Reprinted from ACCOUNTS OF CHEMICAL RESEARCH, 1995' 28.Copyright O 1995 by tlie American Chemical Society and reprinted by permission of the copyright owner. 2r9

Patterned Self-Assembled Monolayers and Meso'ScalePhenomena

Anrrr KuMAR, Nrcsoles L. Asnorr, ENoclt KIM, Haxs

Department of Chemistry, Haruard Uniuersity,

Receiued October 26,

A. BrneuycK. AND Gnoncn M. WHTTESIDES*

Cambridge, Massachusetts 02 1 38

1994

Introduction

Meso-scale systems, that is, structures and phenom-ena having spatial dimensions in the range extendingfrom large molecules (perhaps 10 nm) through virusesto eukaryotic cells (10 pm), are one of the frontiers ofchemistry. These systems are the home of complexity,and understanding this complexity requires new ap-proaches to synthesis and fabrication. Among theseapproaches are those based on chemical concepts suchas molecular self-assembly and synthesis of structuresat thermodynamic equilibrium. 1'2

Meso-scale systems offer opportunities to explorephenomena that occur at dimensions larger thanmolecules but smaller than cells. The distinctiveproperties of meso-scale systems arise when thecharacteristic length of a process of interest, such asballistic movement of an electron,3 excitation of acollective resonance by light,a diffusion of a redox-active molecule close to an electrode,s or attachmentand spreading of a eukaryotic ceII,6 is similar to adimension of the structure in (or on) which it occurs.These processes involve interactions with many atomsor molecules rather than interactions with small,localized ensembles of atoms or molecules. Meso-scalesystems bridge the molecular and the macroscopic.They display collective and often nonlinear behavior.Some meso-scale structures, although short-lived,arise because they are thermodynamically stablestates; examples include statistical aggregates suchas micelles and microemulsion particlesT and liquidcrystals.s Biology provides many other examples oflonger-lived structures (for example, folded proteinse

Amit Kumar received an A.B. in chemistry from Occidental College and a Ph.D.in chemistry from the California Institute of Technology, before going on to postdoctoralresearch at Haryard Universitv under Prof. Whitesides. His current position is ProiectLeader for New Technologieb at ldetek Corporation.

Nicholas Abbott was born in Adelaide, Australia, in 1963. He received a B.Eng.from the University of Adelaide in 1985 and a Ph.D. in chemical engineering fromthe Massachusetts Institute of Technology in 1991. Following postdoctoral researchin the Chemistry Department at Harvard University, Abbott joined the Department ofChemical Engineerrng and Materials Science at the University of California at Davisas an assistant professor. His research focuses on principles for active control ofthe self-organization of amphiphilic molecules rn aqueous solutions and the anchoringof liquid crystals on organic surfaces.

Enoch Kim was born on Feb 8, 1968, in Pusan, Korea. He received an A.B.from Hamrlton College, Clinton, NY. Since 1990, he has been working under Prof.Whitesides in developing new ways of fabricating and using patterned SAMs. Hewas an Eli Lilly predoctoral fellow from 1992 to 1993.

Hans Biebuyck was born in Deinze, Belgium, in 1961. He received a B.S. inchemistry from the University of Delaware in 1983 and then worked forthree yearsat Rohm & Haas Co., following which he earned a Ph.D. in physical chemistry atHarvard under Prof. Whitesides (1994). He is now a oostdoc at IBM Research inZurich working on microwave frequency scanning tunneling microscopy and itsapplication to problems in interfacial science.

George M. Whitesides was born on Aug 3, 1939, in Louisville, KY. He receivedan A.B. deoree from Harvard Universitv in 1960 and a Ph.D. from the CaliforniaInstitute of iechnology (with J. D. Robert's) in 1964. He was a member of the facultyof the Massachusetts Institute of Technology from 1963 to 1982. He joined theDepartment of Chemistry of Harvard University in 1982 and was Department Chairmanin 1986-1989. He is now Mallinckrodt Professor of Chemistrv at Harvard Universitv.

and the nucleocapsides of virusesl0). Nonlinear, dy-namic processes can also involve meso-scale struc-tures: representative processes include aggregationof colloids into fractal structures,ll phase separationof polymers into microdomains,l2 and heterogeneousnuileation on surfaces (e.g., condensation,l3 crystal-lization,la and electrodepositionl5).

