A5000361518- Viral Infectious Diseases and Gene Expression in Insects
- SARS-CoV-2 and COVID-19 Research
- Protein purification and stability
- SARS-CoV-2 detection and testing
- Advanced Control Systems Optimization
- Microfluidic and Bio-sensing Technologies
- Microfluidic and Capillary Electrophoresis Applications
- Fluid Dynamics and Mixing
- Fault Detection and Control Systems
- COVID-19 Clinical Research Studies
- Viral Infections and Immunology Research
- Optimal Experimental Design Methods
- Microencapsulation and Drying Processes
- Ultrasound and Hyperthermia Applications
- Ultrasound and Cavitation Phenomena
- Spectroscopy and Chemometric Analyses
- Microbial Inactivation Methods
- Viral Infections and Outbreaks Research
- Monoclonal and Polyclonal Antibodies Research
- Biofuel production and bioconversion
- Genomics and Phylogenetic Studies
- Proteins in Food Systems
- Respiratory viral infections research
- Advanced machining processes and optimization
- Viral gastroenteritis research and epidemiology
BOKU University
2019-2022
Austrian Centre of Industrial Biotechnology (Austria)
2017-2018
Boehringer Ingelheim (Austria)
2014
The reported impact of shear stress on protein aggregation has been contradictory. At high rates, the occurrence cavitation or entrapment air is reasonable and their effects possibly misattributed to stress. Nine different proteins (α‐lactalbumin, two antibodies, fibroblast growth factor 2, granulocyte colony stimulating [GCSF], green fluorescence [GFP], hemoglobin, human serum albumin, lysozyme) are tested for behavior vapor/liquid interfaces generated by compared it isolated air/liquid...
Abstract Process characterization is necessary in the biopharmaceutical industry, leading to concepts such as design of experiments (DoE) combination with process modeling. However, these methods still have shortcomings, including large numbers required experiments. The concept intensified (iDoE) proposed, that is, intra‐experimental shifts critical parameters (CPP) combine hybrid modeling more rapidly screen a particular space. To demonstrate advantages, comprehensive experimental...
Cross-flow ultrafiltration is a powerful tool used in bioprocesses to concentrate and separate biopharmaceuticals. However, there major challenge for its effective use: the fouling rate decrease permeate flux vary substantially depending on concentration characteristics of incoming feed, which causes variations process durations. We developed hybrid model use predicting evolution duration cross-flow processes various proteins, membrane types, input parameters, filtration modes. The trained...
Abstract Upstream bioprocess characterization and optimization are time resource‐intensive tasks. Regularly in the biopharmaceutical industry, statistical design of experiments (DoE) combination with response surface models (RSMs) used, neglecting process trajectories dynamics. Generating understanding time‐resolved, dynamic allows to understand impact temporal deviations, production dynamics, provides a better variations that stem from biological subsystem. The authors propose use DoE...
Antibody tests are essential tools to investigate humoral immunity following SARS-CoV-2 infection or vaccination. While first-generation antibody have primarily provided qualitative results, accurate seroprevalence studies and tracking of levels over time require highly specific, sensitive quantitative test setups.
The fast exploration of a design space and identification the best process conditions facilitating highest space-time yield are great interest for manufacturers. To obtain this information, depending on space, large number practical experiments must be performed, analyzed, evaluated. reduce experimental effort increase understanding, we evaluated model-based to rapidly identify optimum in maximizing yield. From small initial dataset, hybrid models were implemented used as digital bioprocess...
Despite the advantages of mathematical bioprocess modeling, successful model implementation already starts with experimental planning and accordingly can fail at this early stage. For study, two different modeling approaches (mechanistic hybrid) based on a four-dimensional antibody-producing CHO fed-batch process are compared. Overall, 33 experiments performed in fractional factorial design space separated into four complex data partitions subsequently used for comparison evaluation. The...
Abstract Neither the influence of high shear rates nor impact cavitation on protein aggregation is fully understood. The effect bubble collapse‐derived hydroxyl radicals behavior human serum albumin (HSA) was investigated. Radicals were generated by pumping through a micro‐orifice, ultra‐sonication, or chemically Fenton's reaction. amount produced two mechanical methods (0.12 and 11.25 nmol/(L min)) not enough to change integrity. In contrast, reaction resulted in 382 min) radicals, inducing...
Reliable process development is accompanied by intense experimental effort. The utilization of an intensified design experiments (iDoE) (intra-experimental critical parameter (CPP) shifts combined) with hybrid modeling potentially reduces burden. iDoE can provide more response information in less overall time, whereas serves as a commodity to describe this behavior the best way. Therefore, combination both approaches appears beneficial for faster screening and especially interest at larger...
