Themengebiete für Studien- & Abschlussarbeiten - KIT

Themengebiete für Studien- & Abschlussarbeiten

Doktoranden des MAB

Institute of Process Engineering in Life Sciences
Section IV: Biomelecular Separation Engineering

KIT – University of the State of Baden-Wuerttemberg and
National Research Center of the Helmholtz Association www.kit.edu

Allgemeines

 Die folgende Übersicht dient dazu, Interessenten von Studien- bzw.
 Abschlussarbeiten (BA, MA) einen Überblick über die Arbeitsgebiete
 am Institut für „Molekulare Aufarbeitung von Bioprodukten“ zu geben.
 Interessenten mit konkreten Themenwünschen können sich direkt bei
 den jeweiligen Doktoranden melden oder allgemein bei Sebastian
 Andris (sebastian.andris@kit.edu).

2 24.01.2020 Themengebiete für Bachelor- und Masterarbeiten Institute of Process Engineering in Life Sciences
 Section IV: Biomolecular Separation Engineering

Laura Rolinger
Multimodale Spektroskopie als Process Analytical Tool
Jede Spektroskopieart kann Variationen in mindestens einer Proteinstrukturebene nutzen, um zwischen
verschiedenen, strukturell ähnlichen Proteinen zu unterscheiden. Aufgrund der Komplexität und
biophysikalischen Ähnlichkeit von biopharmazeutischen Proteinen und Kontaminanten, kann nur eine
Kombination verschiedener Spektroskopiearten alle interessanten Proteine während des Prozesses in Echtzeit
quantifizieren und charakterisieren.
 Techniken
 Unit operations im Downstream Processing
 (Chromatographie, Präzipitation, UF/DF)
 Analytik (UHPLC, ELISA)
 Spektrometrie (UV/Vis, FT-IR, Raman,
 Dynamische und Statische Lichtstreuung)
 Datenauswertung
 Datenpräprozessierung
 Multivariate Datenanalyse (SIMCA, MATLAB)
 Artifical neural networks
 Datenfusionsmethoden (Kalmanfilter, etc.)
 Sensorentwicklung
 Sensor design
 M. Rüdt, T. Briskot und J. Hubbuch, „Advances in downstream processing of
 biologics – Spectroscopy: An emerging process analytical technology,“ Journal of
 Software und Softsensor Programmierung
 Chromatography A, 15 11 2016 (MATLAB)

3 24.01.2020 Themengebiete für Bachelor- und Masterarbeiten Institute of Process Engineering in Life Sciences
 Section IV: Biomolecular Separation Engineering

Svenja Strauß – 3D Bioprinting

 Background:
 Automated, reproducible

 © Anton-Paar
 manufacturing and analysis of
 complex structures with biomaterials
 containing viable cells

 Experimental:
 - Printing optimisation of biomaterials
 - Development of standardised analytical

 © Tecan
 methods

 Analytics and tools:
 - Rheometry
 - Microscopy
 - Image processing
 - Matlab

4 24.01.2020 Themengebiete für Bachelor- und Masterarbeiten

Nils Hillebrandt
 Entwicklung eines hochdurchsatzfähigen Hochfrequenz-Rheometers zur Analyse der
 viskoelastischen Eigenschaften hochkonzentrierter Proteinlösungen [1]

 Ziel Techniken/Arbeitsbereiche
 Korrelation viskoelastischer Ansteuerung von
 Eigenschaften mit der Lösungsstabilität piezokeramischen Aktoren und
 von Proteinlösungen [2] Sensoren
 Aufgaben Schwingungsanalyse
 Evaluierung und konzeptionelle Programmierung mit MATLAB
 Optimierung von Ansteuerung der peripheren
 Messaufbau/Konstruktion Bauteile (Pumpen, Peltier-
 Design und Implementierung der Element, Temperatur-
 Automatisierungs- und Controller
 Temperierungseinheit
 [1] Kooperation mit dem Institut für Automation und angewandte Informatik (IAI), Ansprechpartner: Prof. Dr. Christian Pylatiuk

 [2] Schermeyer et al. (2016). Squeeze flow rheometry as a novel tool for the characterization of highly concentrated protein solutions.
 Biotechnology and Bioengineering, 113(3), 576–587. https://doi.org/10.1002/bit.25834

5 24.01.2020 Themengebiete für Bachelor- und Masterarbeiten

Nils Hillebrandt

 Online-
 Monitoring
 Source:
 http://spectrumlabs.com/filtration/K
 R2System.html

 Advancing
 ultra- and
 diafiltration In collaboration with
 High-
 Throughput
 Modeling
 Source: https://gosilico.com/

 Source:
 https://www.sartorius.com/en/products/
 process-filtration-purification/process-
 filtration-hardware/crossflow-holders-
 systems/crossflow-systems/ambr-
 crossflow

6 24.01.2020 Themengebiete für Bachelor- und Masterarbeiten

Dennis Weber
 PROTEIN STABILITY IN FREEZE-THAW OPERATIONS
 Background Material & Methods

 © Grant
 Freezing and thawing are necessary Experiments
 process units during the production of • µL- and mL cryodevices

 biopharmaceuticals.

