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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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Publication Open Access Understanding the link between inflammasome and apoptosis through the response of THP-1 cells against drugs using droplet-based microfluidics(American Chemical Society (ACS), 2022) Gençtürk, E.; Kasım, M.; Ülgen, K.O.; Department of Physics; Department of Electrical and Electronics Engineering; Kiraz, Alper; Morova, Berna; Faculty Member; Researcher; Department of Physics; Department of Electrical and Electronics Engineering; College of Sciences; College of Engineering; 22542; N/ADroplet-based microfluidic devices are used to investigate monocytic THP-1 cells in response to drug administration.Consistent and reproducible droplets are created, each of which acts as a bioreactor to carry out single cell experiments withminimized contamination and live cell tracking under an invertedfluorescence microscope for more than 2 days. Here, the effects ofthree different drugs (temsirolimus, rifabutin, and BAY 11-7082) on THP-1 are examined and the results are analyzed in the contextof the inflammasome and apoptosis relationship. The ASC adaptor gene tagged with GFP is monitored as the inflammasomereporter. Thus, a systematic way is presented for deciphering cell-to-cell heterogeneity, which is an important issue in cancertreatment. The drug temsirolimus, which has effects of disrupting the mTOR pathway and triggering apoptosis in tumor cells, causesTHP-1 cells to express ASC and to be involved in apoptosis. Treatment with rifabutin, which inhibits proliferation and initiatesapoptosis in cells, affects ASC expression byfirst increasing and then decreasing it. CASP-3, which has a role in apoptosis and isdirectly related to ASC, has an increasing level in inflammasome conditioning. Thus, the cell under the effect of rifabutin might befaced with programmed cell death faster. The drug BAY 11-7082, which is responsible for NF Kappa B inhibition, shows similar results totemsirolimus with more than 60% of cells having highfluorescence intensity (ASC expression). The microfluidic platform presentedhere offers strong potential for studying newly developed small-molecule inhibitors for personalized/precision medicine.Publication Open Access Exciton recycling via InP quantum dot funnels for luminescent solar concentrators(Tsinghua University, 2021) Ow-Yang, Cleva W.; N/A; N/A; Department of Physics; Department of Electrical and Electronics Engineering; Jalali, Houman Bahmani; Sadeghi, Sadra; Toker, Işınsu Baylam; Han, Mertcan; Sennaroğlu, Alphan; Nizamoğlu, Sedat; PhD Student; Master Student; Faculty Member; Faculty Member; Department of Physics; Department of Electrical and Electronics Engineering; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; N/A; N/A; 23851; 130295Luminescent solar concentrators (LSC) absorb large-area solar radiation and guide down-converted emission to solar cells for electricity production. Quantum dots (QDs) have been widely engineered at device and quantum dot levels for LSCs. Here, we demonstrate cascaded energy transfer and exciton recycling at nanoassembly level for LSCs. The graded structure composed of different sized toxic-heavy-metal-free InP/ZnS core/shell QDs incorporated on copper doped InP QDs, facilitating exciton routing toward narrow band gap QDs at a high nonradiative energy transfer efficiency of 66%. At the final stage of non-radiative energy transfer, the photogenerated holes make ultrafast electronic transitions to copper-induced mid-gap states for radiative recombination in the near-infrared. The exciton recycling facilitates a photoluminescence quantum yield increase of 34% and 61% in comparison with semi-graded and ungraded energy profiles, respectively. Thanks to the suppressed reabsorption and enhanced photoluminescence quantum yield, the graded LSC achieved an optical quantum efficiency of 22.2%. Hence, engineering at nanoassembly level combined with nonradiative energy transfer and exciton funneling offer promise for efficient solar energy harvesting.Publication Open Access In vitro and in vivo biolasing of fluorescent proteins suspended in liquid microdroplet cavities(Royal Society of Chemistry (RSC), 2014) Jonas, Alexandr; Anand, Suman; McGloin, David; Department of Physics; Department of Chemistry; Bayraktar, Halil; Kiraz, Alper; Aas, Mehdi; Karadağ, Yasin; Manioğlu, Selen; Faculty Member; Faculty Member; PhD Student; Department of Physics; Department of