| 2023 | Book Chapter: Chemometrics & Process Control (from: Springer Handbook for Advanced Catalyst Characterization) |
| A book chapter describing the typical procedures in quantitative analysis of spectra along the common workflows. On-the-fly introduction of the fundamental methodology behind the most relevant chemometric methods, using real-life application cases. Valuable overview reading for the practical user! | |
| https://link.springer.com/chapter/10.1007/978-3-031-07125-6_48 | |
| 2021 | Inline Raman Spectroscopy of an Emulsion Copolymerization in an Industrial Pilot Plant Using Indirect Hard Modeling |
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Raman spectroscopy was used to determine the concentrations of monomers and polymers in the second stage of a two-stage emulsion polymerization process. Spectral hard modeling was applied to monitor inline the reaction in semi-batch operation in lab scale and pilot scale. |
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| 2021 | Inline Raman Spectroscopy and Indirect Hard Modeling for Concentration Monitoring of Dissociated Acid Species |
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Monitoring the concentration of dissociated carboxylic acid species in dilute aqueous solution was demonstrated. The dissociated acid species are quantified employing inline Raman spectroscopy in combination with Indirect Hard Modeling (IHM) and multivariate curve resolution (MCR). |
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| DOI: 10.1177/0003702820973275 | |
| 2021 | Standardization and Control of Grignard Reactions in a Universal Chemical Synthesis Machine using online NMR |
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A chemical synthesis platform was extended by online NMR spectroscopy to allow real-time adjustments of encoded reactions. The approach was demonstrated on Grignard reactions. Real-time process analytics and the use of a straightforward feedback control algorithm enable the synthesis in full automation. |
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| DOI: 10.1002/anie.202106323 | |
| 2021 | Method for Automated Generation of Indirect Hard Models using crossvalidation (MAGIC) for the spectral analysis of mixture spectra |
| Indirect Hard Modeling (IHM) requires user decisions regarding the number of peak functions and model flexibility. A method for the Automatic Generation of Indirect Hard Models using Crossvalidation (MAGIC) is presented that jointly chooses the number of peak functions and peak parameter adjustments such that the crossvalidation error of calibration is minimized. | |
| DOI: 10.1016/j.chemolab.2021.104419 | |
| 2021 | Advanced Real?Time Process Analytics for Multistep Synthesis in Continuous Flow |
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The integration of four complementary process analytical technology tools (NMR, UV/Vis, IR and UHPLC) in the multistep synthesis of an active pharmaceutical ingredient (mesalazine) is reported. Advanced data analysis models were developed (IHM, deep learning and PLSR), to quantify the desired reactants. The automated flow system has been demonstrated by operating both steady state and dynamic experiments. |
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| DOI: 10.1002/anie.202016007 | |
| 2020 | Process analytical technology (PAT) as a versatile tool for real-time monitoring and kinetic evaluation of photocatalytic reactions |
| Process analytical technology (PAT) was applied to disclose kinetic insights into photocatalytic reactions. The eosin Y catalyzed photooxidation of 4-methoxythiophenol (4-MTP) to bis(4-methoxyphenyl)disulfide (4-MPD) was monitored with Raman and UV/Vis spectroscopy. The evaluation by indirect hard modelling approach (IHM) disclosed the contributions of rate limiting effects like the oxygen mass transport and the degradation of eosin Y. | |
| DOI: 10.1039/D0RE00256A | |
| 2020 | Artificial neural networks for quantitative online NMR spectroscopy |
| Data augmentation procedure for the generation of synthetic (simulated) NMR spectra based on spectral hard modeling enables the development of data-driven models such as neural nets because the initial training dataset can be sized and distributed along various prediction variables arbitrarily. | |
