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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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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 Thiophene-based trimers for in vivo electronic functionalization of tissues(American Chemical Society (ACS), 2020) Mantione, Daniele; Dufil, Gwennael; Vallan, Lorenzo; Parker, Daniela; Brochon, Cyril; Cloutet, Eric; Hadziioannou, Georges; Berggren, Magnus; Stavrinidou, Eleni; Pavlopoulou, Eleni; Department of Mechanical Engineering; İstif, Emin; Faculty Member; Master Student; Department of Mechanical Engineering; College of EngineeringElectronic materials that can self-organize in vivo and form functional components along the tissue of interest can result in a seamless integration of the bioelectronic interface. Previously, we presented in vivo polymerization of the conjugated oligomer ETE-S in plants, forming conductors along the plant structure. The EDOT-thiophene-EDOT trimer with a sulfonate side group polymerized due to the native enzymatic activity of the plant and integrated within the plant cell wall. Here, we present the synthesis of three different conjugated trimers based on thiophene and EDOT or purely EDOT trimers that are able to polymerize enzymatically in physiological pH in vitro as well as in vivo along the roots of living plants. We show that by modulating the backbone and the side chain, we can tune the electronic properties of the resulting polymers as well as their localization and penetration within the root. Our work paves the way for the rational design of electronic materials that can self-organize in vivo for spatially controlled electronic functionalization of living tissue.Publication Open Access Wireless MRI-powered reversible orientation-locking capsule robot(Wiley, 2021) Erin, Önder; Boyvat, Mustafa; Lazovic, Jelena; Tiryaki, Mehmet Efe; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; College of Engineering; School of Medicine; 297104Magnetic resonance imaging (MRI) scanners do not provide only high-resolution medical imaging but also magnetic robot actuation and tracking. However, the rotational motion capabilities of MRI-powered wireless magnetic capsule-type robots have been limited due to the very high axial magnetic field inside the MRI scanner. Medical functionalities of such robots also remain a challenge due to the miniature robot designs. Therefore, a wireless capsule-type reversible orientation-locking robot (REVOLBOT) is proposed that has decoupled translational motion and planar orientation change capability by locking and unlocking the rotation of a spherical ferrous bead inside the robot on demand. Such an on-demand locking/unlocking mechanism is achieved by a phase-changing wax material in which the ferrous bead is embedded inside. Controlled and on-demand hyperthermia and drug delivery using wireless power transfer-based Joule heating induced by external alternating magnetic fields are the additional features of this robot. The experimental feasibility of the REVOLBOT prototype with steerable navigation, medical function, and MRI tracking capabilities with an 1.33 Hz scan rate is demonstrated inside a preclinical 7T small-animal MRI scanner. The proposed robot has the potential for future clinical use in teleoperated minimally invasive treatment procedures with hyperthermia and drug delivery capabilities while being wirelessly powered and monitored inside MRI scanners.nd. Such an on-demand locking/unlocking mechanism is achieved by a phase-changing wax material in which the ferrous bead is embedded inside. Controlled and on-demand hyperthermia and drug delivery using wireless power transfer-based Joule heating induced by external alternating magnetic fields are the additional features of this robot. The experimental feasibility of the REVOLBOT prototype with steerable navigation, medical function, and MRI tracking capabilities with an 1.33 Hz scan rate is demonstrated inside a preclinical 7T small-animal MRI scanner. The proposed robot has the potential for future clinical use in teleoperated minimally invasive treatment procedures with hyperthermia and drug delivery capabilities while being wirelessly powered and monitored inside MRI scanners.Publication Open Access Finger-actuated microneedle array for sampling body fluids(Multidisciplinary Digital Publishing Institute (MDPI), 2021) Ahmadpour, Abdollah; Yetişen, Ali K.; Department of Mechanical Engineering; Taşoğlu, Savaş; Sarabi, Misagh Rezapour; 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); College of Engineering; Graduate School of Sciences and Engineering; 291971; N/AThe application of microneedles (MNs) for minimally invasive biological fluid sampling is rapidly emerging, offering a user-friendly approach with decreased insertion pain and less harm to the tissues compared to conventional needles. Here, a finger-powered microneedle array (MNA) integrated with a microfluidic chip was conceptualized to extract body fluid samples. Actuated by finger pressure, the microfluidic device enables an efficient approach for the user to collect their own body fluids in a simple and fast manner without the requirement for a healthcare worker. The processes for extracting human blood and interstitial fluid (ISF) from the body and the flow across the device, estimating the amount of the extracted fluid, were simulated. The design in this work can be utilized for the minimally invasive personalized medical equipment offering a simple usage procedure.Publication Open Access 3D microprinting of iron platinum nanoparticle-based magnetic mobile microrobots(Wiley, 2021) Giltinan, Joshua; Sridhar, Varun; Bozüyük, Uğur; Sheehan, Devin; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; School of Medicine; College of Engineering; 297104Wireless magnetic microrobots are envisioned to revolutionize minimally invasive medicine. While many promising medical magnetic microrobots are proposed, the ones using hard magnetic materials are not mostly biocompatible, and the ones using biocompatible soft magnetic nanoparticles are magnetically very weak and, therefore, difficult to