Materials and methods for modular microfluidic devices

This thesis work concerns the investigation of materials and methods that can be applied to the realization of microfluidic devices (MFDs). In particular, the attention is placed on modular MFDs, as opposed to fully integrated ones. The reasons behind this choice are given in detail in Section 1.2 of this work, but they can be here summarized in the fact that while integrated MFDs offer great advantages in terms of portability, modular devices are more versatile, and so particularly well suited for research applications. The first part of the work here reported describes the microfabrication techniques employed for the realization of single-function microfluidic modules. Devices have been fabricated through PDMS replica molding from SU-8 masters. Masters have been in turn realized through masked UV-lithography or one- or two-photon direct laser writing, depending on the resolution requirements. The replica molding method is a very fast and efficient way to realize MFDs, but suffers from some limitations in the structure shapes that can be successfully replicated. In light of this, a photopolymerizable hybrid organic/inorganic sol-gel blend is proposed and tested as alternative material for MFDs fabrication. The characterization results reveal that this material is biocompatible and features better mechanical properties than PDMS, but structures with more than one dimension exceeding a few micrometers tend to crack during fabrication, making this blend unusable as bulk material. Still, this material could be efficiently employed to fabricate sub-structuration inside PDMS channels. Following this investigation on materials, a microfluidic mixing module is proposed and tested. Since laminar flow conditions dominate inside microchannels, efficient mixing in MFDs require the use of specifically designed mixers. The proposed module makes use of obstructions inside a microchannel to perturb the laminar flow and thus enhance mixing of two species. The most efficient geometries have been selected with the aid of numerical simulations, and two promising layouts have been fabricated and experimentally tested by measuring the dilution of a fluorophore (mixing between a fluorophore solution and pure solvent) through confocal fluorescence microscopy. Thirdly, the fabrication and characterization of an optofluidic light switching module is reported. This device employs a water/air segmented flow generated by a T-junction to alternatively transmit or total-reflect a laser beam. This deflection is proved to be periodical, and its frequency can be varied nonlinearly by adjusting the injection flow rates of air and water. The duty cycle of the module is also characterized, and a method to modulate it by increasing the water temperature is proposed and verified. Finally, a number of attempts to generate a nanoporous, low refractive index PDMS are described. The identification of an efficient procedure to fabricate this kind of material would lead to the possibility of using common microfluidic channels as water-core waveguides. To date, these attempts have not been totally successful, but critical points are identified, and viable strategies for future works on the subject are proposed

Gas Flows in Microsystems

International audienc

Development of Gate-Controlled DC Electrokinetic Micropumps

Lab-on-chip (LOC) devices have received considerable attention in research and development for automated, high-throughput biological and chemical analysis. While much progress has been accomplished; however, fluid flow control still needs improvement and reminds one of the significant challenges for the future practical LOC devices. This thesis explores the application of electroosmosis (EO) technique and field effect flow control (FEFC) technology for micropumps, an important microfluidic component of LOC systems. In this work, electroosmosis method was employed to electro-kinetically move the working fluid under a longitudinal electric field, and the FEFC technique was also utilized to manipulate the Electroosmotic Flow (EOF) through applying a normal electric field to influence the surface charge at the fluid-microchannel wall interface for an independent control over the EOF. Major accomplishments in this thesis are, study on channel geometry effect with no gate control component, and a single microchannel with gate control component. A number of micropumps with different channel geometries were fabricated using soft lithography technique. PDMS prepolymer served as a top wall and both side walls of the microchannel, with a glass slide as the bottom (in the case of gate control, Indium Tin Oxide glass slides were used). On the gate control region, through adjusting the secondary electric field over the gate, FEFC can locally manipulate EOF. It helps produce a range of flow rates, enhance flow rates, and control flow direction. Moreover, micropumps were interfaced with another microchannel section for sample delivery. To improve the microfluidic device, electro-fluid flow models were developed to describe and predict electric field distribution, velocity field distribution, flow direction, and FEFC phenomena using Finite Element Analysis tool (FEMLAB). The simulation results agreed well with experimental results

Magnetic Nanoparticle Enhanced Actuation Strategy for mixing, separation, and detection of biomolecules in a Microfluidic Lab-on-a-Chip System

