Advanced Materials in Medicine

There are a wide variety of techniques associated with the manufacture of models, components and devices. For biomedical materials, digital manufacture and fibre fabrication are two main areas.

Below are groupings of facilities with short descriptions of general capability. For more information, or to access the facilities and equipment listed below, please contact ammfacilities@manchester.ac.uk.

Some equipment can be booked via the PPMS system.

Digtal manufacture

Digital manufacture is commonly used for developing polymer/composite suspensions and dispersions to trial or printing biologically relevant models using CAD models or STL files. Applications include printable electronics (inc. conductive materials), medical engineering, graded or phases of materials (extruded, spun and solutions in one model, or blended properties of separate materials in one model), rapid production or high-volume production (intermediate scale-up by SLA). 

Materials can be polymeric (inc. co-polymers), ceramic dispersions, metal nanoparticles and UV-curable resins. Using Bioprinting, polymer materials can be printed to form tissue-like architectures and the cells are printed directly into those architectures.

Techniques: Extrusion, Fused Deposition Modelling, Inkjet, Selective Laser Sintering (SLS), Selective Laser Melting (SLM), Stereolithography (SLA / SL), Bioprinting.

User information links

• Royce biomedical materials facilities 
• Royce Inkjet Suite for Developmental Projects 
• Royce Stereolithography (SLA) Suite 

Fibre fabrication

Fibre fabrication technologies have been used in many sectors. They can be used for replicating tissue structures, typically made from collagen fibres. Fibre technologies are also used for fabricating protective clothing, filtration system, packaging, etc.

There are several techniques, which include wet spinning, melt spinning, electrospinning, electrospray, melt electrospinning, solution blow spinning on pilot-scale semi industrial scale manufacture, e.g. roll to roll continuous production with environmental and quality control systems. Techniques are used to make stratified architectures, oriented materials and devices requiring multi-material and multi-modal fabrication.

Techniques: Melt Spinning, Electro-spinning, Electro-spraying, Melt electro-spinning, Solution blow-spinning, Wet spinning.

User information links

• Royce biomedical materials facilities 
• FSE Research facilities 
• FBMH Research facilities
• MACE facilities 
• NGI capabilities

Equipment can be booked via PPMS

Many of the equipment in the above section are also useful for the biological characterisations and testing of native cells and tissues, as well as their interactions with biomaterials (e.g. an implant), either in vitro or in vivo, fixed or live. For example, the structure of a biological molecule can be imaged by AFM when adhered to a biomaterial (drug activity in delivery system), the microstructure of a healed bone by CT, and the mechanics of osteoarthritic cartilage by cyclic compression testing.

Beside those, histology and molecular biology are two broadly used techniques in biology, and as useful tools to analyse biomaterials such as tissue-engineered implants and cell-laden scaffolds.

Histology 

Histology is an important tool for assessing microanatomy of tissues linking tissue structure to its function. It is also useful for studying tissue responses to biomaterials in close proximity or assessing regeneration of native tissues upon integration with a biodegradable implant scaffold. Across the university, we provide a broad range of histology equipment from tissue processing, embedding, sectioning to staining. Automated and scale-up machines are available to allow the processing and staining of large quantity samples, and various sectioning machines including cryostats are available for different tissue and biomaterial types.

Techniques: Tissue processing, Tissue embedding, Tissue sectioning, Staining (IHC), Stating (Tinctorial), Staining (IHC, ISH and FISH staining), Staining (Immuno), Staining.

User information links

• Royce biomedical materials facilities
• FBMH core histology facility
  

Molecular biology 

Molecular biology studies biological activities at a molecular level either within a cell or between cells. Many techniques sit in this field such flow cytometry, ELISA (Enzyme Linked Immunosorbent Assay) and PCR (polymerase chain reaction). Here we include a wide range of equipment across the university that are for molecular biology, which are frequently used to especially understand cellular events, such as the changed expressions of certain genes / proteins in response to a drug delivered by a polymeric carrier material.

Techniques: Flow cytometry, cell sorting, mass cytometry, Imaging cytometry, Imaging Mass Cytometry, Cell counter, Mitochondrial respiration and glycolysis analyser, PCR (Polymerase chain reaction), Laser micro-dissection, Staining including immunostaining, Microplate photometry (plate readers).

