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1
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Huaroto JJ, Misra S. Size and Illumination Matters: Local Magnetic Actuation and Fluorescence Imaging for Microrobotics. J Indian Inst Sci 2025; 104:745-763. [PMID: 40370769 PMCID: PMC12069155 DOI: 10.1007/s41745-024-00453-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 11/26/2024] [Indexed: 05/16/2025]
Abstract
Combining local magnetic actuation with fluorescence imaging modalities promises to introduce significant advances in microrobotic-guided procedures. This review presents the advantages and challenges of this approach, emphasizing the need for careful design considerations to optimize performance and compatibility. Traditional microrobotic actuation systems rely on bulky electromagnets, which are unsuitable for clinical use due to high power requirements and limited operational workspace. In contrast, miniaturized electromagnets can be integrated into surgical instruments, offering low power consumption and high actuation forces at the target site. Fluorescence imaging modalities have been explored in microrobotics, showcasing spatiotemporal resolution and the capability to provide information from biological entities. However, limitations, such as shallow penetration depth and out-of-focus fluorescence, have motivated the development of advanced techniques such as two-photon microscopy. The potential of two-photon microscopy to overcome these limitations is highlighted, with supporting evidence from previous studies on rat tissue samples. Current challenges in optical penetration depth, temporal resolution, and field of view are also addressed in this review. While integrating miniaturized electromagnets with fluorescence imaging modalities holds the potential for microrobotic-guided procedures, ongoing research and technological advancements are essential to translating this approach into clinical practice.
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Affiliation(s)
- Juan J. Huaroto
- Surgical Robotics Laboratory, Department of Biomechanical Engineering, University of Twente, 7522 NB, Enschede, The Netherlands
| | - Sarthak Misra
- Surgical Robotics Laboratory, Department of Biomechanical Engineering, University of Twente, 7522 NB, Enschede, The Netherlands
- Surgical Robotics Laboratory, Department of Biomaterials and Biomedical Technology, University Medical Centre Groningen and University of Groningen, 9713 GZ, Groningen, The Netherlands
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2
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Mazeika V, Mirsanaye K, Castaño LU, Krouglov S, Alizadeh M, Maciulis M, Kontenis L, Karabanovas V, Barzda V. Double Stokes polarimetric microscopy for chiral fibrillar aggregates. Sci Rep 2025; 15:4464. [PMID: 39915558 PMCID: PMC11803116 DOI: 10.1038/s41598-025-86893-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Accepted: 01/14/2025] [Indexed: 02/09/2025] Open
Abstract
Second harmonic generation (SHG) microscopy is a powerful tool for imaging collagen and other noncentrosymmetric fibrillar structures in biological tissue. Polarimetric SHG measurements provide ultrastructural information about the fibrillar organization in a focal volume (voxel). We present a reduced nonlinear polarimetry method named double Stokes polarimetry (DSP) for quick characterization of chiral C 6 symmetry fibers without data fitting that simplifies and speeds up the polarimetric analysis. The method is based on double Stokes-Mueller polarimetry and uses linear and circular incident and outgoing polarization states. The analytical expressions of DSP polarimetric parameters are defined in terms of conventional SHG Stokes vector components. A complex chiral susceptibility (CCS) model is assumed to derive expressions of ultrastructural parameters consisting of the magnitude and phase of molecular complex-valued chiral susceptibility ratio, real-valued achiral ratio, and fiber orientation in a voxel. The ultrastructural parameters are expressed in terms of directly measurable DSP polarimetric parameters. DSP is validated with rat tail tendons sectioned at different orientations. DSP can be applied to investigate the origin of chiral complex-valued susceptibility of collagen, to study modifications of collagen in cancerous tissue, and to map ultrastructural parameters of large areas for whole-slide histopathology.
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Affiliation(s)
- Viktoras Mazeika
- Institute of Biosciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania
- Laser Research Centre, Faculty of Physics, Vilnius University, Vilnius, Lithuania
| | - Kamdin Mirsanaye
- Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada
- Department of Physics, University of Toronto, Toronto, ON, Canada
- Wellman Center for Photomedicine and Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Leonardo Uribe Castaño
- Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada
- Department of Physics, University of Toronto, Toronto, ON, Canada
| | - Serguei Krouglov
- Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada
- Department of Physics, University of Toronto, Toronto, ON, Canada
| | - Mehdi Alizadeh
- Laser Research Centre, Faculty of Physics, Vilnius University, Vilnius, Lithuania
- Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada
- Department of Physics, University of Toronto, Toronto, ON, Canada
| | - Mykolas Maciulis
- Laser Research Centre, Faculty of Physics, Vilnius University, Vilnius, Lithuania
| | - Lukas Kontenis
- Laser Research Centre, Faculty of Physics, Vilnius University, Vilnius, Lithuania
- Light Conversion, Vilnius, Lithuania
| | - Vitalijus Karabanovas
- Laser Research Centre, Faculty of Physics, Vilnius University, Vilnius, Lithuania
- Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania
| | - Virginijus Barzda
- Laser Research Centre, Faculty of Physics, Vilnius University, Vilnius, Lithuania.
- Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada.
- Department of Physics, University of Toronto, Toronto, ON, Canada.
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3
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Castanha N, Challois S, Grenier D, Le-Bail P, Dubreil L, Lucas T. Multiphoton microscopy is a nondestructive label-free approach to investigate the 3D structure of gas cell walls in bread dough. Sci Rep 2023; 13:13971. [PMID: 37634004 PMCID: PMC10460382 DOI: 10.1038/s41598-023-39797-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Accepted: 07/31/2023] [Indexed: 08/28/2023] Open
Abstract
During the different steps of bread-making, changes in the microstructure of the dough, particularly in the gas cell walls (GCW), have a major influence on the final bread crumb texture. Investigation of the spatial conformation of GCWs is still a challenge because it requires both high resolutions and 3D depth imaging. The originality of the present work lies in the use of label-free non-destructive multiphoton microscopy (NLOM) to image the 3D structure of GCWs, shedding light on their behavior and organization in wheat bread dough. We demonstrated that second and third harmonic generation (SHG, THG) allow imaging, respectively, of starch granules and interfaces in bread dough, while the gluten matrix was detected via two-photon excitation fluorescence (TPEF). Last, a distinction between the gluten network and starch granules was achieved using gluten endogenous fluorescence (EF) imaging, while the position, size, and 3D orientation of starch granules in GCWs were determined from harmonic imaging, made possible by the acquisition of backward and forward SHG with linear polarization. These innovative experiments highlight the strengths of NLOM for a label-free characterization of bread dough microstructure for the first time, in order to understand the role of starch granules in dough stabilization.
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Affiliation(s)
| | | | | | - Patricia Le-Bail
- INRAE, UR1268 Biopolymers Interactions Assemblies, BP 71627, 44316, Nantes, France
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4
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Welton TA, George NM, Ozbay BN, Gentile Polese A, Osborne G, Futia GL, Kushner JK, Kleinschmidt-DeMasters B, Alexander AL, Abosch A, Ojemann S, Restrepo D, Gibson EA. Two-photon microendoscope for label-free imaging in stereotactic neurosurgery. BIOMEDICAL OPTICS EXPRESS 2023; 14:3705-3725. [PMID: 37497482 PMCID: PMC10368057 DOI: 10.1364/boe.492552] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 05/26/2023] [Accepted: 06/15/2023] [Indexed: 07/28/2023]
Abstract
We demonstrate a gradient refractive index (GRIN) microendoscope with an outer diameter of ∼1.2 mm and a length of ∼186 mm that can fit into a stereotactic surgical cannula. Two photon imaging at an excitation wavelength of 900 nm showed a field of view of ∼180 microns and a lateral and axial resolution of 0.86 microns and 9.6 microns respectively. The microendoscope was tested by imaging autofluorescence and second harmonic generation (SHG) in label-free human brain tissue. Furthermore, preliminary image analysis indicates that image classification models can predict if an image is from the subthalamic nucleus or the surrounding tissue using conventional, bench-top two-photon autofluorescence.
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Affiliation(s)
- Tarah A. Welton
- Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Nicholas M. George
- Neuroscience Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Baris N. Ozbay
- Intelligent Imaging Innovations, Denver, Colorado, 80216, USA
| | - Arianna Gentile Polese
- Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Gregory Osborne
- Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Gregory L. Futia
- Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - J. Keenan Kushner
- Neuroscience Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Bette Kleinschmidt-DeMasters
- Department of Pathology, University of Colorado School of Medicine, Aurora, CO 80045, USA
- Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA
- Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO 80045, USA
| | - Allyson L. Alexander
- Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO 80045, USA
- Division of Pediatric Neurosurgery, Children’s Hospital Colorado, Aurora CO 80045, USA
| | - Aviva Abosch
- Department of Neurosurgery, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Steven Ojemann
- Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO 80045, USA
| | - Diego Restrepo
- Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Emily A. Gibson
- Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
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5
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Line-Shaped Illumination: A Promising Configuration for a Flexible Two-Photon Microscopy Setup. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12083938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
An innovative two-photon microscope exploiting a line-shaped illumination has been recently devised and then implemented. Such configuration allows to carry out a real-time detection by means of standard CCD cameras and is able to maintain the same resolution as commonly used point-scanning devices, thus overcoming what is usually regarded as the main limitation of line-scanning microscopes. Here, we provide an overview of the applications in which this device has been tested and has proved to be a flexible and efficient tool, namely imaging of biological samples, in-depth sample reconstruction, two-photon spectra detection, and dye cross-section measurements. These results demonstrate that the considered setup is promising for future developments in many areas of research and applications.
