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Publication Open Access 3D printed personalized magnetic micromachines from patient blood-derived biomaterials(American Association for the Advancement of Science (AAAS), 2021) Ceylan, Hakan; Doğan, Nihal Olcay; Yaşa, İmmihan Ceren; Department of Mechanical Engineering; Sitti, Metin; Musaoğlu, Miraç Nur; Kulalı, Zeynep Umut; Faculty Member; Department of Mechanical Engineering; College of Engineering; School of Medicine; 297104; N/A; N/AWhile recent wireless micromachines have shown increasing potential for medical use, their potential safety risks concerning biocompatibility need to be mitigated. They are typically constructed from materials that are not intrinsically compatible with physiological environments. Here, we propose a personalized approach by using patient blood-derivable biomaterials as the main construction fabric of wireless medical micromachines to alleviate safety risks from biocompatibility. We demonstrate 3D printed multiresponsive microswimmers and microrollers made from magnetic nanocomposites of blood plasma, serum albumin protein, and platelet lysate. These micro-machines respond to time-variant magnetic fields for torque-driven steerable motion and exhibit multiple cycles of pH-responsive two-way shape memory behavior for controlled cargo delivery and release applications. Their proteinaceous fabrics enable enzymatic degradability with proteinases, thereby lowering risks of long-term toxicity. The personalized micromachine fabrication strategy we conceptualize here can affect various future medical robots and devices made of autologous biomaterials to improve biocompatibility and smart functionality.Publication Open Access A new type of microphotoreactor with integrated optofluidic waveguide based on solid-air nanoporous aerogels(Royal Society of Chemistry (RSC), 2018) Jonas, Alexandr; Department of Chemistry; Department of Electrical and Electronics Engineering; Department of Physics; Özbakır, Yaprak; Erkey, Can; Kiraz, Alper; PhD Student; Faculty Member; Faculty Member; Department of Chemistry; Department of Electrical and Electronics Engineering; Department of Physics; College of Engineering; College of Sciences; N/A; 29633; 22542In this study, we developed a new type of microphotoreactor based on an optofluidic waveguide with aqueous liquid core fabricated inside a nanoporous aerogel. To this end, we synthesized a hydrophobic silica aerogel monolith with a density of 0.22 g cm(-3) and a low refractive index of 1.06 that-from the optical point of view-effectively behaves like solid air. Subsequently, we drilled an L-shaped channel within the monolith that confined both the aqueous core liquid and the guided light, the latter property arising due to total internal reflection of light from the liquid-aerogel interface. We characterized the efficiency of light guiding in liquid-filled channel and-using the light delivered by waveguiding-we carried out photochemical reactions in the channel filled with aqueous solutions of methylene blue dye. We demonstrated that methylene blue could be efficiently degraded in the optofluidic photoreactor, with conversion increasing with increasing power of the incident light. The presented optofluidic microphotoreactor represents a versatile platform employing light guiding concept of conventional optical fibres for performing photochemical reactions.Publication Open Access A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model(BioMed Central, 2021) Hu, Yun; Paris, Sebastien; Barsoumian, Hampartsoum; Abana, Chike O.; He, Kewen; Wasley, Mark; Masrorpour, Fatemeh; Chen, Dawei; Yang, Liangpeng; Dunn, Joe D.; Gandhi, Saumil; Nguyen, Quynh-Nhu; Cortez, Maria Angelica; Welsh, James W.; Sezen, Duygu; Faculty Member; School of Medicine; 170535Background: combining radiotherapy with PD1 blockade has had impressive antitumor effects in preclinical models of metastatic lung cancer, although anti-PD1 resistance remains problematic. Here, we report results from a triple-combination therapy in which NBTXR3, a clinically approved nanoparticle radioenhancer, is combined with high-dose radiation (HDXRT) to a primary tumor plus low-dose radiation (LDXRT) to a secondary tumor along with checkpoint blockade in a mouse model of anti-PD1-resistant metastatic lung cancer. Methods: mice were inoculated with 344SQR cells in the right legs on day 0 (primary tumor) and the left legs on day 3 (secondary tumor). Immune checkpoint inhibitors (ICIs), including anti-PD1 (200 mu g) and anti-CTLA4 (100 mu g) were given intraperitoneally. Primary tumors were injected with NBTXR3 on day 6 and irradiated with 12-Gy (HDXRT) on days 7, 8, and 9; secondary tumors were irradiated with 1-Gy (LDXRT) on days 12 and 13. The survivor mice at day 178 were rechallenged with 