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Publication Open Access 3D printed microneedles for point of care biosensing applications(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Department of Mechanical Engineering; Sarabi, Misagh Rezapour; Nakhjavani, Sattar Akbar; Taşoğlu, Savaş; Faculty Member; Department of Mechanical Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 291971Microneedles (MNs) are an emerging technology for user-friendly and minimally invasive injection, offering less pain and lower tissue damage in comparison to conventional needles. With their ability to extract body fluids, MNs are among the convenient candidates for developing biosensing setups, where target molecules/biomarkers are detected by the biosensor using the sample collected with the MNs. Herein, we discuss the 3D printing of microneedle arrays (MNAs) toward enabling point-of-care (POC) biosensing applications.Publication Open Access 3D spatial organization and network-guided comparison of mutation profiles in Glioblastoma reveals similarities across patients(Public Library of Science, 2019) Dinçer, Cansu; Kaya, Tuğba; Tunçbağ, Nurcan; Department of Chemical and Biological Engineering; Department of Computer Engineering; Keskin, Özlem; Gürsoy, Attila; Faculty Member; Department of Chemical and Biological Engineering; Department of Computer Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; 26605; 8745Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor. Molecular heterogeneity is a hallmark of GBM tumors that is a barrier in developing treatment strategies. In this study, we used the nonsynonymous mutations of GBM tumors deposited in The Cancer Genome Atlas (TCGA) and applied a systems level approach based on biophysical characteristics of mutations and their organization in patient-specific subnetworks to reduce inter-patient heterogeneity and to gain potential clinically relevant insights. Approximately 10% of the mutations are located in "patches" which are defined as the set of residues spatially in close proximity that are mutated across multiple patients. Grouping mutations as 3D patches reduces the heterogeneity across patients. There are multiple patches that are relatively small in oncogenes, whereas there are a small number of very large patches in tumor suppressors. Additionally, different patches in the same protein are often located at different domains that can mediate different functions. We stratified the patients into five groups based on their potentially affected pathways, revealed from the patient-specific subnetworks. These subnetworks were constructed by integrating mutation profiles of the patients with the interactome data. Network-guided clustering showed significant association between each group and patient survival (P-value = 0.0408). Also, each group carries a set of signature 3D mutation patches that affect predominant pathways. We integrated drug sensitivity data of GBM cell lines with the mutation patches and the patient groups to analyze the therapeutic outcome of these patches. We found that Pazopanib might be effective in Group 3 by targeting CSF1R. Additionally, inhibiting ATM that is a mediator of PTEN phosphorylation may be ineffective in Group 2. We believe that from mutations to networks and eventually to clinical and therapeutic data, this study provides a novel perspective in the network-guided precision medicine.Publication Open Access 3D-printed microneedles in biomedical applications(Elsevier, 2021) Rahbarghazi, Reza; Yetişen, Ali Kemal; N/A; Department of Mechanical Engineering; Dabbagh, Sajjad Rahmani; Sarabi, Misagh Rezapour; Sokullu, Emel; Taşoğlu, Savaş; Faculty Member; Faculty Member; Department of Mechanical Engineering; KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Social Sciences and Humanities; Graduate School of Sciences and Engineering; School of Medicine; College of Engineering; N/A; N/A; 163024; 291971Conventional needle technologies can be advanced with emerging nano- and micro-fabrication methods to fabricate microneedles. Nano-/micro-fabricated microneedles seek to mitigate penetration pain and tissue damage, as well as providing accurately controlled robust channels for administrating bioagents and collecting body fluids. Here, design and 3D printing strategies of microneedles are discussed with emerging applications in biomedical devices and healthcare technologies. 3D printing offers customization, cost-efficiency, a rapid turnaround time between design iterations, and enhanced accessibility. Increasing the printing resolution, the accuracy of the features, and the accessibility of low-cost raw printing materials have empowered 3D printing to be utilized for the fabrication of microneedle platforms. The development of 3D-printed microneedles has enabled the evolution of pain-free controlled release drug delivery systems, devices for extracting fluids from the cutaneous tissue, biosignal acquisition, and point-of-care diagnostic devices in personalized medicine.Publication Open Access 3D-printed microrobots from design to translation(Nature Portfolio, 2022) Department of Mechanical Engineering; N/A; Dabbagh, Sajjad Rahmani; Sarabi, Misagh Rezapour; Birtek, Mehmet Tuğrul; Sitti, Metin; Taşoğlu, Savaş; Faculty Member; Faculty Member; Department of Mechanical Engineering; KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; Graduate School of Sciences and Engineering; School of Medicine; College of Engineering; N/A; N/A; N/A; N/A; 297104; 291971Microrobots have attracted the attention of scientists owing to their unique features to accomplish tasks in hard-to-reach sites in the human body. Microrobots can be precisely actuated and maneuvered individually or in a swarm for cargo delivery, sampling, surgery, and imaging applications. In addition, microrobots have found applications in the environmental sector (e.g., water treatment). Besides, recent advancements of three-dimensional (3D) printers have enabled the high-resolution fabrication of microrobots with a faster design-production turnaround time for users with limited micromanufacturing skills. Here, the latest end applications of 3D printed microrobots are reviewed (ranging from environmental to biomedical applications) along with a brief discussion over the feasible actuation methods (e.g., on- and off-board), and practical 3D printing technologies for microrobot fabrication. In addition, as a future perspective, we discussed the potential advantages of integration of microrobots with smart materials, and conceivable benefits of implementation of artificial intelligence (AI), as well as physical intelligence (PI). Moreover, in order to facilitate bench-to-bedside translation of microrobots, current challenges impeding clinical translation of microrobots are elaborated, including entry obstacles (e.g., immune system attacks) and cumbersome standard test procedures to ensure biocompatibility.