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6
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Costanzo V, D’Apolito L, Sardella D, Iervolino A, La Manna G, Capasso G, Frische S, Trepiccione F. Single nephron glomerular filtration rate measured by linescan multiphoton microscopy compared to conventional micropuncture. Pflugers Arch 2022; 474:733-741. [PMID: 35397662 PMCID: PMC9192459 DOI: 10.1007/s00424-022-02686-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 03/27/2022] [Accepted: 03/28/2022] [Indexed: 12/19/2022]
Abstract
Renal micropuncture, which requires the direct access to the renal tubules, has for long time been the technique of choice to measure the single nephron glomerular filtration rate (SNGFR) in animal models. This approach is challenging by virtue of complex animal preparation and numerous technically difficult steps. The introduction of intravital multiphoton microscopy (MPM) offers another approach to the measure of the SNGFR by mean of the high laser-tissue penetration and the optical sectioning capacity. Previous MPM studies measuring SNGFR in vivo relied on fast full-frame acquisition during the filtration process obtainable with high performance resonant scanners. In this study, we describe an innovative linescan–based MPM method. The new method can discriminate SNGFR variations both in conditions of low and high glomerular filtration, and shows results comparable to conventional micropuncture both for rats and mice. Moreover, this novel approach has improved spatial and time resolution and is faster than previous methods, thus enabling the investigation of SNGFR from more tubules and improving options for data-analysis.
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7
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Borah BJ, Sun CK. A rapid denoised contrast enhancement method digitally mimicking an adaptive illumination in submicron-resolution neuronal imaging. iScience 2022; 25:103773. [PMID: 35169684 PMCID: PMC8829796 DOI: 10.1016/j.isci.2022.103773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 12/07/2021] [Accepted: 01/12/2022] [Indexed: 12/02/2022] Open
Abstract
Optical neuronal imaging often shows ultrafine structures, such as a nerve fiber, coexisting with ultrabright structures, such as a soma with a substantially higher fluorescence-protein concentration. Owing to experimental and environmental factors, a laser-scanning multiphoton optical microscope (MPM) often encounters a high-frequency background noise that might contaminate such weak-intensity ultrafine neuronal structures. A straightforward contrast enhancement often leads to the saturation of the brighter ones, and might further amplify the high-frequency background noise. We report a digital approach called rapid denoised contrast enhancement (DCE), which digitally mimics a hardware-based adaptive/controlled illumination technique by means of digitally optimizing the signal strengths and hence the visibility of such weak-intensity structures while mostly preventing the saturation of the brightest ones. With large field-of-view (FOV) two-photon excitation fluorescence (TPEF) neuronal imaging, we validate the effectiveness of DCE over state-of-the-art digital image processing algorithms. With compute-unified-device-architecture (CUDA)-acceleration, a real-time DCE is further enabled with a reduced time complexity.
A real-time applicable CUDA-accelerated Noise-suppressed Contrast Enhancement method Digitally mimics a traditional hardware-based adaptive/controlled illumination Drastically improves the visibility of noise-contaminated ultrafine neuronal structures Applicable in large-field high-NFOM multiphoton optical microscopes
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Affiliation(s)
- Bhaskar Jyoti Borah
- Department of Electrical Engineering and Graduate Institute of Photonics and Optoelectronics, National Taiwan University, Taipei 10617, Taiwan
| | - Chi-Kuang Sun
- Department of Electrical Engineering and Graduate Institute of Photonics and Optoelectronics, National Taiwan University, Taipei 10617, Taiwan.,Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan.,Molecular Imaging Center, National Taiwan University, Taipei 10617, Taiwan
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8
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Flores-Moreno JM, De La Torre MH, Frausto-Reyes C, Casillas R. Imaging of bee honey sugar crystals by second-harmonic generation microscopy. APPLIED OPTICS 2021; 60:7706-7713. [PMID: 34613240 DOI: 10.1364/ao.431309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 08/01/2021] [Indexed: 06/13/2023]
Abstract
Bee honey is an exceptionally nutritious food with unique chemical and mineral contents. This report introduces the use of the second-harmonic generation (SHG) microscopy for imaging honey sugar crystals' morphology as an alternative for its authentication process. The crystals and their boundaries are clearly observed with SHG compared with bright-field microscopy, where the liquid honey avoids the visualization of a sharp image. Four different honey samples of Mexico's various floral origins and geographical regions are analyzed in our study. These samples are representative of the diversity and valuable quality of bee honey production. The SHG image information is complemented with Raman spectroscopy (RS) analysis, since this optical technique is widely used to validate the bee's honey composition stated by its floral origin. We relate the SHG imaging of honey crystals with the well-defined fructose and glucose peaks measured by RS. Size measurement is introduced using the crystal´s length ratio to differentiate its floral origin. From our observations, we can state that SHG is a promising and suitable technique to provide a sort of optical fingerprint based on the floral origin of bee honey.
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9
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Wirthl V, Maisenbacher L, Weitenberg J, Hertlein A, Grinin A, Matveev A, Pohl R, Hänsch TW, Udem T. Improved active fiber-based retroreflector with intensity stabilization and a polarization monitor for the near UV. OPTICS EXPRESS 2021; 29:7024-7048. [PMID: 33726212 DOI: 10.1364/oe.417455] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 01/31/2021] [Indexed: 06/12/2023]
Abstract
We present an improved active fiber-based retroreflector (AFR) providing high-quality wavefront-retracing anti-parallel laser beams in the near UV. We use our improved AFR for first-order Doppler-shift suppression in precision spectroscopy of atomic hydrogen, but our setup can be adapted to other applications where wavefront-retracing beams with defined laser polarization are important. We demonstrate how weak aberrations produced by the fiber collimator may remain unobserved in the intensity of the collimated beam but limit the performance of the AFR. Our general results on characterizing these aberrations with a caustic measurement can be applied to any system where a collimated high-quality laser beam is required. Extending the collimator design process by wave optics propagation tools, we achieved a four-lens collimator for the wavelength range 380-486 nm with the beam quality factor of M2 ≃ 1.02, limited only by the not exactly Gaussian beam profile from the single-mode fiber. Furthermore, we implemented precise fiber-collimator alignment and improved the collimation control by combining a precision motor with a piezo actuator. Moreover, we stabilized the intensity of the wavefront-retracing beams and added in-situ monitoring of polarization from polarimetry of the retroreflected light.
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10
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He Z, Wang P, Ye X. Novel endoscopic optical diagnostic technologies in medical trial research: recent advancements and future prospects. Biomed Eng Online 2021; 20:5. [PMID: 33407477 PMCID: PMC7789310 DOI: 10.1186/s12938-020-00845-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 12/23/2020] [Indexed: 12/20/2022] Open
Abstract
Novel endoscopic biophotonic diagnostic technologies have the potential to non-invasively detect the interior of a hollow organ or cavity of the human body with subcellular resolution or to obtain biochemical information about tissue in real time. With the capability to visualize or analyze the diagnostic target in vivo, these techniques gradually developed as potential candidates to challenge histopathology which remains the gold standard for diagnosis. Consequently, many innovative endoscopic diagnostic techniques have succeeded in detection, characterization, and confirmation: the three critical steps for routine endoscopic diagnosis. In this review, we mainly summarize researches on emerging endoscopic optical diagnostic techniques, with emphasis on recent advances. We also introduce the fundamental principles and the development of those techniques and compare their characteristics. Especially, we shed light on the merit of novel endoscopic imaging technologies in medical research. For example, hyperspectral imaging and Raman spectroscopy provide direct molecular information, while optical coherence tomography and multi-photo endomicroscopy offer a more extensive detection range and excellent spatial-temporal resolution. Furthermore, we summarize the unexplored application fields of these endoscopic optical techniques in major hospital departments for biomedical researchers. Finally, we provide a brief overview of the future perspectives, as well as bottlenecks of those endoscopic optical diagnostic technologies. We believe all these efforts will enrich the diagnostic toolbox for endoscopists, enhance diagnostic efficiency, and reduce the rate of missed diagnosis and misdiagnosis.
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Affiliation(s)
- Zhongyu He
- Biosensor National Special Laboratory, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, 310027, People's Republic of China
| | - Peng Wang
- Biosensor National Special Laboratory, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, 310027, People's Republic of China
| | - Xuesong Ye
- Biosensor National Special Laboratory, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, 310027, People's Republic of China.
- State Key Laboratory of CAD and CG, Zhejiang University, Hangzhou, 310058, People's Republic of China.
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11
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Mizuguchi T, Nuriya M. Applications of second harmonic generation (SHG)/sum-frequency generation (SFG) imaging for biophysical characterization of the plasma membrane. Biophys Rev 2020; 12:10.1007/s12551-020-00768-4. [PMID: 33108561 PMCID: PMC7755958 DOI: 10.1007/s12551-020-00768-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Accepted: 10/20/2020] [Indexed: 12/12/2022] Open
Abstract
The plasma membrane is a lipid bilayer of < 10 nm width that separates intra- and extra-cellular environments and serves as the site of cell-cell communication, as well as communication between cells and the extracellular environment. As such, biophysical phenomena at and around the plasma membrane play key roles in determining cellular physiology and pathophysiology. Thus, the selective visualization and characterization of the plasma membrane are crucial aspects of research in wide areas of biology and medicine. However, the specific characterization of the plasma membrane has been a challenge using conventional imaging techniques, which are unable to effectively distinguish between signals arising from the plasma membrane and those from intracellular lipid structures. In this regard, interface-specific second harmonic generation (SHG) and sum-frequency generation (SFG) imaging demonstrate great potential. When combined with exogenous SHG/SFG active dyes, SHG/SFG can specifically highlight the plasma membrane as the most prominent interface associated with cells. Furthermore, SHG/SFG imaging can be readily extended to multimodal multiphoton microscopy with simultaneous occurrence of other multiphoton phenomena, including multiphoton excitation and coherent Raman scattering, which shed light on the biophysical properties of the plasma membrane from different perspectives. Here, we review traditional and current applications, as well as the prospects of long-known but unexplored SHG/SFG imaging techniques in biophysics, with special focus on their use in the biophysical characterization of the plasma membrane.
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Affiliation(s)
- Takaha Mizuguchi
- Department of Pharmacology School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Mutsuo Nuriya
- Department of Pharmacology School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
- Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Saitama, 332-0012, Japan.
- Keio Advanced Research Center for Water Biology and Medicine, Keio University, 2-15-45 Mita, Minato-ku, Tokyo, 108-8345, Japan.
- Graduate School of Environment and Information Sciences, Yokohama National University, 79-7 Tokiwadai, Hodogaya, Yokohama, Kanagawa, 240-8501, Japan.
