Optical amplification of molecular interactions using liquid crystals

Interactions between molecules which are components of self-assembled monolayers and other molecules can be amplified and transduced into an optical signal through the use of a mesogenic layer. The invention provides a device and methods for detecting analytes. The device comprises a substrate onto which a self-assembled monolayer is attached and a mesogenic layer which is anchored by the self-assembled monolayer. The mesogenic layer undergoes a change in conformation in response to the molecular interaction.

FIELD OF THE INVENTION
 This invention relates to devices containing liquid crystals which are
 optionally patterned. Also provided are methods of using these devices as
 sensors. More particularly, the present invention relates to liquid
 crystal devices for detecting the interaction an analyte to a recognition
 moiety that is contained within the device.
 BACKGROUND OF THE INVENTION
 Liquid crystals possess physical properties which are normally associated
 with both solids and liquids. Similar to fluids, the molecules in liquid
 crystals are free to diffuse about, however, a small degree of long range
 orientational and sometimes positional order is maintained causing the
 substance to be anisotropic as is typical of solids.
 A vast array of organic and metal-containing substances exhibit liquid,
 crystallinity. A common feature of these molecules is either an elongated
 or flattened, somewhat inflexible molecular framework which is usually
 depicted as either cigar- or disk-shaped. The orientational and positional
 order in a liquid crystal phase is only partial, with the intermolecular
 forces striking a very delicate balance between attractive and repulsive
 forces. As a result, liquid crystals display an extraordinary sensitivity
 to external perturbations (e.g., temperature, pressure, electric and
 magnetic fields, shearing stress or foreign vapors).
 The phenomenon of orientation, or anchoring, of liquid crystals by surfaces
 has been known nearly as long as have liquid crystals themselves.
 Anchoring of a liquid crystal by a surface fixes the mean orientation
 taken by the molecules with respect to the surface. This fixed direction
 is called the anchoring direction of the liquid crystal. A liquid
 population of mesogenic molecules can undergo a transition, between two or
 more anchoring directions, as a result of an external perturbation.
 Several anchoring transitions have been observed. These transitions
 involve a change in the orientation of the liquid crystal in the plane of
 the substrate which can be continuous or discontinuous. The transitions
 can be induced by a number of different perturbations, including the
 adsorption of foreign molecules. Such adsorption modifies the interface
 between the substrate and the liquid crystal, thereby inducing a
 "switching" between anchoring directions. See, Jerome, B; Shen, Y. R.,
 Phys. Rev. E, 48:4556-4574 (1993) and Bechhoefer et al., Phase Transitions
 33:227-36 (1991).
 Past interest in the orientations assumed by liquid crystals near surfaces
 has been largely driven by their use in electrooptical devices such as
 flat-panel displays (FPDs). A goal of many studies has, therefore, been
 the development of methods for the fabrication of surfaces that uniformly
 orient liquid crystals over large areas. Future uses of liquid crystals in
 electrooptic devices, in contrast, will rely increasingly on liquid
 crystals with patterned orientations over small areas (Gibbons et al.
 Appl. Phys. Lett. 65:2542 (1994); Bos et al., J. Soc. Inf. Disp. 3-4: 195
 (1995); Morris et al., Emmel, Proc. Soc. Photo-Opt. Instrum. Eng. 2650,
 112 (1996); Mural et al., ibid, 1665:230 (1992); Patel et al., Opt. Lett.
 16:532 (1991); Zhang et al., J. Am. Chem. Soc. 114:1506 (1992); W. P.
 Parker, Proc. Soc. Photo-Opt. Instrum. Eng. 2689:195 (1996)). For example,
 light can be diffracted or redirected by using patterned mesogenic layer
 structures that are tuned by application of a uniform electric field (W.
 P. Parker, Proc. Soc. Photo-Opt. Instrum. Eng. 2689:195 (1996)), and FPDs
 with wide viewing angles and broad gray scales can be fabricated by using
 pixels that are divided into subpixels, where each sub-pixel is defined by
 a different orientation of the liquid crystal (Schadt et al., Nature
 381:212 (1996)). Methods capable of patterning mesogenic layers on curved
 surfaces are also required for the development of new types of tunable
 electrooptic mesogenic layer devices, including devices that combine the
 diffraction of light from the patterned mesogenic layer structure with the
 refraction of light at the curved surface (Resler et al., Opt. Lett.
 21:689 (1996); S. M. Ebstein, ibid, p.1454; M. B. Stem, Microelectron.
 Eng. 32:369 (1996): Goto et al., Jpn. J. Appl. Phys. 31:1586 (1992);
 Magiera et al., Soc. PhotoOpt. Instrum. Eng., 2774:204(1996)).
 Current procedures for the fabrication of patterned mesogenic layer
 structures use either spatially nonuniform electric fields from patterned
 electrodes or patterned "anchoring" surfaces. Fringing of electric fields
 from patterned electrodes prevents high-resolution patterning of mesogenic
 layers by this method (Gibbons et al. Appl. Phys. Lett. 65:2542 (1994);
 Williams et al., Proc. Soc. PhotoOpt. Instrum. Eng. 1168:352 (1989)).
 Patterned anchoring surfaces have been prepared by using mechanical rubbing
 of spin-coated polymer films, photolithographic masking, and a second
 rubbing step performed in a direction orthogonal to the first (Patel et
 al., Opt. Lett. 16:532 (1991); W. P. Parker, Proc. Soc. Photo-Opt.
 Instrum. Eng. 2689:195 (1996); Chen et al., Appl. Phys. Lett. 67:2588
 (1995)). This method of patterning mesogenic layers on surfaces is complex
 and suffers from the disadvantages of rubbing-based methods, such as the
 generation of dust and static charge. Recently developed photo-alignment
 techniques for orienting mesogenic layers provide promising alternatives
 (Gibbons et al. Appl. Phys. Lett. 65:2542 (1994); Schadt et al., Nature
 381:212 (1996); Chen et al., Appl. Phys. Lett. 68:885 (1996); Gibbons et
 al., Nature 351:49 (1991); Gibbons et al., ibid 377:43 (1995); Shannon et
 al. 368:532 (1994); Ikeda et al., Science 268:1873 (1995); Schadt et al.,
 Jpn. J. Appl. Phys. 34:3240.(1995)). However, because light-based methods
 generally require surfaces to be spin-coated by uniformly thin films of
 photopolymer, and because the orientations of mesogenic layers on
 photo-aligned surfaces are determined by the angle of incidence of the
 light used for alignment, these methods are not easily applied to the
 patterning of mesogenic layers on nonplanar surfaces.
 The methods of the present invention permit fabrication of complex
 mesogenic layer structures in two simple processing steps. Surfaces can be
 patterned with regions of mesogenic layers that differ in shape and have
 sizes ranging from micrometers to centimeters. The mesogenic layers can
 also be patterned on nonplanar surfaces (mesogenic layers have been
 anchored within pores of alumina and vycor glass coated with
 surface-active reagents, Crawford. et al. Phys. Rev. E 53:3647 (1996), and
 references therein). The present invention differs from this past work in
 two principal ways. (i) Scale: Mesogenic layers have been anchored on
 curved surfaces with radii of curvature that are large compared with the
 thickness, of the mesogenic layer. The local state of the mesogenic layer
 is similar to that of mesogenic layers anchored on a planar surface and
 thus properties of the mesogenic layer are not dominated by elastic
 energies caused by curvature. Methodologies used for anchoring mesogenic
 layers on planar surfaces (for example, twisted nematic cells) can be
 translated to our curved surfaces; and (ii) Patterns: The methods of the
 invention allow the formation of patterned curved surfaces.
 Self-assembled monolayers formed by the chemisorption of alkanethiols on
 gold are likely to now be the most intensively characterized synthetic
 organic monolayers prepared to date. See, Ulman, A., 1991, An Introduction
 to Ultrathin Organic Films: From Langmuir-Blodgett to Self Assembly (San
 Diego, Calif.: Academic Press); Dubois, L. H. et al., 1992, Annu. Rev.
 Phys. Chem., 43, 437. These monolayers form spontaneously during immersion
 of evaporated films of gold in solutions of alkanethiols as a result of
 chemisorption of sulfur on the (111) textured surface of the films. The
 molecules self-organize into a commensurate .sub.-- 3.times..sub.--
 3R30.degree. lattice on the surface of the Au(111). See, "Porter, M. D.
 1987, J. Am. Chem. Soc., 109, 3559; Camillone III, N. et al., 1993, Chem.
 Phys., 98, 3503; Fenter, P. et al., 1994, Science, 266, 1216; 20; Chidsey,
 C. E. D. et al., 1990, Langmuir, 6, 682; Sun, F.; Mao, G.; Grainger, D. W.
 et al., 1994, Thin Solid Films, 242, 106. For monolayers formed from
 CH.sub.3 (CH.sub.2).sub.n SH, n&gt;9, at least, the aliphatic chains of the
 monolayers are extended in the all-trans conformation and tilted
 approximately 30.degree. from the normal of the surface. Because the
 spacing between sulfur groups on the .sub.-- 3.times.3R30.degree. lattice
 is, on average, 4.9 .ANG., whereas the van der Waals diameter of an
 aliphatic chains is, only .about.4 .ANG., the aliphatic chains within
 these SAMs tilt from the normal so as to come into van der Waals contact
 and thereby maximize their cohesive dispersive interactions. Studies of
 the lateral structure within monolayers using X-ray diffraction reveal the
 existence of domains of size .about.100 .ANG., where each domain has one
 of six different tilt directions relative to the Au(111) face. See,
 Fenter, P. et al., 1994, Science, 266, 1216.; Recent studies have shown
 the existence a c(4.times.2) superlattice, the cause of which remains
 unresolved.
 Surfaces prepared by the chemisorption of organosulfur compounds on
 evaporated films of gold are not limited to the alkanethiols.
 Self-assembled monolayers formed from perfluorinated organosulfur
 compounds have also been reported. See, Lenk, T. J., et al. 1994,
 Langmuir, 10, 4610.; Drawhorn, R. A. et al., 1995, J. Phys. Chem., 99,
 16511. These surfaces, too, can be highly ordered, although,
 interestingly, the origin of the order within the monolayer is largely
 intramolecular and contrasts, therefore, to monolayers formed from
 alkanethiols (where the order largely reflects the cohesive intermolecular
 dispersion force). Steric interactions between adjacent fluorine atoms of
 a perfluorinated chain cause the chain to twists itself into a rigid,
 helical conformation. That is, an isolated perfluoro chain is stiff, as
 compared to an aliphatic chain. Because perfluorinated chains have larger
 cross-sectional areas than alkanethiols, monolayers formed on gold from
 perfluorinated thiols are not tilted from the normal to the same degree as
 alkanethiols. See, Drawhorn, R. A. et al., 1995, J. Phys. Chem., 99,
 16511. Estimates by IR studies place the tilt of the perfluorinated chains
 at 0.about.10.degree.. Because perfluorinated chains within SAMs on
 Au(111) are not tilted to the same degree as the alkanethiols, their
 surfaces are not expected to possess domains formed from regions of
 monolayer with different tilt directions (as occurs with monolayers formed
 from alkanethiols). Past reports do not describe the anchoring of liquid
 crystals on densely-packed monolayers formed from semifluorinated chains.
 Past investigations on fluorocarbon surfaces have focused on surfaces
 coated with films of fluorinated polymers such as
 poly-(tetrafluoroethylene) (Teflon.TM.) and poly-(vinylidene fluoride)
 (Tedlar.TM.), or fluorine containing surface reagents that pack loosely
 and host polar/charged groups. See, Cognard, J., 1982, Mol. Cryst. Liq.
 Cryst. Supp., 78, 1; Uchida, T. et al., 1992, Liquid Crystals Applications
 and Uses, edited by Bahadur, B. (New Jersey: World Scientific), p.2;
 Hoffman, C. L.; Tsao, M.-W; Rabolt, J. F.; Johnson, H. et al., unpublished
 results. Due to differences in the method of preparation (e.g., plasma
 polymerization of teflon vs. sliding contact of a teflon block) results
 reported in the past for the anchoring of liquid crystals on fluorinated
 surfaces are variable. In general, however, the fluorocarbon surface,
 which is a low energy surface, is reported to cause homeotropic anchoring.
 See, Uchida, T. et al., 1992, Liquid Crystals Applications and Uses,
 edited by Bahadur, B. (New Jersey: World Scientific), p.2.
 The use of self-assembled monolayers formed from noon-fluorinated,
 semifluorinated and perfluorinated organosulfur compounds permits the
 preparation of well-defined fluorocarbon surfaces for the anchoring
 mesogenic layers. Mesogenic layers anchored onto these well-defined
 surfaces are sensitive to perturbations caused from a wide range of
 sources.
 Numerous practical applications of the mesogenic layer's sensitivity to
 perturbation have been realized. For example, liquid crystals have been
 used as temperature sensors (U.S. Pat. No. 5,130,828, issued to Fergason
 on Jul. 14, 1992). Devices containing liquid crystal components have also
 been used as sensors for indicating the concentration of ethylene oxide in
 the workplace (U.S. Pat. No. 4,597,942, issued to Meathrel on Jul. 1,
 1986). Meathral teaches a device which has an absorbent layer on top of a
 paper substrate. Neither Meathral not Fergason teach the switchable
 anchoring of liquid crystals on self-assembled monolayers. Additional
 information on the use of liquid crystals as vapor sensors is available in
 Poziomek et al., Mol. Cryst. Liq. Cryst., 27:175-185 (1973).
 Liquid crystal devices which undergo anchoring transitions as a result of
 protein-ligand binding have been reported by Gupta, V. K., Abbott, N. L.,
 Science 276:1533-1536 (1998). Switchable liquid crystals supported on
 self-assembled monolayers were used to detect the binding of avidin and
 goat-anti-biotin to a biotinylated self-assembled monolayer. Biotin
 exhibits a very specific, high affinity binding to both avidin
 (Kd.about.10.sup.-15) and anti-biotin (Kd.about.10.sup.-9). Gupta et al.
 teaches the binding of biotin to the self-assembled monolayer and the
 interaction of this ligand with proteins which are known to display
 specific and strong binding to biotin.
 There is a recognized need in the chemical and pharmaceutical arts for
 devices having patterned liquid crystals as a component thereof. Further,
 there is a need for a facile method to produce such patterned liquid
 crystals. In addition, there is a long recognized need for both methods
 and devices to detect and characterize analytes in a simple, inexpensive
 and reliable manner. Even more desirable are systems that can detect the
 specific interaction of an analyte with another molecule. A device having
 a detection spatial resolution on approximately the micrometer scale would
 prove ideal for numerous applications including the synthesis and analysis
 of combinatorial libraries of compounds. If detecting molecular
 interactions could be accomplished without the need for prelabeling the
 analyte with, for example a radiolabel or a fluorescent moiety, this would
 represent a significant advancement. Quite surprisingly, the present
 invention provides such devices and methods.
 SUMMARY OF THE INVENTION
 It has now been discovered that liquid crystals can be used to amplify, and
 transduce into an optical signal, the interaction of a wide array of
 molecules with various surfaces. The interaction of the molecule with the
 surface can be converted into an easily detected optical output.
 A variety of surfaces, including spontaneously organized surfaces, can be
 designed so that molecules, on interacting with these surfaces, trigger
 changes in the orientations of films of mesogenic compounds. When the
 molecule interacting with the surface has a size on the order of a
 protein, the interaction can result in the reorientation of approximately
 10.sup.5 -10.sup.6 mesogens per molecule. Interaction-induced changes in
 the intensity of light transmitted through the mesogenic layer can be
 easily seen with the naked eye.
 Thus, in a first aspect, the present invention provides a device
 comprising: a first substrate having a surface, the surface comprising a
 recognition moiety; a mesogenic layer oriented on the surface; and an
 interface between the mesogenic layer and a member selected from the group
 consisting of gases, liquids, solids and combinations thereof.
 In a second aspect, the present invention provides a device comprising: a
 first substrate having a surface; a second substrate having a surface, the
 first substrate and the second substrate being aligned such that the
 surface of the first substrate opposes the surface of the second
 substrate; a first organic layer attached to the surface of the first
 substrate, wherein the first organic layer comprises a first recognition
 moiety; and a mesogenic layer between the first substrate and the second
 substrate, the mesogenic layer comprising a plurality of mesogenic
 compounds.
 In a third aspect, the present invention provides a device for detecting an
 interaction between an analyte and a recognition moiety, the device
 comprising: a first substrate having a surface; a second substrate having
 a surface, the first substrate and the second substrate being aligned such
 that the surface of the first substrate opposes the surface of the second
 substrate; a first organic layer attached to the surface of the first
 substrate, wherein the organic layer comprises a first recognition moiety
 which interacts with the analyte; and a mesogenic layer between the first
 substrate and the second substrate, the mesogenic layer comprising a
 plurality of mesogens, wherein at least a portion of the plurality of
 mesogens undergo a detectable switch in orientation upon interaction
 between the first recognition moiety and the analyte, whereby the
 interaction between the analyte and the first recognition moiety is
 detected.
 In a fourth aspect, the present invention provides a method for detecting
 an analyte, comprising:
 (a) contacting with the analyte a recognition moiety for the analyte,
 wherein the contacting causes at least a portion of a plurality of
 mesogens proximate to the recognition moiety to detectably switch from a
 first orientation to a second orientation upon contacting the analyte with
 the recognition moiety; and
 (b) detecting the second configuration of the at least a portion of the
 plurality of mesogens, whereby the analyte is detected.
 In a fifth aspect, the present invention provides a device for synthesizing
 and screening a library of compounds, comprising:
 (1) a synthesis component, comprising:
 (a) a first substrate having a surface;
 (b) a self-assembled monolayer on the surface, the monolayer comprising a
 reactive functionality; and
 (2) an analysis component, comprising:
 (a) a second substrate having a surface; and
 (b) a mesogenic layer between the surface of the first substrate and the
 surface of the second substrate.
 In a sixth aspect, the present invention provides a library of compounds
 synthesized on a self-assembled monolayer.
 In a seventh aspect, the invention provides a low energy surface having a
 mesogenic layer anchored planarly thereon.
 In an eighth aspect, the invention provides a method for controlling tilt
 in an organic layer comprising a haloorganosulfur moiety, having a halogen
 content, adsorbed onto a substrate, the method comprising selecting the
 halogen content of the haloorganosulfur.
 In a ninth aspect, the invention provides a method for controlling optical
 texture in a mesogenic layer anchored by an organic layer comprising a
 haloorganosulfur moiety, having a halogen content, the method comprising:
 selecting the halogen content of the haloorganosulfur.
 Other features, objects and advantages of the present invention and its
 preferred embodiments will become apparent from the detailed description
 that follows.

DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS
 Abbreviations and Definitions
 SAM, self assembled monolayer.
 The terms used to describe the preferred embodiments of the present
 invention will generally have their art-recognized meanings. The
 definitions offered below are intended to supplement, not supplant, the
 art-recognized meanings.
 As used herein, the terms, "mesogen," "mesogenic" and "liquid crystal" are
 used essentially interchangeably to refer to molecules that form a liquid
 crystal phase.
 The term "attached," as used herein encompasses interaction including, but
 not limited to, covalent bonding, ionic bonding, chemisorption,
 physisorption and combinations thereof.
 The term "independently selected" is used herein to indicate that the
 groups so described can be identical or different
 The term "alkyl" is used herein to refer to a branched or unbranched,
 saturated or unsaturated, monovalent hydrocarbon radical having from 1-30
 carbons and preferably, from 4-20 carbons and more preferably from 6-18
 carbons. When the alkyl group has from 1-6 carbon atoms, it is referred to
 as a "lower alkyl." Suitable alkyl radicals include, for example,
 structures containing one or more methylene, methine and/or methyne
 groups. Branched structures have a branching motif similar to i-propyl,
 t-butyl, i-butyl, 2-ethylpropyl, etc. As used herein, the term encompasses
 "substituted alkyls."
 "Substituted alkyl" refers to alkyl as just described including one or more
 functional groups such as lower alkyl, aryl, acyl, halogen (i.e.,
 alkylhalos, e.g., CF.sub.3), hydroxy, amino, alkoxy, alkylamino,
 acylamino, thioamido, acyloxy, aryloxy, aryloxyalkyl, mercapto, thia, aza,
 oxo, both saturated and unsaturated cyclic hydrocarbons, heterocycles and
 the like. These groups may be attached to any carbon of the alkyl moiety.
 Additionally, these groups may be pendent from, or integral to, the alkyl
 chain.
 The term "aryl" is used herein to refer to an aromatic substituent which
 may be a single aromatic ring or multiple aromatic rings which are fused
 together, linked covalently, or linked to a common group such as a
 methylene or ethylene moiety. The common linking group may also be a
 carbonyl as in benzophenone. The aromatic ring(s) may include phenyl,
 naphthyl, biphenyl, diphenylmethyl and benzophenone among others. The term
 "aryl" encompasses "arylalkyl."
 The term "arylalkyl" is used herein to refer to a subset of "aryl" in which
 the aryl group is attached to the nucleus shown in Formulae 1-4 by an
 alkyl group as defined herein.
 "Substituted aryl" refers to aryl as just described including one or more
 functional groups such as lower alkyl, acyl, halogen, alkylhalos (e.g.
 CF.sub.3), hydroxy, amino, alkoxy, alkylamino, acylamino, acyloxy,
 phenoxy, mercapto and both saturated and unsaturated cyclic hydrocarbons
 which are fused to the aromatic ring(s), linked covalently or linked to a
 common group such as a methylene or ethylene moiety. The linking group may
 also be a carbonyl such as in cyclohexyl phenyl ketone. The term
 "substituted aryl" encompasses "substituted arylalkyl."
 "Substituted arylalkyl" defines a subset of "substituted aryl" wherein the
 substituted aryl group is attached to the nucleus shown in Formulae 1-4 by
 an alkyl group as defined herein.
 The term "acyl" is used to describe a ketone substituent, --C(O)R, where R
 is alkyl or substituted alkyl, aryl or substituted aryl as defined herein.
 The term "halogen" is used herein to refer to fluorine, bromine, chlorine
 and iodine atoms.
 The term "hydroxy" is used herein to refer to the group --OH.,
 The term "amino" is used to describe primary amines, R--NH.sub.2.
 The term "alkoxy" is used herein to refer to the R group, where R is a
 lower alkyl, substituted lower alkyl, aryl, substituted aryl, arylalkyl or
 substituted arylalkyl wherein the alkyl, aryl, substituted aryl, arylalkyl
 and substituted arylalkyl groups are as described herein. Suitable alkoxy
 radicals include, for example, methoxy, ethoxy, phenoxy, substituted
 phenoxy, benzyloxy, phenethyloxy, t-butoxy, etc.
 The term "alkylamino" denotes secondary and tertiary amines wherein the
 alkyl groups may be either the same or different and are as described
 herein for "alkyl groups."
 As used herein, the term "acylamino" describes substituents of the general
 formula RC(O)NR', wherein R' is a lower alkyl group and R represents the
 nucleus shown in Formulae 1-4 or an alkyl group, as defined herein,
 attached to the nucleus.
 The term "acyloxy" is used herein to describe an organic radical derived
 from an organic acid by the removal of the acidic hydrogen. Simple acyloxy
 groups include, for example, acetoxy, and higher homologues derived from
 carboxylic acids such as ethanoic, propanoic, butanoic, etc. The acyloxy
 moiety may be oriented as either a forward or reverse ester (i.e. RC(O)OR'
 or R'OC(O)R, respectively, wherein R comprises the portion of the ester
 attached either directly or through an intermediate hydrocarbon chain to
 the nucleus shown in Formulae 1-4).
 As used herein, the term "aryloxy" denotes aromatic groups which are linked
 to the nucleus shown in Formulae 1-4 directly through an oxygen atom. This
 term encompasses "substituted aryloxy" moieties in which the aromatic
 group is substituted as described above for "substituted aryl."
 As used herein "aryloxyalkyl" defines aromatic groups attached, through an
 oxygen atom to an alkyl group, as defined herein. The alkyl group is
 attached to the nucleus shown in Formula 1-4. The term "aryloxyalkyl"
 encompasses "substituted aryloxyalkyl" moieties in which the aromatic
 group is substituted as described for "substituted aryl."
 As used herein, the term "mercapto" defines moieties of the general
 structure R--S--R' wherein R and R' are the same or different and are
 alkyl, aryl or heterocyclic as described herein.
 The term "saturated cyclic hydrocarbon" denotes groups such as the
 cyclopropyl, cyclobutyl, cyclopentyl, etc., and substituted analogues of
 these structures. These cyclic hydrocarbons can be single- or multi-ring
 structures.
 The term "unsaturated cyclic hydrocarbon" is used to describe a monovalent
 non-aromatic group with at least one double bond, such as cyclopentene,
 cyclohexene, etc. and substituted analogues thereof. These cyclic
 hydrocarbons can be single- or multi-ring structures.
 The term "heteroaryl" as used herein refers to aromatic rings in which one
 or more carbon atoms of the aromatic ring(s) are substituted by a
 heteroatom such as nitrogen, oxygen or sulfur. Heteroaryl refers to
 structures which may be a single aromatic ring, multiple aromatic ring(s),
 or one or more aromatic rings coupled to one or more non-aromatic ring(s).
 In structures having multiple rings, the rings can be fused together,
 linked covalently, or linked to a common group such as a methylene or
 ethylene moiety. The common linking group may also be a carbonyl as in
 phenyl pyridyl ketone. As used herein, rings such as thiophene, pyridine,
 isoxazole, phthalimide, pyrazole, indole, furan, etc. or benzo-fused
 analogues of these rings are defined by the term
 "heteroaryl.""Heteroarylalkyl" defines a subset of "heteroaryl" wherein an
 alkyl group, as defined herein, links the heteroaryl group to the nucleus
 shown in Formulae 1-4.
 "Substituted heteroaryl" refers to heteroaryl as just described wherein the
 heteroaryl nucleus is substituted with one or more functional groups such
 as lower alkyl, acyl, halogen, alkylhalos (e.g. CF.sub.3), hydroxy, amino,
 alkoxy, alkylamino, acylamino, acyloxy, mercapto, etc. Thus, substituted
 analogues of heteroaromatic rings such as thiophene, pyridine, isoxazole,
 phthalimide, pyrazole, indole, furan, etc. or benzo-fused analogues of
 these rings are defined by the term "substituted heteroaryl."
 "Substituted heteroarylalkyl" refers to a subset of "substituted
 heteroaryl" as described above in which an alkyl group, as defined herein,
 links the heteroaryl group to the nucleus shown in Formulae 1-4.
 The term "heterocyclic" is used herein to describe a monovalent saturated
 or unsaturated non-aromatic group having a single ring or multiple
 condensed rings from 1-12 carbon atoms and from 14 heteroatoms selected
 from nitrogen, sulfur or oxygen within the ring. Such heterocycles are,
 for example, tetrahydrofuran, morpholine, piperidine, pyrrolidine, etc.
 The term "substituted heterocyclic" as used herein describes a subset of
 "heterocyclic" wherein the heterocycle nucleus is substituted with one or
 more functional groups such as lower alkyl, acyl, halogen, alkylhalos
 (e.g. CF.sub.3), hydroxy, amino, alkoxy, alkylamino, acylamino, acyloxy,
 mercapto, etc.
 The term "heterocyclicalkyl" defines a subset of "heterocyclic" wherein an
 alkyl group, as defined herein, links the heterocyclic group to the
 nucleus shown in Formulae 1-4.
 As used herein, "conical anchoring" refers to an anchoring characterized by
 an infinite number of anchoring directions making a fixed angle .THETA.
 with the normal to the interface which is different from 0 and II/2.
 The term "degenerate anchoring" describes an anchoring mode in which there
 are an infinite number of anchoring directions.
 "Homeotropic anchoring" refers to an anchoring mode characterized by one
 anchoring direction perpendicular to the plane of the interface.
 "Multistable anchoring" refers to an anchoring mode characterized by a
 finite number of anchoring directions greater than one.
 As used herein, the term "planar anchoring" refers to an anchoring
 characterized by anchoring directions parallel to the plane of the
 interface.
 "Tilted anchoring," as used herein, refers to anchoring which makes an
 angle with the normal to the interface different than 0 and II/2.
 The present invention is directed to liquid crystal devices. More
 particularly, the present invention provides liquid crystal devices that
 detect the interaction of an analyte with a surface to which the liquid
 crystal is coupled. The invention provide devices and methods which allow
 for the amplification and transduction of a molecular interaction. The
 amplification provides a high degree of resolution and the transduction
 allows, in its simplest embodiment, the device to be used to optically
 detect the interaction.
 The present invention provides liquid crystal devices and methods of using
 these devices to detect the presence of an analyte of interest. The
 devices and methods of the invention can be used to detect both
 macromolecules (e.g., polymers, proteins, antibodies) and small organic
 and inorganic molecules.
 The devices of the invention are generally multilayered and consist of one
 or more substrates. A recognition moiety can be bound directly to the
 substrate or through an organic layer which has optionally been deposited
 on the substrate. The substrate or the organic layer serves to anchor a
 mesogenic layer which is orientationally sensitive to interactions (e.g,
 binding) between the organic layer and the analyte of interest.
 Thus in a first aspect, the present invention provides a device comprising:
 a first substrate having a surface, said surface comprising a recognition
 moiety; a mesogenic layer oriented on said surface; and an interface
 between said mesogenic layer and a member selected from the group
 consisting of gases, liquids, solids and combinations thereof.
 This aspect of the present invention allows for the formation of devices of
 both simple planar and also more complex geometries (e.g., curved,
 cylindrical, sinusoidal). In a presently preferred embodiment, the
 substrate of the device is a mesh, for example a TEM grid. In this
 embodiment, the recognition moiety can be attached to the spaces between
 the mesh members (i.e., in wells) and the mesogenic layer is floated on
 the top of the substrate.
 In a presently preferred embodiment of this aspect of the invention, the
 recognition moiety is attached to the surface of the substrate by any of a
 number of interaction types. Useful attachment modes include, for example,
 covalent bonding, ionic bonding, chemisorption and physisorption. Devices
 in which more than one of these modes is used in combination are also
 within the scope of the present invention.
 In another preferred embodiment, the device utilizes a substrate which
 further comprises an organic layer attached thereto. Similar to the
 recognition moiety, the organic layer can be attached to the substrate by
 covalent bonding, ionic bonding, chemisorption, physisorption or
 combinations of these attachment modes.
 In a still further preferred embodiment, the recognition moiety is attached
 to one or more components of the organic layer. The attachment of the
 recognition moiety and the organic layer can utilize covalent bonding,
 ionic bonding, chemisorption, physisorption or combinations of these
 attachment modes.
 In yet a further preferred embodiment, the mesogenic layer is a polymeric
 mesogen. An array of suitable polymeric mesogens is known to those of
 skill in the art. See, for example, Imrie et al., Macromolecules
 26:545-550 (1993); and Percec, V., In, HANDBOOK OF LIQUID CRYSTAL
 RESEARCH, Collings and Patel, Eds., 1997.
 In another preferred embodiment, the interface is between the ambient
 atmosphere and the mesogen that is layered on either the substrate or on
 an organic layer. In another presently preferred embodiment, the interface
 is between the mesogenic layer and a liquid. In a still further preferred
 embodiment, the interface is between the mesogenic layer and a solid, for
 example, a second substrate.
 In a second aspect, the present invention provides a device comprising: a
 first substrate having a surface; a second substrate having a surface,
 said first substrate and said second substrate being aligned such that
 said surface of said first substrate opposes said surface of said second
 substrate; a first organic layer attached to said surface of said first
 substrate, wherein said first organic layer comprises a first recognition
 moiety; and a mesogenic layer between said first substrate and said second
 substrate, said mesogenic layer comprising a plurality of mesogenic
 compounds.
 In a third aspect, the present invention provides a device for detecting an
 interaction between an analyte and a recognition moiety, said device
 comprising: a first substrate having a surface; a second substrate having
 a surface, said first substrate and said second substrate being aligned
 such that said surface of said first substrate opposes said surface of
 said second substrate; a first organic layer attached to said surface of
 said first substrate, wherein said organic layer comprises a first
 recognition moiety which interacts with said analyte; and a mesogenic
 layer between said first substrate and said second substrate, said
 mesogenic layer comprising a plurality of mesogens, wherein at least a
 portion of said plurality of mesogens undergo a detectable switch in
 orientation upon interaction between said first recognition moiety and
 said analyte, whereby said interaction between said analyte and said first
 recognition moiety is detected.
 In a fourth aspect, the present invention provides a method for detecting
 an analyte, comprising:
 (a) contacting with said analyte a recognition moiety for said analyte,
 wherein said contacting causes at least a portion of a plurality of
 mesogens proximate to said recognition moiety to detectably switch from a
 first orientation to a second orientation upon contacting said analyte
 with said recognition moiety; and
 (b) detecting said second configuration of said at least a portion of said
 plurality of mesogens, whereby said analyte is detected.
 A. Substrates
 Substrates that are useful in practicing the present invention can be made
 of practically any physicochemically stable material. In a preferred
 embodiment, the substrate material is non-reactive towards the
 constituents of the mesogenic layer. The substrates can be either rigid or
 flexible and can be either optically transparent or optically opaque. The
 substrates can be electrical insulators, conductors or semiconductors.
 Further the substrates can be substantially impermeable to liquids, vapors
 and/or gases or, alternatively, the substrates can be permeable to one or
 more of these classes of materials.
 Exemplary substrate materials include, but are not limited to, inorganic
 crystals, inorganic glasses, inorganic oxides, metals, organic polymers
 and combinations thereof.
 A.1 Inorganic crystal and glasses
 Inorganic crystals and inorganic glasses that are appropriate for substrate
 materials include, for example, LiF, NaF, NaCl, KBr, KI, CaF.sub.2,
 MgF.sub.2, HgF.sub.2, BN, AsS.sub.3, ZnS, Si.sub.3 N.sub.4 and the like.
 The crystals and glasses can be prepared by art standard techniques. See,
 for example, Goodman, C. H. L., Crystal Growth Theory and Techniques,
 Plenum Press, New York 1974. Alternatively, the crystals can be purchased
 commercially (e.g., Fischer Scientific). The crystals can be the sole
 component of the substrate or they can be coated with one or more
 additional substrate components. Thus, it is within the scope of the
 present invention to utilize crystals coated with, for example one or more
 metal films or a metal film and an organic polymer. Additionally, a
 crystal can constitute a portion of a substrate which contacts another
 portion of the substrate made of a different material, or a different
 physical form (e.g., a glass) of the same material. Other useful substrate
 configurations utilizing inorganic crystals and/or glasses will be
 apparent to those of skill in the art.
 A.2 Inorganic oxides
 Inorganic oxides can also form a substrate of the device of the present
 invention. Inorganic oxides of use in the present invention include, for
 example, Cs.sub.2 O, Mg(OH).sub.2, TiO.sub.2, ZrO.sub.2, CeO.sub.2,
 Y.sub.2 O.sub.3, Cr.sub.2 O.sub.3, Fe.sub.2 O.sub.3, NiO, ZnO, Al.sub.2
 O.sub.3, SiO.sub.2 (glass), quartz, In.sub.2 O.sub.3, SnO.sub.2, PbO.sub.2
 and the like. The inorganic oxides can be utilized in a variety of
 physical forms such as forms, supported powders, glasses, crystals and the
 like. A substrate can consist of a single inorganic oxide or a composite
 of more than one inorganic oxide. For example, a composite of inorganic
 oxides can have a layered structure (i.e., a second oxide deposited on a
 first oxide) or two or more oxides can be arranged in a contiguous
 non-layered structure. In addition, one or more oxides can be admixed as
 particles of various sizes and deposited on a support such as a glass or
 metal sheet. Further, a layer of one or more inorganic oxides can be
 intercalated between two other substrate layers (e.g., metal-oxide-metal,
 metal-oxide-crystal).
 In a presently preferred embodiment, the substrate is a rigid structure
 that is impermeable to liquids and gases. In this embodiment, the
 substrate consists of a glass plate onto which a metal, such as gold is
 layered by evaporative deposition. In a still further preferred
 embodiment, the substrate is a glass plate (SiO.sub.2) onto which a first
 metal layer such as titanium has been layered. A layer of a second metal
 such as gold is then layered on top of the first metal layer.
 A.3 Metals
 Metals are also of use as substrates in the present invention. The metal
 can be used as a crystal, a sheet or a powder. The metal can be deposited
 onto a backing by any method known to those of skill in the art including,
 but not limited to, evaporative deposition, sputtering and electroless
 deposition.
 Any metal that is chemically inert towards the mesogenic layer will be
 useful as a substrate in the present invention. Metals that are presently
 preferred as substrates include, but are not limited to, gold, silver,
 platinum, palladium, nickel and copper. In one embodiment, more than one
 metal is used. The more than one metal can be present as an alloy or they
 can be formed into a layered "sandwich" structure, or they can be
 laterally adjacent to one another. In a preferred embodiment, the metal
 used for the substrate is gold. In a particularly preferred embodiment the
 metal used is gold layered on titanium.
 The metal layers can be either permeable or impermeable to materials such
 as liquids, solutions, vapors and gases.