User information links

• Royce biomedical materials facilities

Biomaterials can be characterised in many different ways. Here we indicate facilities available for physical properties (bulk mechanical and microstructure properties), chemical properties (surface chemistry, spectroscopy and spectrometry), imaging (surface, bulk characteristics, cross-sectional features).

Imaging

The interface between materials and biology can be observed with different techniques in order to understand mechanisms of interaction with cells, or the response of a material to a biological environment, e.g. protein adsorption, materials degradation and integration. The dynamic exposure of the environment (pH, fluid flow, mechanical forces, enzymes, etc) play a role on the suitability of materials for biological applications and ultimately their success in the diagnosis and treatment of disease or damage in tissues. Surface imaging and bulk imaging techniques are included here and also time-lapse imaging techniques such as 2-photon confocal fluorescence microscopy.

Techniques: Atomic force microscopy, Scanning Probe Microscope, Imaging Mass Spectrometry, X-ray Imaging, Computed Tomography, Raman Imaging, Electron microscopy, Plasma Field Emission Beam with Scanning Electron microscopy, Single-photon Emission Computed Tomography (SPECT), 2D/3D optical tomography, Optical microscopy (including visible luminescence, fluorescence, laser), Optical coherence tomography, Opto-acoustic (OA) Microscopy, Stochastic Optical Reconstruction Microscopy (STORM), Ultra-fast particle tracking microscope, 2-photon microscopy (with electrical stimulation chamber), Magnetic resonance imaging, PET (Positron emission tomography) – MR, Positron emission tomography (PET), PET-CT (preclinical), Magnetic resonance imaging (preclinical).

User information links

• FBMH Imaging Facilities: PET Suite
• FBMH Imaging Facilities: Preclinical CT
• Royce Multidisciplinary Characterisation Facility (MCF)
• Royce biomedical materials facilities
• Imaging Facilities FBMH
• National Research Facility (Previously HMXIF)/Royce
• WMIC (Wolfson Medical Imaging Centre)
• Magnetic Resonance Imaging (MR) facilities

Mechanical testing

Introduction to mechanical testing: The bulk mechanical properties of materials can indicate their suitability for biological applications. However, there are varied architectures or arrangements of naturally occurring fibres within a mineral or other matrices, which demonstrates unique tensile properties in a specific directions, for example. The facilities included here include nanomechanical properties (suitable for assessing microstructural mechanical properties) and bioindenters for looking a softer, hydrated materials like hydrogels and cartilage-like materials.

In addition, mechanical suites are able to replicate the biological environments, for example, fluid flow of biological media with tensile or compressive forces applied over time. Likewise, biaxial testing allows us to observe and test the properties of organised matrices, e.g. tendon tissue has oriented collagen fibres, with high tensile properties in one direction, but lower tensile properties in the transverse direction.

Techniques: Nanomechanical testing, Biointender for nanomechanical measurement, biomechanics, general mechanics.

User information links

• Royce Multidisciplinary Characterisation Facility (MCF)
• Royce biomedical materials facilities
• FBMH research facilities

Spectroscopy

Spectroscopy is widely used across most of the pure and applied sciences, and uses the interaction of matter with light and particles to study the compositional, physical, chemical and electronic properties of matter. Spectra obtained from a variety of different techniques (utilising different frequencies of light, or using a variety of different ion sources) yield signatures of these properties, and careful interpretation and peak fitting of the spectra is often required.

X-ray photoelectron spectroscopy utilises the photoelectric effect to remove electrons and measure their energies. Their kinetic energy is related to their binding energy which is a function of the chemical bonding environment, enabling quantified elemental composition and chemical state identification (the more electronegative an environment an atom sits in leads to chemical shifts in the electron binding energy). Electron escape depths are usually very small so the technique is generally very surface sensitive, with sampling depths on the scale of 3-10 nm.

At Manchester there are several cutting edge XPS techniques available including XPS, High energy XPS (HAXPES) where the sampling depth is extended towards the bulk (30-100 nm, element dependent), and near ambient pressure (NAP) XPS where samples may be measured as they are exposed to up to 10 mbar gas (i.e. simulating real conditions); XPS is generally measured under ultra-high vacuum conditions. UPS is also available for sensitive valence band measurements.