Chemistry has been hindered in its exploration ofmany meso-scale phenomena by its limited ability tofabricate appropriate experimental systems: tech-niques for synthesizing molecules are much moreadvanced than techniques for fabricating ensemblesof molecules. The work summarized in this Accountuses self-assembled monolayers (SAMs) of organicmolecules on metallic substrates,lG and procedures forforming patterns in the plane of the monolayer, toprovide new approaches to two- and three-dimen-sional, quasi-planar, meso-scale structures. SAMsoffer exquisite control over structure perpendicular tothe plane of the monolayer: by varying the structureof the molecular constituents of the SAM, thicknesscan be manipulated at the 0.1-nm level, and interfacialcomposition and properties can be controlled over awide range.16 Until recently, it has been diffrcult tocontrol the composition or properties of SAMs in theplane of the monolayer, although e-beam writinglT andphotolithographyls' rs provide method s for decompo singSAMs in patterns. We have developed methods to

(1 )L indsey , J . S . Neru J . Chem.199 l , 15 , 153- i80 .(2) Whitesides. G. M.; Mathias, J. P.; Seto, C. T. Science 1991,254,

13 12 - 1319 .(3) Bell, L. D.; Kaiser, W. J. Phys. Reu. Lett. 1988. 61, 2368-2370.(4) Bube, R. H. ELectrons in Solids; Academic: New York, 1981.(5) For reviews on microelectrodes, see" Microelectrodes'. Theory and

Applications; Montenegro, M. I., Queiros, M. A., Daschbach, J. L., Eds';Kluwer Academic: Boston, 1991. Wightman, R' M.; Wipf, D. O. InElectroanalytical Chemistry: A Series of Aduances; Bard, 4 J.' na.;Dekker: New York, 1989; Vol. 15, pp 267 -353' Fleischmann, M.; Pons,S.: Rolison, D. R.; Schmidt, P. P. Ultramicroelectrodes; Datatech Sys-tems: Morgantown, NC, 1987 and references cited therein.

(6) Folkman, J.; Moscona, A. Nature 1978,273,345-347 . Ingber, D.E. Proc. Natl. Acad. Sci. U.SA. 1990, 87, 3579-3583.

(7) Chevalier, Y.; Zemb, T. Rep. Prog. Phys' 1990, 53, 279-371'.(8)de Gennes, P. G.; Prost, J. The Physics of Liquid Crystals;

Clarendon: Oxford, 1993.(9) Creighton, T. E. Proteins'. Structure and Molecular Principles;

Freeman: New York, 1983.(10) Klug, A. Angew. Chem., Int. Ed. Engl. L983,22,565.(11)Lin, M. Y. ; L indsay, H. M.; Wei tz, D. A. ; Bal l , R. C. ; Kle in, R. ;

Meakin, P. Nature 1989, 339, 360-362. Wilcoxon, J. P'; Martin, J. E.;Schaefer, D. W. Phys. Reu. A 1989, 39, 2675-2688.

(12) Noshay, A.; McGrath, J. E. Block Copolymers: Oueruiew andCritical Suruey; Academic: New York, 1977.

(13) Dimeglio, J. M.; Gandeboeuf, P. J. Chim. Phys. Phys.'Chim. Biol.1992, 89, 1357-1371. Briscoe, B. J.; Galvin, K. P. Colloids Surfaces1991, 56, 263-278. Fritter, D.; Knobler, C. M.; Beysens. D A. PA1s.Reu. A I9gl, 43, 2858-2869.

(14) Heywood, B. R. ; Mann, S. Chem. Mater. 1994, 6, 311-318.Heywood, B. R. ; Mann, S. Adu. Mater. 1994,6,9-20.

(15) Dini, J.W. Electrodepositioru: The Materials Science of Coatirugsand Substrales; Noyes: Park Ridge, NJ, 1993.

(16) For a review, see: Dubois, L. H.; Nuzzo, R. G. Annu. Reu. Phys.Chem. 1992, 43, 437 - 463.

1995 American Chemical Societv0001-484219510128-0219$09.00/0 0

220 Acc. Chem. Res., Vol. 28, Ir{o. 5, 1995

fabricate SAMs with 100 nm to 100 trrm patterns.2o-2eThey require only limited (and in some cases no)access to facilities for optical lithography and are thusparticularly convenient for use in chemistry labora-tories. They use molecular self-assembly to formSAMs selectively in meso-scale areas.

The procedures have been developed using SAMsformed from alkanethiols on gold, copper, and silver,and they rely on several characteristics of these SAMs.(i) SAMs formed from a long-chain, hydrophobic al-kanethiol on gold, copper, or silver are effectivenanoresislr.20'21'25'26'30 For example, oxidative dissolu-tion of goldzO'zt'25'26 and electroless plating of nickelz0are inhibited or prevented by the presence of a SAM.(ii) A SAM of a short-chain alkanethiolate (especiallya hydrophilic one) does not protect against corrosion,but does provide limited but very useful protectionagainst formation of another alkanethiolate when thesurface is exposed to a solution of an alkanethiol ordialkyl disulfide.2l (iii) It is possible to form patternsof SAMs by contact printing using an elastomericstamp20'22'23'25 (or by other processes such as micro-writing26) and to modify or remove SAMs on a surfaceselectively by mechanical scribing (micromachin-ing;,zt z0-2e photooxidation,le electrochemical reduc-tion,31 or exposure to electrons, atoms, or X-rays.17,32SAMs can confer on surfaces a broad range of inter-facial free energies and composition; they therefore

t lT rN l ino . N . : Ozak i . S . : Oga iva . K . ; Ha tada , M. Th tn SoL id F iLms1994.21|1.371-3i t - . Sondag-Huethorst , J . A. ; van Hel leput te, H.R.;Fokkink. L. G. Appl . Phys. Let t . 1994,64,285-287. Marr ian, C. R. ;Perkins. F ' . K. ; Brandow, S. L. ; Koloski , T. S. ; Dobisz,E. A. ; Calvert , J .I I . App1. Ph1's. Let t . 1994,64,390-392. Tiber io, R. C. ; Craighead, H.G.. Lercel . X ' { . ; Lau. T. ; Sheen, C. W.; Al lara, D.L. Appl . Phys. Let t .1993,62. 4 i6 ,+78.