344SQR cells and tumor growth monitored thereafter. Results: NBTXR3 + HDXRT + LDXRT + ICIs had significant antitumor effects against both primary and secondary tumors, improving the survival rate from 0 to 50%. Immune profiling of the secondary tumors revealed that NBTXR3 + HDXRT + LDXRT increased CD8 T-cell infiltration and decreased the number of regulatory T (Treg) cells. Finally, none of the re-challenged mice developed tumors, and they had higher percentages of CD4 memory T cells and CD4 and CD8 T cells in both blood and spleen relative to untreated mice. Conclusions: NBTXR3 nanoparticle in combination with radioimmunotherapy significantly improves anti-PD1 resistant lung tumor control via promoting antitumor immune response.Publication Open Access Comparison of the results of blood glucose self-monitoring and continuous glucose monitoring in pregnant women with previous diabetes mellitus(Moscow Region Research and Clinical Institute (MONIKI), 2015) Dreval, A. V.; Shestakova, T. P.; Dreval, O. A.; Kulikov, D. A.; Medvedev, O. S.; Department of Industrial Engineering; Türkay, Metin; Faculty Member; Department of Industrial Engineering; College of Engineering; 24956Background: Pregnancy is one of the indications for continuous glucose monitoring (CGM). The data on its efficiency in pregnant women are contradictory. Aim: To compare the results of blood glucose self-monitoring (SMBG) and CGM in pregnant women with previous diabetes mellitus. Materials and methods: We performed a cross-sectional comparative study of glycemia in 18 pregnant women with previous type 1 (87.8% of patients) and type 2 diabetes (22.2% of patients) with various degrees of glycemic control. Their age was 27.7 ± 4.9 year. At study entry, the patients were at 17.2 ± 6.1 weeks of gestation. CGM and SMBG were performed in and by all patients for the duration of 5.4 ± 1.5 days. Depending on their hba1c levels, all patients were divided into two groups: group 1 – 12 women with the hba1c above the target (8.5 ± 1%), and group 2 – 6 women with the hba1c levels within the target (5.6 ± 0.3%). Results: According to SMBG results, women from group 2 had above-the-target glycemia levels before breakfast, at 1 hour after breakfast and at bedtime: 6.2 ± 1.6, 8.7 ± 2.1, and 5.7 ± 1.9 mmol/L, respectively. According to CGM, patients from group 1 had higher postprandial glycemia than those from group 2 (8.0 ± 2.1 and 6.9 ± 1.8 mmol/L, respectively, p = 0.03). The analysis of glycemia during the day time revealed significant difference between the groups only at 1 hour after dinner (7.1 ± 1.4 mmol/L in group 1 and 5.8 ± 0.9 mmol/L in group 2, р = 0.041) and the difference was close to significant before lunch (6.0 ± 2.2 mmol/L in group 1 and 4.8 ± 1.0 mmol/L in group 2, р = 0.053). Comparison of SMBG and CGM results demonstrated significant difference only at one timepoint (at 1 hour after lunch) and only in group 1: median glycemia was 7.4 [6.9; 8.1] mmol/L by SMBG and 6 [5.4; 6.6] mmol/L by CGM measurement (р = 0.001). Lower median values by CGM measurement could be explained by averaging of three successive measurements carried out in the period of rapid changes of glycemia. Conclusion: The achievement of control of diabetes by hba1c doesn't necessarily reflect current achievement of the target glycemic levels. As long as there was no significant difference in glycemia measured by SMBG and CGM, we conclude that CGM doesn't have any advantage over routine frequent SMBG in pregnant women.Publication Open Access Comparison of the trifecta outcomes of robotic and open nephron-sparing surgeries performed in the robotic era of a single institution(SpringerOpen, 2015) Isik, Esin Ozturk; Mut, Tuna; Saglican, Yesim; Vural, Metin; Musaoğlu, Ahmet; N/A; N/A; Acar, Ömer; Onay, Aslıhan; Esen, Tarık; Faculty Member; Faculty Member; School of Medicine; 237530; N/A; 50536Purpose: In this study we aimed to report a comparative analysis between open and robotic nephron sparing surgeries (NSS) from a single institutional database. Methods: Patients who have undergone NSS during the robotic era of our institution were included in this study. Open (n = 74) and robotic (n = 59) groups were compared regarding trifecta outcome. Trifecta was defined as; warm ischemia time (WIT) <25 min, negative surgical margins and the absence of perioperative complications. Results: A total of 57 (77 %) and 45 (76 %) patients in the open and robotic groups, respectively achieved the trifecta outcome. Overall trifecta rate was 77 % (n = 102/133). The only statistically significant difference between trifecta positive and trifecta negative patients was the length of hospitalization (LOH). Except LOH; none of the tested parameters were shown to be predictive of trifecta outcome on univariate and multivariate analyses. Concerning