNR (Italy); Claudio Macaluso, Stefano Selleri, Univ. degli Studi di Parma (Italy)
    On demand
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    Additive manufacturing technologies support the realization of surgical training devices using, typically, photopolymers-based materials. Unfortunately, the material jetting family, able to print a large range of soft and hard polymers, requires expensive machines and materials, which are not always available. On the other hand, vat polymerization fails in the resolution/volume ratio and in the mechanical properties reconstruction. Stereolithographic 3D printers, mostly used in dental surgery, make possible to realize cheap and sustainable models for training activity using only one material, reducing the possibility to obtain different mechanical characteristics. Moreover, the printed objects have to be treated (i.e. curing post-processing) in order to obtain the required performances, that could be preserved for long term storing. The aim of the proposed approach is to assure the surgeons’ skills improvement through bionic-based surgical 3D printed models and smart devices, able to reproduce the same perception of a real surgical activity. We demonstrated how it is possible develop smart devices capable to take into account the same characteristics of different materials (i.e. bone and spongy bone) even if stored for a long time.
    11786-47
    Author(s): Foroogh Khozeymeh Sarbishe, Stefano Selleri, Univ. degli Studi di Parma (Italy); Golshan Hamzeh, Mohammad Razaghi, Univ. of Kurdistan (Iran, Islamic Republic of)
    On demand
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    In this work, we present an ultra-high sensitivity (S) refractive index (RI) sensor for biological applications. Silicon on insulator (SOI) ring resonator (RR) based RI sensors have been extensively investigated. Light propagation is studied in the small SOI RRs based on sub-wavelength grating (SWG) waveguides with aqueous claddings. For the device analysis, the two-dimensional conformal transformation method is jointly used with the effective index method. Furthermore, FEM simulations of this structure have been also performed in both the air and water claddings. These good-matched results are further compared with experimental and FDTD results in other valid references. Having found a high data matching between our results and experimental results, we repeat our calculation for different side-widths (d=150-225 nm) and ring radii (7-10 µm). For each ring radius, the best amount of side-width is found. Then bulk refractive index sensing experiments are simulated using changing cladding RI in the range of nc=1.332-1.350 RIU. These RI changes correspond to concertation changes of glucose-water solutions in the cladding. Finally, we obtain the highest sensitivity of 24946 nm/RIU in the case of a radius 7 µm, 500 nm width, 220 nm height, 150 nm side-width, and T of 50 nm between the grating arrays on the RR. It is worth noting that this proposed structure shows 150 times sensitivity enhancement compared to a standard SOI RR-based biosensor with the same radius, w, and h. In addition, the RI sensor suggested in this work shows ultra-high sensitivity in a dynamic range of 1.332-1.352 RIU. This range of RI variation covers almost all the RI variations of the blood components. These results show excellent potential for employing the proposed SOI RR based on SWG waveguides in a liquid-biopsy analysis of patients with cancer. These might pave the way toward the early detection of cancers.
    11786-48
    Author(s): Fulvio Ratto, Istituto di Fisica Applicata "Nello Carrara" (Italy); Alessio Milanesi, Univ. degli Studi di Firenze (Italy); Giada Magni, Sonia Centi, Istituto di Fisica Applicata "Nello Carrara" (Italy); Gioacchino Schifino, Annalisa Aluigi, Istituto per la Sintesi Organica e la Fotoreattività, Consiglio Nazionale delle Ricerche (Italy); Boris N. Khlebtsov, Institute of Biochemistry and Physiology of Plants and Microorganisms RAS (Russian Federation); Lucia Cavigli, Andrea Barucci, Paolo Matteini, Istituto di Fisica Applicata "Nello Carrara" (Italy); Nikolai G. Khlebtsov, Institute of Biochemistry and Physiology of Plants and Microorganisms RAS (Russian Federation), Saratov State Univ. (Russian Federation); Roberto Pini, Francesca Rossi, Istituto di Fisica Applicata "Nello Carrara" (Italy)
    On demand
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    We disclose a new composite featuring Au@Ag core@shell nanorods in porous chitosan/polyvinyl alcohol mats or sponges for applications in wound healing and monitoring. The bimetallic construct provides synergistic opportunities for the optical activation of functions as near-infrared laser welding, and the remote assessment of parameters of prognostic relevance in wound monitoring, like the environmental level of oxidative stress. At the same time, the polymeric blend is ideal to bind connective tissue upon photothermal activation, and to support fabrication processes that ensure high porosity, such as electrospinning, thus paving the way to cellular repopulation and antimicrobial protection.
