Master of Science in Chemical Engineering, Cleveland State University, 2019, Washkewicz College of Engineering

Magnetophoresis of red blood cells (RBCs) at varying partial pressures of oxygen (pO2) is hypothesized to rejuvenate stored blood to be utilized beyond the FDA regulated 42-day storage time. Magnetophoresis is a particle or cells motion induced by an applied magnetic field in a viscous media. The average magnetophoretic mobility of an oxygenated RBC is -0.126x10-6 mm3-s/kg, and a deoxygenated RBC is 3.66x10-6 mm3-s/kg, presenting magnetophoresis as a resource for RBC rejuvenation in hopes of storing it longer than 42 days. The main objective of this paper was to determine if controlling the pO2 within an RBC suspension, can singly- doubly- triply- or fully deoxygenated RBCs be identified by means of cell tracking velocimetry (CTV). These results agreed with the cooperative binding scheme developed by Hill, especially from ~30-40 to 160 mmHg. From 0 to 30 mmHg, further research must be completed to characterize the binding behavior of oxygen and hemoglobin. The validation of the magnetic energy density gradient value (Sm, currently at 365 T-A/mm2) utilized within CTV, and the exact location for the field of view (FOV, currently set to 4.5 mm from the edge of the magnet assembly) were needed to state particle motion was independent of location within the CTV channel. The FOV location was successfully verified 4.5 mm from the edge of the magnet assembly, however, the Sm value, 880 T-A/mm2, was 140% higher than the original. Spectrophotometry was utilized to validate the oxygenation state of RBCs. Results confirmed spectrophotometry was a reliable model for RBC magnetophoresis. CTV post-processing was tested with glioma progenitor cells. Scatter plots generated for these experiments demonstrated cells with different magnetic mobilities in a sample can be detected. To fully characterize the glioma progenitor cells, more experiments must be completed. Lastly, applying a temperature gradient to the magnetic deposition microscopy (MDM) assembly to enhance the separation of (open full item for complete abstract)

Committee: Maciej Zborowski (Committee Member); Joanne Belovich (Committee Member); Jeffrey Chalmers (Committee Member) Subjects: Biomedical Engineering; Biomedical Research; Chemical Engineering

PhD, University of Cincinnati, 2006, Engineering : Electrical Engineering

In this work, a new passive on-chip blood cell/plasma separator using self-assembly of microspheres as a physical filter and a smart on-chip dynamic blood cell/plasma separator based on a series of pressure pulses in microchannel have been proposed, developed, and successfully characterized for as a part of the disposable polymer lab-on-a-chip point-of-care testing (POCT) clinical diagnostics. A method for self-assembly crystallization of silica microspheres has been investigated for the application as a physical filter. Combination of the vertical deposition method using capillary forces on a hydrophillic substrate with plasma polymer surface modification is used for developing selectively deposited self-assembled microspheres over a specific site of a microchannel. The developed 3D self-assembled silica microspheres over the filter region of the microchannel with their uniform porosity and structure have been fully characterized for separating blood cell/plasma in microchannel. Secondly, a new pulse-assisted dynamic separation technique has been introduced and developed for the application of blood cell/plasma separation without physical filters. The dynamic separation has been attained from the differential forces exerted by applying high amplitude, short duration pressure pulses to the blood sample in microchannels. In addition, the motion of the particles in liquid suspension solution in microchannel experienced by both various forces on particles and pressure pulses on suspension solution has been simulated to validate the principle and to optimize performance by computational analysis and parametric study. The developed pulse-assisted dynamic separator has been successfully developed and characterized on blood cell/plasma from human whole blood sample in microchannel. An on-chip pressure actuator for transporting a fixed-volume of the biofluid sample into a desired site in a lab-on-a-chip or mTAS has been investigated and implemented. A new solid energetic ma (open full item for complete abstract)

Committee: Dr. Chong Ahn (Advisor) Subjects:

