Constant-pattern design method for displacement chromatography.

Displacement chromatography can be used for the purification of many types of chemicals and biochemicals. In the constant-pattern mode, this method can be used for concentrating and separating various mixtures, leading to higher yields and sorbent productivities than elution chromatography. There are, however, no commercial-scale applications of displacement chromatography. One major barrier is the difficulty in specifying the design variables for reaching a constant-pattern state. A second barrier is that productivity is limited when the feed mixture contains a minority component. In this study, a constant-pattern design method is developed to overcome the first barrier. Theoretical analyses and strategically chosen combinations of key dimensionless groups are used for reducing the multi-dimensional parameter space into a two-dimensional space. Systematic rate model simulations are used to find a general correlation, which divides the two-dimensional space into a transient region and a constant-pattern region. A predictive design method based on the general correlation is developed to find the designs for achieving required product purities and yields with the highest productivities. The design method was shown to increase significantly the productivities or yields for the separations of three binary mixtures. To overcome the second barrier, a multi-zone displacement chromatography method is presented for dividing the separation tasks in multiple zones. For a specific ternary mixture containing a minority component, the sorbent productivity for a two-zone design was 680 times higher than that of a single-column design. This method can be used for developing efficient displacement chromatography processes for purifying a wide range of complex mixtures.

Constant-pattern design method for the separation of ternary mixtures of rare earth elements using ligand-assisted displacement chromatography.

A constant-pattern design method for separating ternary mixtures using ligand-assisted displacement chromatography was developed for non-ideal systems. The general correlation for the minimum column length required to achieve the constant-pattern state for binary separations from our previous study was extended to ternary separations. Additionally, an equation for the yield of a target component as a function of key dimensionless groups was derived based on the constant-pattern mass transfer zone lengths. The column length and operating velocity solved from the two equations ensured the yields and the constant-pattern state for the target components. A selectivity weighted composition factor was developed to allow the design method to specify a minimum target yield for one or multiple components. The design method was verified using simulations and experiments for different targeted yields (70-95%), ligand concentrations (0.03-0.06 M), and feed compositions (1/12-5/6). The targeted yields were achieved or exceeded in all cases tested. The minimum column length required to achieve a constant pattern-state and the productivity of LAD are limited by the lowest selectivity or by a minority component with a low concentration in the feed, even when it does not have the lowest selectivity. Sacrificing the yields of minor components can increase the total productivity significantly. The productivities achieved using this design method are 839 times higher than literature results for ternary separations with the same purity and similar yields.

Key parameters controlling the development of constant-pattern isotachic trains of two rare earth elements in ligand-assisted displacement chromatography.

Ligand-assisted displacement chromatography (LAD) has been developed for separating rare earth elements since the 1950's. Isotachic displacement trains, which are similar to those in conventional displacement chromatography, were reported previously. However, there has been no general theory delineating the conditions required to form constant-pattern displacement trains for non-ideal systems (or systems with significant mass transfer resistance). The constant-pattern state is critical for obtaining pure products with high yield and high productivity. Without theoretical guidance, all the previous studies found the constant-pattern state by experimental trial and error, which was time consuming and costly. In this study, an efficient rate model and simulations of LAD were developed and verified with experimental data for non-ideal systems. Verified simulations were used to understand the mechanisms of separations and the transition from the transient state to the constant-pattern state. The key dimensionless factors affecting the transition for binary non-ideal systems were identified. Dimensionless groups were developed to reduce the number of variables. Simulations were used to find the transition points fromthe transient state to the constant-pattern state, which indicates the minimum dimensionless column lengths in the multi-parameter space. Strategic combination of the key dimensionless groups allows the minimum dimensionless column lengths to correlate with the combined groups in a two-dimensional diagram (or a map). The correlation curve divides the multi-dimensional space into the transient region and the constant-pattern region. The correlation was further verified with five sets of experiments. It can be used to find, without process simulations or experiments, the minimum column lengths for developing constant-pattern isotachic trains for non-ideal systems, which is useful for designing efficient ligand-assisted displacement chromatography at any scale.

Standing wave design and optimization of a simulated moving bed chromatography for separation of xylobiose and xylose under the constraints on product concentration and pressure drop.

