Journal of Biophotonics

Cover image for Vol. 8 Issue 4

Early View (Online Version of Record published before inclusion in an issue)

Editor: Jürgen Popp

Impact Factor: 3.856

ISI Journal Citation Reports © Ranking: 2013: 17/78 (BIOCHEMICAL RESEARCH METHODS); 17/74 (Biophysics)

Online ISSN: 1864-0648

Associated Title(s): Laser & Photonics Reviews


  1. 1 - 67
  1. Letters

    1. Laser speckle spatiotemporal variance analysis for noninvasive widefield measurements of blood pulsation and pulse rate on a camera-phone

      Itay Remer and Alberto Bilenca

      Article first published online: 23 APR 2015 | DOI: 10.1002/jbio.201500156

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      Laser speckle imaging (LSI) is a well-established noncontact technique for widefield, high spatial resolution imaging of tissue blood perfusion via temporal analysis of time-integrated speckle. Here, precise, widefield estimation of blood pulsation and heart-rate frequency is shown by measuring local temporal variations of speckle patterns of light backscattered from subcutaneous skin. The LSI instrument is realized using a camera-phone, demonstrating the potential of LSI-based functional imaging with a simple imager.

  2. Full Articles

    1. Investigation on the potential of Mueller matrix imaging for digital staining

      Wenfeng Wang, Lee Guan Lim, Supriya Srivastava, Jimmy Bok-Yan So, Asim Shabbir and Quan Liu

      Article first published online: 22 APR 2015 | DOI: 10.1002/jbio.201500006

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      This study demonstrated the potential of Muller matrix imaging on digital staining. The regions of interest of different sizes in gastric samples were classified into three categories i.e. cancer, dysplasia and intestinal metaplasia/normal glands based on polarization parameters, Mueller matrix elements and principal component scores. A two-step classification method significantly improved the accuracy. Mueller matrix images with high spatial resolution revealed more morphological details than those with low resolution.

    2. Label-free in vivo imaging of peripheral nerve by multispectral photoacoustic tomography

      Rui Li, Evan Phillips, Pu Wang, Craig J. Goergen and Ji-Xin Cheng

      Article first published online: 22 APR 2015 | DOI: 10.1002/jbio.201500004

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      Iatrogenic damage to peripheral nerves is a leading cause of morbidity attributed to surgical procedures. Unintentional surgical damage to nerves is mainly due to poor visualization of nerve tissue relative to adjacent structures. Multispectral photoacoustic tomography can provide chemical information with specificity and ultrasonic spatial resolution with centimeter imaging depth, making it a potential tool for noninvasive neural imaging.

    3. Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy enhances real-time in vivo diagnosis of adenomatous polyps during colonoscopy

      Mads Sylvest Bergholt, Kan Lin, Jianfeng Wang, Wei Zheng, Hongzhi Xu, Qingwen Huang, Jian-lin Ren, Khek Yu Ho, Ming Teh, Supriya Srivastava, Benjamin Wong, Khay Guan Yeoh and Zhiwei Huang

      Article first published online: 7 APR 2015 | DOI: 10.1002/jbio.201400141

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      This work aims to apply a unique simultaneous fiber-optic fingerprint (FP) and high wavenumber (HW) Raman spectroscopy technique developed for real-time in vivo assessment of adenomatous polyps at colonoscopy. The simultaneous FP/HW Raman endoscopic technique provides a high diagnostic accuracy for differentiating adenoma from hyperplastic polyps in vivo, demonstrating its potential to be a clinically powerful tool for improving early detection and diagnosis of adenomatous polyps during colonoscopic examination.

    4. Ex vivo investigations on the potential of optical coherence tomography (OCT) as a diagnostic tool for reproductive medicine in a bovine model

      Matthias Trottmann, Sabine Kölle, Regina Leeb, Daniel Doering, Sven Reese, Christian G. Stief, Kate Dulohery, Myles Leavy, Julia Kuznetsova, Christian Homann and Ronald Sroka

      Article first published online: 23 MAR 2015 | DOI: 10.1002/jbio.201500009

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      Routine infertility investigations in the male and female include imaging techniques such as ultrasonography and endoscopy (fertiloscopy). However, these techniques lack the resolution to localize vital sperm or to reveal detailed morphological analysis of the oviduct which is often the cause of infertility in females. Here, the efficiency of optical coherence tomography (OCT) as a diagnostic imaging tool for micron-scale visualization of the male and female genital tract is evaluated.

    5. An infrared sensor analysing label-free the secondary structure of the Abeta peptide in presence of complex fluids

      Andreas Nabers, Julian Ollesch, Jonas Schartner, Carsten Kötting, Just Genius, Ute Haußmann, Hans Klafki, Jens Wiltfang and Klaus Gerwert

      Article first published online: 23 MAR 2015 | DOI: 10.1002/jbio.201400145

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      An Attenuated Total Reflection (ATR) sensor modified with a specific antibody to extract minute amounts of Abeta peptide out of a complex fluid is presented. The Abeta peptide secondary structure was determined in its physiological aqueous environment by FTIR-difference-spectroscopy. The presented results open the door for label-free Alzheimer diagnostics in cerebrospinal fluid or blood. It can be extended to further neurodegenerative diseases.

    6. Molecular profiling of sepsis in mice using Fourier Transform Infrared Microspectroscopy

      Rekha Gautam, Mukta Deobagkar-Lele, Shamik Majumdar, Bhagawat Chandrasekar, Emmanuel Victor, Syed Moiz Ahmed, Nitin Wadhwa, Taru Verma, Srividya Kumar, Nagalingam Ravi Sundaresan, Siva Umapathy and Dipankar Nandi

      Article first published online: 23 MAR 2015 | DOI: 10.1002/jbio.201400089

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      Sepsis is the systemic inflammatory response syndrome that may occur during infections. This disorder is the leading cause of deaths in intensive care units and a major health care problem. In this study, mice models to study the progression of sepsis are used involving injection with live Salmonella Typhimurium or lipopolysacharride. The utility of using a combination of immune assays and spectroscopy in following the progression of sepsis is discussed.