    11786-50
    Author(s): Annalisa Aluigi, Giovanna Sotgiu, Tamara Posati, Marianna Barbalinardo, Consiglio Nazionale delle Ricerche (Italy)
    On demand
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    The electrospinning and direct-writing electrospinning of protein based solutions are additive manufacturing technologies enabling the fabrication of 3D constructs which mimic the fibrous extracellular matrices (ECM) of the human tissues for geometry ad structure, as well as for its chemical composition. In the native ECM, the collagen is the most abundant fibrous protein and it is present in form of interconnected nanofibers with a diameter of 50–500 nm, which offer structural support and topographic guidance through specific orientations to surrounding cells facilitating cell–cell interactions. The electrospinning is a top-down process that offers several advantages such as, simplicity, low cost, high production rate and easy industrial scale-up. This process uses the action of a high electric field to draw very fine fibers from a polymer solution. Direct-writing electrospinning technology is an integration of electrospinning and additive manufacturing in which the jet is focused to travel in a straight line via auxiliary electrodes, melt electrospinning, or near-field electrospinning. Together with predefining translational movement of the collector or the spinneret, 3D constructs with designed patterns and accurately controlled features such as pore size can be produced. The protein nature guarantees a non-toxic biodegradability of the scaffolds and this allows to avoid the need to remove bandages or surgical implants and the consequent traumas that derive from such removal. This communication presents the potential applications of protein electrospun nanofibers in wound healing, tissue engineering, drug delivery and biosensors, particularly focusing on the processing of wool keratin proteins. Keratin is a biodegradable and biocompatible polymer possessing the amino acid sequences responsible for cell adhesion (Arg-Gly-Asp and Leu-Asp-Val). This is why it is a valid alternative to collagen and an excellent candidate for biomedical applications. Current challenges and future perspectives of keratin processing by electrospinning and additive manufacturing technologies will be here mentioned.
    Session 10: Scaffolds and Advanced Materials

    Presentations scheduled in this session will be live-streamed on Wednesday 23 June, 11:45 to 12:50 hrs CEST


    To view the presentation timing and to connect to this live session, please follow the Live Link at:
    https://spie.org/optical-metrology/event/wednesday-live-stream-presentations-optical-methods-for-inspection-characterization-and-imaging-of-biomaterials/2601595

    The link will be live 15 minutes prior to the announced start of the session.
    Note that times for the live broadcast are all Central European Summer Time, CEST (UTC+2:00 hours)
    11786-51
    Author(s): Sima Rekstyte, Edvinas Skliutas, Mangirdas Malinauskas, Vilnius Univ. (Lithuania)
    On demand
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    An ultrafast laser assisted mesoscale lithography will be introduced by presenting its technological principles, current state-of-the-art and potential in 3D printing of diverse materials ranging from biocompatible, biodegradable and renewable organics to amorphous, ceramic and crystalline inorganics. Its applications towards prototyping and producing bio-medical implants, micro-optics and nano-photonics as well as creating micro-fluidic sensors will be shown. A special emphasis on the development and applications of microfabricated structures for life-sciences will be given, namely customization of laser direct write lithography-made 3D scaffolds for optimized in vivo outcome. Furthermore, the possibility to employ the technique for precision additive manufacturing out of plant-based resins and pure inorganics will be demonstrated. Finally, some unique functional properties of selected prototypes will be provided in detail validating their high efficiency performance.
