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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 Metadata only A review of bioresorbable implantable medical devices: materials, fabrication, and implementation(Wiley, 2020) N/A; N/A; Department of Mechanical Engineering; Department of Mechanical Engineering; Singh, Rahul; Bathaei, Mohammad Javad; İstif, Emin; Beker, Levent; PhD Student; PhD Student; Researcher; Faculty Member; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; N/A; 354990; 308798Implantable medical devices (IMDs) are designed to sense specific parameters or stimulate organs and have been actively used for treatment and diagnosis of various diseases. IMDs are used for long-term disease screening or treatments and cannot be considered for short-term applications since patients need to go through a surgery for retrieval of the IMD. Advances in bioresorbable materials has led to the development of transient IMDs that can be resorbed by bodily fluids and disappear after a certain period. These devices are designed to be implanted in the adjacent of the targeted tissue for predetermined times with the aim of measurement of pressure, strain, or temperature, while the bioelectronic devices stimulate certain tissues. They enable opportunities for monitoring and treatment of acute diseases. To realize such transient and miniaturized devices, researchers utilize a variety of materials, novel fabrication methods, and device design strategies. This review discusses potential bioresorbable materials for each component in an IMD followed by programmable degradation and safety standards. Then, common fabrication methods for bioresorbable materials are introduced, along with challenges. The final section provides representative examples of bioresorbable IMDs for various applications with an emphasis on materials, device functionality, and fabrication methods.Publication Metadata only Controlled drug delivery through a novel PEG hydrogel encapsulated silica aerogel system(Wiley, 2012) N/A; N/A; N/A; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Giray, Seda; Bal, Tuğba; Kartal, Ayşe Meriç; Kızılel, Seda; Erkey, Can; Master Student; PhD Student; Master Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; N/A; N/A; N/A; College of Engineering; College of Engineering; N/A; 353534; N/A; 28376; 29633A novel composite material consisting of a silica aerogel core coated by a poly(ethylene) glycol (PEG) hydrogel was developed. The potential of this novel composite as a drug delivery system was tested with ketoprofen as a model drug due to its solubility in supercritical carbon dioxide. The results indicated that both drug loading capacity and drug release profiles could be tuned by changing hydrophobicity of aerogels, and that drug loading capacity increased with decreased hydrophobicity, while slower release rates were achieved with increased hydrophobicity. Furthermore, higher concentration of PEG diacrylate in the prepolymer solution of the hydrogel coating delayed the release of the drug which can be attributed to the lower permeability at higher PEG diacrylate concentrations. The novel composite developed in this study can be easily implemented to achieve the controlled delivery of various drugs and/or proteins for specific applications. (C) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.Publication Metadata only Effect of preservation period on the viscoelastic material properties of soft tissues with implications for liver transplantation(Asme, 2010) N/A; N/A; N/A; Department of Mechanical Engineering; Department of Mechanical Engineering; Öcal, Sina; Özcan, Mustafa Umut; Başdoğan, İpek; Başdoğan, Çağatay; Master Student; Master Student; Faculty Member; Faculty Member; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; N/A; 179940; 125489The liver harvested from a donor must be preserved and transported to a suitable recipient immediately for a successful liver transplantation. In this process, the preservation period is the most critical, since it is the longest and most tissue damage occurs during this period due to the reduced blood supply to the harvested liver and the change in its temperature. We investigate the effect of preservation period on the dynamic material properties of bovine liver using a viscoelastic model derived from both impact and ramp and hold experiments. First, we measure the storage and loss moduli of bovine liver as a function of excitation frequency using an impact hammer. Second, its time-dependent relaxation modulus is measured separately through ramp and hold experiments performed by a compression device. Third, a Maxwell solid model that successfully imitates the frequency- and time-dependent dynamic responses of bovine liver is developed to estimate the optimum viscoelastic material coefficients by minimizing the error between the experimental data and the corresponding values generated by the model. Finally, the variation in the viscoelastic material coefficients of bovine liver are investigated as a function of preservation period for the liver samples tested 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 36 h, and 48 h after harvesting. The results of our experiments performed with three animals show that the liver tissue becomes stiffer and more viscous as it spends more time in the preservation cycle.Publication Open Access Haemodynamic recovery properties of the torsioned testicular Artery Lumen(Nature Publishing Group (NPG), 2017) Göktaş, Selda; Pişkin, Şenol; Çapraz, Can T.; Çakmak, Yusuf O.; N/A; Department of Mechanical Engineering; Yalçın, Özlem; Ermek, Erhan; Pekkan, Kerem; Other; Faculty Member; Department of Mechanical Engineering; School of Medicine; College of Engineering; 218440; 109991; 161845Testicular artery torsion (twisting) is one such severe vascular condition that leads spermatic cord injury. In this study, we investigate the recovery response of a torsioned ram testicular artery in an isolated organ-culture flow loop with clinically relevant twisting