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1.
J Chromatogr A ; 1722: 464904, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38626539

RESUMO

A continuously regenerated cationic impurity removal device (CR-CRD) has been fabricated and applied for ion chromatography (IC). The removal of cationic impurities is realized by electrodialytically replacing the cationic impurities with hydronium ions. The device is configured in a sandwich structure and the central eluent channel is respectively isolated from both electrodes by stacked cation exchange membranes and a bipolar membrane (BPM) plus stacked anion exchange membranes. The eluent channel is packed with cation exchange resins in hydronium form and their continuous regeneration can be achieved by electrodialysis. A desirable feature of the device is gas-free, and no degasser is required. It showed sufficient ability to remove cationic impurities, as indicated by > 99.9 % removal of 10 mL of 1 mM LiOH solution injected (∼10 µmol) or continuous removal of 1 mM LiOH solution at the flow rate of 1 mL/min (1 µmol/min). A useful application was for sample pretreatment in nuclear power industry, by eliminating strong matrix interference of the sample containing LiOH (1 mM) and boric acid (2000 mg/L) with trace anion analysis.


Assuntos
Cátions , Cromatografia por Troca Iônica/métodos , Cromatografia por Troca Iônica/instrumentação , Cátions/química , Membranas Artificiais , Resinas de Troca de Cátion/química , Desenho de Equipamento
2.
J Chromatogr A ; 1718: 464717, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38354506

RESUMO

Although antibody fragments are a critical impurity to remove from process streams, few platformable purification techniques have been developed to this end. In this work, a novel size-exclusion-mixed-mode (SEMM) resin was characterized with respect to its efficacy in mAb fragment removal. Inverse size-exclusion chromatography showed that the silica-based resin had a narrow pore size distribution and a median pore radius of roughly 6.2 nm. Model-based characterization was carried out with Chromatography Analysis and Design Toolkit (CADET), using the general rate model and the multicomponent Langmuir isotherm. Model parameters were obtained from fitting breakthrough curves, performed at multiple residence times, for a mixture of mAb, aggregates, and an array of fragments (varying in size). Accurate fits were obtained to the frontal chromatographic data across a range of residence times. Model validation was then performed with a scaled-up column, altering residence time and feed composition from the calibration run. Accurate predictions were obtained, thereby illustrating the model's interpolative and extrapolative capabilities. Additionally, the SEMM resin achieved 90% mAb yield, 37% aggregate removal, 29% [Formula: see text] removal, 54% Fab/Fc removal, 100% Fc fragments removal, and a productivity of 72.3 g mAbL×h. Model predictions for these statistics were all within 5%. Simulated batch uptake experiments showed that resin penetration depth was directly related to protein size, with the exception of the aggregate species, and that separation was governed by differential pore diffusion rates. Additional simulations were performed to characterize the dependence of fragment removal on column dimension, load density, and feed composition. Fragment removal was found to be highly dependent on column load density, where optimal purification was achieved below 100 mg protein/mL column. Furthermore, fragment removal was dependent on column volume (constant load mass), but agnostic to whether column length or diameter was changed. Lastly, the dependence on feed composition was shown to be complex. While fragment removal was inversely related to fragment mass fraction in the feed, the extent depended on fragment size. Overall, the results from this study illustrated the efficacy of the SEMM resin in fragment and aggregate removal and elucidated relationships with key operational parameters through model-based characterization.


Assuntos
Anticorpos Monoclonais , Fragmentos de Imunoglobulinas , Cromatografia em Gel , Difusão , Resinas de Troca de Cátion/química
3.
J Chromatogr A ; 1717: 464672, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38350166

