Geckeler K.E., Nishide H. (Eds.) Advanced Nanomaterials

3.4 External Stimuli 105

3.4.2

Light

The attractive feature of light - responsive polymeric assemblies is that the drug

release can be induced at a speciﬁ c time and site of light exposure, with ultraviolet

( UV ), visible ( VIS ) or NIR light being applied as the trigger. Since NIR light shows

a deeper tissue penetration and minimal damage to healthy cells, its use is of

particular interest for biomedical applications [58] . The structural changes of the

nanoassemblies induced by light can be either irreversible or reversible; for

example, cleavage of the side chains of the block copolymers induced an irrevers-

ible destabilization of the structures. The micelles prepared from PEG - b - polymeth-

acrylate copolymers bearing a photolabile pyrene chromophore moiety in the side

chain (PPy) demonstrated photosensitivity [59] . Likewise, pyrenyl methyl esters

were cleaved following UV irradiation, thus transforming the hydrophobic

polymethacrylate segment to hydrophilic poly(methacrylic acid) ( PMA ). The same

group also developed a PEG - b - poly(2 - nitrobenzyl methacrylate) system [60] , where

the cleavage of 2 - nitrobenzyl moieties occurred by photolysis either via one - photon

UV (365 nm) or two - photon NIR (700 nm) excitation. The formation of carboxylic

acid after irradiation shifted the hydrophilic/hydrophobic balance and resulted in

either break - up of the micelles or in swelling of the micelle core when it was

crosslinked with a diamine.

The exposure of photoactive groups to light may also generate reversible struc-

tural changes due to deviations in the hydrophilic – hydrophobic balance. The

molecular units showing photochemical - induced transitions include azobenzenes

(Figure 3.9 a), cinnamoyl derivatives (Figure 3.9 b), and spirobenzopyran (Figure

3.9 c).

A reversible isomerization between the trans ( E ) and cis ( Z ) geometric isomers

of azobenzenes can be induced by light or heat (Figure 3.9 a). The cis isomer is

thermodynamically less stable, and isomerizes to the trans form due to thermal

energy; the illumination can reduce this conversion time to minutes. Moreover,

the photoisomerization wavelengths can be tuned by modulating the substituent

groups at the chromophores. In that way, azo - functionalized hyperbranched poly-

esters [61] and polypeptides [62] showed photoinduced transformations. Photosen-

sitive polymeric rods were formed with helical polypeptides by the hydrophobic

interactions between the azo groups in a planar, apolar, trans conﬁ guration [63] .

The photoisomerization of these azo - moieties to the skewed, polar, cis conﬁ gura-

tion, inhibited the interactions between azo - groups, leading to a disintegration of

the nanoassemblies. Moreover, azobenzene – polymethacrylate - b - poly(acrylic acid)

copolymers self - assembled in dioxane – water mixtures into micelles and vesicles

[64] , although the nanoassemblies broke up after UV irradiation. Subsequent

illumination with visible light led to all of the nanoassemblies being reformed due

to the cis - to - trans isomerization of the azobenzene, thus indicating the reversibility

of the system.

Cinnamate undergoes either trans - to - cis photoisomerization, thus generating

cinnamate residues with an increased hydrophilicity, or photodimerization after

106 3 Smart Nanoassemblies of Block Copolymers for Drug and Gene Delivery

Figure 3.9 Light - sensitive groups normally

used to modify block copolymers in order to

obtain light - sensitive nanostructures.

(a) Azobenzenes undergo isomerization by

light and heat between the trans and cis

geometric isomers; (b) Cinnamate undergoes

trans - to - cis photoisomerization, producing

residues with higher hydrophilicity or dimers;

(c) Spirobenzopyran undergoes reversible

photoisomerization into a zwitterionic

merocyanine.

irradiation with UV light (Figure 3.9 b). Accordingly, the partial modiﬁ cation of

poly(HPMA) by cinnamate (9 mol%) produced both temperature - and light - sensi-

tive polymers [65] . UV irradiation of the polymer in aqueous solution resulted in

a 6 ° C increase in the LCST due to trans - to - cis isomerization. However, at a high

cinnamate content the polymer was photocrosslinked due to the photodimeriza-

3.4 External Stimuli 107

tion. The parameters that affect the LCST in this system are the polymer concen-

tration, the amount of cinnamate moieties per polymer chain, and the extent of

isomerization. Moreover, photocrosslinked cinnamoyl microcapsules were used

to encapsulate cyclodextrin, and subsequently release it by UV illumination as a

result of photocleavage and microcapsular break - up [66] .

