Biomedical subjects

B A Grimes

Publications and source records attributed to B A Grimes.

11 recordsLinked to original sources

PubMed2006

Sulphonic acid strong cation-exchange restricted access columns in sample cleanup for profiling of endogenous peptides in multidimensional liquid chromatography. Structure and function of strong cation-exchange restricted access materials.

In this work, the pore structural parameters and size exclusion properties of LiChrospher strong cation-exchange and reverse phase restricted access materials (RAM) are analysed. The molecular weight size exclusion limit for polystyrenes was found to be about 17.7 kDa, while for standard proteins, the molecular weight size exclusion limit was higher, at approximately 25 kDa. The average pore diameter on a volume basis calculated from the pore network model changes from 8.5 nm (native LiChrospher) to 8.6 nm (diol derivative) to 8.2 nm (sulphonic acid derivative) to 6.9 nm (n-octadecyl derivative). Additional characterisations were performed on restricted access materials with nitrogen sorption at 77 K, water adsorption at 25 degrees C, intrusion-extrusion of water (in order to evaluate the hydrophobic properties of the pores of the hydrophobic RAM), and zeta potential measurements by microelectrophoresis. For peptide analysis out of the biofluids, the strong cation-exchange functionality seems to be particularly suitable mainly because of the high loadability of the strong cation-exchange restricted access material (SCX-RAM) and the fact that one can work under non-denaturing conditions to perform effective chromatographic separations. For bacitracin, the dynamic capacity of the SCX-RAM columns does not reach its maximum value in the analysed range. For lysozyme, the dynamic capacity reaches a value of 0.08 mg/ml of column volume before column is overloaded. Additionally, the proper column operating conditions that lead to the total effective working time of the RAM column to be equal to approximately 500 injections (depending on the type of sample), is comprehensively described. The SCX-RAM column was used in the same system analysing urine samples for the period of 1 month (approximately 150 injections) with run-to-run reproducibility below 5% RSD and below 10% RSD for the relative fractions.

Cation Exchange Resins↗

PubMed2005

Dynamic electric field assisted multi-dimensional liquid chromatography of biological samples.

Complex biological samples require very high resolution separation strategies. The platform introduced here capitalises on the hyphenation of liquid chromatographic (LC) and electric potential gradient electrochromatographic multi-dimensional separation genres. First-dimension selectivity is provided by simultaneous size exclusion (SEC) and strong cation exchange (SCX) chromatography modes, while the second dimension comprises reversed phase (RP) characteristics in a dynamic (time-variant) electric field. The time-variant potential gradient with reversal of polarity is applied across the second dimension monolithic capillary throughout the duration of the solvent strength gradient elution. Hence, the platform offers comprehensive on-line sample clean-up (matrix depletion, analyte enrichment), fractionation (first dimention LC), and separation (second dimension LC) with the prospect of altering selectivity via polarity reversal dynamic electric field tuning.

Blood Chemical Analysis↗

PubMed2004

Analysis and parametric sensitivity of the behavior of overshoots in the concentration of a charged adsorbate in the adsorbed phase of charged adsorbent particles: practical implications for separations of charged solutes.

In this work, an analysis of the parametric sensitivity of the overshoot in the concentration of the adsorbate in the adsorbed phase, which occurs under certain conditions during an ion-exchange adsorption process, is presented and used to suggest practical implications of the concentration overshoot phenomenon on operational policies and configurations of chromatographic columns and finite bath adsorption systems. The results presented in this work demonstrate and explain how the development of an overshoot in the concentration of the adsorbate in the adsorbed phase could be enhanced or suppressed by (i) varying the diffusion coefficient, D3, of the adsorbate relative to the diffusion coefficients, D1 and D2, of the cations and anions, respectively, of the background/buffer electrolyte, (ii) altering the initial surface charge density, delta0, of the charged adsorbent particles, (iii) varying the Debye length, lambda, and (iv) changing the initial concentration, Cd3(0), of the adsorbate in the bulk liquid of the finite bath. The influence of the pH and ionic strength, Iinfinity, of the liquid solution on the development of an overshoot in the concentration of the adsorbate in the adsorbed phase is also presented and discussed through the relationships of these parameters to delta0 and lambda, respectively. Furthermore, a detailed explanation of the effects of each parameter on the interplay between the diffusive and electrophoretic molar fluxes, as well as on the structure and functioning of the electrical double layer, which are responsible for the concentration overshoot phenomenon, is presented.