    11786-52
    Author(s): Petra Paiè, CNR-Istituto di Fotonica e Nanotecnologie (Italy); Federico Sala, Roberto Memeo, Andrea Bassi, Politecnico di Milano (Italy); Roberto Osellame, Francesca Bragheri, CNR-Istituto di Fotonica e Nanotecnologie (Italy)
    On demand
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    In this work we present a microscope on chip based on Light Sheet Fluorescence Microscopy, capable to automatically perform 3D and dual-color imaging of specimens diluted in a liquid suspension. A microfluidic channel is used for automatic sample delivery, while integrated optical components such as optical waveguides and lenses are used to illuminate the sample flowing in the channel. The device is fabricated by femtosecond laser micromachining in a glass substrate. Benefiting from the versatility of the fabrication technique we present two prototypes that have been optimized for different samples such as single cells and Drosophila embryos.
    11786-53
    Author(s): Jadze P. C. Narag, Nayere Taebnia, Rujing Zhang, Thomas L. Andresen, Niels B. Larsen, Emil B. Kromann, Technical Univ. of Denmark (Denmark)
    On demand
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    Oral drug delivery is a preferred method for drug administration because it is economical and convenient to the patient [1]. Uptake from the gut to the blood is mediated by the intestinal barrier, which exhibits some selectivity, i.e., mechanisms in the intestinal barrier define which compounds are absorbed and which are not. The limited understanding of these mechanisms impedes the design and development of new oral drugs. On the horizon: Emerging organ-on-a-chip models of the intestine may provide new insights into structure-function relationships in biological barriers like the gut-blood interface of the intestine. These small ‘artificial organs’ can host biological cells, which mimic the natural behavior of intestinal cells, thus providing a highly controlled platform for fundamental bioresearch and, ultimately, drug-screening [2]. Our group develops and implements optical imaging technologies specifically geared for imaging organ-on-a-chip systems. At the SPIE conference “Optical Methods for Inspection, Characterization, and Imaging of Biomaterials V” we will present the application of two-photon microscopy for imaging of relatively thick 3D printed organ-on-a-chip systems and discuss imaging-challenges related to sample-induced aberrations and scattering. We will also present our ongoing work to implement an adaptive optics-enabled lattice light sheet microscope [3], which (we anticipate) will enable high-resolution imaging inside complex organ-on-a-chip systems by compensating the sample-induced aberrations. [1] P. Viswanathan, Y. Muralidaran, and G. Ragavan, "Challenges in oral drug delivery: a nano-based strategy to overcome", Nanostructures for Oral Medicine, Elsevier (2017) 173-201. [2] R. Zhang and N.B. Larsen, "Stereolithographic hydrogel printing of 3D culture chips with biofunctionalized complex 3D perfusion networks", Lab on a Chip 17.24 (2017) 4273-4282. [3] T. Liu, S. Upadhyayula, et al., "Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms", Science 360.6386 (2018) eaaq1392.
    11786-55
    Author(s): Manuela T. Raimondi, Politecnico di Milano (United States); Bianca Barzaghini, Alberto Bocconi, Claudio Conci, Chiara Martinelli, Alessandra Nardini, Carolina Testa, Politecnico di Milano (Italy); Stephana Carelli, University of Milan (Italy); Giulio Cerullo, Politecnico di Milano (Italy); Giuseppe Chirico, Bicocca University of Milano (Italy); Riccardo Gottardi, University of Pennsylvania (United States), Children’s Hospital of Philadelphia (United States); Roberto Osellame, Istituto di Fotonica e Nanotecnologie IFN-CNR (Italy); Andrea Remuzzi, University of Bergamo (Italy); Matteo Laganà, Gemma Prototipi Studio (Italy); Emanuela Jacchetti, Politecnico di Milano (Italy)
    On demand
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    In this talk, we describe the frontier tools for cell modelling, including micro engineered stem cell niches, microfluidic bioreactors and miniaturized windows for intravital imaging, developed by our group with a focus on optical accessibility. Our long-term goal is to develop the potential of engineered tissue-equivalents and organoids in cell modelling, drug discovery and regenerative medicine. By working at the interface between engineering and biology, we investigate specifically the spatial and temporal effects of various micro-environmental factors, including three dimensionality (3D) of the cell environment and isotropy of the applied forces, on stem cell renewal and differentiation.
