SARS-COV-2 detection paper now published in ACS Central Science
There is an urgent, global, need for new therapeutic, vaccine and diagnostic interventions to address the COVID-19 challenge. Current diagnostics are mostly based upon PCR (polymerase chain reaction) methods where the genetic material of the SARS-COV-2 virus is isolated and sequenced. A challenge with this method is that significant infrastructure and trained personnel are needed, and the results are not instant. In this work, conducted in collaboration with Iceni Diagnostics (and MANY UoW colleagues) we hijacked a pregnancy test set up, to enable rapid detection. Crucial to this was the identification that sialic acids (a type of cell-surface glycan) bind the SARS-COV_2 spike protein. By incorporating sialic acids onto the ends of polymers, immobilized onto gold nanoparticles we made a paper-based tool, enabling rapid detection of the spike protein, a virus mimic and also a virus engineered to 'look like' SARS-COV-2. This method may enable ultra rapid and low cost screening to identify individuals who carry the virus, to triage for the PCR testing. We are actively pursuing the development of this technology.
Read the paper here
Latest work published in Materials Horizons exploits new polymeric nanomaterials to modulate ice growth.
Polymerisation-induced self-assembly (PISA), a scalable and versatile method to obtain soft nano-objects is utilised for the first time to introduce ice recrystallisation inhibiting (IRI) polymer nanomaterials. Crucially we developed a method to ensure the particles are saline stable which is essential for IRI testing but current PISA formulations cannot tolerate any salt. Uniquely, we achieved this by tuning the core, enabling us to retain our IRI active corona (based on poly(vinyl alcohol)). The resulting particles showed remarkable activity, inhibiting all ice growth below 1 mg.mL-1. These results are significant as they show that Nature’s approach to hyperactivity, based upon aggregation/self-assembly, can be mimicked using polymer self-assembly.
Our recent work using a photochemical high-throughput discovery platform to identify new macromolecular cryoprotectants has been published in Macro Letters.
In this study we used a liquid handling system to produce 120 unique terpolymers using photopolymerisation with RAFT agents. These terpolymers were screened using a red blood cell freezing assay to identify the best and the worst polymer cryoprotectants, allowing us to explore the chemical space in a short time frame. Testing the hit polymers with a nucleated cell line demonstrated that the high throughput screen was able predict how well the polymers would perform as cryoprotective agents in a more complex assay. This new high throughput approach will allow us to identify new, potent macromolecular cryoprotectants.
Read the paper here:
Our recent work into how macromolecular antifreeze agents interact with ice was recently published in ACS Macroletters.
Enhancement of Macromolecular Ice Recrystallisation Inhibition Activity by Exploiting Depletion Forces
We have shown that the ice recrystallisation inhibition of poly(vinyl alcohol) can be improved by the addition of other, inactive macromolecules, in this case poly(ethylene glycol). The additive causes a depletant effect in the liquid channels between ice grains, driving PVA out of solution and on to the the ice crystal surface.
These results give greater insight into the mechanism behind poly(vinyl alcohol)'s antifreeze activity and open up a new suite of tools we can use to make potent antifreeze/cryopreservation agents.
Our perspective article on polyampholytes as emerging macromolecular cryoprotectants has been published in Biomacromolecules.
Polyampholytes as Emerging Macromolecular Cryoprotectants
This perspective is the first review type article on polyampholytes as cryoprotectants and it covers important contributions from both our group and other global leaders in this area.In this perspective we summarise typical methods of cryopreservation for mammalian cells and highlight some of the specific challenges. We then discuss the synthesis and properties of polyampholytes as macromolecular cryoprotectants and detail ways in which polyampholytes have been used to enhance mammalian cell cryopreservation. We further hypothesise about their specific function and how this exciting new field will develop.
Freezing cells made safer thanks to new polymer made at University of Warwick
- A new polymer that's a cryoprotectant dramatically improves the freezing of cells, has been discovered by Gibson Group researchers at the University of Warwick
- The new polymers can reduce the amount of organic solvent required in cryopreservation (freezing cells) as well as giving more and healthier cells after thawing.
