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    Publication
    10-NJ multipass-cavity femtosecond CR3+: LiCAF laser pumped by low-power single-mode diodes
    (Optical Society of America, 2009) Kärtner, Franz X.; Fujimoto, James G.; Demirbaş, Ümit; Department of Physics; Sennaroğlu, Alphan; Faculty Member; Department of Physics; College of Sciences; 23851
    We report on the generation of 9.9-nJ, 95-fs pulses at a repetition rate of 9.58 MHz from a multipass-cavity Cr3+:LiCAF laser pumped by single-mode diodes with a total absorbed pump power of only 540 mW.
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    A leucine aminopeptidase activatable photosensitizer for cancer cell selective photodynamic therapy action
    (Elsevier Sci Ltd, 2021) N/A; N/A; N/A; Department of Chemistry; N/A; Department of Physics; Department of Chemistry; Department of Chemistry; Arslan, Büşra; Bilici, Kübra; Demirci, Gözde; Almammadov, Toghrul; Khan, Minahil; Sennaroğlu, Alphan; Acar, Havva Funda Yağcı; Kölemen, Safacan; Master Student; PhD Student; Master Student; Researcher; PhD Student; Faculty Member; Faculty Member; Faculty Member; Department of Physics; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Koç University Boron and Advanced Materials Application and Research Center (KUBAM) / Koç Üniversitesi Bor ve İleri Malzemeler Uygulama ve Araştırma Merkezi (KUBAM); Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; College of Sciences; N/A; N/A; N/A; N/A; N/A; 23851; 178902; 272051
    Activity based photosensitizers (PS) continue to attract great attention as they enable selective photodynamic therapy action on cancer cells while sparing normal cells even under light irradiation. Sensitivity to specific enzymes that are differentially overexpressed in cancer cells is crucial in the design of activatable PSs. In this direction, we report here, for the first time, a leucine aminopeptidase (LAP) activatable PDT agent (HCL), which is a red-shifted, water soluble and photostable brominated hemicyanine derivative. HCL was activated by endogenous LAP enzyme selectively in A549 (lung) and HCT116 (colon) cancer cells containing high LAP levels and induced effective photocytotoxicity with negligible dark toxicity. Furthermore, the fluorescence of the parent bromo-hemicyanine core was restored upon LAP-based activation in cancer cells. On the other side, no remarkable phototoxicity or fluorescence turn-on was detected in healthy L929 cells. Thus, HCL serves as an effective and tumour associated LAP-sensitive phototheranostic agent. We believe different cancer-associated analytes can be utilized in combination with near-IR absorbing scaffolds in the scope of activatable PDT designs to enrich the tumour-selective PS arsenal.
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    Acousto-optic mode-locking of a Cr2+: ZnSe laser
    (Optica Publishing Group, 2000) Carrig, Timothy J.; Wagner, Gregory J.; Jeong, Jay Y.; Pollock, Clifford R.; Department of Physics; Sennaroğlu, Alphan; Faculty Member; Department of Physics; College of Sciences; 23851
    Acousto-optic mode-locking of a Cr2+:ZnSe laser that produces 4.4 psec duration, transform-limited, Gaussian shaped pulses is described. The laser outputs 82 mW of output power at an 81 MHz pulse repetition frequency.
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    Aerogels for optofluidic waveguides
    (MDPI, 2017) Jonas, Alexandr; N/A; Department of Physics; Department of Chemical and Biological Engineering; Özbakır, Yaprak; Erkey, Can; Kiraz, Alper; PhD Student; Faculty Member; Faculty Member; Department of Physics; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Sciences; College of Engineering; N/A; 29633; 22542
    Aerogels-solid materials keeping their internal structure of interconnected submicron-sized pores intact upon exchanging the pore liquid with a gas-were first synthesized in 1932 by Samuel Kistler. Overall, an aerogel is a special form of a highly porous material with a very low solid density and it is composed of individual nano-sized particles or fibers that are connected to form a three-dimensional network. The unique properties of these materials, such as open pores and high surface areas, are attributed to their high porosity and irregular solid structure, which can be tuned through proper selection of the preparation conditions. Moreover, their low refractive index makes them a remarkable solid-cladding material for developing liquid-core optofluidic waveguides based on total internal reflection of light. This paper is a comprehensive review of the literature on the use of aerogels for optofluidic waveguide applications. First, an overview of different types of aerogels and their physicochemical properties is presented. Subsequently, possible techniques to fabricate channels in aerogel monoliths are discussed and methods to make the channel surfaces hydrophobic are described in detail. Studies in the literature on the characterization of light propagation in liquid-filled channels within aerogel monoliths as well as their light-guiding characteristics are discussed. Finally, possible applications of aerogel-based optofluidic waveguides are described.