Single-pass tangential flow filtration (SPTFF) is a promising and increasingly important tool for continuous biomanufacturing intensified bioprocessing. SPTFF operates at high product concentrations often limiting the number of process development experiments therefore understanding. We developed hybrid model structures to predict concentration performance in serial parallel mode with up three membranes various pressures, feed flows protein concentrations. A single experiment gather training...
Introduction: For the implementation of robust bioprocesses, understanding temporal cell behavior with respect to relevant inputs is crucial. Intensified Design Experiments (iDoE) an efficient tool assess joint influence input parameters by including intra-experimental changes. Methods: We applied iDoE production phase a monoclonal antibody in mammalian bioprocess. The multidimensional design space spanned temperature, dissolved oxygen (DO), timing change, and growth category was...
The accurate estimation of cell growth or the substrate consumption rate is crucial for understanding current state a bioprocess. Rates unveil actual status, making them valuable quality-by-design concepts. However, in bioprocesses, real rates are commonly not accessible due to analytical errors. We simulated Escherichia coli fed-batch fermentations, sampled at four different intervals and added five levels noise mimic inaccuracy. computed stepwise integral estimations with without using...
Abstract In bioprocesses, specific process responses such as the biomass cannot typically be measured directly on‐line, since analytical sampling is associated with unavoidable time delays. Accessing those in real‐time essential for Quality by Design and technology concepts. Soft sensors overcome these limitations indirectly measuring variables of interest using a previously derived model actual data real time. this study, soft sensor based on 2D‐fluorescence data, was developed...
Ultrafiltration is a powerful method used in virtually every pharmaceutical bioprocess. Depending on the process stage, product-to-impurity ratio differs. The impact of impurities depends various factors. Solely mechanistic models are currently not sufficient to entirely describe these complex interactions. We have established two hybrid for predicting flux evolution, protein rejection factor and components’ concentration during crossflow ultrafiltration. were compared standard modeling...
Background Serological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity specificity of test systems is often poor, leaving room false positive negative results. However, conventional methods to increase decrease vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: "Sensitivity Improved Two-Test" or "SIT 2 " algorithm. Methods SIT involves confirmatory re-testing samples with...
Multicellular organisms cultivated in continuous stirred tank reactors (CSTRs) are more sensitive to environmental conditions the suspension culture than microbial cells. The hypothesis, that stirring induced shear stress is main problem, persists, although it has been shown these cells not so shear. As results largely based on Chinese Hamster Ovary (CHO) cell experiments question remains if similar behavior valid for insect with a higher specific oxygen demand. requirement of transfer rates...
Serological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity specificity of test systems often poor, leaving room false-positive false-negative results. However, conventional methods were to increase decrease vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: 'sensitivity improved two-test' or 'SIT²' algorithm.SIT² involves confirmatory retesting samples with results falling...
The applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and robustness for recombinant adeno-associated virus (rAAV) producing HEK 293 bioprocesses was evaluated. We present structured workflow extract process relevant information from PTR-MS data.Reproducibility volatile organic compound (VOC) measurements demonstrated with spiking experiments the data sets used evaluation consisted cell culture triplicates...
Abstract Objectives SARS-CoV-2 infection induces the formation of different antibodies. However, not all which might prevent virus from entering cell, although their concentrations correlate with titers viral neutralization tests (NTs). Antibodies against nucleocapsid (NC), e.g., can be classified as such. We aimed to prove hypothesis that apparent correlation between NC-antibody levels and NT-titers is mediated by simultaneously occurring antibodies spike-protein components. Methods...
Objectives Austria, and particularly its westernmost federal state Vorarlberg, developed an extremely high incidence rate during the COVID-19 pandemic. Healthcare workers (HCWs) worldwide are known to have increased risk of contracting disease within working environment and, therefore, seroprevalence in this population is particular interest. We thus aimed analyse SARS-CoV-2-specific antibody dynamics Vorarlberg HCWs. Design Prospective cohort study HCWs including testing at three different...
Abstract Background Austria, and particularly its westernmost federal state Vorarlberg, developed an extremely high COVID-19 incidence rate in November 2020. Health care workers (HCW) may be at higher risk of contracting the disease within working environment therefore seroprevalence this population is particular interest. Here, we analyzed SARS-CoV-2-specific antibody response Vorarlberg HCW a prospective cohort study. Methods A total 395 have been tested three different time points for...