The use of fibre optic probes for flow monitoring within a small-scale tube

This paper demonstrates the effectiveness of using fibre optic micro-probes for the measurement of dispersion and mixing in continuous flow within small-scale tubes under oscillatory flow conditions. The experimental data was modelled and compared either by three different well-known non-ideal models: a) tanks-inseries (with no backflow); b) differential backmixing; c) stagewise backmixing, and by one two-parameter flow model consisting of a plug flow and a stirred tank reactor in series. Model parameters were found by fitting the theoretical response with experimental data in both Laplace and time domains by different methods. In addition, specific results are presented relating to a small scale tube provided with smooth periodic constrictions (SPCs), the basic element of a novel screening reactor presented by Harvey et al. (Proceedings of the ECCE-4, Granada (2003) 0-6.4- 004). The unsteady tracer injection technique was used at different oscillation conditions, with oscillation frequencies from 0 to 20 Hz and amplitudes from 0 to 3 mm (centre-to-peak). An intermediate mixing behaviour (between plug flow and stirred tank reactor) was achieved in that range of oscillation frequencies and amplitudes. Dispersion was found to be dependent on the oscillation conditions (amplitude and frequencies) and related with the fluid backflow and with the breaking of flow symmetry. The discrete (stagewise) backmixing model was considered as the best model representing residence time behaviour in the small-scale tube.Fundação para a Ciência e a Tecnologia (FCT

Residence times and mixing of a novel continuous oscillatory flow meso reactor

A novel meso reactor based on oscillatory flow technology (Harvey et al., 2001) has been recently presented in Harvey et al. (2003) as a new technology for reaction engineering and particle suspension applications. Due to the demonstrated enhanced performances for fluid micro mixing and suspension of catalyst beads and to the small volume of the reactor, this novel miniature reactor is suitable for applications at specialist chemical manufacture and high throughput screening. Furthermore, a high control of environment conditions (e.g. mixing intensity, temperature) coupled with an online monitoring turns this reactor suitable for smallscale applications to the bioengineering field, such as for fast parallel bioprocessing tasks. This work concerns with the fluid dynamics characterisation of a novel miniature reactor. Experimental results using state-of-art fibre-optic technology is used in order to demonstrate that an accurate control of the residence time distribution (RTD) of liquid and solid phases can be achieved within this reactor as well as enhanced (oxygen) mass transfer rates. Furthermore, numerical simulations using Fluent ® software will be presented where simulated RTDs agrees with the experimental results. The meso reactor unit consists of 4.4 mm internal diameter and 35 cm long jacketed glass tubes, with a unit volume of 4.5 ml and provided with smooth periodic constrictions (SPCs), with an average baffle spacing of 13 mm. The internal diameter at the constricted zone (baffle internal diameter) is 1.6 mm, leading to a reduction of the baffle free are of 87 %. This unit is able to support batch or continuous operations mode, simply by configuring the tubes in parallel or in series, according to the intended application. Mixing is achieved by oscillating the fluid at the bottom or the top of the reactor by means of a piston pump, using oscillation amplitudes and frequencies ranging from 0 to 4 mm centre-to-peak and 0 to 25 Hz, respectively. Experimental studies using the Particle Image Velocimetry (PIV) technique (Harvey et al., 2003) showed that different fluid mechanics are originated at different oscillation conditions (oscillation amplitudes and frequencies). A plug flow or a stirred tank behaviour can be obtained just by controlling the oscillation conditions. At low oscillatory Reynolds numbers (Reo), e.g. 10 to 100, the formation of axisymmetric eddies detached from the constrictions is coupled with low axial velocities and makes it possible to continuously operate the reactor in a plug flow mode. Increasing the Reo to values higher than 100, the eddy symmetry is broken and a complete mixing state is achieved inside the meso reactor. Low oscillation amplitudes must be used if axial dispersion is intended to be minimized, namely at plug flow setup. Through an overall oscillation cycle, changes of the location of the main flow stream from near the wall to the centre of each cavity and vice-versa was observed and is expected to lead to high mass and heat transfer rates (Perry, 2002). Due to the observed high radial velocities, narrow residence times distributions are expected to be obtained (Perry, 2002). Also high axial circulation rates were also observed at high Reos (above 100) and it was proved to lead to an enhanced performance on catalyst beads suspension. The relation of this fluid mechanics with the real performance of this novel meso reactor will be demonstrated. Tracer injection technique is applied to perform RTD studies inside a single SPC tube of the meso reactor. Spectroscopy UV/VIS technique is used to measure the concentration of a coloured tracer at the inlet and outlet (at continuous mode) or at the bottom and the top of the tube (at batch mode). A fibre optic apparatus is employed in order to obtain highly accurate online measurements of the UV/VIS absorbance. Mixing times are calculated for experiments at batch mode. Different flow rates are used to determine the effect of the flow rate over the RTD at continuous operation and axial dispersion is presented by the Bodenstein number, Bo. Determination of KL.a values is achieved by online measurement of the oxygen concentration using a special fibre optic probe. The working tip of the probe was dip-coated with a ruthenium complex immobilised in a sol-gel matrix. This complex is excited to fluorescence by a blue led (470 nm outpuk peak) and the level of the fluorescence is inversely related to the concentration of the oxygen through the Stern-Volmer equation (Wang et al., 1999), which is measured by the fibre-optic apparatus. Retention of solid phases (e.g. catalyst beads and yeast cells) inside the meso reactor will also be tested. Further studies using the Computation Fluid Dynamics (CFD) technique will be presented where accurate prediction of the distribution of residence times is achieved. The use of the distributionfunctions permits to classify the flow behaviour inside this novel meso reactor patterns and to calculate mixing efficiencies and axial dispersion coefficients (expressed by the Bo number) at different oscillation conditions. A simple 2-D axisymmetric laminar model showed good agreement with flow patterns visualisations using PIV for Reo below 100 but a 3-D model with a very fine mesh was required to simulate breakage of axisymmetry. Consequently, 3-D models based on laminar and Large Eddy Simulations (LES) will be used to maximize the matching of RTD at higher oscillation conditions. Main intended application of CFDs to this novel meso reactor is the design of a meso reactor unit, which could operate at the best oscillation conditions and flow rate for cell cultures and biocatalyst applications