Block copolymers bearing merocyanine were self - assembled due to the attractive

electrostatic dipole – dipole interaction of the zwitterionic moieties. The zwitteri-

onic merocyanine is the photoisomerization product from spirobenzopyran ( SBP )

after UV irradiation (Figure 3.9 c). For example, HPMA copolymers bearing various

amounts of spirobenzopyran moieties aggregated into large clusters after UV

exposure in water due to zwitterionic formation after 20 min illumination [67] .

After incubation under visible light, however, the rapid reversal of the metastable

zwitterionic form to the neutral form caused the nanostructures to be dissociated.

As the neutral form of this copolymer had a low solubility at high ionic strength,

this photoreversible cluster behavior was of completely opposite nature in 1 M

NaCl.

3.4.3

Ultrasound

Ultrasound has been used successfully as a noninvasive trigger for the in vitro and

in vivo release of drugs from PEG - b - poly(propylene oxide) (PPO) - b - PEG (poloxamer)

micelles (Figure 3.10 ) [68 – 70] . Ultrasound not only causes the release of drug from

these micelles but also enhances the intracellular uptake of both the released and

encapsulated drug. Moreover, ultrasound can penetrate deeply into the interior of

the body, and can also be focused and precisely controlled. The application of

ultrasound in the frequency range of 20 to 90 kHz to pluronic micelles loaded with

DOX or ruboxyl (a paramagnetic anthracyclin, an analogue of Rubomicin; Rb)

Figure 3.10 Poloxamers (Pluronics

®

) have been used for the

preparation of DOX - loaded polymeric micelles [68 – 70] . Upon

ultrasound application, the micelles release the drug, whereas

eliminating the ultrasound leads to reformation of the micelle.

108 3 Smart Nanoassemblies of Block Copolymers for Drug and Gene Delivery

caused release of the drug. The highest rate of release was observed at 20 kHz, but

fell with increasing ultrasonic frequency, despite much higher power densities.

The release of DOX was also higher than that of Rb, due to a stronger interaction

and a deeper incorporation of Rb into the micelle cores. When using pulsed ultra-

sound, there is a rapid release and re - encapsulation behavior that takes within half

a second for each pulse. The released drug is quickly re - encapsulated between

ultrasound pulses; this suggests that, on leaving the sonicated volume, the non-

extravasated and noninternalized drug would circulate in the encapsulated form,

thus preventing any unwanted drug interactions with normal tissues. The in vivo

enhancement of cellular drug uptake for this system was attributed to an increase

in drug release from the micelles, which implied that ultrasound could be focused

on a localized tumor and an anti - cancer agent released from the micelles and

delivered directly to the malignant tissues. Unfortunately, ultrasound may also

promote permeabilization of the cell membrane, followed by an increase in cel-

lular drug incorporation.

3.5

Future Perspectives

Several approaches to the development of smart nanoassemblies have been dis-

cussed in this chapter, with a combination of stimuli - sensitive processes being

used to control the properties of the nanostructures and provide a precise customi-

zation of drug delivery behavior in vivo .

Moreover, external stimuli - responsive nanoassemblies – the fate of which can

be followed in vivo (e.g., smart drug delivery systems loaded with magnetic reso-

nace imaging (MRI) contrast agents [71] , or ﬂ uorescent dyes for NIR imaging

[72] ) – will facilitate the use of an external trigger and enhance the therapeutic

effects of smart drug carriers.

