On-chip Temperature Sensing and Control for Cell Immobilization

Proceedings of the 2nd IEEE International Conference on Nano/Micro Engineered and Molecular Systems, January 16 - 19, 2007, Bangkok, Thailan

Magnetically Modified Polymeric Microsorter for On-chip Particle Manipulations

2008 IEEE/RSJ International Conference on Intelligent Robots and Systems, Acropolis Convention Center, Nice, France, Sept, 22-26, 200

On-chip Cell Manipulation by Magnetically Modified Soft Microactuators

Proceedings of the 2008 IEEE International Conference on Robotics and Automation / 2008 IEEE International Conference on Robotics and Automation, Pasadena, CA, USA, May 19-23, 200

Magnetically modified PDMS microtools for micro particle manipulation

Proceedings of the 2007 IEEE/RSJ International Conference on Intelligent Robots and Systems, San Diego, CA, USA, Oct 29 - Nov 2, 200

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

Investigation of microparticle behavior in Newtonian, viscoelastic, and shear-thickening flows in straight microchannels

Sorting and separation of small substances such as cells, microorganisms, and micro- and nano-particles from a heterogeneous mixture is a common sample preparation step in many areas of biology, biotechnology, and medicine. Portability and inexpensive design of microfluidic-based sorting systems have benefited many of these biomedical applications. Accordingly, we have investigated microparticle hydrodynamics in fluids with various rheological behaviors (i.e., Newtonian, shear-thinning viscoelastic and shear-thickening non-Newtonian) flowing in straight microchannels. Numerical models were developed to simulate particles trajectories in Newtonian water and shear-thinning polyethylene oxide (PEO) solutions. The validated models were then used to perform numerical parametric studies and non-dimensional analysis on the Newtonian inertia-magnetic and shear-thinning elasto-inertal focusing regimes. Finally, the straight microfluidic device that was tested for Newtonian water and shear-thinning viscoelastic PEO solution, were adopted to experimentally study microparticle behavior in SiO2/Water shear-thickening nanofluid

A centrifugal microfluidic platform for capturing, assaying and manipulation of beads and biological cells

Microfluidics is deemed a field with great opportunities, especially for applications in medical diagnostics. The vision is to miniaturize processes typically performed in a central clinical lab into small, simple to use devices - so called lab-on-a-chip (LOC) systems. A wide variety of concepts for liquid actuation have been developed, including pressure driven flow, electro-osmotic actuation or capillary driven methods. This work is based on the centrifugal platform (lab-on-a-disc). Fluid actuation is performed by the forces induced due to the rotation of the disc, thus eliminating the need for external pumps since only a spindle motor is necessary to rotate the disc and propel the liquids inside of the micro structures. Lab-on-a-disc systems are especially promising for point-of-care applications involving particles or cells due to the centrifugal force present in a rotating system. Capturing, assaying and identification of biological cells and microparticles are important operations for lab-on-a-disc platforms, and the focus of this work is to provide novel building blocks towards an integrated system for cell and particle based assays. As a main outcome of my work, a novel particle capturing and manipulation scheme on a centrifugal microfluidic platform has been developed. To capture particles (biological cells or micro-beads) I designed an array of V-shaped micro cups and characterized it. Particles sediment under stagnant flow conditions into the array where they are then mechanically trapped in spatially well-defined locations. Due to the absence of flow during the capturing process, i.e. particle sedimentation is driven by the artificial gravity field on the centrifugal platform, the capture efficiency of this approach is close to 100% which is notably higher than values reported for typical pressure driven systems. After capturing the particles, the surrounding medium can easily be exchanged to expose them to various conditions such as staining solutions or washing buffers, and thus perform assays on the captured particles. By scale matching the size of the capturing elements to the size of the particles, sharply peaked single occupancy can be achieved. Since all particles are arrayed in the same focal plane in spatially well defined locations, operations such as counting or fluorescent detection can be performed easily. The application of this platform to perform multiplexed bead-based immunoassays as well as the discrimination of various cell types based on intra cellular and membrane based markers using fluorescently tagged antibodies is demonstrated. Additionally, methods to manipulate captured particles either in batch mode or on an individual particle level have been developed and characterized. Batch release of captured particles is performed by a novel magnetic actuator which is solely controlled by the rotation frequency of the disc. Furthermore, the application of this actuator to rapidly mix liquids is shown. Manipulation of individual particles is performed using an optical tweezers setup which has been developed as part of this work. Additionally, this optical module also provides fluorescence detection capabilities. This is the first time that optical tweezers have been combined with a centrifugal microfluidic system. This work presents the core technology for an integrated centrifugal platform to perform cell and particle based assays for fundamental research as well as for point-of- care applications. The key outputs of my specific work are: 1. Design, fabrication and characterization of a novel particle capturing scheme on a centrifugal microfluidic platform (V-cups) with very high capture efficiency (close to 100%) and sharply peaked single occupancy (up to 99.7% single occupancy). 2. A novel rotation frequency controlled magnetic actuator for releasing captured particles as well as for rapidly mixing liquids has been developed, manufactured and characterized. 3. The V-cup platform has successfully been employed to capture cells and perform multi-step antibody staining assays for cell discrimination. 4. An optical tweezers setup has been built and integrated into a centrifugal teststand, and successful manipulation of individual particles trapped in the V-cup array is demonstrated