Publication Metadata only [BMIM] [PF6] incorporation doubles CO2 selectivity of ZIF-8: elucidation of interactions and their consequences on performance(Amer Chemical Soc, 2016) N/A; N/A; N/A; N/A; N/A; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Kınık, Fatma Pelin; Altıntaş, Çiğdem; Balcı, Volkan; Koyutürk, Burak; Uzun, Alper; Keskin, Seda; Master Student; Researcher; PhD Student; Master Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; 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; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; N/A; N/A; N/A; 59917; 40548Experiments were combined with atomically detailed simulations and density functional theory (DFT) calculations to understand the effect of incorporation of an ionic liquid (IL), 1-n-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]), into a metal organic framework (MOF with a zeolitic imidazolate framework), ZIF-8, on the CO2 separation performance. The interactions between [BMIM] [PF6] and ZIF-8 were examined in deep detail, and their consequences on CO2/CH4, CO2/N-2, and CH4/N-2 separation have been elucidated by using experimental measurements complemented by DFT calculations and atomically detailed simulations. Results suggest that IL-MOF interactions strongly affect the gas affinity of materials at low pressure, whereas available pore volume plays a key role for gas adsorption at high pressures. Direct interactions between IL and MOF lead to at least a doubling of CO2/CH4 and CO2/N-2 selectivities of ZIF-8. These results provide opportunities for rational design and development of IL-incorporated MOFs with exceptional selectivity for target gas separation applications.Publication Open Access A cartridge based sensor array platform for multiple coagulation measurements from plasma(Royal Society of Chemistry (RSC), 2015) Bulut, Serpil; Yaralioglu, G. G.; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Çakmak, Onur; Ermek, Erhan; Kılınç, Necmettin; Barış, İbrahim; Kavaklı, İbrahim Halil; Ürey, Hakan; PhD Student; Other; Researcher; Teaching Faculty; Faculty Member; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; College of Engineering; Graduate School of Sciences and Engineering; College of Sciences; N/A; 109991; N/A; 111629; 40319; 8579This paper proposes a MEMS-based sensor array enabling multiple clot-time tests for plasma in one disposable microfluidic cartridge. The versatile LoC (Lab-on-Chip) platform technology is demonstrated here for real-time coagulation tests (activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT)). The system has a reader unit and a disposable cartridge. The reader has no electrical connections to the cartridge. This enables simple and low-cost cartridge designs and avoids reliability problems associated with electrical connections. The cartridge consists of microfluidic channels and MEMS microcantilevers placed in each channel. The microcantilevers are made of electroplated nickel. They are actuated remotely using an external electro-coil and the read-out is also conducted remotely using a laser. The phase difference between the cantilever oscillation and the coil drive is monitored in real time. During coagulation, the viscosity of the blood plasma increases resulting in a change in the phase read-out. The proposed assay was tested on human and control plasma samples for PT and aPTT measurements. PT and aPTT measurements from control plasma samples are comparable with the manufacturer's datasheet and the commercial reference device. The measurement system has an overall 7.28% and 6.33% CV for PT and aPTT, respectively. For further implementation, the microfluidic channels of the cartridge were functionalized for PT and aPTT tests by drying specific reagents in each channel. Since simultaneous PT and aPTT measurements are needed in order to properly evaluate the coagulation system, one of the most prominent features of the proposed assay is enabling parallel measurement of different coagulation parameters. Additionally, the design of the cartridge and the read-out system as well as the obtained reproducible results with 10 mu l of the plasma samples suggest an opportunity for a possible point-of-care application.Publication Metadata only A chemically inducible organelle rerouting assay to probe primary cilium assembly, maintenance, and disassembly in cultured cells(Humana Press Inc., 2024) Department of Molecular Biology and Genetics; İşsezer, Fatma Başak Turan; Ercan, Muhammed Erdem; Karalar, Elif Nur Fırat; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of SciencesThe primary cilium is a conserved, microtubule-based organelle that protrudes from the surface of most vertebrate cells as well as sensory cells of many organisms. It transduces extracellular chemical and mechanical cues to regulate diverse cellular processes during development and physiology. Loss-of-function studies via RNA interference and CRISPR/Cas9-mediated gene knockouts have been the main tool for elucidating the functions of proteins, protein complexes, and organelles implicated in cilium biology. However, these methods are limited in studying acute spatiotemporal functions of proteins as well as the connection between their cellular positioning and functions. A