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Optimization of particle separation methods in Lab-on-a-Chip systems with the help of CFD and DEM coupling
Alexander Göhring, , EAH Jena
Particle separation takes a central role in a lot of clinical examinations and analytical processes: such as isolating microorganism from urine or other body fluids, separating blood components from one another or extracting tumor cells out of blood. With the help of a microfluidic separation device it is possible to reach response level of pathogens by accumulation, before they are analyzed. Therefore, separation is the basis for many significant applications in diagnosis, analysis or sample preparation. Simulation models have been created to examine and improve different passive separation methods by coupling the finite volume method and the discrete element method. The research is specialized on passive solutions. Thus only forces resulting from the channel geometry, the flow and the characteristics of the particles are used. With the help of forces affecting against each other, depending on the particle properties (size, density etc.) the particle can be moved within the channel cross-section and separated.
One further advantage is that such miniaturized separation chip systems are easily capable of being integrated into the flow chain of any sample preparation and analytical procedure which opens a broad variety of applications in health care, pharmaceutical research and development and related branches.
Magnetophoretic water-in-water droplet microfluidics
Maryam Navi, First Author ; Graduate Student, Ryerson University
Droplet microfluidics using water-oil systems has been used for single-cell encapsulation purposes. Post-sorting of cell-containing droplets from empty droplets is a required step in this method of cell-encapsulation. Aqueous two-phase systems (ATPS) has been recently proposed as an all-aqueous biocompatible alternative for replacing water-in-oil with water-in-water droplet microfluidics. We present a lab-on-a-chip platform for magnetophoretic manipulation and separation of particle/cell containing water-in-water droplets. We use a polymeric aqueous two-phase system (ATPS) to generate the droplets. By adding ferrofluid to the ATPS, we can manipulate the droplets using magnetophoretic forces. By controlling the partitioning of ferrofluid in ATPS, we show both magnetic and diamagnetic manipulation of particle/cell-containing droplets. When the ferrofluid partitions to the top phase (the continuous phase in the microfluidic chip), size-based diamagnetic separation of particle/cell-encapsulating droplets is possible. When the ferrofluid partitions to the bottom phase (the dispersed phase in the microfluidic chip), we can magnetically separate the particle/cell-encapsulating droplets. This all-aqueous biocompatible magnetophoretic lab-on-a-chip platform has biomedical applications in single-cell analysis and drug delivery.
Investigation of Epithelial-to-Mesenchymal Transition through Microcontact Transition
Huma Inayat, PhD Student, Ryerson University
We have used microcontact printing as a means of simulating injury or wounds in a healthy monolayer of LLC PK1 cells to study the expression of Epithelial-to-Mesenchymal Transition (EMT) signature proteins. Our goal is to investigate the concept that epithelial wounding or injury (simulated in vitro by the absence of cell-cell contacts), predisposes the injured cells for various features of EMT, including the expression of EMT signature proteins (such as alpha-Smooth Muscle Actin). We also aim to investigate the proportional secretory response (termed profibrotic epithelial phenotype or PEP) caused by the loss of cell-cell contacts (or injury) which holds true even if EMT is just partial. We hypothesize that the length of free epithelial edges in a monolayer is proportional to the propensity of the epithelium to acquire a profibrotic epithelial phenotype.
Acoustic based flow cytometry: detecting circulating tumor cells (CTCs)
Vaskar Gnyawali, PhD candidate, Ryerson University
We have developed an acoustic-based flow cytometer with simultaneous detection of ultrasound backscatter (US) and photoacoustic (PA) waves from individual cells flowing in a microfluidic channel.
Our polydimethylsiloxane based hydrodynamic 3D flow-focusing microfluidic device contains a cross-junction channel, a micro-needle insert, and a 3D printed frame to hold and align a US transducer (center frequency 375 MHz). Individual cells pass through an interrogation zone where pulsed ultrasound and laser (532 nm wavelength) beams are confocally aligned. The cells interact with US and laser to generate US backscatter and PA waves, which are detected by the same transducer. The detected signals are strongly dependent on the cell size, morphology, biomechanical properties, and chromophore composition. Comparing the measured power spectra of US and PA signals with theoretical models we are able to calculate the diameter of the scattering or absorbing micron size object. Here, we determine the diameter of nucleus and cell to calculate the nucleus-to-cytoplasmic(N:C) ratio of thousands of nucleus stained AML cells in few minutes. This N:C ratio is often used to diagnose malignant disease while assessing histology. Eventually, our goal is to detect label-free CTC’s using PA (nucleus size) and US (cell size) to calculate N:C ratio.
Soft lithography based on photolithography and two-photon polymerization
Yang Lin, Assistant Professor, University of Rhode Island
Over the past decades, soft lithography has greatly facilitated the development of microfluidics due to its simplicity and cost-effectiveness. Besides, numerous fabrication techniques such as multi-layer photolithography, stereolithography and other methods have been developed to fabricate moulds with complex 3D structures nowadays. But these methods are usually not beneficial for microfluidic applications either because of low resolution or sophisticated fabrication procedures. Besides, high-resolution methods such as two-photon lithography, electron-beam lithography, and focused ion beam are often restricted by fabrication speed and total fabricated volume. Nonetheless, the region of interest in typical microfluidic devices is usually very small while the rest of the structure does not require complex 3D fabrication methods. Herein, conventional photolithography and two-photon polymerization are combined for the first time to form a simple hybrid approach in fabricating master moulds for soft lithography. It not only benefits from convenience of photolithography, but also gives rise to complex 3D structures with high resolution based on two-photon polymerization. In this paper, various tests have been conducted to further study its performance, and a passive micromixer has been created as a demonstration for microfluidic applications.
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