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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 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 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 Metadata only 3D-printed micrometer-scale wireless magnetic cilia with metachronal programmability(Amer Assoc Advancement Science, 2023) Zhang, Shuaizhong; Hu, Xinghao; Li, Meng; Bozuyuk, Ugur; Zhang, Rongjing; Suadiye, Eylul; Han, Jie; Wang, Fan; Onck, Patrick; Department of Mechanical Engineering; Sitti, Metin; Department of Mechanical Engineering; College of Engineering; School of MedicineBiological cilia play essential roles in self-propulsion, food capture, and cell transportation by performing coor-dinated metachronal motions. Experimental studies to emulate the biological cilia metachronal coordination are challenging at the micrometer length scale because of current limitations in fabrication methods and ma-terials. We report on the creation of wirelessly actuated magnetic artificial cilia with biocompatibility and meta-chronal programmability at the micrometer length scale. Each cilium is fabricated by direct laser printing a silk fibroin hydrogel beam affixed to a hard magnetic FePt Janus microparticle. The 3D-printed cilia show stable actuation performance, high temperature resistance, and high mechanical endurance. Programmable meta-chronal coordination can be achieved by programming the orientation of the identically magnetized FePt Janus microparticles, which enables the generation of versatile microfluidic patterns. Our platform offers an unprecedented solution to create bioinspired microcilia for programmable microfluidic systems, biomedical en-gineering, and biocompatible implants.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 Open Access 3D-printed multi-stimuli-responsive mobile micromachines(American Chemical Society (ACS), 2020) Lee, Yun-Woo; Ceylan, Hakan; Yasa, İmmihan Ceren; Department of Mechanical Engineering; Kılıç, Uğur; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; School of Medicine; College of EngineeringMagnetically actuated and controlled mobile micromachines have the potential to be a key enabler for various wireless lab-on-a-chip manipulations and minimally invasive targeted therapies. However, their embodied, or physical, task execution capabilities that rely on magnetic programming and control alone can curtail their projected performance and functional diversity. Integration of stimuli-responsive materials with mobile magnetic micromachines can enhance their design toolbox, enabling independently controlled new functional capabilities to be defined. To this end, here, we show three-dimensional (3D) printed size-controllable hydrogel magnetic microscrews and microrollers that respond to changes in magnetic fields, temperature, pH, and divalent cations. We show two-way size-controllable microscrews that can reversibly swell and shrink with temperature, pH, and divalent cations for multiple cycles. We present the spatial adaptation of these microrollers for penetration through narrow channels and their potential for controlled occlusion of small capillaries (30 μm diameter). We further demonstrate one-way size-controllable microscrews that can swell with temperature up to 65% of their initial length. These hydrogel microscrews, once swollen, however, can only be degraded enzymatically for removal. Our results can inspire future applications of 3D- and 4D-printed multifunctional mobile microrobots for precisely targeted obstructive interventions (e.g., embolization) and lab- and organ-on-a-chip manipulations.Publication Open Access A bacteria-derived tail anchor localizes to peroxisomes in yeast and mammalian cells(Nature Publishing Group (NPG), 2018) Seferoğlu, Ayşe Bengisu; Department of Molecular Biology and Genetics; Dunn, Cory David; Keskin, Abdurrahman; Akdoğan, Emel; Lutfullahoglu-Bal, Guleycan; Department of Molecular Biology and Genetics; College of SciencesProkaryotes can provide new genetic information to eukaryotes by horizontal gene transfer (HGT), and such transfers are likely to have been particularly consequential in the era of eukaryogenesis. Since eukaryotes are highly compartmentalized, it is worthwhile to consider the mechanisms by which newly transferred proteins might reach diverse organellar destinations. Toward this goal, we have focused our attention upon the behavior of bacteria-derived tail anchors (TAs) expressed in the eukaryote Saccharomyces cerevisiae. In this study, we report that a predicted membrane-associated domain of the Escherichia coli YgiM protein is specifically trafficked to peroxisomes in budding yeast, can be found at a pre-peroxisomal compartment (PPC) upon disruption of peroxisomal biogenesis, and can functionally replace an endogenous, peroxisome-directed