The incorporation of molecules that target speciﬁ c cellular signals on the outer

surfaces of smart nanoconstructs [21, 36, 73 – 76] , or the construction of

nanoassemblies with copolymers that have speciﬁ c interaction with cells [77] , is

essential for designing carrier systems with speciﬁ c cellular recognition. Such

recognition can be precisely tuned by constructing end - functionalized block

copolymers, the self - assembly of which will lead to the formation of nanostruc-

tures with pilot molecules on their exterior. In this way, a speciﬁ c drug delivery

to a target tissue and speciﬁ c activation of that delivered drug within the targeted

cell, may enhance the efﬁ cacy and minimize any adverse side effects during drug

targeting. The combination of a speciﬁ c cellular uptake of nanoassemblies with

intracellular drug release might also permit the accurate management of drug

distribution, leading to an enhanced or innovative therapeutic activity. Although

several of the pilot molecule - directed block - copolymer assemblies reported here

have still to be optimized, in some cases the activities achieved are elevated to a

signiﬁ cant extent, thus highlighting the huge potential of cell - targeted, smart

nanoassemblies.

References 109

References

1 Lazzari , M. and L ó pez - Quintela , M.A.

( 2003 ) Adv. Mater. , 15 , 1583 – 1594 .

2 Hamley , I.W. ( 2003 ) Angew. Chem. Int.

Ed. Engl. , 42 , 1692 – 1712 .

3 Kataoka , K. , Harada , A. and Nagasaki , Y.

( 2001 ) Adv. Drug Deliv. Rev. , 47 , 113 – 131 .

4 Allen , C. , Maysinger , D. and Eisenberg ,

A. ( 1999 ) Colloids Surf. B Biointerfaces , 16 ,

3 – 27 .

5 Matsumura , Y. ( 2007 ) J. Drug Target. , 15 ,

507 – 517 .

6 Martina , M. and Hutmacher , D.W. ( 2007 )

Polym. Int. , 56 , 145 – 157 .

7 Hasirci , V. , Vrana , E. , Zorlutuna , P. ,

Ndreu , A. , Yilgor , P. , Basmanav , F.B. , and

Aydin , E. ( 2006 ) J. Biomater. Sci. Polym.

Ed. , 17 , 1241 – 1268 .

8 Jagur - Grodzinski , J. ( 2006 ) Polym. Adv.

Tech. , 17 , 395 – 418 .

9 Matsumura , Y. and Maeda , H. ( 1986 )

Cancer Res. , 46 , 6387 – 6392 .

10 Maeda , H. , Wu , J. , Sawa , T. , Matsumura ,

Y. and Hori , K. ( 2000 ) J. Control. Release ,

65 , 271 – 284 .

11 Stolnik , S. , Illum , L. and Davis , S.S.

( 1995 ) Adv. Drug Deliv. Rev. , 16 ,

195 – 214 .

12 Kwon , G. , Suwa , S. , Yokoyama , M. ,

Okano , T. , Sakurai , Y. and Kataoka , K.

( 1994 ) J. Control. Release , 29 , 17 – 23 .

13 Avgoustakis , K. , Beletsi , A. , Panagi , Z. ,

Klepetsanis , P. , Livaniou , E. , Evangelatos ,

G. and Ithakissios , D.S. ( 2003 ) Int. J.

Pharm. , 259 , 115 – 127 .

14 Engin , K. , Leeper , D.B. , Cater , J.R. ,

Thistlethwaite , A.J. , Tupchong , L. and

McFarlane , J.D. ( 1995 ) Int. J.

Hyperthermia , 11 , 211 – 216 .

15 Murphy , R.F. , Powers , S. and Cantor ,

C.R. ( 1984 ) J. Cell Biol. , 98 , 1757 – 1762 .

16 Savic , R. , Luo , L. , Eisenberg , A. and

Maysinger , D. ( 2003 ) Science , 300 ,

615 – 618 .

17 Bae , Y. , Fukushima , S. , Harada , A. and

Kataoka , K. ( 2003 ) Angew. Chem. Int. Ed.

Engl. , 42 , 4640 – 4643 .