t l 8 r W o l l m a n , E . W . ; K a n g , D . ; F r i s b i e , C . D . ; L o r k o v i c , I . M . ;Wrighton. N{. S. J. Am. Chem, Soc. 1994, 116, 4395-4404. Rozsnyai,t,. F.: Wrighton, M. 5.,1. Am. Chent. Soc. 1994, 116,5993-5994. Frisbie,C. D.r Wollman. E. W.: Martin, J. R.: Wrighton, M. S. J.Vac. Sci. Technol.A 1993. 11.2368-2372. Wol lman, E. W.; Fr isbie, C. D. ; Wrighton, M.S. Lartgnt t t i r 1993, I ,1517-1520. Kang, D. ;Wrighton, M. S. Langmuir1991 . 7 .2769-2174 .

t 19 r Huang. J. Y.; Dahlgren, D. A.; Hemminger, J. C. Langmttir 1994,10.626-628. Tar lov, M. J. ; Burgess, D. R. ; Gi l len, G. J. Am. Chem.Soc . 1993 . 115 .5305-5306 . Huang , J . Y . ; Hemminger , J . C . J . Am.Chent. Sor ' . 1993. 115.3342-3343. Calvert . J . M. J.Vac. Sci .Technol .B 1993, 11.2155-2163. Dressick, W. J. ; Dulcey, C. S. ; Georger, J. H. ;Clalvert , J . NI . Chem. Mater. 1993,5, 148-150. Calvert , J .M.; Chen,M. S. ; Dulcey. C. S. ; Georger, J. H. ; Peckerar, M. C. ; Schnur, J. M.;Schoen. P. E. J. Vac. Sci . Technol . B 1991, 9,3447-3450.

t20tKumar, A.; Biebuyck, H. A.; Whitesides, G. M. Langmuir L994,1 0 . 1 4 9 8 - 1 5 1 1 .

t21t Abbott, N. L.: Kumar, A.; Whitesides, G. M. Chem. Mater. 1994,6. 596-602.

t22tSinghvi . R. ; Kumar, A. ; Lopez, G. P. ; Stephanopoulos, G. N. ;Wang. D. I . ; Whi tesides, G. M.; Ingber, D. E. Science 1994,264,696-698.

(23tKumar, A. ; Whi tesides, G. M. Science 1994,263,60-62.t24lLopez, G. P.; Biebuyck, H. A.; Harter, R.; Kumar, A.;Whitesides,

G. M. J . An t . Chem. Soc . 1993 , 115 ,10774- 10781 .t25tKumar, A. ; Whi tesides, G. M. Appl . Phys. Let t .1993,63, 2002-

2004.t26tKumar. A. ; Biebuyck, H. A. ; Abbott , N. L. ; Whi tesides, G. M. J.

Am. Chem. Soc . 1992 , l 14 ,9188-9189 .t27 t Abbott, N. L.; Whitesides, G. M. Langmuir 1994, 10, 1493-1497 .t28 )Abbo t t , N . L . ;Wh i tes ides , G . N{ . ;Racz , L .M. ; Szeke ly , J . J .Am.

Chem. Soc. 1994. 116,290-294.(29)Abbott , N. L. ;Folkers, J. P. ;Whitesides, G.M. Science 1992,257,

1380- 1 i182 .(30) Sabatani, E.; Rubinstein, L J. Electroanal. Chem. 1987,219,365-

371. Sabatani , E. ;Rubinstein, L J. Phys. Chem.1987,91,6663-6669.Finklea, H. O.; Avery, S.; Lynch, M.: Fursch, T. Langmuir \987,3, 409-413. Laib in is, P. E. ; Whi tesides, G. M. J. Am. Chem. Soc. 1992, 114,9022-9028.

(31)Widr ig, C. A. ; Chung. C. ; Porter , M. D. J. Electroanal . Chem.f991.310, 335. Walczak, M. M.; Popenoe, D. D. ; Deinhammer, R. S. ;Lamp, B. D. ; Chung, C. ; Porter . M. D. Langmuir 199L,7,2687. Abbott ,N. L. ; Gorman, C. B. ; Whi tesides, G. M. Langmuir 1995, 11 ( l ) , 16-18.

Kut t tor t , t c t l .

al low control of wettabi l i ty,23'27-2e j i chemici i l trnci

electrical permeab llity,zo'zt'25'26'30'34 inte ract i o n s ri. i t hbiomolecules,24'35 and other properties.