 A.4 Organic polymers
 Organic polymers are a useful class of substrate materials. Organic
 polymers useful as substrates in the present invention include polymers
 which are permeable to gases, liquids and molecules in solution. Other
 useful polymers are those which are impermeable to one or more of these
 same classes of compounds.
 Organic polymers that form useful substrates include, for example,
 polyalkenes (e.g., polyethylene, polyisobutene, polybutadiene),
 polyacrylics (e.g., polyacrylate, polymethyl methacrylate,
 polycyanoacrylate), polyvinyls (e.g., polyvinyl alcohol, polyvinyl
 acetate, polyvinyl butyral, polyvinyl chloride), polystyrenes,
 polycarbonates, polyesters, polyurethanes, polyamides, polyimides,
 polysulfone, polysiloxanes, polyheterocycles, cellulose derivative (e.g.,
 methyl cellulose, cellulose acetate, nitrocellulose), polysilanes,
 fluorinated polymers, epoxies, polyethers and phenolic resins. See,
 Cognard, J. ALIGNMENT OF NEMATIC LIQUID CRYSTALS AND THEIR MIXTURES, in
 Mol. Cryst. Liq. Cryst. 1:1-74 (1982). Presently preferred organic
 polymers include polydimethylsiloxane, polyethylene, polyacrylonitrile,
 cellulosic materials, polycarbonates and polyvinyl pyridinium.
 In a presently preferred embodiment, the substrate is permeable and it
 consists of a layer of gold, or gold over titanium, which is deposited on
 a polymeric membrane, or other material, that is permeable to liquids,
 vapors and/or gases. The liquids and gases can be pure compounds (e.g.,
 chloroform, carbon monoxide) or they can be compounds which are dispersed
 in other molecules (e.g., aqueous protein solutions, herbicides in air,
 alcoholic solutions of small organic molecules). Useful permeable
 membranes include, but are not limited to, flexible cellulosic materials
 (e.g., regenerated cellulose dialysis membranes), rigid cellulosic
 materials (e.g., cellulose ester dialysis membranes), rigid polyvinylidene
 fluoride membranes, polydimethylsiloxane and track etched polycarbonate
 membranes.
 In a further preferred embodiment, the layer of gold on the permeable
 membrane is itself permeable. In a still further preferred embodiment, the
 permeable gold layer has a thickness of about 70 .ANG. or less.
 In those embodiments wherein the permeability of the substrate is not a
 concern and a layer of a metal film is used, the film can be as thick as
 is necessary for a particular application. For example, if the film is
 used as an electrode, the film can be thicker than in an embodiment in
 which it is necessary for the film to be transparent or semi-transparent
 to light.
 Thus, in a preferred embodiment, the film is of a thickness of from about
 0.01 nanometer to about 1 micrometer. In a further preferred embodiment,
 the film is of a thickness of from about 5 nanometers to about 100
 nanometers. In yet a further preferred embodiment, the film is of a
 thickness of from about 10 nanometers to about 50 nanometers.
 A.5 Substrate surfaces
 The nature of the surface of the substrate has a profound effect on the
 anchoring of the mesogenic layer which is associated with the surface. The
 surface can be engineered by the use of mechanical and/or chemical
 techniques. The surface of each of the above enumerated substrates can be
 substantially smooth. Alternatively, the surface can be roughened or
 patterned by rubbing, etching, grooving, stretching, oblique deposition or
 other similar techniques known to those of skill in the art. Of particular
 relevance is the texture of the surface which is in contact with the
 mesogenic compounds.
 Thus, in one preferred embodiment, the substrate is glass or an organic
 polymer and the surface has been prepared by rubbing. Rubbing can be
 accomplished using virtually any material including tissues, paper,
 brushes, polishing paste, etc. In a preferred embodiment, the rubbing is
 accomplished by use of a diamond rubbing paste. In another preferred
 embodiment, the face of the substrate that contacts the mesogenic
 compounds is a metal layer that has been obliquely deposited by
 evaporation. In a further preferred embodiment, the metal layer is a gold
 layer.
 The substrate can also be patterned using techniques such as
 photolithography (Kleinfield et al., J. Neurosci. 8:4098-120 (1998)),
 photoetching, chemical etching and microcontact printing (Kumar et al.,
 Langmuir 10:1498-511 (1994)). Other techniques for forming patterns on a
 substrate will be readily apparent to those of skill in the art.
 The size and complexity of the pattern on the substrate is limited only by
 the resolution of the technique utilized and the purpose for which the
 pattern is intended. For example, using microcontact printing, features as
 small as 200 nm have been layered onto a substrate. See, Xia, Y.;
 Whitesides, G., J. Am. Chem. Soc. 117:3274-75 (1995). Similarly, using
 photolithography, patterns with features as small as 1 .mu.m have been
 produced. See, Hickman et al., J. Vac. Sci. Technol. 12:607-16(1994).
 Patterns which are useful in the present invention include those which
 comprise features such as wells, enclosures, partitions, recesses, inlets,
 outlets, channels, troughs, diffraction gratings and the like.
 In a presently preferred embodiment, the patterning is used to produce a
 substrate having a plurality of adjacent wells, wherein each of the wells
 is isolated from the other wells by a raised wall or partition and the
 wells do not fluidically communicate. Thus, an analyte, or other
 substance, placed in a particular well remains substantially confined to
 that well. In another preferred embodiment, the patterning allows the
 creation of channels through the device whereby an analyte can enter
 and/or exit the device.
 The pattern can be printed directly onto the substrate or, alternatively, a
 "lift off" technique can be utilized. In the lift off technique, a
 patterned resist is laid onto the substrate, an organic layer is laid down
 in those areas not covered by the resist and the resist is subsequently
 removed. Resists appropriate for use with the substrates of the present
 invention are known to those of skill in the art. See, for example,
 Kleinfield et al., J. Neurosci. 8:4098-120 (1998). Following removal of
 the photoresist, a second organic layer, having a structure different from
 the first organic layer can be bonded to the substrate on those areas
 initially covered by the resist. Using this technique, substrates with
 patterns having regions of different chemical characteristics can be
 produced. Thus, for example, a pattern having an array of adjacent wells
 can be created by varying the hydrophobicity/hydrophilicity, charge and
 other chemical characteristics of the pattern constituents. In one
 embodiment, hydrophilic compounds can be confined to individual wells by
 patterning walls using hydrophobic materials. Similarly, positively or
 negatively charged compounds can be confined to wells having walls made of
 compounds with charges similar to those of the confined compounds. Similar
 substrate configurations are accessible through microprinting a layer with
 the desired characteristics directly onto the substrate. See, Mrkish, M.;
 Whitesides, G. M., Ann. Rev. Biophys. Biomol. Struct. 25:55-78 (1996).
 In yet another preferred embodiment, the patterned substrate controls the
 anchoring alignment of the liquid crystal. In a particularly preferred
 embodiment, the substrate is patterned with an organic compound which
 forms a self-assembled monolayer. In this embodiment, the organic layer
 controls the azimuthal orientation and/or polar orientation of a supported
 mesogenic layer.
 B. Organic Layers
 In addition to the ability of a substrate to anchor a mesogenic layer, an
 organic layer attached to the substrate is similarly able to provide such
 anchoring. A wide range of organic layers can be used in conjunction with
 the present invention. These include organic layers formed from
 organothiols, organosilanes, amphiphilic molecules, cyclodexins, polyols
 (e.g., poly(ethyleneglycol), poly(propyleneglycol), fullerenes, and
 biomolecules. Other useful compounds will be apparent to those of skill in
 the art.
 B.1 Anchoring
 An organic layer that is bound to, supported on or adsorbed onto, the
 surface of the substrate can anchor a mesogenic layer. As used herein, the
 term "anchoring") refers to the set of orientations adopted by the
 molecules in the mesogenic phase. The mesogenic layer will adopt
 particular orientations while minimizing the free energy of the interface
 between the organic layer and the mesogenic layer. The orientation of the
 mesogenic layer is referred to as an "anchoring direction." A number of
 anchoring directions are possible.
 The particular anchoring direction adopted will depend upon the nature of
 the mesogenic layer, the organic layer and the substrate. Anchoring
 directions of use in the present invention include, for example, conical
 anchoring, degenerate anchoring, homeotropic anchoring, multistable
 anchoring, planar anchoring and tilted anchoring. Planar anchoring and
 homeotropic anchoring are preferred with homeotropic anchoring being most
 preferred.
 The anchoring of mesogenic compounds by surfaces has been extensively
 studied for a large number of systems. See, for example, Jerome, B., Rep.
 Prog. Phys. 54:391-451 (1991). The anchoring of a mesogenic substance by a
 surface is specified, in general, by the orientation of the director of
 the bulk phase of the mesogenic layer. The orientation of the director,
 relative to the surface, is described by a polar angle (measured from the
 normal of the surface) and an azimuthal angle (measured in the plane of
 the surface).
 Control of the anchoring of mesogens has been largely based on the use of
 organic surfaces prepared by coating surface-active molecules or polymer
 films on inorganic (e.g., silicon oxide) substrates followed by surface
 treatments such as rubbing. Other systems which have been found useful
 include surfaces prepared through the reactions of organosilanes with
 various substrates. See, for example, Yang et al., In, MICROCHEMISTRY:
 SPECTROSCOPY AND CHEMISTRY IN SMALL DOMAINS; Masuhara et al., Eds.;
 North-Holland, Amsterdam, 1994; p.441.
 Molecularly designed surfaces formed by organic layers on a substrate can
 be used to control both the azimuthal and polar orientations of a
 supported mesogenic layer. SAMs can be patterned on a surface. For
 example, patterned organic layers made from CH.sub.3 (CH.sub.2).sub.14 SH
 and CH.sub.3 (CH.sub.2).sub.15 SH on obliquely deposited gold produce a
 supported mesogenic layer which is twisted 90.degree.. Other anchoring
 modes are readily accessible by varying the chain length and the number of
 species of the organic layer constituents. See, Gupta, V. K.; Abbott, N.
 L., Science 276:1533-1536 (1997).
 Transitions between anchoring modes have been obtained on a series of
 organic layers by varying the structure of the organic layer. The
 structural features which have been found to affect the anchoring of
 mesogenic compounds include, for example, the density of molecules within
 the organic layer, the size and shape of the molecules constituting the
 organic layer and the number of individual layers making up the bulk
 organic layer.
 The density of the organic layer on the substrate has been shown to have an
 effect on the mode of mesogen anchoring. For example, transitions between
 homeotropic and degenerate anchorings have been obtained on surfactant
 monolayers by varying the density of the monolayers. See, Proust et al.,
 Solid State Commun. 11:1227-30 (1972). Thus, it is within the scope of the
 present invention to tailor the anchoring mode of a mesogen by controlling
 the density of the organic layer on the substrate.
 The molecular structure, size and shape of the individual molecules making
 up the organic layer also affects the anchoring mode. For example, it has
 been demonstrated that varying the length of the aliphatic chains of
 surfactants on a substrate can also induce anchoring transitions: with
 long chains, a homeotropic anchoring is obtained while with short chains,
 a conical anchoring is obtained with the tilt angle .kappa. increasing as
 the chain becomes shorter. See, for example, Porte, J. Physique 37:1245-52
 (1976). Additionally, recent reports have demonstrated that the polar
 angle of the mesogenic phase can be controlled by the choice of the
 constituents of the organic layer. See, Gupta, V. K.; Abbott, N. L.,
 Langmuir 12:2587-2593 (1996). Thus, it is within the scope of the present
 invention to engineer the magnitude of the anchoring shift as well as the
 type of shift by the judicious choice of organic layer constituents.
 A wide variety of organic layers are useful in practicing the present
 invention. These organic layers can comprise monolayers, bilayers and
 multilayers. Furthermore, the organic layers can be attached by covalent
 bonds, ionic bonds, physisorption, chemisorption and the like, including,
 but not limited to, hydrophobic interactions, hydrophilic interactions,
 van der Waals interactions and the like.
 In a presently preferred embodiment, organic layers which form self-
 assembled monolayers are used.
 The use of self-assembled monolayers (SAMs) formed from alkanethiols on
 thin, semitransparent films of gold in studies on the anchoring of liquid
 crystals on surfaces has been reported. See, Drawhorn, R. A.; Abbott, N.
 L., J. Phys. Chem. 45:16511 (1995). The principal result of that work was
 the demonstration that SAMs formed from n-alkanethiols with long (CH.sub.3
 (CH.sub.2).sub.15 SH) and short (CH.sub.3 (CH.sub.2).sub.4 SH or CH.sub.3
 (CH.sub.2).sub.9 SH) aliphatic chains can homeotropically anchor mesogens.
 In contrast, single-component SAMs (CH.sub.3 (CH.sub.2).sub.n SH, 2&lt;n&gt;15)
 caused non-uniform, planar, or tilted anchoring at room temperature.
 In the discussion that follows, self-assembled monolayers are utilized as
 an exemplary organic layer. This use is not intended to be limiting. It
 will be understood that the various configurations of the self-assembled
 monolayers and their methods of synthesis, binding properties and other
 characteristics are equally applicable to each of the organic layers of
 use in the present invention.
 B.2 Self-Assembled Monolayers
 Self-assembled monolayers are generally depicted as an assembly of
 organized, closely packed linear molecules. There are two widely-used
 methods to deposit molecular monolayers on solid substrates:
 Langmuir-Blodgett transfer and self-assembly. Additional methods include
 techniques such as depositing a vapor of the monolayer precursor onto a
 substrate surface.
 The composition of a layer of a SAM useful in the present invention, can be
 varied over a wide range of compound structures and molar ratios. In one
 embodiment, the SAM is formed from only one compound. In a presently
 preferred embodiment, the SAM is formed from two or more components. In
 another preferred embodiment, when two or more components are used, one
 component is a long-chain hydrocarbon having a chain length of between 10
 and 25 carbons and a second component is a short-chain hydrocarbon having
 a chain length of between 1 and 9 carbon atoms. In particularly preferred
 embodiments, the SAM is formed from CH.sub.3 (CH.sub.2).sub.15 SH and
 CH.sub.3 (CH.sub.2).sub.4 SH or CH.sub.3 (CH.sub.2).sub.15 SH and CH.sub.3
 (CH.sub.2).sub.9 SH. In any of the above described embodiments, the carbon
 chains can be functionalized at the .omega.-terminus (e.g., NH.sub.2,
 COOH, OH, CN), at internal positions of the chain (e.g., aza, oxa, thia)
 or at both the .omega.-terminus and internal positions of the chain.
 The mesogenic layer can be layered on top of one SAM layer or it can be
 sandwiched between two SAM layers. In those embodiments in which the
 mesogenic layer is sandwiched between two SAMs, a second substrate,
 optionally substantially identical in composition to that bearing the SAM
 can be layered on top of the mesogenic layer. Alternatively a
 compositionally different substrate can be layered on top of the mesogenic
 layer. In a preferred embodiment, the second substrate is permeable.
 In yet another preferred embodiment two substrates are used, but only one
 of the substrates has an attached organic layer.
 When the mesogenic layer is sandwiched between two layers of SAMs several
 compositional permutations of the layers of SAMs are available. For
 example, in one embodiment, the first organic layer and the second organic
 layer have substantially identical compositions and both of the organic
 layers bear an attached recognition moiety. A variation on this embodiment
 utilizes first and second organic layers with substantially similar
 compositions, wherein only one of the layers bears a recognition moiety.
 In another embodiment, the first and second organic layers have
 substantially different compositions and only one of the organic layers
 has an attached recognition moiety. In a further embodiment, the first
 organic layer and said second organic layer have substantially different
 compositions and both of the organic layers have an attached recognition
 moiety.
 In a presently preferred embodiment, the organic layers have substantially
 identical compositions and one or both of the organic layers has attached
 thereto a recognition moiety.
 A recognition moiety can be attached to the surface of a SAM by any of a
 large number of art-known attachment methods. In one preferred embodiment,
 a reactive SAM component is attached to the substrate and the recognition
 moiety is subsequently bound to the SAM component via the reactive group
 on the component and a group of complementary reactivity on the
 recognition moiety. See, for example, Hegner et al. Biophys. J.
 70:2052-2066 (1996). In another preferred embodiment, the recognition
 moiety is attached to the SAM component prior to immobilizing the SAM
 component on the substrate surface: the recognition moiety-SAM component
 cassette is then attached to the substrate. In a still further preferred
 embodiment, the recognition moiety is attached to the substrate via a
 displacement reaction. In this embodiment, the SAM is preformed and then a
 fraction of the SAM components are displaced by a recognition moiety or a
 SAM component bearing a recognition moiety.
 B.3 Functionalized SAMs
 The discussion which follows focuses on the attachment of a reactive SAM
 component to the substrate surface. This focus is for convenience only and
 one of skill in the art will understand that the discussion is equally
 applicable to embodiments in which the SAM component-recognition moiety is
 preformed prior to its attachment to the substrate. As used herein,
 "reactive SAM components" refers to components which have a functional
 group available for reaction with a recognition moiety or other species
 following the attachment of the component to the substrate.
 Currently favored classes of reactions available with reactive SAM
 components are those which proceed under relatively mild conditions. These
 include, but are not limited to nucleophilic substitutions (e.g.,
 reactions of amines and alcohols with acyl halides), electrophilic
 substitutions (e.g, enamine reactions) and additions to carbon--carbon and
 carbon-heteroatom multiple bonds (e.g., Michael reaction, Diels-Alder
 addition). These and other useful reactions are discussed in March, J.,
 ADVANCED ORGANIC CHEMISTRY, Third Ed., John Wiley & Sons, New York, 1985.
 According to the present invention, a substrate's surface is functionalized
 with SAM components and other species by covalently binding a reactive SAM
 component to the substrate surface in such a way as to derivatize the
 substrate surface with a plurality of available reactive functional
 groups. reactive groups which can be used in practicing the present
 invention include, for example, amines, hydroxyl groups, carboxylic acids,
 carboxylic acid derivatives, alkenes, sulfhydryls, siloxanes, etc.
 A wide variety of reaction types is available for the functionalization of
 a substrate surface. For example, substrates constructed of a plastic such
 as polypropylene, can be surface derivatized by chromic acid oxidation,
 and subsequently converted to hydroxylated or aminomethylated surfaces.
 Substrates made from highly crosslinked divinylbenzene can be surface
 derivatized by chloromethylation and subsequent functional group
 manipulation. Additionally, functionalized substrates can be made from
 etched, reduced polytetrafluoroethylene
 When the substrates are constructed of a siliceous material such as glass,
 the surface can be derivatized by reacting the surface Si--OH, SiO--H,
 and/or Si--Si groups with a functionalizing reagent. When the substrate is
 made of a metal film, the surface can be derivatized with a material
 displaying avidity for that metal.