18 Bae , Y. , Nishiyama , N. , Fukushima , S. ,

Koyama , H. , Yasuhori , M. and Kataoka ,

K. ( 2005 ) Bioconj. Chem. , 16 , 122 – 130 .

19 Gillies , E.R. and Frechet , J.M. ( 2003 )

Chem. Commun. , 14 , 1640 – 1641 .

20 Lee , E.S. , Shin , H.J. , Na , K. and Bae , Y.H.

( 2003 ) J. Control. Release , 90 , 363 – 374 .

21 Lee , E.S. , Na , K. and Bae , Y.H. ( 2003 )

J. Control. Release , 91 , 103 – 113 .

22 Martin , T.J. , Prochazka , K. , Munk , P. and

Webber , S.E. ( 1996 ) Macromolecules , 29 ,

6071 – 6073 .

23 Tang , Y. , Liu , S.Y. , Armes , S.P. and

Billingham , N.C. ( 2003 )

Biomacromolecules , 4 , 1636 – 1645 .

24 Leroux , J. , Roux , E. , Le Garrec , D. , Hong ,

K. and Drummond , D.C. ( 2001 ) J. Control.

Release , 72 , 71 – 84 .

25 Taillefer , J. , Jones , M.C. , Brasseur , N. , van

Lier , J.E. and Leroux , J.C. ( 2000 ) J. Pharm.

Sci. , 89 , 52 – 62 .

26 Sant , V.P. , Smith , D. and Leroux , J. - C.

( 2004 ) J. Control. Release , 97 , 301 – 312 .

27 Merdan , T. , Kopecek , J. and Kissel , T.

( 2002 ) Adv. Drug Deliv. Rev. , 54 , 715 – 758 .

28 Wagner , E. ( 2004 ) Pharm. Res. , 21 , 8 – 14 .

29 De Smedt , S.C. , Demeester , J. and

Hennink , W.E. ( 2000 ) Pharm. Res. , 17 ,

113 – 126 .

30 Brown , M.D. , Schatzlein , A.G. and

Uchegbu , I.F. ( 2001 ) Int. J. Pharm. , 229 ,

1 – 21 .

31 Han , S. , Mahato , R.I. , Sung , Y.K. and

Kim , S.W. ( 2000 ) Mol. Ther. , 2 , 302 – 317 .

32 Behr , J.P. ( 1997 ) Chimia , 51 , 34 – 36 .

33 Boeckle , S. ( 2004 ) J. Gene Med. , 6 ,

1102 – 1111 .

34 Zauner , W. ( 1998 ) Adv. Drug Deliv. Rev. ,

30 , 97 – 113 .

35 Putnam , D. ( 2001 ) Proc. Natl Acad. Sci.

USA , 98 , 1200 – 1205 .

36 Oishi , M. , Nagatsugi , F. , Sasaki , S. ,

Nagasaki , Y. and Kataoka , K. ( 2005 )

Chembiochem , 6 , 718 – 725 .

37 Fukushima , S. , Miyata , K. , Nishiyama , N. ,

Kanayama , N. , Yamasaki , Y. and Kataoka ,

K. ( 2005 ) J. Am. Chem. Soc. , 127 ,

2810 – 2811 .

38 Kanayama , N. , Fukushima , S. , Nishiyama ,

N. , Itaka , K. , Jang , W. - D. , Miyata , K. and

Kataoka , K. ( 2006 ) ChemMedChem , 1 ,

439 – 444 .

39 Akagi , D. , Oba , M. , Koyama , H. ,

Nishiyama , N. , Fukushima , S. , Miyata , T. ,

Nagawa , H. and Kataoka , K. ( 2007 ) Gene

Ther. , 14 , 1029 – 1038 .

110 3 Smart Nanoassemblies of Block Copolymers for Drug and Gene Delivery

40 Lee , Y. , Fukushima , S. , Bae , Y. , Hiki , S. ,

Ishii , T. and Kataoka , K. ( 2007 ) J. Am.

Chem. Soc. , 129 , 5362 – 5363 .

41 Napoli , A. , Valentini , M. , Tirelli , N. ,

Muller , M. and Hubbell , J.A. ( 2004 ) Nat.