Design, test and biological validation of microfluidic systems for blood plasma separation

Sample preparation has been described as the weak link in microfluidics. In particular, plasma has to be extracted from whole blood for many analysis including protein analysis, cell-free DNA detection for prenatal diagnosis and transplant monitoring. The lack of suitable devices to perform the separation at the microscale means that Lab On Chip (LOC) modules cannot be fully operated without sample preparation in a full-scale laboratory. In order to address this issue, blood flow in microchannels has been studied, and red blood cells behaviours in different geometrical environments have been classified. Several designs have been subsequently proposed to exploit some natural properties of blood flow and extract pure plasma without disturbing the cells. Furthermore, a high-level modelling method was developed to predict the behaviour of passive microfluidic networks. Additionally, the technique proposed provides useful guidance over the use of systems in more complex external environments. Experimental results have shown that plasma could be separated from undiluted whole blood in 10μm width microchannels at a flow rate of 2mL/hr. Using slightly larger structures (20μm) suitable for mass-manufacturing, diluted blood can be separated with 100% purity efficiency at high flow rate. An extensive biological validation of the extracted plasma was carried out to demonstrate its quality. To this effect Polymerase Chain Reaction (PCR) was performed to amplify targeted human genomic sequence from cell-free DNA present in the plasma. Furthermore, the influence of the sample dilution and separation efficiency on the amplification was characterised. It was shown that the sample dilution does have an influence on the amplification of house-keeping gene, but that amplification can be achieved even on high diluted samples. Additionally amplification can also be obtained on plasma samples with a range of separation efficiencies from 100% to 84%. In particular, two main points have been demonstrated (i) the extraction of plasma using combination of constrictions and bifurcations, (ii) the biological validation of the extracted plasma

Integrated manipulation, detection and counting of cells in biofluids

The manipulation, trapping, detection and counting of cells in biological fluids is of critical importance to the areas of disease diagnosis, drug delivery and genomic applications in biomedical research. In recent times, this research has focussed on utilising the superior metering, separation, routing, mixing and incubation capabilities of centrifugal microfluidic “Lab on a Disk” (LOAD) technologies to tackle the challenge of handling numerous types of cells, proteins, genes and their reagents simultaneously. Furthermore, integrated optical detection systems are being developed in parallel to the aforementioned microfluidic technologies, to facilitate the accurate and inexpensive detection, imaging and counting of cells. This thesis describes a number of novel centrifugal microfluidic approaches towards the separation, capture and detection of white blood cells from whole blood. Firstly, a thorough review of the state-of-the art research in the areas of centrifugo-microfluidic cell handling and detection is outlined. Secondly, a series of physical size filtration and microcontact printing approaches for the capture and detection of biomimetic particles are described. Finally, the author assesses the suitability of sol-gel materials for waveguiding applications on disposable LOAD platforms and outlines areas of future work that would build upon the research undertaken in this thesis

Microdevices and Microsystems for Cell Manipulation

Microfabricated devices and systems capable of micromanipulation are well-suited for the manipulation of cells. These technologies are capable of a variety of functions, including cell trapping, cell sorting, cell culturing, and cell surgery, often at single-cell or sub-cellular resolution. These functionalities are achieved through a variety of mechanisms, including mechanical, electrical, magnetic, optical, and thermal forces. The operations that these microdevices and microsystems enable are relevant to many areas of biomedical research, including tissue engineering, cellular therapeutics, drug discovery, and diagnostics. This Special Issue will highlight recent advances in the field of cellular manipulation. Technologies capable of parallel single-cell manipulation are of special interest