Infrared attenuated total reflection and 2D fluorescence spectroscopy for the discrimination of differently aggregated monoclonal antibodies

The Analyst ◽  
2019 ◽  
Vol 144 (21) ◽  
pp. 6334-6341
Author(s):  
Alina Handl ◽  
Ángela I. López-Lorente ◽  
René Handrick ◽  
Boris Mizaikoff ◽  
Friedemann Hesse
Keyword(s):  
Monoclonal Antibodies ◽  
Ionic Strength ◽  
Fluorescence Spectroscopy ◽  
Protein Concentration ◽  
Total Reflection ◽  
Attenuated Total Reflection ◽  
Aggregate Formation ◽  
Shear Forces ◽  
By Products

Antibody aggregates may occur as undesirable by-products during manufacturing of biopharmaceutical proteins since parameters such as pH, temperature, ionic strength, protein concentration, oxygen, and shear forces can lead to aggregate formation.

Gas Cell Infrared and Attenuated Total Reflection Infrared Spectroscopic Studies for Organic–Inorganic Interactions in Adsorption of Fulvic Acid on the Goethite Surface Generating Carbon Dioxide

2021 ◽  
pp. 000370282199121
Author(s):  
Yuki Nakaya ◽  
Satoru Nakashima ◽  
Takahiro Otsuka
Keyword(s):  
Carbon Dioxide ◽  
Activation Energy ◽  
Fulvic Acid ◽  
Spectroscopic Studies ◽  
Reaction Model ◽  
Total Reflection ◽  
Attenuated Total Reflection ◽  
Gas Cell ◽  
Rate Determining Step ◽  
Ir Spectroscopic

The generation of carbon dioxide (CO2) from Nordic fulvic acid (FA) solution in the presence of goethite (α-FeOOH) was observed in FA–goethite interaction experiments at 25–80 ℃. CO2 generation processes observed by gas cell infrared (IR) spectroscopy indicated two steps: the zeroth order slower CO2 generation from FA solution commonly occurring in the heating experiments of the FA in the presence and absence of goethite (activation energy: 16–19 kJ mol–1), and the first order faster CO2 generation from FA solution with goethite (activation energy: 14 kJ mol–1). This CO2 generation from FA is possibly related to redox reactions between FA and goethite. In situ attenuated total reflection infrared (ATR-IR) spectroscopic measurements indicated rapid increases with time in IR bands due to COOH and COO– of FA on the goethite surface. These are considered to be due to adsorption of FA on the goethite surface possibly driven by electrostatic attraction between the positively charged goethite surface and negatively charged deprotonated carboxylates (COO–) in FA. Changes in concentration of the FA adsorbed on the goethite surface were well reproduced by the second order reaction model giving an activation energy around 13 kJ mol–1. This process was faster than the CO2 generation and was not its rate-determining step. The CO2 generation from FA solution with goethite is faster than the experimental thermal decoloration of stable structures of Nordic FA in our previous report possibly due to partial degradations of redox-sensitive labile structures in FA.

scholarly journals Distinguishing active from quiescent disease in ANCA-associated vasculitis using attenuated total reflection Fourier-transform infrared spectroscopy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adam D. Morris ◽  
Camilo L. M. Morais ◽  
Kássio M. G. Lima ◽  
Daniel L. D. Freitas ◽  
Mark E. Brady ◽  
...  
Keyword(s):  
Fourier Transform ◽  
Unmet Need ◽  
Fourier Transform Infrared ◽  
Total Reflection ◽  
Attenuated Total Reflection ◽  
Remission Induction ◽  
Disease Remission ◽  
Anca Associated Vasculitis ◽  
Active Disease ◽  
Quiescent Disease

AbstractThe current lack of a reliable biomarker of disease activity in anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitis poses a significant clinical unmet need when determining relapsing or persisting disease. In this study, we demonstrate for the first time that attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy offers a novel and functional candidate biomarker, distinguishing active from quiescent disease with a high degree of accuracy. Paired blood and urine samples were collected within a single UK centre from patients with active disease, disease remission, disease controls and healthy controls. Three key biofluids were evaluated; plasma, serum and urine, with subsequent chemometric analysis and blind predictive model validation. Spectrochemical interrogation proved plasma to be the most conducive biofluid, with excellent separation between the two categories on PC2 direction (AUC 0.901) and 100% sensitivity (F-score 92.3%) for disease remission and 85.7% specificity (F-score 92.3%) for active disease on blind predictive modelling. This was independent of organ system involvement and current ANCA status, with similar findings observed on comparative analysis following successful remission-induction therapy (AUC > 0.9, 100% sensitivity for disease remission, F-score 75%). This promising technique is clinically translatable and warrants future larger study with longitudinal data, potentially aiding earlier intervention and individualisation of treatment.

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