| DOI: 10.1007/s00216-020-02687-5 | |
| 2019 | Kinetics of Formic Acid Decomposition in Subcritical and Supercritical Water - A Raman Spectroscopic Study |
| In-situ Raman spectroscopy is used to produce real-time data and accurately quantify product yields of H2, CO2, and CO of the decomposition of formic acid in sub- or supercritical water. PEAXACT allowed for efficient analysis of the large data set. | |
| DOI: 10.1016/j.ijhydene.2019.10.070 | |
| 2018 | Investigating phase separation in amorphous solid dispersions via Raman mapping |
| Phase-separation kinetics and the compositions of the two amorphous phases evolving due to amorphous solid dispersions were quantitatively determined for the first time using confocal Raman spectroscopy and Indirect Hard Modeling (IHM). | |
| DOI: 10.1016/j.ijpharm.2017.11.014 | |
| 2018 | Choosing Appropriate Solvents for the preparation of amorphous solid dispersions (ASD) |
| ASDs are often used for formulating poorly water-soluble active pharmaceutical ingredients (APIs). Raman measurements were carried out and Indirect Hard Modeling (IHM) was used to quantify the API distribution in ASD films as well as to investigate the compositions in the films during drying. | |
| DOI: 10.1021/acs.molpharmaceut.8b00892 | |
| 2018 | Reliable spectroscopic process monitoring using an optimal acquisition time procedure determined by signal-to-noise ratio |
| Monitoring chemical processes with optical spectroscopy involves a trade-off between high-frequency sampling to capture process dynamics and good signal-to-noise ratio (SNR). This contribution presents a strategy to maximize sampling frequency while maintaining a high SNR during in-line process monitoring using IHM. | |
| DOI: 10.1016/j.measurement.2018.02.061 | |
| 2017 | Robust analysis of spectra with strong background signals by First-Derivative Indirect Hard Modeling (FD-IHM) |
| First-Derivative Indirect Hard Modeling (FD-IHM) is a form of the IHM-method using the derivative of peak-functions for fitting the derivative of a spectrum, which is robust against strong background signals. | |
| DOI: 10.1016/j.chemolab.2017.11.005 | |
| 2016 | In-line Monitoring of Monomer and Polymer Content During Microgel Synthesis Using Precipitation Polymerization via Raman Spectroscopy and Indirect Hard Modeling |
| Indirect Hard Modeling (IHM) enables the quantitative analysis during microgel synthesis with Raman spectroscopy, having a model which is robust against changes in microgel particle size and temperature. | |
| DOI: 10.1177/0003702815626663 | |
| 2015 | Model-Based Recognition of Mid-Infrared Sensor Fouling in Paracetamol Crystallization |
| API deposition on a fibre-optic ATR immersion probe for MIR spectroscopy is detected in a crystallization process, applying an intelligent Indirect Hard Modeling (IHM) approach for spectral analysis. | |
| DOI: 10.1002/ceat.201400585 | |
| 2015 | Automated data evaluation and modelling of simultaneous 19F– 1H medium-resolution NMR spectra for online reaction monitoring |
| Benchtop NMR instruments are applied as online process analysers for the monitoring of reacting mixtures. Essential contribution of Indirect Hard Modeling to quantitative Data Analysis. | |
| DOI: 10.1002/mrc.4216 | |
| 2013 | Application of ATR-MIR Spectroscopy in the Pilot Plant – Scope and Limitations using the Example of Paracetamol Crystallizations |
| MIR spectroscopic monitoring of an API crystallisation; successful method transfer from lab to pilot plant scale and compensation of perturbations through Indirect Hard Modeling. | |
| DOI: 10.1016/j.cep.2013.04.003 | |
| 2013 | Comprehensive monitoring of a biphasic switchable solvent synthesis |
| MIR and UV spectroscopic monitoring of a high pressure synthesis with simultaneous measurements in both active phases. | |
| DOI: 10.1039/c2an36044f | |
| 2012 | Concentration Measurements in Ionic Liquid–Water Mixtures by Mid-Infrared Spectroscopy and Indirect Hard Modeling |
| Quantitative characterization of binary mixtures of water and ionic liquids using Mid-IR spectroscopy in combination with Indirect Hard Modeling. | |
| DOI: 10.1366/11-06427 | |
| 2011 | Diffusion of poly(ethylene glycol) and ectoine in NIPAAm hydrogels with confocal Raman spectroscopy |