RESUMO

The monoclonal antibody (mAb) industry is becoming increasingly digitalized. Digital twins are becoming increasingly important to test or validate processes before manufacturing. High-Throughput Process Development (HTPD) has been progressively used as a tool for process development and innovation. The combination of High-Throughput Screening with fast computational methods allows to study processes in-silico in a fast and efficient manner. This paper presents a hybrid approach for HTPD where equal importance is given to experimental, computational and decision-making stages. Equilibrium adsorption isotherms of 13 protein A and 16 Cation-Exchange resins were determined with pure mAb. The influence of other components in the clarified cell culture supernatant (harvest) has been under-investigated. This work contributes with a methodology for the study of equilibrium adsorption of mAb in harvest to different protein A resins and compares the adsorption behavior with the pure sample experiments. Column chromatography was modelled using a Lumped Kinetic Model, with an overall mass transfer coefficient parameter (kov). The screening results showed that the harvest solution had virtually no influence on the adsorption behavior of mAb to the different protein A resins tested. kov was found to have a linear correlation with the sample feed concentration, which is in line with mass transfer theory. The hybrid approach for HTPD presented highlights the roles of the computational, experimental, and decision-making stages in process development, and how it can be implemented to develop a chromatographic process. The proposed white-box digital twin helps to accelerate chromatographic process development.


Assuntos
Anticorpos Monoclonais , Cromatografia , Anticorpos Monoclonais/química , Resinas de Troca de Cátion , Adsorção , Proteína Estafilocócica A/química , Cromatografia por Troca Iônica/métodos
4.
Water Res ; 247: 120806, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37925860

RESUMO

Fe based chemically enhanced primary sedimentation (CEPS) is an effective method of capturing the colloidal particles and inorganic phosphorous (P) from wastewater but also produces Fe-CEPS sludge. Anaerobic digestion is recommended to treat the sludge for energy and phosphorus recovery. However, the aggregated sludge flocs caused by the coagulation limited sludge hydrolysis and P release during anaerobic digestion process. In this study, cation exchange resin (CER) was employed during anaerobic digestion of Fe-CEPS sludge with aims of prompting P release and carbon recovery. CER addition effectively dispersed the sludge flocs. However, the greater dispersion of sludge flocs could not translate to higher sludge hydrolysis. The maximum hydrolysis and acidification achieved at lower CER dosage of 0.5 g CER/g TS. It was observed that the extents of sludge hydrolysis and acidification had a strongly negative correlation with the organic binding iron (OBI) concentration. The presence of CER during anaerobic digestion favored Fe(III) reduction to Fe(II), and then further induced iron phase transformation, leading to the OBI formation from the released organic matters. Meanwhile, higher CER dosage resulted in higher P release efficiency and the maximum efficiency at 4 g CER/g TS was four times than that of the control. The reduction of BD-P, NaOH-P and HCl-P in solid phase contributed most P release into the supernatant. A new two-stage treatment process was further developed to immigrate the OBI formation and improve the carbon recovery efficiency. Through this process, approximately 45% of P was released, and 63% of carbon was recovered as methane from Fe-CEPS sludge via CER pretreatment.


Assuntos
Resinas de Troca de Cátion , Esgotos , Anaerobiose , Compostos Férricos , Eliminação de Resíduos Líquidos/métodos , Ferro , Carbono , Metano
5.
Chemosphere ; 341: 140102, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37683954

RESUMO

In decades, anaerobic fermentation with short-chain fatty acids (SCFAs) recovery from excess sludge have attained rising attention. However, rigid particulate organic matter (POMs) structure with slow hydrolysis limited anaerobic fermentation performance of excess sludge. Remarkable sludge hydrolysis performance was supposed to be achievable by the synchronous EPS repture and microbial cell lysis. This study clarified the improvement of overall anaerobic fermentation performance by combination treatment of lysozyme (Lyso) catalysis and metal regulation (MR). The Lyso + MR treatment triggered EPS rupture by protein structure deflocculation while catalyzing microbial cell lysis, which promoted massive extracellular and intracellular POMs hydrolysis. As a result, a significant amount of SCOD (5646.67 mg/L) was produced. Such endogenous organic matters hydrolysis led to considerable SCFAs accumulation (3651.14 mg COD/L) through 48-h anaerobic fermentation at 1.75 g/g SS cation-exchange resin and Lyso dosage of 10% (w/w), which was 5.945 times higher than that in the control. Additionally, it suggested that most of the recovered SCFAs remained in fermentative liquid after chemical conditioning and mechanical dewatering towards solid-liquid separation, which provided considerable economic benefit of 363.6-1059.1 CNY/ton SS.