Journal Article↗

PubMed2003

Expressions for evaluating the possibility of slip at the liquid-solid interface in open tube capillary electrochromatography.

In this work, expressions are constructed and solved that describe the velocity field of electroosmotic flow (EOF) in open tube capillary electrochromatography (CEC) systems when the possibility of having unequal tangential velocities at the liquid-solid interface is considered and a slip condition is employed as a boundary condition for the velocity of the EOF at the capillary wall. The coupled equations of hydrodynamics (momentum balance equation) and electrostatics (Poisson equation) are solved numerically in order to obtain the distribution of the velocity field as well as the value of the volumetric flow rate in the open tube. Also, expressions for the velocity field and the volumetric flow rate of the EOF are presented that are valid for certain electrolytic systems and for certain parameter values for which analytical solutions to the momentum balance and Poisson equations could be obtained. The results presented in this work indicate that having slip in the velocity of the EOF at the wall of the capillary could (i) substantially increase the electroosmotic velocity in the plug-flow region of the radial domain of the open capillary tube and (ii) increase the portion of the radial domain of the open capillary tube where the velocity of the EOF has a plug-flow profile, which in turn could increase the average velocity and volumetric flow rate of the EOF in the open capillary tube. Furthermore, the modeling approach and the results presented in this work indicate a method for experimentally evaluating the possibility of having slip in the velocity of the EOF at the capillary wall.

Journal Article↗

PubMed2002

Novel general expressions that describe the behavior of the height equivalent of a theoretical plate in chromatographic systems involving electrically-driven and pressure-driven flows.

Novel general expressions are constructed and presented that describe the behavior of the height equivalent of a theoretical plate (plate height), H, as a function of the linear velocity, Vx, along the axis, x, of the column and the kinetic parameters that characterize the mass transfer and adsorption mechanisms in chromatographic columns. Open tube capillaries as well as columns packed with either non-porous or porous particles are studied. The porous particles could have unimodal or bimodal pore-size distributions and intraparticle convective fluid flow and pore diffusion are considered. The expressions for the plate height, H, presented in this work could be applicable to high-performance liquid chromatography (HPLC) and capillary electrochromatography (CEC) systems, and could be used together with experimental plate height, H, versus linear velocity, Vx, data to determine the values of the parameters that characterize intraparticle convective fluid flow and pore diffusion. Furthermore, chromatographic systems under unretained as well as under retained conditions are examined. The experimental values of the plate height, H, versus the linear velocity, Vx, for a CEC system involving charged porous silica C8 particles and an uncharged analyte are compared with the theoretical results for the plate height, H, obtained from the expressions presented in this work. The agreement between theory and experiment is good, and the results indicate that the magnitude of the intraparticle electroosmotic flow (EOF) in the pores of the particles is substantial while the pore diffusion coefficient was of small magnitude. But the overall intraparticle mass transfer resistance in these particles was low because of the significant contribution of the intraparticle EOF. Simulation results are also presented (i) for a hybrid HPLC-CEC system, and (ii) for different CEC systems involving open capillaries as well as packed columns having non-porous or porous particles. The analysis of the results indicates (a) the reasons for the superior performance exhibited by the hybrid HPLC-CEC system over the performance obtained when the system is operated only in the HPLC mode, and (b) the operational configuration and the properties that the structure of the porous particles would have to have in CEC systems involving uncharged or charged analytes under unretained or retained conditions in order to obtain high CEC efficiency (low values of the plate height, H).