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12
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Tokarz D, Cisek R, Joseph A, Asa SL, Wilson BC, Barzda V. Characterization of pathological thyroid tissue using polarization-sensitive second harmonic generation microscopy. J Transl Med 2020; 100:1280-1287. [PMID: 32737408 DOI: 10.1038/s41374-020-0475-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/07/2020] [Accepted: 07/09/2020] [Indexed: 11/09/2022] Open
Abstract
Polarization-sensitive second harmonic generation (SHG) microscopy is an established imaging technique able to provide information related to specific molecular structures including collagen. In this investigation, polarization-sensitive SHG microscopy was used to investigate changes in the collagen ultrastructure between histopathology slides of normal and diseased human thyroid tissues including follicular nodular disease, Grave's disease, follicular variant of papillary thyroid carcinoma, classical papillary thyroid carcinoma, insular or poorly differentiated carcinoma, and anaplastic or undifferentiated carcinoma ex vivo. The second-order nonlinear optical susceptibility tensor component ratios, χ(2)zzz'/χ(2)zxx' and χ(2)xyz'/χ(2)zxx', were obtained, where χ(2)zzz'/χ(2)zxx' is a structural parameter and χ(2)xyz'/χ(2)zxx' is a measure of the chirality of the collagen fibers. Furthermore, the degree of linear polarization (DOLP) of the SHG signal was measured. A statistically significant increase in χ(2)zzz'/χ(2)zxx' values for all the diseased tissues except insular carcinoma and a statistically significant decrease in DOLP for all the diseased tissues were observed compared to normal thyroid. This finding indicates a higher ultrastructural disorder in diseased collagen and provides an innovative approach to discriminate between normal and diseased thyroid tissues that is complementary to standard histopathology.
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Affiliation(s)
- Danielle Tokarz
- Department of Chemistry, Saint Mary's University, Halifax, NS, Canada.
| | - Richard Cisek
- Department of Chemistry, Saint Mary's University, Halifax, NS, Canada
| | - Ariana Joseph
- Department of Chemistry, Saint Mary's University, Halifax, NS, Canada
| | - Sylvia L Asa
- University Health Network, University of Toronto, Toronto, ON, Canada.,University Hospitals Cleveland Medical Center, Cleveland, OH, USA.,Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
| | - Brian C Wilson
- Princess Margaret Cancer Centre/University Health Network, Toronto, ON, Canada. .,Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
| | - Virginijus Barzda
- Department of Physics, University of Toronto, Toronto, ON, Canada. .,Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada.
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13
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Wang H, Gupta SK, Xie B, Lu M. Topological photonic crystals: a review. FRONTIERS OF OPTOELECTRONICS 2020; 13:50-72. [PMID: 36641586 PMCID: PMC9743952 DOI: 10.1007/s12200-019-0949-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 10/16/2019] [Indexed: 06/13/2023]
Abstract
The field of topological photonic crystals has attracted growing interest since the inception of optical analog of quantum Hall effect proposed in 2008. Photonic band structures embraced topological phases of matter, have spawned a novel platform for studying topological phase transitions and designing topological optical devices. Here, we present a brief review of topological photonic crystals based on different material platforms, including all-dielectric systems, metallic materials, optical resonators, coupled waveguide systems, and other platforms. Furthermore, this review summarizes recent progress on topological photonic crystals, such as higherorder topological photonic crystals, non-Hermitian photonic crystals, and nonlinear photonic crystals. These studies indicate that topological photonic crystals as versatile platforms have enormous potential applications in maneuvering the flow of light.
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Affiliation(s)
- Hongfei Wang
- National Laboratory of Solid State Microstructures and Department of Materials Science and Engineering, Nanjing University, Nanjing, 210093, China
| | - Samit Kumar Gupta
- National Laboratory of Solid State Microstructures and Department of Materials Science and Engineering, Nanjing University, Nanjing, 210093, China
| | - Biye Xie
- National Laboratory of Solid State Microstructures and Department of Materials Science and Engineering, Nanjing University, Nanjing, 210093, China
| | - Minghui Lu
- National Laboratory of Solid State Microstructures and Department of Materials Science and Engineering, Nanjing University, Nanjing, 210093, China.
- Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China.
- Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, 210093, China.
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14
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Repgen P, Wandt D, Morgner U, Neumann J, Kracht D. Sub-50 fs, µJ-level pulses from a Mamyshev oscillator-amplifier system. OPTICS LETTERS 2019; 44:5973-5976. [PMID: 32628196 DOI: 10.1364/ol.44.005973] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 11/12/2019] [Indexed: 06/11/2023]
Abstract
In this Letter, we present a Mamyshev oscillator with an output power of 332 mW and a pulse energy of 31 nJ, which is directly amplified in an additional fiber section. By balancing the gain-narrowing effect with self-phase modulation during the amplification, we achieved an average output power of 11 W, corresponding to a pulse energy of more than 1 µJ. The pulse duration can be compressed to sub-50 fs behind the amplification stage.
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15
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Gomes JAC, Barbano EC, Misoguti L. Cross-section profile of the nonlinear refractive index of Gorilla Glass obtained by nonlinear ellipse rotation measurements. APPLIED OPTICS 2019; 58:7858-7861. [PMID: 31674472 DOI: 10.1364/ao.58.007858] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 08/30/2019] [Indexed: 06/10/2023]
Abstract
In this work we determined the influence of potassium-to-sodium ion exchange in the nonlinear refractive value (n2) of Corning's Gorilla Glass (GG). Due to the production process, GG has a rich potassium surface in comparison to the original sodium matrix glass. In order to determine the nonlinear cross-section profile, we have used a highly sensitive nonlinear elliptical rotation spatial measurement. Using a simple model, where the nonlinearity varies exponentially with depth, we observed that the value of the nonlinear refraction at the surface is about 22% greater than that of the matrix interior with a penetration depth constant of ∼50 μm.
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16
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Lee JH, Rico-Jimenez JJ, Zhang C, Alex A, Chaney EJ, Barkalifa R, Spillman DR, Marjanovic M, Arp Z, Hood SR, Boppart SA. Simultaneous label-free autofluorescence and multi-harmonic imaging reveals in vivo structural and metabolic changes in murine skin. BIOMEDICAL OPTICS EXPRESS 2019; 10:5431-5444. [PMID: 31646056 PMCID: PMC6788598 DOI: 10.1364/boe.10.005431] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 09/11/2019] [Accepted: 09/24/2019] [Indexed: 05/10/2023]
Abstract
Simultaneous quantification of multifarious cellular metabolites and the extracellular matrix in vivo has been long sought. Simultaneous label-free autofluorescence and multi-harmonic (SLAM) microscopy has achieved simultaneous four-channel nonlinear imaging to study tissue structure and metabolism. In this study, we implemented two laser systems and directly compared SLAM microscopy with conventional two-photon microscopy for in vivo imaging. We found that three-photon imaging of adenine dinucleotide (phosphate) (NAD(P)H) in SLAM microscopy using our tailored laser source provided better resolution, contrast, and background suppression than conventional two-photon imaging of NAD(P)H. We also integrated fluorescence lifetime imaging with SLAM microscopy, and enabled differentiation of free and bound NAD(P)H. We imaged murine skin in vivo and showed that changes in tissue structure, cell dynamics, and metabolism can be monitored simultaneously in real-time. We also discovered an increase in metabolism and protein-bound NAD(P)H in skin cells during the early stages of wound healing.
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Affiliation(s)
- Jang Hyuk Lee
- Center for Optical Molecular Imaging, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Co-first authors with equal contribution
| | - Jose J. Rico-Jimenez
- Center for Optical Molecular Imaging, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Co-first authors with equal contribution
| | - Chi Zhang
- Center for Optical Molecular Imaging, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Aneesh Alex
- GlaxoSmithKline, Collegeville, PA 19426, USA
| | - Eric J. Chaney
- Center for Optical Molecular Imaging, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Ronit Barkalifa
- Center for Optical Molecular Imaging, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Darold R. Spillman
- Center for Optical Molecular Imaging, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Marina Marjanovic
- Center for Optical Molecular Imaging, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Zane Arp
- GlaxoSmithKline, Collegeville, PA 19426, USA
| | | | - Stephen A. Boppart
- Center for Optical Molecular Imaging, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA
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17
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Purvis K, Brittain K, Joseph A, Cisek R, Tokarz D. Third-order nonlinear optical properties of phycobiliproteins from cyanobacteria and red algae. Chem Phys Lett 2019. [DOI: 10.1016/j.cplett.2019.136599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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18
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Cohen SR, Fourkas JT. Extracting Information on Linear and Nonlinear Absorption from Two-Beam Action Spectroscopy Data. J Phys Chem A 2019; 123:7314-7322. [PMID: 31352785 DOI: 10.1021/acs.jpca.9b06068] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Two-beam action (2-BA) spectroscopies are a recently developed class of techniques for determining the order(s) of absorption (one-photon, two-photon, etc.) that contribute to an observable signal. When only a single order of absorption is present, 2-BA spectroscopies allow for the determination of that order from data obtained at a single value of the observable. It has been shown previously that when two orders of absorption are present, they can be determined unambiguously from measurements made at several values of the observable. However, this latter approach cannot be used for single-valued observables, such as a polymerization threshold. Here we develop a theoretical comparison between conventional methods that determine the order(s) of absorption using logarithmic plots and 2-BA-based techniques. We also explore how 2-BA plots arising from two orders of absorption deviate from a plot with a single, noninteger exponent. We demonstrate that these deviations can usually be used to identify the two orders of absorption and their relative contributions to the signal on the basis of measurements made at a single value of the observable.
