| 1. |
- Kulakova, Alina, et al.
(författare)
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Chemometrics in Protein Formulation : Stability Governed by Repulsion and Protein Unfolding
- 2023
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Ingår i: Molecular Pharmaceutics. - 1543-8384. ; 20:6, s. 2951-2965
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic proteins can be challenging to develop due to their complexity and the requirement of an acceptable formulation to ensure patient safety and efficacy. To date, there is no universal formulation development strategy that can identify optimal formulation conditions for all types of proteins in a fast and reliable manner. In this work, high-throughput characterization, employing a toolbox of five techniques, was performed on 14 structurally different proteins formulated in 6 different buffer conditions and in the presence of 4 different excipients. Multivariate data analysis and chemometrics were used to analyze the data in an unbiased way. First, observed changes in stability were primarily determined by the individual protein. Second, pH and ionic strength are the two most important factors determining the physical stability of proteins, where there exists a significant statistical interaction between protein and pH/ionic strength. Additionally, we developed prediction methods by partial least-squares regression. Colloidal stability indicators are important for prediction of real-time stability, while conformational stability indicators are important for prediction of stability under accelerated stress conditions at 40 °C. In order to predict real-time storage stability, protein-protein repulsion and the initial monomer fraction are the most important properties to monitor.
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| 2. |
- Laegsgaard, E, et al.
(författare)
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A high-pressure scanning tunneling microscope
- 2001
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 72:9, s. 3537-3542
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Tidskriftsartikel (refereegranskat)abstract
- We present the design and performance of a high-pressure scanning tunneling microscope (HP-STM), which allows atom-resolved imaging of metal surfaces at pressures ranging from ultrahigh vacuum (UHV) to atmospheric pressures (1 x 10(-10)-1000 mbar) on a routine basis. The HP-STM is integrated in a gold-plated high-pressure cell with a volume of only similar to0.5 l, which is attached directly to an UHV preparation/analysis chamber. The latter facilitates quick sample transfer between the UHV chamber and the high-pressure cell, and allows for in situ chemical and structural analysis by a number of analytical UHV techniques incorporated in the UHV chamber. Reactant gases are admitted to the high-pressure cell via a dedicated gas handling system, which includes several stages of gas purification. The use of ultrapure gasses is essential when working at high pressures in order to achieve well-defined experimental conditions. The latter is demonstrated in the case of H/Cu(110) at atmospheric H-2 pressures where impurity-related structures were observed. (C) 2001 American Institute of Physics.
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| 3. |
- Österlund, Lars, 1967-, et al.
(författare)
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Bridging the pressure gap in surface science at the atomic level : H/Cu(110)
- 2001
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 86:3, s. 460-463
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Tidskriftsartikel (refereegranskat)abstract
- The structural response of the Cu(110) surface to H-2 gas pressures ranging from 10(-13) to 1 bar is studied using a novel high-pressure scanning tunneling microscope (HP-STM). We find that at H-2 pressures larger than 2 mbar the Cu(110) surface reconstructs into the (1 X 2) "missing-row" structure. From a quantitative analysis of the pressure dependence of the surface reconstruction, we conclude that Cu(110) responds identically to hydrogen at ultrahigh vacuum conditions and at atmospheric pressures. From the HP-STM data, we extract refined values for the adsorption and desorption rate constants.
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