Mater. , 3 , 183 – 189 .

42 Napoli , A. , Boerakker , M.J. , Tirelli , N. ,

Nolte , R.J. , Sommerdijk , N.A. and

Hubbell , J.A. ( 2004 ) Langmuir , 20 ,

3487 – 3491 .

43 Takeoka , Y. , Aoki , T. , Sanui , K. , Ogata ,

N. , Yokoyama , M. , Okano , T. , Sakurai , Y.

and Watanabe , M. ( 1995 ) J. Control.

Release , 33 , 79 – 87 .

44 Kakizawa , Y. , Harada , A. and Kataoka , K.

( 1999 ) J. Am. Chem. Soc. , 121 ,

11247 – 11248 .

45 Kakizawa , Y. , Harada , A. and Kataoka , K.

( 2001 ) Biomacromolecules , 2 , 491 – 497 .

46 Miyata , K. , Kakizawa , Y. , Nishiyama , N. ,

Harada , A. , Yamasaki , Y. , Koyama , H.

and Kataoka , K. ( 2004 ) J. Am. Chem. Soc. ,

126 , 2355 – 2361 .

47 Miyata , K. , Kakizawa , Y. , Nishiyama , N. ,

Yamasaki , Y. , Watanabe , T. , Kohara , M.

and Kataoka , K. ( 2005 ) J. Control. Release ,

109 , 15 – 23 .

48 Katayama , Y. , Fujii , K. , Ito , E. ,

Sakakihara , S. , Sonoda , T. , Murata , M.

and Maeda , M. ( 2002 ) Biomacromolecules ,

3 , 905 – 909 .

49 Schild , H.G. ( 1992 ) Prog. Polym. Sci. , 17 ,

163 – 249 .

50 Chung , J.E. , Yokoyama , M. and Okano , T.

( 2000 ) J. Control. Release , 65 , 93 – 103 .

51 Kohori , F. , Sakai , K. , Aoyagi , T. ,

Yokoyama , M. , Yamato , M. , Sakurai , Y.

and Okano , T. ( 1999 ) Colloids Surf. B

Biointerface , 16 , 195 – 205 .

52 Topp , M.D.C. , Dijkstra , P.J. , Talsma , H.

and Feijen , J. ( 1997 ) Macromolecules , 30 ,

8518 – 8520 .

53 Uyama , H. and Kobayashi , S. ( 1992 )

Chem. Lett. , 1643 – 1646 .

54 Park , J. - S. , Akiyama , Y. , Winnik , F.M. and

Kataoka , K. ( 2004 ) Macromolecules , 37 ,

6786 – 6792 .

55 Park , J. - S. , Akiyama , Y. , Yamasaki , Y. and

Kataoka , K. ( 2007 ) Langmuir , 23 , 138 – 146 .

56 Park , J. - S. and Kataoka , K. ( 2007 )

Macromolecules , 40 , 3599 – 3609 .

57 Sershen , S.R. , Westcott , S.L. , Halas , N.J.

and West , J.L. ( 2000 ) J. Biomed. Mater.

Res. , 5 , 293 – 298 .

58 Weissleder , R. ( 2001 ) Nat. Biotechnol. , 19 ,

327 – 331 .

59 Jiang , J. and Tong , Z. ( 2005 ) J. Am. Chem.

Soc. , 127 , 8290 – 8291 .

60 Jiang , J. , Tong , X. , Morris , D. and Zhao ,

Y. ( 2006 ) Macromolecules , 39 , 4633 – 4640 .

61 Wang , G. and Wang , X. ( 2002 ) Polym.

Bull. , 49 , 1 – 8 .

62 Pieroni , O. , Fissi , A. and Popova , G.

( 1998 ) Prog. Polym. Sci. , 23 , 81 – 123 .

63 Minoura , N. , Higuchi , M. and Kinoshita ,

T. ( 1997 ) Mater. Sci. Eng. C. Biomim.

Mater. Sens. Syst. , 4 , 249 – 254 .