The feasibility of a simulated moving bed (SMB) technology for the continuous separation of high-purity xylobiose (X2) from the output of a ß-xylosidase X1→X2 reaction has recently been confirmed. To ensure high economical efficiency of the X2 production method based on the use of xylose (X1) as a starting material, it is essential to accomplish the comprehensive optimization of the X2-separation SMB process in such a way that its X2 productivity can be maximized while maintaining the X2 product concentration from the SMB as high as possible in consideration of a subsequent lyophilization step. To address this issue, a suitable SMB optimization tool for the aforementioned task was prepared based on standing wave design theory. The prepared tool was then used to optimize the SMB operation parameters, column configuration, total column number, adsorbent particle size, and X2 yield while meeting the constraints on X2 purity, X2 product concentration, and pressure drop. The results showed that the use of a larger particle size caused the productivity to be limited by the constraint on X2 product concentration, and a maximum productivity was attained by choosing the particle size such that the effect of the X2-concentration limiting factor could be balanced with that of pressure-drop limiting factor. If the target level of X2 product concentration was elevated, higher productivity could be achieved by decreasing particle size, raising the level of X2 yield, and increasing the column number in the zones containing the front and rear of X2 solute band.

Speedy standing wave design and simulated moving bed splitting strategies for the separation of ternary mixtures with linear isotherms.

Simulated Moving Bed (SMB) has advantages over batch chromatography in terms of productivity and solvent efficiency. However, SMB applications in large scale production are still limited because of the many design parameters that must be specified and the multiple splitting strategies that can be implemented. To overcome these barriers, this study extends the Speedy Standing Wave Design (SSWD) method of Weeden and Wang for binary linear systems to ternary linear adsorption systems. The dimensionless operating parameters, sorbent productivity, and solvent efficiency can be quickly calculated without process simulations. SSWD also gives an overview of the productivity and solvent efficiency as a function of two key dimensionless groups. This overview can be used for optimization of separation costs and for comparison of splitting strategies. The SSWD method was verified using rate model simulations for the separation of three amino acids. The simulated yields agree with the SSWD target yields within 1% for all components. The example was also used to illustrate the key design rules for ternary separations. High productivity and solvent efficiency can be achieved with a large difference in the retention factors of the heavy key and light key, which are the components that define the split of the feed between extract and raffinate products. For ternary ideal systems, solvent efficiency is inversely proportional to the largest difference in retention factors. For this reason, minimizing the overall range of retention factors can significantly improve the solvent efficiency and product concentration without sacrificing productivity. If more than one SMB is needed, the easiest split should be done first for higher productivity, solvent efficiency, and product concentration. In the example case study, both the productivity and solvent efficiency were about an order of magnitude higher when the easiest split was done in the first ring. The SSWD method can be used to design a wide array of multi-component separations with high yield, productivity, and solvent efficiency.

Design of simulated moving bed for separation of fumaric acid with a little fronting phenomenon.

The production of fumaric acid through a biotechnological pathway has grown in importance because of its potential value in related industries. This has sparked an interest in developing an economically-efficient process for separation of fumaric acid (product of interest) from acetic acid (by-product). This study aimed to develop a simulated moving bed (SMB) chromatographic process for such separation in a systematic way. As a first step for this work, commercially available adsorbents were screened for their applicability to the considered separation, which revealed that an Amberchrom-CG71C resin had a sufficient potential to become an adsorbent of the targeted SMB. Using this adsorbent, the intrinsic parameters of fumaric and acetic acids were determined and then applied to optimizing the SMB process under consideration. The optimized SMB process was tested experimentally, from which the yield of fumaric-acid product was found to become lower than expected in the design. An investigation about the reason for such problem revealed that it was attributed to a fronting phenomenon occurring in the solute band of fumaric acid. To resolve this issue, the extent of the fronting was evaluated quantitatively using an experimental axial dispersion coefficient for fumaric acid, which was then considered in the design of the SMB of interest. The SMB experimental results showed that the SMB design based on the consideration of the fumaric-acid fronting could guarantee the attainment of both high purity (>99%) and high yield (>99%) for fumaric-acid product under the desorbent consumption of 2.6 and the throughput of 0.36L/L/h.

Speedy standing wave design, optimization, and scaling rules of simulated moving bed systems with linear isotherms.

