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Reversible addition-fragmentation chain transfer (RAFT) mediated dispersion polymerisation in supercritical carbon dioxide (scCO2) is an efficient and green method for synthesising block copolymer microparticles with internal nanostructures. Here we report for the first time the synthesis of phase separated poly(methyl methacrylate-block-styrene-block-4-vinylpyridine) (PMMA-b-PS-b-P4VP) triblock terpolymer microparticles using a simple two-pot sequential synthesis procedure in scCO2, with high monomer conversions and no purification steps. The microparticles, produced directly and without further processing, show a complex internal nanostructure, appearing as a “lamellar with spheres” [L+S(II)] type morphology. The P4VP block is then exploited as a structure-directing agent for the fabrication of TiO2 microparticles. Through a simple and scalable sol-gel and calcination process we produce hollow TiO2 microparticles with a mesoporous outer shell. When directly compared to porous TiO2 particles fabricated using an equivalent PMMA-b-P4VP diblock copolymer, increased surface area and enhanced photocatalytic efficiencies are observed.

Devices featuring electrophoretic displays (EPD) have become extremely popular in recent years because of their low power consumption, high readability and thin display designs, but a product with a full colour gamut comparable with liquid crystal displays (LCDs) has not yet been commercialised. In this article, we demonstrate that staggering the addition of methyl methacrylate (MMA) monomer and low quantities of a coloured dye crosslinker is an effective route to producing well-defined and covalently-linked, strongly coloured PMMA microparticles in one-pot, via dispersion polymerisation in supercritical carbon dioxide (scCO2). This novel methodology is synthetically simple, readily scalable and has the added cachet of being cost effective because the functional molecules can be confined on the microparticle surface such that even at low concentrations, the resulting materials are brightly coloured. We then demonstrate the applicability of this approach to another functional comonomer/crosslinker system in 2-dimethylaminoethyl methacrylate (DMAEMA)/ethyleneglycol dimethacrylate (EGDMA), in this case allowing hierarchically structured ‘pomegranate-like’ microparticles with polarisable charge to be produced over a range of DMAEMA loadings as high as 44 wt%. Finally, the performance of these materials in out-of-plane EPD test cells is compared against analogues synthesised in dodecane. These tests revealed that the coloured microparticles fabricated in scCO2 performed as well as or better than their dodecane synthesised counterparts, consistently producing the cleanest white state and achieving effective colour switching over ten cycles.

© 2018 American Chemical Society. Metal oxide microparticles with well-defined internal mesostructures are promising materials for a variety of different applications, but practical routes to such materials that allow the constituent structural length scales to be precisely tuned have thus far been difficult to realize. Herein, we describe a novel platform methodology that utilizes self-assembled block copolymer (BCP) microparticles synthesized by dispersion polymerization in supercritical CO 2 (scCO 2 ) as universal structure directing agents for both hydrolytic and nonhydrolytic sol-gel routes to metal oxides. Spherically structured poly(methyl methacrylate-block-4-vinylpyridine) (PMMA-b-P4VP) BCP microparticles are translated into a series of the corresponding organic/inorganic composites and pure inorganic derivatives with a high degree of fidelity for the metal oxides TiO 2 and LiFePO 4 . The final products are comprised of particles close to 1 μm in size with a highly ordered internal morphology of interconnected spheres between 20-40 nm in size. Furthermore, our approach is readily scalable, enabling grams of pure or carbon-coated TiO 2 and LiFePO 4 , respectively, to be fabricated in a facile two step route involving ambient temperature mixing and drying stages. Given that both length scales within these BCP microparticles can be controlled independently by minor variations in the reagent quantities used, the present general strategy could represent a milestone in the design and synthesis of hierarchical metal oxides with completely tunable dimensions.

