Binbing Han

A new method of processing the time-concentration data of reaction kinetics

Experimental data of reaction kinetics are usually in the form of concentration versus time. For kinetics investigation it is more convenient to have the data in the form of reaction rate versus concentration. Converting time-concentration data into concentration-reaction rate data is an ill-posed problem in the sense that if inappropriate methods are used the noise in the original data will be amplified leading to unreliable results. This paper describes a conversion procedure, independent of reaction rate model or mechanism, that manages to keep noise amplification under control. The performance of this procedure is demonstrated by applying it to several sets of published kinetic data. Since these data are accompanied by their rate equations, the computed rates are used to obtain the unknown parameters in these equations. Comparison of these parameters with published figures and the ease with which they are obtained highlights the advantages of the new procedure.

Purification of Densonucleosis Virus by Tangential Flow Ultrafiltration

Purification at commercial scale of viruses and virus vectors for gene therapy applications and viral vaccines is a major separations challenge. Tangential flow ultrafiltration has been developed for protein purification. Here tangential flow ultrafiltration of parvoviruses has been investigated. Because these virus particles are small (18–26 nm), removal of host cell proteins will be challenging. The results obtained here indicate that 30, 50, and 100 kDa membranes reject the virus particles, whereas 300 kDa membranes allow some virus particles to pass into the permeate. The decrease in permeate flux for the 300 kDa ultrafiltration membrane is much greater than for the 30, 50, and 100 kDa membranes, indicating possible entrapment of virus particle in the membrane pores. The permeate flux and level of protein rejection is strongly affected by the cell culture growth medium. The results indicate that when developing a new process, it is essential that the cell culture and purification operations be developed in parallel.

Effects of degree of formaldehyde acetal treatment and maleic acid crosslinking on solubility and diffusivity of water in PVA membranes

The sorption, desorption and solubility of vapour and liquid water in polyvinyl alcohol (PVA) membranes treated by formaldehyde was studied. The sorption and solubility of water in PVA membranes with different degrees of maleic acid crosslinking was also investigated and compared with that of the formaldehyde-treated membranes. The structural differences that arise as a consequence of these two treatment methods and the corresponding differences in the diffusivity and solubility of water molecules are discussed. In addition, the key step involved in the dehydration of benzene using PVA membranes treated by formaldehyde was analysed. Three common models for pervaporation process are compared.

Mass and momentum transfer in hollow fibre blood oxygenators

Mass transfer and friction factor correlations for microporous hollow fibre blood oxygenators (BOs) have been determined experimentally. Water and glycerol water solutions were used as a substitute for blood. The diffusion of oxygen into and out of water and glycerol water solutions has been studied. The liquid stream flowed outside and across bundles of woven hollow fibres while the gas stream flowed inside the fibres. In previous studies, it has been assumed that the Sherwood number varies with the one-third power of the Schmidt number. By conducting experiments using various glycerol water mixtures the kinematic viscosity of the liquid and the diffusivity of oxygen in the liquid phase have been varied. The results obtained here experimentally confirm the dependence of the Sherwood number on the Schmidt number raised to the one-third power. The experimental mass transfer and friction factor results for hollow fibre BOs are compared to the j factor analysis presented by Chilton and Colburn. These results may be used to further optimize the design of BOs.

Mass transfer in blood oxygenators using blood analogue fluids.

Mass transfer correlations for hollow fiber blood oxygenators have been determined experimentally using Newtonian and non‐Newtonian blood analogue fluids. The Newtonian fluids consisted of deionized water and glycerol/water mixtures. The non‐Newtonian fluids were prepared by adding small amounts of xanthan gum to the Newtonian blood analogue fluids. The rheological behavior of the non‐Newtonian blood analogue fluids was modeled using the power law. The diffusion of oxygen into and out of the Newtonian and non‐Newtonian blood analogue fluids has been studied. The liquid stream flowed outside and across bundles of woven hollow fibers, while the gas stream flowed inside the fibers.