Simulated Moving Bed (SMB) systems with linear adsorption isotherms have been used for many different separations, including large-scale sugar separations. While SMBs are much more efficient than batch operations, they are not widely used for large-scale production because there are two key barriers. The methods for design, optimization, and scale-up are complex for non-ideal systems. The Speedy Standing Wave Design (SSWD) is developed here to reduce these barriers. The productivity (PR) and the solvent efficiency (F/D) are explicitly related to seven material properties and 13 design parameters. For diffusion-controlled systems, the maximum PR or F/D is controlled by two key dimensionless material properties, the selectivity (α) and the effective diffusivity ratio (η), and two key dimensionless design parameters, the ratios of step time/diffusion time and pressure-limited convection time/diffusion time. The optimum column configuration for maximum PR or F/D is controlled by the weighted diffusivity ratio (η/α2). In general, high α and low η/α2 favor high PR and F/D. The productivity is proportional to the ratio of the feed concentration to the diffusion time. Small particles and high diffusivities favor high productivity, but do not affect solvent efficiency. Simple scaling rules are derived from the two key dimensionless design parameters. The separation of acetic acid from glucose in biomass hydrolysate is used as an example to show how the productivity and the solvent efficiency are affected by the key dimensionless material and design parameters. Ten design parameters are optimized for maximum PR or minimum cost in one minute on a laptop computer. If the material properties are the same for different particle sizes and the dimensionless groups are kept constant, then lab-scale testing consumes less materials and can be done four times faster using particles with half the particle size.

Improvement of the performances of a tandem simulated moving bed chromatography by controlling the yield level of a key product of the first simulated moving bed unit.

One of the trustworthy processes for ternary separation is a tandem simulated moving bed (SMB) process, which consists of two subordinate four-zone SMB units (Ring I and Ring II). To take full advantage of a tandem SMB as a means of recovering all three products with high purities and high economical efficiency, it is important to understand how the separation condition in Ring II is affected by that in Ring I, and further to reflect such point in the stage of designing a tandem SMB. In regard to such issue, it was clarified in this study that the Ring I factors affecting the Ring II condition could be represented by the yield level of a key product of Ring I (YkeyRingI). As the YkeyRingI level became higher, the amount of the Ring I key-product that was reloaded into Ring II was reduced, which affected favorably the Ring II separation condition. On the other hand, the higher YkeyRingI level caused a larger dilution for the stream from Ring I to Ring II, which affected adversely the Ring II separation condition. As a result, a minimum in the desorbent usage of a tandem SMB occurred at the YkeyRingI level where the two aforementioned factors could be balanced with each other. If such an optimal YkeyRingI level was adopted, the desorbent usage could be reduced by up to 25%. It was also found that as the throughput of a tandem SMB became higher, the factor related to the migration of the Ring I key-product into Ring II was more influential in the performances of a tandem SMB than the factor related to the dilution of the stream from Ring I to Ring II.

Highly efficient recovery of xylobiose from xylooligosaccharides using a simulated moving bed method.

Xylobiose (X2), which is currently available from xylooligosaccharides (XOS), has been reported to have outstanding prebiotic function and to be highly suitable for application in food industries. This has sparked an interest in the economical production of X2 of high purity (> 99%) in food and prebiotic industries. To address such issue, we developed a highly-efficient chromatographic method for the recovery of X2 from XOS with high purity and high recovery. As a first step for this work, an eligible adsorbent for a large-scale separation between X2 and other XOS components was selected. For the selected adsorbent, a single-column experiment was carried out to determine the intrinsic parameters of all the XOS components, which were then used in the optimal design of the continuous X2-recovery process based on a simulated moving bed (SMB) chromatographic method. Finally, the performance of the designed X2-recovery SMB process was verified by the relevant SMB experiments, which confirmed that the developed process in this study could recover X2 from XOS with the purity of 99.5% and the recovery of 92.3% on a continuous-separation mode. The results of this study will be useful in enabling the economical production of high-purity X2 on a large scale.

Continuous recovery of valine in a model mixture of amino acids and salt from Corynebacterium bacteria fermentation using a simulated moving bed chromatography.

The economical efficiency of valine production in related industries is largely affected by the performance of a valine separation process, in which valine is to be separated from leucine, alanine, and ammonium sulfate. Such separation is currently handled by a batch-mode hybrid process based on ion-exchange and crystallization schemes. To make a substantial improvement in the economical efficiency of an industrial valine production, such a batch-mode process based on two different separation schemes needs to be converted into a continuous-mode separation process based on a single separation scheme. To address this issue, a simulated moving bed (SMB) technology was applied in this study to the development of a continuous-mode valine-separation chromatographic process with uniformity in adsorbent and liquid phases. It was first found that a Chromalite-PCG600C resin could be eligible for the adsorbent of such process, particularly in an industrial scale. The intrinsic parameters of each component on the Chromalite-PCG600C adsorbent were determined and then utilized in selecting a proper set of configurations for SMB units, columns, and ports, under which the SMB operating parameters were optimized with a genetic algorithm. Finally, the optimized SMB based on the selected configurations was tested experimentally, which confirmed its effectiveness in continuous separation of valine from leucine, alanine, ammonium sulfate with high purity, high yield, high throughput, and high valine product concentration. It is thus expected that the developed SMB process in this study will be able to serve as one of the trustworthy ways of improving the economical efficiency of an industrial valine production process.

