Virtual ToolBox

Light-based 3D printing equipment which can create curved 3D substrates based on biocompatible and/or cell-interactive polymers (in a wide range of resolutions ranging from sub-µm to µm). The constructs can have dimensions up to cm³ scale.

Multiphoton polymerisation is the highest resolution additive manufacturing technique, capable of printing features down to ~200nm. At Nottingham, we have both a Nanoscribe GT2 and an UpNano NanoOne. Our Nanoscribe is also fitted with the Heteromerge module, allowing multi-material 3D printing. The UpNano is capable of printing in a sterile, heated, humidified environment suitable for live cells.

The NMRC is an inter-disciplinary facility dedicated to supporting and promoting world-leading nanoscience and materials characterisation.

Facilities include:
Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM), Raman Spectroscopy, Secondary Ion Mass Spectrometry (SIMS), X-ray Photoelectron Spectroscopy (XPS), Nanofabrication Suite (ebeam lithography), Biophysical Analysis, Cryogenic Materials Characterisation, Particle Sizing, Confocal Laser Scanning Microscopy, and a dedicated suite for CL2 cell culture.

Allows for the measurement of the electric properties (resistance and capacitance) of planar lipid bilayers

A method to generate protein patterns on (flat or curved) surfaces.

The method for the bending elasticity measurement of lipid membranes via thermal shape fluctuation analysis (TSFA) is based on the autocorrelation analysis of thermal shape fluctuations of quasispherical giant (~10-100 micrometers in diameter) unilamellar vesicles (GUV). The TSFA exploits the relation between the bending elasticity of the lipid bilayer, its membrane tension and the amplitudes of GUV's shape fluctuations, due to the Brownian motion of the water molecules, surrounding the membrane. The non-invasive approach consists in videomicroscopy of the fluctuating GUV membrane, followed by digitization of vesicle images and mathematical analysis of the recorded fluctuations, yielding the bending modulus of the membrane with high accuracy (~ 5%) due to the stroboscopic illumination of the sample.

We developed a light-based method to create stable microscale topographies on diverse types of hydrogels (including polyacrylamide, GelMA, etc). Gradients and complex-shape topographies can also be robustly created.

We developed a method to non-invasively create and erase microscale topograhies on cell-compatible photoresponsive hydrogel.

A microfabricated PDMS chip containing a library of curved structures (convex and concave cylinders, spheres, torus).

Bioprinter enables the production of designed three dimensional structures using cell-laden soft polymers (also known as bioinks typically hydrogels+cells). The structure of the bioprinted object can be digitally designed and given the use of rheologically and structurally competent bioinks. Each filament extruded can be 100-200 micrometers in diameter and mm - cm structures can be typically produced. Besides extrusion bioprinting we also offer laser assisted bioprinting which can print droplets of 10-100 micrometers containing cells. This technology can generate larger tissue structures bottom up in additive manufacturing mode of operation.

A fluidic chip that allows for template casting channels in custom gels. Allows for apical and basolateral sampling, fluorescent imaging and 4 channels run parallel both flow or left staticly.

We obtain CAD data by scanning surfaces with the 3D optical scanning system in our laboratory. Then, we can physically produce three-dimensional prototype models from this data by using 3D printers. We can perform dimensional, geometric and surface analysis of the models we produce.

Microscope ZEISS Lightsheet Z1

Light Sheet Microscopy allows measurements of 3D Cell Cultures and tissues. The measurements can be performed on fixed and living cell cultures. The sample chamber is set up to allow for controlled conditions of humidity, temperature and CO2. A range of laser sources are available (405nm, 488nm, 561nm, and 638nm) to allow for standard measurements of typical fluorophores. 10x and 20x water objectives are available.

The system also allows measuring of cleared samples after refractive index matching with a 20x clearing objective and the respective sample chamber.

Projection microstereolithograohy is a layer-by-layer 3D printing technique. Compared to 2PP/MPL, it is much faster at manufacturing, but at lower resolution. We have two Boston Microfabrication (BMF) systems, the S130 (2um pixel size) and the S240 (10um pixel size). These systems are designed for industrial manufacturing and can achieve scale versus smaller systems. The S240 is also housed within a microbiological safety cabinet for live cell printing.

Electrophysiological study of membranes and assessment of transmembrane resistance and ionic currents.