Assuntos
Resinas de Troca de Cátion , Esgotos , Hidrólise , Esgotos/química , Muramidase , Fermentação , Ácidos Graxos Voláteis , Biopolímeros , Concentração de Íons de Hidrogênio , Anaerobiose
6.
J Chromatogr A ; 1707: 464293, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37579702

RESUMO

Purification of extracellular vesicles for research and therapeutic applications requires updated methodology to address the limitations of traditional ultracentrifugation and other size-based separation techniques. Their downfalls include induced extracellular vesicle aggregation, low yields, poor scalability and one-dimensionality of the separation process, as the size or sedimentation speed of extracellular vesicles is often the only selection criterion. Ion exchange chromatography is a promising alternative or supplementary method candidate, as it offers a different approach for extracellular vesicle separation, which is surface charge. For now, mostly anion exchange chromatography has been evaluated for extracellular vesicle purification, as it successfully relies on the strongly negative surface charge of extracellular vesicles. However, as extracellular vesicles are very complex in their structure, also cation exchange chromatography could be applicable, due to individual cationic domains on the extracellular vesicle surface. Here, we compare anion exchange chromatography to different types of cation exchange chromatography for the purification of platelet extracellular vesicle samples also containing plasma-derived impurities. We found that the choice of resin structure used for cation exchange chromatography is critical for binding platelet extracellular vesicles, as a conventional-type cation exchanger was found to only capture and elute less than 20% of extracellular vesicles. With the tentacle-type resin, it was possible to obtain comparable platelet extracellular vesicle yields (over 90%) with cation exchange chromatography compared to anion exchange chromatography, as well as superior purity, especially when it was combined to conventional cation exchange resin.


Assuntos
Vesículas Extracelulares , Ligantes , Cromatografia por Troca Iônica/métodos , Ultracentrifugação , Vesículas Extracelulares/química , Resinas de Troca de Cátion/química
7.
AAPS PharmSciTech ; 24(5): 114, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37127745

RESUMO

The purpose of this investigation was to formulate and evaluate the interaction between cation exchange resins and verapamil hydrochloride. The uptake studies were conducted using the rotating bottle apparatus. The Langmuir-like equation was applied to the experimental data and the maximum drug loading was determined from the Langmuir-like parameters. The drug-resin complexes were evaluated using XRD, SEM, and particle size analysis. Release studies were performed using USP dissolution apparatus 2. The resin with the lowest percentage of cross-linking had the highest uptake capacity. The percent increase in particle size due to complexation was found to be associated with drug loading; the highest drug loading had the highest increase in particle size. The X-ray diffraction patterns of the resins and the drug-resin complexes showed that they were both amorphous. The maximum drug release was approximately 40% when conventional dissolution testing was used. Results showed that sink conditions could not be maintained using conventional dissolution methods. Maximum drug release increased dramatically by increasing the volume of samples withdrawn and fresh dissolution medium added. Excellent correlation was obtained between sample volume and drug release rate with an R-value of 0.988. Particle diffusion-controlled model and film diffusion-controlled model were both applied to the experimental data. The results indicated that the rate-limiting step is the diffusion of the exchanging cations through the liquid film. The modified release formulation was prepared successfully and correlated very well with the USP monograph for verapamil hydrochloride extended release capsules.


Assuntos
Resinas de Troca Iônica , Verapamil , Preparações de Ação Retardada , Verapamil/química , Resinas de Troca Iônica/química , Liberação Controlada de Fármacos , Resinas de Troca de Cátion
8.
Chemosphere ; 331: 138837, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37146777