    7. Quantitative multi-spectral oxygen saturation measurements independent of tissue optical properties

      Karin Radrich and Vasilis Ntziachristos

      Article first published online: 12 MAR 2015 | DOI: 10.1002/jbio.201400092

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      This paper proposes a new methodology using optical imaging technology for accurate detection of blood oxygenation. Low oxygen saturation values of blood often result from or can be the cause of a variety of diseases, like different types of cancer or diabetes. Accurate blood oxygenation monitoring is therefore crucial and optical imaging offer the possibility of early, rapid and noninvasive detection of malfunctions of the body.

    8. Quantitative and rapid estimations of human sub-surface skin mass using ultra-high-resolution spectral domain optical coherence tomography

      Wen-Chuan Kuo, Yue-Ming Kuo and Su-Ying Wen

      Article first published online: 9 MAR 2015 | DOI: 10.1002/jbio.201400153

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      Early detection of morphological and volumetric changes, especially in non-invasive method, is crucially important to assist the clinicians in monitoring the tumor growth or progression. In this study, a high-speed, non-invasive, and ultra-high-resolution spectral domain optical coherence tomography (UHR-SDOCT) imaging platform was developed for the quantitative measurement of human sub-surface skin mass. Clinically, this is the first step towards an automated skin lesion measurement system.

    9. Fluorescence life-time imaging and steady state polarization for examining binding of fluorophores to gold nanoparticles

      Shmulik Schwartz, Dror Fixler, Rachela Popovtzer, Orit Shefi

      Article first published online: 6 MAR 2015 | DOI: 10.1002/jbio.201400136

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      Nanoparticles are commonly used for imaging and cell biology technologies. One of the most popular nanoparticle-based complexes is the conjugation of nanoparticles to fluorescent molecules. The conventional methods used for validation of the conjugation process such as spectroscopy analysis and surface potential measurements, are not sufficient. In this paper we present a new approach that uses the combination of (1) fluorescence spectrum, (2) fluorescence lifetime, and (3) steady state fluorescence polarization measurements, to differentiate between samples of nanoparticles coated with Lucifer yellow and samples of the free dye.

    10. Detecting concentrations of milk components by an iterative optical technique

      Inbar Yariv, Yaara Kapp-Barnea, Eran Genzel, Hamootal Duadi and Dror Fixler

      Article first published online: 26 FEB 2015 | DOI: 10.1002/jbio.201400144

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      Milk contents analyses however challenging, are essential in the dairy food industry to define milk value for quality control and the upturn of cow health and milk yield. We suggest the utilization of a novel optical technique for milk contents determination. The technique, based on Gerchberg- Saxton (G-S) algorithm, was able to detect the possibility of lactose and milk proteins' quantitative signature, en-route to the design of a novel milk content monitoring tool.

    11. Label-free, zeptomole cancer biomarker detection by surface-enhanced fluorescence on nanoporous gold disk plasmonic nanoparticles

      Greggy M. Santos, Fusheng Zhao, Jianbo Zeng, Ming Li and Wei-Chuan Shih

      Article first published online: 26 FEB 2015 | DOI: 10.1002/jbio.201400134

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      A label-free biosensor for the ERBB2 cancer gene DNA target based on the distance-dependent detection of surface-enhanced fluorescence (SEF) on nanoporous gold disk (NPGD) plasmonic nanoparticles is demonstrated. The NPGD substrate as an SEF platform was shown to provide higher net fluorescence for visible and NIR fluorophores compared to glass and non-porous gold substrates. The enhanced fluorescence signals in patterned nanoporous gold nanoparticles make NPGD a viable material for further reducing detection limits for biomolecular targets used in clinical assays.

    12. Toward the measurement of multiple fluorescence lifetimes in flow cytometry: maximizing multi-harmonic content from cells and microspheres

      Patrick Jenkins, Mark A. Naivar and Jessica P. Houston

      Article first published online: 26 FEB 2015 | DOI: 10.1002/jbio.201400115

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      In this contribution fluorescence decay-dependent parameters to the data space of flow cytometry are introduced. A stream-in-air FACS™ instrument is modified with new laser modulation hardware and a data acquisition system that could be readily adapted onto other cytometers when there is a need to capture the fluorescence lifetime, which is an intensity-independent parameter. Using square wave modulation, the ability to resolve more than one fluorescence lifetime from individual fluorescently labeled cells and microspheres that are counted at rapid cytometric throughputs is shown.

  3. Letters

    1. Maintaining polarization in polarimetric multiphoton microscopy

      Erik Bélanger, Raphaël Turcotte, Amy Daradich, Grégory Sadetsky, Pierre Gravel, Karine Bachand, Yves De Koninck and Daniel C. Côté

      Article first published online: 17 FEB 2015 | DOI: 10.1002/jbio.201400116

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      Polarimetric measurements in multiphoton microscopy can reveal information about the local molecular order of a sample. However, the presence of a dichroic through which the excitation beam propagates will generally scramble its polarization. A simple scheme is proposed whereby a second properly-oriented compensation dichroic is used to negate any alteration regardless of the wavelength and the initial polarization. It is demonstrated how this robust and rapid approach simplifies polarimetric measurements in second-harmonic generation, two-photon excited fluorescence and coherent anti-Stokes Raman scattering.

