AN INTEGRATED MULTI-FUNCTIONAL MICROFLUIDICDEVICE WITH PUMPING, PARTICLE SORTING,AND MIXING FUNCTIONS

Currently, multiple functions are performed in microfluidic devices in a separate manner or in a manner that needs unnecessary transportation from one location, where one function is performed, to another, where another function is performed. There is a need to integrate these functions holistically to eliminate unnecessary steps and improve the performance of microfluidic system. This thesis was devoted to design and fabricate a microfluidic device that allows pumping, mixing, and particle separating functions to be performed simultaneously (or by eliminating any unnecessary transportation). A design concept by introducing membranes into microfluidic devices was proposed based on Axiomatic design theory. Simulation was performed via the multi-physics software COMSOL and was validated with acceptable accuracy by experiments. The UV light lithography and soft lithography were employed to fabricate the device. A microfluidic device consisting of a main channel height of 50 μm, a main channel width of 30 μm, and membranes with a thickness of 10 μm, lengths of 300 μm and 200 μm was fabricated using Polydimethylsiloxane (PDMS). The experiments were conducted to test the feasibility of the expected functions. The microbeads with diameters of 15 μm, 3 μm, and 200 nm were used to mimic the circulating tumor cells (CTC), normal blood cells and anti-cancer drugs, respectively. The experiment demonstrated the device effectiveness in terms of the mixing and particle separating functions. Unfortunately, the pumping function was not measured with the instrument available. There are two main contributions. First, in the field of microfluidics, especially microfluidic device technology, the device is novel to the best of the author’s knowledge. Existing devices perform more than one function but have a distinct time stamp to each of the functions and unnecessary transportations between each function unit. Second, in the field of biomedical engineering, this thesis provides a proof that the size- and deflection-based principle to separate two groups of particles, CTCs from the blood stream in this case, is working. Subsequently, it is promising to further shape it to a practically viable device to separate CTCs from the blood stream

A parallel interaction potential approach coupled with the immersed boundary method for fully resolved simulations of deformable interfaces and membranes

In this paper we show and discuss the use of a versatile interaction potential approach coupled with an immersed boundary method to simulate a variety of flows involving deformable bodies. In particular, we focus on two kinds of problems, namely (i) deformation of liquid-liquid interfaces and (ii) flow in the left ventricle of the heart with either a mechanical or a natural valve. Both examples have in common the two-way interaction of the flow with a deformable interface or a membrane. The interaction potential approach (de Tullio & Pascazio, Jou. Comp. Phys., 2016; Tanaka, Wada and Nakamura, Computational Biomechanics, 2016) with minor modifications can be used to capture the deformation dynamics in both classes of problems. We show that the approach can be used to replicate the deformation dynamics of liquid-liquid interfaces through the use of ad-hoc elastic constants. The results from our simulations agree very well with previous studies on the deformation of drops in standard flow configurations such as deforming drop in a shear flow or a cross flow. We show that the same potential approach can also be used to study the flow in the left ventricle of the heart. The flow imposed into the ventricle interacts dynamically with the mitral valve (mechanical or natural) and the ventricle which are simulated using the same model. Results from these simulations are compared with ad- hoc in-house experimental measurements. Finally, a parallelisation scheme is presented, as parallelisation is unavoidable when studying large scale problems involving several thousands of simultaneously deforming bodies on hundreds of distributed memory computing processors

Functional optimization of the arterial network

We build an evolutionary scenario that explains how some crucial physiological constraints in the arterial network of mammals - i.e. hematocrit, vessels diameters and arterial pressure drops - could have been selected by evolution. We propose that the arterial network evolved while being constrained by its function as an organ. To support this hypothesis, we focus our study on one of the main function of blood network: oxygen supply to the organs. We consider an idealized organ with a given oxygen need and we optimize blood network geometry and hematocrit with the constraint that it must fulfill the organ oxygen need. Our model accounts for the non-Newtonian behavior of blood, its maintenance cost and F\aa hr\ae us effects (decrease in average concentration of red blood cells as the vessel diameters decrease). We show that the mean shear rates (relative velocities of fluid layers) in the tree vessels follow a scaling law related to the multi-scale property of the tree network, and we show that this scaling law drives the behavior of the optimal hematocrit in the tree. We apply our scenario to physiological data and reach results fully compatible with the physiology: we found an optimal hematocrit of 0.43 and an optimal ratio for diameter decrease of about 0.79. Moreover our results show that pressure drops in the arterial network should be regulated in order for oxygen supply to remain optimal, suggesting that the amplitude of the arterial pressure drop may have co-evolved with oxygen needs.Comment: Shorter version, misspelling correctio

Nanogels for pharmaceutical and biomedical applications and their fabrication using 3D printing technologies

Nanogels are hydrogels formed by connecting nanoscopic micelles dispersed in an aqueous medium, which give an opportunity for incorporating hydrophilic payloads to the exterior of the micellar networks and hydrophobic payloads in the core of the micelles. Biomedical and pharmaceutical applications of nanogels have been explored for tissue regeneration, wound healing, surgical device, implantation, and peroral, rectal, vaginal, ocular, and transdermal drug delivery. Although it is still in the early stages of development, due to the increasing demands of precise nanogel production to be utilized for personalized medicine, biomedical applications, and specialized drug delivery, 3D printing has been explored in the past few years and is believed to be one of the most precise, efficient, inexpensive, customizable, and convenient manufacturing techniques for nanogel production

Research on real-time physics-based deformation for haptic-enabled medical simulation

This study developed a multiple effective visuo-haptic surgical engine to handle a variety of surgical manipulations in real-time. Soft tissue models are based on biomechanical experiment and continuum mechanics for greater accuracy. Such models will increase the realism of future training systems and the VR/AR/MR implementations for the operating room