    11786-56
    Author(s): Mario Marini, Amirbahador Zeynali, Univ. degli Studi di Milano-Bicocca (Italy); Margaux Bouzin, Univ. degli Studi di Milano Bicocca (Italy); Laura Sironi, Laura D'Alfonso, Univ. degli Studi di Milano-Bicocca (Italy); Piersandro Pallavicini, Univ. degli Studi di Pavia (Italy); Maddalena Collini, Giuseppe Chirico, Univ. degli Studi di Milano-Bicocca (Italy)
    On demand
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    We exploit two-photon laser writing to fabricate 3D biocompatible proteinaceous microstructures (∼1 to 50 𝜇m in lateral size) with tunable elasticity and photo-thermal activity in the near-infrared. Structure printing relies on the photo-crosslinking of the protein bovine serum albumin (BSA, 50 mg/mL) initiated by the Rose Bengal dye (2 mM concentration), whereas photo-thermal functionality is achieved by the dispersion of non-spherically symmetric metallic nanoparticles into the ink. Aiming at a subsequent application of the fabricated microstructures as platforms for cell growth and stimulation, we carry out a thorough characterization of their mechanical and photo-thermal properties. Preliminary data obtained by AFM indentation have quantified the structures Young modulus in the broad 100-1000 kPa range depending on the BSA concentration. Stiffness is further characterized here by subjecting the fabricated microstructures to steady flow in a microfluidic device, and by quantifying their real-time bending by a conventional transmitted light microscope. In parallel, we focus on the optimization of the photo-thermal activity of the structures. Anisotropic gold nanoparticles, dispersed in the ink, get trapped into the structure during photo-crosslinking and lead to localized heat release upon excitation in the near-infrared. The temperature increment is rapidly (∼1 s) reached and maintained under continuous wave laser irradiation at 800 nm; the amplitude of the temperature variation is quantified as a function of the incident laser power by means of infrared thermography and is correlated to both the structure thickness and the nanoparticles concentration. The resulting spatially confined heat loads could be exploited to induce highly localized responses in cells. In this direction, proteinaceous photo-thermal microstructures can be used to physically induce the differentiation of cells (e.g. neurons or fibroblasts) in a spatially controlled manner.
    Session PS: Poster Session

    Posters will be available for viewing during the two live-streamed sessions on Friday 25 June, 10:00 to 11:30 hrs AND 15:30 to 17:00 hrs CEST


    Select the best time available for your time zone and join us and the poster presenters for the live poster sessions on Friday 25 June!
    Note that times for the live broadcast are all Central European Summer Time, CEST (UTC+2:00 hours)
    The poster session will be hosted on the Remo platform, allowing visitors to move freely between presentations, meet the authors, and ask questions about their research. Use this opportunity to meet your colleagues and coauthors online.

    Learn more about the Remo platform on the How to Participate page. [{https://spie.org/conferences-and-exhibitions/EOM/how-to-participate+{https://spie.org/conferences-and-exhibitions/EOM/how-to-participate}]
    11786-63
    Author(s): Andrés Puerto Vivar, Carmen López Fernández, Jose Luis Bella, Iris Elvira Rodríguez, Gladis Minguez-Vega, Ángel García-Cabañes, Mercedes Carrascosa Rico, Univ. Autónoma de Madrid (Spain)
    On demand
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    Photovoltaic optoelectronic tweezers are a powerful tool for trapping and patterning micro- and nanoparticles. By using this technique, metal nanoparticle structures have been assembled on LiNbO3:Fe. These metallic structures trapped on the ferroelectric crystal have been used as platforms to enhance the fluorescent emission of tagged biomaterials such as DNA and spermatozoa. Promising results have been obtained showing the potential of the method for improving bio-imaging procedures.