Purpose Cataract is a clinically and genetically heterogeneous disorder of the ocular lens and an important cause of visual impairment. The aim of this study was to map and identify the gene underlying autosomal dominant cataract segregating in a four-generation family, determine the lens expression profile of the identified gene, and test for its association with age-related cataract in a case-control cohort. Methods Genomic DNA was prepared from blood leukocytes, and genotyping was performed by means of single-nucleotide polymorphism markers and microsatellite markers. Linkage analyses were performed using the GeneHunter and MLINK programs, and mutation detection was achieved by dideoxy cycle sequencing. Lens expression studies were performed using reverse-transcription polymerase chain reaction (RT–PCR) and in situ hybridization. Results Genome-wide linkage analysis with single nucleotide polymorphism markers in the family identified a likely disease-haplotype interval on chromosome 19q (rs888861-[~17Mb]-rs8111640) that encompassed the microsatellite marker D19S879 (logarithm of the odds score [Z]=2.03, recombination distance [θ]=0). Mutation profiling of positional-candidate genes detected a heterozygous, noncoding G-to-T transversion (c.-168G>T) located in the iron response element (IRE) of the gene coding for ferritin light chain (FTL) that cosegregated with cataract in the family. Serum ferritin levels were found to be abnormally elevated (~fourfold), without evidence of iron overload, in an affected family member; this was consistent with a diagnosis of hereditary hyperferritinemia-cataract syndrome. No sequence variations located within the IRE were detected in a cohort of 197 cases with age-related cataract and 102 controls with clear lenses. Expression studies of human FTL, and its mouse counterpart FTL1, in the lens detected RT–PCR amplicons containing full-length protein-coding regions, and strong in situ localization of FTL1 transcripts to the lens equatorial epithelium and peripheral cortex. Conclusions The data are consistent with robust transcription of FTL in the lens, and suggest that whereas variations clustered in the IRE of the FTL gene are directly associated with hereditary hyperferritinemia-cataract syndrome, such IRE variations are unlikely to play a significant role in the genetic etiology of age-related cataract.

Purpose To map and identify the genetic defect underlying autosomal dominant cataract segregating in a 5-generation Caucasian American family. Methods Genomic DNA was prepared from blood leukocytes, genotyping was performed using microsatellite markers, and logarithm of the odds (LOD) scores were calculated using the LINKAGE programs. Mutation profiling was performed using direct exon cycle-sequencing and restriction fragment analysis. Protein function effects were evaluated using in silico prediction algorithms. Results Significant evidence of linkage was obtained at marker D13S175 (maximum LOD score [Zmax]=3.67; maximum recombination fraction [θmax]=0.04) and D13S1316 (Zmax=2.80, θmax=0.0). Haplotyping indicated that the disease lay in the ~170 Kb physical interval between D13S1316 and D13S175, which contained the gene for gap-junction protein alpha-3 (GJA3) or connexin-46. Sequencing of GJA3 detected a heterozygous transition (c.130G>A) in exon-2 that resulted in gain of an Hsp92 II restriction site. Allele-specific PCR amplification and restriction analysis confirmed that the novel Hsp92 II site co-segregated with cataract in the family but was not detected in 192 normal unrelated individuals. The c.130G>A transition was predicted to result in a non-conservative substitution of valine-to-methionine at codon 44 (p.V44M) with damaging effects on protein function. Conclusions These data confirm GJA3 as one of the most frequently mutated genes that underlie autosomal dominant cataract in humans, and further emphasize the importance of connexin function in maintaining lens transparency.

Purpose Cataracts are a clinically and genetically heterogeneous disorder affecting the ocular lens, and the leading cause of treatable vision loss and blindness worldwide. Here we identify a novel gene linked with a rare autosomal dominant form of childhood cataracts segregating in a four generation pedigree, and further show that this gene is likely associated with much more common forms of age-related cataracts in a case-control cohort. Methods Genomic DNA was prepared from blood leukocytes, and genotyping was performed by means of single nucleotide polymorphism (SNP) markers, and short tandem repeat (STR) markers. Linkage analyses were performed with the GeneHunter and MLINK programs, and association analyses were performed with the Haploview and Exemplar programs. Mutation detection was achieved by PCR amplification of exons and di-deoxy cycle-sequencing. Results Genome-wide linkage analysis with SNP markers, identified a likely disease-haplotype interval on chromosome 1p (rs707455-[~10 Mb]-rs477558). Linkage to chromosome 1p was confirmed using STR markers D1S2672 (LOD score [Z]=3.56, recombination distance [θ]=0), and D1S2697 (Z=2.92, θ=0). Mutation profiling of positional-candidate genes detected a heterozygous transversion (c.2842G>T) in exon 17 of the gene coding for Eph-receptor type-A2 (EPHA2) that cosegregated with the disease. This missense change was predicted to result in the non-conservative substitution of a tryptophan residue for a phylogenetically conserved glycine residue at codon 948 (p.G948W), within a conserved cytoplasmic domain of the receptor. Candidate gene association analysis further identified SNPs in the EPHA2 region of chromosome 1p that were suggestively associated with age-related cataracts (p=0.007 for cortical cataracts, and p=0.01 for cortical and/or nuclear cataracts). Conclusions These data provide the first evidence that EPHA2, which functions in the Eph-ephrin bidirectional signaling pathway of mammalian cells, plays a vital role in maintaining lens transparency.