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19
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Kazarine A, Gopal AA, Wiseman PW. Nonlinear microscopy of common histological stains reveals third harmonic generation harmonophores. Analyst 2019; 144:3239-3249. [PMID: 30920574 DOI: 10.1039/c9an00267g] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Since its invention over a hundred years ago, histological analysis using coloured dye staining remains the gold standard for histopathology. While these stains provide critical information for a variety of diagnostic purposes, they offer limited two-dimensional histological information. Extending classical histological analysis to three dimensions requires novel imaging approaches such as multiphoton microscopy. Multiphoton microscopy enables multimodal, three-dimensional imaging of histologically stained samples. Specifically, third harmonic generation (THG), a nonlinear optical process in which three incident photons are combined into one by the sample, allows high contrast imaging of tissues stained with absorbing dyes, which in turn act as harmonophores. While this technique has previously been applied to hematoxylin and eosin (H&E) tissue sections, we extend this approach to other commonly used histological stains to demonstrate further potential applications of the technique. We demonstrate THG imaging of both human skin and liver tissue stained with H&E, Verhoeff-Van Gieson (VVG) and Picrosirius Red stains. We find that these stains provide excellent contrast as THG harmonophores, enabling high resolution imaging of histological samples. THG imaging of the Verhoeff stain enables easy detection of elastic fibers while Picrosirius Red acts as an effective harmonophore for imaging collagen fibers of all sizes.
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Affiliation(s)
- Alexei Kazarine
- Department of Chemistry, McGill University, 801 Sherbrooke St West, Montreal, QC H3A 0B8, Canada.
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20
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Next-generation imaging of the skeletal system and its blood supply. Nat Rev Rheumatol 2019; 15:533-549. [PMID: 31395974 DOI: 10.1038/s41584-019-0274-y] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2019] [Indexed: 12/16/2022]
Abstract
Bone is organized in a hierarchical 3D architecture. Traditionally, analysis of the skeletal system was based on bone mass assessment by radiographic methods or on the examination of bone structure by 2D histological sections. Advanced imaging technologies and big data analysis now enable the unprecedented examination of bone and provide new insights into its 3D macrostructure and microstructure. These technologies comprise ex vivo and in vivo methods including high-resolution computed tomography (CT), synchrotron-based imaging, X-ray microscopy, ultra-high-field magnetic resonance imaging (MRI), light-sheet fluorescence microscopy, confocal and intravital two-photon imaging. In concert, these techniques have been used to detect and quantify a novel vascular system of trans-cortical vessels in bone. Furthermore, structures such as the lacunar network, which harbours and connects osteocytes, become accessible for 3D imaging and quantification using these methods. Next-generation imaging of the skeletal system and its blood supply are anticipated to contribute to an entirely new understanding of bone tissue composition and function, from macroscale to nanoscale, in health and disease. These insights could provide the basis for early detection and precision-type intervention of bone disorders in the future.
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21
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Clancy B, Moree B, Salafsky J. Angular Mapping of Protein Structure Using Nonlinear Optical Measurements. Biophys J 2019; 117:500-508. [PMID: 31349993 PMCID: PMC6697465 DOI: 10.1016/j.bpj.2019.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 06/12/2019] [Accepted: 07/02/2019] [Indexed: 11/22/2022] Open
Abstract
Proteins are inherently dynamic, flexible molecules that execute precise conformational changes to perform their functions, but existing techniques to directly measure relevant structural changes in solution at room temperature remain limited. Here, we demonstrate a structural technique using second-harmonic generation and two-photon fluorescence under single-laser excitation to map both the mean angular orientation and the distribution width of a probe at various sites throughout the protein with high sensitivity. Our work resolves distinct dihydrofolate reductase (DHFR) ligand-protein conformations, allows interrogation of regions unresolvable by other techniques, and reveals structural differences between DHFR and a point mutant (DHFR-G121V). The technique, angular mapping of protein structure, enables direct and rapid determination of previously unseen aspects of protein structure in a benchtop optical system.
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22
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Ultrasonic Influence on Plasmonic Effects Exhibited by Photoactive Bimetallic Au-Pt Nanoparticles Suspended in Ethanol. MATERIALS 2019; 12:ma12111791. [PMID: 31163572 PMCID: PMC6600762 DOI: 10.3390/ma12111791] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Revised: 05/15/2019] [Accepted: 05/16/2019] [Indexed: 12/14/2022]
Abstract
The optical behavior exhibited by bimetallic nanoparticles was analyzed by the influence of ultrasonic and nonlinear optical waves in propagation through the samples contained in an ethanol suspension. The Au-Pt nanoparticles were prepared by a sol-gel method. Optical characterization recorded by UV-vis spectrophotometer shows two absorption peaks correlated to the synergistic effects of the bimetallic alloy. The structure and nanocrystalline nature of the samples were confirmed by Scanning Transmission Electron Microscopy with X-ray energy dispersive spectroscopy evaluations. The absorption of light associated with Surface Plasmon Resonance phenomena in the samples was modified by the dynamic influence of ultrasonic effects during the propagation of optical signals promoting nonlinear absorption and nonlinear refraction. The third-order nonlinear optical response of the nanoparticles dispersed in the ethanol-based fluid was explored by nanosecond pulses at 532 nm. The propagation of high-frequency sound waves through a nanofluid generates a destabilization in the distribution of the nanoparticles, avoiding possible agglomerations. Besides, the influence of mechanical perturbation, the container plays a major role in the resonance and attenuation effects. Ultrasound interactions together to nonlinear optical phenomena in nanofluids is a promising alternative field for a wide of applications for modulating quantum signals, sensors and acousto-optic devices.
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23
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Tokarz D, Cisek R, Joseph A, Golaraei A, Mirsanaye K, Krouglov S, Asa SL, Wilson BC, Barzda V. Characterization of Pancreatic Cancer Tissue Using Multiphoton Excitation Fluorescence and Polarization-Sensitive Harmonic Generation Microscopy. Front Oncol 2019; 9:272. [PMID: 31058080 PMCID: PMC6478795 DOI: 10.3389/fonc.2019.00272] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 03/25/2019] [Indexed: 12/31/2022] Open
Abstract
Thin tissue sections of normal and tumorous pancreatic tissues stained with hematoxylin and eosin were investigated using multiphoton excitation fluorescence (MPF), second harmonic generation (SHG), and third harmonic generation (THG) microscopies. The cytoplasm, connective tissue, collagen and extracellular structures are visualized with MPF due to the eosin stain, whereas collagen is imaged with endogenous SHG contrast that does not require staining. Cellular structures, including membranous interfaces and nuclear components, are seen with THG due to the aggregation of hematoxylin dye. Changes in the collagen ultrastructure in pancreatic cancer were investigated by a polarization-sensitive SHG microscopy technique, polarization-in, polarization-out (PIPO) SHG. This involves measuring the orientation of the linear polarization of the SHG signal as a function of the linear polarization orientation of the incident laser radiation. From the PIPO SHG data, the second-order non-linear optical susceptibility ratio, χ(2) zzz '/χ(2) zxx ', was obtained that serves as a structural parameter for characterizing the tissue. Furthermore, by assuming C6 symmetry, an additional second-order non-linear optical susceptibility ratio, χ(2) xyz '/χ(2) zxx ', was obtained, which is a measure of the chirality of the collagen fibers. Statistically-significant differences in the χ(2) zzz '/χ(2) zxx ' values were found between tumor and normal pancreatic tissues in periductal, lobular, and parenchymal regions, whereas statistically-significant differences in the full width at half maximum (FWHM) of χ(2) xyz '/χ(2) zxx ' occurrence histograms were found between tumor and normal pancreatic tissues in periductal and parenchymal regions. Additionally, the PIPO SHG data were used to determine the degree of linear polarization (DOLP) of the SHG signal, which indicates the relative linear depolarization of the signal. Statistically-significant differences in DOLP values were found between tumor and normal pancreatic tissues in periductal and parenchymal regions. Hence, the differences observed in the χ(2) zzz '/χ(2) zxx ' values, the FWHM of χ(2) xyz '/χ(2) zxx ' values and the DOLP values could potentially be used to aid pathologists in diagnosing pancreatic cancer.
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Affiliation(s)
- Danielle Tokarz
- Department of Chemistry, Saint Mary's University, Halifax, NS, Canada
| | - Richard Cisek
- Department of Chemistry, Saint Mary's University, Halifax, NS, Canada
| | - Ariana Joseph
- Department of Chemistry, Saint Mary's University, Halifax, NS, Canada
| | - Ahmad Golaraei
- Department of Physics, University of Toronto, Toronto, ON, Canada
- Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada
- Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - Kamdin Mirsanaye
- Department of Physics, University of Toronto, Toronto, ON, Canada
- Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada
| | - Serguei Krouglov
- Department of Physics, University of Toronto, Toronto, ON, Canada
- Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada
| | - Sylvia L. Asa
- University Health Network, University of Toronto, Toronto, ON, Canada
| | - Brian C. Wilson
- Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
| | - Virginijus Barzda
- Department of Physics, University of Toronto, Toronto, ON, Canada
- Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada
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24
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Sederberg S, Firby CJ, Elezzabi AY. Efficient, broadband third-harmonic generation in silicon nanophotonic waveguides spectrally shaped by nonlinear propagation. OPTICS EXPRESS 2019; 27:4990-5004. [PMID: 30876106 DOI: 10.1364/oe.27.004990] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Accepted: 01/20/2019] [Indexed: 06/09/2023]
Abstract
Optical emission from silicon is most practically accessible through nonlinear optical wave mixing, due to the indirect bandgap of the material. Although silicon is a material that absorbs visible light, third-harmonic generation driven by infrared signals can be used to generate visible light in silicon structures. In this work, we present a comprehensive investigation into third-harmonic generation in silicon-on-insulator waveguides. We demonstrate that few-micrometer length waveguides can be used to up-convert ultrafast 1550nm laser pulses to their third-harmonic with efficiencies up to ηTHG=2.8×10-5, the highest third-harmonic generation conversion efficiency reported to date in a silicon-based structure. Nonlinear propagation through 200μm long waveguides produces self-compressing temporal solitons, which dramatically broaden and blue shift the observed third-harmonic spectrum. Such devices are envisioned to provide a method for generating coherent visible signals within an integrated, CMOS compatible platform.