RESUMO

Cationic exchange resins (CERs) were applied for purification and clarifying process of radioactive wastewater in nuclear industry, which was a kind of sulfur-containing organic material. Molten-salt oxidation (MSO) method can be applied for the treatment of spent CERs and the absorption of acid gas (such as SO2). The experiments about the molten salt destruction of the original resin and Cu ions doped resin were conducted. The transformation of organic sulfur in Cu ions doped resin was investigated. Compared with the original resin, the content of tail gas (such as CH4, C2H4, H2S and SO2) released from the decomposition of Cu ions doped resin was relatively high at 323-657 °C. Sulfur elements in the form of sulfates and copper sulfides were fixed in spent salt through XRD analysis. The XPS result revealed that the portion of functional sulfonic acid groups (-SO3H) in Cu ions doped resin was converted into sulfonyl bridges (-SO2-) at 325 °C. With the enhancement of temperature, sulfonyl bridges (-SO2-) were further decomposed to sulfoxides sulfur (-SO-) and organic sulfide sulfur. The destruction of thiophenic sulfur to H2S and CH4 was prompted by copper ions in copper sulfide. Sulfoxide were oxidized to the sulfone sulfur in molten salt. Sulfones sulfur consumed by reduction of Cu ions at 720 °C was more than it produced by oxidation of sulfoxide through XPS analysis, and the relative proportion of sulfone sulfur was 16.51%.


Assuntos
Resinas de Troca de Cátion , Cobre , Enxofre , Sulfetos , Cloreto de Sódio , Sulfonas , Sódio , Lítio
9.
J Sci Food Agric ; 103(9): 4676-4684, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36905092

RESUMO

BACKGROUND: Caffeic acid (CA) has anti-oxidation and anti-inflammatory. However, the poor hydrophilicity of CA limits its biological activities. In this work, hydrophilic glyceryl monocaffeate (GMC) was synthesized by esterification using different caffeoyl donors (deep eutectic solvent and solid CA). Cation-exchange resins were used as the catalysts. The effects of reaction conditions were also investigated. RESULTS: The mass transfer limitation of esterification was eliminated using deep eutectic solvent. Compared with the previous catalysts (immobilized lipase Novozym 435), an economic cation-exchange resin, Amberlyst-35 (A-35), showed good catalytic performance for GMC preparation. The activation energies of GMC synthesis and CA conversion were 43.71 kJ mol-1 and 43.07 kJ mol-1 , respectively. The optimal reaction conditions were a temperature reaction of 90 °C, catalyst load of 7%, glycerol/CA molar ratio of 5:1 (mol mol-1 ), and reaction time of 24 h, which resulted in a maximum GMC yield and CA conversion of 69.75 ± 1.03% and 82.23 ± 2.02%, respectively. CONCLUSION: The results of the work showed a promising alternative for the synthesis of GMC. © 2023 Society of Chemical Industry.


Assuntos
Resinas de Troca de Cátion , Solventes Eutéticos Profundos , Solventes , Lipase/metabolismo , Esterificação , Interações Hidrofóbicas e Hidrofílicas , Enzimas Imobilizadas/metabolismo , Cátions
10.
J Chromatogr A ; 1695: 463934, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-36972662

RESUMO

Cation-exchange stationary phases were characterized in different chromatographic modes (HILIC, RPLC, IC) and applied to the separation of non-charged hydrophobic and hydrophilic analytes. The set of columns under investigation included both commercially available cation-exchangers and self-prepared PS/DVB-based columns, the latter consisting of adjustable amounts of carboxylic and sulfonic acid functional groups. The influence of cation-exchange site and polymer substrate on the multimodal properties of cation-exchangers was identified using selectivity parameters, polymer imaging and excess adsorption isotherms. Introducing weakly acidic cation-exchange functional groups to the unmodified PS/DVB-substrate effectively reduced hydrophobic interactions, whilst a low degree of sulfonation (0.09 to 0.27% w/w sulphur) mainly influenced electrostatic interactions. Silica substrate was found to be another important factor for inducing hydrophilic interactions. The presented results demonstrate that cation-exchange resins are suitable for mixed-mode applications and offer versatile selectivity.


