Vacancies

The main objective of this project is to investigated filtration behaviour of flexible particles and components (e.g. gel particles, droplets, cells), and to design membrane separation processes in such a way that they take this as a starting point of design. The deformability of these particles under actual filtration conditions is far from understood, and likely is influenced by bulk and surface characteristics. For this the following techniques will be used: 

1) Microfluidic tools with which membrane structures can be emulated will be used to investigate the effect of pore geometry, and orientation, on retention.

2) Modelling of the permeation behaviour of flexible particles based on general bulk and interfacial properties.

3) Design or select membranes based on the identified behaviours, together with the industrial partners.

4) Show a proof of principle using an application system relevant for one of the industrial partners. 

Preparative scale cross-flow filtration devices typically contain several layers of soft materials. Different membrane and spacer materials are stacked to achieve optimal retention and capacity for the respective target molecules. These stacks are arranged in cassettes to achieve high surface areas at low footprints. The devices usually have complex internal geometries with channels and flow redirections to direct the liquid flow and hold the filter material in place. Non-homogeneous flow along the filter surface, local compression of the filter material and hydrodynamic bypasses are unavoidable by design. Flow resistance and mechanical compression versus defects due to overstress need to be analysed and balanced. Special attention will be given to scalability of the filtration process and to the transferability of the findings between laboratory and production scales. 

Enrolment in Doctoral degree: RWTH Aachen University

This project aims to design smart membranes with bio-inspired gradient pore structure to achieve precise fractionation of flexible BMs from body fluids, which is to overcome a major challenge in conventional membranes due to limitation in pore structure versatility. To fill this research gap, this project proposes to

1) Design membrane with a gradient of porosity and/or a gradient of interactions along the pore length, i.e. the architecture of the pores. The manufacturing of the new membrane will be based on phase separation techniques with new additives having a nano-structuring effect (developed by the company Polymem) in order to ensure the specific design of the pores.

2) Conduct filtration experiments to demonstrate that the transmission of RNA can be greatly improved when asymmetric membranes are used in a reverse mode, i.e., the filtration flux is directed from the macro-porous support towards the denser skin of an asymmetric microfiltration membrane. The operating conditions will be optimized in order to benefit from a higher selectivity during the separation.

3) Use advanced characterization to identify specific pore/ molecule interaction within the sheared flow in an hourglass pore can explain this mechanism (interact with DC1).

4) Carry out theoretical modelling of the transport of molecules through membranes to describe how the control of a porosity gradient across a membrane would allow to reduce concentration polarization and to increase the transmission of macromolecules.

The objective of this PhD project is to design separation units with novel electrospun membranes for in-situ virus removal from simulated bio-fluids. Specifically, this project aims to:

1) Screen through biocompatible materials that can form mechanically strong thin-film structure, fabricate a series of nanofibrous membranes with selected polymers as the blank control.

2) Fabricate a series of composite membrane by blending the selected polymer with pre-functionalized copolymers to a selected virus. The formation of membrane morphology will be optimized. Characterize the membrane morphology, chemistry and conduct biocompatibility testing.

3) Assemble the as-fabricated membranes into the housing to form a separation unit, whereby the hydrodynamics will be optimized. 

4) Set-up and evaluate the separation performance of the membrane unit using synthetic feedstocks, examine the viral removal efficiency.

5) Establish a mathematical model to understand the transport mechanisms of the membranes by examining the synergistic separation effects; examine the structure-chemistry-fluid relationship. Develop a mechanistic model by integrating factors associated with the mass transport and flow dynamics, verify the model via experimental data.

This project addresses critical challenges in dealing with highly concentrated streams particularly relevant to protein harvesting and fractionation, providing an energy-efficient and high throughput alternative with accurate control of protein crystallization, purity and yield. Thus, the main objectives are:

1) The design of functional patterned membranes with desirable 3D topography to promote heterogeneous crystallization on the surface;

2) The synergistic effect between membrane-protein interaction and solvent removal rate will influence protein crystallization, yield and purity;

3) Design an integrated process with optimal operating conditions to allow effective control of the supersaturation level of the protein solutions, including the solvent types, removal rate and process parameters;

4) Process routes to successfully produce protein crystals of various forms and size distribution will be an important outcome.