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25
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Sun Y, Cheng Y, Zeng KY. Metal–Organic Frameworks (MOFs) as Potential Hybrid Ferroelectric Materials. LAYERED MATERIALS FOR ENERGY STORAGE AND CONVERSION 2019. [DOI: 10.1039/9781788016193-00197] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
This chapter presents new findings of intrinsic and induced ferroelectricity in Metal–Organic Frameworks (MOFs) with a polar system, capable of forming an electronic structure in an asymmetric lattice. Multiple experimental techniques and simulation methods are reviewed in detail. The characteristics of ferroelectrics such as discontinuity in temperature-dependent dielectric constant, polarization hysteresis loops, etc. have been observed from several MOF large crystals and crystalline powders. A relationship between polarization and bond polarity for MOFs has been established. In addition, we emphasize the significance of mechanical strength of MOFs in real applications. This chapter reviews MOF materials for energy storage and utilization, aiming to provide an insight into the design of novel MOF-based ferroelectrics.
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Affiliation(s)
- Y. Sun
- Department of Mechanical Engineering, National University of Singapore 117576 Singapore
| | - Y. Cheng
- Institute of High Performance Computing, Agency for Science Technology and Research 138632 Singapore
| | - K. Y. Zeng
- Department of Mechanical Engineering, National University of Singapore 117576 Singapore
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26
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HASANI E, PARRAVICINI J, TARTARA L, TOMASELLI A, TOMASSINI D. Measurement of two-photon-absorption spectra through nonlinear fluorescence produced by a line-shaped excitation beam. J Microsc 2018; 270:210-216. [DOI: 10.1111/jmi.12675] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Accepted: 12/12/2017] [Indexed: 01/06/2023]
Affiliation(s)
- E. HASANI
- Dipartimento di Ingegneria Industriale e dell'Informazione; Università di Pavia; I-27100 Pavia Italy
| | - J. PARRAVICINI
- Dipartimento di Scienza dei Materiali; Università di Milano-Bicocca; I-20125 Milano Italy
| | - L. TARTARA
- Dipartimento di Ingegneria Industriale e dell'Informazione; Università di Pavia; I-27100 Pavia Italy
| | - A. TOMASELLI
- Dipartimento di Ingegneria Industriale e dell'Informazione; Università di Pavia; I-27100 Pavia Italy
| | - D. TOMASSINI
- Dipartimento di Ingegneria Industriale e dell'Informazione; Università di Pavia; I-27100 Pavia Italy
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27
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Small DM, Jones JS, Tendler II, Miller PE, Ghetti A, Nishimura N. Label-free imaging of atherosclerotic plaques using third-harmonic generation microscopy. BIOMEDICAL OPTICS EXPRESS 2018; 9:214-229. [PMID: 29359098 PMCID: PMC5772576 DOI: 10.1364/boe.9.000214] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 11/24/2017] [Accepted: 12/02/2017] [Indexed: 05/18/2023]
Abstract
Multiphoton microscopy using laser sources in the mid-infrared range (MIR, 1,300 nm and 1,700 nm) was used to image atherosclerotic plaques from murine and human samples. Third harmonic generation (THG) from atherosclerotic plaques revealed morphological details of cellular and extracellular lipid deposits. Simultaneous nonlinear optical signals from the same laser source, including second harmonic generation and endogenous fluorescence, resulted in label-free images of various layers within the diseased vessel wall. The THG signal adds an endogenous contrast mechanism with a practical degree of specificity for atherosclerotic plaques that complements current nonlinear optical methods for the investigation of cardiovascular disease. Our use of whole-mount tissue and backward scattered epi-detection suggests THG could potentially be used in the future as a clinical tool.
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Affiliation(s)
- David M. Small
- Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, 526 N. Campus Rd., Ithaca, NY 14853, USA
- Contributed equally
| | - Jason S. Jones
- Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, 526 N. Campus Rd., Ithaca, NY 14853, USA
- Contributed equally
| | - Irwin I. Tendler
- Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, 526 N. Campus Rd., Ithaca, NY 14853, USA
| | - Paul E. Miller
- Anabios Corporation, 3030 Bunker Hill St., San Diego, CA 92109, USA
| | - Andre Ghetti
- Anabios Corporation, 3030 Bunker Hill St., San Diego, CA 92109, USA
| | - Nozomi Nishimura
- Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, 526 N. Campus Rd., Ithaca, NY 14853, USA
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28
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Tang W, Zhao J, Li T, Yang K, Zhao S, Li G, Li D, Qiao W. High-peak-power mode-locking pulse generation in a dual-loss-modulated laser with BP-SA and EOM. OPTICS LETTERS 2017; 42:4820-4823. [PMID: 29216119 DOI: 10.1364/ol.42.004820] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Accepted: 10/03/2017] [Indexed: 06/07/2023]
Abstract
In this Letter, a high-quality black phosphorus saturable absorber (BP-SA) with a multilayer structure was prepared, and its corresponding characteristics were investigated. Based on the BP-SA and an electro-optic modulator (EOM), a dual-loss-modulated mode-locked laser with a controllable repetition rate and high peak power was realized, which has the repetition rate of EOM and the mode-locking pulse width in the Q-switching and mode-locking laser. The output performances versus the pump power were measured. The maximum pulse peak power of 3.89 MW was obtained with the minimum pulse duration of 119 ps. To the best of our knowledge, this is the highest pulse peak power with BP-SA reported.
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29
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Kong C, Pilger C, Hachmeister H, Wei X, Cheung TH, Lai CSW, Huser T, Tsia KK, Wong KKY. Compact fs ytterbium fiber laser at 1010 nm for biomedical applications. BIOMEDICAL OPTICS EXPRESS 2017; 8:4921-4932. [PMID: 29188091 PMCID: PMC5695941 DOI: 10.1364/boe.8.004921] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Revised: 09/23/2017] [Accepted: 10/02/2017] [Indexed: 05/30/2023]
Abstract
Ytterbium-doped fiber lasers (YDFLs) working in the near-infrared (NIR) spectral window and capable of high-power operation are popular in recent years. They have been broadly used in a variety of scientific and industrial research areas, including light bullet generation, optical frequency comb formation, materials fabrication, free-space laser communication, and biomedical diagnostics as well. The growing interest in YDFLs has also been cultivated for the generation of high-power femtosecond (fs) pulses. Unfortunately, the operating wavelengths of fs YDFLs have mostly been confined to two spectral bands, i.e., 970-980 nm through the three-level energy transition and 1030-1100 nm through the quasi three-level energy transition, leading to a spectral gap (990-1020 nm) in between, which is attributed to an intrinsically weak gain in this wavelength range. Here we demonstrate a high-power mode-locked fs YDFL operating at 1010 nm, which is accomplished in a compact and cost-effective package. It exhibits superior performance in terms of both short-term and long-term stability, i.e., <0.3% (peak intensity over 2.4 μs) and <4.0% (average power over 24 hours), respectively. To illustrate the practical applications, it is subsequently employed as a versatile fs laser for high-quality nonlinear imaging of biological samples, including two-photon excited fluorescence microscopy of mouse kidney and brain sections, as well as polarization-sensitive second-harmonic generation microscopy of potato starch granules and mouse tail muscle. It is anticipated that these efforts will largely extend the capability of fs YDFLs which is continuously tunable over 970-1100 nm wavelength range for wideband hyperspectral operations, serving as a promising complement to the gold-standard Ti:sapphire fs lasers.
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Affiliation(s)
- Cihang Kong
- Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China
- These authors contributed equally to the paper
| | - Christian Pilger
- Biomolecular Photonics, Department of Physics, University of Bielefeld, Universitätsstr, 25, 33615 Bielefeld, Germany
- These authors contributed equally to the paper
| | - Henning Hachmeister
- Biomolecular Photonics, Department of Physics, University of Bielefeld, Universitätsstr, 25, 33615 Bielefeld, Germany
- These authors contributed equally to the paper
| | - Xiaoming Wei
- Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China
| | - Tom H Cheung
- Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China
| | - Cora S W Lai
- Department of Physiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Thomas Huser
- Biomolecular Photonics, Department of Physics, University of Bielefeld, Universitätsstr, 25, 33615 Bielefeld, Germany
| | - Kevin K Tsia
- Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China
| | - Kenneth K Y Wong
- Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China
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30
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Tokarz D, Cisek R, Wein MN, Turcotte R, Haase C, Yeh SCA, Bharadwaj S, Raphael AP, Paudel H, Alt C, Liu TM, Kronenberg HM, Lin CP. Intravital imaging of osteocytes in mouse calvaria using third harmonic generation microscopy. PLoS One 2017; 12:e0186846. [PMID: 29065178 PMCID: PMC5655444 DOI: 10.1371/journal.pone.0186846] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 10/09/2017] [Indexed: 01/27/2023] Open
Abstract
Osteocytes are the most abundant cell in the bone, and have multiple functions including mechanosensing and regulation of bone remodeling activities. Since osteocytes are embedded in the bone matrix, their inaccessibility makes in vivo studies problematic. Therefore, a non-invasive technique with high spatial resolution is desired. The purpose of this study is to investigate the use of third harmonic generation (THG) microscopy as a noninvasive technique for high-resolution imaging of the lacunar-canalicular network (LCN) in live mice. By performing THG imaging in combination with two- and three-photon fluorescence microscopy, we show that THG signal is produced from the bone-interstitial fluid boundary of the lacuna, while the interstitial fluid-osteocyte cell boundary shows a weaker THG signal. Canaliculi are also readily visualized by THG imaging, with canaliculi oriented at small angles relative to the optical axis exhibiting stronger signal intensity compared to those oriented perpendicular to the optical axis (parallel to the image plane). By measuring forward- versus epi-detected THG signals in thinned versus thick bone samples ex vivo, we found that the epi-collected THG from the LCN of intact bone contains a superposition of backward-directed and backscattered forward-THG. As an example of a biological application, THG was used as a label-free imaging technique to study structural variations in the LCN of live mice deficient in both histone deacetylase 4 and 5 (HDAC4, HDAC5). Three-dimensional analyses were performed and revealed statistically significant differences between the HDAC4/5 double knockout and wild type mice in the number of osteocytes per volume and the number of canaliculi per lacunar surface area. These changes in osteocyte density and dendritic projections occurred without differences in lacunar size. This study demonstrates that THG microscopy imaging of the LCN in live mice enables quantitative analysis of osteocytes in animal models without the use of dyes or physical sectioning.