Assuntos
Cromatografia , Dióxido de Silício , Cromatografia/métodos , Dióxido de Silício/química , Resinas de Troca de Cátion , Interações Hidrofóbicas e Hidrofílicas , Cátions/química , Polímeros , Cromatografia por Troca Iônica/métodos
11.
Biotechnol Bioeng ; 120(6): 1592-1604, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36814367

RESUMO

There is significant interest in identifying the preferred binding domains of biological products to various chromatographic materials. In this work, we develop a biophysical technique that uses diethyl pyrocarbonate (DEPC) based covalent labeling in concert with enzymatic digestion and mass spectrometry to identify the binding patches for proteins bound to commercially available multimodal (MM) cation exchange chromatography resins. The technique compares the changes in covalent labeling of the protein in solution and in the bound state and uses the differences in this labeling to identify residues that are sterically shielded upon resin binding and, therefore, potentially involved in the resin binding process. Importantly, this approach enables the labeling of many amino acids and can be carried out over a pH range of 5.5-7.5, thus enabling the protein surface mapping at conditions of interest in MM cation exchange systems. The protocol is first developed using the model protein ubiquitin and the results indicate that lysine residues located on the front face of the protein show dramatic changes in DEPC labeling while residues present on other regions have minimal or no reductions. This indicates that the front face of ubiquitin is likely involved in resin binding. In addition, surface property maps indicate that the hypothesized front face binding region consists of overlapping positively charged and hydrophobic patches. The technique is then employed with an IgG1 FC and the results indicate that residues on the CH 2-CH 3 interface and the hinge are significantly sterically shielded upon binding to the resin. Further, these regions are again associated with significant overlap of positively charged and hydrophobic patches. On the other hand, while, residues on the CH 2 and the front face of the IgG1 FC also exhibited some changes in DEPC labeling upon binding, these regions have less distinct charged and hydrophobic patches. Importantly, the hypothesized binding patches identified for both ubiquitin and FC using this approach are shown to be consistent with previously reported NMR studies. In contrast to NMR, this new approach enables the identification of preferred binding regions without the need for isotopically labeled proteins or chemical shift assignments. The technique developed in this work sets the stage for the evaluation of the binding domains of a wide range of biological products to chromatographic surfaces, with important implications for designing biomolecules with improved biomanufacturability properties.


Assuntos
Resinas de Troca de Cátion , Ubiquitina , Ubiquitina/química , Imunoglobulina G , Espectrometria de Massas , Lisina
12.
J Chromatogr A ; 1689: 463730, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36592480

RESUMO

The objective of this scientific work was to model and simulate the complex anti-Langmuir elution behavior of a bispecific monoclonal antibody (bsAb) under high loading conditions on the strong cation exchange resin POROS™ XS. The bsAb exhibited anti-Langmuirian elution behavior as a consequence of self-association expressed both in uncommon retentions and peak shapes highly atypical for antibodies. The widely applied Steric Mass Action (SMA) model was unsuitable here because it can only describe Langmuirian elution behavior and is not able to describe protein-protein interactions in the form of self-association. For this reason, a Self-Association SMA (SAS-SMA) model was applied, which was extended by two activity coefficients for the salt and protein in solution. This model is able to describe protein-protein interactions in the form of self-dimerization and thus can describe anti-Langmuir elution behavior. Linear gradient elution (LGE) experiments were carried out to obtain a broad dataset ranging from pH 4.5 to 7.3 and from 50 to 375 mmol/L Na+ for model parameter determination. High loading LGE experiments were conducted with an increasing load from 0.5 up to 75.0 mgbsAb/mLresin. Thereby, pH-dependent empirical correlations for the activity coefficient of the solute protein, for the equilibrium constant of the self-dimerization process and for the shielding factor could be set up and ultimately incorporated into the SAS-SMA model. This pH-dependent SAS-SMA model was thus able to simulate anti-Langmuir behavior over extended ranges of pH, counterion concentration, and column loading. The model was confirmed by experimental verification of simulated linear pH gradient elutions up to a load of 75.0 mgbsAb/mLresin.


