Biomedical subjects

Massimo Morbidelli

Publications and source records attributed to Massimo Morbidelli.

At least 19 recordsLinked to original sources

PubMed2006

A generalized model for the stability of polymer colloids.

A generalized model has been proposed to describe the stability of polymer colloids stabilized with ionic surfactants by accounting simultaneously for the interactions among three important physicochemical processes: colloidal interactions, surfactant adsorption equilibrium, and association equilibria of surface charge groups with counterions at the particle-liquid interface. A few Fuchs stability ratio values, determined experimentally for various salt types and concentrations through measurements of the doublet formation kinetics, are used to estimate the model parameters, such as the surfactant adsorption and counterion association parameters. With the estimated model parameters, the generalized model allows one to monitor the dynamics of surfactant partitioning between the particle surface and the disperse medium, to analyze the variation of surface charge density and potential as a function of the electrolyte type and concentration, and to predict the critical coagulant concentration for fast coagulation. Three fluorinated polymer colloids, stabilized by perfluoropolyether-based carboxylate surfactant, have been used to demonstrate the feasibility of the proposed colloidal stability model.

Journal Article↗

PubMed2006

A continuous, counter-current multi-column chromatographic process incorporating modifier gradients for ternary separations.

The existing literature of continuous chromatographic process indicates the scarcity of processes which allow the continuous separation of a ternary mixture and which also exploit the power of modifier gradients and counter-currency. A new process filling this gap is presented and analyzed using an equilibrium theory model and linear isotherms. The analysis leads to the explicit formulation of an operating region, where 100% purity and yield can be obtained. A normalized flow rate ratio is introduced, which allows an easy description and understanding of the process behavior. The gained insights are verified using a detailed simulation model, where the influence of changes in the normalized flow rate ratios on the unit performance is investigated.

Computer Simulation↗

PubMed2006

Detailed model of the aggregation event between two fractal clusters.

A model has been developed for describing the aggregation process of two fractal clusters under quiescent conditions. The model uses the approach originally proposed by Smoluchowski for the diffusion-limited aggregation of two spherical particles but accounts for the possibility of interpenetration between the fractal clusters. It is assumed that when a cluster diffuses toward a reference cluster their center-to-center distance can be smaller than the sum of their radii, and their aggregation process is modeled using a diffusion-reaction equation. The reactivity of the clusters is assumed to depend on the reactivity and number of their particles involved in the aggregation event. The model can be applied to evaluate the aggregation rate constant as a function of the prevailing operating conditions by simply changing the value of the particle stability ratio, without any a priori specification of a diffusion-limited cluster aggregation, reaction-limited cluster aggregation, or transition regime. Furthermore, the model allows one to estimate the structure properties of the formed cluster after the aggregation, based on the computed distance between the aggregating clusters in the final cluster.

Journal Article↗

PubMed2006

Experimental verification of sample-solvent induced modifier-solute peak interactions in biochromatography.

In a previous theoretical analysis based on equilibrium theory it has been shown how differences in the sample and elution modifier concentrations can lead to unexpected behavior of the solute eluted peaks such as retention time distortion, peak deformation and peak doubling. All these features are verified experimentally in this work using the polypeptide calcitonin and a variant of a specific monoclonal antibody as chromatographic model systems. For both experimental systems, the retention time distortion can be predicted with high accuracy by the solution of the equilibrium theory model. For the polypeptide, the predictions from the theory about the occurrence of peak deformation and double peaks has been successfully verified by a series of tailored experiments with positive as well as negative modifier perturbations.

Antibodies, Monoclonal↗

PubMed2005

Enantioseparation of 1-phenyl-1-propanol by supercritical fluid-simulated moving bed chromatography.

The enantioseparation of 1-phenyl-1-propanol through the supercritical fluid-simulated moving bed (SF-SMB) process is studied. Non-linear isotherms were measured on an analytical column, and used together with the triangle theory for SMB design to select operating conditions for the SF-SMB. Experiments were carried out on a pilot-scale SF-SMB plant at conditions that corresponded to the non-linear range of the isotherm. Under conditions of low feed concentration, complete separation (extract purity = 99.5%; raffinate purity = 98.4%) was achieved. Under conditions of larger feed concentration, the best separation corresponded to an extract purity of 98.0% and a raffinate purity of 94.0%, and yielded a productivity of 110 g of racemate per kg stationary phase per day.

Adsorption↗

PubMed2005

Optimizing control of simulated moving beds--experimental implementation.