64 Wang , G. , Tong , X. and Zhao , Y. ( 2004 )

Macromolecules , 37 , 8911 – 8917 .

65 Laschewsky , A. and Rekai , E.D. ( 2000 )

Macromol. Rapid Commun. , 21 , 937 – 940 .

66 Yuan , Z. , Fischer , K. and Sch ä rtl , W.

( 2005 ) Langmuir , 21 , 9374 – 9380 .

67 Konak , C. , Rathi , R.C. , Kopeckova , P. and

Kopecek , J. ( 1997 ) Macromolecules , 30 ,

5553 – 5556 .

68 Pitt , W.G. , Husseini , G.A. and Staples ,

B.J. ( 2004 ) Expert Opin. Drug Deliv. , 1 ,

37 – 56 .

69 Husseini , G.A. , Myrup , G.D. , Pitt , W.G. ,

Christensen , D.A. and Rapoport , N.Y.

( 2000 ) J. Control. Release , 69 , 43 – 52 .

70 Marin , A. , Muniruzzaman , M. and

Rapoport , N. ( 2001 ) J. Control. Release , 10 ,

69 – 81 .

71 Nakamura , E. , Makino , K. , Okano , T. ,

Yamamoto , T. and Yokoyama , M. ( 2006 )

J. Control. Release , 114 , 325 – 333 .

72 Ghoroghchian , P.P. , Frail , P.R. , Susumu ,

K. , Blessington , D. , Brannan , A.K. , Bates ,

F.S. , Chance , B. , Hammer , D.A. and

Therien , M.J. ( 2005 ) Proc. Natl Acad. Sci.

USA , 102 , 2922 – 2927 .

73 Yamamoto , Y. , Nagasaki , N. , Kato , M. and

Kataoka , K. ( 1999 ) Colloids Surf. B

Biointerfaces , 16 , 135 – 146 .

74 Nagasaki , Y. , Yasugi , K. , Yamamoto , Y. ,

Harada , A. and Kataoka , K. ( 2001 )

Biomacromolecules , 2 , 1067 – 1070 .

75 Torchilin , V. , Lukyanov , A.N. , Gao , Z. and

Papahadjopoulos - Sternberg , B. ( 2003 )

Proc. Natl Acad. Sci. USA , 100 ,

6039 – 6044 .

76 Bae , Y. , Nishiyama , N. and Kataoka , K.

( 2007 ) Bioconj. Chem , 18 , 1131 – 1139 .

77 Holowka , E.P. , Sun , V.Z. , Kamei , D.T.

and Deming , T.J. ( 2007 ) Nat. Mater. , 6 ,

52 – 57 .

A Comprehensive Approach to the Alignment and

Ordering of Block Copolymer Morphologies

Massimo Lazzari and Claudio De Rosa

111

Advanced Nanomaterials. Edited by Kurt E. Geckeler and Hiroyuki Nishide

ISBN: 978-3-527-31794-3

4

4.1

Introduction

4.1.1

Motivation

Self - assembly is an enormously powerful concept in modern materials science,

which was ﬁ rst associated with the use of synthetic strategies for the preparation

of nanostructures only about 15 years ago [1 – 3] . Since then, a large variety of care-

fully designed building blocks have been proposed and employed for working

“ from atoms up ” with the aim of fabricating two - dimensional ( 2 - D ) and three -

dimensional ( 3 - D ) structures. In particular, within the past decade, interest in a

potentially ideal nanoscale tool has been growing exponentially, namely phase -

separated block copolymer s ( BC s) [4 – 17] .

Immiscibility among the BC constituents is common, and phase separation

results in the series of morphologies, for example, lamellar, gyroid, hexagonal

and body - centered cubic for diblock copolymers [4, 7, 9] , the size and shape of

which may be conveniently tuned by changing the molecular weights and com-

positions of the BCs [5, 18 – 20] . Part of the enormous potential for nanomaterial

fabrication of these self - organized patterns of chemically distinct domains that

have periodicity in the mesoscale – that is, between a few tens and hundreds of

nanometers – has already been demonstrated [21 – 40] . However, in our opinion

their development into practical routes suitable for industrial applications will

probably only be fully exploited when a few key limitations have been efﬁ ciently

overcome. As an example, writing and replication processes in microelectronics

require spatial and orientational control of patterns which, in the case of BCs,

entails the solution of the nontrivial problem of large - area ordering and precise

orientation of domains.