- Findings may help reduce cost and improve distribution of cells for cell-based therapies, diagnostics and research.
Cell freezing (cryopreservation) – which is essential in cell transfusions as well as basic biomedical research – can be dramatically improved using a new polymeric cryoprotectant, discovered at the University of Warwick, which reduces the amount of ‘anti-freeze’ needed to protect cells.
The ability to freeze and store cells for cell-based therapies and research has taken a step forward in the paper ‘A synthetically scalable poly(ampholyte) which dramatically Enhances Cellular Cryopreservation.’ published by the University of Warwick’s Department of Chemistry and Medical School in the journal Biomacromolecules. The new polymer material protects the cells during freezing, leading to more cells being recovered and less solvent-based antifreeze being required.
Cryopreservation of cells is an essential process, enabling banking and distribution of cells, which would otherwise degrade. The current methods rely on adding traditional ‘antifreezes’ to the cells to protect them from the cold stress, but not all the cells are recovered and it is desirable to lower the amount of solvent added.
The new Warwick material was shown to allow cryopreservation using less solvent. In particular, the material was very potent at protecting cell monolayers – cells which are attached to a surface, which is the format of how they are grown and used in most biomedical research.
Having more, and better quality cells, is crucial not just for their use in medicine, but to improve the quality and accessibility of cells for the discovery of new drugs for example.
Cell-based therapies are emerging as the “fourth pillar” of chemo-therapy. New methods to help distribute and bank these cells will help make them more accessible and speed up their roll-out, and this new material may aid this process.
Our latest paper is ACS Editors' Choice Article
Optimization and Stability of Cell-Polymer Hybrids Obtained by ‘Clicking’ Synthetic Polymers to Metabolically-Labeled Cell Surface Glycans
Re-engineering of mammalian cell surfaces with polymers enables the introduction of functionality including imaging agents, drug cargoes or antibodies for cell-based therapies, without resorting to genetic techniques. Glycan metabolic labeling has been reported as a tool for engineering cell surface glycans with synthetic polymers through the installation of biorthogonal handles, such as azides. Quantitative assessment of this approach and the robustness of the engineered coatings has yet to be explored. Here, we graft poly(hydroxyethyl acrylamide) onto azido-labeled cell surface glycans using strain-promoted azide-alkyne ‘click’ cycloaddition and, using a combination of flow cytometry and confocal microscopy, evaluate the various parameters controlling the outcome of this ‘grafting to’ process. In all cases, homogenous cell coatings were formed with > 95% of the treated cells being covalently modified, superior to non-specific ‘grafting to’ approaches. Controllable grafting densities could be achieved through modulation of polymer chain length and/ or concentration, with longer polymers having lower densities. Cell surface bound polymers were retained for at least 72 hours, persisting through several mitotic divisions during this period. Furthermore, we postulate that glycan/membrane recycling is slowed by the steric bulk of the polymers, demonstrating robustness and stability even during normal biological processes. This cytocompatible, versatile and simple approach shows potential for re-engineering of cell surfaces with new functionality for future use in cell tracking or cell-based therapies.
Our latest work in ACS MacroLetters
Our latest work in the design of new materials to mimic complex glycan function and to inhibit bacterial toxins has been published in ACS Macro Letters. We have previously shown that synthetic polymers bearing carbohydrates in specific orientations or densities on polymer chains can give rise to increased affinity towards bacterial lectins (toxins) and may have application as decoys to prevent infection. However, many glycopolymers are rather basic simply having lots of glycans on a flexible polymer chain. In this work, we collaborated with Prof Filip du Prez (Gent, Belgium) using their thiolactone chemistry to enable us to introduce two functional units per repeat unit of the polymer. This was advantageous as it enabled us to mimic how GM-1 - a glycolipid on our cells - presents its glycans, but in a very simple manner. Using this, we made a library of glycopolymers with either 2 glycans or a hydrophobic unit. Using a combination of inhibitory assays and biolayer interferometry we unraveled the crucial design features to obtain highly active inhibits of lectin binding. This approach shows that moving from 'boring' homo-glycopolymers to those of increased complexity may help guide the development of materials to address the spread of infection.
Read the paper here