Methods for Fabricating Patterns in SAIVIs

Microcontact Printing. Perhaps the most usefuland versatile method of pattern formation is micro-contact printing Q"ICP, Figure l).20'22'23'25 In prCP, anelastomeric stamp is produced by casting poly(di-methylsiloxane) (PDMSI onto an appropriate master.A negative image of the master is produced in thecured PDMS. A range of techniques can be used toproduce the masters. We often use photolithographyor X-ray lithography, but other structures exhibitingcorrugations (e.9., mechanically ruled diffraction grat-ings) have also been used as masters. The elastomericstamp of PDMS is inked with an ethanolic solution ofhexadecanethiol (HDT) and placed in contact with thesurface of a polycrystalline film of gold for 20-30 s.Hexadecanethiol transfers from the protruding regionsof the stamp to the surface and forms a SAM in theregion of contact. Because SAMs formed from HDTare not wetted by HDT, excess HDT on the stampremains on the stamp and is not transferred to thesurface. (This remarkable property, "autophobicity",is key to the formation of patterns with sharplydefined edges.)36 Because the recessed features of thestamp do not touch the surface of the gold, andbecause the system of neat HDT and the SAM formedfrom it is autophobic, the regions of the gold that arenot contacted by the stamp are also not derivatizedby the HDT.

After removal of the stamp, the gold surface can becontacted with a dilute ethanolic solution containinga second alkanethiol (for example, 1l-mercaptounde-canol, HS(CHz)roCHzOH) or dialkyl disulfide; thissecond thiolate precursor selectively derivatizes thebare regions of the gold. Figure 1b shows the processof pCP and an example of a stamp and correspondingcircuit pattern that was fabricated on a gold surfaceusing this technique. Variants in this procedurepermit a hydrophilic thiol to be used as the initialmaterial for formation of a pattern. In favorable cases,features as small as 200 nm have been generated by

PCP.,OMicrowriting. Microwriting (Figure 2), performed

(32) Laibinis, P. E.; Graham, R. L.; Biebuyck, H. A.; Whitesides, G.M. Science lggl , 254,981-983. Graham, R. L. ; Bain, C. D. ; Biebuyck,H. A. ; Laib in is, P. E. ; Whi tesides, G. M. J. Phys. Chem.1993,97,9456-9464. Schoer, J. K.; Ross, C. B.; Crooks, R. M.;Corbitt, T. S.; Hampden-Smith, M. J. Langmuir 1994,10, 615-618. Ross, C. B. ; Sun, L. ; Crooks.R. M. Langmuir 1993,9, 632-636.

(33) Bain, C. D. ; Whi tesides, G. M. J. Am. Chem. Soc. 1988, 110.5897-5898. Bain, C. D. ; Whi tesides, G. M. Langmuir 1989, 5. 13701378. Dubois, L. H. ; Zegarski , B. R. ; Nuzzo, R. G. J. Am. Chem. Sr,<1990, 112,570-579. Laib in is, P. E. ; Whi tesides, G. M. J. Arn. Ch, 'ntSoc. 1992. 114. 1990*1995. See also: Whitesides, G. M.: Laih in i . . PE. Langmuir 1990, 6, 87-96 and references cited within.

(34) Porter , M. D. ; Br ight , T. B. ; Al lara, D. L. ; Chidsev. C. Fl I ) . /Am. Chem. Soc. 1987, 109,3559. Sabatani , E. ; Rubinstein. I . . . / . 1 ' l rvsChem.1987,91,6663. Finklea, H. O.;Avery, S. ; Lynch, N{. : Furts.h.

- l '

Langmuir 1987,3,409. Chidsey, C. E. D. ; Loiacono, D. N. Lr t r tgrr t r r t r1990,6,682. Chidsey, C. E.D.; Bertozzi , C. R. ; Putv inski . T. ̂ \1 ' / .1nrChem. Soc . 1990 , 112 ,4301 . H ickman, J . J . ; O fc r . D . .Lou . ( ' F . :Wrighton, M.S.; Laib in is, P. E. ; Whi tesides, G. M. J. Ant . ( 'h tnt . \ t , tL991, 113, 1128. Mi l ler , C. ; Cuendet, P. ; Gratzel . \ I . . / . Pl r . r 's ( 'htnt1991,95, 877. Finklea, H. O.; Hanshew, D. D. J. Arn. ( 'hent .Srx. 1992.114 ,3173 . Becka , A . M. ; M i l l e r , C . J . J . Phys . Chen t . 1993 . 97 .62 :33 .

(35)Bhat ia, S. K. ; Teixeira, J. L. ; Anderson. NI . : Shr i r -er lake. L. Cl . ;Calvert , J . M.; Georger, J. H. ; Hickman, J. J . r Dulcer ' . C. S.r Schoen. P.E. ; L ig ler , F. S. Anol . Biochem. 1993,208.197-205.

(36)Biebuyck, H. A. ; Whi tesides, G. M. I 'angmrt i r 1994. 10 t l2t .458r-4587.