  4. Full Articles

    1. Intravascular magnetomotive optical coherence tomography of targeted early-stage atherosclerotic changes in ex vivo hyperlipidemic rabbit aortas

      Jongsik Kim, Adeel Ahmad, Joanne Li, Marina Marjanovic, Eric J. Chaney, Kenneth S. Suslick and Stephen A. Boppart

      Article first published online: 16 FEB 2015 | DOI: 10.1002/jbio.201400128

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      The development of an intravascular magnetomotive optical coherence tomography (IV-MM-OCT) system used with targeted protein microspheres to detect early-stage atherosclerotic fatty streaks/plaques is reports. The alternating magnetic field gradient was provided by a unique pair of external custom-built electromagnetic coils that modulated the targeted magnetic MSs. The results showed a statistically significant MM-OCT signal from the aorta samples specimens injected with targeted MSs.

    2. Handheld photoacoustic probe to detect both melanoma depth and volume at high speed in vivo

      Yong Zhou, Guo Li, Liren Zhu, Chiye Li, Lynn A. Cornelius and Lihong V. Wang

      Article first published online: 9 FEB 2015 | DOI: 10.1002/jbio.201400143

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      A linear-array-based photoacoustic probe is applied to detect melanin-containing melanoma tumor depth and volume in nude mice in vivo. The system can image melanomas at five frames per second. In addition to the higher frame rate, almost the entire boundary of the melanoma can be detected. The volume detection ability also enables to accurately calculate the rate of growth of the tumor, which is an important parameter in quantifying the tumor activity.

    3. Hyperspectral imaging in medicine: image pre-processing problems and solutions in Matlab

      Robert Koprowski

      Article first published online: 9 FEB 2015 | DOI: 10.1002/jbio.201400133

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      A new application in Matlab intended for preliminary analysis of hyperspectral images. The available full source code and the description of the results obtained. Lack of licensing restrictions on the use and modification of the proposed application. Testing of the operation correctness on dozens of hyperspectral images.

    4. You have full text access to this OnlineOpen article
      Topographic prominence as a method for cluster identification in single-molecule localisation data

      Juliette Griffié, Lies Boelen, Garth Burn, Andrew P. Cope and Dylan M. Owen

      Article first published online: 6 FEB 2015 | DOI: 10.1002/jbio.201400127

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      The goal of this study is to present a new cluster analysis method adapted to single-molecule localisation microscopy, based on a topographic approach. By using the relative heights of the peaks in the local molecular density heat maps, cluster characteristics can be identified more accurately than with previously demonstrated height thresholds. The algorithm is validated using simulated and experimental data and found to significantly outperform previous cluster identification methods.

    5. Synergistic effects of atmospheric pressure plasma-emitted components on DNA oligomers: a Raman spectroscopic study

      Eugen Edengeiser, Jan-Wilm Lackmann, Erik Bründermann, Simon Schneider, Jan Benedikt, Julia E. Bandow and Martina Havenith

      Article first published online: 6 FEB 2015 | DOI: 10.1002/jbio.201400123

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      Plasma is a partially ionized gas containing free electrons, ions, and neutral particles. Recent developments in cold atmospheric-pressure plasmas have led to increased interest in their disinfecting properties. Despite an ongoing clinical evaluation, little is known about the mechanisms that lead to molecular modifications. The study aims to gain insight into inactivation mechanisms of plasmas. The focus is on the impact of plasma components of an indirect plasma on DNA oligomers in vitro.

    6. Photobleaching and phototoxicity of KillerRed in tumor spheroids induced by continuous wave and pulsed laser illumination

      Daria S. Kuznetsova, Marina V. Shirmanova, Varvara V. Dudenkova, Pavel V. Subochev, Ilya V. Turchin, Elena V. Zagaynova, Sergey A. Lukyanov, Boris E. Shakhov and Vladislav A. Kamensky

      Article first published online: 3 FEB 2015 | DOI: 10.1002/jbio.201400130

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      The article is devoted to study the photobleaching of the genetically encoded photosensitizer KillerRed. The work was performed on tumor spheroids upon different regimes of laser irradiation and included the analysis of fluorescence and mechanisms of cancer cell death after the treatment. These results can improve the understanding of the photobleaching mechanisms in phototoxic proteins and show the importance of appropriate selection of the treatment regime for PDT.

    7. Scheimpflug camera in the quantitative assessment of reproducibility of high-speed corneal deformation during intraocular pressure measurement

      Robert Koprowski, Renato Ambrósio Jr., Sven Reisdorf

      Article first published online: 26 JAN 2015 | DOI: 10.1002/jbio.201400137

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      Corvis ST (Oculus, Wetzlar, Germany) uses ultra-high-speed Scheimpflug photography during air-puff non-contact tonometry (NCT) that enables to measure intraocular pressure and dynamically evaluate corneal/ocular response. Many parameters derived from corneal deformation and vibration responses and ocular movement are calculated. Analysis of corneal deformation response with a frequency above 100 Hz is proposed using advanced image analysis and processing. The paper also presents the assessment of reproducibility of the performed measurements. It is a valuable contribution to the analysis of patients with diabetes, keratoconus or patients after surgery.

    8. A new approach for optical assessment of directional anisotropy in turbid media

      Pejhman Ghassemi, Lauren T. Moffatt, Jeffrey W. Shupp and Jessica C. Ramella-Roman

      Article first published online: 19 JAN 2015 | DOI: 10.1002/jbio.201400124

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      A study of polarized light transport in scattering media exhibiting directional anisotropy or linear birefringence is presented. Novel theoretical and experimental methodologies for the quantification of birefringent alignment based on out-of-plane polarized light transport are demonstrated. A polarized Monte Carlo model and a polarimetric imaging system were devised to predict and measure the impact of birefringence on an impinging linearly polarized light beam. Ex-vivo experiments conducted on bovine tendon showed good agreement with the analytical results.