Size-exclusion simulated moving bed for separating organophosphorus flame retardants from a polymer.

Over 500,000t of flame retardants in electronic wastes are consigned to landfills each year. A room-temperature, size-exclusion simulated moving bed (SEC-SMB) was developed to recover high purity (>99%) flame retardants with high yield (>99%). The SSWD method for ternary mixtures was developed for SEC-SMB. Fourteen decision variables were optimized to obtain the lowest separation cost within 1min. The estimated cost is less than 10% of the purchase cost of the flame retardants. The estimated cost of the optimized SEC-SMB is less than 3% of that of a conventional batch SEC processes. Fast start-up methods were developed to reduce the SMB start-up time by more than 18-fold. SEC-SMB can be an economical method for separating small molecules from polymers.

Speedy standing wave design of size-exclusion simulated moving bed: Solvent consumption and sorbent productivity related to material properties and design parameters.

Size-exclusion simulated moving beds (SEC-SMB) have been used for large-scale separations of linear alkanes from branched alkanes. While SEC-SMBs are orders of magnitude more efficient than batch chromatography, they are not widely used. One key barrier is the complexity in design and optimization. A four-zone SEC-SMB for a binary separation has seven material properties and 14 design parameters (two yields, five operating parameters, and seven equipment parameters). Previous optimization studies using numerical methods do not guarantee global optima or explicitly express solvent consumption (D/F) or sorbent productivity (PR) as functions of the material properties and design parameters. The standing wave concept is used to develop analytical expressions for D/F and PR as functions of 14 dimensionless groups, which consist of 21 material and design parameters. The resulting speedy standing wave design (SSWD) solutions are simplified for two limiting cases: diffusion or dispersion controlled. An example of SEC-SMB for insulin purification is used to illustrate how D/F and PR change with the dimensionless groups. The results show that maximum PR for both diffusion and dispersion controlled systems is mainly determined by yields, equipment parameters, material properties, and two key dimensionless groups: (1) the ratio of step time to diffusion time and (2) the ratio of diffusion time to pressure-limited convection time. A sharp trade off of D/F and PR occurs when the yield is greater than 99%. The column configuration for maximum PR is analytically related to the diffusivity ratio and the selectivity. To achieve maximum sorbent productivity, one should match step time, diffusion time, and pressure-limited convection time for diffusion controlled systems. For dispersion controlled systems, the axial dispersion time should be about 10 times the step time and about 50 times the pressure-limited convection time. Its value can be estimated from given yields, material properties, and column configuration. Among the material properties, selectivity and particle size have the largest impact on D/F and PR. Particle size and 14 design parameters can be optimized for minimum D/F, maximum PR, or minimum cost on a laptop computer.

Simulated moving bed separation of agarose-hydrolyzate components for biofuel production from marine biomass.

The economically-efficient separation of galactose, levulinic acid (LA), and 5-hydroxymethylfurfural (5-HMF) in acid hydrolyzate of agarose has been a key issue in the area of biofuel production from marine biomass. To address this issue, an optimal simulated moving bed (SMB) process for continuous separation of the three agarose-hydrolyzate components with high purities, high yields, and high throughput was developed in this study. As a first step for this task, the adsorption isotherm and mass-transfer parameters of each component on the qualified adsorbent were determined through a series of multiple frontal experiments. The determined parameters were then used in optimizing the SMB process for the considered separation. Finally, the optimized SMB process was tested experimentally using a self-assembled SMB unit with four zones. The SMB experimental results and the relevant computer simulations verified that the developed process in this study was quite successful in the economically-efficient separation of galactose, LA, and 5-HMF in a continuous mode with high purities and high yields. It is thus expected that the developed SMB process in this study will be able to serve as one of the trustworthy ways of improving the economic feasibility of biofuel production from marine biomass.

Ligand-assisted elution chromatography for separation of lanthanides.