Chromatography, High Pressure Liquid↗

PubMed2002

The interplay of diffusional and electrophoretic transport mechanisms of charged solutes in the liquid film surrounding charged nonporous adsorbent particles employed in finite bath adsorption systems.

A model that describes the diffusive and electrophoretic mass transport of the cation and anion species of a buffer electrolyte and of a charged adsorbate in the liquid film surrounding nonporous adsorbent particles in a finite bath adsorption system, in which adsorption of the charged adsorbate onto the charged surface of the nonporous particles occurs, is constructed and solved. The dynamic behavior of the mechanisms of this model explicitly demonstrates (a) the interplay between the diffusive and electrophoretic molar fluxes of the charged adsorbate and of the species of the buffer electrolyte in the liquid film surrounding the nonporous adsorbent particles, (b) the significant effect that the functioning of the electrical double layer has on the transport of the charged species and on the adsorption of the charged adsorbate, and (c) the substantial effect that the dynamic behavior of the surface charge density has on the functioning of the electrical double layer. It is found that at equilibrium, the value of the concentration of the charged adsorbate in the fluid layer adjacent to the surface of the adsorbent particles is significantly greater than the value of the concentration of the adsorbate in the finite bath, while, of course, the net molar flux of the charged adsorbate in the liquid film is equal to zero at equilibrium. This result is very different than that obtained from the conventional model that is currently used to describe the transport of a charged adsorbate in the liquid film for systems involving the adsorption of a charged adsorbate onto the charged surface of nonporous adsorbent particles; the conventional model (i) does not consider the existence of an electrical double layer, (ii) assumes that the transport of the charged adsorbate occurs only by diffusion in the liquid film, and (iii) causes at equilibrium the value of the charged adsorbate in the liquid layer adjacent to the surface of the particles to become equal to the value of the concentration of the charged adsorbate in the liquid of the finite bath. Furthermore, it was found that a maximum can occur in the dynamic behavior of the concentration of the adsorbate in the adsorbed phase when the value of the free molecular diffusion coefficient of the adsorbate is relatively large, because the increased magnitude of the synergistic interplay between the diffusive and electrophoretic molar fluxes of the adsorbate in the liquid film allows the adsorbate to accumulate (to be entrapped) in the liquid layer adjacent to the surface of the adsorbent particles faster than the concentrations of the electrolyte species, whose net molar fluxes are significantly hindered due to their opposing diffusive and electrophoretic molar fluxes, can adjust to account for the change in the surface charge density of the particles that arises from the adsorption of the charged adsorbate. The results presented in this work also have significant implications in finite bath adsorption systems involving the adsorption of a charged adsorbate onto the surface of the pores of charged porous adsorbent particles, because the diffusion and the electrophoretic migration of the charged solutes (cations, anions, and charged adsorbate) in the pores of the adsorbent particles will depend on the dynamic concentration profiles of the charged solutes in the liquid film surrounding the charged porous adsorbent particles. The results of the present work are also used to illustrate how the functioning of the electrical double layer could contribute to the development of inner radial humps (concentration rings) in the concentration of the adsorbate in the adsorbed phase of charged porous adsorbent particles.

Adsorption↗

PubMed2001

Quantitative analysis and synthesis of the electrokinetic mass transport and adsorption mechanisms of a charged adsorbate in capillary electrochromatography systems employing charged adsorbent particles.