 In a preferred embodiment, wherein the substrates are made from glass, the
 covalent bonding of the reactive group to the glass surface is achieved by
 conversion of groups on the substrate's surface by a silicon modifying
 reagent such as:
EQU (RO).sub.3 --Si--R.sup.1 --X.sup.1 (1)
 where R is an alkyl group, such as methyl or ethyl, R.sup.1 is a linking
 group between silicon and X and X is a reactive group or a protected
 reactive group. The reactive group can also be a recognition moiety as
 discussed below. Silane derivatives having halogens or other leaving
 groups beside the displayed alkoxy groups are also useful in the present
 invention.
 A number of siloxane functionalizing reagents can be used, for example:
 1. Hydroxyalkyl siloxanes (Silylate surface, functionalize with diborane,
 and H.sub.2 O.sub.2 to oxidize the alcohol)
 a. allyl trichlorosilane.fwdarw..fwdarw.3-hydroxypropyl
 b. 7-oct-1-enyl trichlorchlorosilane.fwdarw..fwdarw.8-hydroxyoctyl
 2. Diol (dihydroxyalkyl) siloxanes (silylate surface and hydrolyze to diol)
 a. (glycidyl trimethoxysilane.fwdarw..fwdarw.(2,3-dihydroxypropyloxy)propyl
 3. Aminoalkyl siloxanes (amines requiring no intermediate functionalizing
 step)
 a. 3-aminopropyl trimethoxysilane.fwdarw..fwdarw.aminopropyl
 4. Dimeric secondary aminoalkyl siloxanes
 a. bis (3-trimethoxysilylpropyl) amine.fwdarw.bis(silyloxylpropyl)amine.
 It will be apparent to those of skill in the art that an array of similarly
 useful functionalizing chemistries are available when SAM components other
 than siloxanes are used. Thus, for example similarly functionalized alkyl
 thiols can be attached to metal films and subsequently reacted to produce
 the functional groups such as those exemplified above
 In another preferred embodiment, the substrate is at least partially a
 metal film, such as a gold film, and the reactive group is tethered to the
 metal surface by an agent displaying avidity for that surface. In a
 presently preferred embodiment, the substrate is at least partially a gold
 film and the group which reacts with the metal surface comprises a thiol,
 sulfide or disulfide such as:
EQU Y--S--R.sup.2 --X.sup.2 (2)
 R.sup.2 is a linking group between sulfur and X.sup.2 and X.sup.2 is a
 reactive group or a protected reactive group. X.sup.2 can also be a
 recognition moiety as discussed below. Y is a member selected from the
 group consisting of H, R.sup.3 and R.sup.3 --S--, wherein R.sup.2 and
 R.sup.3 are independently selected. When R.sup.2 and R.sup.3 are the same,
 symmetrical sulfides and disulfides result, and when they are different,
 asymmetrical sulfides and disulfides result.
 A large number of functionalized thiols, sulfides and disulfides are
 commercially available (Aldrich Chemical Co., St. Louis). Additionally,
 those of skill in the art have available to them a manifold of synthetic
 routes with which to produce additional such molecules. For example,
 amine-functionalized thiols can be produced from the corresponding
 halo-amines, halo-carboxylic acids, etc. by reaction of these halo
 precursors with sodium sulfhydride. See, for example, Reid, ORGANIC
 CHEMISTRY OF BIVALENT SULFUR, vol. 1, pp. 21-29, 32-35, vol. 5, pp. 27-34,
 Chemical Publishing Co., New York, 1958, 1963. Additionally,
 functionalized sulfides can be prepared via alkylthio-de-halogenation with
 a mercaptan salt. See, Reid, ORGANIC CHEMISTRY OF BIVALENT SULFUR, vol. 2,
 pp. 16-21, 24-29, vol. 3, pp. 11-14, Chemical Publishing Co., New York,
 1960. Other methods for producing compounds useful in practicing the
 present invention will be apparent to those of skill in the art.
 In another preferred embodiment, the functionalizing reagent provides for
 more than one reactive group per each reagent molecule. Using reagents
 such as Compound 3, below, each reactive site on the substrate surface is,
 in essence, "amplified" to two or more functional groups:
EQU (RO).sub.3 --Si--R.sup.1 --(X.sup.1).sub.n (3)
 where R is an alkyl group, such as methyl, R.sup.1 is a linking group
 between silicon and X.sup.1, X.sup.1 is a reactive group or a protected
 reactive group and n is an integer between 2 and 50, and more preferably
 between 2 and 20.
 Similar amplifying molecules are also of use in those embodiments wherein
 the substrate is at least partially a metal film. In these embodiments the
 group which reacts with the metal surface comprises a thiol, sulfide or
 disulfide such as in Formula (4):
EQU Y--S--R.sup.2 --(X.sup.2).sub.n (4)
 As discussed above, R.sup.2 is a linking group between sulfur and X.sup.2
 and X.sup.2 is a reactive group or a protected reactive group. X.sup.2 can
 also be a recognition moiety. Y is a member selected from the group
 consisting of H, R.sup.3 and R.sup.3 --S--, wherein R.sup.2 and R.sup.3
 are independently selected.
 R groups of use for R.sup.1, R.sup.2 and R.sup.3 in the above described
 embodiments of the present invention include, but are not limited to,
 alkyl, substituted alkyl, aryl, arylalkyl, substituted aryl, substituted
 arylalkyl, acyl, halogen, hydroxy, amino, alkylamino, acylamino, alkoxy,
 acyloxy, aryloxy, aryloxyalkyl, mercapto, saturated cyclic hydrocarbon,
 unsaturated cyclic hydrocarbon, heteroaryl, heteroarylalkyl, substituted
 heteroaryl, substituted heteroarylalkyl, heterocyclic, substituted
 heterocyclic and heterocyclicalkyl groups
 In each of Formulae 1-4, above, each of R.sup.1, R.sup.2 and R.sup.3 are
 either stable or they can be cleaved by chemical or photochemical
 reactions. For example, R groups comprising ester or disulfide bonds can
 be cleaved by hydrolysis and reduction, respectively. Also within the
 scope of the present invention is the use of R groups which are cleaved by
 light such as, for example, nitrobenzyl derivatives, phenacyl groups,
 benzoin esters, etc. Other such cleaveable groups are well-known to those
 of skill in the art.
 In another preferred embodiment, the organosulfur compound is partially or
 entirely halogenated. An example of compounds useful in this embodiment
 include:
EQU X.sup.1 Q.sub.2 C(CQ.sup.1.sub.2)mZ.sup.1 (CQ.sup.2.sub.2).sub.n SH (5)
 wherein, X.sup.1 is a member selected from the group consisting of H,
 halogen reactive groups and protected reactive groups. Reactive groups can
 also be recognition moieties as discussed below. Q, Q.sup.1 and Q.sup.2
 are independently members selected from the group consisting of H and
 halogen. Z.sup.1 is a member selected from the group consisting of
 --CQ.sub.2 --, --CQ.sup.1.sub.2 --, --C Q.sup.2.sub.2 --, --O--, --S--,
 --NR.sup.4 --, --C(O)NR.sup.4 and R.sup.4 NC(O)--, in which R.sup.4 is a
 member selected from the group consisting of H, alkyl, substituted alkyl,
 aryl, substituted aryl, heteroaryl and heterocyclic groups and m and n are
 independently a number between 0 and 40.
 In yet another preferred embodiment, the organic layer comprises a compound
 according to Formula 5 above, in which Q, Q.sup.1 and Q.sup.2 are
 independently members selected from the group consisting of H and
 fluorine. In a still further preferred embodiment, the organic layer
 comprises compounds having a structure according to Formulae (6) and (7):
EQU CF.sub.3 (CF.sub.2).sub.m Z.sup.1 (CH.sub.2).sub.n SH (6)
EQU CF.sub.3 (CF.sub.2).sub.o Z.sup.2 (CH.sub.2).sub.p SH (7)
 wherein, Z.sup.1 and Z.sup.2 are members independently selected from the
 group consisting of --CH.sub.2 --, --O--, --S--, --NR.sup.4 --,
 --C(O)NR.sup.4 and R.sup.4 NC(O)-- in which R.sup.4 is a member selected
 from the group consisting of H, alkyl, substituted alkyl, aryl,
 substituted aryl, heteroaryl and heterocyclic groups. In a presently
 preferred embodiment, the Z groups of adjacent molecules participate in
 either an attractive (e.g., hydrogen bonding) or repulsive (e.g., van der
 Waals) interaction.
 In Formula 7, m is a number between 0 and 40, n is a number between 0 and
 40, o is a number between 0 and 40 and p is a number between 0 and 40.
 In a further preferred embodiment, the compounds of Formulae 6 and 7 are
 used in conjunction with an organosulfur compound, either halogentated or
 unhalogenated, that bears a recognition moiety.
 When the organic layer is formed from a halogenated organosulfur compound,
 the organic layer can comprise a single halogenated compound or more than
 one halogenated compound having different structures. Additionally, these
 layers can comprise a non-halogenated organosulfur compound.
 The reactive functional groups (X.sup.1 and X.sup.2) are, for example:
 (a) carboxyl groups and various derivatives thereof including, but not
 limited to, N-hydroxysuccinimide esters, N-hydroxybenztriazole esters,
 acid halides, acyl imidazoles, thioesters, p-nitrophenyl esters, alkyl,
 alkenyl, alkynyl and aromatic esters;
 (b) hydroxyl groups which can be converted to esters, ethers, aldehydes,
 etc.
 (c) haloalkyl groups wherein the halide can be later displaced with a
 nucleophilic group such as, for example, an amine, a carboxylate anion,
 thiol anion, carbanion, or an alkoxide ion, thereby resulting in the
 covalent attachment of a new group at the site of the halogen atom;
 (d) dienophile groups which are capable of participating in Diels-Alder
 reactions such as, for example, maleimido groups;
 (e) aldehyde or ketone groups such that subsequent derivatization is
 possible via formation of carbonyl derivatives such as, for example,
 imines, hydrazones, semicarbazones or oximes, or via such mechanisms as
 Grignard addition or alkyllithium addition;
 (f) sulfonyl halide groups for subsequent reaction with amines, for
 example, to form sulfonamides;
 (g) thiol groups which can be converted to disulfides or reacted with acyl
 halides;
 (h) amine or sulfhydryl groups which can be, for example, acylated or
 alkylated;
 (i) alkenes which can undergo, for example, cycloadditions, acylation,
 Michael addition, etc; and
 (i) epoxides which can react with, for example, amines and hydroxyl
 compounds.
 The reactive moieties can also be recognition moieties. The nature of these
 groups is discussed in greater detail below.
 The reactive functional groups can be chosen such that they do not
 participate in, or interfere with, the reaction controlling the attachment
 of the functionalized SAM component onto the substrate's surface.
 Alternatively, the reactive functional group can be protected from
 participating in the reaction by the presence of a protecting group. Those
 of skill in the art will understand how to protect a particular functional
 group from interfering with a chosen set of reaction conditions. For
 examples of useful protecting groups, See Greene et al., PROTECTIVE GROUPS
 IN ORGANIC SYNTHESIS, John Wiley & Sons, New York, 1991.
 In a preferred embodiment, the SAM component bearing the recognition moiety
 is attached directly and essentially irreversibly via a "stable bond" to
 the surface of the substrate. A "stable bond", as used herein, is a bond
 which maintains its chemical integrity over a wide range of conditions
 (e.g., amide, carbamate, carbon--carbon, ether, etc.). In another
 preferred embodiment the SAM component bearing the recognition moiety is
 attached to the substrate surface by a "cleaveable bond". A "cleaveable
 bond", as used herein, is a bond which is designed to undergo scission
 under conditions which do not degrade other bonds in the recognition
 moiety-analyte complex. Cleaveable bonds include, but are not limited to,
 disulfide, imine, carbonate and ester bonds.
 In certain embodiments, it is advantageous to have the recognition moiety
 attached to a SAM component having a structure that is different than that
 of the constituents of the bulk SAM. In this embodiment, the group to
 which the recognition moiety is bound is referred to as a "spacer arm" or
 "spacer." Using such spacer arms, the properties of the SAM adjacent to
 the recognition moiety can be controlled. Properties that are usefully
 controlled include, for example, hydrophobicity, hydrophilicity,
 surface-activity and the distance of the recognition moiety from the plane
 of the substrate and/or the SAM. For example, in a SAM composed of
 alkanethiols, the recognition moiety can be attached to the substrate or
 the surface of the SAM via an amine terminated poly(ethyleneglycol).
 Numerous other combinations of spacer arms and SAMs are accessible to
 those of skill in the art.
 The hydrophilicity of the substrate surface can be enhanced by reaction
 with polar molecules such as amine-, hydroxyl- and polyhydroxyl-containing
 molecules. Representative examples include, but are not limited to,
 polylysine, polyethyleneimine, poly(ethyleneglycol) and
 poly(propyleneglycol). Suitable functionalization chemistries and
 strategies for these compounds are known in the art. See, for example,
 Dunn, R. L., et al., Eds. POLYMERIC DRUGS AND DRUG DELIVERY SYSTEMS, ACS
 Symposium Series Vol. 469, American Chemical Society, Washington, D.C.
 1991.
 The hydrophobicity of the substrate surface can be modulated by using a
 hydrophobic spacer arm such as, for example, long chain diamines,
 long-chain thiols, .alpha., .omega.-amino acids, etc. Representative
 hydrophobic spacers include, but are not limited to, 1,6-hexanediamine,
 1,8-octanediamine, 6-aminohexanoic acid and 8-aminooctanoic acid.
 The substrate surface can also be made surface-active by attaching to the
 substrate surface a spacer which has surfactant properties. Compounds
 useful for this purpose include, for example, aminated or hydroxylated
 detergent molecules such as, for example, 1-aminododecanoic acid.
 In another embodiment, the spacer serves to distance the recognition moiety
 from the substrate or SAM. Spacers with this characteristic have several
 uses. For example, a recognition moiety held too closely to the substrate
 or SAM surface may not react with incoming analyte, or it may react
 unacceptably slowly. When an analyte is itself sterically demanding, the
 reaction leading to recognition moiety-analyte complex formation can be
 undesirably slowed, or not occur at all, due to the monolithic substrate
 hindering the approach of the two components.
 In another embodiment, the physicochemical characteristics (e.g.,
 hydrophobicity, hydrophilicity, surface activity, conformation) of the
 substrate surface and/or SAM are altered by attaching a monovalent moiety
 which is different in composition than the constituents of the bulk SAM
 and which does not bear a recognition moiety. As used herein, "monovalent
 moiety" refers to organic molecules with only one reactive functional
 group. This functional group attaches the molecule to the substrate.
 "Monovalent moieties" are to be contrasted with the bifunctional "spacer"
 groups described above. Such monovalent groups are used to modify the
 hydrophilicity, hydrophobicity, binding characteristics, etc. of the
 substrate surface. Examples of groups useful for this purpose include long
 chain alcohols, amines, fatty acids, fatty acid derivatives,
 poly(ethyleneglycol) monomethyl ethers, etc.
 When two or more structurally distinct moieties are used as components of
 the SAMs, the components can be contacted with the substrate as a mixture
 of SAM components or, alternatively, the components can be added
 individually. In those embodiments in which the SAM components are added
 as a mixture, the mole ratio of a mixture of the components in solution
 results in the same ratio in the mixed SAM. Depending on the manner in
 which the SAM is assembled, The two components do not phase segregate into
 islands. See, Bain, C. D.; Whitesides, G. M., J. Am. Chem. Soc. 111:7164
 (1989). This feature of SAMs can be used to immobilize recognition
 moieties or bulky modifying groups in such a manner that certain
 interactions, such as steric hindrance, between these molecules is
 minimzed.
 The individual components of the SAMs can also be bound to the substrate in
 a sequential manner. Thus, in one embodiment, a first SAM component is
 attached to the substrate's surface by "underlabeling" the surface
 functional groups with less than a stoichiometric equivalent of the first
 component. The first component can be a SAM component liked to a terminal
 reactive group or recognition group, a spacer arm or a monovalent moiety.
 Subsequently, the second component is contacted with the substrate. This
 second component can either be added in stoichiometric equivalence,
 stoichiometric excess or can again be used to underlabel to leave sites
 open for a third component.
 C. Recognition Moieties
 As used herein, the term "recognition moiety" refers to molecules which are
 attached to either .omega.-functionalized spacer arms or
 .omega.-functionalized SAM components. Furthermore, a recognition moiety
 can be presented by a polymer surface (e.g., a rubbed polymer surface).
 The recognition moieties bind to, or otherwise interact with, the analyte
 of interest.
 In a preferred embodiment, the recognition moiety comprises an organic
 functional group. In presently preferred embodiments, the organic
 functional group is a member selected from the group consisting of amines,
 carboxylic acids, drugs, chelating agents, crown ethers, cyclodextrins or
 a combination thereof.
 In another preferred embodiment, the recognition moiety is a biomolecule.
 In still further preferred embodiments, the biomolecule is a protein,
 antibody, peptide, nucleic acid (e.g., single nucleotides or nucleosides,
 oligo nucleotides, polynucleotides and single- and higher-stranded nucleic
 acids) or a combination thereof. In a presently preferred embodiment, the
 recognition moiety is biotin.
 When the recognition moiety is an amine, in preferred embodiments, the
 recognition moiety will interact with a structure on the analyte which
 reacts by binding to the amine (e.g., carbonyl groups, alkylhalo groups).
 In another preferred embodiment, the amine is protonated by an acidic
 moiety on the analyte of interest (e.g., carboxylic acid, sulfonic acid).
 In certain preferred embodiments, when the recognition moiety is a
 carboxylic acid, the recognition moiety will interact with the analyte by
 complexation (e.g., metal ions). In still other preferred embodiments, the
 carboxylic acid will protonate a basic group on the analyte (e.g. amine).
 In another preferred embodiment, the recognition moiety is a drug moiety.
 The drug moieties can be agents already accepted for clinical use or they
 can be drugs whose use is experimental, or whose activity or mechanism of
 action is under investigation. The drug moieties can have a proven action
 in a given disease state or can be only hypothesized to show desirable
 action in a given disease state. In a preferred embodiment, the drug
 moieties are compounds which are being screened for their ability to
 interact with an analyte of choice. As such, drug moieties which are
 useful in practicing the instant invention include drugs from a broad
 range of drug classes having a variety of pharmacological activities.
