Doctoral Candidates
DC1: Fluidic force microscopy for soft matter mechanics
Host: Aarhus University
Supervisor: Mingdong Dong
Judith Zubia Aranburu

Project description:
Mechanobiology is the study of how cells sense and respond to mechanical signals, and it is an emerging multidisciplinary field that combines biophysics, engineering, medicine, and biology. The aim of this project is to establish a soft matter metrology framework and develop new methodologies based on atomic force microscopy (AFM) and Fluidic Force Microscopy (FluidFM) for the quantitative analysis of soft matter such as proteins, mammalian cells, and to apply these techniques for identifying how mechanical cues contribute to development, differentiation, physiology and disease.
Potential research directions include: development of hybrid techniques implementing AFM and FluidFM with optical and electromechanical systems; standardisation of nanomechanics, single-molecule and single-cell force spectroscopy; studying the interaction mechanisms for example between virus and cell.
The project will be run in collaboration with the Danish National Metrology Institute, where the candidate will perform experiments and work on a user-case in collaboration with a corporate partner.
DC2: Fast nanomechanical spectroscopy for soft matter
Host: Consejo Superior de Investigaciones Científicas
Supervisor: Ricardo Garcia
Luca Franco

Project description:
The objective of the project is to develop and optimize a high-speed nanoscale mechanical property mapping of soft matter in their native condition. Soft matter involves a wide variety of materials ranging from polymer blends, biomolecules and live cells. The results of the project will have implications in different societal challenges such as energy storage, sustainability and health. The project will involve AFM methods, artificial intelligence, instrumentation and materials preparation.
DC3: 3D mechanical stimulation for studying mechanotransduction of MSCs in a hydrogel
Host: Aarhus University
Supervisor: Menglin Chen
TBA
Project description:
This project focuses on the development of multi-modal cell stimuli systems. The objective is to develop a unique system that can realise mechanical, electrical and biochemical cell stimuli, while deciphering the role of different factors such as the mechanics, porosity, chemical composition, presence of integrin binding sites and viscoelastic properties of the scaffold in dictating the stem cell differentiation. Potential research directions include: development of a novel piezoelectric cellulose nanocrystal system for cell mechanotransduction; establishing advanced sensing, measurement, actuation and control methodologies for precision mechanical stimulation and characterisation; development of a picobalance based on a photothermally excited cantilever to link cell mass to cellular state and morphology.
DC4: Electrochemical Exploration of Soft Matter Interfaces: Nanoscale Probing and Advanced Microscopy
Host: Université Paris Cité
Supervisor: Frédéric Kanoufi
Mina Orouji

Project description:
Electrochemistry is a field that enables the probing and manipulation of soft matter, which is becoming increasingly important in the context of societal electrification. Examples include the production of green hydrogen and the utilization of water in salt electrolytes for energy storage or conversion devices, both of which involve understanding liquid/liquid or solid/liquid/gas interfaces influenced by electrochemical processes.
In this study, and within the context of soft matter for energy applications, we will utilize nanoscale electrochemical methodologies to investigate soft matter at the level of individual micro/nano objects. However, to unveil the complexity of these objects, such as the growth, motion, or deformation of liquid nanolayers, drops, bubbles, or polymer microgels, nanoscale electrochemistry techniques need to be integrated with complementary in situ information. We will leverage our platform of refractive-index-based optical microscopies, including interference reflection and interference scattering (iSCAT) microscopies, to image and quantify in situ or operando the physical and chemical phenomena associated with the electrochemical triggering or interrogation of soft matter objects at high throughput.
DC5: Broadband nano-electrical spectroscopy for soft matter
Host: Johannes Kepler University
Supervisor: Georg Gramse
José Huertas Pedroche

Project description:
The objective of this project is the implementation and optimization of a new broadband electrostatic force microscope for fast acquisition of electrical properties (permittivity and loss/ conductivity) in a wide frequency range from kHz to GHz. The aim is to acquire full electrical spectra of the sample under study during one AFM image, which requires synchronized high-speed data acquisition and storage while standard imaging. In an initial step the system will be optimized for operation in air environment. In a second step also in-liquid measurement will be implemented.
DC6: Fundamentals of liquid – liquid biopolymer phase separation
Host: Norwegian University of Science and Technology
Supervisor: Bjørn Torger Stokke
Madhura Bhaiyasaheb Bonde