Assuntos
Anticorpos Biespecíficos , Anticorpos Monoclonais , Cromatografia por Troca Iônica , Anticorpos Monoclonais/metabolismo , Cloreto de Sódio , Cátions , Resinas de Troca de Cátion , Concentração de Íons de Hidrogênio
13.
Environ Sci Pollut Res Int ; 30(6): 16729-16740, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36525196

RESUMO

Molten salt oxidation (MSO) is an advanced method for waste resins treatment; nevertheless, the research about gas product variations of resins under different stoichiometric air feed coefficient (α) is rare. The optimal working condition of hazardous waste disposal is obtained through thermodynamic equilibrium calculation, and the method to improve the treatment efficiency is found to guide the optimization of the actual experiment. In this paper, Fact Sage was used to calculate the oxidation products of cation exchange resins (CERs) at different temperatures and α, focusing on the similarities and differences through the contents of CO, CH4, CO2, and SO2 during the oxidation of CERs, the MSO of CERs, and the theoretical calculation. The results indicated that the gas products of the calculation and reality of the oxidation process of CERs are quite different, while the CO contents of CERs during MSO are close to the calculated values. The main reason for this consequence is that in the oxidation process of CERs, the S in the sulfonic acid group will form thermally stable C-S with the styrene-divinylbenzene skeleton. Moreover, the introduction of carbonate can promote the destruction of C-S and absorb SO2 as sulfate, weakening the influence of C-S on the oxidation products of CERs. The gas chromatograph results indicated that the SO2 content is reduced from 0.66% in the process of CERs oxidation to 0.28% in MSO of CERs. When 1.25 times stoichiometric air feed coefficient is fed, the sulfate content in the carbonate is the highest at 900 °C, which is 23.4%.


Assuntos
Resinas de Troca de Cátion , Gases , Cloreto de Sódio , Cloreto de Sódio na Dieta , Carbonatos , Oxigênio
14.
Am J Emerg Med ; 65: 59-64, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36586223

RESUMO

BACKGROUND: Hyperkalemia accounts for over 800,000 emergency department (ED) visits in the United States each year, and has been associated with significant morbidity and mortality likely due to fatal cardiac dysrhythmias. Previous studies have demonstrated reductions in mortality when potassium levels are normalized in the ED. Cation exchange resins, such as sodium polystyrene sulfonate (SPS) and sodium zirconium cyclosilicate (SZC), may be administered as a means of definitively eliminating potassium from the body. This practice is based on physician preference and is not supported by high quality data. Two studies evaluating the use of cation exchange resins versus standard treatment in the ED demonstrated reductions in serum potassium levels within two hours of administration; however, there have been no published studies investigating these agents in a head-to-head comparison. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of SPS versus SZC in lowering serum potassium in patients presenting to the ED with hyperkalemia. METHODS: This was an institutional review board-approved, retrospective cohort study conducted at a single-site ED. All patients who received medications under the "ED Hyperkalemia Treatment" order set between August 26, 2019 and May 13, 2021 were eligible for inclusion. The primary outcome was the change in serum potassium from baseline to first repeat level following SPS or SZC administration in the ED. RESULTS: A total of 885 patients were screened with 54 patients in the SPS group and 51 patients in the SZC group included in the final analyses. The mean change in serum potassium from baseline to first repeat level following administration of the cation exchange resin was -1.1 mEq/L for both groups. CONCLUSION: Administration of SPS or SZC for the treatment of hyperkalemia in the ED resulted in similar reductions in serum potassium.


Assuntos
Hiperpotassemia , Humanos , Hiperpotassemia/tratamento farmacológico , Resinas de Troca de Cátion/uso terapêutico , Estudos Retrospectivos , Potássio
15.
J Chromatogr A ; 1687: 463696, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36508767

