Predictable duty cycle modulation through coupled pairing of syringes with microfluidic oscillators

The ability to elicit distinct duty cycles from the same self-regulating microfluidic oscillator device would greatly enhance the versatility of this micro-machine as a tool, capable of recapitulating in vitro the diverse oscillatory processes that occur within natural systems. We report a novel approach to realize this using the coordinated modulation of input volumetric flow rate ratio and fluidic capacitance ratio. The demonstration uses a straightforward experimental system where fluid inflow to the oscillator is provided by two syringes (of symmetric or asymmetric cross-sectional area) mounted upon a single syringe pump applying pressure across both syringes at a constant linear velocity. This produces distinct volumetric outflow rates from each syringe that are proportional to the ratio between their cross-sectional areas. The difference in syringe cross-sectional area also leads to differences in fluidic capacitance; this underappreciated capacitive difference allows us to present a simplified expression to determine the microfluidic oscillators duty cycle as a function of cross-sectional area. Examination of multiple total volumetric inflows under asymmetric inflow rates yielded predictable and robust duty cycles ranging from 50% to 90%. A method for estimating the outflow duration for each inflow under applied flow rate ratios is provided to better facilitate the utilization of this system in experimental protocols requiring specific stimulation and rest intervalsopen1

Development of Micro-actuators and Micro-sensors for the On-chip Interrogation of Cells and In Vitro Generated Tissues.

Microscale systems enable interrogation of biological mechanisms beyond the capacity of conventional macroscale techniques. The large surface-to-volume ratio of microscale platforms allows investigators to better control the spatial and temporal microenvironment presented to biological samples, manipulating samples at scales reminiscent of their native microenvironments. This research describes microscale technologies to advance the design, complexity, and control of tissue culture microenvironments in three areas – chemical stimulation, regulating cell culture dimensionality, and oxygen monitoring. These tools improve in vitro models to better emulate the native biological response. To regulate temporal patterns of biochemical stimulation I developed an autonomous microfluidic oscillator circuit that enables dynamic control of delivered fluids without external control signals. This work produced to (1) a practical system to modulate the duty cycle of an applied stimulus in a user-defined manner without requiring modification of the device itself; and (2) a method to couple multiple independent oscillators together to ensure uniformity of experimental parameters, such as frequency and duty cycle, across multiple devices. In other work, reproducibility of three-dimensional spheroid cultures was achieved by culture additives to generate increasingly complex, and robust microscale cultures. We also developed dispersible microsensors for tissue culture oxygen measurements. When recreating physiologic microenvironments, it is critical to monitor and quantify the presence of oxygen. The untethered biocompatible oxygen sensors can be embedded or dispersed within diverse culture conditions for the real-time/continuous detection of oxygen in vitro. Dispersible microsensors were used to visualize the oxygen environment within in vitro tumor models, which allow for the informed generation of tumor models to more accurately capitulate the necessary oxygen environments.PhDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113506/1/sashacai_1.pd

Capacitive coupling synchronizes autonomous microfluidic oscillators

Even identically designed autonomous microfluidic oscillators have deviceâ toâ device oscillation variability that arises due to inconsistencies in fabrication, materials, and operation conditions. This work demonstrates, experimentally and theoretically, that with appropriate capacitive coupling these microfluidic oscillators can be synchronized. The size and characteristics of the capacitive coupling needed and the range of input flow rate differences that can be synchronized are also characterized. In addition to deviceâ toâ device variability, there is also withinâ device oscillation noise that arises. An additional advantage of coupling multiple fluidic oscillators together is that the oscillation noise decreases. The ability to synchronize multiple autonomous oscillators is also a first step towards enhancing their usefulness as tools for biochemical research applications where multiplicate experiments with identical temporalâ stimulation conditions are required.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143674/1/elps6428_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143674/2/elps6428.pd