powerful approach based on inducible recruitment of plus or minus end-directed molecular motors to the protein of interest enables fast and precise control of protein activity in time and in space. In this chapter, we present a chemically inducible heterodimerization method for functional perturbation of centriolar satellites, an emerging membrane-less organelle involved in cilium biogenesis and function. The method we present is based on rerouting of centriolar satellites to the cell center or the periphery in mammalian epithelial cells. We also describe how this method can be applied to study the temporal functions of centriolar satellites during primary cilium assembly, maintenance, and disassembly.Publication Open Access A hybrid broadband metalens operating at ultraviolet frequencies(Nature Publishing Group (NPG), 2021) Department of Physics; Ali, Farhan; Ramazanoğlu, Serap Aksu; Faculty Member; Department of Physics; Graduate School of Sciences and Engineering; College of Sciences; N/A; 243745The investigation on metalenses have been rapidly developing, aiming to bring compact optical devices with superior properties to the market. Realizing miniature optics at the UV frequency range in particular has been challenging as the available transparent materials have limited range of dielectric constants. In this work we introduce a low absorption loss and low refractive index dielectric material magnesium oxide, MgO, as an ideal candidate for metalenses operating at UV frequencies. We theoretically investigate metalens designs capable of efficient focusing over a broad UV frequency range (200–400 nm). The presented metalenses are composed of sub-wavelength MgO nanoblocks, and characterized according to the geometric Pancharatnam–Berry phase method using FDTD method. The presented broadband metalenses can focus the incident UV light on tight focal spots (182 nm) with high numerical aperture (NA ≈ 0.8). The polarization conversion efficiency of the metalens unit cell and focusing efficiency of the total metalens are calculated to be as high as 94%, the best value reported in UV range so far. In addition, the metalens unit cell can be hybridized to enable lensing at multiple polarization states. The presented highly efficient MgO metalenses can play a vital role in the development of UV nanophotonic systems and could pave the way towards the world of miniaturization.Publication Open Access A multi-state coarse grained modeling approach for an intrinsically disordered peptide(American Institute of Physics (AIP) Publishing, 2017) Department of Chemical and Biological Engineering; N/A; Sayar, Mehmet; Dalgıçdır, Cahit; Ramezanghorbani, Farhad; Faculty Member; PhD Student; Department of Chemical and Biological Engineering; College of Engineering; Graduate School of Sciences and Engineering; 109820; N/A; N/AMany proteins display a marginally stable tertiary structure, which can be altered via external stimuli. Since a majority of coarse grained (CG) models are aimed at structure prediction, their success for an intrinsically disordered peptide's conformational space with marginal stability and sensitivity to external stimuli cannot be taken for granted. In this study, by using the LK alpha 14 peptide as a test system, we demonstrate a bottom-up approach for constructing a multi-state CG model, which can capture the conformational behavior of this peptide in three distinct environments with a unique set of interaction parameters. LK alpha 14 is disordered in dilute solutions; however, it strictly adopts the alpha-helix conformation upon aggregation or when in contact with a hydrophobic/hydrophilic interface. Our bottom-up approach combines a generic base model, that is unbiased for any particular secondary structure, with nonbonded interactions which represent hydrogen bonds, electrostatics, and hydrophobic forces. We demonstrate that by using carefully designed all atom potential of mean force calculations from all three states of interest, one can get a balanced representation of the nonbonded interactions. Our CG model behaves intrinsically disordered in bulk water, folds into an alpha-helix in the presence of an interface or a neighboring peptide, and is stable as a tetrameric unit, successfully reproducing the all atom molecular dynamics simulations and experimental results.Publication Open Access A narrow-band multi-resonant metamaterial in near-ir(Multidisciplinary Digital Publishing Institute (MDPI), 2020) Ali, Farhan; Department of Physics; Ramazanoğlu, Serap Aksu; Faculty Member; Department of Physics; College of Sciences; 243745We theoretically investigate a multi-resonant plasmonic metamaterial perfect absorber operating between 600 and 950 nm wavelengths. The presented device generates 100% absorption at two resonance wavelengths and delivers an ultra-narrow band (sub-20 nm) and high quality factor (Q = 44) resonance. The studied perfect absorber is a metal–insulator–metal configuration where a thin MgF2 spacer is sandwiched between an optically thick gold layer and uniformly patterned gold circular nanodisc antennas. The localized and propagating nature of the plasmonic resonances are characterized and confirmed theoretically. The origin of the perfect absorption is investigated using the impedance matching and critical coupling phenomenon. We calculate the effective impedance of the perfect absorber and confirm the matching with the free space impedance. We also investigate the scattering properties of the top antenna layer and confirm the minimized reflection at resonance wavelengths by calculating the absorption and scattering cross sections. The excitation of plasmonic resonances boost the near-field intensity by three orders of magnitude which enhances the interaction between the metamaterial surface and the incident energy. The refractive index sensitivity of the perfect absorber could go as high as S = 500 nm/RIU. The presented optical characteristics make the proposed narrow-band multi-resonant perfect absorber a favorable platform for biosensing and contrast agent based bioimaging.