 Classes of useful agents include, for example, non-steroidal anti-
 inflammatory drugs (NSAIDS). The NSAIDS can, for example, be selected from
 the following categories: (e.g., propionic acid derivatives, acetic acid
 derivatives, fenamic acid derivatives, biphenylcarboxylic acid derivatives
 and oxicams); steroidal anti-inflammatory drugs including hydrocortisone
 and the like; antihistaminic drugs (e.g., chlorpheniramine, triprolidine);
 antitussive drugs (e.g., dextromethorphan, codeine, carmiphen and
 carbetapentane); antipruritic drugs (e.g., methidilizine and
 trimeprizine); anticholinergic drugs (e.g., scopolamine, atropine,
 homatropine, levodopa); anti-emetic and antinauseant drugs (e.g.,
 cyclizine, meclizine, chlorpromazine, buclizine); anorexic drugs (e.g.,
 benzphetamine, phentermine, chlorphentermine, fenfluramine); central
 stimulant drugs (e.g., amphetamine, methamphetamine, dextroamphetamine and
 methylphenidate); antiarrhythmic drugs (e.g., propanolol, procainamide,
 disopyraminde, quinidine, encainide); .beta.-adrenergic blocker drugs
 (e.g., metoprolol, acebutolol, betaxolol, labetalol and timolol);
 cardiotonic drugs (e.g., milrinone, amrinone and dobutamine);
 antihypertensive drugs (e.g., enalapril, clonidine, hydralazine,
 minoxidil, guanadrel, guanethidine);diuretic drugs (e.g., amiloride and
 hydrochlorothiazide); vasodilator drugs (e.g., diltazem, amiodarone,
 isosuprine, nylidrin, tolazoline and verapamil); vasoconstrictor drugs
 (e.g., dihydroergotamine, ergotamine and methylsergide); antiulcer drugs
 (e.g., ranitidine and cimetidine); anesthetic drugs (e.g., lidocaine,
 bupivacaine, chlorprocaine, dibucaine); antidepressant drugs (e.g.,
 imipramine, desipramine, amitryptiline, nortryptiline); tranquilizer and
 sedative drugs (e.g., chlordiazepoxide, benacytyzine, benzquinamide,
 flurazapam, hydroxyzine, loxapine and promazine); antipsychotic drugs
 (e.g., chlorprothixene, fluphenazine, haloperidol, molindone, thioridazine
 and trifluoperazine); antimicrobial drugs (antibacterial, antifungal,
 antiprotozoal and antiviral drugs).
 Antimicrobial drugs which are preferred for incorporation into the present
 composition include, for example, pharmaceutically acceptable salts of
 .beta.-lactam drugs, quinolone drugs, ciprofloxacin, norfioxacin,
 tetracycline, erythromycin, amikacin, triclosan, doxycycline, capreomycin,
 chlorhexidine, chlortetracycline, oxytetracycline, clindamycin,
 ethambutol, hexamidine isothionate, metronidazole, pentamidine,
 gentamycin, kanamycin, lineomycin, methacycline, methenamine, minocycline,
 neomycin, netilmycin, paromomycin, streptomycin, tobramycin, miconazole
 and amanfadine.
 Other drug moieties of use in practicing the present invention include
 antineoplastic drugs (e.g., antiandrogens (e.g., leuprolide or flutamide),
 cytocidal agents (e.g., adriamycin, doxorubicin, taxol, cyclophosphamide,
 busulfan, cisplatin, .alpha.-2-interferon) anti-estrogens (e.g.,
 tamoxifen), antimetabolites (e.g., fluorouracil, methotrexate,
 mercaptopurine, thioguanine).
 The recognition moiety can also comprise hormones (e.g.,
 medroxyprogesterone, estradiol, leuprolide, megestrol, octreotide or
 somatostatin); muscle relaxant drugs (e.g., cinnamedrine, cyclobenzaprine,
 flavoxate, orphenadrine, papaverine, mebeverine, idaverine, ritodrine,
 dephenoxylate, dantrolene and azumolen); antispasmodic drugs; bone-active
 drugs (e.g., diphosphonate and phosphonoalkylphosphinate drug compounds);
 endocrine modulating drugs (e.g., contraceptives (e.g., ethinodiol,
 ethinyl estradiol, norethindrone, mestranol, desogestrel,
 medroxyprogesterone), modulators of diabetes (e.g., glyburide or
 chlorpropamide), anabolics, such as testolactone or stanozolol, androgens
 (e.g., methyltestosterone, testosterone or fluoxymesterone), antidiuretics
 (e.g., desmopressin) and calcitonins).
 Also of use in the present invention are estrogens (e.g.,
 diethylstilbesterol), glucocorticoids (e.g., triamcinolone, betamethasone,
 etc.) and progenstogens, such as norethindrone, ethynodiol, norethindrone,
 levonorgestrel; thyroid agents (e.g., liothyronine or levothyroxine) or
 anti-thyroid agents (e.g., methimazole); antihyperprolactinemic drugs
 (e.g., cabergoline); hormone suppressors (e.g., danazol or goserelin),
 oxytocics (e.g., methylergonovine or oxytocin) and prostaglandins, such as
 mioprostol, alprostadil or dinoprostone, can also be employed.
 Other useful recognition moieties include immunomodulating drugs (e.g.,
 antihistamines, mast cell stabilizers, such as lodoxamide and/or cromolyn,
 steroids (e.g., triamcinolone, beclomethazone, cortisone, dexamethasone,
 prednisolone, methylprednisolone, beclomethasone, or clobetasol),
 histamine H.sub.2 antagonists (e.g., famotidine, cimetidine, ranitidine),
 immunosuppressants (e.g., azathioprine, cyclosporin), etc. Groups with
 anti-inflammatory activity, such as sulindac, etodolac, ketoprofen and
 ketorolac, are also of use. Other drugs of use in conjunction with the
 present invention will be apparent to those of skill in the art.
 When the recognition moiety is a chelating agent, crown ether or
 cyclodextrin, host-guest chemistry will dominate the interaction between
 the recognition moiety and the analyte. The use of host-guest chemistry
 allows a great degree of recognition-moiety-analyte specificity to be
 engineered into a device of the invention. The use of these compounds to
 bind to specific compounds is well known to those of skill in the art.
 See, for example, Pitt et al. "The Design of Chelating Agents for the
 Treatment of Iron Overload," In, INORGANIC CHEMISTRY IN BIOLOGY AND
 MEDICINE; Martell, A. E., Ed.; American Chemical Society, Washington,
 D.C., 1980, pp. 279-312; Lindoy, L. F., THE CHEMISTRY OF MACROCYCLIC
 LIGAND COMPLEXES; Cambridge University Press, Cambridge,1989; Dugas, H.,
 BIOORGANIC CHEMISTRY; Springer-Verlag, New York, 1989, and references
 contained therein.
 Additionally, a manifold of routes allowing the attachment of chelating
 agents, crown ethers and cyclodextrins to other molecules is available to
 those of skill in the art. See, for example, Meares et al., "Properties of
 In Vivo Chelate-Tagged Proteins and Polypeptides." In, MODIFICATION OF
 PROTEINS: FOOD, NUTRITIONAL, AND PHARMACOLOGICAL ASPECTS;" Feeney, R. E.,
 Whitaker, J. R., Eds., American Chemical Society, Washington, D.C., 1982,
 pp.370-387; Kasina et al. Bioconjugate Chem. 9:108-117 (1998); Song et
 al., Bioconjugate Chem. 8:249-255 (1997).
 In a presently preferred embodiment, the recognition moiety is a
 polyaminocarboxylate chelating agent such as ethylenediaminetetraacetic
 acid (EDTA) or diethylenetriaminepentaacetic acid (DTPA). These
 recognition moieties can be attached to any amine-terminated component of
 a SAM or a spacer arm, for example, by utilizing the commercially
 available dianhydride (Aldrich Chemical Co., Milwaukee, Wis.).
 In still further preferred embodiments, the recognition moiety is a
 biomolecule such as a protein, nucleic acid, peptide or an antibody.
 Biomolecules useful in practicing the present invention can be derived
 from any source. The biomolecules can be isolated from natural sources or
 can be produced by synthetic methods. Proteins can be natural proteins or
 mutated proteins. Mutations can be effected by chemical mutagenesis,
 site-directed mutagenesis or other means of inducing mutations known to
 those of skill in the art. Proteins useful in practicing the instant
 invention include, for example, enzymes, antigens, antibodies and
 receptors. Antibodies can be either polyclonal or monoclonal. Peptides and
 nucleic acids can be isolated from natural sources or can be wholly or
 partially synthetic in origin.
 In those embodiments wherein the recognition moiety is a protein or
 antibody, the protein can be tethered to a SAM component or a spacer arm
 by any reactive peptide residue available on the surface of the protein.
 In preferred embodiments, the reactive groups are amines or carboxylates.
 In particularly preferred embodiments, the reactive groups are the
 .epsilon.-amine groups of lysine residues. Furthermore, these molecules
 can be adsorbed onto the surface of the substrate or SAM by non-specific
 interactions (e.g., chemisorption, physisorption).
 Recognition moieties which are antibodies can be used to recognize analytes
 which are proteins, peptides, nucleic acids, saccharides or small
 molecules such as drugs, herbicides, pesticides, industrial chemicals and
 agents of war. Methods of raising antibodies for specific molecules are
 well-known to those of skill in the art. See, U.S. Pat. No. 5/147,786,
 issued to Feng et al. on Sep. 15, 1992; No. 5/334,528, issued to Stanker
 et al. on Aug. 2, 1994; No. 5/686,237, issued to Al-Bayati, M. A. S. on
 Nov. 11, 1997; and No. 5/573,922, issued to Hoess et al. on Nov. 12, 1996.
 Methods for attaching antibodies to surfaces are also art-known. See,
 Delamarche et al. Langmuir 12:1944-1946 (1996).
 Peptides and nucleic acids can be attached to a SAM component or spacer
 arm. Both naturally-derived and synthetic peptides and nucleic acids are
 of use in conjunction with the present invention. These molecules can be
 attached to a SAM component or spacer arm by any available reactive group.
 For example, peptides can be attached through an amine, carboxyl,
 sulfhydryl, or hydroxyl group. Such a group can reside at a peptide
 terminus or at a site internal to the peptide chain. Nucleic acids can be
 attached through a reactive group on a base (e.g., exocyclic amine) or an
 available hydroxyl group on a sugar moiety (e.g., 3'- or 5'-hydroxyl). The
 peptide and nucleic acid chains can be further derivatized at one or more
 sites to allow for the attachment of appropriate reactive groups onto the
 chain. See, Chrisey et al. Nucleic Acids Res. 24:3031-3039 (1996).
 When the peptide or nucleic acid is a fully or partially synthetic
 molecule, a reactive group or masked reactive group can be incorporated
 during the process of the synthesis. Many derivatized monomers appropriate
 for reactive group incorporation in both peptides and nucleic acids are
 know to those of skill in the art. See, for example, THE PEPTIDES:
 ANALYSIS, SYNTHESIS, BIOLOGY, Vol. 2: "Special Methods in Peptide
 Synthesis," Gross, E. and Melenhofer, J., Eds., Academic Press, New York
 (1980). Many useful monomers are commercially available (Bachem, Sigma,
 etc.). This masked group can then be unmasked following the synthesis, at
 which time it becomes available for reaction with a SAM component or a
 spacer arm.
 In other preferred embodiments, the peptide is attached directly to the
 substrate. See, Frey et al. Anal. Chem. 68:3187-3193 (1996). In a
 particularly preferred embodiment, the peptide is attached to a gold
 substrate through a sulfhydryl group on a cysteine residue. In another
 preferred embodiment, the peptide is attached through a thiol to a spacer
 arm which terminates in, for example, an iodoacetamide, chloroacetamide,
 benzyl iodide, benzyl bromide, alkyl iodide or alkyl bromide. Similar
 immobilization techniques are known to those of skill in the art. See, for
 example, Zull et al. J. Ind. Microbiol. 13:137-143 (1994).
 In another preferred embodiment, the recognition moiety forms an inclusion
 complex with the analyte of interest. In a particularly preferred
 embodiment, the recognition moiety is a cyclodextrin or modified
 cyclodextrin. Cyclodextrins are a group of cyclic oligosaccharides
 produced by numerous microorganisms. Cyclodextrins have a ring structure
 which has a basket-like shape. This shape allows cyclodextrins to include
 many kinds of molecules into their internal cavity. See, for example,
 Szejtli, J., CYCLODEXTRINS AND THEIR INCLUSION COMPLEXES; Akademiai Klado,
 Budapest, 1982; and Bender et al., CYCLODEXTRIN CHEMISTRY,
 Springer-Verlag, Berlin, 1978.
 Cyclodextins are able to form inclusion complexes with an array of organic
 molecules including, for example, drugs, pesticides, herbicides and agents
 of war. See, Tenjarla et al., J. Pharm. Sci. 87:425-429 (1998); Zughul et
 al., Pharm. Dev. Technol. 3:43-53 (1998); and Albers et al., Crit. Rev.
 Ther. Drug Carrier Syst. 12:311-337 (1995). Importantly, cyclodextrins are
 able to discriminate between enantiomers of compounds in their inclusion
 complexes. Thus, in one preferred embodiment, the invention provides for
 the detection of a particular enantiomer in a mixture of enantiomers. See,
 Koppenhoefer et al. J. Chromatogr. A 793:153-164 (1998).
 The cyclodextrin recognition moiety can be attached to a SAM component,
 through a spacer arm or directly to the substrate. See, Yamamoto et al.,
 J. Phys. Chem. B 101:6855-6860 (1997). Methods to attach cyclodextrins to
 other molecules are well known to those of skill in the chromatographic
 and pharmaceutical arts. See, Sreenivasan, K. J. Appl. Polym. Sci.
 60:2245-2249 (1996).
 D. Mesogenic Layer
 Any compound or mixture of compounds which forms a mesogenic layer can be
 used in conjunction with the present invention. The mesogens can form
 thermotropic or lyotropic liquid crystals. The mesogenic layer can be
 either continuous or it can be patterned.
 As used herein, "thermotropic liquid crystal" refers to liquid crystals
 which result from the melting of mesogenic solids due to an increase in
 temperature. Both pure substances and mixtures form thermotropic liquid
 crystals.
 "Lyotropic," as used herein, refers to molecules which form phases with
 orientational and/or positional order in a solvent Lyotropic liquid
 crystals can be formed using amphiphilic molecules (e.g., sodium laurate,
 phosphatidylethanolamine, lecithin).
 Both the thermotropic and lyotropic liquid crystals can exist in a number
 of forms including nematic, chiral nematic, smectic, polar smectic, chiral
 smectic, frustrated phases and discotic phases.
 As used herein, "nematic" refers to liquid crystals in which the long axes
 of the molecules remain substantially parallel, but the positions of the
 centers of mass are randomly distributed. Nematic crystals can be
 substantially oriented by a nearby surface.
 "Chiral nematic," as used herein refers to liquid crystals in which the
 mesogens are optically active. Instead of the director being held locally
 constant as is the case for nematics, the director rotates in a helical
 fashion throughout the sample. Chiral nematic crystals show a strong
 optical activity which is much higher than can be explained on the bases
 of the rotatory power of the individual mesogens. When light equal in
 wavelength to the pitch of the director impinges on the liquid crystal,
 the director acts like a, diffraction grating, reflecting most and
 sometimes all of the light incident on it. If white light is incident on
 such a material, only one color of light is reflected and it is circularly
 polarized. This phenomenon is known as selective reflection and is
 responsible for the iridescent colors produced by chiral nematic crystals.
 "Smectic," as used herein refers to liquid crystals which are distinguished
 from "nematics" by the presence of a greater degree of positional order in
 addition to orientational order; the molecules spend more time in planes
 and layers than they do between these planes and layers. "Polar smectic"
 layers occur when the mesogens have permanent dipole moments. In the
 smectic A2 phase, for example, successive layers show anti ferroelectric
 order, with the direction of the permanent dipole alternating from layer
 to layer. If the molecule contains a permanent dipole moment transverse to
 the long molecular axis, then the chiral smectic phase is ferroelectric. A
 device utilizing this phase can be intrinsically bistable.
 "Frustrated phases," as used herein, refers to another class of phases
 formed by chiral molecules. These phases are not chiral, however, twist is
 introduced into the phase by an array of grain boundaries. A cubic lattice
 of defects (where the director is not defined) exist in a complicated,
 orientationally ordered twisted structure. The distance between these
 defects is hundreds of nanometers, so these phases reflect light just as
 crystals reflect x-rays.
 "Discotic phases" are formed from molecules which are disc shaped rather
 than elongated. Usually these molecules have aromatic cores and six
 lateral substituents. If the molecules are chiral or a chiral dopant is
 added to a discotic liquid crystal, a chiral nematic discotic phase can
 form.
 TABLE 1
 ##STR1##
 X Name
 ##STR2## Schiff bases
 ##STR3## diazo compounds
 ##STR4## azoxy compounds
 ##STR5## nitrones
 ##STR6## stilbenes
 ##STR7## tolans
 ##STR8## esters
 -- biphenyls
 Presently preferred mesogens are displayed in Table 1. In Table 1, R.sup.11
 and R.sup.21 are independently selected R groups. Presently preferred R
 groups include, but are not limited to, alkyl groups, lower alkyl,
 substituted alkyl groups, aryl groups, acyl groups, halogens, hydroxy,
 cyano, amino, alkoxy, alkylamino, acylamino, thioamido, acyloxy, aryloxy,
 aryloxyalkyl, mercapto, thia, aza, oxo, both saturated and unsaturated
 cyclic hydrocarbons, heterocycles, arylalkyl, substituted aryl, alkylhalo,
 acylamino, mercapto, substituted arylalkyl, heteroaryl, heteroarylalkyl,
 substituted heteroaryl, substituted heteroarylalkyl, substituted
 heterocyclic, heterocyclicalkyl
 In a presently preferred embodiment, X.sup.11 is a bond linking the two
 phenyl groups and the mesogen is a biphenyl. In another preferred
 embodiment X.sup.11 is a C.dbd.N bond and the mesogen is a Schiff base. In
 still further preferred embodiments, R.sup.11 and R.sup.21 are
 independently selected from the group consisting of alkyl, alkoxy and
 cyano moieties.
 In a particularly preferred embodiment, the mesogen is a member selected
 from the group consisting of 4-cyano4'-pentylbiphenyl,
 N-(4-methoxybenzylidene)-4-butlyaniline and combinations thereof.
 The mesogenic layer can be a substantially pure compound, or it can contain
 other compounds which enhance or alter characteristics of the mesogen.
 Thus, in one preferred embodiment, the mesogenic layer further comprises a
 second compound, for example and alkane, which expands the temperature
 range over which the nematic and isotropic phases exist. Use of devices
 having mesogenic layers of this composition allows for detection of the
 analyte recognition moiety interaction over a greater temperature range.