The operation of simulated moving beds (SMBs) at their optimal operating conditions is difficult and not robust. Therefore, it is common practice to operate SMB units far from their economic optimum in order to tolerate uncertainties in the system and minimize the effect of disturbances. Recently, we have proposed an on-line optimization based SMB control scheme that allows to exploit the full economic potential of SMB technology. The goal of this work is two-fold. Firstly, to experimentally evaluate and demonstrate the capability of the controller to optimize and operate the SMB units, thus delivering the products with maximum productivity and minimum solvent consumption. Secondly, to show the suitability of the controller even using a minimum of system information, thus making the detailed isotherm measurements redundant and saving time in the separation design phase. This paper reports and discusses the first experimental implementation of the control concept on a high purity separation of nucleosides (uridine, guanosine) with an eight-column four-section SMB where the species to be separated are retained on the source 30RPC stationary phase according to a linear isotherm.

Chromatography, Liquid↗

PubMed2005

Effect of pressure drop on solute retention and column efficiency in supercritical fluid chromatography.

The effect of pressure drop on the performance of supercritical fluid chromatographic systems is studied. Experiments have been conducted at different pressures and at 55 and 65 degrees C. Experiments at conditions leading to large and small pressure drops have been performed. Parameters to describe the pressure drop, retention time and efficiency have been extracted from these experiments. Using these parameters the dynamics of the chromatographic column have been modeled. Darcy's law was used to describe the pressure drop. The efficiency was modeled by considering the contributions from axial dispersion, resistance to mass transfer from the fluid film, and to diffusion in the pores. Good description of the pressure drop, retention time and mass transfer characteristics under normal operating conditions was obtained. The parameters extracted were used to predict the elution profile by numerical simulations. Considerable loss in column efficiency was observed when operating the column at lower values of the back pressure.

Chromatography, Supercritical Fluid↗

PubMed2005

Analysis of sample-solvent induced modifier-solute peak interactions in biochromatography using equilibrium theory and detailed simulations.

Batch liquid chromatographic columns are often equilibrated with an eluent stream being a mixture of inert compounds and so-called modifiers. The sample injected into the eluent stream usually consists of the solutes to be separated and of a mixture of the same solvents as in the eluent but in general with different concentration values. This results in two groups of peaks moving along the column: the solute peaks and the modifier pertubations. If the adsorptivity of the solute depends strongly on the modifier, as it is often the case in biochromatography, the interference between the two groups of peaks leads to peculiar phenomena like double peaks, split peaks, distorted peaks with anti-Langmurian shape, etc. In this work, these phenomena are analyzed based on an analytical solution of the equilibrium theory model and the results are compared with detailed simulations and experimental data. It is shown that the qualitative behavior is well predicted in the frame of equilibrium theory and general guidelines how to avoid these kinds of interactions are developed.

Acetonitriles↗

PubMed2005

Enantioseparation of 1-phenyl-1-propanol on Chiralcel OD by supercritical fluid chromatography. I. Linear isotherm.

The supercritical fluid chromatography (SFC) separation of the enantiomers of 1-phenyl-1-propanol on the chiral stationary phase Chiralcel OD under linear conditions is studied. Supercritical CO2 modified with methanol is used as a mobile phase. The effect of modifier concentration, pressure and temperature is studied. An empirical isotherm to account for the effect of density of the mobile phase and modifier concentration has been used to model the experimental results. It was observed that the selectivity and resolution were higher at 30 degrees C as compared to those at 40 degrees C.

Adsorption↗

PubMed2005

Scattering structure factor of colloidal gels characterized by static light scattering, small-angle light scattering, and small-angle neutron scattering measurements.

The scattering structure factor of a colloidal gel in a q range of 5 orders of magnitude has been determined by combining static light scattering, small-angle light scattering, and neutron scattering measurements. It exhibits simultaneously two types of structure information: a mass fractal scaling within the clusters that constitute the gel and a surface fractal scaling for length scales larger than that of the clusters. Such scattering behavior can be well interpreted by the pair-correlation function proposed in the literature to model an ideal structure constituted of mass fractal objects inside surface fractal objects.

Journal Article↗

PubMed2005

Scaling of the kinetics of slow aggregation and gel formation for a fluorinated polymer colloid.