modes (90°, 180°, 270° and 360° angles). Quantitative optical coherence tomography technique was employed to track changes in the lumen diameter, wall thickness and the three-dimensional shape of the vessel in the physiological pressure range (10–50 mmHg). As a control, pressure-flow characteristics of the untwisted arteries were studied when subjected to augmented blood flow conditions with physiological flow rates up to 36 ml/min. Both twist and C-shaped buckling modes were observed. Acute increase in pressure levels opened the narrowed lumen of the twisted arteries noninvasively at all twist angles (at ∼22 mmHg and ∼35 mmHg for 360°-twisted vessels during static and dynamic flow experiments, respectively). The association between the twist-opening flow rate and the vessel diameter was greatly influenced by the initial twist angle. The biomechanical characteristics of the normal (untwisted) and torsioned testicular arteries supported the utilization of blood flow augmentation as an effective therapeutic approach to modulate the vessel lumen and recover organ reperfusion.Publication Metadata only Heart valve inspired and multi-stream aortic cannula: novel designs for cardiopulmonary bypass improvement in neonates(Wiley, 2019) Department of Mechanical Engineering; Department of Mechanical Engineering; Rasooli, Reza; Pekkan, Kerem; Researcher; Faculty Member; Department of Mechanical Engineering; College of Engineering; College of Engineering; N/A; 161845In a typical open-heart surgery, the blood flow through the aortic cannula is a critical element of the cardiopulmonary bypass (CPB) procedure. Especially for the neonatal and pediatric CPB flow conditions, the need for small hydraulic diameter and large blood flow results confined turbulent jet flow regimes that exacerbate blood damage and platelet activation. Simultaneously, the confined jet wake leads to complex stagnation and recirculating flows that cause considerable thrombosis, blood, and endothelial cell damage through the aorta. Thus, an ideal neonatal CPB cannula should be able to generate optimal jet expansion so that sufficient cerebral perfusion is achieved through the head-neck vessels to avoid postoperative neurological complications and developmental defects in children. To address these challenges, a formal bio-inspired design framework is conducted to reach the desired cannula function through novel analogous biological components, first-time in literature. Among the biological jet flow regimes studied, the ventricle filling-jet generated through the atrio-ventricle (AV) valves are found to be the most promising. Inspired from human AV valve shapes, 8 different novel cannula designs, considering the size constrains of neonatal and pediatric patients are built via high-accurate micro stereo-lithography. Using 2-dimensional time-resolved particle image velocimetry the turbulent jet wake characteristics are measured and compared. The proposed designs have exhibited a significant improvement as compared to standard circular cannula by around 30% reduction in maximum outflow velocity and more than 80% reduction in potential core length and spatial energy dissipation which results in a lower risk of cardiovascular and blood damage.Publication Metadata only Impact of PDMS surface treatment in cell-mechanics applications(Elsevier, 2020) N/A; N/A; Department of Mechanical Engineering; N/A; Department of Mechanical Engineering; TRUE, Sedat; Aydemir, Duygu; Salman, Naveed; Ulusu, Nuriye Nuray; Alaca, Burhanettin Erdem; Master Student; PhD Student; Other; Faculty Member; Faculty Member; Department of Mechanical Engineering; N/A; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; Graduate School of Health Sciences; College of Engineering; School of Medicine; College of Engineering; N/A; N/A; N/A; 6807; 115108As a widely used elastomer in cell mechanics studies, PDMS is exposed to a variety of surface treatments during cell culture preparation. Considering its viscoelastic nature in particular, effects of the aforementioned treatments on PDMS mechanical behaviour, especially at the relevant length scale of 100 mu m, received limited attention. This is despite the fact that significant errors were reported in the quantification of cellular traction forces as a result of minute changes in PDMS mechanical properties. Hence, the effects of plasma oxidation, sterilization and incubation on PDMS modulus of elasticity, relaxation modulus and Poisson's ratio are studied here through tension and stress relaxation tests, with the results of the latter interpreted via the linear viscoelastic formulation. It is observed that although significant deviations from the properties of untreated PDMS are measured through this cycle of surface treatment, properties of untreated PDMS are almost recovered following incubation in cell medium. For example, the modulus of elasticity of treated PDMS was found to be 6% smaller than that of the untreated PDMS. The corresponding deviation was <3% and <1% for the relaxation modulus and time-averaged Poisson's ratio, respectively. The rate of change of the Poisson's ratio with time was also found to be reduced at the end of incubation process in cell medium. As a result, viscoelastic properties of untreated PDMS can safely be used within the error margins provided by this work.Publication Metadata only Machine learning-based approach to identify formalin-fixed paraffin-embedded glioblastoma and healthy brain tissues(Spie-Int Soc Optical Engineering, 2022) N/A; Department of Electrical and Electronics Engineering; N/A; N/A; N/A; N/A; N/A; Department of Electrical and Electronics Engineering; Torun, Hülya; Batur, Numan; Bilgin, Buse; Esengür, Ömer Tarık; Baysal, Kemal; Kulaç, İbrahim; Solaroğlu, İhsan; Onbaşlı, Mehmet Cengiz; PhD Student; Undergraduate Student; PhD Student; Undergraduate Student; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Department of Electrical and Electronics Engineering; Graduate School of Sciences and Engineering; College of Engineering; Graduate