Towards a Theory of Droplet-Mixing Graphs in Microfluidics

In this work, we study the problem of fluid mixing in microfluidic chips. The motivation for studying this problem comes from the process of sample preparation for chemical, biological, medical and environmental experiments, which often require preparation of fluid mixtures with desired concentrations. We assume that fluids are manipulated in discrete units called droplets. The input set of droplets consist of two distinct fluids: the reactant, which is the fluid of interest, and the buffer fluid that is used to dilute it. The goal is to produce a target set of droplets with prespecified reactant concentrations. In the model we study, the mixing process in a microfluidic chip can be abstractly represented as a mixing graph. A mixing graph is a collection of micro-mixers (nodes) connected by micro-channels (edges) that converts an input set of droplets I into a set of output droplets T, by applying a sequence of 1:1 mixing operations. This graph may also produce some waste, which are superfluous droplets of fluid not used in the target set. Computational complexity of most natural questions regarding such mixing graphs remain open. For example, it is not even known whether it is decidable for a given target set to be produced without waste. Current work in the literature contains only heuristic approaches that compute mixing graphs while attempting to optimize certain objectives, including minimizing waste, reactant usage, the depth of the graphs, and more.Our first contribution is an efficient algorithm for computing mixing graphs for single-droplet targets. Our algorithm produces significantly less waste than state-of-the-art algorithms in an experimental comparison. We also provide a bound on its worst-case performance that is significantly better than those for earlier algorithms. Our second result concerns the variant of the problem where the objective is to design a mixing graph that perfectly mixes a collection of input droplets with arbitrary concentrations. We provide a complete characterization of input sets for which such graphs exist, and an efficient algorithm to construct these graphs. In addition, we provide several other results about properties of mixing graphs and the computational complexity of computing mixing graphs of fixed depth

Micro-Channel Arrays by Two Photon Lithography for Cell Migration Studies

Metastasis is a dynamic process in which cancer cells begin to move. Understanding how these cells acquire increased motility is a stimulating and necessary goal. The goal of this thesis is to produce a microfluidic device that allows the study of chemotaxis of Neuroblastoma cells and the device was fabricated using an innovative two-photon polymerization (2PP) technology.openEmbargo temporaneo per motivi di segretezza e/o di proprietà dei risultati e/o informazioni sensibil

Developing a microfluidic blood preparation device for ATR-FTIR spectroscopy

There are limited healthcare resources in remote parts of the world and ATRFTIR spectroscopy has the potential to be used for point-of-care (POC) diagnostics in these locations, but lacks of a portable blood sample preparation method. This thesis looks at development of a micro fluidic device that would process a single blood sample in order to prepare serum, infected/damaged red blood cells (RBCs), white blood cells (WBCs) and circulating tumour cells (CTCs) for analysis using ATR-FTIR spectroscopy. After exploring a range of micro fluidic blood separation methods and manufacturing techniques, a 4-stage design concept is presented in Chapter 2. ATR-FTIR spectroscopy and bespoke Matlab codes are used, in Chapter 3, to evaluate the serum output quality requirement. A series of experiments to determine how to produce serum was carried out, using horse blood. After which, the difference between the spectra from human plasma and serum was investigated, and concluded that plasma was a better output for a POC application. In Chapter 4, a design tool for creating a micro fluidic module that separates the diagnostic outputs from healthy RBCs was being developed. COMSOL Multiphysics and Matlab was used to develop a continuum effective medium (CEM) model that simulated the creation of a cell-free layer (CFL), from which the diagnostic outputs could be collected. The CEM model was compared with experiments, which used expansion-contraction geometries manufactured using soft lithography, and it has been shown that this CEM model can simulate the CFL, although more work is needed to fully validate the model. The research carried out in this project has shown that further work is needed in the ATRFTIR spectroscopy field in order to ascertain appropriate design requirements to be able to design and develop an efficient device.There are limited healthcare resources in remote parts of the world and ATRFTIR spectroscopy has the potential to be used for point-of-care (POC) diagnostics in these locations, but lacks of a portable blood sample preparation method. This thesis looks at development of a micro fluidic device that would process a single blood sample in order to prepare serum, infected/damaged red blood cells (RBCs), white blood cells (WBCs) and circulating tumour cells (CTCs) for analysis using ATR-FTIR spectroscopy. After exploring a range of micro fluidic blood separation methods and manufacturing techniques, a 4-stage design concept is presented in Chapter 2. ATR-FTIR spectroscopy and bespoke Matlab codes are used, in Chapter 3, to evaluate the serum output quality requirement. A series of experiments to determine how to produce serum was carried out, using horse blood. After which, the difference between the spectra from human plasma and serum was investigated, and concluded that plasma was a better output for a POC application. In Chapter 4, a design tool for creating a micro fluidic module that separates the diagnostic outputs from healthy RBCs was being developed. COMSOL Multiphysics and Matlab was used to develop a continuum effective medium (CEM) model that simulated the creation of a cell-free layer (CFL), from which the diagnostic outputs could be collected. The CEM model was compared with experiments, which used expansion-contraction geometries manufactured using soft lithography, and it has been shown that this CEM model can simulate the CFL, although more work is needed to fully validate the model. The research carried out in this project has shown that further work is needed in the ATRFTIR spectroscopy field in order to ascertain appropriate design requirements to be able to design and develop an efficient device