Regular structures can be generated by controlling the typical disadvantages of

spontaneous phase separation. First, similar to polycrystalline materials, the self -

assembly of BCs in bulk is prone to form grains with a high level of local order

but a very short persistence length, especially in the case of cylinders and lamellae

112 4 Alignment and Ordering of Block Copolymer Morphologies

which, on a larger scale, correspond to bulk materials with isotropic properties.

Although annealing permits a consistent annihilation of the corresponding grain

boundary defects, in addition to other defects such as dislocation, disclination,

terracing and asymmetry defects [41 – 47] , the formation of defect - free structures

points to more efﬁ cient strategies based on the application of external forces or

spatial constraints. In the same way, long - range oriented patterns, for example,

cylindrical or lamellae domains parallel to the substrate, with all of the axes aligned

in a single direction rather than randomly in the parallel plane, may only be

induced through a careful engineering of surface effects or by well - oriented ﬁ elds.

It could be stated that for many technological applications such an appealing

spontaneous organization has to be directed by some form of templating (in this

context considered in its broader sense), where the BC components could not only

interact with each other but also take advantage of external controlling

interactions.

Numerous methods to induce and control BC domain orientation have been

explored, particularly for substrate - supported ﬁ lms to create perfectly periodic 2 - D

patterns, ranging from the ﬁ rst demonstration of the effectiveness of the applica-

tion of electric ﬁ elds [48] to the recent combination of both active and passive

forces to obtain laterally ordered arrays of cylindrical domains with areal densities

of up to 1.5 terabits per cm

2

[39] , through the elegant application of chemically

nanopatterned templates [31] . Most methods proposed to date will be critically

presented in this chapter, and special attention will be given to the combination

of techniques to yield 3 - D control.

4.1.2

Organization of the Chapter

The scope of this chapter is to provide an overview of the variety of methods that

can induce long - range ordered BC morphologies, focusing on the most promising

areas of ongoing research. The main strategies applied so far may be classiﬁ ed

into three different approaches:

1. Control of orientation by applying external ﬁ elds, such as electric, magnetic,

thermal, mechanical and solvent evaporation. Depending on the ﬁ eld imposed,

thin ﬁ lms and/or samples in bulk may be oriented.

2. Induction of large - area ordering by facilitating the self - assembly, generally of

thin ﬁ lms, on templates either topographically or chemically nanopatterned.

3. Modulation of substrate and surface interactions as a result of:

a) Preferential interaction of one block with the surface.

b) Neutralization of attractions to the substrate or to the surface.

c) Epitaxial crystallization of domains onto a crystalline substrate.

d) Directional eutectic crystallization of a BC solvent.

e) Graphoepitaxy.

f) 2 - D geometric conﬁ nements.

4.2 How to Help Phase Separation 113

Before highlighting recent advances in such control strategies, a preliminary

section speciﬁ cally for all researchers who are new to this ﬁ eld will offer practical

information on ﬁ lm preparation, and on the methods used in practice to achieve

thermodynamic equilibrium morphologies. Because one of the aims of this book

is to offer solutions to experimental difﬁ culties and research needs, the decision

was taken to highlight the practical aspects of phase separation and orientation

with respect to the theoretical concepts.