RESUMO

Immunoglobulins of complex formats possess great potential for increased biopharmaceutical efficacy. However, challenges arise during their purification as the removal of numerous product-related impurities typically requires several expensive chromatographic steps. Additionally, many complex antibody formats have a high hydrophobicity which impairs the use of conventional mixed mode chromatography. In the present study, both of these challenges were addressed through the development of an innovative mixed mode resin with 2-amino-4methylpentanoic acid ligands that combines weak cation exchange with moderate hydrophobic interactions. Supported by high throughput partition coefficient screens for identification of preferable pH and salt concentration ranges in bind and elute mode, this mixed mode resin successfully demonstrated efficient impurity separation from an extremely hydrophobic bispecific antibody with a single unit operation. High purity (>97%) was obtained as a result of significant reduction of product-related impurities as well as process-related host cell proteins (>3 log scale), while maintaining satisfactory recovery (70%). This also supports that highly hydrophobic antibody formats can be efficiently purified using a resin with moderate hydrophobic characteristics. Studies involving additional antibodies possessing different formats and a wide range of hydrophobicity confirmed the broad applicability of the new resin. In view of its high selectivity and robust operating ranges, as well as the elimination of the need for an additional column step, the novel resin enables simplified downstream processing and economic manufacturing of complex antibody formats.


Assuntos
Anticorpos Monoclonais , Resinas de Troca de Cátion , Anticorpos Monoclonais/química , Cromatografia , Cloreto de Sódio , Interações Hidrofóbicas e Hidrofílicas , Cromatografia por Troca Iônica/métodos
16.
Environ Sci Technol ; 56(22): 16134-16143, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36223185

RESUMO

Ion exchange (IX) is a promising technology for selective nitrogen recovery from urine; however, IX requires chemical-intensive regeneration that escalates energy consumption and carbon emissions. To overcome this barrier, we demonstrated and investigated a novel electrified IX stripping process (EXS) enabling electrochemical in situ IX regeneration with simultaneous ammonia stripping. EXS combines a weak acid cation exchange resin (WAC) to concentrate ammonia, a bipolar membrane to produce protons for WAC regeneration, and membrane stripping to recover the eluted ammonium from WAC. We observed over 80% regeneration (elution from resin) and recovery (membrane stripping) efficiencies during multiple adsorption-recovery cycles with synthetic and real urine. Comparing WAC with a strong acid cation exchange resin illustrated the critical role of the proton affinity of resin moieties in regulating resin regenerability and conductivity in EXS, which we distinguished from the rationale for material choice in electrodeionization. Compared to other electrochemical recovery methods using unamended wastewater as an electrolyte, EXS enabled control of electrolyte composition during recovery by separating and equalizing influent ammonium via WAC-mediated removal. This electrolyte engineering facilitated tunable EXS energy efficiency (100-300 MJ/kg N). This study informs the design of electrified, intensified systems that enable decentralized nitrogen recovery from urine.


Assuntos
Compostos de Amônio , Nitrogênio , Troca Iônica , Amônia , Água , Resinas de Troca de Cátion , Águas Residuárias
17.
J Chromatogr A ; 1682: 463449, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36162250

RESUMO

Conventional Simulated Moving Bed Chromatography (C-SMBC) characterized by a single operating point comprising of the internal flow rates and switching period, yields a single fraction of the extract and raffinate, at cyclic steady state. In the current work, we deal with two-fraction yielding Dual Switch SMBC (DS-SMBC) characterized by two operating points implemented during alternate switches. The higher degrees of freedom in Dual Switch SMBC give it the potential of obtaining a higher average extract purity, for one of its two fractions, compared to conventional SMBC, at a certain minimum feed flow rate and minimum average extract recovery. This becomes possible with a trade-off in the average purity of the other extract fraction of Dual Switch SMBC, without any addition to the conventional SMBC equipment. We solve a multi-objective optimization problem wherein we maximize the average purity of one of the extract fractions of Dual Switch SMBC, with the requirement of certain minimum feed flow rate, minimum average extract recovery and minimum average purity of the non-objective extract fraction. One of the aims of the current work is deduction of the working principle of Dual Switch SMBC, that facilitates superior average extract purity. Next, we analyze the trade-offs due to the said process bounds on the objective i.e. average purity of objective extract fraction of Dual Switch SMBC. This has been done for the two case studies of separation: 1) linear isotherm based separation of fructose-glucose in deionized water on cation exchange resin 2) non-linear isotherm based separation of enantiomers of Tröger's base in ethanol on microcrystalline cellulose triacetate. The findings from the trade-offs in the multi-objective optimization problem, further corroborate our understanding of the working principle.


