In this thesis, a new microfluidic device is presented for sorting of deformable particles based on the hydrodynamic resistance induced in a microchannel. Hydrodynamic resistance can be related to physical properties, including size and deformability of the particle, and can also be influenced by particle-wall interactions, hence allowing sorting based on any of these characteristics. This device could find application in cell sorting and bioseparation for therapeutics, research, and point-of-care diagnostics, as well as in sorting of droplets and emulsions for research and industrial applications (e.g., pharmaceutics, food industry, etc.). The device design is carried out using an equivalent resistance model, and numerical simulations are used to validate the design. The device is fabricated in PDMS, flow velocities are characterized using particle streak velocimetry, and sorting experiments are conducted to sort deformable gelatin particles according to size, and droplets of water and glycerol according to deformability. A sorting resolution of approximately 1 pm was obtained when sorting based on size, and droplets of water and glycerol were sorted into separate streams when sorting based on deformability. The main strength of the device over existing technology lies in its simplicity: sorting is carried out passively in the microfluidic circuit, eliminating the need for additional detection or sorting modules. Moreover, the device could be easily customized to change the sorting parameter or the sorting threshold, and multiple devices can be combined in parallel (to increase throughput) or in series (to increase resolution).

Sorting of microparticles has numerous applications in science and technology, from cell analysis to sample purification for biomaterials, photonics, and drug delivery. Methods used for particle separation relied only on procedures that involved sedimentation, filtration through porous material or other physical procedures that could be performed macroscopically and in bulk; only recently has miniaturization of fluid systems enabled individual particle separation at the macroscopic level. In the 1980's, as new fabrication techniques originally used to miniaturize circuits became available, they were used to miniaturize structures used for filtration, creating new membranes for filtration with sub millimeter thickness and new fluidic devices that enabled completely new functionalities. Hydrodynamic resistance, the extra resistance induced by a particle as it flows through a microfluidic channel, has been recently proposed as a viable property for particle characterization. Particle-induced hydrodynamic resistance can be linked to relevant biological properties, e.g. deformability, which is an important parameter in diseases like sickle cell anemia, malaria, sepsis and some kinds of cancers. In this work we propose the concept of 'hydrodynamic resistance sorting', which adds to the repertoire of current sorting technologies. We propose a microfluidic circuit capable of sorting particles according to the hydrodynamic resistance they induce in micro channel as they flow through. The circuit has two flow modes: rejection and sorting modes. The microfluidic circuit switches from rejection to sorting mode automatically when a particle induces an increment in hydrodynamic resistance larger than a designed threshold value. The circuit uses the concept of microfluidic logic, in which a microfluidic system has multiple discrete output modes, (sorting and rejecting particle modes), which are activated by an input variable, in this case the hydrodynamic resistance. As opposed to previous logic microfluidic circuits based on droplets, the sorting circuit uses particle self-interactions and does not require particle synchronization to enable microfluidic logic; hence the circuit is asynchronous. Further, we showed the circuit's ability to work with cells by sorting red blood cells and tested the circuit's capacity to sort particles based on mechanical properties by sorting cured and uncured droplets made of a UV-curable solution. Finally, in addition to development of circuits to sort particles based on hydrodynamic resistance, we investigated the link between hydrodynamic resistance and the change in mechanical properties experienced by cells. From first principles it is unclear exactly how and to what extent cell mechanical properties affect cell passage through constrained channels. The force opposing cell passage could be proportional to the cell velocity, as it occurs during lubrication of rigid objects, or proportional to normal forces, as it occurs in the case of many macroscopic objects sliding on surfaces. We used a microfluidic differential manometer, particle image velocimetry, high-speed imaging, confocal microscopy and non-dimensional analysis to investigate the relationship between cell mechanical properties, friction forces and hydrodynamic resistance. The results revealed that the transport of cells through constrained channels is a soft lubrication flow, where the driving force depends primarily on viscous dissipation and secondarily on the compressive forces acting on the cell. This work advances our understanding of the flow of deformable particles through constrained channels and provides a method to sort single particles based on their hydrodynamic resistance. The devices developed here have potential applications in biomechanical analysis of cells, bioseparation, point-of-care diagnostics, as well as in two-phase microfluidics.