 In another preferred embodiment, the analyte first interacts with the
 recognition moiety and the mesogenic layer is introduced in its isotropic
 phase. The mesogenic layer is subsequently cooled to form the liquid
 crystalline phase. The presence of tie analyte within regions of the
 mesogenic layer will disturb the equilibrium between the nematic and
 isotropic phases leading to different rates and magnitudes of nucleation
 at those sites. The differences between the nematic and isotropic regions
 are clearly detectable.
 D. Patterned Liquid Crystals
 One approach to the patterning of the mesogenic layer on flat and curved
 surfaces is based on the use of patterned SAMs of molecules to direct both
 the polar (away from the surface) and azimuthal (in the plane of the
 surface) orientations of the mesogenic layer. This method is simple and
 flexible, and any of the recently established procedures for patterning
 SAMs on surfaces (for example, microcontact printing or photo-patterning)
 (Talov et al., J. Am. Chem. Soc. 115: 5305 (1993); Kumar et al., Acc.
 Chem. Res. 28: 219 (1995), and references therein; Xia et al., J. Am.
 Chem. Soc. 117: 3274 (1995), and references therein can be used; Jackman
 et al., Science 269: 664 (1995)). Using any of these methods, SAMs which
 pattern liquid crystals can be easily extended to sizes ranging from
 hundreds of nanometers (Xia et al., J. Am. Chem. Soc. 117: 3274 (1995),
 and references therein) to millimeters and permit both planar (parallel to
 the surface) and homeotropic (perpendicular to the surface) orientation of
 mesogenic layers; methods based on the rubbing of polymer films mainly
 provide manipulation of the in-plane alignment of mesogenic layers and
 cannot homeotropically align mesogenic layers. One class of useful SAMs
 has surface energies (.about.19 mJ/m.sup.2) about half those of films of
 polyimides used for alignment of liquid crystals; low-energy surfaces are
 less prone to contamination by molecular adsorbates and dust particles
 than are high-energy ones. Because SAMs can also be patterned on
 non-planar surfaces (Jackman et al., Science 269: 664 (1995)), patterned
 mesogenic structures formed with SAMs can be replicated on curved
 surfaces.
 The capacity to pattern mesogenic layer orientations on nonplanar surfaces
 provides procedures for the fabrication of tunable hybrid
 diffractive-refractive devices. For example, devices based on combinations
 of diffractive and refractive optical processes permit aplanatic or
 chromatic correction in lenses, spectral dispersion, imaging from a single
 optical element, and other manipulations of light (Resler et al., Opt.
 Lett. 21, 689 (1996); S. M. Ebstein, ibid., p. 1454; M. B. Stem,
 Microelectron. Eng. 32, 369 (1996): Goto et al., Jpn. J. Appl. Phys. 31,
 1586 (1992); Magiera et al., Soc. Photo-Opt. Instrum. Eng., 2774, 204
 (1996)). The capability to pattern mesogenic layers on curved surfaces
 also provides routes for the fabrication of displays with wide viewing
 angles.
 In a presently preferred embodiment, the tunable hybrid device permits the
 manipulation of light. In a further preferred embodiment, the device is a
 refractive-diffractive device. In a still further preferred embodiment,
 the device permits imaging from a single optical element. In yet another
 preferred embodiment, the device permits aplanatic or chromatic correction
 in lenses. In still another preferred embodiment, the device allows for
 spectral dispersion.
 In another presently preferred embodiment, the SAM is layered on a material
 suitable for use as an electrode. In a preferred embodiment, the material
 is a metal film. In a further preferred embodiment, the metal film is a
 gold film.
 The patterned mesogenic layers of the instant invention can be tuned by the
 use of electric fields. In a preferred embodiment, the electric field is
 used to reversibly orient the mesogenic layer. In a still further
 preferred embodiment, the electric field is applied either perpendicular
 to, or in the plane of, the surface of the mesogenic layer. In another
 preferred embodiment, the oriented mesogenic layer modulates the intensity
 of light diffracted from the layer.
 The discussion above, concerning SAM components, SAM components with
 reactive groups and SAM components bearing recognition moieties is equally
 applicable in the context of this aspect of the invention. Thus, the
 constituents of the SAM can be chosen from any of a wide variety of
 appropriate molecules. In a presently preferred embodiment, the SAM
 comprises mixtures of R.sup.21 CH.sub.2 (CH.sub.2).sub.14 SH and R.sup.31
 CH.sub.2 (CH.sub.2).sub.15 SH, where R.sup.21 and R.sup.31 are
 independently members elected from the group consisting of hydrogen,
 reactive groups and recognition groups, as discussed above.
 E. Analytes
 The devices and methods of the present invention can be used to detect any
 analyte, or class of analytes, which interact with a recognition moiety in
 a manner that perturbs the mesogenic layer in a detectable manner. The
 interaction between the analyte and recognition moiety can be any
 physicochemical interaction, including covalent bonding, ionic bonding,
 hydrogen bonding, van der Waals interactions, repulsive electronic
 interactions, attractive electronic interactions and
 hydrophobic/hydrophilic interactions.
 In a preferred embodiment, the interaction is an ionic interaction. In this
 embodiment, an acid, base, metal ion or metal ion-binding ligand is the
 analyte. In a still further preferred embodiment, the interaction is a
 hydrogen bonding interaction. In a particularly preferred embodiment, the
 hybridization of an immobilized nucleic acid to a nucleic acid having a
 complementary sequence is detected. In another preferred embodiment, the
 interaction is between an enzyme or receptor and a small molecule which
 binds thereto.
 In another embodiment, the analyte competes for the recognition moiety with
 another agent which has been bound to the recognition moiety prior to
 introducing the analyte of interest. In this embodiment, it is the process
 or result of the analyte displacing the pre-bound agent which causes the
 detectable perturbation in the mesogenic layer. Suitable combinations of
 recognition moieties and analytes will be apparent to those of skill in
 the art.
 In presently preferred embodiments, the analyte is a member selected from
 the group consisting of acids, bases, organic ions, inorganic ions,
 pharmaceuticals, herbicides, pesticides, chemical warfare agents, noxious
 gases and biomolecules. Importantly, each of these agents can be detected
 as a vapor or a liquid. These agents can be present as components in
 mixtures of structurally unrelated compounds, racemic mixtures of
 stereoisomers, non-racemic mixtures of stereoisomers, mixtures of
 diastereomers, mixtures of positional isomers or as pure compounds. Within
 the scope of the invention is a device and a method to detect a particular
 analyte of interest without interference from other substances within a
 mixture.
 Both organic and inorganic acids can be detected using the device and
 method of the present invention. In a preferred embodiment, the
 recognition moiety comprises a group which is protonated by the acid. The
 result of this protonation is a detectable perturbation in the
 configuration of the mesogenic layer. While not wishing to be bound by any
 particular theory of operation, the inventors currently believe that this
 perturbation can be achieved by a change in the size or conformation of
 the recognition moiety on protonation. Alternatively, the protonation may
 induce repulsion between proximate recognition moieties bearing charges of
 the same sign. Further, the protonation can induce an overall positive
 charge across the SAM which perturbs the electronic distribution of the
 molecules in the mesogenic layer. This perturbation can be due to an
 electronic redistribution in the mesogenic molecules or can be due to
 repulsive or attractive interaction between a charged mesogen and a
 similarly, or oppositely, charged SAM.
 In another preferred embodiment, the invention provides a device and a
 method for detecting bases. The methods for the detection and the
 mechanisms which allow such detection of bases are substantially similar
 to those discussed above in the context of acid detection; the notable
 exception being that the base will preferably deprotonate a group on a SAM
 component, spacer arm or substrate.
 Organic ions which are substantially non-acidic and non-basic (e.g.,
 quaternary alkylammonium salts) can be detected by a recognition moiety.
 For example, a recognition moiety with ion exchange properties is useful
 in the present invention. A specific example is the exchange of a cation
 such as dodecyltrimethylammonium cation for a metal ion such as sodium,
 using a SAM presenting. Recognition moieties that form inclusion complexes
 with organic cations are also of use. For example, crown ethers and
 cryptands can be used to form inclusion complexes with organic ions such
 as quaternary ammonium cations.
 Inorganic ions such as metal ions and complex ions (e.g., SO.sub.4.sup.-2,
 PO.sub.4.sup.-3) can also be detected using the device and method of the
 invention. Metal ions can be detected, for example, by their complexation
 or chelation by agents bound to a SAM component, spacer arm or the
 substrate. In this embodiment, the recognition moiety can be a simple
 monovalent moiety (e.g., carboxylate, amine, thiol) or can be a more
 structurally complex agent (e.g., ethylenediaminepentaacetic acid, crown
 ethers, aza crowns, thia crowns). The methods of detection and the
 mechanisms allowing such detection are substantially similar to those
 discussed in the context of acid detection.
 Complex inorganic ions can be detected by their ability to compete with
 ligands for bound metal ions in ligand-metal complexes. When a ligand
 bound to a SAM component, a spacer arm or a substrate forms a
 metal-complex having a thermodynamic stability constant which is less than
 that of the complex between the metal and the complex ion, the complex ion
 will cause the dissociation of the metal ion from the immobilized ligand.
 The dissociation of the metal ion will perturb the mesogenic layer in a
 detectable manner. Methods of determining stability constants for
 compounds formed between metal ions and ligands are well known to those of
 skill in the art. Using these stability constants, devices which are
 specific for particular ions can be manufactured. See, Martell, A. E.,
 Motekaitis, R. J., DETERMINATION AND USE OF STABILITY CONSTANTS, 2d Ed.,
 VCH Publishers, New York 1992.
 Small molecules such as pesticides, herbicides, agents of war, and the like
 can be detected by the use of a number of different recognition moiety
 motifs. Acidic or basic components can be detected as described above. An
 agent's metal binding capability can also be used to advantage, as
 described above for complex ions. Additionally, if these agents bind to an
 identified biological structure (e.g., a receptor), the receptor can be
 immobilized on the substrate, a SAM component or a spacer arm. Techniques
 are also available in the art for raising antibodies which are highly
 specific for a particular small molecule. Thus, it is within the scope of
 the present invention to make use of antibodies against small molecules
 for detection of those molecules.
 In a preferred embodiment, the affinity of an analyte for a particular
 metal ion is exploited by having a SAM component, spacer arm or substrate
 labeled with an immobilized metal ion. The metal ion generally must have
 available at least one empty coordination site to which the analyte can
 bind. Alternatively, at least one bond between the metal and the
 metal-immobilizing agent must be sufficiently labile in the presence of
 the analyte to allow the displacement of at least one bond of the
 immobilizing reagent by the analyte
 In a preferred embodiment, the agent detected by binding to an immobilized
 metal ion is an organophosphorous compound such as an insecticide or an
 agent of war (e.g., VX,
 O-ethyl-S-(2-diisopropylaminoethyl)-methylthiophosphonate). Exemplary
 compounds which exhibit affinity for organophosphorous agents include, but
 are not limited to, Cu.sup.+2 -diamine, triethylentetraamine-Cu.sup.+2
 -chloride, tetraethylenediamine-Cu.sup.+2 -chloride and
 2,2'-bipyridine-Cu.sup.+2 -chloride. See, U.S. Pat. No. 4/549,427, issued
 to Kolesar, Jr., E. S. on Oct. 29, 1985.
 In another preferred embodiment, antibodies to the particular agents are
 immobilized on the substrate, a SAM component or a spacer arm. Techniques
 for raising antibodies to herbicides, pesticides and agents of war are
 known to those of skill in the art. See, Harlow, Lane, MONOCLONAL
 ANTIBODIES: A LABORATORY MANUAL, Cold Springs Harbor Laboratory, Long
 Island, N.Y., 1988.
 In a preferred embodiment, the herbicides are preferably members of the
 group consisting of triazines, haloacetanilides, carbamates, toluidines,
 ureas, plant growth hormones and diphenyl ethers. Included within these
 broad generic groupings are commercially available herbicides such as
 phenoxyl alkanoic acids, bipyridiniums, benzonitriles, dinitroanilines,
 acid amides, carbamates, thiocarbamates, heterocyclic nitrogen compounds
 including triazines, pyridines, pyridazinones, sulfonylureas, imidazoles,
 substituted ureas, halogenated aliphatic carboxylic acids, inorganics,
 organometallics and derivatives of biologically important amino acids.
 In the embodiments discussed above, the preferred agent of war is a member
 of the group consisting of mustard and related vesicants including the
 agents known as HD, Q, T, HN1, HN2, HN3, nerve agents, particularly the
 organic esters of substituted phosphoric acid including tabun, sarin,
 isopropyl methylphosphonofluoridate, soman pinacolyl
 methylphosphonofluoridate. Other detectable analytes include incapacitants
 such as BZ, 3-quinuclidinyl benzilate and irritants such as the riot
 control compound CS.
 Pesticides preferred for detection using the present invention include
 bactericides (e.g, formaldehyde), fumigants (e.g., bromomethane),
 fungicides (e.g., 2-phenylphenol, biphenyl, mercuric oxide, imazalil),
 acaricides (e.g., abamectin, bifenthrin), insecticides (e.g.,
 imidacloprid, pralletbrin, cyphenothrin)
 The present invention also provides a device and a method for detecting
 noxious gases such as CO, CO.sub.2, SO.sub.3, H.sub.2 SO.sub.4, SO.sub.2,
 NO, NO.sub.2, N.sub.2 O.sub.4 and the like. In a preferred embodiment, the
 SAM, the substrate or a spacer arm includes at least one compound capable
 of detecting the gas. Useful compounds include, but are not limited to,
 palladium compounds selected from the group consisting of palladium
 sulfate, palladium sulfite, palladium pyrosulfite, palladium chloride,
 palladium bromide, palladium iodide, palladium perchlorate, palladium
 complexes with organic complexing reagents and mixtures thereof.
 Other compounds of use in practicing this embodiment of the present
 invention include, molybdenum compounds such as silicomolybdic acid, salts
 of silicomolybdic acid, molybdenum trioxide, heteropolyacids of molybdenum
 containing vanadium, copper or tungsten, ammonium molybdate, alkali metal
 or alkaline earth salts of molybdate anion, heteropolymolybdates and
 mixtures thereof.
 Still further useful gas detecting compounds include, copper salts and
 copper complexes with an available coordination site. Alpha-cyclodextrin,
 beta-cyclodextrin, modified alpha- and beta-cyclodextrins,
 gamma-cyclodextrin and mixtures thereof are of use in practicing the
 present invention. See, U.S. Pat. No. 5/618,493, issued to Goldstein et
 al. on Apr. 8, 1997 and No. 5/071,526, issued to Pletcher et al. on Dec.
 10, 1991.
 In another preferred gas detecting embodiment, the substrate, SAM component
 or spacer arm is derivatized with a compound selected from the group
 consisting of amorphous hemoglobin, crystalline hemoglobin, amorphous
 heme, crystalline heme and mixtures thereof. The heme serves as a
 recognition moiety which is reactive towards the gas. See, U.S. Pat. No.
 3/693,327, issued to Scheinberg, I. A. on Sep. 26, 1972.
 When the analyte is a biomolecule, any recognition moiety which interacts
 with the biomolecule is useful in practicing the present invention. Thus,
 when the analyte is a nucleic acid, in one embodiment, the recognition
 moiety is a nucleic acid having a sequence which is at least partially
 complementary to the recognition moiety sequence. When the recognition
 moiety is a peptide, an antibody specific for that peptide can be used as
 the analyte. In another preferred embodiment, a protein, other than an
 antibody (e.g., enzyme, receptor) is the analyte.
 In a presently preferred embodiment, the recognition moiety interacts with
 biotin and is avidin or an anti-biotin antibody. Other recognition
 moieties of use when the analyte is a biomolecule will be apparent to
 those of skill in the art.
 F. Compound Libraries
 The synthesis and screening of chemical libraries to identify compounds
 which have novel pharmacological and material science properties is a
 common practice. Libraries which have been synthesized include, for
 example, collections of oligonucleotides, oligopeptides, small or large
 molecular weight organic or inorganic molecules. See, Moran et al., PCT
 Publication WO 97/35198, published Sep. 25, 1997; Baindur et al., PCT
 Publication WO 96/40732, published Dec. 19, 1996; Gallop et al., J. Med.
 Chem. 37:1233-51(1994).
 Thus, in a fourth aspect, the invention provides a device for synthesizing
 and screening a library of compounds, comprising:
 (1) a synthesis component, comprising:
 (a) a first substrate having a surface;
 (b) a self-assembled monolayer on said surface, said monolayer comprising a
 reactive functionality; and
 (2) an analysis component, comprising:
 (a) a second substrate having a surface; and
 (b) a mesogenic layer between said surface of said first substrate and said
 surface of said second substrate.
 In a preferred embodiment, the second substrate has a self-assembled
 monolayer attached thereto. In yet another preferred embodiment, the
 second substrate is permeable to liquids, vapors, gases and combinations
 thereof. The permeable substrate allows analytes to come into contact with
 the self-assembled monolayer(s) and the mesogenic layer, while maintaining
 the overall integrity of the optical cell.
 The discussion above concerning substrates, organic layers and mesogenic
 layers is applicable to each of the embodiments of this aspect of the
 invention. In a presently preferred embodiment, the substrate comprises a
 metal film. In a further preferred embodiment, the metal film is a member
 selected from the group consisting of gold, nickel, platinum, silver,
 palladium and copper. In a still further preferred embodiment, the metal
 film is obliquely deposited.
 The organic layer can be constructed of any organic substance which
 associates with the substrate, preferably, the organic layer constituents
 are moieties selected from the group consisting of alkanethiols,
 functionalized alkanethiols and combinations thereof. In a further
 preferred embodiment, at least one component of the organic layer is a
 moiety which is a member selected from the group consisting of R.sup.21
 CH.sub.2 (CH.sub.2).sub.14 SH and R.sup.31 CH.sub.2 (CH.sub.2).sub.15 SH,
 wherein R.sup.21 and R.sup.31 are independently members selected from the
 group consisting of hydrogen, reactive groups and recognition moieties.
 The discussion above concerning reactive groups is equally applicable to
 this aspect of the invention. In certain preferred embodiments, R.sup.21
 and R.sup.31 are independently members selected from the group consisting
 of hydrogen, amine, carboxylic acid, carboxylic acid derivatives,
 alcohols, thiols, alkenes and combinations thereof.
 The SAM can be patterned by any of the above-discussed methods for
 producing patterned substrates and organic layers. The discussion above
 concerning the patterning of substrates and the construction of organic
 layers from a mixture of components having different properties is
 generally applicable to this embodiment of the invention. In a presently
 preferred embodiment, the SAM is patterned by microcontact printing. In a
 further preferred embodiment, the microcontact printing utilizes a
 component which is distinct from the components of the self-assembled
 monolayer.