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Affiliation(s)
- Danielle Tokarz
- Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Richard Cisek
- Department of Physical and Chemical Sciences, University of Toronto, Mississauga, Ontario, Canada
| | - Marc N. Wein
- Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Raphaël Turcotte
- Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Christa Haase
- Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Shu-Chi A. Yeh
- Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Srinidhi Bharadwaj
- Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Anthony P. Raphael
- Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
- Dermatology Research Centre, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia
| | - Hari Paudel
- Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Clemens Alt
- Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Tzu-Ming Liu
- Institute of Biomedical Engineering and Molecular Imaging Center, National Taiwan University, Taipei, Taiwan. Faculty of Health Sciences, University of Macau, Macau SAR, China
| | - Henry M. Kronenberg
- Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Charles P. Lin
- Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
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Karunendiran A, Cisek R, Tokarz D, Barzda V, Stewart BA. Examination of Drosophila eye development with third harmonic generation microscopy. BIOMEDICAL OPTICS EXPRESS 2017; 8:4504-4513. [PMID: 29082080 PMCID: PMC5654795 DOI: 10.1364/boe.8.004504] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 07/28/2017] [Accepted: 09/05/2017] [Indexed: 05/21/2023]
Abstract
Third harmonic generation (THG) microscopy can exploit endogenous harmonophores such as pigment macromolecules for enhanced image contrast, and therefore can be used without exogenous contrast agents. Previous studies have established that carotenoid compounds are ideal harmonophores for THG microscopy; we therefore sought to determine whether THG from endogenous carotenoid-derived compounds, such as retinal in photoreceptor cells, could serve as a new label-free method for developmental studies. Here we study the development of the pupal eye in Drosophila melanogaster and determine the localization of rhodopsin using THG microscopy technique. Additionally, by altering the chromophore or the opsin protein we were able to detect changes in both the retinal distribution morphology and in THG intensity age-dependent profiles. These results demonstrate that THG microscopy can be used to detect altered photoreceptor development and may be useful in clinically relevant conditions associated with photoreceptor degeneration.
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Affiliation(s)
- Abiramy Karunendiran
- Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, Ontario L5L 1C6, Canada
- Department of Cell and Systems Biology, University of Toronto, 25 Harbord St, Toronto, Ontario M5S 3G5, Canada
| | - Richard Cisek
- Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, Ontario L5L 1C6, Canada
- Department of Physics and Institute for Optical Sciences, University of Toronto, 60 St. George Street, Toronto, Ontario M5S 1A7, Canada
| | - Danielle Tokarz
- Princess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, Ontario M5G 1L7, Canada
| | - Virginijus Barzda
- Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, Ontario L5L 1C6, Canada
- Department of Physics and Institute for Optical Sciences, University of Toronto, 60 St. George Street, Toronto, Ontario M5S 1A7, Canada
| | - Bryan A Stewart
- Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, Ontario L5L 1C6, Canada
- Department of Cell and Systems Biology, University of Toronto, 25 Harbord St, Toronto, Ontario M5S 3G5, Canada
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Cisek R, Tokarz D, Kontenis L, Barzda V, Steup M. Polarimetric second harmonic generation microscopy: An analytical tool for starch bioengineering. STARCH-STARKE 2017. [DOI: 10.1002/star.201700031] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Richard Cisek
- Department of Physics; University of Toronto; Toronto Ontario Canada
- Department of Chemical and Physical Sciences; University of Toronto Mississauga; Mississauga Ontario Canada
| | - Danielle Tokarz
- Wellman Center for Photomedicine, Massachusetts General Hospital; Harvard Medical School; Boston MA USA
| | - Lukas Kontenis
- Department of Physics; University of Toronto; Toronto Ontario Canada
- Department of Chemical and Physical Sciences; University of Toronto Mississauga; Mississauga Ontario Canada
| | - Virginijus Barzda
- Department of Physics; University of Toronto; Toronto Ontario Canada
- Department of Chemical and Physical Sciences; University of Toronto Mississauga; Mississauga Ontario Canada
| | - Martin Steup
- Department of Plant Physiology, Institute of Biochemistry and Biology; University of Potsdam; Potsdam Germany
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Ng JL, Knothe LE, Whan RM, Knothe U, Tate MLK. Scale-up of nature's tissue weaving algorithms to engineer advanced functional materials. Sci Rep 2017; 7:40396. [PMID: 28074876 PMCID: PMC5225443 DOI: 10.1038/srep40396] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Accepted: 12/07/2016] [Indexed: 01/13/2023] Open
Abstract
We are literally the stuff from which our tissue fabrics and their fibers are woven and spun. The arrangement of collagen, elastin and other structural proteins in space and time embodies our tissues and organs with amazing resilience and multifunctional smart properties. For example, the periosteum, a soft tissue sleeve that envelops all nonarticular bony surfaces of the body, comprises an inherently "smart" material that gives hard bones added strength under high impact loads. Yet a paucity of scalable bottom-up approaches stymies the harnessing of smart tissues' biological, mechanical and organizational detail to create advanced functional materials. Here, a novel approach is established to scale up the multidimensional fiber patterns of natural soft tissue weaves for rapid prototyping of advanced functional materials. First second harmonic generation and two-photon excitation microscopy is used to map the microscopic three-dimensional (3D) alignment, composition and distribution of the collagen and elastin fibers of periosteum, the soft tissue sheath bounding all nonarticular bone surfaces in our bodies. Then, using engineering rendering software to scale up this natural tissue fabric, as well as multidimensional weaving algorithms, macroscopic tissue prototypes are created using a computer-controlled jacquard loom. The capacity to prototype scaled up architectures of natural fabrics provides a new avenue to create advanced functional materials.
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Affiliation(s)
- Joanna L. Ng
- Graduate School of Biomedical Engineering, University of New South Wales (UNSW) Australia, Sydney, Australia
| | - Lillian E. Knothe
- Graduate School of Biomedical Engineering, University of New South Wales (UNSW) Australia, Sydney, Australia
- School of Art & Design, University of New South Wales (UNSW) Australia, Sydney, Australia
| | - Renee M. Whan
- Biomedical Imaging Facility, Mark Wainwright Analytical Centre, UNSW Australia, Sydney, Australia
| | - Ulf Knothe
- Cleveland Clinic, Cleveland, USA
- TissuTex Pty Ltd, Wentworth Falls, Australia
| | - Melissa L. Knothe Tate
- Graduate School of Biomedical Engineering, University of New South Wales (UNSW) Australia, Sydney, Australia
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Genetically Encoded Voltage Indicators: Opportunities and Challenges. J Neurosci 2016; 36:9977-89. [PMID: 27683896 DOI: 10.1523/jneurosci.1095-16.2016] [Citation(s) in RCA: 108] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 07/25/2016] [Indexed: 11/21/2022] Open
Abstract
UNLABELLED A longstanding goal in neuroscience is to understand how spatiotemporal patterns of neuronal electrical activity underlie brain function, from sensory representations to decision making. An emerging technology for monitoring electrical dynamics, voltage imaging using genetically encoded voltage indicators (GEVIs), couples the power of genetics with the advantages of light. Here, we review the properties that determine indicator performance and applicability, discussing both recent progress and technical limitations. We then consider GEVI applications, highlighting studies that have already deployed GEVIs for biological discovery. We also examine which classes of biological questions GEVIs are primed to address and which ones are beyond their current capabilities. As GEVIs are further developed, we anticipate that they will become more broadly used by the neuroscience community to eavesdrop on brain activity with unprecedented spatiotemporal resolution. SIGNIFICANCE STATEMENT Genetically encoded voltage indicators are engineered light-emitting protein sensors that typically report neuronal voltage dynamics as changes in brightness. In this review, we systematically discuss the current state of this emerging method, considering both its advantages and limitations for imaging neural activity. We also present recent applications of this technology and discuss what is feasible now and what we anticipate will become possible with future indicator development. This review will inform neuroscientists of recent progress in the field and help potential users critically evaluate the suitability of genetically encoded voltage indicator imaging to answer their specific biological questions.
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Odstrcil M, Baksh P, Gawith C, Vrcelj R, Frey JG, Brocklesby WS. Nonlinear ptychographic coherent diffractive imaging. OPTICS EXPRESS 2016; 24:20245-20252. [PMID: 27607631 DOI: 10.1364/oe.24.020245] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Ptychographic Coherent diffractive imaging (PCDI) is a significant advance in imaging allowing the measurement of the full electric field at a sample without use of any imaging optics. So far it has been confined solely to imaging of linear optical responses. In this paper we show that because of the coherence-preserving nature of nonlinear optical interactions, PCDI can be generalised to nonlinear optical imaging. We demonstrate second harmonic generation PCDI, directly revealing phase information about the nonlinear coefficients, and showing the general applicability of PCDI to nonlinear interactions.