    9. GJIC Enhances the phototoxicity of photofrin-mediated photodynamic treatment by the mechanisms related with ROS and Calcium pathways

      Dengpan Wu, Lixia Fan, Chengfang Xu, Zhen Liu, Yuan Zhang, Lucy Liu, Qin Wang, Liang Tao

      Article first published online: 19 JAN 2015 | DOI: 10.1002/jbio.201400131

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      Despite initially positive responses, recurrences after Photodynamic treatment (PDT) can occur and there is need for improvement in the effectiveness of PDT. It is shown that the presence of GJIC (Connexin32) increased the PDT phototoxicity in cell and animal level, which was related with ROS and calcium pathways. The study indicates the possibility that up-regulation or maintenance of GJ functionality may be used to increase the efficacy of PDT.

    10. Differential remodeling of extracellular matrices by breast cancer initiating cells

      Anju M. Raja, Shuoyu Xu, Shuangmu Zhuo, Dean C.S. Tai, Wanxin Sun, Peter T.C. So, Roy E. Welsch, Chien-Shing Chen and Hanry Yu

      Article first published online: 19 JAN 2015 | DOI: 10.1002/jbio.201400079

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      The extracellular matrix-remodeling effects of cancer initiating cells (CICs) using Second Harmonic Generation (SHG) microscopy is studied to identify potential phenotypic signatures of the CIC-rich tumors. The CIC-rich tumors have less collagen in the tumor interior than in the CIC-poor tumors and collagen fibers are more preferentially aligned perpendicular to the CIC-rich tumor boundary, suggesting more invasive behavior and more effective collagen remodeling capability of the CIC-rich tumors.

    11. Photodamage in deep tissue two-photon optical biopsy of human skin

      Luca Dalbosco, Giulia Zanini, Elvira D'Amato, Francesco Tessarolo, Sebastiana Boi, Paolo Bauer, Albrecht Haase and Renzo Antolini

      Article first published online: 18 DEC 2014 | DOI: 10.1002/jbio.201400083

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      Photodamage was studied in thick samples of human skin tissue (healthy skin and neoplastic lesions). Photobleaching, photoionization, and thermomechanical damage effects were characterized comparatively. The laser power dependence of the damage rates allowed to connect macroscopic effects to underlying molecular processes. Tissue alterations were found only from thermomechanical cavitation and limited to superficial layers of the epidermis. From the depth-dependencies of all damage thresholds a depth-dependent power-compensation scheme was defined allowing for damage-free deep tissue optical biopsy.

    12. Clinical assessment of non carious cervical lesion using swept-source optical coherence tomography

      Ikumi Wada, Yasushi Shimada, Masaomi Ikeda, Alireza Sadr, Syozi Nakashima, Junji Tagami and Yasunori Sumi

      Article first published online: 11 DEC 2014 | DOI: 10.1002/jbio.201400113

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      Non-carious cervical lesions (NCCLs) is a dental hard tissue defect that is unrelated to dental caries. We examined the incidence of occlusal wear and cervical demineralization in relation to NCCL dimensions using SS-OCT. Cervival demineralization was observed in 56.2% of small NCCLs, and the ratio increased to >80% in larger NCCLs. Cervical demineralization and occlusal attrition can be considered as an etiological factor in formation and progress of NCCLs.

    13. Molecularly imprinted hollow sphere array for the sensing of proteins

      Wei Chen, Min Xue, Kenneth J. Shea, Zihui Meng, Zequn Yan, Zhe Wang, Fei Xue, Feng Qu

      Article first published online: 11 DEC 2014 | DOI: 10.1002/jbio.201400100

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      A new type of hollow sphere array for the label-free detection of hemoglobin (Hb) was developed. The molecularly imprinted hollow sphere array (MIHSA) with 3D photonic structure display remarkable selectivity and adsorption capacity to Hb. Furthermore, the reflection of the MIHSA red shifted significantly in response to Hb with obviously color change. The MIHSA showed promising potential for the naked-eye detection of target Hb.

  5. Review Articles

    1. Holographic imaging of unlabelled sperm cells for semen analysis: a review

      Giuseppe Di Caprio, Maria Antonietta Ferrara, Lisa Miccio, Francesco Merola, Pasquale Memmolo, Pietro Ferraro and Giuseppe Coppola

      Article first published online: 9 DEC 2014 | DOI: 10.1002/jbio.201400093

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      Semen analysis has long represented the standard test for evaluating male fertility. Though still useful, the test is not perfect, as it fails to accurately predict fertility status in certain situations. This paper proposes a review of analysis on sperm properties based on Digital Holography. The addition of the third dimension provides a better statistic useful to relate the sperm anomalies with male infertility and to enable cell sorting.

  6. Full Articles

    1. Low-level laser irradiation promotes the proliferation and maturation of keratinocytes during epithelial wound repair

      Felipe F. Sperandio, Alyne Simões, Luciana Corrêa, Ana Cecília C. Aranha, Fernanda S. Giudice, Michael R. Hamblin and Suzana C.O.M. Sousa

      Article first published online: 20 NOV 2014 | DOI: 10.1002/jbio.201400064

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      Low-level laser therapy accelerates the epithelium maturation during wound healing; this picture illustrates how the immunohistochemical expression of cytokeratin 10, a terminal differentiation biomarker, is significantly augmented in the keratinocytes of the laser-irradiated lesion if compared to the control group. The center of the wound (CW) shows complete re-epithelialization; the covering epithelium over the connective tissue (CT) notably expresses cytokeratin 10.