The project aims to apply innovative and sustainable methodologies to recover high added-value compounds from dairy wastes. The use of whey, the most relevant cheese by-product, allows to minimize the environmental impact of dairy industry by recovering greatly exploitable value-added proteins. In more details, the idea is to use whey proteins to develop an edible antimicrobial coating to increase food shelf life and prevent spoilage. In order to reach the proposed objective, the research activity will be based on the development of an integrated membrane-system that will consists of sequential membrane separation processes coupled with hydrolysis bioreactors, to recover and hydrolyse whey proteins. Whey protein enzymatic hydrolysis will be carried out in a membrane bioreactor (EMBR), using proteolytic enzymes. The bioactive peptides obtained from whey proteins hydrolysates will be then purified and fractionated by membrane chromatography. The use of functionalized membrane adsorbers for peptides fractionation is an attractive alternative to chromatographic resins, since they are less expensive, scalable and can operate at fast flow rates. Since most antimicrobial peptides from whey proteins are positively charged at neutral pH, they can be fractionated using cation exchange membranes by tuning the elution gradient. Whey-derived antimicrobial peptides will be characterized and tested in different recipes to obtain an edible coating for a semi- seasoned cheese. The formulation will be tested during cold shelf storage with the aim to reduce biofilm formation and the persistence of spoilage bacteria in food environment.

Membrane adsorbers have smaller footprints and can be operated at higher flow rates as compared to packed bed chromatography which typically provides higher capacities. New membrane materials with micro-porous gel elements and competitive capacities are recently developed at Sartorius. They can be functionalized to facilitate affinity, ion-exchange and mixed-mode chromatography. The combined design of porous structures, functional groups and operating conditions opens a wide portfolio of applications for membrane adsorbers. For example, field flow fractionation can potentially be replaced by chromatography and ultrafiltration. Rapid cycling of single and tandem units or simulated moving bed processes allow moving towards continuous processing. Numerous impact factors pose a challenge for device characterization and process development. Process models similar to the general rate model for packed bed chromatography will be used for tackling this challenge and exploring the applicability of porous membranes in particular for antibodies and small particles. Digital tools will also be made available for smart operation and control of automated systems.

Enrolment in Doctoral degree: RWTH Aachen University

The total cost of ownership is required for process feasibility assessment, that includes process economics and life cycle analysis. Scenario analysis will initially be based on available data from the company and the existing literature. Refined input from other DCs in the network will be included, combined with tailored experiments regarding process design. The effectiveness of the process is influenced by many aspects including design parameters, like module length and membrane area, operation parameters, like flux and recovery, and manufacturing parameters, like choice of materials that affect recyclability and lifetime. A dedicated and sound sensitivity analysis regarding these aspects is required to provide a fair and realistic estimate of the total cost of ownership, benchmarked against conventional industrial practise. Specifically, this project will provide:

1) A full process scenario analysis, including the life cycle analysis, to develop the methodology to establish a technical process strategy decision framework, providing a holistic view of the environmental, economic and health impacts of emerging technologies.

2) Selected scenarios could be analysed amongst the separation processes and involved operational unit designs (e.g., membrane modules, adsorbers, bioreactors) (interacting with DC3–5, DC7). Experimental results from DC11 (on membrane and process conditions), simulations performed by DC2 (on transport mechanisms) and DC7 (process simulation), and alternative integrated membrane processes designed by DC6 and DC12, are expected to provide DC8 with the appropriate information to extend on the available literature.

3) The holistic analysis, from membrane and module design to full scale process operation, provides reliable prediction regarding the overall feasibility.

4) Inversely the scenario analysis by DC8 can provide guidelines/ requirements for novel membranes/devices to be designed by DC3-5.

Enrolment in Doctoral degree: University of Twente

The project will focus on the development of novel units for membrane chromatography. Packed column chromatography is one of the main separation processes in the purification of biomolecules, and membrane chromatography is an emerging technology that shows great promise. However, there are still challenges with the implementation of membrane chromatography in industrial bioprocesses, mainly due to the lack of suitable equipment that can provide reliable performance at different scales. As with conventional packed columns, uniform mobile phase distribution and reduced residence time distribution within the stationary phase are essential to ensure efficiency and resolution in membrane processes. From this perspective, the geometry and architecture of the module play a critical role. Membrane modules can be classified according to the flow path within the bed: axial flow or radial flow. Regardless of the flow path, membrane chromatography modules are characterized by a bed with a high surface area to length ratio, uneven residence time distribution and a high dead volume fraction. These parameters and their effects on the process performance vary significantly with the module size and cannot be accurately predicted based on experimental results obtained on small modules. As the module size increases, the uniformity of fluid distribution deteriorates, the residence time distribution increases, and the ratio of dead volume to membrane volume alters. 