Patterned SAMs and Meso-Scale Phenomena

t 100 nm - 200 molecules I

Acc. Chem. Res., Vol. 28, No. 5, 1995 22L

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Figure 1. Microcontact printing of SAMs on surfaces of gold.The schematic representation at the top shows the structureformed at the smallest current scale of 1rCP. The width of thisfeature is approximately 100 nm across (-200 molecules ofalkanethiolates); its thickness is -2 nm. A number of ir-regularities in the structure contribute to its properties. Thesequence of steps ending in the lower left outlines the processesused in pCP. The top figure is an optical micrograph of a stamp,and the bottom is an electron micrograph of the correspondingcircuit pattern fabricated with this stamp. The light regionsare the hydrophobic regions.

by dispensing neat HDT from the tip of a fine pen orcapillary onto the surface of a film of gold, also relieson the "autophobicity" of SAMs formed from HDT.21'26By controlling the height of the capillary above thesurface, the area of contact between the drop and thesurface can be manipulated to control the "line width"of the resulting SAMs. Self-assembled monolayerswith lateral dimensions of 10 prm and macroscopiclengths (centimeters) can be routinely prepared usingthis method.

ro6mFigure 2. Microwriting: (a) an electron micrograph of arepresentative pen used for microwriting; (b) an optical photo-graph depicting the writing process with a drop of hexa-decanethiol (HDT); (c) an electron micrograph of a patternedSAM prepared by microwriting (the light region is the SAM fromHDT i .

Micromachining. A combination of micromachin-ing and molecular self-assembly provides the basis fora third principle that can be used to form meso-scalestructuree.2l'26 2e The procedure has three steps(Figure 3): (i) formation of an initial SAM on thesurface of a film of gold; (ii) selective removal ofregions of the SAM by micromachining; and (iii)

selective assembly of a second SAM on the machinedregions of gold. Tools that we have used for micro-machining include wires, carbon fibers, glass fibers,scalpel blades, electrochemically sharpened tungstenfibers, profilometer tips, and STM and AFM tips. Byrepeating steps i i and i i i , this procedure can be usedto prepare surfaces patterned with three or fourregions capable of performing different functions;27lateral spatial resolutions of 100 nm have beenachieved using the tip of a carbon fiber as themachining tool.2e The ultimate limit to the spatialresolution of this method may turn out to be the rateof lateral diffusion of molecules in the SAM; this rateis presently unknown.

Other Techniques for Forming Patterns. Thesemethods include modifying or damaglng SAMs usingelectron and atomic beams,1? light,18'le and electro-chemistry.3l The mechanism of photooxidation ofSAMs has been studied by Hemminger and Tarlov andseems to involve photooxidation of alkanethiolates toalkanesulfonates.le

Limits to Performance. For applications of pat-terned SAMs, the primary limits to function aredefects in their two-dimensional structure. For useas resists, even nano-scale defects can nucleate etch

Si

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nU

-s(cH2h r cHs

Figure 3. (a) Schematic illustration of the formation of 0.1-1-7rm hvdrophobic lines in a hydrophilic surface with microma-chining and SAMs: Au, evaporated film of gold; Ti, evaporatedfilm of titanium used to promote adhesion of gold to theunderlying support (silicon or glass). (b) Schematic illustrationof the apparatus used to position the blade and control themachining pressure. The blade was hung between a pair oftweezers that were mounted over anX-Ytranslation stage. Thecombined weight of the blade and attached paper clips main-tained a constant load (-3 mN) on the tip during machining.The tip of the scalpel blade was translated across the film ofgold at a rate of -1 mm/s: this procedure produced grooves withcontinuous, uniform, and reproducible dimensions (-1 4m inwidth). (c) Cross-sectional profiles of the grooves show depthsof -0.05 mm and raised edges (-0.1 pm high and -0.2 prm wide)formed by the plastic deformation of the gold during micro-machining.

pits; for use as diffraction gratings, defects as largeas micrometers may be unimportant. Detailed experi-ments aimed at understanding the processes thatgenerate or eliminate defects are just beginning.s7

(37)Schonenberger, C.; Sondag-Huethorst, J. A.; Jorritsma, J.; Fok-kink, L. G. Langmuir 1994, 10,671-674.

Kumar et al.