    2. Dye distance mapping using waveguide evanescent field fluorescence microscopy and its application to cell biology

      Frederik Fleissner, Michael Morawitz, S. Jeffrey Dixon, Uwe Langbein and Silvia Mittler

      Article first published online: 17 NOV 2014 | DOI: 10.1002/jbio.201400088

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      A microscopy method is described enabling to measure not only distances between an adhesion point of a cell and its substratum at particular locations but to map the distance of the cell's plasma membrane along an entire cell or even along an entire cell population, allowing distinguishing between the various adhesion forms and imaging membrane bending in-between adhesion sites giving more insides into the cell-substratum interaction.

    3. Detection and controlled depletion of cancer cells using photothermal phase microscopy

      Nir Abraham Turko, Itay Barnea, Omry Blum, Rafi Korenstein and Natan Tzvi Shaked

      Article first published online: 17 NOV 2014 | DOI: 10.1002/jbio.201400095

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      Laser therapy for real-time, selective cancer treatment is now one step closer to realization, as a new method for ablating cancer cells specifically is implemented. The system is comprised of a photothermal phase interferometer, which can quantitatively image all cells in an in vitro sample, labeled and unlabeled, and then selectively choose cells for ablation using novel image contrast mechanism that is based on the heat signatures of gold nanoparticles.

    4. Light-emitting diode therapy in exercise-trained mice increases muscle performance, cytochrome c oxidase activity, ATP and cell proliferation

      Cleber Ferraresi, Nivaldo Antonio Parizotto, Marcelo Victor Pires de Sousa, Beatriz Kaippert, Ying-Ying Huang, Tomoharu Koiso, Vanderlei Salvador Bagnato and Michael R. Hamblin

      Article first published online: 6 NOV 2014 | DOI: 10.1002/jbio.201400087

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      Light-emitting diode therapy (LEDT) applied over the leg, gluteus and lower-back muscles of mice using a LED cluster increased muscle performance, ATP and mitochondrial metabolism; oxidative stress and proliferative myocyte markers in mice subjected to acute and progressive strength training. Six bi-daily training sessions LEDT-After and LEDT-Before-After regimens more than doubled muscle performance and increased ATP more than tenfold. The effectiveness of LEDT on improving muscle performance and recovery suggest applicability for high performance sports and in training programs.

    5. Multimodal and multiplex spectral imaging of rat cornea ex vivo using a white-light laser source

      Hiroki Segawa, Yuichi Kaji, Philippe Leproux, Vincent Couderc, Takeaki Ozawa, Tetsuro Oshika and Hideaki Kano

      Article first published online: 6 NOV 2014 | DOI: 10.1002/jbio.201400059

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      Multimodal nonlinear spectral imaging with coherent anti-Stokes Raman scattering (CARS) molecular fingerprinting was applied to ex vivo measurement of rat cornea. Complicated inner structure of the cornea was clearly visualized with molecular structural information produced by combined spectral analysis of multiplex CARS, second harmonic generation (SHG) and multiplex third-order sum frequency generation (TSFG). This study will open the door for molecular level analysis in corneal medical diagnostics.

    6. Polarization second harmonic generation microscopy provides quantitative enhanced molecular specificity for tissue diagnostics

      Rajesh Kumar, Kirsten M. Grønhaug, Elisabeth I. Romijn, Andreas Finnøy, Catharina L. Davies, Jon O. Drogset and Magnus B. Lilledahl

      Article first published online: 3 NOV 2014 | DOI: 10.1002/jbio.201400086

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      Polarization dependent effects introduced by optics present in a commercial microscope can create artifact in susceptibility (χ) image, which ultimately may lead to misleading results. This report discusses the issues responsible for image artifacts in p-SHG analysis and provides the relevant solutions in terms of calibrations. Moreover, as a proof-of-concept, χ-parameters value of a heart muscle, ovary tissue and osteoarthritic cartilage was obtained by p-SHG analysis.

    7. In-vitro investigations on laser-induced smoke generation mimicking the laparoscopic laser surgery purposes

      Wael Y. Khoder, Christian G. Stief, Sebastian Fiedler, Thomas Pongratz, Wolfgang Beyer, Georg Hennig, Adrian Rühm and Ronald Sroka

      Article first published online: 3 NOV 2014 | DOI: 10.1002/jbio.201400061

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      Intraoperative smoke generation is an adherent phenomenon to laser-assisted surgery that could obscure surgical-vision. An experimental setup mimicking clinical laparoscopy is used to detect smoke-production. This time dependent signal correlates to the ablation-rate. Smoke generation depends on the optical properties of tissue and thus on the laser wavelength used for ablation. Laparoscopic surgeons should be aware of specific wave-length-laser-tissue interaction, avoiding carbonization during cutting/coagulation to reduce smoke-generation yielding visual advantages.

    8. The use of optical trap and microbeam to investigate the mechanical and transport characteristics of tunneling nanotubes in tumor spheroids

      Pooja Patheja, Raktim Dasgupta, Alok Dube, Sunita Ahlawat, Ravi Shanker Verma and Pradeep Kumar Gupta

      Article first published online: 29 OCT 2014 | DOI: 10.1002/jbio.201400039

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      The use of optical trap and microbeam for investigating mechanical and transport properties of inter cellular tunneling nanotubes (TnTs) in tumor spheroids has been demonstrated. TnTs in tumor spheroids have been visualized by manipulating TnT connected cells using optical tweezers. Functionality of the TnTs for transferring cytoplasmic vesicles and injected dye molecules by optoporation method has been studied. Further, the TnTs could be longitudinally stretched by manipulating the connected cells and their elastic response was studied.