Lanthanides (Ln's) are the major components of rare earth elements, which are critical components of many high-value products. The ions of adjacent Ln's have the same valence and very similar ionic radii. They cannot be separated using conventional adsorption or ion exchange processes. Current production of high-purity Ln's is based on multiple sequential and parallel solvent extraction processes, which require large amounts of toxic solvents and result in serious negative impact on the environment. In this study, a ligand-assisted elution chromatography process for the separation of Ln's was developed for the first time for titania, which is a robust and inexpensive inorganic sorbent. A selective ligand for Ln's, ethylenediaminetetraacetic acid (EDTA), was found to adsorb on the sorbent. The adsorbed EDTA became strong adsorption sites for the Ln's. Desorption of Ln's was driven by reversible reactions of Ln's with EDTA in the mobile phase. The overall sorbent selectivity for the reaction and adsorption process was approximately equal to the ratio of the sorbent selectivity to the ligand selectivity. The separation mechanisms were tested and verified using rate model simulations and experimental data for the separation of praseodymium (Pr), neodymium (Nd), and samarium (Sm). Simulations based on the model were used to design efficient linear gradient elution and stepwise elution processes. The purity and yield of all three Ln's were found to be above 95% in the designed processes. Stepwise elution can be implemented in a continuous process for increasing sorbent productivity and reducing costs for large-scale separation. Ligand assisted elution processes are much simpler and more environmentally friendly than the conventional solvent extraction processes.

Method for efficient recovery of high-purity polycarbonates from electronic waste.

More than one million tons of polycarbonates from waste electrical and electronic equipment are consigned to landfills at an increasing rate of 3-5% per year. Recycling the polymer waste should have a major environmental impact. Pure solvents cannot be used to selectively extract polycarbonates from mixtures of polymers with similar properties. In this study, selective mixed solvents are found using guidelines from Hansen solubility parameters, gradient polymer elution chromatography, and solubility tests. A room-temperature sequential extraction process using two mixed solvents is developed to recover polycarbonates with high yield (>95%) and a similar purity and molecular weight distribution as virgin polycarbonates. The estimated cost of recovery is less than 30% of the cost of producing virgin polycarbonates from petroleum. This method would potentially reduce raw materials from petroleum, use 84% less energy, reduce emission by 1-6 tons of CO2 per ton of polycarbonates, and reduce polymer accumulation in landfills and associated environmental hazards.

Insights into chromatographic enantiomeric separation of allenes on cellulose carbamate stationary phase.

Allenes are cumulenes with three contiguous carbons linked together through double bonds. 1,3-disubstituted allenes are not superimposable on their mirror image; as a consequence they are chiral. Chiral allenes are increasingly important in organic synthesis due to their interesting reactivity. Because of their applications in the field of asymmetric catalysis and in the pharmaceutical industry their optical purity is always a parameter which needs to be determined. In this article, we report the enantiomeric separation of hexa-3,4-diene-3-ylbenzene, an aromatic allene, on a cellulose carbamate (Chiralcel OD-3) stationary phase, using heptane as the mobile phase. Spectroscopic studies using infrared (IR) and vibrational circular dichroism revealed that, in the presence of heptane, the stationary phase undergoes a conformational change due to intermolecular H-bonding between the CO and NH of the neighboring polymer chains. Van't Hoff plots for the retention factor, k, showed that the retention of the two enantiomers is dominated by the enthalpy, while the plot for the selectivity, α, is entropy driven. This suggests that the enantioselectivity is a result of inclusion of the enantiomers in the cavities of the chrial stationary phase. VCD spectra, along with density functional theory calculation (DFT) of the interaction between each enantiomer and the chiral stationary phase, supported the chromatographic elution order findings.

A new general method for designing affinity chromatography processes.

Affinity chromatography is widely used for selectively recovering a target solute from a complex mixture. The challenge in designing a capture process is to achieve high yield, high column utilization, and high sorbent productivity while satisfying loading time and pressure limit requirements. The conventional design method based on constant-pattern waves cannot be used for small feed batches or short columns, which do not allow the formation of such waves. Other design methods in the literature rely on simulations or experimental trials, and can be time-consuming and costly. In this study, a new design method with no need of simulations is developed for constant pattern and non-constant pattern systems with Langmuir isotherms. Given feed conditions, loading time, and desired yield, the design requires only the values of certain intrinsic parameters, which can be estimated from a small number of bench-scale experiments. The minimum column volume for capture can be estimated either graphically or analytically. The method is tested with Protein A chromatography data for antibody purification. It is applicable to a wide range of production scales and design requirements. The effects of material properties, feed composition, feed volume, and design requirements on the column volume for capture can be found graphically. When the loading time relative to a characteristic diffusion time is 0.5 or larger, the minimum column volume approaches that of an ideal system. A short loading time increases sorbent productivity, but increases the minimum column volume. A high feed concentration, a high equilibrium capacity, and a small diffusion time relative to the loading time can reduce the minimum column volume and increase productivity.