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Adur J, Barbosa G, Pelegati V, Baratti M, Cesar C, Casco V, Carvalho H. Multimodal and non-linear optical microscopy applications in reproductive biology. Microsc Res Tech 2016; 79:567-82. [DOI: 10.1002/jemt.22684] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Revised: 04/18/2016] [Accepted: 05/04/2016] [Indexed: 01/11/2023]
Affiliation(s)
- J. Adur
- Biophotonic Group. Optics and Photonics Research Center (CEPOF); Institute of Physics “Gleb Wataghin,” State University of Campinas; Brazil
- Biofotónica y Procesamiento de Información Biológica (ByPIB); CITER - Centro de Investigación y Transferencia de Entre Ríos, CONICET-UNER; Argentina
- Microscopy Laboratory Applied to Molecular and Cellular Studies, School of Bioengineering; National University of Entre Ríos; Argentina
| | - G.O. Barbosa
- Department of Structural and Functional Biology; Biology Institute, State University of Campinas; Brazil
| | - V.B. Pelegati
- Biophotonic Group. Optics and Photonics Research Center (CEPOF); Institute of Physics “Gleb Wataghin,” State University of Campinas; Brazil
- INFABiC - National Institute of Science and Technology on Photonics Applied to Cell Biology, Campinas; Brazil
| | - M.O. Baratti
- INFABiC - National Institute of Science and Technology on Photonics Applied to Cell Biology, Campinas; Brazil
| | - C.L. Cesar
- Biophotonic Group. Optics and Photonics Research Center (CEPOF); Institute of Physics “Gleb Wataghin,” State University of Campinas; Brazil
- INFABiC - National Institute of Science and Technology on Photonics Applied to Cell Biology, Campinas; Brazil
- Department of Physics of Federal University of Ceara (UFC); Brazil
| | - V.H. Casco
- Biofotónica y Procesamiento de Información Biológica (ByPIB); CITER - Centro de Investigación y Transferencia de Entre Ríos, CONICET-UNER; Argentina
- Microscopy Laboratory Applied to Molecular and Cellular Studies, School of Bioengineering; National University of Entre Ríos; Argentina
| | - H.F. Carvalho
- Department of Structural and Functional Biology; Biology Institute, State University of Campinas; Brazil
- INFABiC - National Institute of Science and Technology on Photonics Applied to Cell Biology, Campinas; Brazil
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Stoltzfus CR, Rebane A. High contrast two-photon imaging of fingermarks. Sci Rep 2016; 6:24142. [PMID: 27053515 PMCID: PMC4823789 DOI: 10.1038/srep24142] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2016] [Accepted: 03/21/2016] [Indexed: 11/09/2022] Open
Abstract
Optically-acquired fingermarks are widely used as evidence across law enforcement agencies as well as in the courts of law. A common technique for visualizing latent fingermarks on nonporous surfaces consists of cyanoacrylate fuming of the fingerprint material, followed by impregnation with a fluorescent dye, which under ultra violet (UV) illumination makes the fingermarks visible and thus accessible for digital recording. However, there exist critical circumstances, when the image quality is compromised due to high background scattering, high auto-fluorescence of the substrate material, or other detrimental photo-physical and photo-chemical effects such as light-induced damage to the sample. Here we present a novel near-infrared (NIR), two-photon induced fluorescence imaging modality, which significantly enhances the quality of the fingermark images, especially when obtained from highly reflective and/or scattering surfaces, while at the same time reducing photo-damage to sensitive forensic samples.
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Affiliation(s)
- Caleb R Stoltzfus
- Physics Department, Montana State University, Bozeman MT. 59717, USA
| | - Aleksander Rebane
- Physics Department, Montana State University, Bozeman MT. 59717, USA.,National Institute of Chemical Physics and Biophysics, Tallinn, Estonia, 12618
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Fischer MC, Wilson JW, Robles FE, Warren WS. Invited Review Article: Pump-probe microscopy. THE REVIEW OF SCIENTIFIC INSTRUMENTS 2016; 87:031101. [PMID: 27036751 PMCID: PMC4798998 DOI: 10.1063/1.4943211] [Citation(s) in RCA: 108] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 02/07/2016] [Indexed: 05/17/2023]
Abstract
Multiphoton microscopy has rapidly gained popularity in biomedical imaging and materials science because of its ability to provide three-dimensional images at high spatial and temporal resolution even in optically scattering environments. Currently the majority of commercial and home-built devices are based on two-photon fluorescence and harmonic generation contrast. These two contrast mechanisms are relatively easy to measure but can access only a limited range of endogenous targets. Recent developments in fast laser pulse generation, pulse shaping, and detection technology have made accessible a wide range of optical contrasts that utilize multiple pulses of different colors. Molecular excitation with multiple pulses offers a large number of adjustable parameters. For example, in two-pulse pump-probe microscopy, one can vary the wavelength of each excitation pulse, the detection wavelength, the timing between the excitation pulses, and the detection gating window after excitation. Such a large parameter space can provide much greater molecular specificity than existing single-color techniques and allow for structural and functional imaging without the need for exogenous dyes and labels, which might interfere with the system under study. In this review, we provide a tutorial overview, covering principles of pump-probe microscopy and experimental setup, challenges associated with signal detection and data processing, and an overview of applications.
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Affiliation(s)
- Martin C Fischer
- Department of Chemistry, Duke University, Durham, North Carolina 27708, USA
| | - Jesse W Wilson
- Department of Chemistry, Duke University, Durham, North Carolina 27708, USA
| | - Francisco E Robles
- Department of Chemistry, Duke University, Durham, North Carolina 27708, USA
| | - Warren S Warren
- Departments of Chemistry, Biomedical Engineering, Physics, and Radiology, Duke University, Durham, North Carolina 27708, USA
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Barbano EC, Harrington K, Zilio SC, Misoguti L. Third-harmonic generation at the interfaces of a cuvette filled with selected organic solvents. APPLIED OPTICS 2016; 55:595-602. [PMID: 26835935 DOI: 10.1364/ao.55.000595] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
We report on the third-harmonic generation (THG) of tightly focused femtosecond laser pulses at the interfaces of a cuvette filled with organic solvents. Such a system presents four interfaces separating two materials of different refractive indices and third-order nonlinear susceptibilities where the THG takes place because the symmetry around the focus is broken. We selected two cuvettes (silica and B270 crown glass) filled with different organic solvents (acetone, chloroform, and dimethyl sulfoxide) in order to have a variety of interfaces with different linear and nonlinear optical properties. For some of the peaks, the self-focusing modifies the expected cubic power law dependence for THG and as a consequence the four peak profiles may be quite uneven. Although the THG is due to the electronic part of the nonlinear susceptibility, it can suffer from the influence of the self-focusing effect, a Kerr nonlinearity that can have both instantaneous electronic and slow nuclear contributions. This mixture of two distinct third-order nonlinear processes was never considered for such interfaces. All the THG signals could be understood by taking into account the self-focusing effect. Furthermore, the nonlinear refractive indices, n(2), and third-order nonlinear susceptibilities of the solvents, χ((3)), could be determined simultaneously by the THG signals using the cuvette walls as a reference.
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Sotor J, Pasternak I, Krajewska A, Strupinski W, Sobon G. Sub-90 fs a stretched-pulse mode-locked fiber laser based on a graphene saturable absorber. OPTICS EXPRESS 2015; 23:27503-27508. [PMID: 26480410 DOI: 10.1364/oe.23.027503] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
In this paper a stretched-pulse, mode-locked Er-doped fiber laser based on graphene saturable absorber (SA) is presented. A 60 layer graphene/polymer composite was used as a SA. The all-fiber dispersion managed laser resonator with the repetition frequency of 21.15 MHz allows for Gaussian pulses generation with the full width at half maximum (FWHM) of 48 nm. The generated chirped pulses were compressed outside the cavity to the 88 fs using a piece of standard single mode fiber. The average output power and pulse energy were of 1.5 mW and 71 pJ, respectively.
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Cisek R, Tokarz D, Steup M, Tetlow IJ, Emes MJ, Hebelstrup KH, Blennow A, Barzda V. Second harmonic generation microscopy investigation of the crystalline ultrastructure of three barley starch lines affected by hydration. BIOMEDICAL OPTICS EXPRESS 2015; 6:3694-700. [PMID: 26504621 PMCID: PMC4605030 DOI: 10.1364/boe.6.003694] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 08/24/2015] [Accepted: 08/25/2015] [Indexed: 05/03/2023]
Abstract
Second harmonic generation (SHG) microscopy is employed to study changes in crystalline organization due to altered gene expression and hydration in barley starch granules. SHG intensity and susceptibility ratio values (R'SHG ) are obtained using reduced Stokes-Mueller polarimetric microscopy. The maximum R'SHG values occur at moderate moisture indicating the narrowest orientation distribution of nonlinear dipoles from the cylindrical axis of glucan helices. The maximum SHG intensity occurs at the highest moisture and amylopectin content. These results support the hypothesis that SHG is caused by ordered hydrogen and hydroxyl bond networks which increase with hydration of starch granules.
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Affiliation(s)
- Richard Cisek
- Department of Chemical and Physical Sciences, Department of
Physics and Institute for Optical Sciences, University of Toronto, 3359 Mississauga Road,
Mississauga, ON, L5L 1C6, Canada
| | - Danielle Tokarz
- Department of Chemical and Physical Sciences, Department of
Physics and Institute for Optical Sciences, University of Toronto, 3359 Mississauga Road,
Mississauga, ON, L5L 1C6, Canada
| | - Martin Steup
- Department of Plant Physiology, Institute of Biochemistry and
Biology, University of Potsdam, Karl-Liebknecht-Strasse 24-25 Building 20, 14476 Potsdam,
Germany
- Department of Molecular and Cellular Biology, College of
Biological Science, Summerlee Science Complex, University of Guelph, 50 Stone Road East,
Guelph, ON, N1G 2W1, Canada
| | - Ian J. Tetlow
- Department of Molecular and Cellular Biology, College of
Biological Science, Summerlee Science Complex, University of Guelph, 50 Stone Road East,
Guelph, ON, N1G 2W1, Canada
| | - Michael J. Emes
- Department of Molecular and Cellular Biology, College of
Biological Science, Summerlee Science Complex, University of Guelph, 50 Stone Road East,
Guelph, ON, N1G 2W1, Canada
| | - Kim H. Hebelstrup
- Department of Molecular Biology and Genetics, Aarhus University,
Forsøgsvej 1, 4200 Slagelse, Denmark
| | - Andreas Blennow
- Department of Plant and Environmental Sciences, University of
Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark
| | - Virginijus Barzda
- Department of Chemical and Physical Sciences, Department of
Physics and Institute for Optical Sciences, University of Toronto, 3359 Mississauga Road,
Mississauga, ON, L5L 1C6, Canada
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Trägårdh J, Robb G, Gadalla KKE, Cobb S, Travis C, Oppo GL, McConnell G. Label-free imaging of thick tissue at 1550 nm using a femtosecond optical parametric generator. OPTICS LETTERS 2015; 40:3484-7. [PMID: 26258338 DOI: 10.1364/ol.40.003484] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
We have developed a simple wavelength-tunable optical parametric generator (OPG), emitting broadband ultrashort pulses with peak wavelengths at 1530-1790 nm, for nonlinear label-free microscopy. The OPG consists of a periodically poled lithium niobate crystal, pumped at 1064 nm by a ultrafast Yb:fiber laser with high pulse energy. We demonstrate that this OPG can be used for label-free imaging, by third-harmonic generation, of nuclei of brain cells and blood vessels in a >150 μm thick brain tissue section, with very little decay of intensity with imaging depth and no visible damage to the tissue at an incident average power of 15 mW.