    9. Raman spectroscopy analysis of lipid droplets content, distribution and saturation level in Non-Alcoholic Fatty Liver Disease in mice

      Kamila Kochan, Edyta Maslak, Christoph Krafft, Renata Kostogrys, Stefan Chlopicki and Malgorzata Baranska

      Article first published online: 24 OCT 2014 | DOI: 10.1002/jbio.201400077

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      This work presents a confocal Raman microspectroscopic study of the alterations in the composition of NAFLD-affected liver. We confirm the NAFLD development, manifested by the presence of lipid droplets of different sizes, in models of macrovesicular and microvesicular steatosis. In both we observe a significant decrease in the degree of unsaturation of lipids, compared to control. These changes are reversed in the initial stage of medical treatment.

    10. Assessment of ALA-induced PpIX production in porcine skin pretreated with microneedles

      Phamilla Gracielli Sousa Rodrigues, Priscila Fernanda Campos de Menezes, Alessandra Keiko Lima Fujita, André Escobar, Andrigo Barboza de Nardi, Cristina Kurachi and Vanderlei S. Bagnato

      Article first published online: 15 OCT 2014 | DOI: 10.1002/jbio.201400081

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      Photodynamic therapy (PDT) for skin treatment of premalignant and cancer lesions combines tissue photosensitization and subsequent exposure to light to induce cell death. As it is limited to the treatment of superficial lesions, mainly due to the low cream penetration, the improvement of transdermal distribution of aminolevulinic acid (ALA) is needed. In this study, the kinetics and homogeneity of production of ALA-induced PpIX after the skin pre-treatment with microneedle rollers were investigated.

    11. In vivo nonlinear optical imaging to monitor early microscopic changes in a murine cutaneous squamous cell carcinoma model

      Giju Thomas, Johan van Voskuilen, Hoa Truong, Hans C. Gerritsen and H.J.C.M. Sterenborg

      Article first published online: 15 OCT 2014 | DOI: 10.1002/jbio.201400074

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      In vivo nonlinear optical imaging (NLOI) based on two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) was used to non-invasively detect microscopic changes in murine skin treated topically with 7,12-dimethylbenz(a)anthracene (DMBA). NLOI was able to clearly detect early cytostructural changes in DMBA treated skin that appeared clinically normal. The method has great potential as a diagnostic non-invasive tool to monitor early cancerous changes in skin..

    12. Biophysical effects in off-resonant gold nanoparticle mediated (GNOME) laser transfection of cell lines, primary- and stem cells using fs laser pulses

      Markus Schomaker, Doreen Killian, Saskia Willenbrock, Dag Heinemann, Stefan Kalies, Anaclet Ngezahayo, Ingo Nolte, Tammo Ripken, Christian Junghanß, Heiko Meyer, Hugo Murua Escobar and Alexander Heisterkamp

      Article first published online: 9 OCT 2014 | DOI: 10.1002/jbio.201400065

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      Gold nanoparticle mediated (GNOME) laser transfection is a powerful technique to deliver small biologically relevant molecules into cells. However, the transfection of larger and especially charged molecules like plasmid DNA remains challenging. To get a deeper understanding of the uptake process, the biophysical mechanisms involved in GNOME laser transfection were investigated. Furthermore, successful transfection of stem cells was performed providing an alternative method for the development of molecular medical approaches.

    13. Effects of multispectral excitation on the sensitivity of molecular optoacoustic imaging

      Stratis Tzoumas, Antonio Nunes, Nikolaos C. Deliolanis and Vasilis Ntziachristos

      Article first published online: 3 OCT 2014 | DOI: 10.1002/jbio.201400056

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      Molecular optoacoustic (photoacoustic) imaging typically relies on the spectral identification of absorption signatures from molecules of interest. To achieve this, two or more excitation wavelengths are employed to sequentially illuminate tissue. Due to depth-related spectral dependencies and detection related effects, the multispectral optoacoustic tomography (MSOT) spectral unmixing problem presents a complex non-linear inversion operation. The impact of the number of excitation wavelengths employed on the sensitivity and accuracy achieved by molecular optoacoustic tomography is studied. A quantitative analysis, based on synthetic MSOT datasets is presented and a trend of sensitivity increase for up to 20 wavelengths is observed.

    14. Ensemble multivariate analysis to improve identification of articular cartilage disease in noisy Raman spectra

      Wade Richardson, Dan Wilkinson, Ling Wu, Frank Petrigliano, Bruce Dunn and Denis Evseenko

      Article first published online: 26 SEP 2014 | DOI: 10.1002/jbio.201300200

      Thumbnail image of graphical abstract

      To combat cartilage diseases like osteoarthritis, orthopedists need better tools for early diagnosis in patients. Raman spectroscopy is a promising candidate for early diagnosis, but obtaining enough representative spectra to train a diagnostic algorithm will be difficult, especially for low quality patient spectra. This work finds evidence that supplementing training with spectra from more easily obtained disease-modeling materials may be useful for identifying cartilage disease in noisy Raman spectra.

    15. Ultra-sensitive immunoassay biosensors using hybrid plasmonic-biosilica nanostructured materials

      Jing Yang, Le Zhen, Fanghui Ren, Jeremy Campbell, Gregory L. Rorrer and Alan X. Wang

      Article first published online: 25 SEP 2014 | DOI: 10.1002/jbio.201400070

      Thumbnail image of graphical abstract

      An ultra-sensitive immunoassay biosensor is experimentally demonstrated, using diatom biosilica with self-assembled plasmonic nanoparticles. As the nature-created photonic crystal structures, diatoms have been adopted to enhance surface plasmon resonances of metal nanoparticles on the surfaces of diatom frustules and to increase the sensitivity of surface-enhanced Raman scattering (SERS). A sandwich SERS immunoassay is developed based on the hybrid plasmonic-biosilica nanostructured materials that are functionalized with goat anti-mouse IgG.