Assuntos
Resinas de Troca de Cátion , Cromatografia , Cromatografia/métodos , Etanol , Frutose , Glucose , Água
18.
Int J Pharm Compd ; 26(5): 436-439, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36053770

RESUMO

Calcium polystyrene sulfonate, a cation exchange resin preparation, is used to treat hyperkalaemia. The effects of switching from dry syrup to oral solution forms have been rarely evaluated. We investigated changes in serum potassium levels, incidence of adverse events, and patients' perception and satisfaction associated with the change in calcium polystyrene sulfonate dosage forms from dry syrup to oral solution in chronic kidney disease patients. The study population was comprised of 24 patients. The chronic kidney disease cause, glomerular filtration rate category, and albuminuria category was G4 in 10 cases (41.7%) and G5 in 8 cases (33.3%). No significant difference was observed between groups before and after the change in dosage form. Contrastingly, the ease of intake (P=0.0047), taste (P=0.0056), and satisfaction (P<0.001) indicated positive significant improvements. Changing the calcium polystyrene sulfonate dosage form from dry syrup to oral solution in patients with chronic kidney disease improved patient satisfaction while maintaining efficacy and safety. For patients in whom weight gain is not a problem, we recommend changing the dosage form from dry syrup to oral solution for calcium polystyrene sulfonate.


Assuntos
Hiperpotassemia , Insuficiência Renal Crônica , Resinas de Troca de Cátion/efeitos adversos , Humanos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/tratamento farmacológico , Poliestirenos/efeitos adversos , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico
19.
Protein Expr Purif ; 199: 106155, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35970491

RESUMO

Cation exchange (CEX) chromatography has been widely used as a polishing step in downstream processing of therapeutic monoclonal antibodies (mAbs). It has been well documented that the performance of a particular CEX resin heavily relies on buffer type, pH and conductivity. In this work, with a case study, we screened six commercial CEX resins under different pHs and conductivities. Initial screening was conducted on Tecan to find conditions under which high binding capacity was achieved. Next, performance of each resin was further evaluated using a small column under the identified optimum binding conditions. Variations in binding capacity and purity of eluate were observed among these resins. The adopted approach allows for identification of resins exhibiting good binding capacity, aggregate clearance and recovery.


Assuntos
Anticorpos Monoclonais , Resinas de Troca de Cátion , Anticorpos Monoclonais/química , Resinas de Troca de Cátion/química , Cátions/química , Cromatografia por Troca Iônica/métodos , Cinética
20.
Chemosphere ; 307(Pt 3): 135920, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35948103

RESUMO

Short-chain fatty acids (SCFAs) generation through anaerobic fermentation has been regarded as a promising pathway to achieve carbon recovery and economic benefits in waste activated sludge management. Despite the cation exchange resin (CER) assistant anaerobic fermentation strategy has been previously reported for enhancing anaerobic fermentation, the overlarge CER usage and serious CER pollution have limited its engineering application. This study provided a reconsideration for the operation pattern modification. Through 4-day anaerobic fermentation with CER residence period shrinking to 1 day, 40.9% sludge VSS solubilization and reduction were achieved, triggering a considerable sludge hydrolysis rate of 28.4%. Thereby, SCFAs production was improved to 264.8 mg COD/g VSS. Such performances were approximately 80.2-87.8% of those with conventional CER residence period (8 days). The organic composition distribution and parallel factor analysis demonstrated that similar biodegradability and utilizability of fermentative liquid were achievable with various operation patterns. Compared with the conventional operation pattern, the modified operation pattern with shortened CER residence period (1 day) also displayed satisfying anaerobic fermentation efficiency and numerous engineering bene fits, e.g. decreased CER usage, reduced engineering footprint, relieved CER fouling, and increased operation convenience. The findings might provide sustainable development for CER assistant anaerobic fermentation strategy and enlighten the direction of anaerobic fermentation process.


Assuntos
Incrustação Biológica , Esgotos , Anaerobiose , Incrustação Biológica/prevenção & controle , Carbono , Resinas de Troca de Cátion , Cátions , Ácidos Graxos Voláteis , Fermentação , Concentração de Íons de Hidrogênio
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