The aggregation and gelation kinetics in moderately concentrated (0.004 </= phi(0) </= 0.1) colloidal dispersions of fluorinated polymer particles has been studied. The aggregation was adjusted to proceed slowly enough to allow a convenient characterization of the kinetics through static and dynamic light scattering on quenched and diluted samples. A population balance model based on second-order aggregation rates is developed to compute the time evolution of the cluster mass distribution, from which we calculate the values of the average radii and structure factor measured by light scattering, so as to allow a direct comparison between measured and calculated quantities. The model suggests the introduction of a dimensionless time which allows the scaling of all the aggregation data on unique master curves defined by only two parameters: the exponent of the power-law aggregation kernel, lambda, and the aggregate fractal dimension, d(f). The predicted master curves were observed experimentally, which confirms the validity of the aggregation model and allows the unique determination of the kinetic and structural parameters of the aggregation process. The cluster growth behavior, although significantly slower than DLCA, shows power-law kinetics rather than the exponential one typical of RLCA and the cluster structure is characterized by an unexpectedly small fractal dimension, d(f) = 1.7. The occurrence of gelation has been characterized using small amplitude oscillatory shearing to monitor the time evolution of the elastic modulus. It is found that also these curves, together with the gel time value, scale with the stability ratio of primary particles for a given solid volume fraction. We further use the model to calculate the cumulative occupied volume fraction of the growing aggregates and quantify in this way the increasing space filling, which is solid volume fraction dependent. The experimentally determined dimensionless gel times, which are also solid volume fraction dependent, scale then directly with the dimensionless time to reach a certain degree of the space filling in the model. This finding suggests that, like the aggregation kinetics, the gelation kinetics is governed by a second-order rate process.

Journal Article↗

PubMed2005

Further insights into the universality of colloidal aggregation.

Dynamic light scattering (DLS) performed at various scattering wave vectors provides detailed information about the aggregation kinetics and the cluster mass distribution (CMD) in colloidal dispersions. Detailed modeling of the aggregation kinetics with population balance equations requires a quantitative connection between the CMD and measurable quantities such as the angle dependent hydrodynamic radii obtained by DLS. For this purpose we evaluate and compare various models for the structure factor of fractal aggregates. Additionally, we introduce a simple scattering model that accounts for the contribution of internal cluster dynamics of fractal clusters to the first cumulant of the dynamic structure factor. We show that this contribution allows to quantitatively describe previously measured experimental data on the scattering wave vector dependence of the hydrodynamic radius in diffusion limited cluster-cluster aggregation (DLCA), which was shown to exhibit some kind of universality behavior (master curve). Using the same scattering model, we analyze a similar set of experimental data but in reaction limited cluster-cluster aggregation (RLCA). We find that in this case the crossover from RLCA to DLCA and gravitational settling both have a significant influence on the CMD and consequently on the scattering wave vector dependent DLS data. Only when accounting for both these effects they temporarily compensate each other and a satisfactory representation of the aggregation master curve is possible for the RLCA data at longer times. Indeed, we find that either crossover from RLCA to DLCA or gravitational settling, when present individually, causes the loss of a master curve for aggregation.

Biophysics↗

PubMed2004

Rotational diffusivity of fractal clusters.

The rotational diffusion behavior of fractal clusters generated through an off-lattice cluster-cluster aggregation algorithm in both diffusion-limited cluster aggregation and reaction-limited cluster aggregation conditions is investigated. The extended Kirkwood-Riseman theory (Garcia de la Torre et al., Macromolecules, 1987) is used to estimate the cluster rotational diffusion tensor. The three eigenvalues of this tensor, which correspond to the three main rotational diffusivity values of the cluster, have been computed for each generated cluster. Once the eigenvalues have been sorted in ascending order, each of them has been averaged over several thousands of clusters. It is found that one of the three main average rotational diffusivities is substantially larger than the other two, indicating significant anisotropy of fractal clusters. Moreover, a rotational hydrodynamic radius Rh,r has been determined on the basis of the mean value of the three average rotational diffusivities, which is about 25% larger than the mean translational hydrodynamic radius Rh calculated through the same Kirkwood-Riseman theory. Finally, the obtained Rh,r values have been applied to interpret dynamic light scattering data from aggregating colloidal systems and to investigate the reliability of the assumption, Rh = Rh,r, typically made in the literature.

Journal Article↗

PubMed2004

Experimental investigation of colloidal gel structures.