| Characterisation of diffusion in hydrogels by measuring time- and space-resolved concentration profiles using confocal Raman spectroscopy | |
| DOI: 10.1007/s00396-011-2399-7 | |
| 2010 | Bridging the gap: A nested-pipe reactor for slow reactions in continuous flow chemical synthesis |
| Characterisation of a novel pilot-scale reactor for continuous production of Fine Chemicals | |
| DOI: 10.1016/j.cej.2010.09.004 | |
| 2009 | Determination of the Dispersion Characteristics of Miniaturized Coiled Reactors with Fiber-Optic Fourier Transform Mid-infrared Spectroscopy |
| Characterisation of a miniaturised continuous lab reactor | |
| DOI: 10.1021/ie901094q | |
| 2009 | An Ozonolysis-Reduction Sequence for the Synthesis of Pharmaceutical Intermediates in Microstructured Devices |
| Reaction monitoring of a pharmaceutical synthesis in a microstructured device | |
| DOI: 10.1021/op9000669 | |
| 2009 | Direct determination of the concentration dependence of diffusivities using combined model-based Raman and NMR experiments |
| Determination of diffusion behaviour in multi-component system with Raman and NMR spectroscopy | |
| DOI: 10.1016/j.fluid.2008.10.012 | |
| 2008 | Identification of unknown pure component spectra by indirect hard modeling |
| Hard Modeling Factor Analysis (HMFA): Calibration-free spectral analysis based on Indirect Hard Modeling | |
| DOI: 10.1016/j.chemolab.2008.05.002 | |
| 2007 | In situ monitoring of an isocyanate reaction by fiber-optic FT-IR/ATR-spectroscopy |
| Reaction monitoring and kinetic studies of a polyurethane synthesis | |
| DOI: 10.1016/j.vibspec.2006.07.004 | |
| 2007 | Process monitoring and control in microreactors with ATR IR Spectroscopy |
| Micro-structured flow cell for miniaturised fibre optical mid-infrared sensors | |
| DOI: 10.1002/cite.200750089 | |
| 2007 | Fully automated indirect hard modeling of mixture spectra |
| Automated modelling of spectra with IHM: Validation with mid-infrared and Raman spectra | |
| DOI: 10.1016/j.chemolab.2007.11.004 | |
| 2006 | Highly Flexible Fibre-Optic ATR-IR Probe for Inline Reaction Monitoring |
| Applications of fibre-optical spectroscopy in organic synthesis | |
| DOI: 10.1021/op0601767 | |
| 2006 | Combining reaction calorimetry and ATR-IR spectroscopy for the operando monitoring of ionic liquids synthesis |
| A combination of fibre-optical spectroscopy with reaction calorimetry | |
| DOI: 10.1016/j.cattod.2006.12.007 | |
| 2006 | Mid-infrared monitoring of gas-liquid reactions in vitamin D analog synthesis with a novel fiber optical diamond ATR sensor |
| Reaction monitoring in a vitamin synthesis | |
| DOI: 10.1002/ceat.200600110 | |
| 2006 | Ternary diffusivities by model-based analysis of raman spectroscopy measurements |
| Elucidation of diffusion processes in complex systems | |
| DOI: 10.1002/aic.11021 | |
| 2005 | Method for quantitative determination of spatial polymer distribution in alginate beads using Raman spectroscopy |
| Raman spectroscopy for the characterisation of polymer beads | |
| DOI: 10.1366/0003702053585363 | |
| 2004 | Indirect Spectral Hard Modeling for the analysis of reacting and interacting mixtures |
| Indirect Hard Modeling (IHM): New model-based method for spectral analysis | |
| DOI: 10.1366/0003702041655368 | |
| 2004 | Automatic generation of peak-shaped models |
| Automatic generation of peak-shaped models: Foundation for Indirect Hard Modeling | |
| DOI: 10.1366/0003702041655421 | |
| 2003 | Novel infrared optical probes for process monitoring and analysis based on next-generation silver halide fibers |
| Recent developments in optical fibres for reaction monitoring | |
| DOI: 10.1007/s00216-003-1782-8 | |
| 2003 | Model-based measurement of diffusion using Raman spectroscopy |
| Monitoring of multi-component diffusion with Raman spectroscopy | |
| DOI: 10.1002/aic.690490205 | |
| 2002 | Bio-analytical applications of mid-infrared spectroscopy using silver halide fiber-optic probes |
| Applications from biomedical analytics | |
| DOI: 10.1016/S0584-8547(02)00103-9 | |
| 2001 | Novel developments in mid-IR fiber-optic spectroscopy for analytical applications |
| Overview over new fibre-optical sensors for mid-infrared spectroscopy | |
| DOI: 10.1016/S0022-2860(00)00804-8 |