Applications of Patterned SAIIs

Planar Microfabrication. When a gold surfaceis exposed to a solution containing cyanide ion (CN-)and an oxidant such as oxygen (Oz), the gold dis-solves.38 SAMs having 16-18 carbon atoms block thisdissolution'20'2r'25'26 other etchants can also be used.20The ability of SAMs having thicknesses of only 1-2nm to provide protection against etching, used incombination with patterning, provides the basis for afamily of methods for fabricating microstructures ofgold. These planar structures, in turn, provide entriesinto more complex planar and three-dimensionalstructures. Figure 4 shows a series of electron mi-crographs that display the versatility of patternedSAMs in microfabrication. The smallest feature sizethat has been obtained is 200 nm (Figure 4b); the edgeresolution in this structure is less than 50 nm.20

In addition to producing microstructures of gold byselective etching, it is also possible to produce pat-terned substrates on which metals can be platedselectively.2O When a surface with a patterned SAMof hexadecanethiolate is exposed to an electrolessplating solution, nickel plates selectively on the bareregions. Selective electrochemical deposition of metalssuch as copper and lead, and of organic conductorssuch as poly(3-methylthiophene), also takes place onthese bare regions.3e

Electrochemistry: Microelectrodes. Microelec-trodes, that is, electrodes with at ieast one micrometer-scale dimension, make possible electrochemical mea-surements with a spatial resolution on the order ofthe size of the electrode.s When micromachining andmolecular self-assembly are combined, microelectrodeswith a variety of geometries (glooves, wires, andmicrometer-spaced pairs) can be readily prototyped ingold:40 Their fabrication relies on two characteristicsof SAMs. First, SAMs can effectively block thetransfer of electrons between a film of gold and acontacting aqueous solution of redox-active molecules;micrometer-scale regions of bare gold machined intothese surfaces behave as microelectrodes. Second, asdescribed above, the selective etching of frlms of goldpatterned with regions of monolayers formed fromCHa(CHz)rsSH and HO(CH2)2SH forms microstruc-tures of gold; these supported structures function asmicroelectrodes.

Spectroscopy: Patterned Substrates for Elec-tron and Scanning Probe Microscopies. Whenexperiments are conducted with scanning probe mi-croscopies, whether the probe is a beam of electronsor a conducting or nonconducting tip, it is oftenadvantageous to examine a single substrate withseveral well-defined regions of contrast. Such asubstrate provides internal standards and frees theuser from having to replace samples.20lr

As an example, Figure 5a shows an atomic forcemicroscopy (AFM) image and corresponding scanningelectron microscopy (SEM) of a patterned series oflines produced through pCP. The thin lines were

(38 )Br i t t an , A . M. Am. Sc i . 1974 ,62 ,402 . Puddepha t t .R . J . TheChemistry of Gold; Elsevier: Amsterdam, 1978. Cotton. F. A.; Will<rnson,G. Aduanced Inorganic Chemistry,4th ed.; Wiley: New York, 1980.

(39) Gorman, C. B.; Biebuyck, H. A.;Whitesrdes, G. M. Chem. Mater.1995,7,252-254.

(40) Abbott, N. L.; Rolison, D. R.; Whitesides, G. M. Langmuir 1994,10,2672-2682.

(41) Wilbur, J. L.; Biebuyck, H. A.; MacDonald, J. C.; Whitesides, G.M. Langmulr, in press.

1995

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Patterned SAMs and Meso-Scale Phenomena

(a)

(e)

Figure 4. Microstructures fabricated using ,rrCP. (a) Goldstructures generated by ,irCP and etching. (b) The smallestfeatures produced, to date, by rrCP. The width of the lines is200 nm with edge resolution of 50 nm. (c) A microelectrodeprepared by micromachining: collinear, l-1rm wide, 100-nm-thick wires of gold separated by a O.8-rrm-wide electricallyinsulating gap (indicated by the arrows). (d) Structures of nickelproduced through selective electroless deposition on gold afterzCP. (e) Etched silicon structure produced through anisotropicetching of silicon (in KOlV2-propanol) using a mask of goldproduced through,rrCP and etching in a solution of cyanide ion.

produced by stamping a pattern of HS(CHz)isCHs ontoa gold surface. The thicker lines were formed bysubsequent exposure of the surface to HS(CHz)rs-COOH. Since the CH3-terminated regions adsorbfewer contaminants than the COOH-terminated re-

Acc. Chem. Res., Vol. 28, I{o. 5, 1995 223

(a)

(b)

Figure 5. Images of surfaces after rrCP obtained by atomic forcemicroscopy (Af'M). (a) AFM image of a series of alternatinghydrophobic and hydrophilic lines and an electron micrographofa corresponding region. The hydrophobic regions are darkerthan the hydrophilic regions in the AFM image, whereas thehydrophilic regions are darker than the hydrophobic in thebackscattered electron image. The contrast is reversed for thetwo images due to the differences in the imaging mechanisms.20(b-d) AFM images of features at successively increasingmagnifications. The dark regions are hydrophobic SAMs (formedfrom HS(CHz)rsCHs), and the light regions are hydrophobic(formed from HS(CH2)15COOH).

gions, backscattered electrons are attenuated less thanby the CHs-terminated reg"ions, and the gray-scaleimage is reversed when examined by SEM. Figuresb-d shows AFM images of a pal,terned surface atsuccessive magnifications.