 © Tecan
 • Robotic liquid handling station

 During the freezing process, freeze
 concentration might occur. This may
 lead to: Analytics

 © Malvern
 • Protein aggregation • SLS, DLS
 ice
 • Surface denaturation • Melting temperature
 • pH denaturation • FT-IR
 • Cold denaturation • …
 • …

 T / °C
 CFD simulations
 It is the aim of my thesis to evaluate the
 r/m
 protein stability during freezing/thawing.

7 24.01.2020 Themengebiete für Bachelor- und Masterarbeiten

Sandra Haas
 Development and establishment of bioinks made of specially developed
 elastic proteins for 3D printing of high-performance materials

 Theoretical background
 Elastic materials are mostly petroleum-based and not biodegradable. The goal of my work is the use of biotechnologically
 produced, elastin-like proteins (ELP) to produce highly elastic, 3D-printed hydrogels. Therefore, it is necessary to develop an
 understanding of the factors influencing the later mechanical properties of the resulting hydrogels.

 Elastin-like proteins (ELP) Ink development 3D-Printing

• Development of protein analytics • Formulation of bioinks (model proteins and ELPs) • 3D printing using different techniques
• Optimisation of downstream processes • Characterisation of formulated bioinks and hydrogels (Stereolithography, Extrusion)

 8 24.01.2020 Themengebiete für Bachelor- und Masterarbeiten

Christina Wegner – Protein Crystallization
 Purification of biopharmaceuticals by protein crystallization is an attractive alternative to costly
 chromatography. Up to now, proper conditions for crystallization of proteins on a technical
 scale can only be identified empirically and therefore knowledge on phase behaviour and
 rheology of complex protein solutions is required for crystallization process development.

 Current projects:
 Spectroscopy
 - Creation of HTS for selective crystallization
 
 - Development of HTS analytics for specific protein On-line
 quantification 
 analytics
 - Development of automated image recognition software

 Methods:
 - Tecan – LHS
 - Formulatrix – protein crystallography screen builder Phase behaviour Prediction
 - Light scattering HT screening
 - Spectroscopic methods Rheology
 Nucleation rate
 - Multivariate data analysis © Formulatrix 
 © Tecan 
 ′
 © Wyatt
 © Tecan
 ′′

9 24.01.2020 Themengebiete für Bachelor- und Masterarbeiten

Angela Valentic
 Changes in dispersity, structure and phase behaviour of
 virus-like particles (VLPs) in the presence of nucleic acids
 Motivation: Virus-like particles as carrier system for gene therapy

 Tasks: Analytical development + method development

 Disassembly
 and effect of
 host cell nucleic
 acids

 Reassembly in
 the presence of
 nucleic acids
 VLP loaded
 VLP with RNA

 Analytics: Experimental:
 - qPCR - Process development + characterization of process
 - cGE parameters by common and nucleic acid specific
 - SLS, DLS analytical tools
 - RP-/SEC- UHPLC - VLP production by cultivation in E.coli and purification by
 - Spectroscopic methods e.g. precipitation, chromatography methods and UF/DF

PhD project started 09/2019 @Wyatt @ThermoFisher @ThermoFisher

 10 24.01.2020 Themengebiete für Bachelor- und Masterarbeiten

Horizon 2020
 Marie Sklodowska-Curie Actions
 Innovative training network Narmin Suvarli
 Synthesis of Hybrid Nanoparticles via Aerosol Thiol-ene Photopolymerization
 Process

 Bio-agent

 HS

 Atomization Photoreaction Bioconjugation
 HS SH

 Aerosol Polymer
 Spray Solution Droplets Nanoparticles Bioconjugated
 Nanoparticles
 Applications

 Imaging
 • Cancer Screening and and Diagnostics

 treatment

 • Drug delivery

 • Encapsulation into hydrogels
 for enzymatic reactions Photothermal
 therapy

Legend:
 HS
 Gold Nanoparticle 3-functional thiol Photoinitiator 3-functional ene Cancer tumor
 HS SH

11 24.01.2020 Themengebiete für Bachelor- und Masterarbeiten

David Grijalva – 3D Bioprinting

 Background:
 Automated, reproducible manufacturing and analysis of
 complex structures with biomaterials containing viable
 cells

 Experimental:
 - Evaluation of biomaterials for 3D printing
 applications
 - Characterisation cell metabolic activities

 Analytics:

 © Anton-Paar
 - Rheometry
 - Flow cytometry
 - Microscopy
 - UV/Vis spectroscopy
 © Miltenyi Biotec

 © Tecan

 © Zeiss
12 24.01.2020 Themengebiete für Bachelor- und Masterarbeiten

Marieke Klijn
 Partners BE-BASIC project

 Protein solubility and stability:
 An experimental toolbox and generation of descriptions

 Experimental Prediction

 Correlation
 Phase behavior Characterization Protein structure
 of solution conditions
 QSAR
 QSPR
 MD

Current activities
• Automated phase recognition algorithm Industry
• Building database for previously obtained
 Phase behavior studies
 characterization results DSP steps influence
Updated: 22.10.2015, PhD project started in sept. 2015 Model-based process development
13 24.01.2020 Themengebiete für Bachelor- und Masterarbeiten Institute of Process Engineering in Life Sciences
 Section IV: Biomolecular Separation Engineering