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Patient derived organoids have the potential to improve the physiological relevance of in vitro disease models. However, the 3D architecture of these self-assembled cellular structures makes probing their biochemistry more complex than in traditional 2D culture. We explore the application of surface enhanced Raman scattering microsensors (SERS-MS) to probe local pH gradients within patient derived airway organoid cultures. SERS-MS consist of solid polymer cores decorated with surface immobilised gold nanoparticles which are functionalised with pH sensitive reporter molecule 4-mercaptobenzoic acid (MBA). We demonstrate that by mixing SERS-MS into the extracellular matrix (ECM) of airway organoid cultures the probes can be engulfed by expanding organoids and report on local pH in the organoid lumen and ECM.

A highly sensitive optical probe for the detection of activated neutrophils and Neutrophil Extracellular Traps (NETs) is reported. It is based on a triple-quenched, super-silent tri-branched probe that generates >20 fold increase in fluorescence upon cleavage. The probe was highly specific for human neutrophil elastase, a protease that mediates a variety of inflammatory diseases, and detected NETosis and neutrophil activation in in vitro differentiated neutrophils and isolated human neutrophils.

A probe that allows specific 'painting' of human tumours is described. Probe activation was mediated by specific matrix metalloproteinases, resulting not only in disruption of a FRET pair, but in the generation of a fragment that "fluorescently paints" human tumours. This probe demonstrated rapid and effective human tumour labelling with the potential to allow margin detection during surgical resection.

A homogeneous carbene-based palladium catalyst was conjugated to a cell-penetrating peptide, allowing intracellular delivery of catalytically active Pd complexes that demonstrated bioorthogonal activation of a profluorophore within prostate cancer cells.

Polymer microarrays were prepared using inkjet printing mixtures of acrylate monomers each with a common fluorescent fluorene co-polymer. Fluorescence analysis of each of the features on the array allowed identification of polymers that could tune the fluorescence under a variety of insults. The "hit" polymers were made into beads via reverse suspension polymerization and their fluorescence properties were analyzed.

For the first time the influence of the chirality of the gel fibers in protein crystallogenesis has been studied. Enantiomeric hydrogels 1 and 2 were tested with model proteins lysozyme and glucose isomerase and a formamidase from B. cereus. Crystallization behaviour and crystal quality of these proteins in both hydrogels are presented and compared., MICINN (Spain) projects BIO2010-16800 (JAG), CTQ-2011.22455 (LAC & JMC), CTQ2012-34778 (JJDM & ALG), “Factoría Española de Cristalización” Consolider-Ingenio 2010 (JAG & MCM) and EDRF Funds (JAG, LAC & JMC), P12-FQM-2721 (LAC) Junta de Andalucía., MINECO,Project No. FIS2013-41821-R.

As a novel prodrug activation strategy Pd(0) nanoparticles, entrapped within a modular polymeric support, were used in cell culture, to synthesise the anticancer agent PP-121 from two non-toxic precursors, thereby inducing cell death in the first example of in situ mediated drug synthesis.

Herein we report a highly-efficient solid-phase strategy for the modular synthesis of 63 double-tailed lipid-peptide conjugates and their application in DNA delivery.

The solid phase synthesis of tetrabutylammonium oxo- (mercaptoacetylglycylglycylglycine) rhenate(V) has been achieved by utilising ReOCl3(PPh3)2 as a stable source of Re(V) and provides a synthesis of bi-functional chelates for use in nuclear medicine.

Resin beads with a loading of 200 nmol per bead have been prepared using a Generation 2.0 tris-based dendrimer to amplify resin loading sites.

Micron-sized polymeric "doughnuts" prepared via dispersion polymerization were found to be highly selective in their cellular translocation abilities.

Fluorescent confocal microscopy is a practical and very sensitive (fmol bead(-1)) and non-destructive tagging technique for use in combinatorial chemistry.

A safety catch linker has been developed that allows efficient compound release into buffered aqueous solutions and agarose gels.

pH indicating resins were prepared by covalently attaching carboxylic acid derivatives of sulfthalein dyes, synthesized using a Suzuki cross-coupling, onto resin beads. The resin-bound indicators showed the expected colour changes according to pH and their behaviour was analysed using a micro UV/Vis spectrometer.

Self-indicating methylisocyanate resin, which functions as both a scavenger and an indicator for amines, was used for in-situ reaction monitoring and purification of a urea based library.

Dyad beads, bearing both a substrate and a catalyst, were prepared to enable direct split and mix bead based screening for catalysis.

Using a highly efficient solid-phase route a series of fluorescein conjugated peptoid oligomers were synthesised and observed to display remarkable cell penetrating properties, offering the possibility of highly efficient cellular targeting.

A variety of diprotected polymines are anchored to a solid support and used in solid phase chemistry and library generation.