 The mesogenic layer can comprise one or more mesogenic compounds. The
 discussion above concerning the nature of the mesogenic layer is generally
 applicable to this embodiment of the invention. In a presently preferred
 embodiment, the mesogenic layer comprises a mesogen which is a member
 selected from the group consisting of 4-cyano-4'-pentylbiphenyl,
 N-(4-methoxybenzylidene)4-butylanailine and combinations thereof.
 In another preferred embodiment, the present invention provides a method
 for synthesizing and analyzing a combinatorial library of compounds using
 the above described device. The method comprises,
 (a) adding a first component of a first compound to a first region of said
 surface of said first substrate and a first component of a second compound
 to a second region of said surface of said first substrate;
 (b) adding a second component of said first compound to said first region
 of said surface of said first substrate and adding a second component of
 said second compound to said second region on said surface of said first
 substrate;
 (c) reacting said first and second components to form a first product and a
 second product;
 (d) applying said mesogenic layer to said surface of said first substrate;
 (e) adding an analyte to said first region and said second region; and
 (f) detecting said switch in said mesogenic layer from a first orientation
 to said second orientation, whereby said analyzing is achieved.
 The sequential addition of components can be repeated as many times as
 necessary in order to assemble the desired library of compounds.
 Additionally, any number of solvents, catalysts and reagents necessary to
 effect the desired molecular transformations can be added before,
 concurrently or after the addition of the component.
 Virtually any type of compound library can be synthesized using the method
 of the invention, including peptides, nucleic acids, saccharides, small
 and large molecular weight organic and inorganic compounds.
 In a presently preferred embodiment, when the synthesis is complete, a
 second substrate is layered on top of the mesogenic layer. In a further
 preferred embodiment, the second substrate has an attached second
 self-assembled monolayer contacts said mesogenic layer. The discussion
 above concerning the permutations available when two substrates are
 utilized is generally applicable to this embodiment. In a still further
 preferred embodiment, the second substrate is a permeable substrate. In
 yet another preferred embodiment, the second substrate is patterned
 similar to the first substrate.
 In a presently preferred embodiment, the libraries synthesized comprise
 more than 10 unique compounds, preferably more than 100 unique compounds
 and more preferably more than 1000 unique compounds.
 In a fifth aspect, the present invention also provides a library of
 compounds synthesized on a self-assembled monolayer. The discussion above
 concerning libraries, SAMs, functionalized SAM components, mesogenic
 layers, and the like is generally applicable to this aspect of the
 invention.
 G. The Device
 The device of the present invention can be of any configuration which
 allows for the support of a mesogenic layer on an organic layer. The only
 limitations on size and shape are those which arise from the situation in
 which the device is used or the purpose for which it is intended. The
 device can be planar or non-planar. Thus, it is within the scope of the
 present invention to use any number of polarizers, lenses, filters lights,
 and the like to practice the present invention.
 Although many changes in the mesogenic layer can be detected by visual
 observation under ambient light, any means for detecting the change in the
 mesogenic layer can be incorporated into, or used in conjunction with, the
 device. Thus, it is within the scope of the present invention to use
 lights, microscopes, spectrometry, electrical techniques and the like to
 aid in the detection of a change in the mesogenic layer.
 In those embodiments utilizing light in the visible region of the spectrum,
 the light can be used to simply illuminate details of the mesogenic layer.
 Alternatively, the light can be passed through the mesogenic layer and the
 amount of light transmitted, absorbed or reflected can be measured. The
 device can utilize a backlighting device such as that described in U.S.
 Pat. No. 5,739,879, issued to Tsai, T.-S on Apr. 14, 1998. Light in the
 ultraviolet and infrared regions is also of use in the present invention.
 Microscopic techniques can utilize simple light microscopy, confocal
 microscopy, polarized light microscopy, atomic force microscopy (Hu et
 al., Langmuir 13:5114-5119 (1997)), scanning tunneling microscopy (Evoy et
 al., J. Vac. Sci. Technol A 15:1438-1441, Part 2 (1997)), and the like.
 Spectroscopic techniques of use in practicing the present invention
 include, for example, infrared spectroscopy (Zhao et al., Langmuir
 13:2359-2362 (1997)), raman spectroscopy (Zhu et al., Chem. Phys. Lett.
 265:334-340 (1997)), X-ray photoelectron spectroscopy (Jiang et al.,
 Bioelectroch. Bioener. 42:15-23 (1997)) and the like. Visible and
 ultraviolet spectroscopies are also of use in the present invention.
 Other useful techniques include, for example, surface plasmon resonance
 (Evans et al., J. Phys. Chem. B 101:2143-2148 (1997), ellipsometry (Harke
 et al., Thin Solid Films 285:412-416 (1996)), impedometric methods
 (Rickert et al., Biosens. Bioelectron. 11:757:768 (1996)), and the like.
 In a presently preferred mode of using the device of the present invention,
 the optical cell comprises two substrates that are spaced from about 10
 micrometers to about 10 millimeters apart, preferably from about 20
 micrometers to about 5 millimeters apart, more preferably from about 50
 micrometers to about 0.5 millimeters apart. In this embodiment, the
 analyte is drawn into the optical cell by any of a number of techniques
 including, but not limited to, capillarity, electroosmosis,
 electophoresis, and centrifugation. Once the analyte has entered the
 optical cell, it is then displaced by drawing a mesogenic phase into the
 cell.
 In yet another preferred embodiment, the optical cell (i.e., substrate) is
 of approximately cylindrical cross-section and the recognition moieties
 are attached to the inner surface of the cylinder.
 In a seventh aspect, the invention provides a low energy surface having a
 mesogenic layer anchored planarly thereon. Low energy surfaces offer the
 advantage of being easy to clean. Thus, devices constructed from these
 surfaces have fewer defects and will display enhanced optical proerties.
 In an eighth aspect, the invention provides a method for controlling tilt
 in an organic layer comprising a haloorganosulfur moiety, having a halogen
 content, adsorbed onto a substrate, the method comprising selecting the
 halogen content of the haloorganosulfur. In a preferred embodiment, the
 tilt is selected to provide a desired optical texture in a mesogenic
 layer.
 Thus, in another aspect, the invention provides a method for varying the
 optical texture of a mesogenic layer comprising a haloorganosulfur. The
 haloorganosulfur has a halogen content. The optical texture of the
 mesogenic layer is controlled by selecting the halogen content of the
 haloorganosulfur.
 Other techniques and devices of use in the present invention will be
 apparent to those of skill in the art.
 The following examples further illustrate the invention and should not be
 construed as further limiting. The contents of all references, patents and
 patent applications cited throughout this application are expressly
 incorporated by reference.
 EXAMPLES
 The detailed examples which follow illustrate the device and methods of the
 invention as applied to amplifying, and transducing into an optical
 signal, the interaction of a recognition moiety hosted in a self-assembled
 monolayer and an analyte which interacts with the recognition moiety.
 Example 1 illustrates the use of SAMs bearing biotin to detect avidin and
 an anti-biotin antibody (goat anti-biotin). The binding of avidin or an
 antibody to the biotin produces a marked change in the appearance of the
 mesogenic layer which allows the presence of both the avidin and
 anti-biotin to be detected by visual inspection.
 Example 2 illustrates the use of a SAM bearing a carboxylic acid
 recognition moiety to detect the presence of hexylamine vapor. Similar to
 the results in example 1, the binding of the analyte to the recognition
 moiety produced a marked change in the appearance of the mesogenic layer,
 which could be visually detected.
 Example 3, illustrates that the orientation of a mesogenic layer is
 dependent on the ionization state and pKa of acidic recognition moieties
 on the SAM components. The liquid crystal used in Example 3 is a nematic
 liquid crystal and the SAM is formed from (.omega.-mercaptoundecanoic
 acid.
 Example 4 illustrates the quantitative detection of metal ions by their
 binding to SAMs with carboxylic acid terminal groups. Similar to the
 examples above the binding is amplified and transduced into an optical
 signal.
 Example 5 demonstrates the patterning of SAMs on a substrate. Further,
 Example 5 demonstrates that the anchoring orientation of a mesogenic layer
 can be controlled by the nature of the SAM components and the features of
 the pattern.
 Example 6 demonstrates that the anchoring of mesogneic layers can be varied
 by using surfaces comprising fluorinated organosulfur compounds.
 EXAMPLE 1
 Example 1 illustrates the amplification and transduction into optical
 outputs of receptor-mediated binding of proteins at surfaces.
 Spontaneously organized surfaces hosting ligands were designed so that
 protein molecules, upon binding to the ligands triggered changes in 1- to
 20-micrometer thick films of supported liquid crystals.
 Surfaces were designed with nanometer-scale topographies that could be
 erased by the specific binding of a protein to surface-immobilized ligands
 (FIG. 1A), thus leading to macroscopic changes in the orientations of
 liquid crystals supported on these surfaces. First, thin fins of
 polycrystalline gold were prepared (FIG. 1B) with roughnesses
 characterized by a maximum amplitude of .apprxeq.2 nm and a maximum
 wavelength of .apprxeq.50 nm (FIG. 1C). The deposition of the gold films
 was controlled so as to introduce an anisotropic roughness within the
 films (called hereafter "anisotropic gold films (V. K. Gupta et al.,
 Langmuir 12, 2587 (1996)). Although subtle, the anisotropic roughness was
 easily detected by observing the orientations of supported liquid crystals
 (V. K. Gupta et al., Langmuir 12, 2587 (1996)). Second, mixed,
 self-assembled monolayers (SAMs) were formed from Biotin-(CH.sub.2).sub.2
 [(CH.sub.2).sub.2 O].sub.2 NHCO(CH.sub.2).sub.11 SH (BiSH) (J. Spinke et
 al., J. Chem. Phys. 99, 7012 (1993)) and CH.sub.3 (CH.sub.2).sub.7 SH
 (C.sub.8 SH) by immersion of the films of anisotropic gold in ethanolic
 solutions containing 9.6 .mu.M of BiSH and 70.4 .mu.M of C.sub.8 SH for 8
 hours (Mixed SAMs were also formed in a few minutes by using solutions
 that contained millimolar concentrations of the organothiols). The mixed
 SAMs were estimated to consist of 27% biotinylated species by linear
 interpolation of thicknesses (.DELTA.) of single component SAMs formed
 from BiSH (.DELTA..sub.BiSH =3.8 nm) and C.sub.8 SH (.DELTA..sub.C8SH =1
 nm) (All thickness measurements were performed using a Rudolph Auto
 ellipsometer with light (633 nm) incident at an angle of 70.degree.. A
 refractive index of 1.45 was used to estimate the thickness of bound
 layers of thiols and proteins. Standard deviations of ellipsometric
 thicknesses (.DELTA.) reported in this paper are +/-0.2 nm). Binding of
 the protein avidin (Av, 4.2 nm.times.4.2 nm.times.5.6 nm) (P. C. Weber et
 al., Science, 243, 85 (1989)) to biotin hosted within these SAMs was
 achieved by incubating the SAMs for 10-15 minutes in phosphate-buffered
 saline (PBS) (pH 7.4, 100 mM NaCl, 0.004% by volume Triton X-100)
 containing 0.5 .mu.M of Av (K. L. Prime et al., J. Am. Chem. Soc. 115,
 10714 (1993)). The surfaces were then rinsed in deionized water for
 .about.30 seconds and dried with a stream of nitrogen for .about.30
 seconds. To form liquid crystal cells, two SAMs were spaced apart using
 thin plastic film Mylar.TM. or Saranwrap.TM.) and then secured using paper
 clips (FIG. 2). Using capillarity, a drop of 4-cyano-4'-pentylbiphenyl
 (5CB) was drawn in its isotropic phase (isotropic-nematic transition
 .about.34.degree. C.) into the cavity formed by the two surfaces. The
 liquid crystal was then cooled towards room temperature: a nematic texture
 was observed to spread across a 1 cm.times.1 cm-sized cell in .about.5-10
 seconds. Optical images of the cell were recorded on a polarization
 microscope using transmission mode.
 When two mixed SAMs supported on anisotropic gold films were paired to form
 a liquid crystal cell, the polarized light image of the liquid crystal
 cell was uniform and featureless (FIG. 3A). The liquid crystal within the
 cell was, therefore, uniformly oriented (FIG. 2A). When a second liquid
 crystal cell was prepared using mixed SAMs that were pretreated with PBS
 containing Av prior to filling with liquid crystal (.DELTA..sub.Av =2.6
 nm), the polarized light image was highly non-uniform and colored (FIG.
 3B). The orientation of the liquid crystal showed no memory of the
 anisotropic roughness of the gold film (When rotated between crossed
 polars, the intensity of light transmitted through the sample did not show
 a large modulation in intensity. This result indicates the absence of a
 preferred orientation of the liquid crystal within the cell. The general
 features of the optical textures were not influenced by variations in
 rates of cooling of the liquid crystal to the ambient temperature) and
 resembled optical images of liquid crystal supported on mixed SAMs formed
 on gold films with no anisotropic roughness (FIG. 3C). In contrast, the
 liquid crystal remained uniformly oriented when mixed SAMs were pretreated
 with PBS containing Av blocked with biotin (100-fold excess)
 (.DELTA..sub.blkd Av =0.9 nm, FIG. 3D) or a SAM formed from C.sub.8 SH
 that was pretreated in PBS containing Av (.DELTA..sub.Av =0.4 nm) (K. L.
 Prime et al., J. Am. Chem. Soc. 115, 10714 (1993)). Therefore, specific
 binding of Av to mixed SAMs erases the effect of the nanometer-scale,
 anisotropic roughness of the gold on the orientation of the bulk liquid
 crystal and thus leads to a readily visualized change in the optical
 texture of the liquid crystal cell. It was estimated that within a 1
 mm.sup.2 area of the mixed SAM (an easily visible area), .about.10.sup.10
 Av molecules (.about.1 ng or .about.2.6 nm of coverage) control the
 orientations of .about.2.times.10.sup.15 mesogens (a 2 .mu.m-thick film of
 liquid crystal). The binding of each Av molecule to the surface is,
 therefore, amplified into a reorientation of &gt;10.sup.5 mesogens. Because
 less than half a monolayer of Av can change the orientation of the liquid
 crystal, and because liquid crystal films as thick as 100 .mu.m can be
 oriented by surfaces, higher levels of amplification are possible (it has
 been demonstrated that specific binding of Av can cause reorientation of
 films of liquid crystals as thick as 20 .mu.m (.about.2.times.10.sup.6
 mesogens/protein).
 Because the binding of Av to biotin is unusually strong for a
 protein-ligand interaction (dissociation constant,
 K.sub.d.about.10.sup.-15 M), the use of liquid crystals to detect the
 binding of antibodies to antigens (K.sub.d 10.sup.-9 M) was also
 demonstrated (H. Bagci et al., FEBS, 322, 47 (1993)). For example, the
 binding of affinity isolated, goat anti-biotin antibody (anti-Bi IgG)
 (Anti-Bi IgG was purchased from Sigma BioScience and antiFITC IgG was
 purchased from Molecular Probes. All measurements were performed in PBS
 containing 0.5 .mu.M anti-Bi IgG and 0.004% Triton X-100. After binding
 the IgG in PBS, the samples were rinsed with deionized water and dried
 under a stream of nitrogen) to a mixed SAM formed from BiSH and C.sub.8 SH
 (.DELTA..sub.anti-Bi IgG =5.5 nm) caused the orientation of a supported
 liquid crystal to become non-uniform (FIG. 3E). In contrast, neither a
 non-specific antibody such as rabbit polyclonal anti-fluorescein antibody
 (anti-FITC IgO, .DELTA..sub.anti-FITC IgC =0 nm) (FIG. 3F) nor bovine
 serum albumin (BSA, .DELTA.BSA=1.4 nm) (the optical texture was the same
 as FIG. 3F) caused a change in the orientation of the liquid crystal. In
 addition, a SAM formed from C.sub.8 SH did not significantly bind anti-Bi
 IgG (.DELTA..sub.anti-Bi IgG =0.1 nm) and thus oriented 5CB uniformly (the
 optical texture was the same as FIG. 3F).
 The results above demonstrate two further principles. First, it is possible
 to control the anisotropy within gold films so that the immobilization of
 ligands (such as BiSH) on these surfaces does not disturb the uniform
 orientation of the liquid crystal prior to binding of proteins.
 Oligopeptides (e.g., Ala-Ala-Pro-Phe) have also been introduced into SAMs
 without disturbing the uniform orientation of liquid crystals (Uniform
 anchoring of nematic 5CB was measured on mixed SAMs formed on anisotropic
 gold films by coadsorption from an ethanolic solution of 9 mM C.sub.11 SH
 and 1 mM HS(CH.sub.2).sub.11 -Ala-Ala-Pro-Phe-pNA, where Ala is alanine,
 Pro is proline, Phe is phenylalanine and pNA is p-nitroanilide.).
 Second, the roughness of the gold film used in these experiments was such
 that the threshold surface concentration of Av or anti-Bi IgG needed to
 change the orientation of 5CB was greater than the level of non-specific
 adsorption but less than specific adsorption. This characteristic makes
 possible a sandwich-type assay in which a capture protein (macromolecular
 ligand) is supported on a surface, and the binding of a second protein
 (e.g., detecting antibody) to the capture protein is detected by a change
 in orientation of the liquid crystal. To demonstrate this principle, a
 mixed SAM was first treated with fluorescein-labeled avidin (FITC-Av) for
 10 minutes (Fluorescein-labeled streptavidin (FITC-Av) was purchased from
 Pierce. All measurements were performed in PBS containing 0.5 .mu.M
 FITC-Av and 0.004% Triton X-100. After binding the FITC-Av in PBS, the
 samples were rinsed with deionized water.). The bound FITC-Av
 (.DELTA..sub.FITC-Av =1 nm) was below the threshold required to trigger a
 change in the orientation of 5CB (FIG. 3G). The SAM supporting the bound
 FITC-Av was immersed into a solution of 0.5 .mu.M anti-FITC IgG in PBS.
 The ellipsometric thickness of the bound protein after the second step was
 3.5 nm and thus sufficient to trigger a change in the orientation of the
 liquid crystal (FIG. 3H). Anti-FITC IgG did not bind to a mixed SAM in the
 absence of bound FITC-Av (.DELTA..sub.anti-FITC IgG =-0.1 nm) nor did
 anti-FITC IgG blocked with fluorescein bind to a surface presenting
 FITC-Av (.DELTA..sub.FITC-Av/anti-FITC IgG =0.7 nm): both control
 experiments produced uniformly oriented liquid crystals (FIG. 3F and 3I).