Microfluidic platforms are increasingly being used for separating a wide variety of particles based on their physical and chemical properties. In the past two decades, many practical applications have been found in chemical and biological sciences, including single cell analysis, clinical diagnostics, regenerative medicine, nanomaterials synthesis, environmental monitoring, etc. In this Special Issue, we invited contributions to report state-of-the art developments in the fields of micro- and nanofluidic separation, fractionation, sorting, and purification of all classes of particles, including, but not limited to, active devices using electric, magnetic, optical, and acoustic forces; passive devices using geometries and hydrodynamic effects at the micro/nanoscale; confined and open platforms; label-based and label-free technology; and separation of bioparticles (including blood cells), circulating tumor cells, live/dead cells, exosomes, DNA, and non-bioparticles, including polymeric or inorganic micro- and nanoparticles, droplets, bubbles, etc. Practical devices that demonstrate capabilities to solve real-world problems were of particular interest.

Particle sorting, counting, and separation are crucial precursor steps to a host of biomedical assays, and various macroscale tools have been developed over the past several decades in response. In more recent years, microfluidic technologies have gained significant popularity as a means of performing these same tasks and more, all at reduced power, reagent volume, time, and user difficulty. This raises the possibility that every fluidic, optical, and electronic system in a biomedical laboratory could soon be reduced to a microscale equivalent, and incorporated onto a single handheld device, a hypothetical lab-on-a-chip. However, while the sorting technologies at the heart of this new class of device have developed at a dramatic pace, the devices themselves remain costly to fabricate, difficult to manufacture at large scales, and poorly integrated with auxiliary systems such as power supplies and peristaltic pumps. As such, they rarely develop beyond the proof-of-concept stage and have yet to achieve any significant acceptance in the biomedical community. This work seeks to move microfluidic sorters beyond this obstacle. First, it was demonstrated that multiple components could be implemented onto a single platform, eliminating cumbersome external fluidics in the process. Next, methods from the mature microelectronics industry were used to build an electronic microfluidic cell sorter on a printed circuit board platform, yielding a dramatic improvement in device manufacturability and user friendliness, as well as ease of integration with other electronics, micro or otherwise. Finally, building on this, a method was developed to manufacture large numbers of three-dimensional microelectrodes and then incorporate them into a microfluidic device using pick-and-place methods, again a technique adapted from the microelectronics industry. Together, this shifts microfluidics away from the established standard of cumbersome devices monolithically constructed using costly materials and methods and towards a novel standard of more manufacturable and user-friendly devices, and represents a step towards this class of device gaining mainstream acceptance in the biomedical community.

Biological fluids, composed of polymeric solutions or suspensions of deformable particles, commonly present complex rheological behaviour. It is well known that particle-fluid interactions at the microscale dictate the macroscopic flow behaviour of these fluids, however the exact link in numerous situations is still missing. Recently, microfluidic techniques have been widely employed to study the dynamics of microscopic particles under flow.

The first book offering a global overview of fundamental microfluidics and the wide range of possible applications, for example, in chemistry, biology, and biomedical science. As such, it summarizes recent progress in microfluidics, including its origin and development, the theoretical fundamentals, and fabrication techniques for microfluidic devices. The book also comprehensively covers the fluid mechanics, physics and chemistry as well as applications in such different fields as detection and synthesis of inorganic and organic materials. A useful reference for non-specialists and a basic guideline for research scientists and technicians already active in this field or intending to work in microfluidics.

The ability to mix minute quantities of fluids is critical in a range of recent and emerging techniques in engineering, chemistry and life sciences, with applications as diverse as inkjet printing, pharmaceutical manufacturing, specialty and hazardous chemical manufacturing, DNA analysis and disease diagnosis.The multidisciplinary nature of this field – intersecting engineering, physics, chemistry, biology, microtechnology and biotechnology – means that the community of engineers and scientists now engaged in developing microfluidic devices has entered the field from a variety of different backgrounds.Micromixers is uniquely comprehensive, in that it deals not only with the problems that are directly related to fluidics as a discipline (aspects such as mass transport, molecular diffusion, electrokinetic phenomena, flow instabilities, etc.) but also with the practical issues of fabricating micomixers and building them into microsystems and lab-on-chip assemblies.With practical applications to the design of systems vital in modern communications, medicine and industry this book has already established itself as a key reference in an emerging and important field.The 2e includes coverage of a broader range of fabrication techniques, additional examples of fully realized devices for each type of micromixer and a substantially extended section on industrial applications, including recent and emerging applications. - Introduces the design and applications of micromixers for a broad audience across chemical engineering, electronics and the life sciences, and applications as diverse as lab-on-a-chip, ink jet printing, pharmaceutical manufacturing and DNA analysis - Helps engineers and scientists to unlock the potential of micromixers by explaining both the scientific (microfluidics) aspects and the engineering involved in building and using successful microscale systems and devices with micromixers - The author's applied approach combines experience-based discussion of the challenges and pitfalls of using micromixers, with proposals for how to overcome them