Residence times and mixing of a novel continuous oscillatory flow screening reactor

This paper is concernedwith the fluidmechanics andmixing performance of a novel oscillatory flow screening reactor. Using fibre optic probes, a mixing coefficient k_m is determinedfor the system as a function of the applied fluid oscillation frequency and amplitud. In a continuous operation mean residence time and a backmixing coefficient g are estimatedas a function of the oscillation conditions. Finally, in order to compare data with numerical simulations steady state flow data are also included. The screening reactor presented an intermediate mixing behaviour throughout all the studied range of oscillation amplitudes (0–3mm centre-to-peak) and frequencies (0–20 Hz). The backmixing was foundto be highly dependent of the oscillation frequency and amplitud. Nevertheless, a stronger effect of the oscillation amplitude over the axial dispersion was detected presumably due to the increase of the mixing length. On the other hand, the increase of the oscillation frequency was concluded to have the increase in the radial mixing rates as the main effect. Thus, it was possible to achieve a decrease in the axial dispersion with the screening reactor using oscillatory flow, when compared to the laminar steady flow in a plain tube with the same mean internal diameter.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/6954/2001

Enhanced mass transfer rates of a novel oscillatory flow screening reactor

A novel continuous small-scale reactor based on the oscillatory flow technology (Harvey et al 2001) is being developed for application to specialist chemical manufacture and high throughput continuous screening (Harvey et al 2003). This novel reactor is able to perform continuous multiphase reactions, including those involving the suspension of catalyst beads. Extensive potential use in chemistry, biological and pharmaceutical laboratories is envisaged. Optimum operation conditions for applications in the bioengineering field depend on at least four parameters: 1) fluid mixing, 2) residence time characteristics, 3) particle suspension and 4) (oxygen) mass transfer rates. This work particularly concerns the establishment of the operation conditions in relation to oxygen mass transfer rates, KL.a. Furthermore, KL.a values are correlated with the fluid mixing, axial dispersion coefficients and finally with the fluid mechanics observed experimentally by particle image velocimetry (PIV) technique and numerically simulated using Fluent® software. The screening reactor is composed of a 35 cm length glass jacketed tubes (Figure 1), provided with smooth periodic constrictions (SPCs). The internal diameter of the tube is 4.4 mm. The diameter in the constricted zone (the baffle internal diameter) is about 1.6 mm, representing an 87 % reduction in the cross-sectional area. Mixing intensity is controlled by setting up the frequency and the amplitude (centre-to-peak) of the fluid oscillations. Typical oscillation frequencies and amplitudes are from 0 to 20 Hz and from 0 to 4 mm, respectively. A screening arrangement based on some SPC tubes (say 10 to 20) placed at different configurations (serial or parallel) makes this novel reactor suitable for parallel processing and/or for sequential reactions procedures. State-of-the-art fibre-optical technology was used for on-line monitoring of the oxygen concentration inside the screening reactor by using a special fibre optical micro-probe. The working tip of the probe was dip-coated with a ruthenium complex immobilised in a sol-gel matrix. This complex was excited to fluorescence by a blue led (≈ 470 nm output peak) and the level of such fluorescence is inversely related with the concentration of the oxygen through the Stern-Volmer equation (Wang et al., 1999). Continuous fluorescence levels are accurately measured by an UV/VIS/NIR multi-channel spectrometer. Numerical simulations by the computational fluid dynamics (CFD) technique, using Fluent ® software, permitted us to conclude that either near plug flow or stirred tank behaviour can be approached in a single SPC tube, by controlling the fluid oscillation conditions, i.e. the oscillation frequency and/or amplitude. For oscillatory Reynolds numbers (Reo) between 10 and 100, the formation of axisymmetric vortex rings leads to a good radial mixing of the fluid and to low axial dispersions, which suggests that a performance near a plug flow reactor is achieved. For Reo above 100 the high intensity and asymmetry of the vortex rings leads to an increase of the axial dispersion and the fluid behaviour approach that of a stirred tank. All these results were experimentally validated by PIV observations. High radial rates of flow exchange were numerically simulated and experimentally observed during a complete oscillation cycle, coupled with a high degree of velocity gradients. Thus, enhancements of heat and mass transfer rates are expectable within this novel screening reactor. Further, an increase of bubbles breakage is also expected (leading to a decrease of bubble diameter, i.e. an increase of the specific bubble area, a, and also of the gas hold-up), conducting to a significant improvement of oxygen mass transfer. This will be demonstrated with the present work