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Stoltzfus CR, Barnett LM, Drobizhev M, Wicks G, Mikhaylov A, Hughes TE, Rebane A. Two-photon directed evolution of green fluorescent proteins. Sci Rep 2015; 5:11968. [PMID: 26145791 PMCID: PMC4491718 DOI: 10.1038/srep11968] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2015] [Accepted: 06/12/2015] [Indexed: 01/15/2023] Open
Abstract
Directed evolution has been used extensively to improve the properties of a variety of fluorescent proteins (FPs). Evolutionary strategies, however, have not yet been used to improve the two-photon absorption (2PA) properties of a fluorescent protein, properties that are important for two-photon imaging in living tissues, including the brain. Here we demonstrate a technique for quantitatively screening the two-photon excited fluorescence (2PEF) efficiency and 2PA cross section of tens of thousands of mutant FPs expressed in E. coli colonies. We use this procedure to move EGFP through three rounds of two-photon directed evolution leading to new variants showing up to a 50% enhancement in peak 2PA cross section and brightness within the near-IR tissue transparency wavelength range.
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Affiliation(s)
| | - Lauren M. Barnett
- Cell Biology Neuroscience Department, Montana State University, Bozeman MT. 59717
| | | | - Geoffrey Wicks
- Physics Department, Montana State University, Bozeman MT. 59717
| | | | - Thomas E. Hughes
- Cell Biology Neuroscience Department, Montana State University, Bozeman MT. 59717
| | - Aleksander Rebane
- Physics Department, Montana State University, Bozeman MT. 59717
- National Institute of Chemical Physics and Biophysics, Tallinn, Estonia, 12618
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Young MD, Field JJ, Sheetz KE, Bartels RA, Squier J. A pragmatic guide to multiphoton microscope design. ADVANCES IN OPTICS AND PHOTONICS 2015; 7:276-378. [PMID: 27182429 PMCID: PMC4863715 DOI: 10.1364/aop.7.000276] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/18/2023]
Abstract
Multiphoton microscopy has emerged as a ubiquitous tool for studying microscopic structure and function across a broad range of disciplines. As such, the intent of this paper is to present a comprehensive resource for the construction and performance evaluation of a multiphoton microscope that will be understandable to the broad range of scientific fields that presently exploit, or wish to begin exploiting, this powerful technology. With this in mind, we have developed a guide to aid in the design of a multiphoton microscope. We discuss source selection, optical management of dispersion, image-relay systems with scan optics, objective-lens selection, single-element light-collection theory, photon-counting detection, image rendering, and finally, an illustrated guide for building an example microscope.
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Affiliation(s)
- Michael D. Young
- Center for Microintegrated Optics for Advanced Biological Control, Department of Physics, Colorado School of Mines, 1500 Illinois Street, Golden, Colorado 80401, USA
| | - Jeffrey J. Field
- W. M. Keck Laboratory for Raman Imaging of Cell-to-Cell Communications, Colorado State University, Fort Collins, Colorado 80523, USA
- Department of Electrical and Computer Engineering, Colorado State University, Fort Collins, Colorado 80523, USA
| | - Kraig E. Sheetz
- Photonics Research Center, Department of Physics and Nuclear Engineering, United States Military Academy, West Point, New York 10996, USA
| | - Randy A. Bartels
- W. M. Keck Laboratory for Raman Imaging of Cell-to-Cell Communications, Colorado State University, Fort Collins, Colorado 80523, USA
- Department of Electrical and Computer Engineering, Colorado State University, Fort Collins, Colorado 80523, USA
- School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523, USA
| | - Jeff Squier
- Center for Microintegrated Optics for Advanced Biological Control, Department of Physics, Colorado School of Mines, 1500 Illinois Street, Golden, Colorado 80401, USA
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Cisek R, Tokarz D, Hirmiz N, Saxena A, Shik A, Ruda HE, Barzda V. Crystal lattice determination of ZnSe nanowires with polarization-dependent second harmonic generation microscopy. NANOTECHNOLOGY 2014; 25:505703. [PMID: 25431947 DOI: 10.1088/0957-4484/25/50/505703] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
We demonstrate a noninvasive optical microscopy technique based on polarization-dependent second harmonic generation for determining the crystal lattice structure and microscopic heterogeneities within individual nanostructures. Differentiation between periodically twinned and wurtzite ZnSe nanowires (NWs) was demonstrated, and measurement of the cubic lattice rotation orientation around the NW axis was determined within 1° accuracy. Zinc blende NWs were differentiated from wurtzite. The technique can be used for quality inspection and optimization of growth conditions for nanostructures.
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Affiliation(s)
- Richard Cisek
- Department of Chemical and Physical Sciences, Department of Physics, and Institute for Optical Sciences, University of Toronto, 3359 Mississauga Road, Mississauga, Ontario L5L 1C6, Canada
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Cisek R, Tokarz D, Krouglov S, Steup M, Emes MJ, Tetlow IJ, Barzda V. Second Harmonic Generation Mediated by Aligned Water in Starch Granules. J Phys Chem B 2014; 118:14785-94. [DOI: 10.1021/jp508751s] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Galli R, Uckermann O, Andresen EF, Geiger KD, Koch E, Schackert G, Steiner G, Kirsch M. Intrinsic indicator of photodamage during label-free multiphoton microscopy of cells and tissues. PLoS One 2014; 9:e110295. [PMID: 25343251 PMCID: PMC4208781 DOI: 10.1371/journal.pone.0110295] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Accepted: 09/11/2014] [Indexed: 12/04/2022] Open
Abstract
Multiphoton imaging has evolved as an indispensable tool in cell biology and holds prospects for clinical applications. When addressing endogenous signals such as coherent anti-Stokes Raman scattering (CARS) or second harmonic generation, it requires intense laser irradiation that may cause photodamage. We report that increasing endogenous fluorescence signal upon multiphoton imaging constitutes a marker of photodamage. The effect was studied on mouse brain in vivo and ex vivo, on ex vivo human brain tissue samples, as well as on glioblastoma cells in vitro, demonstrating that this phenomenon is common to a variety of different systems, both ex vivo and in vivo. CARS microscopy and vibrational spectroscopy were used to analyze the photodamage. The development of a standard easy-to-use model that employs rehydrated cryosections allowed the characterization of the irradiation-induced fluorescence and related it to nonlinear photodamage. In conclusion, the monitoring of endogenous two-photon excited fluorescence during label-free multiphoton microscopy enables to estimate damage thresholds ex vivo as well as detect photodamage during in vivo experiments.
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Affiliation(s)
- Roberta Galli
- Clinical Sensoring and Monitoring, Anesthesiology and Intensive Care Medicine, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Ortrud Uckermann
- Neurosurgery, Carl Gustav Carus University Hospital, TU Dresden, Dresden, Germany
| | - Elisabeth F. Andresen
- Neurosurgery, Carl Gustav Carus University Hospital, TU Dresden, Dresden, Germany
- CRTD/DFG-Center for Regenerative Therapies Dresden - Cluster of Excellence, Dresden, Germany
| | - Kathrin D. Geiger
- Neuropathology, Institute for Pathology, Carl Gustav Carus University Hospital, TU Dresden, Dresden, Germany
| | - Edmund Koch
- Clinical Sensoring and Monitoring, Anesthesiology and Intensive Care Medicine, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Gabriele Schackert
- Neurosurgery, Carl Gustav Carus University Hospital, TU Dresden, Dresden, Germany
| | - Gerald Steiner
- Clinical Sensoring and Monitoring, Anesthesiology and Intensive Care Medicine, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Matthias Kirsch
- Neurosurgery, Carl Gustav Carus University Hospital, TU Dresden, Dresden, Germany
- CRTD/DFG-Center for Regenerative Therapies Dresden - Cluster of Excellence, Dresden, Germany
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Chen MY, Zhuo GY, Chen KC, Wu PC, Hsieh TY, Liu TM, Chu SW. Multiphoton imaging to identify grana, stroma thylakoid, and starch inside an intact leaf. BMC PLANT BIOLOGY 2014; 14:175. [PMID: 24969621 PMCID: PMC4104400 DOI: 10.1186/1471-2229-14-175] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Accepted: 06/18/2014] [Indexed: 05/24/2023]
Abstract
BACKGROUND Grana and starch are major functional structures for photosynthesis and energy storage of plant, respectively. Both exhibit highly ordered molecular structures and appear as micrometer-sized granules inside chloroplasts. In order to distinguish grana and starch, we used multiphoton microscopy, with simultaneous acquisition of two-photon fluorescence (2PF) and second harmonic generation (SHG) signals. SHG is sensitive to crystallized structures while 2PF selectively reveals the distribution of chlorophyll. RESULT Three distinct microstructures with different contrasts were observed, i.e. "SHG dominates", "2PF dominates", and "SHG collocated with 2PF". It is known that starch and grana both emit SHG due to their highly crystallized structures, and no autofluorescence is emitted from starch, so the "SHG dominates" contrast should correspond to starch. The contrast of "SHG collocated with 2PF" is assigned to be grana, which exhibit crystallized structure with autofluorescent chlorophyll. The "2PF dominates" contrast should correspond to stroma thylakoid, which is a non-packed membrane structure with chrolophyll. The contrast assignment is further supported by fluorescence lifetime measurement. CONCLUSION We have demonstrated a straightforward and noninvasive method to identify the distribution of grana and starch within an intact leaf. By merging the 2PF and SHG images, grana, starch and stroma thylakoid can be visually distinguished. This approach can be extended to the observation of 3D grana distribution and their dynamics in living plants.
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Affiliation(s)
| | | | | | | | | | | | - Shi-Wei Chu
- Department of Physics, National Taiwan University, Taipei, Taiwan.
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