4.2

How to Help Phase Separation

Except for some speciﬁ c instances – for example, direct use as photonic crystals or

in the case of amphiphilic BC for drug and genetic delivery – applications of BCs

require the preparation of thin ﬁ lms with thicknesses ranging from a few tens of

nanometers (in some cases down to thicknesses of less than the corresponding

equilibrium period of the BC) to several micrometers. Films with low surface

roughness may be produced by spin - coating or dip - coating from relatively dilute

solutions, that is, approximately 1 – 5% by weight, onto solid substrates with

uniform ﬂ atness. The thickness and the uniformity of the ﬁ lm surface mainly

depend on the concentration of the solution, the volatility of the solvent, and the

speciﬁ c instrumental speed – that is, the spin speed or withdrawal speed, respec-

tively. Silicon wafers, eventually coated with metals, semiconductors, carbon or

polymers are often utilized as the support. During dip - coating processes, and also

for ﬁ lms prepared from direct casting, the solvent may evaporate slowly, thus

allowing a stable organization of macromolecules close to thermodynamic equi-

librium. In contrast, in the case of spun - cast ﬁ lms the solvent is driven off so

quickly that nonequilibrium structures could be observed. Moreover, the concen-

tration gradient due to fast solvent evaporation can in fact have a signiﬁ cant effect

on domain orientation, as discussed in Section 4 .

In thin ﬁ lms, the self - assembled BC morphologies are inﬂ uenced not only by

molecular weights, polydispersity and composition, but also by other variables

such as the selectivity of the solvent for one block, surface – interfacial interactions,

and the interplay between structure periodicity and ﬁ lm thickness, which can

cause signiﬁ cant deviations from the predicted phases in the bulk state. An elegant

demonstration and a didactic example of the inﬂ uence of surface effects in thin

ﬁ lms has been reported by Krausch and coworkers [49] . Their experimental data

for a triblock copolymer of ABA type are compared with those of the simulated

ﬁ lm in Figure 4.1 . Several more studies have demonstrated the importance of

conﬁ nement effects, and will be treated in detail later.

Independently of the casting techniques, even for a ﬁ lm prepared taking all

necessary precautions, it is not possible to obtain a perfectly ordered morphol-

ogy over a large area. In fact, an optimization of the nanostructures is almost

indispensable and can be carried out by different annealing processes, with the

double objective of obtaining the equilibrium morphology and eliminating the

114 4 Alignment and Ordering of Block Copolymer Morphologies

defects. Annealing is usually performed before any further manipulation, even

though some approaches include the alignment of domains within the orienta-

tion process.

In principle, thermal annealing is the simplest option and the most commonly

used method. This consists of controlled heating at a temperature above the glass

transition temperature ( T

g

) of the constituent blocks, preferably in an inert atmos-

phere or under vacuum, for a speciﬁ c time. For polymers with high molecular

weights and complex architectures, the high degree of chain entanglements and

the difﬁ cult diffusion of one polymer block through the domains of the other

blocks pose large kinetic barriers to equilibrium. In such cases, and for partially

crystalline BCs with high fusion temperatures, the annealing window for the

relevant conditions of temperature and time that are theoretically necessary and

those of the order – disorder transition or polymer decomposition, may be insuf-

ﬁ cient to reach equilibrium. On the other hand, the degradation of one or more

blocks has been used to stabilize the morphologies for further applications,

through decomposition, partial oxidation or crosslinking [23, 26, 27, 50 – 53] , or

even to induce a hierarchical transition of morphologies [54] .

Alternative annealing approaches entail an increase in chain mobility by the

addition of some type of plasticizer, either transient, such as a solvent, or low -

Figure 4.1 (a,b) Tapping - mode scanning force

microscopy phase images of thin ﬁ lms of a

cylinder - forming polystyrene - block -

polybutadiene - block - polystyrene (PS - b - PB - b -

PS) after solvent annealing, showing a

sequence of phases as a function of the

height proﬁ le (c), which is in good agreement

with the simulation of an A

3

B

12

A

3

copolymer

ﬁ lm (d). Owing to preferential wetting, the

silicon substrate is covered with a

homogeneous 10 nm - thick PB layer which,

with increasing thickness from left to right, is

followed by isolated domains of PS, parallel -

oriented PS cylinders, perforated lamella,

parallel - oriented PS cylinders again, and ﬁ nally

two layers of parallel - oriented cylinders.

Reproduced with permission from Ref. [49] ;

Geckeler K.E., Nishide H. (Eds.) Advanced Nanomaterials

Подождите немного. Документ загружается.