trifecta positive patients; those in the open surgery group had larger tumors with a higher degree of morphometric complexity and were hospitalized for a longer period of time. Additionally, operative duration was significantly higher in the robotic group. Conclusions: In our cohort, no significant difference in achieving the trifecta outcome was reported after open and robotic NSS. Length of hospitalization was the only parameter that differed significantly between trifecta positive and trifecta negative patients. Surgical approach was not a significant predictor of simultaneous achievement of trifecta outcomes. Irrespective of the trifecta definition; larger and more complicated tumors were handled via open NSS.Publication Open Access Computational screening of MOF-based mixed matrix membranes for CO2/N2 separations(Hindawi, 2016) Department of Chemical and Biological Engineering; Keskin, Seda; Sümer, Zeynep; Master Student; Department of Chemical and Biological Engineering; College of Engineering; Graduate School of Sciences and Engineering; 40548; N/AAtomically detailed simulations were used to examine CO2/N-2 separation potential of metal organic framework- (MOF-) based mixed matrix membranes (mmms) in this study. Gas permeability and selectivity of 700 new mmms composed of 70 different mofs and 10 different polymers were calculated for CO2/N-2 separation. This is the largest number of MOF-based mmms for which computational screening is done to date. Selecting the appropriate mofs as filler particles in polymers resulted in mmms that have higher CO2/N-2 selectivities and higher CO2 permeabilities compared to pure polymer membranes. We showed that, for polymers that have low CO2 permeabilities but high CO2 selectivities, the identity of the MOF used as filler is not important. All mofs enhanced the CO2 permeabilities of this type of polymers without changing their selectivities. Several MOF-based mmms were identified to exceed the upper bound established for polymers. The methods we introduced in this study will create many opportunities to select the MOF/polymer combinations with useful properties for CO2 separation applications.Publication Open Access Creating three-dimensional magnetic functional microdevices via molding-integrated direct laser writing(Springer Nature, 2022) Liu, Z.; Li, M.; Dong, X.; Ren, Z.; Hu, W.; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; School of Medicine; College of Engineering; 297104Magnetically driven wireless miniature devices have become promising recently in healthcare, information technology, and many other fields. However, they lack advanced fabrication methods to go down to micrometer length scales with heterogeneous functional materials, complex three-dimensional (3D) geometries, and 3D programmable magnetization profiles. To fill this gap, we propose a molding-integrated direct laser writing-based microfabrication approach in this study and showcase its advanced enabling capabilities with various proof-of-concept functional microdevice prototypes. Unique motions and functionalities, such as metachronal coordinated motion, fluid mixing, function reprogramming, geometrical reconfiguring, multiple degrees-of-freedom rotation, and wireless stiffness tuning are exemplary demonstrations of the versatility of this fabrication method. Such facile fabrication strategy can be applied toward building next-generation smart microsystems in healthcare, robotics, metamaterials, microfluidics, and programmable matter.Publication Open Access CRISPR-Cas-Integrated LAMP(Multidisciplinary Digital Publishing Institute (MDPI), 2022) N/A; Department of Mechanical Engineering; Özdalgıç, Berin; Taşoğlu, Savaş; Yığcı, Defne; Atçeken, Nazente; PhD Student; 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); Graduate School of Sciences and Engineering; College of Engineering; School of Medicine; N/A; 291971; N/A; N/APathogen-specific point-of-care (PoC) diagnostic tests have become an important need in the fight against infectious diseases and epidemics in recent years. PoC diagnostic tests are designed with the following parameters in mind: rapidity, accuracy, sensitivity, specificity, and ease of use. Molecular techniques are the gold standard for pathogen detection due to their accuracy and specificity. There are various limitations in adapting molecular diagnostic methods to PoC diagnostic tests. Efforts to overcome limitations are focused on the development of integrated molecular diagnostics by utilizing the latest technologies available to create the most successful PoC diagnostic platforms. With this point of view, a new generation technology was developed by combining loop-mediated isothermal amplification (LAMP) technology with clustered regularly interspaced short palindromic repeat (CRISPR)-associated (CRISPR-Cas) technology. This integrated approach benefits from the properties of LAMP technology, namely its high efficiency, short turnaround time, and the lack of need for a complex device. It also makes use of the programmable function of CRISPR-Cas technology and the collateral cleavage activity of certain Cas proteins that allow for convenient reporter detection. Thus, this combined technology enables the development of PoC diagnostic tests with high sensitivity, specificity, and ease of use without the need for complicated devices. In this review, we discuss the advantages and limitations of the CRISPR/Cas combined LAMP technology. We review current limitations to convert CRISPR combined LAMP into pathogen-specific PoC platforms. Furthermore, we point out the need to design more useful PoC platforms using microfabrication technologies by developing strategies that overcome the limitations of this new technology, reduce its complexity, and reduce the risk of contamination.Publication Open Access Determination of the elastic behavior of silicon nanowires within a scanning electron microscope(Hindawi, 2016) Wollschloeger, Nicole; Haeusler, Ines; Leblebici, Yusuf; Oesterle, Werner; Department of Mechanical Engineering; Alaca, Burhanettin Erdem; Taşdemir, Zuhal; Faculty Member; Department of Mechanical Engineering; College of Engineering; 115108; N/AThree-point bending tests were performed on double-anchored, < 110 > silicon nanowire samples in the vacuum chamber of a scanning electron microscope ( SEM) via a micromanipulator equipped with a piezoresistive force sensor. Nanowires with widths of 35nm and 74 nm and a height of 168nm were fabricated. The nanowires were obtained monolithically along with their 10 mu m tall supports through a top-down fabrication approach involving a series of etching processes. The exact dimension of wire cross sections was determined by transmission electron microscopy ( TEM). Conducting the experiments in an SEM chamber further raised the opportunity of the direct observation of any deviation from ideal loading conditions such as twisting, which could then be taken into consideration in simulations. Measured force-displacement behavior was observed to exhibit close resemblance to simulation results obtained by finite element modeling, when the bulk value of 169gpa was taken as the modulus of elasticity for < 110 > silicon. Hence, test results neither show any size effect nor show evidence of residual stresses for the considered nanoscale objects. The increased effect of the native oxide with reduced nanowire dimensions was captured as well. The results demonstrate the potential of the developed nanowire fabrication approach for the incorporation in functional micromechanical devices.Publication Open Access Diffraction data from aerosolized Coliphage PR772 virus particles imaged with the Linac Coherent Light Source(Nature Publishing Group (NPG), 2020) Li, H.; Nazari, R.; Abbey, B.; Alvarez, R.; Aquila, A.; Ayyer, K.; Barty, A.; Berntsen, P.; Bielecki, J.; Pietrini, A.; Bucher, M.; Carini, G.; Chapman, H. N.; Contreras, A.; Daurer, B. J.; Flűckiger, L.; Frank, M.; Hajdu, J.; Hantke, M. F.; Hogue, B. G.; Hosseinizadeh, A.; Hunter, M. S.; Jönsson, H. O.; Kirian, R. A.; Kurta, R. P.; Loh, D.; Maia, F. R. N. C.; Mancuso, A. P.; Morgan, A. J.; McFadden, M.; Muehlig, K.; Munke, A.; Reddy, H. K. N.; Nettelblad, C.; Ourmazd, A.; Rose, M.; Schwander, P.; Marvin, Seibert M.; Sellberg, J. A.; Sierra, R. G.; Sun, Z.; Svenda, M.; Vartanyants, I. A.; Walter, P.; Westphal, D.; Williams, G.; Xavier, P. L.; Yoon, C. H.; Zaare, S.; Department of Molecular Biology and Genetics; Demirci, Hasan; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 307350Single Particle Imaging (SPI) with intense coherent X-ray pulses from X-ray free-electron lasers (XFELs) has the potential to produce molecular structures without the need for crystallization or freezing. Here we present a dataset of 285,944 diffraction patterns from aerosolized Coliphage PR772 virus particles injected into the femtosecond X-ray pulses of the Linac Coherent Light Source (LCLS). Additional exposures with background information are also deposited. The diffraction data were collected at the Atomic, Molecular and Optical Science Instrument (AMO) of the LCLS in 4 experimental beam times during a period of four years. The photon energy was either 1.2 or 1.7 keV and the pulse energy was between 2 and 4 mJ in a focal spot of about 1.3 μm x 1.7 μm full width at half maximum (FWHM). The X-ray laser pulses captured the particles in random orientations. The data offer insight into aerosolised virus particles in the gas phase, contain information relevant to improving experimental parameters, and provide a basis for developing algorithms for image analysis and reconstruction.