    11786-65
    Author(s): Jadze P. C. Narag, Nayere Taebnia, Rujing Zhang, Thomas L. Andresen, Niels B. Larsen, Emil B. Kromann, Technical Univ. of Denmark (Denmark)
    On demand
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    The symbiosis between the development of biomaterials and the invention of imaging techniques has kept both fields advancing towards sometimes similar other times completely separate goals. Our goal is to improve the oral delivery of biopharmaceuticals – Specifically, we seek a deeper understanding of the mechanisms that govern the transport of biological entities across the intestinal barrier. Our approach is multidisciplinary: One branch of our consortium develops biomaterials that mimic the morphological and functional properties of the intestinal barrier, thus providing a controlled arena for investigation (1). Another branch of our consortium implements a lattice light-sheet microscope with adaptive optics capability specifically geared to observe transport phenomena. The lattice light sheet, which is a thin laser beam pattern formed by the interference of multiple Bessel beams, is scanned through the sample to generate a live 3-dimensional visualization of subcellular structure and dynamics. Additionally, the system has a deformable mirror that can compensate for optical aberrations induced by the sample (cells and 3D printed scaffold), thus allowing the acquisition of high-resolution images deep in the sample (2). In this poster presentation, we will discuss how the instrument works and how it can be applied for imaging artificial organ-on-chip models of the stratified intestinal barrier. We will also discuss the possible pitfalls and challenges of working with the device. References: (1) Zhang, R., & Larsen, N. B. (2017). Stereolithographic hydrogel printing of 3D culture chips with biofunctionalized complex 3D perfusion networks. Lab on a Chip, 17(24), 4273-4282. (2) Liu, T. L., Upadhyayula, S., Milkie, D. E., Singh, V., Wang, K., Swinburne, I. A., ... & Betzig, E. (2018). Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms. Science, 360(6386).
    Conference Chair
    Institute of Applied Sciences and Intelligent Systems (ISASI-CNR) (Italy)
    Conference Chair
    Institute of Applied Sciences and Intelligent Systems (ISASI-CNR) (Italy)
    Conference Chair
    Medizinische Univ. Innsbruck (Austria)
    Conference Chair
    Medizinische Univ. Wien (Austria)
    Program Committee
    Luigi Ambrosio
    CNR (Italy)
    Program Committee
    Univ. Autónoma de Madrid (Spain)
    Program Committee
    Univ. degli Studi di Milano-Bicocca (Italy)
    Program Committee
    Gabriella Cincotti
    Univ. degli Studi di Roma Tre (Italy)
    Program Committee
    Jonathan M. Cooper
    Univ. of Glasgow (United Kingdom)
    Program Committee
    TU Dresden (Germany)
    Program Committee
    Istituto Italiano di Tecnologia (Italy)
    Program Committee
    Frank Dubois
    Univ. Libre de Bruxelles (Belgium)
    Program Committee
    Leibniz Univ. Hannover (Germany)
    Program Committee
    Technische Univ. Delft (Netherlands)
    Program Committee
    Jochen R. Guck
    Technische Univ. Dresden (Germany)
    Program Committee
    Pasquale Memmolo
    Istituto di Scienze Applicate e Sistemi Intelligenti (ISASI-CNR) (Italy)
    Program Committee
    Ctr. de Investigaciones en Óptica, A.C. (Mexico)
    Program Committee
    Institute of Applied Sciences and Intelligent Systems (ISASI-CNR) (Italy)
    Program Committee
    Institut Fresnel (France)
    Program Committee
    Vrije Univ. Brussel (Belgium)
    Program Committee
    Pablo D. Ruiz
    Loughborough Univ. (United Kingdom)
    Program Committee
    The Univ. of Western Australia (Australia)
    Program Committee
    Univ. degli Studi di Parma (Italy)
    Program Committee
    Tel Aviv Univ. (Israel)
    Program Committee
    VTT Technical Research Ctr. of Finland Ltd. (Finland)
    Program Committee
    Bar-Ilan Univ. (Israel)