School of Sciences and Engineering; School of Medicine; School of Medicine; School of Medicine; School of Medicine; College of Engineering; N/A; N/A; N/A; N/A; 119184; 170305; 102059; 258783Glioblastoma is the most malignant and common high-grade brain tumor with a 14-month overall survival length. According to recent World Health Organization Central Nervous System tumor classification (2021), the diagnosis of glioblastoma requires extensive molecular genetic tests in addition to the traditional histopathological analysis of Formalin-Fixed Paraffin-Embedded (FFPE) tissues. Time-consuming and expensive molecular tests as well as the need for clinical neuropathology expertise are the challenges in the diagnosis of glioblastoma. Hence, an automated and rapid analytical detection technique for identifying brain tumors from healthy tissues is needed to aid pathologists in achieving an error-free diagnosis of glioblastoma in clinics. Here, we report on our clinical test results of Raman spectroscopy and machine learning-based glioblastoma identification methodology for a cohort of 20 glioblastoma and 18 white matter tissue samples. We used Raman spectroscopy to distinguish FFPE glioblastoma and white matter tissues applying our previously reported protocols about optimized FFPE sample preparation and Raman measurement parameters. One may analyze the composition and identify the subtype of brain tumors using Raman spectroscopy since this technique yields detailed molecule-specific information from tissues. We measured and classified the Raman spectra of neoplastic and non-neoplastic tissue sections using machine learning classifiers including support vector machine and random forest with 86.6% and 83.3% accuracies, respectively. These proof-of-concept results demonstrate that this technique might be eventually used in the clinics to assist pathologists once validated with a larger and more diverse glioblastoma cohort and improved detection accuracies.Publication Metadata only Noise in neuronal and electronic circuits: a general modeling framework and non-monte carlo simulation techniques(Ieee-Inst Electrical Electronics Engineers Inc, 2017) N/A; N/A; Department of Electrical and Electronics Engineering; Kılınç, Deniz; Demir, Alper; PhD Student; Faculty Member; Department of Electrical and Electronics Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 3756The brain is extremely energy efficient and remarkably robust in what it does despite the considerable variability and noise caused by the stochastic mechanisms in neurons and synapses. Computational modeling is a powerful tool that can help us gain insight into this important aspect of brain mechanism. A deep understanding and computational design tools can help develop robust neuromorphic electronic circuits and hybrid neuroelectronic systems. In this paper, we present a general modeling framework for biological neuronal circuits that systematically captures the nonstationary stochastic behavior of ion channels and synaptic processes. In this framework, fine-grained, discrete-state, continuous-time Markov chain models of both ion channels and synaptic processes are treated in a unified manner. Our modeling framework features a mechanism for the automatic generation of the corresponding coarse-grained, continuous-state, continuous-time stochastic differential equation models for neuronal variability and noise. Furthermore, we repurpose non-Monte Carlo noise analysis techniques, which were previously developed for analog electronic circuits, for the stochastic characterization of neuronal circuits both in time and frequency domain. We verify that the fast non-Monte Carlo analysis methods produce results with the same accuracy as computationally expensive Monte Carlo simulations. We have implemented the proposed techniques in a prototype simulator, where both biological neuronal and analog electronic circuits can be simulated together in a coupled manner.Publication Open Access Transition from the fetal to neonatal circulation: Modeling the effects of umbilical cord clamping(Elsevier, 2015) Yiğit, Mehmet B.; Kowalski, William J.; Hutchon, David J.R.; Department of Mechanical Engineering; Pekkan, Kerem; Faculty Member; Department of Mechanical Engineering; College of Engineering; 161845Hemodynamics of the fetal to neonatal transition are orchestrated through complex physiological changes and results in cardiovascular adaptation to the adult biventricular circulation. Clinical practice during this critical period can influence vital organ physiology for normal newborns, premature babies and congenital heart defect patients. Particularly, the timing of the cord clamping procedure, immediate (ICC) vs. delayed cord clamping (DCC), is hypothesized to be an important factor for the transitory fetal hemodynamics. The clinical need for a quantitative understanding of this physiology motivated the development of a lumped parameter model (LPM) of the fetal cardio-respiratory system covering the late-gestation to neonatal period. The LPM was validated with in vivo clinical data and then used to predict the effects of cord clamping procedures on hemodynamics and vital gases. Clinical time-dependent resistance functions to simulate the vascular changes were introduced. For DCC, placental transfusion (31.3ml) increased neonatal blood volume by 11.7%. This increased blood volume is reflected in an increase in preload pressures by ~20% compared to ICC, which in turn increased the cardiac output (CO) by 20% (CO.sub.ICC =993ml/min; CO.sub.DCC =1197ml/min). Our model accurately predicted dynamic flow patterns in vivo. DCC was shown to maintain oxygenation if the onset of pulmonary respiration was delayed or impaired. On the other hand, a significant 25% decrease in oxygen saturations was observed when applying ICC under the same physiological conditions. We conclude that DCC has a significant impact on newborn hemodynamics, mainly because of the improved blood volume and the sustained placental respiration.