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    Ag2S-Glutathione quantum dots for NIR image guided photothermal therapy
    (Royal Soc Chemistry, 2020) N/A; N/A; N/A; N/A; Department of Physics; Department of Chemistry; Hashemkhani, Mahshid; Bilici, Kübra; Muti, Abdullah; Sennaroğlu, Alphan; Acar, Havva Funda Yağcı; PhD Student; PhD Student; PhD Student; Faculty Member; Faculty Member; Department of Physics; Department of Chemistry; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; N/A; N/A; N/A; 23851; 178902
    Aqueous synthesis of glutathione (GSH) coated Ag2S quantum dots (QD) with strong emission in the medical imaging window (700-900 nm) was performed from AgNO3. Variations in temperature, time, pH and sulfur source (Na2S and thioacetamide) were studied to tune the emission wavelength and intensity of the QDs. The optimum synthesis conditions to produce the smallest QDs (ca. 7 nm) with the highest quantum yield (70%) and excellent stability were determined as 50 degrees C and pH 10 where Na2S was used in 2 h reactions. The cytotoxicity was evaluated with MTT assay on the HT29 and MCF7 cancer cell lines and indicated no significant toxicity of the QDs up to 200 mu g mL(-1). The Photothermal Therapy (PTT) potential was first investigated using a 795 nm, continuous-wave fiber coupled diode laser using aqueous solutions of QDs and then on HT29 and MCF7 cells. QD (150 mu g mL(-1)) treated MCF7 cells almost quantitatively died after 10 min irradiation at 795 nm (700 mW, 1.82 W cm(-2)) and the viability of HT29 cells dropped to 40%. Most cell death was late apoptotic/necrotic. This study indicates that such a laser irradiation procedure and the QDs are safe, yet their combination provides dramatic cell death upon short laser treatment. PTT coupled with strong intracellular optical signal promotes Ag2S-GSH QDs as potential theranostic nanoparticles.
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    PublicationOpen Access
    An easy-to-fabricate microfluidic shallow trench induced three-dimensional cell culturing and imaging (STICI3D) platform
    (American Chemical Society (ACS), 2022) Coşkun, Umut Can; Rehman, Ateeq Ur; Gülle, Merve; Erten, Ahmet; N/A; Department of Physics; Department of Electrical and Electronics Engineering; N/A; Başer, Hatice Nur; Baysal, Kemal; Kiraz, Alper; Kul, Demet; Kuş, Funda; Morova, Berna; Faculty Member; Faculty Member; Researcher; Department of Physics; Department of Electrical and Electronics Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; School of Medicine; College of Sciences; College of Engineering; N/A; 119184; 22542; N/A; N/A; N/A
    Compared to the established monolayer approach of two-dimensional cell cultures, three-dimensional (3D) cultures more closely resemble in vivo models; that is, the cells interact and form clusters mimicking their organization in native tissue. Therefore, the cellular microenvironment of these 3D cultures proves to be more clinically relevant. In this study, we present a novel easy-to-fabricate microfluidic shallow trench induced 3D cell culturing and imaging (STICI3D) platform, suitable for rapid fabrication as well as mass manufacturing. Our design consists of a shallow trench, within which various hydrogels can be formed in situ via capillary action, between and fully in contact with two side channels that allow cell seeding and media replenishment, as well as forming concentration gradients of various molecules. Compared to a micropillar-based burst valve design, which requires sophisticated microfabrication facilities, our capillary-based STICI3D can be fabricated using molds prepared with simple adhesive tapes and razors alone. The simple design supports the easy applicability of mass-production methods such as hot embossing and injection molding as well. To optimize the STICI3D design, we investigated the effect of individual design parameters such as corner radii, trench height, and surface wettability under various inlet pressures on the confinement of a hydrogel solution within the shallow trench using Computational Fluid Dynamics simulations supported with experimental validation. We identified ideal design values that improved the robustness of hydrogel confinement and reduced the effect of end-user dependent factors such as hydrogel solution loading pressure. Finally, we demonstrated cultures of human mesenchymal stem cells and human umbilical cord endothelial cells in the STICI3D to show that it supports 3D cell cultures and enables precise control of cellular microenvironment and real-time microscopic imaging. The easy-to-fabricate and highly adaptable nature of the STICI3D platform makes it suitable for researchers interested in fabricating custom polydimethylsiloxane devices as well as those who are in need of ready-to-use plastic platforms. As such, STICI3Ds can be used in imaging cell-cell interactions, angiogenesis, semiquantitative analysis of drug response in cells, and measurement of transport through cell sheet barriers.
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    Attosecond timing jitter pulse trains from semiconductor saturable absorber mode-locked Cr:LiSAF lasers
    (Optical Society of America, 2012) Kärtner, Franz X.; Fujimoto, James G.; Demirbaş, Ümit; Benedick, Andrew; Li, Duo; Department of Physics; Sennaroğlu, Alphan; Faculty Member; Department of Physics; College of Sciences; 23851
    An integrated timing jitter of 43 as [10 kHz-50 MHz] is measured from a semiconductor saturable absorber modelocked Cr:LiSAF laser. AM-to-PM transfer functions' characterization shows self-steepening is the dominant effect of excess timing jitter. © OSA 2012.