    16. Raman spectroscopy of blood serum for Alzheimer's disease diagnostics: specificity relative to other types of dementia

      Elena Ryzhikova, Oleksandr Kazakov, Lenka Halamkova, Dzintra Celmins, Paula Malone, Eric Molho, Earl A. Zimmerman and Igor K. Lednev

      Article first published online: 25 SEP 2014 | DOI: 10.1002/jbio.201400060

      Thumbnail image of graphical abstract

      The key moment for efficiently and accurately diagnosing dementia occurs during the early stages. In this proof-of-concept study, applied near infrared (NIR) Raman microspectroscopy of blood serum is studied together with advanced multivariate statistics for the selective identification of Alzheimer's disease (AD). NIR Raman microspectroscopy differentiated AD patients with more than 95% sensitivity and specificity. The high discriminative power of artificial neural network (ANN) classification models is demonstrated, revealing the high potential of this developed methodology for the differential diagnosis of AD.

    17. Label-free and non-invasive monitoring of porcine trophoblast derived cells: differentiation in serum and serum-free media

      Qifei Li, Edison Suasnavas, Lifu Xiao, Sierra Heywood, Xiaojun Qi, Anhong Zhou1,* and S. Clay Isom2,*

      Article first published online: 22 SEP 2014 | DOI: 10.1002/jbio.201400062

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      Raman microspectroscopy (RM) and atomic force microscopy (AFM) – both considered as non-invasive techniques – are applied to detect the biochemical and biophysical properties of trophoblast derived stem-like cells incubated up to 10 days under conditions designed to induce differentiation. Significant biochemical and biophysical differences between control cells and differentiated cells were observed. The relationship between cell differentiation and associated cellular biochemical and biomechanical changes are discussed.

    18. Oxygenation measurement by multi-wavelength oxygen-dependent phosphorescence and delayed fluorescence: catchment depth and application in intact heart

      Gianmarco M. Balestra, Maurice C.G. Aalders, Patricia A.C. Specht, Can Ince and Egbert G. Mik

      Article first published online: 22 SEP 2014 | DOI: 10.1002/jbio.201400054

      Thumbnail image of graphical abstract

      Oxygen delivery and metabolism represent key factors for organ function in health and disease. The optical key characteristics of a technique to comprehensively measure oxygen tension (PO2) in myocardium is described. Oxygen-dependent quenching of phosphorescence and delayed fluorescence of porphyrins by means of Monte Carlo simulations and ex vivo experiments are used. The feasibility to detect changes in oxygenation within separate anatomical compartments is demonstrated in rat heart in vivo.

    19. High-definition optical coherence tomography of melanocytic skin lesions

      Thilo Gambichler, Iris Plura, Monika Schmid-Wendtner, Konstantinos Valavanis, Daniela Kulichova, Markus Stücker, Azem Pljakic, Carola Berking and Tanja Maier

      Article first published online: 18 SEP 2014 | DOI: 10.1002/jbio.201400085

      Thumbnail image of graphical abstract

      Micromorphological high-definition optical coherence tomography (HD-OCT) correlates of benign naevi (BN) and malignant melanoma (MM) are assessed. Epidermal honeycomb/cobblestone pattern, regular junctional cell nests, and edged papillae are more often observed in BN, whereas fusion of rete ridges, pagetoid cells and junctional and/or dermal nests with atypical cells are more frequently seen in MM. Using HD-OCT, architectural and cellular alterations of melanocytic skin lesions (MSL) can be visualized.

    20. You have full text access to this OnlineOpen article
      Multi-modal acousto-optic/ultrasound imaging of ex vivo liver tumors at 790 nm using a Sn2P2S6 wavefront adaptive holographic setup

      Jean-Baptiste Laudereau, Emilie Benoit à La Guillaume, Vincent Servois, Pascale Mariani, Alexander A. Grabar, Mickaël Tanter, Jean-Luc Gennisson and François Ramaz

      Article first published online: 18 SEP 2014 | DOI: 10.1002/jbio.201400071

      Thumbnail image of graphical abstract

      Acousto-optic imaging is a light-ultrasound coupling technique that takes advantage of the ballistic propagation of ultrasound in biological tissues to access optical contrast with a millimeter resolution. A photorefractive-crystal-based system has been developed that performs self-adaptive wavefront holography and works within the optical therapeutic window. As it works at an appropriate wavelength range for biological tissues imaging, it was tested on ex vivo liver samples containing tumors as a pre-clinical study. Optical contrast was obtained even if acoustical one was not significant.

  7. Review Articles

    1. Real-time in vivo cancer diagnosis using raman spectroscopy

      Wenbo Wang, Jianhua Zhao, Michael Short and Haishan Zeng

      Article first published online: 12 SEP 2014 | DOI: 10.1002/jbio.201400026

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      An overview on the latest development of real-time in vivo Raman systems for cancer detection is provided. Instrumentation, data handling, as well as oncology applications of Raman techniques are covered. Optic fiber probes designs for Raman spectroscopy are discussed and spectral data pre-processing, feature extraction, and classification between normal/benign and malignant tissues are surveyed. Applications of Raman techniques for clinical diagnosis for different types of cancers are summarized.

