混合模型开发用于参数估计和流程优化,用于疏水性相互作用染色学
Chaoying Ding1, Christopher Gerberich2, Marianthi Ierapetritou1
1Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA.
Journal of chromatography. A
|June 2, 2023
概括
一个混合模型结合了多组件的兰木尔异热和神经网络,准确地预测了用于治疗性蛋白质净化的疏水相互作用色谱 (HIC) 行为,提高了过程开发效率.
科学领域:
- 生物制药工艺开发 生物制药过程开发
- 染色学分离科学 染色学分离科学
- 计算建模 计算建模
背景情况:
- 疏水相互作用色谱 (HIC) 对于治疗性蛋白质净化至关重要,但其复杂的,依赖盐的吸附机制阻碍了准确的建模.
- 由于蛋白质-树脂相互作用不清楚,开发HIC精确的机械模型具有挑战性.
- 加快过程开发和降低成本需要基于先进模型的设计和优化策略.
研究的目的:
- 开发一个准确和高效的混合模型,用于疏水性相互作用染色学 (HIC) 过程.
- 在捕捉复杂的HIC行为方面克服传统机械模型的局限性.
- 为了实现更快的过程开发和优化治疗性蛋白质净化.
主要方法:
- 一个混合模型是通过将多组件的兰迈尔等热体与神经网络 (NN) 集成而构建的.
- 修改后的同温和和平衡分散模型被用来表示HIC过程.
- 在参数估计过程中,纳入了规范化策略,以防止过拟合和调查NN结构.
主要成果:
- 混合模型,特别是具有简单的NN结构的混合模型,在准确性方面明显优于机械模型 (62%的校准,31.4%的验证).
- 发现模型结构对于预测准确性至关重要.
- 开发的混合模型通过in-silico测试证明了通用性,并在产品质量约束下实现了流程优化.
结论:
- 一种混合多元件的朗格穆尔异温和神经网络模型为准确的HIC过程建模提供了一种强大的方法.
- 这种混合建模策略提高了治疗性蛋白质净化过程开发的效率和准确性.
- 开发的模型有助于确定最佳运行条件,有助于节省成本和更快的开发时间表.
相关概念视频
High-Performance Liquid Chromatography: Elution Process
546
In High-Performance Liquid Chromatography (HPLC), the elution process is critical to the separation of analytes and the quality of chromatographic results. Elution describes how compounds move through the column and separate based on their interactions with the mobile and stationary phases. This process determines the resolution, peak shape, and retention times in the chromatogram, which are essential for identifying and quantifying components in complex mixtures. Understanding the elution...
546
Optimizing Chromatographic Separations
442
Optimizing chromatographic separations is crucial for obtaining clean separations in a minimum amount of time. Optimization is required for several factors, including kinetic effects related to band broadening, plate height, capacity factor, and separation factor.
Band broadening refers to spreading solute bands as they travel through the column. This broadening can impact resolution. Plate height (H) represents the length required for one theoretical plate. A lower plate height corresponds to...
Band broadening refers to spreading solute bands as they travel through the column. This broadening can impact resolution. Plate height (H) represents the length required for one theoretical plate. A lower plate height corresponds to...
442
High-Performance Liquid Chromatography: Introduction
2.1K
High-performance liquid chromatography(HPLC), formerly referred to as High-pressure liquid chromatography, is a powerful technique used to separate, identify, and quantify components in complex mixtures. The term "high pressure" refers to using high pressure to push the liquid mobile phase through the tightly packed columns.
In HPLC, two phases play a critical role in the separation process:
In HPLC, two phases play a critical role in the separation process:
2.1K
High-Performance Liquid Chromatography: Instrumentation
1.9K
High-performance liquid chromatography, or HPLC, is an analytical technique that separates liquid samples under high pressures. An HPLC instrument consists of glass bottles for storing solvents called mobile phase reservoirs. HPLC-grade solvents are used to maintain high purity, and the dissolved gases are removed using a degasser, such as a vacuum pumping system or sparging with helium. The solvents are then pumped into the analytical column using a screw-driven syringe or reciprocating pumps.
1.9K
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
101
Pharmacokinetic models are mathematical constructs that represent and predict the time course of drug concentrations in the body, providing meaningful pharmacokinetic parameters. These models are categorized into compartment, physiological, and distributed parameter models.
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
101
Mass Spectrometry: Complex Analysis
832
Mass spectrometry is an important technique for the identification of pure compounds. However, it has some limitations for the analysis of complex mixtures, often due to excessive fragmentation making the spectrum too complicated to decipher. Mass spectrometry can be combined with suitable separation methods in sequence, forming hyphenated methods, which are useful in the analysis of complex mixtures.
GC–MS is a powerful hyphenated method commonly used in forensics and environmental...
GC–MS is a powerful hyphenated method commonly used in forensics and environmental...
832