A bioreactor that can be used to culture tubular constructs with controlled and independent application of shear flow and stretch.

An interactive tool for recognizing bicontinuous structures in TEM sections based on comparison to mathematical "nodal surface" models.

I use the methods of differential geometry in the consideration of curves and surfaces. In particular, I study curvature-based functions and their variations during infinitesimal bending .

Python codes for taking an stl file and calculating local curvatures, using libigl-based implementations. Simple to use, and easy to visualise in VTK (VTK files are automatically generated). Also possible to create interface shape distributions (k1k2 plots), and generate the input files for Karambola (software for Minkowski functional calculation).

A tool developed by Kenneth Brakke to simulate energy minimisation of surfaces. (Ideally we should try to create a list of "power users" who know how to do various tricks in the software and are willing to help and collaborate).

BiaPy is an open source ready-to-use all-in-one library that provides deep-learning workflows for a large variety of bioimage analysis tasks, including 2D and 3D semantic segmentation, instance segmentation, object detection, image denoising, single image super-resolution, self-supervised learning, image classification and image-to-image translation.

An image-based algorithm to quantify morphology of stress fibers and focal adhesions from microscopy images of cells.

I use continuous equations based on physical principles: conservation laws (hydrodynamics), electromagnetism, phase transition to capture dynamics in soft materials such as lipid membranes and polyelectrolyte gels that may be relevant for biological functions. To give one example, I use these tools to unravel the role of nonelectric aspects of action potentials in information processing.

3D Simulations of the optical response of a given nanostructure

A software tool able to implement simulations of single or multi-component epithelial tissues including gene regulation, mechanical properties of cells, and mechanobiology feedbacks.

We introduce CartoCell, a deep-learning-based pipeline that uses small datasets to generate accurate labels for hundreds of whole 3D epithelial cysts. Our method detects the realistic morphology of epithelial cells and their contacts in the 3D structure of the tissue. CartoCell enables the quantification of geometric and packing features at the cellular level. Our single-cell cartography approach then maps the distribution of these features on 2D plots and 3D surface maps, revealing cell morphology patterns in epithelial cysts. Additionally, we show that CartoCell can be adapted to other types of epithelial tissues.

open-source simulation platform for agent-based modelling of biological systems

Phase-field models have appeared in the context of materials science and have been extensively used to study biological systems, such as tumour growth, vessel development, cell monolayers, axonal development in neurons, immune system response and cellular motility. These models are focused on describing the membrane dynamics as a function of its mechanical properties. It is straightforward to assign a surface tension or a bending rigidity to the membrane in the context of phase-field modeling. A major advantage of these models is the low number of parameters when compared to other established methods such as cellular potts models, agent-based models or mixture models.

BioDynaMo is a high-performance software for the computational modelling of tissue development. It is an agent-based modelling software, so the user can specify behaviours that individual cellular elements follow, in order to model collective cellular behaviour, including tissue dynamics. In particular, one can simulate biomechanics and biological behaviours, such as for instance the development of curvature.

suite of open-source solvers and simulation tools relevant to biomechanical modelling

Finite element analysis is a numerical method used to approximate solutions to complex engineering problems by breaking down structures into smaller elements. It is particularly powerful in Multiphysics applications, where it can simultaneously solve coupled physical phenomena such as diffusion and structural interaction.

BioDynaMo is a high-performance simulation software that allows to model single cells as well as tissues. In particular, one can simulate biomechanics and biological behaviours, such as for instance the development of curvature.

After T. Willmore, many authors sought hypersurfaces, which are the critical points of curvature functionals. Such functionals (or generalized Willmore energies) have applications in biology. I recently defined Willmore-type functionals for foliated hypersurfaces, see https://arxiv.org/abs/2402.17565, and gave examples of critical rotational surfaces.
The topic can be useful for cells and tissue biology, as well as for technologies related to layered materials.
My expertise also includes modelling in Applied Mathematics using symbolic/numeric calculations and visualizations (using Maple and Matlab programs).

Differential and computational geometry of curves and surfaces (curvature, geodesics, variations, etc.)

1. Geometry of Curves and Surfaces with MAPLE.

2. Modeling of Curves and Surfaces with MATLAB

3. Willmore-type variational problem for foliated hypersurfaces.