Droplet Microfluidics

Droplet microfluidics has dramatically developed in the past decade and has been established as a microfluidic technology that can translate into commercial products. Its rapid development and adoption have relied not only on an efficient stabilizing system (oil and surfactant), but also on a library of modules that can manipulate droplets at a high-throughput. Droplet microfluidics is a vibrant field that keeps evolving, with advances that span technology development and applications. Recent examples include innovative methods to generate droplets, to perform single-cell encapsulation, magnetic extraction, or sorting at an even higher throughput. The trend consists of improving parameters such as robustness, throughput, or ease of use. These developments rely on a firm understanding of the physics and chemistry involved in hydrodynamic flow at a small scale. Finally, droplet microfluidics has played a pivotal role in biological applications, such as single-cell genomics or high-throughput microbial screening, and chemical applications. This Special Issue will showcase all aspects of the exciting field of droplet microfluidics, including, but not limited to, technology development, applications, and open-source systems

Formation of Clot Analogs Between Co-Flow Fluid Streams in a Microchannel Device

Hemodynamics plays an important role in the formation of blood clots, for which changes in hydrodynamic stresses and transport phenomena can initiate or inhibit the clotting process. The fibrin network is highly influential in the structural mechanics of a clot. This work demonstrated an ability to produce clot analogs at the boundary between co-flow fluid streams, and investigated the dependence of clot shape and density distribution on flow conditions. The time evolution of fibrin clots formed in microchannel flow was investigated using fluorescence imaging. Clots were formed in a polydimethylsiloxane (PDMS) microfluidic device which consisted of a Y-shaped microchannel with two inlets and a single outlet. The clotting region had a cross-section that was 300 µm wide and 12 µm deep. The first inlet introduced fresh frozen plasma (FFP), while the second inlet introduced thrombin. Clot analogs were formed at the interface of these two parallel streams at withdrawal flow rates of 100 nL/min, 200 nL/min, and 400 nL/min. These clots were shown to be insensitive to initial co-flow shear rates, exhibiting similar clot shape and density distribution across the different flow rates. Clots that are formed in such an engineered device provide opportunities to mimic in vivo scenarios in which clot density and composition gradients depend on flow conditions

Microfluidics and Nanofluidics Handbook

The Microfluidics and Nanofluidics Handbook: Two-Volume Set comprehensively captures the cross-disciplinary breadth of the fields of micro- and nanofluidics, which encompass the biological sciences, chemistry, physics and engineering applications. To fill the knowledge gap between engineering and the basic sciences, the editors pulled together key individuals, well known in their respective areas, to author chapters that help graduate students, scientists, and practicing engineers understand the overall area of microfluidics and nanofluidics. Topics covered include Finite Volume Method for Numerical Simulation Lattice Boltzmann Method and Its Applications in Microfluidics Microparticle and Nanoparticle Manipulation Methane Solubility Enhancement in Water Confined to Nanoscale Pores Volume Two: Fabrication, Implementation, and Applications focuses on topics related to experimental and numerical methods. It also covers fabrication and applications in a variety of areas, from aerospace to biological systems. Reflecting the inherent nature of microfluidics and nanofluidics, the book includes as much interdisciplinary knowledge as possible. It provides the fundamental science background for newcomers and advanced techniques and concepts for experienced researchers and professionals