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    PublicationOpen Access
    Cetuximab-Ag2S quantum dots for fluorescence imaging and highly effective combination of ALA-based photodynamic/chemo-therapy of colorectal cancer cells
    (Royal Society of Chemistry (RSC), 2021) Mohammad Hadi, Layla; Yaghini, Elnaz; Loizidou, Marilena; MacRobert, Alexander J.; Department of Chemistry; N/A; Department of Physics; Acar, Havva Funda Yağcı; Bayır, Ali; Hashemkhani, Mahshid; Demirci, Gözde; Muti, Abdullah; Sennaroğlu, Alphan; Researcher; PhD Student; Master Student; PhD Student; Faculty Member; Department of Chemistry; Department of Physics; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); College of Sciences; Graduate School of Sciences and Engineering; 178902; N/A; N/A; N/A; N/A; 23851
    Colorectal cancer (CRC) has a poor prognosis and urgently needs better therapeutic approaches. 5-Aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) based photodynamic therapy (PDT) is already used in the clinic for several cancers but not yet well investigated for CRC. Currently, systemic administration of ALA offers a limited degree of tumour selectivity, except for intracranial tumours, limiting its wider use in the clinic. The combination of effective ALA-PDT and chemotherapy may provide a promising alternative approach for CRC treatment. Herein, theranostic Ag2S quantum dots (AS-2MPA) optically trackable in near-infrared (NIR), conjugated with endothelial growth factor receptor (EGFR) targeting Cetuximab (Cet) and loaded with ALA for PDT monotherapy or ALA/5-fluorouracil (5FU) for the combination therapy are proposed for enhanced treatment of EGFR(+) CRC. AS-2MPA-Cet exhibited excellent targeting of the high EGFR expressing cells and showed a strong intracellular signal for NIR optical detection in a comparative study performed on SW480, HCT116, and HT29 cells, which exhibit high, medium and low EGFR expression, respectively. Targeting provided enhanced uptake of the ALA loaded nanoparticles by strong EGFR expressing cells and formation of higher levels of PpIX. Cells also differ in their efficiency to convert ALA to PpIX, and SW480 was the best, followed by HT29, while HCT116 was determined as unsuitable for ALA-PDT. The therapeutic efficacy was evaluated in 2D cell cultures and 3D spheroids of SW480 and HT29 cells using AS-2MPA with either electrostatically loaded, hydrazone or amide linked ALA to achieve different levels of pH or enzyme sensitive release. Most effective phototoxicity was observed in SW480 cells using AS-2MPA-ALA-electrostatic-Cet due to enhanced uptake of the particles, fast ALA release and effective ALA-to-PpIX conversion. Targeted delivery reduced the effective ALA concentration significantly which was further reduced with codelivery of 5FU. Delivery of ALA via covalent linkages was also effective for PDT, but required a longer incubation time for the release of ALA in therapeutic doses. Phototoxicity was correlated with high levels of reactive oxygen species (ROS) and apoptotic/necrotic cell death. Hence, both AS-2MPA-ALA-Cet based PDT and AS-2MPA-ALA-Cet-5FU based chemo/PDT combination therapy coupled with strong NIR tracking of the nanoparticles demonstrate an exceptional therapeutic effect on CRC cells and excellent potential for synergistic multistage tumour targeting therapy.
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    Comparative experimental study of continuous-wave power performance in room-temperature Cr4+:forsterite lasers
    (Optica Publishing Group, 1998) Department of Physics; Sennaroğlu, Alphan; Faculty Member; Department of Physics; College of Sciences; 23851
    Comparative experimental study of power performance with three different Cr4+:forsterite crystals yields 900 mW of 1.26-μm continuous-wave output power with 29.5% efficiency at 15oC.
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    Comparative investigation of diode-pumped Tm3+: YAlO3 lasers: influence of doping concentration
    (The Optical Society (OSA) Publishing, 2005) N/A; Department of Physics; Department of Physics; N/A; Kurt, Adnan; Sennaroğlu, Alphan; Kalaycıoğlu, Hamit; Teaching Faculty; Faculty Member; PhD Student; Department of Physics; College of Sciences; College of Sciences; Graduate School of Sciences and Engineering; 194455; 23851; N/A
    We investigated the effect of thulium ion concentration on the continuous-wave power performance of diode single-end-pumped Tm3+:YAlO3 (Tm:YAP) lasers operating at 2 µm by using crystals with 1.5%, 3%, and 4% Tm3+ concentration. Best results were obtained with the 1.5% Tm3+:YAP crystal. Spectroscopic measurements and rate-equation analysis suggest that cross relaxation should already be effective at 1.5% Tm3+ concentration. Increase in reabsorption losses, non-radiative decay rates, and internal heating are likely causes of power degradation with increasing ion concentration. By using the laser efficiency data, the effective stimulated emission cross section was determined to be 4.2×10−21 cm2 at 1.94 µm, in agreement with previous results.