We investigate experimentally the structural properties of colloidal gels, formed under both diffusion-limited and reaction-limited aggregation conditions, using light scattering measurements and compare the results with the literature Monte Carlo (MC) simulations. The scattering structure factors have been measured for the two classes of gels in the range of the particle volume fractions between 0.02 and 0.07. From these, the corresponding fractal dimension values have been estimated. These have been found to be in good agreement with those estimated from the structure factors computed from MC simulated gels. On the basis of our previous research (Lattuada et al. Langmuir 2003, 19, 6312), this confirms that the scattering structure factor of a gel provides erroneously a small fractal dimension value, which decreases as the particle volume fraction increases. Furthermore, it is observed that the average size of the fractal clusters is larger in real gels than in simulated gels.

Journal Article↗

PubMed2004

Kinetics of gel formation in dilute dispersions with strong attractive particle interactions.

We report a combined experimental and modeling study to investigate the kinetics of the transformation of a colloidal dispersion with strong attractive particle interactions into a gel. In the model, a two step mechanism is proposed, where an initial aggregation step is followed by an interconnection step leading to a particle network spanning the entire system volume. Using the Smoluchowski aggregation equation for the first step, we introduce a criterion to determine when the aggregation process is arrested and clusters become caged. In the second step the caged clusters diffuse over short distances and interconnect to form the particle network. The reliability of the gelation times computed by the model has been tested by comparison with a suitable set of experimental data. In addition, we show that the concept of mathematical gelation within the Smoluchowski aggregation equation is not appropriate for the description of the entire gel formation process in this system.

Journal Article↗

PubMed2004

Optimizing control of simulated moving beds--linear isotherm.

A new optimization based adaptive control strategy for simulated moving beds (SMBs) is proposed. A linearized reduced order model, which accounts for the periodic nature of the SMB process, is used for online optimization and control. The manipulated variables are the four inlet flow rates, the outputs are the raffinate and extract concentrations. Concentration measurements at the raffinate and extract outlets are used as the feedback information. The state estimate from the periodic Kalman filter is used for the prediction of the outlet concentrations over a chosen horizon. Predicted outlet concentrations are the basis for the calculation of the optimal input adjustments, which maximize the productivity and minimize the desorbent consumption subject to constraints on product purities. The realization of this concept is discussed and the implementation on a virtual eight column SMB platform is assessed, in the case of binary linear systems. For a whole series of typical plant disturbances it is shown that the proposed approach is effective in minimizing off-spec products and in achieving optimal SMB operation, also in the case where there are significant model uncertainties.

Models, Theoretical↗

PubMed2004

Solvent gradient operation of simulated moving beds. 2. Langmuir isotherms.

Simulated Moving Bed separations of enantiomers or fine chemicals are usually carried out in the isocratic mode, i.e. by applying the same operating conditions (temperature, pressure, mobile phase composition, pH) in the whole SMB unit. However, it has been recently recognized that by properly modulating operating conditions in the SMB sections. i.e. Sections 1-4 normally, separation performance in terms of productivity and solvent consumption can be significantly improved. In this work, we study solvent gradient SMB (SG-SMB) operation, where the concentration of a modifier in the main solvent constituting the mobile phase is adjusted along the SMB unit, so as to have weaker retention of the species to be separated in the first two sections, and stronger retention in Sections 3 and 4. Overload chromatographic conditions are considered, where the adsorption behavior is characterized by a nonlinear competitive adsorption isotherm, e.g. a binary Langmuir isotherm. Design criteria to achieve complete separation are developed in the frame of the equilibrium theory of chromatography. The theoretical findings are discussed in view of typical effects of the modifier concentration on retention times and solubility of the species to be separated, and an overall assessment of the SG-SMB technology is attempted.

Chromatography↗

PubMed2003

A simple model for the structure of fractal aggregates.

Structural properties of small aggregates containing up to 100 particles have been studied through detailed Monte Carlo cluster-cluster aggregation simulations in both diffusion-limited and reaction-limited conditions. First, the radius of gyration, the radius of the smallest sphere encompassing the cluster, and the particle-particle correlation function, g(r), have been computed based on the positions of all the particles in the cluster, and their fractal scaling has been analyzed. Then, an empirical model has been developed to simulate the g(r) function for aggregates of any size and used to determine the corresponding structural properties and scattering structure factors. Finally, in order to illustrate the application of the structural properties thus computed, two experiments on diffusion-limited aggregation have been performed, and the average scattering structure factors have been measured as a function of time using a small-angle light-scattering device. The obtained average scattering structure factors have been simulated using the Smoluchowski population balance equations, using the single aggregate structural properties and scattering structure factor predicted by the developed empirical g(r) model.

Journal Article↗