Model‐Independent Relationships between Hematocrit, Blood Viscosity, and Yield Stress Derived from Couette Viscometry Data

This paper describes a procedure, based on Tikhonov regularization, for obtaining the shear rate function or equivalently the viscosity function of blood from Couette viscometry data. For data sets that include points where the sample in the annulus is partially sheared the yield stress of blood will also be obtained. For data sets that do not contain partially sheared points, provided the shear stress is sufficiently low, a different method of estimating the yield stress is proposed. Both the shear rate function and yield stress obtained in this investigation are independent of any rheological model of blood. This procedure is applied to a large set of Couette viscometer data taken from the literature. Results in the form of shear rate and viscosity functions and yield stress are presented for a wide range of hematocrits and are compared against those reported by the originators of the data and against independently measured shear properties of blood.

Population Balance Approach to Modeling Hairy Root Growth

Though numerous models have been developed to describe the growth of microbial cell cultures, far fewer models are available to describe the growth of hairy root cultures. Here a population balance model is proposed to simulate the growth of hairy roots. The model accounts for the increase in biomass due to elongation of a branch by cell division as well as the formation of new branches. The model incorporates the fact that although the likelihood of the formation of a new lateral branch is a maximum at a specific age of the parent branch, lateral branches can form over a distribution of ages of the parent branch. Model parameters are estimated using the genetic algorithm based on experimental data for batch and continuous bioreactors. The model proposed here may provide a better understanding of the increase in biomass of hairy root cultures.

Designing blood oxygenators.

Abstract: Extracorporeal blood oxygenators are used to provide cardiopulmonary support during open heart surgery. In the study reported here, mass transfer correlations were determined for commercially available blood oxygenators. Two configurations used commercially, flow outside and across bundles of hollow fibers and flow in thin channels between parallel flat sheet membranes, were investigated. Water and glycerol/water mixtures were used as a substitute for blood. Diffusion of oxygen into and out of these solutions was studied. For flow across bundles of hollow fibers, the mass transfer correlations derived here are in agreement with analogous correlations for crossflow heat exchangers. However, for flow in thin channels, the rate of mass transfer is often less than predicted from theory. This compromised mass transfer can be explained by considering slight variations in the thickness of the blood flow channels. The mass transfer correlations developed here could be used to design better blood oxygenators.

Enhanced virus removal by flocculation and microfiltration

In this work we have investigated the feasibility of virus clearance by flocculation and tangential flow microfiltration. Chinese hamster ovary cell feed streams were spiked with minute virus of mice and then flocculated using cationic polyelectrolytes prior to tangential flow microfiltration. Our results indicate that flocculation prior to microfiltration leads to more than 100 fold clearance of minute virus of mice particles in the permeate. Today, validation of virus clearance is a major concern in the manufacture of biopharmaceutical products. Frequently new unit operations are added simply to validate virus clearance thus increasing the manufacturing cost. The results obtained here suggest that virus clearance can be obtained during tangential flow microfiltration. Since tangential flow microfiltration is frequently used for bioreactor harvesting this could be a low cost method to validate virus clearance.

Obtaining the Shear Stress versus Shear Rate Relationship and Yield Stress of Blood from Capillary Viscometry Data by Tikhonov Regularization

This paper describes a procedure, based on Tikhonov regularization, for extracting the shear stress versus shear rate relationship and yield stress of blood from capillary viscometry data. The relevant equations and the mathematical nature of the problem are briefly described. The procedure is then applied to three sets of capillary viscometry data of blood taken from the literature. From each data set the procedure computes the complete shear stress versus shear rate relationship and the yield stress. Since the procedure does not rely on any assumed constitutive equation, the computed rheological properties are therefore model‐independent. These properties are compared against one another and against independent measurements. They are found to be in good agreement for shear stress greater than 0.1 Pa but show significant deviations for shear stress below this level. A possible way of improving this situation is discussed.