actuate. Thus, biocompatible hard magnetic micro/nanomaterials are essential toward easy-to-actuate and clinically viable 3D medical microrobots. To fill such crucial gap, this study proposes ferromagnetic and biocompatible iron platinum (FePt) nanoparticle-based 3D microprinting of microrobots using the two-photon polymerization technique. A modified one-pot synthesis method is presented for producing FePt nanoparticles in large volumes and 3D printing of helical microswimmers made from biocompatible trimethylolpropane ethoxylate triacrylate (PETA) polymer with embedded FePt nanoparticles. The 30 mu m long helical magnetic microswimmers are able to swim at speeds of over five body lengths per second at 200Hz, making them the fastest helical swimmer in the tens of micrometer length scale at the corresponding low-magnitude actuation fields of 5-10mT. It is also experimentally in vitro verified that the synthesized FePt nanoparticles are biocompatible. Thus, such 3D-printed microrobots are biocompatible and easy to actuate toward creating clinically viable future medical microrobots.Publication Open Access Soft-bodied adaptive multimodal locomotion strategies in fluid-filled confined spaces(American Association for the Advancement of Science (AAAS), 2021) Ren, Z.; Zhang, R.; Soon, R. H.; Liu, Z.; Hu, W.; Onck, P. R.; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; School of Medicine; College of Engineering; 297104Soft-bodied locomotion in fluid-filled confined spaces is critical for future wireless medical robots operating inside vessels, tubes, channels, and cavities of the human body, which are filled with stagnant or flowing biological fluids. However, the active soft-bodied locomotion is challenging to achieve when the robot size is comparable with the cross-sectional dimension of these confined spaces. Here, we propose various control and performance enhancement strategies to let the sheet-shaped soft millirobots achieve multimodal locomotion, including rolling, undulatory crawling, undulatory swimming, and helical surface crawling depending on different fluid-filled confined environments. With these locomotion modes, the sheet-shaped soft robot can navigate through straight or bent gaps with varying sizes, tortuous channels, and tubes with a flowing fluid inside. Such soft robot design along with its control and performance enhancement strategies are promising to be applied in future wireless soft medical robots inside various fluid-filled tight regions of the human body.Publication Open Access Top-down technique for scaling to nano in silicon MEMS(American Vacuum Society (AVS), 2017) Wollschlaeger, Nicole; Oesterle, Werner; Leblebici, Yusuf; Department of Mechanical Engineering; Alaca, Burhanettin Erdem; Nadar, Gökhan; Yılmaz, Mustafa Akın; Kılınç, Yasin; Taşdemir, Zuhal; Faculty Member; PhD Student; PhD Student; Department of Mechanical Engineering; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; 115108; N/A; N/A; N/A; N/ANanoscale building blocks impart added functionalities to microelectromechanical systems (MEMS). The integration of silicon nanowires with MEMS-based sensors leading to miniaturization with improved sensitivity and higher noise immunity is one example highlighting the advantages of this multiscale approach. The accelerated pace of research in this area gives rise to an urgent need for batch-compatible solutions for scaling to nano. To address this challenge, a monolithic fabrication approach of silicon nanowires with 10-mu m-thick silicon-on-insulator (SOI) MEMS is developed in this work. A two-step Si etching approach is adopted, where the first step creates a shallow surface protrusion and the second step releases it in the form of a nanowire. It is during this second deep etching step that MEMS-with at least a 2-order-of-magnitude scale difference-is formed as well. The technique provides a pathway for preserving the lithographic resolution and transforming it into a very high mechanical precision in the assembly of micro-and nanoscales with an extreme topography. Validation of the success of integration is carried out via in situ actuation of MEMS inside an electron microscope loading the nanowire up to its fracture. The technique yields nanowires on the top surface of MEMS, thereby providing ease of access for the purposes of carrying out surface processes such as doping and contact formation as well as in situ observation. As the first study demonstrating such monolithic integration in thick SOI, the work presents a pathway for scaling down to nano for future MEMS combining multiple scales.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.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 Bioinspired cilia arrays with programmable nonreciprocal motion and metachronal coordination(American Association for the Advancement of Science (AAAS), 2020) Dong, Xiaoguang; Lum, Guo Zhan; Hu, Wenqi; Zhang, Rongjing; Ren, Ziyu; Onck, Patrick R.; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; School of Medicine; College of Engineering; 297104Coordinated nonreciprocal dynamics in biological cilia is essential to many living systems, where the emergent metachronal waves of cilia have been hypothesized to enhance net fluid flows at low Reynolds numbers (Re). Experimental investigation of this hypothesis is critical but remains challenging. Here, we report soft miniature devices with both ciliary nonreciprocal motion and metachronal coordination and use them to investigate the quantitative relationship between metachronal coordination and the induced fluid flow. We found that only antiplectic metachronal waves with specific wave vectors could enhance fluid flows compared with the synchronized case. These findings further enable various bioinspired cilia arrays with unique functionalities of pumping and mixing viscous synthetic and biological complex fluids at low Re. Our design method and developed soft miniature devices provide unprecedented opportunities for studying ciliary biomechanics and creating cilia-inspired wireless microfluidic pumping, object manipulation and lab- and organ-on-a-chip devices, mobile microrobots, and bioengineering systems.