The fluid mechanics relating to a novel oscillatory flow micro reactor

Fundação para a Ciência e a Tecnologia (FCT) - scholarship SFRH/BD/6954/2001

CO2 dissolution and design aspects of a multiorifice oscillatory baffled column

Dissolution of CO2 in water was studied for a batch vertical multiorifice baffled column (MOBC) with varying orifice diameters (d0) of 6.4-30 mm and baffle open area (α) of 15-42%. Bubble size distributions (BSDs) and the overall volumetric CO2 mass transfer coefficient (KLa) were experimentally evaluated for very low superficial gas velocities, UG of 0.12-0.81 mm s-1, using 5% v/v CO2 in the inlet gas stream at a range of fluid oscillations (f = 0-10 Hz and x0 = 0-10 mm). Remarkably, baffles presenting large do = 30 mm and α = 36%, therefore in the range typically found for single-orifice oscillatory baffled columns, were outperformed with respect to BSD control and CO2 dissolution by the other baffle designs or the same aerated column operating without baffles or fluid oscillations. Flow visualization and bubble tracking experiments also presented in this study established that a small do of 10.5 mm combined with a small value of α = 15% generates sufficient, strong eddy mixing capable of generating and trapping an extremely large fraction of microbubbles in the MOBC. This resulted in increased interfacial area yielding KLa values up to 65 ± 12 h-1 in the range of the UG tested, representing up to 3-fold increase in the rate of CO2 dissolution when compared to the unbaffled, steady column. In addition, a modi fied oscillatory Reynolds number, Re′o and Strouhal number, St' were presented to assist on the design and scale-up of gas-liquid systems based on multiorifice oscillatory ba ffled columns. This work is relevant to gas-liquid or multiphase chemical and biological systems relying on efficient dissolution of gaseous compounds into a liquid medium.BBSRC -European Commissio

Photo inactivation of virus particles in microfluidic capillary systems

It has long been established that UVC light is a very effective method for inactivating pathogens in a fluid, yet the application of UVC irradiation to modern biotechnological processes is limited by the intrinsic short penetration distance of UVC light in optically dense protein solutions. This experimental and numerical study establishes that irradiating a fluid flowing continuously in a microfluidic capillary system, in which the diameter of the capillary is turned to the depth of penetration of UVC light, uniquely treats the whole volume of the fluid to UVC light resulting in fast and effective inactivation of pathogens, with particular focus to virus particles. This was demonstrated by inactivating human herpes simplex virus type-1 (HSV-1, a large enveloped virus) on a dense 10% fetal calf serum solution in a range of fluoropolymer capillary systems, including a 0.75 mm and 1.50 mm internal diameter capillaries and a high-throughput MicroCapillary Film with mean hydraulic diameter of 206 μm. Up to 99.96% of HSV-1 virus particles were effectively inactivated with a mean exposure time of up to 10s, with undetectable collateral damage to proteins. The kinetics of virus inactivation matched well the results from a new mathematical model that considers the parabolic flow profile in the capillaries, and showed the methodology is fully predictable and scalable and avoids both the side effect of UVC light to proteins and the dilution of the fluid in current tubular UVC inactivation systems. This is expected to speed up the industrial adoption of non-invasive UVC virus inactivation in clinical biotechnology and biomanufacturing of therapeutic molecules

A simple device for multiplex ELISA made from melt-extruded plastic microcapillary film

We present a simple device for multiplex quantitative enzyme-linked immunosorbant assays (ELISA) made from a novel melt-extruded microcapillary film (MCF) containing a parallel array of 200µm capillaries along its length. To make ELISA devices different protein antigens or antibodies were immobilised inside individual microcapillaries within long reels of MCF extruded from fluorinated ethylene propylene (FEP). Short pieces of coated film were cut and interfaced with a pipette, allowing sequential uptake of samples and detection solutions into all capillaries from a reagent well. As well as being simple to produce, these FEP MCF devices have excellent light transmittance allowing direct optical interrogation of the capillaries for simple signal quantification. Proof of concept experiments demonstrate both quantitative and multiplex assays in FEP MCF devices using a standard direct ELISA procedure and read using a flatbed scanner. This new multiplex immunoassay platform should find applications ranging from lab detection to point-of-care and field diagnostics