Secondary Ion Mass Spectrometry (SIMS) provides mass spectrometric data from the surface layer, down to micrometer depths of materials, in the form of 2D/3D chemical images. The technique is suitable for elemental/isotopic (NanoSIMS) and molecular (ToF-SIMS) characterisation under ultra-high vacuum conditions. SIMS can detect all elements and molecules up to ~1 kDa with sensitivities down to ppm levels. Lateral resolutions are in the range 50 nm (NanoSIMS) to 1 micron (ToF-SIMS), and depth resolution typically ~10 nm.

Mass spectrometry imaging of biomolecules and polymers up to several kDa can be achieved using MALDI (Matrix-Assisted Laser Desorption/ionisation) and DESI (Desorption Electrospray Ionisation). MALDI is a vacuum ionisation method providing ~20 micron lateral resolution. DESI is an ambient ionisation technique preserving the natural state of the sample and offering ~50 micron lateral resolution. MALDI and DESI mass spectrometry measurements can combine ion-mobility separation for added chemical and structural specificity.

Techniques: Secondary Ion Mass Spectrometry (SIMS), Nano-resolution SIMS (NanoSIMS), X-ray Photoelectron Spectroscopy (XPS), Hard X-ray Photoelectron Spectroscopy (HAXPES), Near-ambient pressure XPS (NAP-XPS), Ultraviolet photoelectron spectroscopy (UPS), ultraviolet-visible (UV-VIS) absorption, Raman spectroscopy, Terahertz spectroscopy, Photoluminescence spectroscopy.

User information links

• Royce Multidisciplinary Characterisation Facility (MCF)

Surface characterisation

The surface properties include both the roughness of a material and also the chemical properties, e.g. the physical barriers at the cell-material interface and the ability of biological materials to 'stick' to the surface. The wettability of a material indicates how fluids interact with a surface with a high contact angle being associated with hydrophobic materials (e.g. PTFE) and low contact angles associated with hydrophilic materials (PEO).

Techniques: surface tension and contact angles.

User information links

• Royce Characterisation Suite
  

Robotics

New bioengineering techniques allow us to harness the enormous chemical space provided by biology, to efficiently produce diverse molecules of interest and to give access to materials design space that is challenging through traditional chemical synthesis. This biomolecule engineering platform provides high throughput methods for enzyme engineering (directed evolution) and synthetic biology protocols that support the synthesis of bio-produced materials. The molecules for materials capability will enable sustainable innovation for the production of materials from biology for advanced bio-based materials.

The robotics platform integrates automated pipette and acoustic based liquid handling with a suite of instruments including centrifuges, PCRs, plate readers and incubators to enable high throughput protocols to be performed without user intervention with 24/7 capability. Additional instruments provide complementary capabilities for next generation sequencing, high throughput colony picking and analytics.

Techniques: Directed Evolution, generation of variant libraries, genetic pathway assembly, cloning and colony picking, synthetic biology protocols, gene sequencing, high throughput analytics.

User information links

• Manufacture, Characterisation and Testing Facilities in the Department of Materials 
• MIB/FBRH/SynBioChem
• NGI capabilities

Equipment can be booked via PPMS

Across Faculties, there are many bio-culture facilities including Class II biosafety cabinets along with centrifuges, water baths, and incubators. Specialised culture systems providing hypoxia or mechanical loadings are also available enabling tests in dynamic and physiological environment.

Manchester Brain Bank

The Manchester Brain Bank collects and supplies human brain tissues for research locally, nationally and internationally. Researchers can apply for use of tissue from the Brain Bank.

Manchester Centre for Health Economics 

The Manchester Centre for Health Economics provides a concentration of expertise in health economics and has a critical mass of health economists to support the development of careers and coherent research programmes, as well as continuing collaboration with colleagues in other disciplines. The centre holds a regular seminar programme, which is open to anyone to attend.

National Graphene Insitute (NGI) clean room

The NGI cleanroom houses 1,500 square metres of ISO class 5 and 6 cleanrooms over two floors. The clean rooms host a variety of activities to enable collaborative research between academia and industry.