Project description:
The objective of the DC project is to investigate fundamental, nanoscale properties of multivalent biopolymer partners undergoing liquid-liquid phase separation (LLPS), an emerging mechanism for membrane-less biological organization and cascading mesoscale structure formation. The project involves development of label-free quantitative imaging procedures, and combine these with other advanced fluorescence based optical imaging and force spectroscopy to elucidate impact of molecular and environmental parameters on LLPS.
DC7: Single cell mechanobiology and soft matter metrology
Host: Aarhus University / DFM
Supervisor: Mingdong Dong / Husnu Aslan
Leyla Nur Akay

Project description:
Mechanobiology is an emerging interdisciplinary field that combines biophysics, engineering, medicine, and biology in the study of how cells sense and respond to mechanical signals. The understanding of how mechanical forces induce change at all levels, from single molecules to cells and tissues, has led to scientific advances in the understanding of cell adhesion, DNA conformation, membrane trafficking and much more. This knowledge has in turn translated to advances in tissue engineering, high speed cancer diagnostics, and improved agricultural products to name but a few examples.
At the forefront of single-cell mechanobiology are nanotechnology techniques such as atomic force microscopy (AFM) and nanopipettes. AFM can be used to measure mechanical properties of cells as well as subjecting individual cells to mechanical stresses, while nanopipettes are powerful sensing tools used for single-molecule detection, monitoring biological processes and as scanning probes for imaging.
In this PhD project, we will apply AFM, nanopipettes and the related fluidic force microscope (FluidFM) for single cell mechanobiology. Potential research directions include: development of combined AFM and nanopipette methods for quantifying the mechanics of soft matter, proteins and mammalian cells; establishing standardised metrics for single-molecule and single-cell force spectroscopy; modelling ion diffusion in the porous structure of hydrogels and biological matter using finite element simulations.
The candidate will be hired by Dansk Fundamental Metrologi A/S (DFM) and enrolled at Aarhus University (AU). You should expect to spend your time primarily at Aarhus University.
DC8: Development of electron diffraction-based techniques for applications to soft matter and nanofibres
Host: Stockholm University
Supervisor: Tom Willhammar
Tine Kalac

Project description:
Biopolymer nanofibres play an important role in the construction of biological systems, where they contribute with mechanical and other physical properties. Fibres can be constructed from proteins, as in amyloids, or polysaccharides, such as cellulose and chitin. Their properties will be defined by the structures ranging from the mesoscale to the atomic level and it is hence of utmost importance to develop techniques to study their structures. Electron microscopy and electron diffraction have evolved over the last years into a new era. Cryo-EM was awarded the Nobel Prize in 2017 for studies of protein structures and methods for 3D electron diffraction have pushed the limits of atomic structure determination into the nanoworld.
In this project, we will utilize emerging opportunities for the rapid collection of electron diffraction data using transmission electron microscopy, called scanning electron diffraction and three-dimensional electron diffraction. These techniques are opening up for studies of electron beam-sensitive specimens, such as biopolymers and proteins, at the nanoscale.
The project will focus on the development of protocols for data collection and data analysis as well as the interpretation and utilization of the resulting data to understand the atomic arrangement and how this knowledge can aid the understanding of the properties of the biomaterials and how they can be used in the development of devices. The technique will generate large amounts of data and hence protocols for the analysis of big data will be necessary.
DC9: Untethered micro- and nanorobotic biotools
Host: Heidelberg University / Max Planck Institute
Supervisor: Peer Fischer
Maria Inmaculada Real De Asua

Project description:
One objective of our research is to develop untethered (wireless) tools with which one can penetrate tissue and achieve targeted delivery of therapeutics and genetic material. The aim of this project is to develop hybrid micro- nano-robotic systems that are controlled by magnetic, acoustic, or chemical fields and that can address one or several of the following challenges:
- Generate forces and penetrate tissues effectively.
- Function as a sensor to probe cells, and the structure of tissues.
- Implement the ability to sense chemical gradients and to autonomously navigate.
- Achieve the assembly of cellular systems into ‘living machines’.
- Aid the development of minimally-invasive surgical tools.
Our research typically starts with a physical effect that we study to then develop tools and experimental systems at the micro- and nano-scale.
DC10: Digitalization of Biomaterial Research via Deep Learning Approaches
Host: Karlsruhe Institute of Technology
Supervisor: Joerg Lahann
Abdelrahman Elrawy