Optical Systems: Environmentally SensitiveDiffraction Gratings. Patterned multiple-compo-nent SAMs, in which the components differ in theirhydrophilicity, can be used to control the condensationof droplets of water in predetermined shapes andarrays (Figure 6).23 When a patterned surface iscooled, water condenses. Condensation occurs first on

H

224 Acc. Chem. Res.,Vol. 28. I{o. 5. Kumar et al.

(a)

1995

HydroPhilic SAIVI u--r-.tila*',.yr iliffiuonr fiS"rfllli1ffil",I r'lo prn I+ -#<- t

Uniform reflectiorunodiltaction

Diffraction app€srsweak

Intense difrraction

Diffraction becorrcsdifruse

Diffirse reflection

l . oo

o7s

o.50

o.25

o.oo

DropofCondensed

t"'- wat€r

T

(c)

a-o lo.o l2.O l ' t .o 16-0 la'o 2o'o

T( oc)

Figure 6. Condensation on patterned SAMs. (a) Pictorial representation of condensation on a patterned SAM. As the t€mperature

l" "-"dr,""d,

,"u4" uupor initially condenses on the hydrophilic regions. As the temperature continues to decrease, all ofthe hydrophilic

."gions are "ou"."d

*ith wate., a.rd shong diffr;ctio; patteias are observed. Eventually the water droplets bridge across the

hyirophobic regions and cover tle entire sriface, and diifraction of light no longer occurs. (b) Electron mic-rograph of a patterned

srirfa"i" *nd thi conesponding diffraction pattern observed by reflecting a He:Ne laser off the surface aller the formation of a

condensation pattern. ic) Ploi of the inteniity of a first-order difrraction spot as a function of temperature at different relative

humidities.

the more hydrophilic regions. The resulting periodic drops, the kinetics ofnucleation, and thermal balancearray ofdrops ofwater diffracts light, and the progress in condensation and evaporation.of c|ndetrsation can be followed by measuiing the Patterned Formation of Crystals- When a sut'

change in intensity of a diffracted beam fiom a l,aser. face having a SAM that is patterned into hydrophobicFigui'e 6b shows a SEM ofa su.face comprising a two- and hydrophilic regions is withdrawn slowly from ancofipo.retrt SAM and the corresponding dilfraction aqueous solution of some solute, the water is retainedpattern formed upon reflection ofa lasei beam after on the hydrophilic regions. -As the water evaporatesiondensation of water. Figure 6c shows plots of the from the surface, crystals of the solute form (Figure

change in intensity of ditTraction as the surface is 7).20 Figure ? shows crystals ofcopper sulfate (CuSOl)

coolei and warmedin atmospheres ofconstant relative formed when patterned_ microdrops of water arehumidities. The tlifference-between the cooling and evaporated. The size ofthese crystals is noteworthy.warming curves is probably due to pinning of the The hydrophobic squares had 50-prn edges; the crys-

48% 51S 55% 58 l i Re la t i ve

a <-v? i Q Humid i tY

Patterned SAMs and Meso-Scale Phenomena

Figure 7. Directed assembly of crystals on patterned SAMs:an array of crystals that formed from microdrops containing 1M CuSO+. The crystals formed in the upper, left corners dueto the tilt of the sample during evaporation of the solution inthe microdrops.

tals were, however, <5 4m in size. Using this tech-nique, stamps having relatively large features couldbe used to produce much smaller structures.

Three-Dimensional Microfabrication: Dropsand Microlenses. We have fabricated small poly-meric shapes using patterned SAMs having regionsof different interfacial free energies to constrain theshapes of drops of prepolymer. Once a pattern con-sisting of hydrophobic and hydrophilic SAMs has beenprinted on gold, one can deposit an organic prepolymerselectively on the desired region of the surface.a2'43Self-organized polymeric structures form shapes thatminimize interfacial free energies. Several polymershave been successfully used in this process: LlV-curedpolyurethane (NOA-60 or NOA-61, Norland) andPMMA (J-91, Summer), thermally cured PMMA (No-volac resin), and thermally cured epoxy resin (Devcon).The best results were obtained with the lfV-curedpolymers because they exhibited minimal shrinkage.

Figure 8a,b shows an array of microlenses made bytranslating patterned SAMs across the interface of aprepolymer of polyurethane and water. Figure 8c,made of PMMA, was fabricated by organizing theprepolymer in air. The shapes of these lenses can becalculated using a finite element analysis that mini-mizes the excess surface free enerry and gravitationalpotential energy of each drop.28

Cell Biology: Spatially Constrained and In-dexed Cells. Many types of eukaryotic cells requireattachment to a surface for growth. This attachmentis typically mediated by specific cell-surface receptors.In the case of synthetic surfaces, proteins adsorbedonto the surface from the culture medium provide theepitopes that are recognized. By using the techniquesof patterned self-assembly, it is possible to direct the

1995 225

2 p m

50 pm50 pm

Figure 8. Assembly of three-dimensional shapes: (a) anelectron micrograph of an array of microlenses fabricated byassembling a liquid prepolymer of polyurethane on a patternedsurface followed by W curing; (b) AFM image of the microlensarray of part a; (c) an electron micrograph of an array of linearpolymeric structures ma.de of PMMA.

adsorption of proteins into spatially well-definedregions and, thereby, to pattern the attachment ofcells. SAMs of alkanethiolates on gold have a sub-stantial advantage over other techniques that havebeen used to pattern cells.aa Because the chemistryof formation of SAMs is well-defined, and the forma-tion of SAMs proceeds under mild conditions, it ispossible to present complex and fragile ligands at theirsurfaces, and to engineer surfaces that resist theadsorption of proteins and attachment of cells.