MS, University of Cincinnati, 2006, Engineering : Mechanical Engineering

Micro Total Analysis System (µTAS) devices frequently need to deal with bio-particle suspensions in solution and separation of certain bio-particles is often desirable. Separation of plasma from the whole blood has become increasingly popular in clinical diagnostics. Using a finite volume method, Volume of Fluid (VOF) and Discrete Phase (DP) governing equations for multiphase flow are used to delineate the effect of non-Newtonian shear-thinning viscosity of blood from Newtonian viscosity of water. It is observed that the Red Blood Cells (RBC) accumulate at the front of the blood column due to the effect of non-Newtonian viscosity, while the opposite is observed in water. For the selected parameters, 20% of the plasma is observed to be separated from the whole blood, while, in contrast, for a 98% diluted blood 45% of the plasma can be separated. Increase in the particle density and size has resulted in a better separation of the beads from the water for a given magnitude of pressure and number of pulses. For a given pressure, increasing the number of pressure pulses provides more separation and with a low number of applied pulses, higher pressures provide better separation. The present calculations can be adopted to design the flow parameters necessary for the instantaneous separation of plasma from the whole and the diluted blood for µTAS; thus reducing the number of experimental studies. The present method can also be used for calculating the separation of other bio-particles in aqueous solutions.

Committee: Dr. Rupak Banerjee (Advisor) Subjects:

MS, University of Cincinnati, 2004, Engineering : Electrical Engineering

In this work, an on-chip magnetic bead separator in an aqueous solution has been implemented on a plastic substrate. The technique has been successfully characterized in separating magnetic microspheres of 4.1 µm diameter from a suspension solution in DI water. µTAS (Micro Total Analysis System) frequently need to deal with bioparticle suspensions in solution. Separation of certain bioparticles is often desirable. Traditionally, methods like physical filtration have been used to separate biomolecules from suspension solutions. These methods, though well-established are not suited for integration on to mass-fabricated plastic lab-on-a-chip devices. The method developed in this work relies on the differential force exerted by application of high amplitude, short duration pressure pulses on a suspension solution, resulting in separation of suspended particles. From a dispensed volume of 500 nl of the suspension solution, up to 300 nl, or 60 % of volume has been cleared of particles.

Committee: Dr. Chong Ahn (Advisor) Subjects:

Doctor of Philosophy, The Ohio State University, 2012, Chemical and Biomolecular Engineering

Magnetic cell separation and related analysis technology continues its maturation with practioners demanding higher system performance using cells with either magnetically labeled or based on the intrinsic magnetic properties of cells. Typical performance metrics include a very high purity and recovery of the targeted cells or a high level of removal of undesired cells while still recovering the majority of desired cells. While this technology is widely used in biological or clinical research laboratories for diagnostic or therapeutic applications, there still exist many engineering challenges. These challenges include unique system designs or cells with various magnetic susceptibilities, and a more fundamental understanding of the magnetic cell separation process. In this dissertation, an instrument referred to as cell tracking velocimetry was used and further perfected as a powerful analytical tool to assist in this continued improvement of magnetic cell separation technology and approaches. For the first time, side by side comparison of two versions of the CTV magnets: permanent verses electromagnet version, on the same targets were compared. The accuracy and sensitivity of the two versions of CTV system was evaluated, and suggestions were made for choice of version for experimental targets with different magnetic susceptibilities. Also, single particle magnetization measurement of micron sized magnetic particles was made possible by the CTV. Three types of commercially available magnetic particles were studied as examples in this study. The average magnetization values from cell tracking velocimetry were found to have good agreements with the reported values from commercially used instruments which usually output only a bulk value. With respect to magnetic cell separation systems, immuno-labeled magnetic cell separation was carried out for the application of T cell depletion for the purpose of a mismatched, bone marrow transplantation. Flow simulations using FL (open full item for complete abstract)

Committee: Jeffrey Chalmers (Advisor) Subjects: Chemical Engineering