The dynamic mathematical model of Grimes and Liapis [J. Colloid Interf. Sci. 234 (2001) 223] for capillary electrochromatography (CEC) systems operated under frontal chromatography conditions is extended to accommodate conditions in CEC systems where a positively charged analyte is introduced into a packed capillary column by a pulse injection (analytical mode of operation) in order to determine quantitatively the electroosmotic velocity, electrostatic potential and concentration profiles of the charged species in the double layer and in the electroneutral core region of the fluid in the interstitial channels for bulk flow in the packed chromatographic column as the adsorbate adsorbs onto the negatively charged fixed sites on the surface of the non-porous particles packed in the chromatographic column. Furthermore, certain key parameters are identified for both the frontal and analytical operational modes that characterize the performance of CEC systems. The results obtained from model simulations for CEC systems employing the analytical mode of operation indicate that: (a) for a given mobile liquid phase, the charged particles should have the smallest diameter, d(p), possible that still provides conditions for a plug-flow electroosmotic velocity field in the interstitial channels for bulk flow and a large negative surface charge density, deltao, in order to prevent overloading conditions; (b) sharp, highly resolute adsorption zones can be obtained when the value of the parameter gamma2min, which represents the ratio of the electroosmotic velocity of the mobile liquid phase under unretained conditions to the electrophoretic velocity of the anions (0>gamma2.min>-1), is very close to negative one, but the rate at which the solute band propagates through the column is slow; furthermore, as the solute band propagates across larger axial lengths, the desorption zone becomes more dispersed relative to the adsorption zone especially when the value of the parameter gamma2,max, which represents the ratio of the electroosmotic velocity of the mobile liquid phase under retained conditions to the electrophoretic velocity of the anions (0>gamma2,max>-1), is significantly greater than gamma2,min; (c) when the value of the equilibrium adsorption constant, K(A),3, is low, very sharp, highly resolved adsorption and desorption zones of the solute band can be obtained as well as fast rates of propagation of the solute band through the column; (d) sharp adsorption zones and fast propagation of the solute band can be obtained if the value of the mobility, v3, of the analyte is high and the value of the ratio v1/v3, where v1 represents the mobility of the cation, is low; however, if the magnitude of the mobility, v3, of the analyte is small, dispersed desorption zones are obtained with slower rates of propagation of the solute band through the column; (e) good separation of analyte molecules having similar mobilities and different adsorption affinities can be obtained in short operational times with a very small column length, L, and the resolution can be increased by providing values of gamma2,min and gamma2,max that are very close to negative one; and (f) the change in the magnitude of the axial current density, i(x), across the solute band could serve as a measurement for the rate of propagation of the solute band.

Adsorption↗

PubMed2000

Determination of the intraparticle electroosmotic volumetric flow-rate, velocity and Peclet number in capillary electrochromatography from pore network theory.

The results obtained from the pore network model employed in this work, clearly show that the magnitudes of the intraparticle electroosmotic volumetric flow-rate, Qintrap, and velocity, (v(intrap,x)), in the pores of the charged porous silica particles considered in this study are greater than zero. The intraparticle Peclet number, Pe(intra, of a solute in these charged porous silica particles would be greater than zero, and, in fact, the magnitude of the intraparticle Peclet number, Pe(intrap), of lysozyme is greater than unity for all the values of the pore connectivity, nT, of the intraparticle pores and of the applied electric potential difference per unit length, Ex, along the axis of the capillary column considered in this work. Furthermore, the values of the intraparticle electroosmotic volumetric flow-rate, Qintrap, and velocity, (v(intrap,x)), as well as the magnitude of the pore diffusion coefficient, Dp, of the solute increase as the value of the pore connectivity, nT, of the intraparticle pores increases. The intraparticle electroosmotic flow can contribute significantly, if the appropriate chemistry is employed in the mobile liquid phase and in the charged porous particles, in (i) decreasing the intraparticle mass transfer resistance, (ii) decreasing the dispersive mass transfer effects, and (iii) increasing the intraparticle mass transfer rates so that high column efficiency and resolution can be obtained.

Diffusion↗

PubMed2000

Modeling the velocity field of the electroosmotic flow in charged capillaries and in capillary columns packed with charged particles: interstitial and intraparticle velocities in capillary electrochromatography systems.