Figure 9 shows an example of geometrically-con-strained attachment of cells that was achieved throughthe use of patterned SAMs.22 A stamp was used topattern the adsorption of HDT on gold. This surfacewas subsequently washed with an ethanolic solutionof polyethylene glycol (PEG)-terminated alkanethiol(HS(CH2)rr(OCH2CH2)6OH). SAMs of this thiol ef-fectively resist the adsorption of proteins.4s Uponexposure of this surface to a solution of the extra-cellular matrix protein, laminin, adsorption of proteinoccurred exclusively on the hydrophobic SAMs formedfrom HDT.

Primary rat hepatocytes were plated on the laminin-coated substrate in defined media. Attachment of thehepatocytes occurred predominantly on the protein-coated islands. In addition to controlling the positionof the attachment of the hepatocytes, the underlyingsubstrate was able to control the size and spreadingcharacteristics of the cells. Figure 9 shows that manycells adopt the shape of the island on which they

(45) Prime, K. L.; Whitesides, G. M. J. Am. Chem. Soc. 1993, 715,1.0714-10721. Prime. K. L.; Whitesides. G. M. Science 1991,252,1164-1 167 .

(a)

(b )

(c)

ta pt

Whitesides, G. M. Langmuir 1994, 10,2790-

1995,

226 Acc. Chem. Res., Vol. 28, No. 5, 1995

Figure 9. Comparisons of cell shapes on patterned and

unpatterned surfaces. Hepatocytes plated on pat terned sub-

strates conformed to the shape of the adhesive is lands (at . whi le

those on unpatterned substrates did not 1bt . The cel l bodies

were v isual ized by f luorescence microscopy.22 (c) An electron

micrograph of attached hepatocl'tes on a region showing several

geometric shapes.

attach. In many cases cells exhibited corners thatapproximated 90". More extensive studies have shownthat the size of the island of attachment controls thephysiological behavior of the cells.22 Cells attachedto large islands tended to go into S-phase (as indicatedby the increase in rate of DNA synthesis), while cellson smaller islands were less likely to be in S-phase,but produced greater amounts of albumin than cellsin S-phase. This simple and flexible method forpatterning the adsorption of mammalian cells throughthe patterned formation of SAMs may frnd use inareas of drug screening, tissue engineering, andfundamental studies in cellular biology.

Summary

Self-Assembled Monolayers. The spontaneousassembly of organic molecules on the surfaces of solids

(46)Dimi l la, P. A. ; Folkers, J. P. ; Biebuyck, H. A. ; Harter , R. ; Lopez,G. P. : Whi tesides, G. M. J. Am. Chem. Soc. 1994, 116,2225-2226'

Kumar et al.

offers a flexible and convenient system with which to

study certain meso-scale phenomena. Self-assembledmonolayers are easily formed at ambient conditionsand are stable for many weeks under normal labora-tory conditions. Patterned and unpatterned SAMs are

useful as resists for etching and plating, as substratesfor microscopic studies of surface interactions in

scanning probe microscopies, as optically addressablesensors, as substrates with which to study the con-densation of liquids and polymer precursors, as mi-

crotemplates for crystallization, as surfaces for the

attachment of proteins and cells, and in many otherapplications.

The ability to produce gold substrates with a wide

range of thickness and optical transparency, and with

electrical conductivity, make it an ideal substrate for

many types of laboratory studies:ao since the films ofgold are relatively thin, the cost of the gold is aminimal consideration. In addition, gold itself can be

used as a resist for etching procedures that woulddegrade the SAM (for example, etching silicon in

strong bases).2O'a3 Although most of the work by us

and others has been done on gold, silver and (to acertain degree) copper substrates are also useful.

Planar Patterning and Extension to 3'D Struc'tures. At present the most flexible method of pat-

terning SAMs is rrCP. The fidelity of printed features

depends on several factors, including conformal con-

tact between stamp and surface and the autophobicityof the system. Simple procedures such as etching,plating, condensation, and polymerization extendsurface meso-fabrication into three dimensions. Com-binations of two or more of these and other processes

may provide methods to produce complex three-dimensional structures that are currently not avail-able.

Applications. The most promising applications are

those where complex surface functionality is required,

or where ease of fabrication is crucial (such as proto-

typing microelectrodes). Although pCP depends on

contact of the stamp with the surface, the stamps have

shown no degradation for over hundreds of uses that

occurred over several months. Complex patterns canbe easily and reproducibly fabricated in a chemicallaboratory without the need for clean rooms or routine

access to photolithographic equipment.

This research was supported in part by the ARPA, ONR,and NSF (PHY 9312572).

AR940068H