Effect of alcohol aggregation on the retention factors of chiral solutes with an amylose-based sorbent: modeling and implications for the adsorption mechanism.

Various displacement models in the literature have been widely used for understanding the adsorption mechanisms of solutes in various chromatography systems. The models were used for describing the often-observed linear plots of the logarithms of the retention factor versus the logarithms of the polar modifier concentration CI(0). The slopes of such a plot was inferred to be equal to the number of the displaced modifier molecules upon adsorption of one solute molecule, and were generally found to be greater than 1. In this study, the retention factors of four structurally related chiral solutes, ethyl lactate (EL), methyl mandelate (MM), benzoin (B), and pantolactone (PL), were measured for the amylose tris[(S)-α-methylbenzylcarbamate] sorbent, or AS, as a function of the concentration of isopropanol (IPA) in n-hexane. With increasing IPA concentration CI(0), the slopes increase from less than 1, at a concentration range from 0.13 to 1.3M, to slightly more than 1 at higher concentrations. Such slopes cannot be explained by the conventional retention models. It was found previously for monovalent solutes that such slopes can only be explained when the aggregation of the mobile phase modifier, isopropyl alcohol, was accounted for. A new retention model is presented here, accounting for alcohol aggregation, multivalent solute adsorption, multivalent solute-alcohol complexation, alcohol adsorption, and solute intra hydrogen-bonding, which occur in these four solutes. The slope is found to be controlled by three key dimensionless groups, the fraction of the sorbent binding sites covered by IPA, the fraction of the solute molecules in complex form, and the fraction of the IPA molecules in aggregate form. The limiting slope at a very high IPA concentration is equal to the value of (x+y)/n, where x is the number of the solute-sorbent binding sites and y is the number of the alcohol molecules in the solute-alcohol complex, and n is the alcohol aggregation number. The model was tested with the HPLC data of two sets of chiral solutes, one set of new data presented here and of one set of literature data by Gyimesi-Forrás et al. (2009), for which there is no known intramolecular H-bonding. For the first set of solutes, the values of the equilibrium constants for intramolecular hydrogen bonding were calculated from our previous IR data. The value of the parameter y was fixed on the basis of the number of the solute functional groups, IR data, and the results of DFT and MD simulations. The retention factors in pure hexane (k0) were found experimentally for EL, MM, and B; for PL they were estimated from the data. Then the values of x and the complexation equilibrium constants were estimated. The model fits fairly well our new data, and less well the more-limited literature data, for which the k0 values were unavailable, and the retention factors were obtained over a narrow range of IPA concentrations. For EL and PL, results of infrared spectroscopy, density functional theory, and molecular dynamics simulations indicated strong solute-IPA complexation, and multiple solute-sorbent binding sites, which are consistent with the fitting results. Hence, the new model has been shown to be more reliable than the previous models for estimating the numbers of the potential binding sites of multivalent solutes.

Capture chromatography for Mo-99 recovery from uranyl sulfate solutions: minimum-column-volume design method.

Molybdenum-99 (Mo-99), generated from the fission of Uranium-235 (U-235), is the radioactive parent of the most widely used medical isotope, technetium-99m (Tc-99m). An efficient, robust, low-pressure process is developed for recovering Mo-99 from uranyl sulfate solutions. The minimum column volume and the maximum column length for required yield, pressure limit, and loading time are determined using a new graphical method. The method is based on dimensionless groups and intrinsic adsorption and diffusion parameters, which are estimated using a small number of experiments and simulations. The design is tested with bench-scale experiments with titania columns. The results show a high capture yield and a high stripping yield (95±5%). The design can be adapted to changes in design constraints or the variations in feed concentration, feed volume, or material properties. The graph shows clearly how the column utilization is affected by the required yield, loading time, and pressure limit. The cost effectiveness of various sorbent candidates can be evaluated based on the intrinsic parameters. This method can be used more generally for designing other capture chromatography processes.