Chemistry; College of Sciences; N/A; 22542; N/A; N/A; N/AFluorescent proteins are indispensable for selective, quantitative visualization of localization, dynamics, and interactions of key molecular constituents of live cells. Incorporation of fluorescent proteins into an optical cavity can lead to a significant increase in fluorescence signal levels due to stimulated emission and light amplification in the cavity, forming a laser with biological gain medium. Utilization of lasing emission from fluorescent biological molecules can then greatly enhance the performance of fluorescence-based biosensors benefiting from the high sensitivity of non-linear lasing processes to small perturbations in the cavity and the gain medium. Here we study optofluidic biolasers that exploit active liquid optical resonators formed by surface-supported aqueous microdroplets containing purified yellow fluorescent protein or a suspension of live E. coli bacterial cells expressing the fluorescent protein. We first demonstrate lasing in fluorescent protein solutions at concentrations as tow as 49 mu M. Subsequently, we show that a single fluorescent bacterial cell of micrometre size confined in a droplet-based cavity can serve as a laser gain medium. Aqueous droplet microcavities allow the maintenance of the bacterial cells under conditions compatible with unimpeded growth. Therefore, our results also suggest a direct route to microscopic sources of laser light with self-regenerating gain media.Publication Open 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/ACompared 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.Publication Open Access Highly luminescent and cytocompatible cationic Ag2S NIR-emitting quantum dots for optical imaging and gene transfection(Royal Society of Chemistry (RSC), 2015) Ozturk, Deniz Gulfem; Gozuacik, Devrim; Department of Chemistry; Department of Physics; Duman, Fatma Demir; Hocaoğlu, İbrahim; Kiraz, Alper; Acar, Havva Funda Yağcı; PhD 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); Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; 22542; 178902The development of non-toxic theranostic nanoparticles capable of delivering a therapeutic cargo and providing a means for diagnosis is one of the most challenging tasks in nano-biotechnology. Gene therapy is a very important mode of therapy and polyethyleneimine (PEI) is one of the most successful vehicles for gene transfection, yet poses significant toxicity. Optical imaging utilizing quantum dots is one of the newer but fast growing diagnostic modalities, which requires non-toxic, highly luminescent materials, preferentially active in the near infrared region. Ag2S NIRQDs fit to this profile perfectly. Here, we demonstrate the aqueous synthesis of cationic Ag2S NIRQDs with a mixed coating of 2-mercaptopropionic acid (2MPA) and PEI (branched, 25 kDa), which are highly luminescent in the NIR-I window (lambda(em) = 810-840 nm) as new theranostic nanoparticles. Synergistic stabilization of the QD surface via the simultaneous use of a small molecule and a polymeric material provided the highest quantum yield, 150% (with respect to LDS 798 at pH 7.4), reported in the literature for Ag2S. These cationic particles show a dramatic improvement in cytocompatibility even without PEGylation, a strong optical signal easily detected by confocal laser microscopy and effective conjugation and transfection of the green fluorescence protein plasmid (pGFP) to HeLa and MCF-7 cell lines (40% efficiency). Overall, these Ag2S NIRQDs show great potential as new theranostics.Publication Open Access Emission tunable, cyto/hemocompatible, near-IR-emitting Ag2S quantum dots by aqueous decomposition of DMSA(Royal Society of Chemistry (RSC), 2014) Sevrin, Chantal; Department of Chemistry; Department of Physics; Birer, Özgür; Hocaoğlu, İbrahim; Kiraz, Alper; Acar, Havva Funda Yağcı; Duman, Fatma Demir; Researcher; 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 Engineering; College of Sciences; Graduate School of Sciences and Engineering; N/A; N/A; N/A; 22542; N/A; 178902Size tunable aqueous Ag2S quantum dots emitting in the near-infrared region were synthesized through decomposition of meso-2,3-dimercaptosuccinic acid (DMSA) in water. The resulting NIR QDs are highly cyto- and hemocompatible, have quantum yields as high as 6.5% and are effective optical imaging agents based on in vitro evaluation.Publication Open 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; 23851Colorectal 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.