Magnetic nanoparticle (MNP) combined with biomolecules in a microfluidic system can be efficiently used in various applications such as mixing, pre-concentration, separation and detection. They can be either integrated for point-of care applications or used individually in the area of bio-defense, drug delivery, medical diagnostics, and pharmaceutical development. The interaction of magnetic fields with magnetic nanoparticles in microfluidic flows will allow simplifying the complexity of the present generation separation and detection systems. The ability to understand the dynamics of these interactions is a prerequisite for designing and developing more efficient systems. Therefore, in this work proof-of-concept experiments are combined with advanced numerical simulation to design, develop and optimize the magnetic microfluidic systems for mixing, separation and detection. Different strategies to combine magnetism with microfluidic technology are explored; a time-dependent magnetic actuation is used for efficiently mixing low volume of samples whereas tangential microfluidic channels were fabricated to demonstrate a simple low cost magnetic switching for continuous separation of biomolecules. A simple low cost generic microfluidic platform is developed using assembly of readily available permanent magnets and electromagnets. Microfluidic channels were fabricated at much lower cost and with a faster construction time using our in-house developed micromolding technique that does not require a clean room. Residence-time distribution (RTD) analysis obtained using dynamic light scattering data from samples was successfully used for the first time in microfluidic system to characterize the performance. Both advanced multiphysics finite element models and proof of concept experimentation demonstrates that MNPs when tagged with biomolecules can be easily manipulated within the microchannel. They can be precisely captured, separated or detected with high efficiency and ease of operation. Presence of MNPs together with time-dependent magnetic actuation also helps in mixing as well as tagging biomolecules on chip, which is useful for point-of-care applications. The advanced mathematical model that takes into account mass and momentum transport, convection & diffusion, magnetic body forces acting on magnetic nanoparticles further demonstrates that the performance of microfluidic surface-based bio-assay can be increased by incorporating the idea of magnetic actuation. The numerical simulations were helpful in testing and optimizing key design parameters and demonstrated that fluid flow rate, magnetic field strength, and magnetic nanoparticle size had dramatic impact on the performance of microfluidic systems studied. This work will also emphasize the importance of considering magnetic nanoparticles interactions for a complete design of magnetic nanoparticle-based Lab-on-a-chip system where all the laboratory unit operations can be easily integrated. The strategy demonstrated in this work will not only be easy to implement but also allows for versatile biochip design rules and provides a simple approach to integrate external elements for enhancing mixing, separation and detection of biomolecules. The vast applications of this novel concept studied in this work demonstrate its potential of to be applied to other kinds of on-chip immunoassays in future. We think that the possibility of integrating magnetism with microfluidic-based bioassay on a disposable chip is a very promising and versatile approach for point-of care diagnostics especially in resource-limited settings

Analysis, Design and Fabrication of Micromixers

This book includes an editorial and 12 research papers on micromixers collected from the Special Issue published in Micromachines. The topics of the papers are focused on the design of micromixers, their fabrication, and their analysis. Some of them proposed novel micromixer designs. Most of them deal with passive micromixers, but two papers report studies on electrokinetic micromixers. Fully three-dimensional (3D) micromixers were investigated in some cases. One of the papers applied optimization techniques to the design of a 3D micromixer. A review paper is also included and reports a review of recently developed passive micromixers and a comparative analysis of 10 typical micromixers

Microfluidic device prototyping via laser processing of glass and polymer materials

In this thesis, three different processes for the fabrication of microchannels in three different base materials were experimentally and numerically modelled in detail in order to understand the effects of processing conditions on process fabrication capabilities. CO2 and Nd:YAG laser processing systems as well as a xurography technique were employed in this work for the development of microfluidic channels. The effects of CO2 laser processing on the process of directly writing microchannels on surface of four different types of glass: soda lime, fused silica, borosilicate and quartz were studied. Mathematical models were developed to relate the process input parameters to the dimensions of the microchannels. The effect of laser processing on the optical transmission capabilities of the glass was also assessed. A novel method, using Nd:YAG laser system, was employed for the fabrication of internal microchannels inside polymeric materials. Microchannels up to three millimetres long were successfully created inside a polycarbonate within a single laser processing step. Mathematical models were developed to express the relationship between laser processing input parameters and the width of these internal microchannels. The Nd:YAG processing parameters for laser welding of polycarbonate sheets were also determined. A new rapid low-cost prototyping method for the fabrication of multilayer microfluidic devices from cyclic olefin copolymer (COC) films was developed. CO2 laser cutting and xurography techniques were employed for the fabrication of the microfluidic features, followed by multilayer lamination via cyclohexane vapour exposure. Process parameters were optimised including solvent exposure time. Functional UV-transparent microfluidic mixing devices were demonstrated which included internally bound polymer monolithic columns within the microfluidic channels. There is a growing interest to use technologies which are in this thesis, the three different developed processes for the fabrication of microchannels in three different base materials provides the basis for achieving higher dimensional accuracies and novel designs within lab-on-a-chip microfluidic sensing devices

Investigation of chaotic advection regime and its effect on thermal performance of wavy walled microchannels

Ph.DDOCTOR OF PHILOSOPH

Development of fluorescence lifetime measurement techniques for use in microfluidic channels

Fluorescence lifetime measurements are a powerful tool in biomedical research and advances in detection technology make them ideally suited for the study of biomolecular interactions. Time-resolved techniques, compared to more conventional methods, provide improved precision and contrast in the monitoring of complex biological processes. Fluorescence lifetimes are extracted by using time-correlated single-photon counting, which offers single photon sensitivity, high temporal resolution and excellent signal to noise ratio. Furthermore, combining this technique with microfluidics offers unprecedented advantages. For example, in analytical applications, apart from the high sensitivity required, the study of analytes often demands low sample consumption and short mixing times to allow for the monitoring of quick reactions. These parameters can nicely be achieved with the use of microfluidics. Hydrodynamic focusing within 3-inlet 1-outlet continuous flow microfluidic devices can be used as a molecular confinement mechanism to improve the detection efficiency as well as a means to enhance mixing within microchannels for the study of fast reaction kinetics. In this work, a powerful combination of confocal microscopy and microfluidics was used to perform fluorescence lifetime measurements on freely diffusing and freely flowing molecules. For this purpose, a home-built scanning confocal system was developed to ensure sufficient reduction in background levels, enabling the detection of fluorescence signal that arises from single molecules. Fluorescence lifetime imaging along with a maximum likelihood estimator adapted from single molecule studies was performed to visualise hydrodynamic focusing and characterise mixing within microfluidic devices. Time-resolved methods were also employed to detect single molecules freely flowing within microchannels. A novel fluorescence lifetime approach was developed to perform Förster resonance energy transfer measurements on freely diffusing molecules and subsequently applied for the study of streptavidin-biotin binding and protein conformational changes upon unfolding