The main objective is to develop smart digitalized processes (combining modelling, in-line sensors and process actuation) to ensure versatile downstream processes for the separation of bio-mixture (micro-organisms, viruses, macromolecules). The separation can be based on various mechanisms: size exclusion (MF), charge repulsion (NF, UF, electrophoresis), diffusion (Flow-Field-Flow Fractionation, diffusiophoresis, forward osmosis). The main challenge is to find the proper combination of mechanisms through the chaining of different processes in an industrial separation line. Modelling and simulation will help to optimize the whole separation process. For a versatile operation of the separation lines, these processes have to be monitored with in-line sensors to allow a smart (possibly with AI) and efficient separation. The PhD will have to couple modelling, design, and process simulation/control/automation:

1) Development of continuous automated FFF with in-line sensors
2) Coupling of FFF and UF/MF (or other techniques) to propose a versatile “smart” separation process
3) Development of the software (relying on process modelling and simulation) allowing the control of the automated processes 4) Application to the fractionation of fermentation broths or cell culture

To provide a better understanding of the conditions that have an effect in membrane harvesting of different microorganisms from culture broth, specifically:

1) Trained to grow various cells (e.g. Escherichia coli, Saccharomyces cerevisiae, Blakeslea trispora, mammalian cells) in different scales and bioreactors (e.g. shaking flasks, small bioreactors, perfusion systems).

2) Screen a number of four available commercial MF and/or four UF membranes with different configurations (e.g., flat sheets, tubular, hollow fibre, etc.) and material (e.g., PES, PVDF, etc) performance initially with a bacterium (E. coli) and a cheap and relatively simple culture broth, such as Luria–Bertani medium.

3) Evaluate and optimize the cell separation conditions (temperature, transmembrane pressure, flow rate, optimum surface area to broth load, etc.) Detailed evaluation of the filtration performance of the two best membranes material/configuration under the optimum operating conditions with different E. coli culture media and culture ages.

4) Evaluate the performance of the two best performing membranes under the optimum conditions derived from the previous stages with S. cerevisiae (yeast) and Blakeslea trispora (fungi) cells and relatively simple and appropriate broth in each case.

5) Compare the different microorganism behaviour and try to get a universal model for the filtration behaviour. Characterize the membrane surface by various spectrophotometric techniques, such as FITR, Raman, etc.

The current PhD main objective is to develop a novel and low-energy simultaneous production of intracellular, carotenoids, and extracellular, hydrolytic enzymes, by using the fungi Blakeslea trispora in a membrane bioreactor using agri- food waste as carbon resource, specifically:

1) Screen a number of available juice industry waste pulp material (e.g., beetroot, apple, citrus etc.) in shake flasks to evaluate fungus yields in the two target products (carotenoids and hydrolytic enzymes). These products yields will be mainly evaluated using the existing previous knowledge and appropriate protocols that are in place.

2) Evaluate in custom made small volume (500 mL) batch bioreactors the short-term performance of submerged MF/UF tubular/hollow fibre membranes. Optimize in these small bioreactors the growth conditions (e.g., carbon source, product and cells removal and cells recycling ratio etc) and the in situ physical cleaning of membrane by backwashing for prolonging the operating periods and achieving the higher possible productivities.

3) Set-up and evaluate long –term performance in a larger capacity (3 L) custom-made membrane bioreactor and appropriate automation and control. The membrane bioreactor will be equipped with a conductivity probe, turbidity probe probe, and an online gas analyser able to record in real time all the products formation providing crucial information for the system kinetics and performance.

4) Use of a second side UF membrane system that will allow the hydrolytic extracellular enzymes to reach higher concentrations.

5) Techno-economical evaluation of the proposed combined extracellular and intracellular biotechnological products formation in comparison with other existing processes.