Project description:
- Development of a deep learning algorithm assisted platform for material research
- Fast screening of biomolecular interactions
Fast screening of biomaterial performance - Develop mathematical relation between biomaterial binding type and surface properties
Expected Results:
- Deep learning-based analysis of fingerprint-like drying droplet patterns by training of convolutional neural networks (CNN)
- Preparation of model biomaterial surfaces using systematic variation of surface chemistry via vapour deposition polymerization of functionalized poly-p-xylylenes
- CNN extracts cellular localization patterns in polarized light microscopy (PLM) images via end-to-end hierarchical feature representations
- Screening of biomolecular interactions (e.g. DNA-protein or drug interactions)
- classify biomolecule interaction levels to predict the optimal ratio for binding between two particular species
- optimize and re-define the pretrained CNN to achieve more data from the images obtained by PLM imaging method
- Scalable and accurate detection schemes for stratification of conformational and structural biomolecule alterations
- Screening of biomaterial performance via investigation of biomolecule-surface interaction via droplet patterns
- classify biomolecule interaction to predict biomaterial binding/adhesion properties
- complementary characterization via elaborate techniques (e.g. Circular Dichroism, Time-of-Flight Secondary Ion Mass Spectrometry, Imaging Ellipsometry)
- improve model management to ensure reproducibility by avoiding information loss
DC11: Mobile soft nanorobotics for nanomedicines
Host: University of Warwick
Supervisor: Yanling Tian
Maria Jose Fernandez

Project description:
The objective of this DC project is to develop nanopipette delivery-based nanoparticle (nanorobot) therapy for single cells. The multifunctional nanopipette technique will be developed for nanoparticle release and manipulation within single cell. Multiphysical field finite element modelling and molecular dynamics simulation methods will be utilised to explore the intrinsic mechanisms acting within the nanopipette delivery and manipulation. The intelligent vision-based trajectory tracking will be established and experimentally validated.
Expected Results:
Development of multifunctional nanopipette suitable for nanoparticle delivery and manipulation within single cell. In-depth understanding of the intrinsic mechanisms underpinning the nanopipette delivery. Enhanced nanoparticle tracking techniques for the nanopipette manipulation. Precise nanomedicine for single cells.
DC12: Video rate super-resolution structured illumination microscopy (SR SIM)
Host: University of Leeds
Supervisor: Michelle Peckham
Greeshma Pradeep S

Project description:
The objective of this DC project is to establish a high speed SR SIM and expand it for multi-color and video rate super-resolved imaging of cells. Using spot-scanning SR SIM with multiple foci produced with improved microlens arrays (e.g. metasurfaces) and scanned across the sample with galvanometric mirrors, the improved imaging resolution can reach up to 80 nm and more than 230 frames for 512×512 pixel region of interest. Based on a Windows+RTX architecture, a raw data acquisition, and CMOS camera control, and on-the-fly 3D image reconstruction and display system will be established and validated based on traditional Wiener deconvolution method. The iterative (Hessian matrix based) deconvolution approach will be utilized obtain super-resolved 3D images during the post-processing steps.
DC13: Autonomous functional nanopipettes: a new imaging platform and the intelligent synthesis of soft nanobots
Host: University of Warwick
Supervisor: Patrick Unwin
Anna Pushkareva

Project description:
This study focuses on the development of nanopipettes for 2 major applications: (1) we shall make an intelligent nanopipette probe imaging platform to facilitate autonomous imaging and manipulation of cells and soft matter. The instrument will integrate an x,y,z piezo positioning system with an inverted microscope that will read optical images to identify regions of interest for investigation or intervention by the nanopipette. The instrument will be based on an existing LabVIEW FPGA architecture and incorporate machine learning protocols. It will be applicable to SICM and other forms of nanopipette probe microscopy (scanning electrochemical cell microscopy and variants thereof); (2) the use of nanopipettes and nanopore arrays for the synthesis of soft nanobots, through the development of a platform that makes use of nanoscale electric fields for mixing reagents and with active (feedback) control in the synthesis process.
Expected Results:
1) An innovative platform for functional nanopipette imaging that will have wide applicability for which the software will be made freely available to the academic community as part of the Warwick Electrochemical-Scanned Probe Microscope; 2) A synthesis platform that will enable the creation and analysis of tailored soft materials with built in functionality for applications as nanobots.
DC14: Mechanics of the actin and microtubule cytoskeletons
Host: Eidgenössische Technische Hochschule Zürich
Supervisor: Tomaso Zambelli
Haishuo Guan

Project description:
The objective of the DC project is quantification of how forces are transmitted to and by the cytoskeleton relying on FluidFM (an AFM-based pipette) for the mechanical-electrical-chemical stimulus combined with forefront fluorescent techniques for the read-out. Cytoplasm consists of a water-containing matrix formed by a cytoskeletal network of interconnected protein fibers constituting the force-generating cell machinery, finally affecting cell shape, motility, division, and proliferation. Cytoskeleton behaviour will be thus modelled from the perspective of hydrogels, a synthetic or natural water-swollen polymeric network containing chemical or physical crosslinks.