  8. Full Articles

    1. Superpulsed (Ga-As, 904 nm) low-level laser therapy (LLLT) attenuates inflammatory response and enhances healing of burn wounds

      Asheesh Gupta, Gaurav K. Keshri, Anju Yadav, Shefali Gola, Satish Chauhan, Ashok K. Salhan and Shashi Bala Singh

      Article first published online: 10 SEP 2014 | DOI: 10.1002/jbio.201400058

      Thumbnail image of graphical abstract

      Low-level laser therapy (LLLT) using superpulsed near-infrared light can penetrate deeper in the injured tissue and could allow non-pharmacological treatment for chronic wound healing. This study investigated the effects of superpulsed laser on the healing of burn wounds in rats, and further explored the probable associated mechanisms of action. It was shown that LLLT using superpulsed 904 nm laser reduced the inflammatory response and was able to enhance cellular proliferation, collagen deposition and wound contraction in the repair process of burn wounds.

    2. Enhancement of optical coherence microscopy in turbid media by an optical parametric amplifier

      Youbo Zhao, Haohua Tu, Yuan Liu, Andrew J. Bower and Stephen A. Boppart

      Article first published online: 8 SEP 2014 | DOI: 10.1002/jbio.201400073


  10. Full Articles

    1. Non-Invasive Multi-Dimensional Two-Photon Microscopy enables optical fingerprinting (TPOF) of immune cells

      Uta Gehlsen, Marta Szaszák, Andreas Gebert, Norbert Koop, Gereon Hüttmann and Philipp Steven

      Article first published online: 3 SEP 2014 | DOI: 10.1002/jbio.201400036

    2. Statistically quantified measurement of an Alzheimer's marker by surface-enhanced Raman scattering

      Ričardas Buividas, Nerijus Dzingelevičius, Reda Kubiliūtė, Paul R. Stoddart, Vi Khanh Truong, Elena P. Ivanova and Saulius Juodkazis

      Article first published online: 13 AUG 2014 | DOI: 10.1002/jbio.201400017

    3. High precision mapping of kidney stones using mu;-IR spectroscopy to determine urinary lithogenesis

      Francisco Blanco, Pilar Ortiz-Alías, Montserrat López-Mesas and Manuel Valiente

      Article first published online: 5 AUG 2014 | DOI: 10.1002/jbio.201300201


    1. Neurite growth acceleration of adult Dorsal Root Ganglion neurons illuminated by low-level Light Emitting Diode light at 645 nm

      Marion Burland, Lambert Paris, Patrice Quintana, Jean-Michel Bec, Lucie Diouloufet, Chamroeun Sar, Hassan Boukhaddaoui, Benoit Charlot, Jefferson Braga Silva, Michel Chammas, Victor Sieso, Jean Valmier and Fabrice Bardin

      Article first published online: 30 JUL 2014 | DOI: 10.1002/jbio.201400052

    2. Brillouin spectroscopy as a new method of screening for increased CSF total protein during bacterial meningitis

      Zachary Steelman, Zhaokai Meng, Andrew J. Traverso and Vladislav V. Yakovlev

      Article first published online: 15 JUL 2014 | DOI: 10.1002/jbio.201400047

    3. Raman spectroscopy of serum: A study on ‘pre’ and ‘post’ breast adenocarcinoma resection in rat models

      Tanmoy Bhattacharjee, Aarif Khan, Piyush Kumar, Arvind Ingle, Girish Maru and C. Murali Krishna

      Article first published online: 15 JUL 2014 | DOI: 10.1002/jbio.201400040

    4. Estimation of anisotropy coefficient of swine pancreas, liver and muscle at 1064 nm based on goniometric technique

      Paola Saccomandi, Vitali Vogel, Babak Bazrafshan, Jürgen Maurer, Emiliano Schena, Thomas J. Vogl, Sergio Silvestri and Werner Mäntele

      Article first published online: 3 JUL 2014 | DOI: 10.1002/jbio.201400057

    5. Probe-based confocal laser endomicroscopy (pCLE) – a new imaging technique for in situ localization of spermatozoa

      Matthias Trottmann, Herbert Stepp, Ronald Sroka, Michael Heide, Bernhard Liedl, Sven Reese, Armin J. Becker, Christian G. Stief and Sabine Kölle

      Article first published online: 3 JUL 2014 | DOI: 10.1002/jbio.201400053

  12. Full Article

    1. Dual-polarization Raman spectral imaging to extract overlapping molecular fingerprints of living cells

      Liang-da Chiu, Almar F. Palonpon, Nicholas I. Smith, Satoshi Kawata, Mikiko Sodeoka and Katsumasa Fujita

      Article first published online: 15 APR 2014 | DOI: 10.1002/jbio.201300204

  13. Full Articles

    1. Transient state imaging of live cells using single plane illumination and arbitrary duty cycle excitation pulse trains

      Jonas Mücksch, Thiemo Spielmann, Evangelos Sisamakis and Jerker Widengren

      Article first published online: 7 APR 2014 | DOI: 10.1002/jbio.201400015

    2. Optical Thromboelastography to evaluate whole blood coagulation

      Zeinab Hajjarian, Markandey M. Tripathi and Seemantini K. Nadkarni

      Article first published online: 3 APR 2014 | DOI: 10.1002/jbio.201300197

    3. Live cell imaging of the intracellular compartmentalization of the contaminate benzo[a]pyrene

      Rizwan Ali, Saskia Trump, Irina Lehmann and Thomas Hanke

      Article first published online: 3 APR 2014 | DOI: 10.1002/jbio.201300170

    4. Combined antibacterial effects of tissue-tolerable plasma and a modern conventional liquid antiseptic on chronic wound treatment

      Martin Klebes, Christin Ulrich, Franziska Kluschke, Alexa Patzelt, Staffan Vandersee, Heike Richter, Adrienne Bob, Johanna von Hutten, Jorien T. Krediet, Axel Kramer, Jürgen Lademann and Bernhard Lange-Asschenfeld

      Article first published online: 21 MAR 2014 | DOI: 10.1002/jbio.201400007


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