Design and Fabrication of Active Bio-hybrid Microsystems for Applications in Biology and Medicine.
My primary research focus is to develop functional micro/nanofabricated systems for fundamental biology and translational medicine applications. My previous research at CWRU included engineering blood vessel mimicking microchannels to investigate blood cell and endothelial wall interactions and developing point-of-care platforms for diagnosis and monitoring of blood disorders. In MPI-IS, I am interested in bio-hybrid mobile microrobotic systems with intelligent control schemes for in-vitro and in-vivo micro-manipulation, biosensing, and drug delivery applications.
PhD: Mechanical and Aerospace Engineering, Case Western Reserve University, OH, USA, 2016
RBCs constitute more than 90% of cells in the blood stream and uniquely specialized to carry maximum loads by losing their nuclei through maturation, which also allows them to deform and squeeze repeatedly without blocking any capillaries that can be as small as half of their diameter. Due to their abundancy and affordability, RBCs ...
Active microswimmers have attracted considerable attention because of their potential applications, especially for biomedical applications such as cargo transport, targeted drug delivery, biosensors, and environment remediation. The main objective of our team is to develop new material platforms and system...
Surface tension gradients induce Marangoni ﬂow, which can be exploited for ﬂuid transport. At the micron scale, these surface-driven ﬂows can be quite signiﬁcant. In this project, we use surface tension gradients to drive bulk ﬂuid ﬂows by introducing ﬂuid-ﬂuid interfaces along the walls of microﬂuidic cha...
Collective control of mobile microrobotic swarms is indispensable for their potential high-impact applications in targeted drug delivery, medical diagnostics, parallel micromanipulation, and environmental sensing and remediation. Lack of on-board computational and sensing capabilities in current microrobotic systems necessitates use of physical interactions among individual microrobots for local physical communication and cooperation. Here, we show that mobile microrobotic swarms with well-defined collective behavior can be designed by engineering magnetic interactions among individual units. Microrobots, consisting of a linear chain of self-assembled magnetic microparticles, locomote on surfaces in response to a precessing magnetic field. Control over the direction of precessing magnetic field allows engineering attractive and repulsive interactions among microrobots and, thus, collective order with well-defined spatial organization and parallel operation over macroscale distances (~ 1 cm). These microrobotic swarms can be guided through confined spaces, while preserving microrobot morphology and function. These swarms can further achieve directional transport of large cargoes on surfaces and small cargoes in bulk fluids. Described design approach, exploiting physical interactions among individual robots, enables facile and rapid formation of self-organized and reconfigurable microrobotic swarms with programmable collective order.
Science Robotics, 3(17):eaar4423, Science Robotics, April 2018 (article)
Bacteria-propelled biohybrid microswimmers have recently shown to be able to actively transport and deliver cargos encapsulated into their synthetic constructs to specific regions locally. However, usage of synthetic materials as cargo carriers can result in inferior performance in load-carrying efficiency, biocompatibility, and biodegradability, impeding clinical translation of biohybrid microswimmers. Here, we report construction and external guidance of bacteria-driven microswimmers using red blood cells (RBCs; erythrocytes) as autologous cargo carriers for active and guided drug delivery. Multifunctional biohybrid microswimmers were fabricated by attachment of RBCs [loaded with anticancer doxorubicin drug molecules and superparamagnetic iron oxide nanoparticles (SPIONs)] to bioengineered motile bacteria, Escherichia coli MG1655, via biotin-avidin-biotin binding complex. Autonomous and on-board propulsion of biohybrid microswimmers was provided by bacteria, and their external magnetic guidance was enabled by SPIONs loaded into the RBCs. Furthermore, bacteria-driven RBC microswimmers displayed preserved deformability and attachment stability even after squeezing in microchannels smaller than their sizes, as in the case of bare RBCs. In addition, an on-demand light-activated hyperthermia termination switch was engineered for RBC microswimmers to control bacteria population after operations. RBCs, as biological and autologous cargo carriers in the biohybrid microswimmers, offer notable advantages in stability, deformability, biocompatibility, and biodegradability over synthetic cargo-carrier materials. The biohybrid microswimmer design presented here transforms RBCs from passive cargo carriers into active and guidable cargo carriers toward targeted drug and other cargo delivery applications in medicine.
Surface tension gradients induce Marangoni flow, which may be exploited for fluid transport. At the micrometer scale, these surface-driven flows can be more significant than those driven by pressure. By introducing fluid-fluid interfaces on the walls of microfluidic channels, we use surface tension gradients to drive bulk fluid flows. The gradients are specifically induced through thermal energy, exploiting the temperature dependence of a fluid-fluid interface to generate thermocapillary flow. In this report, we provide the design concept for a biocompatible, thermocapillary microchannel capable of being powered by solar irradiation. Using temperature gradients on the order of degrees Celsius per centimeter, we achieve fluid velocities on the order of millimeters per second. Following experimental observations, fluid dynamic models, and numerical simulation, we find that the fluid velocity is linearly proportional to the provided temperature gradient, enabling full control of the fluid flow within the microchannels.
Kim, M., Alapan, Y., Adhikari, A., Little, J. A., Gurkan, U. A.
Microcirculation, 24(5):e12374, July 2017 (article)
Abstract Objectives The advancement of microfluidic technology has facilitated the simulation of physiological conditions of the microcirculation, such as oxygen tension, fluid flow, and shear stress in these devices. Here, we present a micro‐gas exchanger integrated with microfluidics to study RBC adhesion under hypoxic flow conditions mimicking postcapillary venules. Methods We simulated a range of physiological conditions and explored RBC adhesion to endothelial or subendothelial components (FN or LN). Blood samples were injected into microchannels at normoxic or hypoxic physiological flow conditions. Quantitative evaluation of RBC adhesion was performed on 35 subjects with homozygous SCD. Results Significant heterogeneity in RBC adherence response to hypoxia was seen among SCD patients. RBCs from a HEA population showed a significantly greater increase in adhesion compared to RBCs from a HNA population, for both FN and LN. Conclusions The approach presented here enabled the control of oxygen tension in blood during microscale flow and the quantification of RBC adhesion in a cost‐efficient and patient‐specific manner. We identified a unique patient population in which RBCs showed enhanced adhesion in hypoxia in vitro. Clinical correlates suggest a more severe clinical phenotype in this subgroup.
Our goal is to understand the principles of Perception, Action and Learning in autonomous systems that successfully interact with complex environments and to use this understanding to design future systems