TA. Furthermore, the YgiM(TA) can localize to peroxisomes in mammalian cells. Since the YgiM(TA) plays no endogenous role in peroxisomal function or assembly, this domain is likely to serve as an excellent tool allowing further illumination of the mechanisms by which TAs can travel to peroxisomes. Moreover, our findings emphasize the ease with which bacteria-derived sequences might target to organelles in eukaryotic cells following HGT, and we discuss the importance of flexible recognition of organelle targeting information during and after eukaryogenesis.Publication Open Access A novel Fontan Y-graft for interrupted inferior vena cava and azygos continuation(Oxford University Press (OUP), 2022) Çicek, Murat; Köse, Banu; Yılmaz, Emine Hekim; Aydemir, Numan Ali; Özkök, Serçin; Yurtseven, Nurgül; Erdem, Hasan; Sasmazel, Ahmet; Department of Mechanical Engineering; Lashkarinia, Seyedeh Samaneh; Pekkan, Kerem; Rezaeimoghaddam, Mohammad; Rasooli, Reza; Faculty Member; Researcher; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 161845; N/A; N/AObjectives: to evaluate the hemodynamicdynamic advantage of a new Fontan surgical template that is intended for complex single-ventricle patients with interrupted inferior vena cava-azygos and hemi-azygos continuation. The new technique has emerged from a comprehensive pre-surgical simulation campaign conducted to facilitate a balanced hepatic flow and somatic Fontan pathway growth after Kawashima procedure. Methods: for 9 patients, aged 2 to 18 years, majority having poor preoperative oxygen saturation, a pre-surgical computational fluid dynamics customization is conducted. Both the traditional Fontan pathways and the proposed novel Y-graft templates are considered. Numerical model was validated against in vivo phase-contrast magnetic resonance imaging data and in vitro experiments. Results: the proposed template is selected and executed for 6 out of the 9 patients based on its predicted superior hemodynamic performance. Pre-surgical simulations performed for this cohort indicated that flow from the hepatic veins (HEP) do not reach to the desired lung. The novel Y-graft template, customized via a right- or left-sided displacement of the total cavopulmonary connection anastomosis location resulted a drastic increase in HEP flow to the desired lung. Orientation of HEP to azygos direct shunt is found to be important as it can alter the flow pattern from 38% in the caudally located direct shunt to 3% in the cranial configuration with significantly reversed flow. The postoperative measurements prove that oxygen saturation increased significantly (P-value = 0.00009) to normal levels in 1 year follow-up. Conclusions: the new Y-graft template, if customized for the individual patient, is a viable alternative to the traditional surgical pathways. This template addresses the competing hemodynamic design factors of low physiological venous pressure, high postoperative oxygen saturation, low energy loss and balanced hepatic growth factor distribution possibly assuring adequate lung development.Publication Open Access A proximity mapping journey into the biology of the mammalian centrosome/cilium complex(Multidisciplinary Digital Publishing Institute (MDPI), 2020) Department of Molecular Biology and Genetics; Arslanhan, Melis Dilara; Gülensoy, Dila; Karalar, Elif Nur Fırat; Faculty Member; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; 206349The mammalian centrosome/cilium complex is composed of the centrosome, the primary cilium and the centriolar satellites, which together regulate cell polarity, signaling, proliferation and motility in cells and thereby development and homeostasis in organisms. Accordingly, deregulation of its structure and functions is implicated in various human diseases including cancer, developmental disorders and neurodegenerative diseases. To better understand these disease connections, the molecular underpinnings of the assembly, maintenance and dynamic adaptations of the centrosome/cilium complex need to be uncovered with exquisite detail. Application of proximity-based labeling methods to the centrosome/cilium complex generated spatial and temporal interaction maps for its components and provided key insights into these questions. In this review, we first describe the structure and cell cycle-linked regulation of the centrosome/cilium complex. Next, we explain the inherent biochemical and temporal limitations in probing the structure and function of the centrosome/cilium complex and describe how proximity-based labeling approaches have addressed them. Finally, we explore current insights into the knowledge we gained from the proximity mapping studies as it pertains to centrosome and cilium biogenesis and systematic characterization of the centrosome, cilium and centriolar satellite interactomes.