Process development using oscillatory baffled mesoreactors

PhD ThesisThe mesoscale oscillatory baffled reactor (meso-OBR) is a flow chemistry platform whose niche is the ability to convert long residence time batch processes to continuous processes. This reactor can rapidly screen reaction kinetics or optimise a reaction in flow with minimal waste. In this work, several areas were identified that could be addressed to broaden the applicability of this platform. Four main research themes were subsequently formulated and explored: (I) development of deeper understanding of the fluid mechanics in meso-OBRs, (II) development of a new hybrid heat pipe meso-OBR for improved thermal management, (III) further improvement of continuous screening using meso-OBRs by removing the solvent and employing better experiment design methodologies, and (IV) exploration of 3D printing for rapid reactor development. I. The flow structures in a meso-OBR containing different helical baffle geometries were studied using computational fluid dynamics simulations, validated by particle image velocimetry (PIV) experiments for the first time. It was demonstrated, using new quantification methods for the meso-OBR, that when using helical baffles swirling is responsible for providing a wider operating window for plug flow than other baffle designs. Further, a new flow regime resembling a Taylor-Couette flow was discovered that further improved the plug flow response. This new double vortex regime could conceivably improve multiphase mixing and enable flow measurements (e.g. using thermocouples inside the reactor) to be conducted without degrading the mixing condition. This work also provides a new framework for validating simulated OBR flows using PIV, by quantitatively comparing turbulent flow features instead of qualitatively comparing average velocity fields. II. A new hybrid heat pipe meso-OBR (HPOBR) was prototyped to provide better thermal control of the meso-OBR by exploiting the rapid and isothermal properties of the heat pipe. This new HPOBR was compared with a jacketed meso-OBR (JOBR) for the thermal control of an exothermic imination reaction conducted without a solvent. Without a solvent or thermal control scheme, this reaction exceeded the boiling point of one of the reactants. A central composite experiment design explored the effects of reactant net flow rate, oscillation intensity and cooling capacity on the thermal and chemical response of the reaction. The HPOBR was able to passively control the temperature below the boiling point of the reactant at all conditions through heat spreading. Overall, a combined 260-fold improvement in throughput was demonstrated compared to a reactor requiring the use of a solvent. Thus, this ii wholly new reactor design provides a new approach to achieving green chemistry that could be theoretically easily adapted to other reactions. III. Analysis of in situ Fourier transform infrared (FTIR) spectroscopic data also suggested that the reaction kinetics of this solventless imination case study could be screened for the first time using the HPOBR and JOBR. This was tested by applying flow-screening protocols that adjusted the reactant molar ratio, residence time, and temperature in a single flow experiment. Both reactor configurations were able to screen the Arrhenius kinetics parameters (pre-exponential factors, activation energies, and equilibrium constants) of both steps of the imination reaction. By defining experiment conditions using design of experiments (DoE) methodologies, a theoretical 70+% reduction in material usage/time requirement for screening was achieved compared to the previous state-of-the-art screening using meso-OBRs in the literature. Additionally, it was discovered that thermal effects on the reaction could be inferred by changing other operating conditions such as molar ratio and residence time. This further simplifies the screening protocols by eliminating the need for active temperature control strategies (such as a jacket). IV. Finally, potential application areas for further development of the meso-OBR platform using 3D printing were devised. These areas conformed to different “hierarchies” of complexity, from new baffle structures (simplest) to entirely new methods for achieving mixing (most complex). This latter option was adopted as a case study, where the passively generated pulsatile flows of fluidic oscillators were tested for the first time as a means for improving plug flow. Improved plug flow behaviour was indeed demonstrated in three different standard reactor geometries (plain, baffled and coiled tubes), where it could be inferred that axial dispersion was decoupled from the secondary flows in an analogous manner to the OBR. The results indicate that these devices could be the basis for a new flow chemistry platform that requires no moving parts, which would be appealing for various industrial applications. It is concluded that, for the meso-OBR platform to remain relevant in the next era of tailor-made reactors (with rapid uptake of 3D printing), the identified areas where 3D printing could benefit the meso-OBR should be further explored

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

Proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress

Published proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress, hosted by York University, 27-30 May 2018

Antioxidant and DPPH-Scavenging Activities of Compounds and Ethanolic Extract of the Leaf and Twigs of Caesalpinia bonduc L. Roxb.

Antioxidant effects of ethanolic extract of Caesalpinia bonduc and its isolated bioactive compounds were evaluated in vitro. The compounds included two new cassanediterpenes, 1α,7α-diacetoxy-5α,6β-dihydroxyl-cass-14(15)-epoxy-16,12-olide (1)and 12α-ethoxyl-1α,14β-diacetoxy-2α,5α-dihydroxyl cass-13(15)-en-16,12-olide(2); and others, bonducellin (3), 7,4’-dihydroxy-3,11-dehydrohomoisoflavanone (4), daucosterol (5), luteolin (6), quercetin-3-methyl ether (7) and kaempferol-3-O-α-L-rhamnopyranosyl-(1Ç2)-β-D-xylopyranoside (8). The antioxidant properties of the extract and compounds were assessed by the measurement of the total phenolic content, ascorbic acid content, total antioxidant capacity and 1-1-diphenyl-2-picryl hydrazyl (DPPH) and hydrogen peroxide radicals scavenging activities.Compounds 3, 6, 7 and ethanolic extract had DPPH scavenging activities with IC50 values of 186, 75, 17 and 102 μg/ml respectively when compared to vitamin C with 15 μg/ml. On the other hand, no significant results were obtained for hydrogen peroxide radical. In addition, compound 7 has the highest phenolic content of 0.81±0.01 mg/ml of gallic acid equivalent while compound 8 showed the highest total antioxidant capacity with 254.31±3.54 and 199.82±2.78 μg/ml gallic and ascorbic acid equivalent respectively. Compound 4 and ethanolic extract showed a high ascorbic acid content of 2.26±0.01 and 6.78±0.03 mg/ml respectively.The results obtained showed the antioxidant activity of the ethanolic extract of C. bonduc and deduced that this activity was mediated by its isolated bioactive compounds