Prof. Steve ArmesDept. of Chemistry, U. Sheffield

Polymerisation -Induced Self-Assembly

FRS Talk, 11.7.2014

Polymers are Long-Chain Molecules

= repeat unit

Polymers (plastics) are ubiquitous in the modern wo rld

Polymers are extremely racist

Get microphase separation on 10-50 nm length scale!

3 µmPhase separation constrained by covalent

bond between red and blue chains

What happens if red and blue polymer chains are attached to each other?

AB diblock

copolymer

Instead, macrophase-separated blends are formed on the micron length scale

+Pairs of red + blue polymers do not mix:

How to make block copolymer nanoparticles

O

O

HO

HO

65

+ O

O

HO

HHHHPPPPMMMMAAAAPGMA65 macroCTA

PGMA 65 – PHPMA X

X = 100

X = 300

X = 30

Efficient aqueous formulation: > 99 % conversion wi thin 2 h at 70 oC

water-solublePGMA65

water-miscibleHPMA

(but PHPMA iswater-insoluble)

Y. T. Li and S. P. Armes, Angewandte Chem., 2010, 49, 4042

Grow a water-insoluble polymer from one end of a water-soluble polymer in water

A. Blanazs et al., JACS, 2011, 133, 16581 Scale bars: 200 nm

75 min = 62 %, DP 123

77.5 min = 68 %, DP 131

84 mins = 75 %, DP 150

225 mins = 100 % DP 200

90 mins = 82 %, DP 164

65 min = 46 %, DP 92

87 mins = 78 % DP 156

1H NMR & TEM Studies: PGMA47-PHPMA200

Predictive Phase Diagrams

Increasing PHPMA DP and copolymer concentration

Spheres Worms Vesicles

Post- mortem TEM analysis of diblock copolymer morphology at > 99 % conversion

A. Blanazs, A. J. Ryan, S. P. Armes, Macromolecules 2012, 45, 5099

PGMA78-PHPMAx

S = spheres, W = worms, V = vesicles

78 x

Phase diagrams serve as a ‘road map’

Enable reproducible synthesis of pure

copolymer morphologies (s, w or v)

Vary relative block volume fractions for rational design of particle size & shape

Effect of Particle Morphology on Flow Properties

Anisotropic worms produce free-standing gels

Entangled ‘worms’ hence higher viscosity?

=

An 8.0 w/v % aqueous solution of PGMA54PHPMA140

Cool

Heat

20oC < 5oC

This sol-gel thermal transition is fully reversible

Thermo-responsive Copolymer Worm Gels

A. Blanazs, A. J. Ryan, S. P. Armes et al., JACS, 2012, 134, 9741

What Causes Reversible Copolymer (De)gelation?

Degelation due to reversible worm -to-sphere transition!

Initial copolymer worms at 21 oC

TEM studies of a PGMA 54-PHPMA140 diblock copolymer:

A. Blanazs, A. J. Ryan, S. P. Armes et al., JACS, 2012, 134, 9741

Copolymer ‘spheres’are formed at 4 oC

Cool

Heat

Stem cells remain undifferentiated within worm gels for 14 days

With Dr. I. Canton and Prof. H. Moore, manuscript in preparation

Optical image of stem cell colonies

within a PGMA-PHPMA worm gel

Pluripotent stem cells receive no mechanical cues from worm gels

Ki-67 and statin bio-assays: worm gel induces stem cell stasis?

Sufficient time to ship human stem cells anywhere in the world?

Cell Biology Applications for Biocompatible Worm Gels

Stem cells readily isolated from worm gel via cold centrifugation

ABC Triblock Copolymer Syntheses via RAFT Seeded Emulsion Polymerisation

P. Chambon, A. Blanazs, G. Battaglia, S. P. Armes Macromolecules, 2012, 45, 5081

PGMA-PHPMA vesicles

BzMA

70oC

PGMA-PHPMA-PBzMA vesicles

PHPMA-PBzMAmixed vesicle

membrane ~ 95 % BzMA conversion in 2 h at 70oC; Mw/Mn < 1.50

Get micro-phase separation between PHPMA & PBzMA chains within membrane

G58-H360 G58-H360-B200 G58-H360-B300 G58-H360-B400

PISA: a versatile generic platform technology

Nanoparticle lubricants (Lubrizol)

Long-term storage of mammalian cells (GE Healthcare )

Next-generation gas-permeable contact lenses (GEO)

Microencapsulation applications (P & G)

Anti-reflective coatings for plastic substrates (DSM)

Improved thickeners (Scott Bader)

Bespoke nanoparticles for CaCO 3 occlusion (EPSRC)

New efficient Pickering emulsifiers (ERC)

ConclusionsSpherical block copolymer

nanoparticles prepared in water

Block copolymer worms obtained over a narrow copolymer composition range

Do worm gels have biomedical applications

for long-term storage of stem cells?

Worms form soft free-standing aqueous gels

Block copolymer worm gels are thermo-responsive

Acknowledgements: “Art is I, Science is We” (Claude Bernard)

Thank you for your attention

Prof. Norman Billingham (long-term collaborator at U. Sussex)

Prof. Tony Ryan OBE (long-term collaborator at U. Sheffield)

~ 50 PhD students and ~ 50 post-docs at U. Sussex and U. Sheffield

£££: EPSRC, ERC, The Royal Society and many industrial companies

Prof. Brian Vincent (PhD supervisor at U. Bristol)

Dr. Matt Aldissi (Post-doc supervisor at LANL, New Mexico)