Mass transfer systems based on electrokinetic phenomena (i.e., capillary electrochromatography (CEC)) have shown practical potential in becoming powerful separation methods for the biotechnology and pharmaceutical industries. A mathematical model has been constructed and solved to describe quantitatively the profiles of the electrostatic potential, pressure, and velocity of the electroosmotic flow (EOF) in charged cylindrical capillaries and in capillary columns packed with charged particles. The results obtained from model simulations (i) provide significant physical insight and understanding with regard to the velocity profile of the EOF in capillary columns packed with charged porous particles which represent systems employed in CEC, (ii) provide the physical explanation for the experimental results which indicate that the velocity of the EOF in capillary columns packed with charged porous particles is a very weak function (it is almost independent) of the diameter of the particles, and (iii) indicate that the intraparticle velocity, nu(p,i), of the EOF can be greater than zero. The intraparticle Peclet number, Pe(int rap), for lysozyme was found to be greater than unity and this intraparticle convective mass transfer mechanism could contribute significantly, if the appropriate chemistry is employed in the mobile liquid phase and in the charged porous particles, in (a) decreasing the intraparticle mass transfer resistance, (b) decreasing the dispersive mass transfer effects, and (c) increasing the intraparticle mass transfer rates so that high column efficiency and resolution can be obtained. Furthermore, the results from model simulations indicate that for a given operationally permissible value of the applied electric potential difference per unit length, Ex, high values for the average velocity of the EOF can be obtained if (1) the zeta potential, zeta(p), at the surface of the particles packed in the column has a large negative magnitude, (2) the value of the viscosity, mu, of the mobile liquid phase is low, (3) the magnitude of the dielectric constant, epsilon, of the mobile liquid phase is reasonably large, and (4) the combination of the values of the concentration, C(infinity), of the electrolyte and of the dielectric constant, epsilon, provide a thin double layer. The theoretical results for the velocity of the EOF obtained from the solution of the model presented in this work were compared with the experimental values of the velocity of the EOF obtained from a fused-silica column packed with charged porous silica C8 particles. Systems with four different particle diameters and three different concentrations of the electrolyte were considered, and the magnitude of the electric field was varied widely. The agreement between theory and experiment was found to be good.

Chromatography, Micellar Electrokinetic Capillary↗

PubMed1985

Primary irritant contact dermatitis from synthetic pyrethroid insecticide exposure.

Synthetic pyrethroids are widely used insecticides with numerous applications, varying from food protection to general pest control. Humans are capable of tolerating greater acute and chronic exposures to the pyrethroids than to many other insecticides. An abnormal cutaneous sensation (paresthesia) is known to occur after dermal contact with the pyrethroids. Recent field studies have indicated that a primary irritant contact dermatitis may also develop. This investigation evaluated dermal irritancy from cutaneous synthetic pyrethroid application to albino rabbits. Through repeated daily applications of either fenvalerate or permethrin, a slight erythema was noted visually which correlated with increased cutaneous blood flow measured by laser Doppler velocimetry. Histopathological changes were also documented, but no significant differences were detected in edema or thermal variation.

Animals↗

PubMed1985

Synthetic pyrethroid insecticides: a dermatological evaluation.

Synthetic pyrethroids are lipophilic insecticides whose biological activity seems to be directly related to their chemical structure. In this investigation differences in cutaneous sensation were detected by human participants between synthetic pyrethroids with a cyano group in the (S)-configuration of the 3-phenoxybenzyl alcohol of their molecular structure (fenvalerate) and those that do not (permethrin). A strong relation was noted between insecticidal potency and degree of induced cutaneous sensation for the alpha-cyano and non-cyano pyrethroids, with a prominent difference between the two. No sensation was observed by any of the same participants on topical exposure to the inert ingredients of these agents. A linear correlation between concentration and degree of induced dysaethesia was observed for both pyrethroids. Regressing the cutaneous sensation on the common logarithm of concentration resulted in a regression equation of Y = 84.0 + 31.0X1 for fenvalerate and Y = 27.5 + 15.8X1 for permethrin. A highly efficacious therapeutic agent for pyrethroid exposure was noted to be dl-alpha tocopherol acetate. An impressive degree of inhibition of paraesthesia resulted from the topical application of vitamin E acetate, with a therapeutic index of almost 100%.

Dose-Response Relationship, Drug↗