{"title":"Pore structure reconstruction to reveal the adsorption capacity limitation of current oligo-dT resins and guide new resin design","authors":"","doi":"10.1016/j.chroma.2024.465454","DOIUrl":null,"url":null,"abstract":"<div><div>In-depth knowledge of the pore structure of chromatographic resins is instrumental for better mechanistic understanding of adsorption performance, which can be translated into strategies to guide the design of new resins. Aiming to reveal the underlying reasons of low mRNA adsorption capacities of commercial oligo-dT resins, three-dimensional (3D) pore structure reconstruction was applied to relate key pore properties to the adsorption performance. The static 3D pore analysis revealed that the amount and connectivity of the accessible pores for 100 nm-sized mRNA reduced by over 90% and 46% compared with initial pore structure of resins, respectively, which led to discontinuous transport paths for mRNA. The dynamic simulations revealed that the strong hindrance of the firstly bound mRNA to the following mRNA molecules led to less than 10% of mRNA being able to penetrate into the resins with a depth of only 1–2 μm. Based on the digital material model, a virtual nanofiber-based macroporous resin was designed to explore its potential. Simulation results demonstrated that due to large pores and high connectivity, the new resin could allow over 91% of mRNA diffusion into the resin interior, showing great potential to improve the adsorption capacity of mRNA. This work provided a new method to evaluate the limitations of commercial oligo-dT resins and obtained some valuable guidance for the structure design of next-generation resins.</div></div>","PeriodicalId":347,"journal":{"name":"Journal of Chromatography A","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chromatography A","FirstCategoryId":"1","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0021967324008288","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
In-depth knowledge of the pore structure of chromatographic resins is instrumental for better mechanistic understanding of adsorption performance, which can be translated into strategies to guide the design of new resins. Aiming to reveal the underlying reasons of low mRNA adsorption capacities of commercial oligo-dT resins, three-dimensional (3D) pore structure reconstruction was applied to relate key pore properties to the adsorption performance. The static 3D pore analysis revealed that the amount and connectivity of the accessible pores for 100 nm-sized mRNA reduced by over 90% and 46% compared with initial pore structure of resins, respectively, which led to discontinuous transport paths for mRNA. The dynamic simulations revealed that the strong hindrance of the firstly bound mRNA to the following mRNA molecules led to less than 10% of mRNA being able to penetrate into the resins with a depth of only 1–2 μm. Based on the digital material model, a virtual nanofiber-based macroporous resin was designed to explore its potential. Simulation results demonstrated that due to large pores and high connectivity, the new resin could allow over 91% of mRNA diffusion into the resin interior, showing great potential to improve the adsorption capacity of mRNA. This work provided a new method to evaluate the limitations of commercial oligo-dT resins and obtained some valuable guidance for the structure design of next-generation resins.
期刊介绍:
The Journal of Chromatography A provides a forum for the publication of original research and critical reviews on all aspects of fundamental and applied separation science. The scope of the journal includes chromatography and related techniques, electromigration techniques (e.g. electrophoresis, electrochromatography), hyphenated and other multi-dimensional techniques, sample preparation, and detection methods such as mass spectrometry. Contributions consist mainly of research papers dealing with the theory of separation methods, instrumental developments and analytical and preparative applications of general interest.