 By repeating the above experiments using Av, and by binding anti-Av IgG to
 an antigenic epitope on Av, concentrations of anti-Av IgG in solution as
 low as 2.3 nM have been detected (Studies based on stress-induced
 chromatic transitions in polymer films have reported limits of detection
 for specific binding of pentavalent cholera toxin to ganglioside G.sub.M1
 (molecular weight .about.10.sup.5 Da, K.sub.d.about.10.sup.-10 M) to be
 100 ppm (.about.1 .mu.M) when using liposomes in solution and 20 ppm
 (.about.0.2 .mu.M) when using supported films of the polymer (D. Charych
 et al, Science 261, 585 (1993); D. Charych et al, Chem & Biol 3, 113
 (1996); J. Pan et al., 13, 1365 (1997)).
 Twisted nematic liquid crystals (TN liquid crystals) are widely used in
 flat panel displays because reorientation of the twisted liquid crystal by
 an electric field provides high optical contrast ratios (The surfaces of a
 TNliquid crystal cell are designed such that the region of liquid crystal
 in contact with one surface is oriented at right angles to the region of
 liquid crystal in contact with the opposing surface (FIG. 2B). The liquid
 crystal sandwiched between the two surface regions of the cell undergoes a
 90.degree. twist-type deformation, and the polarization of linearly
 polarized light transmitted through such a cell is rotated by 90.degree..
 A twisted liquid crystal cell, when viewed between two
 parallel-polarizers, appears dark. In contrast, a cell containing liquid
 crystal that is not twisted appears bright between parallel polars (Liquid
 crystals: APPLICATIONS AND USES, B. Bahadur, Ed. (World Scientific,
 Singapore, 1990).). TNliquid crystals were also used to enhance the
 optical transduction of biotin-mediated binding of avidin to surfaces
 (FIG. 4). Optical read-out of the binding of proteins and ligands at
 surfaces can be further facilitated by using patterned SAMs (A. Kumar, et
 al., Acc. Chem. Res. 28,219 (1995), V. K. Gupta et al., Science 276, 1533
 (1997)). Surfaces were designed such that binding of Av to
 biotin-derivatized regions of a patterned SAM caused area-specific
 untwisting of a TNliquid crystal cell (FIG. 5). Patterns so formed with
 sizes of a few centimeters provide an easily read indicator of the
 presence of a biomolecule in solution (FIG. 5A and 5B). By using
 micrometer-sized patterns, it was also demonstrated that the binding of
 biomolecules at surfaces can be detected optically by the diffraction of
 light from periodic liquid crystal structures which form only when the
 biomolecules are bound to the surfaces (FIG. 5C-E).
 EXAMPLE 2
 The following example illustrates the use of a SAM functionalized with a
 carboxylic acid moiety to detect the presence of hexylamine vapor.
 Liquid crystals supported on surfaces can be used to detect the presence of
 small organic molecules (e.g., airborne pollutants such as hexylamine) or
 ions (e.g., heavy metals). The following experiment was designed to
 explore the effect of a relatively simple, in situ change in the structure
 of a surface (i. e.,transformation of a carboxylic acid into a amine salt)
 on the orientation of a supported liquid crystal.
 The model system used comprised a 4-cyano-4'-pentylbiphenyl (5CB) liquid
 crystal supported on SAMs formed from HS(CH.sub.2).sub.10 COOH on
 obliquely deposited films of gold. n-Hexylamine was used as a model small
 organic molecule. The amine was introduced into the liquid crystal device
 in the vapor phase.
 Experiments were performed to determine whether the reorientation of a 5CB
 liquid crystal supported on monolayers terminated with carboxylic acid in
 the presence of vapor phase n-hexylamine was truly a surface induced
 phenomena. Our experiments compared 5CB orientation on 2 different
 monolayers (each exhibiting different surface functional groups) within
 the same n-hexylamine atmosphere. One surface was the HS(CH.sub.2).sub.10
 COOH monolayer. In the present example, the COOH terminal group is shown
 to interact with n-hexylamine and induce a reorientation of 5CB. The other
 monolayer was formed from HS(CH.sub.2).sub.15 CH.sub.3 which terminates in
 a methyl group. The methyl group is, unreactive towards n-hexylamine.
 Optical cells were formed with SAMs of HS(CH.sub.2).sub.10 COOH or
 HS(CH.sub.2).sub.15 CH.sub.3 and subsequently filled with 5CB. FIG. 6
 illustrates a scheme for an in situ sensor, wherein the transitions in
 orientations of the mesogenic layer caused by small molecules at surfaces
 transduce molecular events into bulk phenomena. FIG. 7a illustrates the
 schematic of vapor diffusion of n-hexylamine into these optical cells.
 FIG. 7b and 7c,d show photographs of these optical cells in a n-hexylamine
 atmosphere over time. No change in the 5CB orientation was observed for
 cell with the SAM formed from HS(CH.sub.2).sub.15 CH.sub.3. All the images
 show that the cell is dark. However, as shown in FIG. 7d, a drastic change
 in the orientation of 5CB was observed traveling from the edge of the cell
 inwards as time progressed. The edge of the optical cell was no longer
 dark and the thickness increases with time.
 The cell photographed in FIG. 7c was exposed to a very low vapor
 concentration of n-hexylamine while the cell in FIG. 7d was exposed to
 higher vapor concentrations. FIG. 8 demonstrates the effect of exposing
 the device to hexylamine over time. The cells shown in FIG. 8a are shown 8
 hours after initial exposure. The cells in FIG. 8b are shown 19 hours
 after exposure.
 These experiments indicate the change in 5CB orientation is induced by an
 interaction between the carboxylic acids at the surface of the SAM and the
 vapor phase analyte, hexylamine.
 EXAMPLE 3
 Example 3 illustrates the pH-dependent orientations of liquid crystals
 supported on self-assembled monolayers. The liquid crystal used in Example
 3 is a nematic liquid crystal. The self-assembled monolayer is formed from
 .omega.-mercaptoundecanoic acid.
 3.1 Materials
 HS(CH.sub.2).sub.10 COOH was synthesized using published methods and
 characterized by NMR spectroscopy (MP 46.5-47.degree. C). The liquid
 crystals tested, 5CB (K15, BDH, T.sub.ni =34.5.degree. C.) and MBBA (TCI
 and Aldrich T.sub.ni =40.degree. C.) have a nematic phase at room
 temperature.
 3.2 Methods
 (3.2a) Cleaning of substrates.
 Microscope slides made from premium float glass (Fishers' Finest) were used
 in these experiments. These slides were cleaned in piranha solution (70%
 H.sub.2 SO.sub.4, 30% H.sub.2 O.sub.2) and then in a base solution (70%
 KOH, 30% H.sub.2 O.sub.2) under nitrogen agitation for 1 hour at
 50.degree. C. Between solutions and after the base wash, the slides were
 rinsed thoroughly in deionized water at 18.2 M .OMEGA. (Millipore). The
 slides were subsequently rinsed in ethanol followed by methanol. This step
 caused the slides to dry without residual spots. The slides were then
 dried in nitrogen and stored in a vacuum oven at 110.degree. C. Storage in
 the oven minimized water adsorption onto the glass slides. All other
 glassware was cleaned in piranha solution prior to use.
 (3.2b) Deposition of gold.
 Semi-transparent films of gold (approximately 100 .ANG. in thickness) were
 evaporated by electron beam (CH A Industries) onto stationary microscope
 slides from a fixed direction with 50.degree. incidence from the surface
 normal. A 20 .ANG. layer of titanium was used to promote adhesion between
 the glass and the gold. The rate of gold and titanium deposition was
 carefully controlled to 0.2 .ANG./sec within a system pressure less than
 1.times.10.sup.-6 Torr. In order to maintain high quality films the gold
 source was routinely cleaned in 3-4 cycles of aqua regia and piranha
 solutions at 50.degree. C. for 30 minutes in each solution. This cycle was
 repeated 3-4 times with rinses in deionized water between each solution.
 (3.2c) Formation of SAMs.
 SAMs were formed in 1 mM HS(CH.sub.2).sub.10 COOH in ethanol for 1 hour.
 The SAMs were then immersed for approximately one minute in aqueous, pH
 solutions buffered between pH 2-12 and then blown dry with a stream of
 nitrogen gas to displace excess solution from the surface. Unless stated
 differently, the buffers were formed using the following salts: pH 1-2,
 0.1 M H.sub.3 PO.sub.4 ; pH 2.5-3.0, 1 mM NaH.sub.2 PO.sub.4 /H.sub.3
 PO.sub.4 ; pH 4-5, 1 mM NaO.sub.2 CCH.sub.3 /HO.sub.2 CCH.sub.3 ; pH 6-7,
 1 mM Na.sub.2 HPO.sub.4 /NaH2PO4; pH 8-9, 1 mM Na.sub.2 CO.sub.3
 /NaHCO.sub.3 ; pH 9-11, 1 mM Na.sub.2 HPO.sub.4 /Na.sub.3 PO.sub.4 ; pH
 11.5-12, 10 mM NaOH; pH 12-13, 0.1 M NaOH. The same counterion, Na+, was
 used throughout. Experiments were also performed using 0.01 mM-1 mM HCl.
 (3.2d) Anchoring of LCs.
 he anchoring of liquid crystals was studied by constructing optical cells
 from SAMs formed from HS(CH.sub.2).sub.10 COOH on each surface at same pH
 or from one surface formed from HS(CH.sub.2).sub.10 COOH and the opposing
 surface formed from CH.sub.3 (CH.sub.2).sub.15 SH. The evaporation
 direction between the opposing gold surfaces in the cell was oriented in
 the same direction. The surfaces were separated by mylar spacers with
 nominal thickness of 2, 12, and 30 .mu.m and clamped together using binder
 clips. By interferometry techniques, 15-20% variation was observed for
 nominal cell thicknesses of 12, 30 .mu.m. The thinner, 2 .mu.m nominal
 thickness had greater variation, ranging from 2-4 .mu.m. The cells were
 filled with liquid crystal by capillarity at a temperature above the
 clearing point in the isotropic state. The resultant optical texture was
 analyzed with a polarizing microscope (Olympus) after the cells were
 cooled to room temperature.
 Surfaces presenting carboxylic acid groups and sodium carboxylate groups
 were prepared by immersion of the SAMs in aqueous solutions at low and
 high pH. The orientations of liquid crystals within cells (thickness 2-4
 .mu.m) was measured using SAMs pretreated at high and low pH.
 3.3 Results
 First, the out-of-plane orientation of the liquid crystals on SAMs
 pretreated at low and high pH was measured. Near planar orientation was
 observed using the crystal rotation technique. The polar angle from the
 surface was less than 1.degree., for 5CB.
 Second, the in-plane (azimuthal) orientation of the liquid crystal was
 measured by using polarized light microscopy. The in-plane orientation of
 liquid crystal with respect to the gold evaporation direction was
 determined by using a quarter wave plate (QWP) and a thin 2 .mu.m cell
 prepared with SAMs (at low or high pH) filled with liquid crystal. Using a
 QWP, the orientation of the director was determined by rotating the cell
 until the greatest the shift in retardation between the slow axis of the
 nematic director and the optical axis of the QWP was observed. The shift
 in retardation was measured on a Michel-Levy color chart from the first
 and second order interference colors. Whereas no changes were observed in
 the out-of-plane orientation of the liquid crystals as a function of the
 pH of pretreatment, the in-plane orientations of nematic 5CB and MBBA were
 observed to be different when both surfaces were pretreated at low and
 high pH. Under these pretreatments, a uniform texture of liquid crystal
 was observed throughout the cell. The in-plane orientation of the 5CB and
 MBBA, however, was observed to shift 90.degree. based on the pH
 pretreatment of the surface at pH 2.5 (low pH) and 11.7 (high pH).
 In cells filled with 5CB or MBBA, using surfaces immersed at pH 2.5, the
 liquid crystal oriented parallel to the direction of gold deposition as
 illustrated in FIG. 9a. However on monolayers conditioned at pH 11.7, the
 liquid crystals oriented perpendicular to the direction of gold deposition
 as shown in FIG. 9b. In both cases, there were no elastic deformation
 (twist, bend, or splay) in the bulk liquid crystal. These SAMs also
 exhibited reversible properties for orienting 5CB. Pretreatment of the SAM
 at pH 3.0 and subsequently at pH 11.7 resulted in 5CB orientation
 perpendicular to the deposition direction. The opposite pretreatment
 scheme results in parallel alignment.
 Although the liquid crystals are known to contain significant amounts of
 water that could potentially erase the effect of the pretreatment of the
 surfaces (and thus the influence of the pretreatment of the surfaces on
 the orientations of the liquid crystals), the results described above
 demonstrate that this is not the case. The effect of the pretreatment of
 the liquid crystal changes the orientation of the liquid crystal. The
 concentration of water in our samples of 5CB was 42.+-.7 mM as measured by
 Karl Fischer titration.
 As described below, this effect can be further evidenced by the lateral
 patterning of a surface with COOH and COO.sup.- Na.sup.+ regions and
 observing the orientation of the liquid crystal in the vicinity of the
 boundary between the low and high pH regions. FIG. 10c shows the optical
 texture of a liquid crystal cell prepared by forming a SAM of
 HS(CH.sub.2).sub.15 CH.sub.3 on one surface while the opposing surface was
 formed from HS(CH.sub.2).sub.10 COOH. The entire surface of
 HS(CH.sub.2).sub.10 COOH was pretreated at pH 3.0 and dried in nitrogen.
 This surface was then reversibly treated by half-dipping at pH 11.7 and
 carefully drying the surface in nitrogen. The anchoring of the liquid
 crystal was observed to be orthogonal on the adjacent regions of the acid
 surface pretreated at differing pHs. If ion exchange between the surfaces
 and the bulk liquid crystal was occurring, then time-dependent changes in
 the vicinity of this boundary would be observed. No change in the
 anchoring of the liquid crystal in the vicinity of the boundary over a
 period of 48 hours was observed.
 In cells designed with SAMs of HS(CH.sub.2).sub.15 CH.sub.3 on one surface
 and HS(CH.sub.2).sub.10 COOH on the opposing surface, pH pretreatment of
 HS(CH.sub.2).sub.10 COOH, can be used to induce a bulk elastic deformation
 of the liquid crystal. As illustrated in FIG. 10a, at low pH, 5CB was
 uniformly oriented since the same in-plane liquid crystal orientation was
 imposed by both surfaces. At high pH, the monolayer of HS(CH.sub.2).sub.10
 COOH imposed an in-plane boundary condition orthogonal to the
 HS(CH.sub.2).sub.15 CH.sub.3 surface resulting in a twisted bulk
 orientation for the liquid crystal. This result demonstrated that the
 strength of anchoring on both surfaces was sufficient to create a
 deformation in the bulk which rotated the polarization of light by
 90.degree..
 In this cell, of nominal thickness 12 .mu.m, 5CB was sandwiched between
 SAMs formed from HS(CH.sub.2).sub.15 CH.sub.3 and HS(CH.sub.2).sub.10 COOH
 at pH 3.0 (region I) or pH 11.7 (region II). When viewed through cross
 polars (FIG. 10c), region I which was composed of surfaces anchoring the
 nematic director in the same direction appears dark due to the extinction
 of transmitted light. The bulk orientation of the liquid crystal was
 uniform and along a single direction. In region II light was uniformly
 transmitted through cross polars suggesting the bulk orientation of the
 liquid crystal was twisted.
 Observation under parallel polars (90.degree. rotation of the analyzer) as
 shown in FIG. 10d indicated that region I turned bright while region II
 turned dark. This result indicates an approximate 90.degree. twist in
 region II but not region I. The bulk orientation of 5CB can be controlled
 between uniform and twisted orientations in cells with surfaces supporting
 SAMs formed from HS(CH.sub.2).sub.15 CH.sub.3 and SAMs formed from
 HS(CH.sub.2).sub.10 COOH (at high or low pH).
 How the liquid crystal bulk orientation changes in 12 .mu.m cells with
 surfaces formed from HS(CH.sub.2).sub.15 CH.sub.3 and HS(CH.sub.2).sub.10
 COOH as a function of pH between 1.7 and 13.2 was also investigated. The
 transition between a uniformly aligned cell to a twisted cell for SAMs
 formed from HS(CH.sub.2).sub.10 COOH occurred, discontinuously between pH
 3.8-4.0. The transition is visually illustrated in FIG. 11a at each pH
 through cross polars. Intermediate twist angles were not observed,
 however, at pH 3.8, twisted regions with dimensions of 100-1000 .mu.m were
 observed within the uniformly oriented sample. The change in orientation
 from uniform to twisted alignment occurred through the proliferation of
 90.degree. twisted domains of liquid crystal.
 The rotation of the polarization through the cell filled with 5CB provided
 a simple, quantitative method of observing the discontinuous change in;
 5CB alignment. The twist angle was determined by simultaneously rotating
 the analyzer and the optical cell with respect to the polarizer to a
 minimum intensity. The twist angle as a function of pH is illustrated in
 FIG. 11b. A sharp discontinuity between pH 3.8 and pH 4.0 indicated a
 sharp, discontinuous, 90.degree. in-plane reorientation of 5CB.
 Loop disclinations formed in twisted areas as shown in region II in FIG.
 10c, 10d and FIG. 11a at pH 11.7, 12.7. The twist angle within these loops
 were, in general, the supplementary angle to the measured twist angle of
 the overall phase. The disclination line appeared dark between cross
 polars and bright between parallel polars indicating a disclination line
 of strength S=1/2.
 Twist angles for cells pretreated at pH&gt;3.8 were approximately
 95-105.degree.. A 5-10.degree. error occurred from the glass slides being
 slightly twisted on the sample holders during the evaporation process.
 Therefore the gold was not deposited exactly along the perpendicular axis
 of the glass slide. Minor errors also occurred (&lt;5.degree.) when aligning
 the two opposing surfaces against each other during cell construction.
 Example 3 demonstrates that liquid crystals can be used to transduce into
 optical signals the transformation of a carboxylic acid group on a surface
 into a carboxylate salt. Small changes in structure of surfaces are known
 to influence the bulk orientation of liquid crystals. A discontinuous,
 90.degree. in-plane reorientation of 5CB is observed depending upon the
 number of methylene groups composing an alkanethiol monolayer. An odd
 number of methylene units resulted in anchoring parallel to the deposition
 direction of the gold while an even number resulted in anchoring
 perpendicular to the deposition direction. The differences in orientation
 are attributed to the different orientations of the terminal methyl group
 within SAMs formed from even and odd numbered alkanethiols.
 The acidity of the SAMs can be decreased using mixtures of
 HS(CH.sub.2).sub.10 COOH and HS(CH.sub.2)nCH.sub.3 . Using this technique,
 the pH transition from uniform to twisted orientation was controlled by
 forming SAMs from a mixture of 1 mM 4:1, 2:1, 1:2 HS(CH.sub.2).sub.10 COOH
 and HS(CH.sub.2).sub.12 CH.sub.3. The pH dependent transition was shifted
 to pH 7, pH 10, and pH 14, respectively. FIG. 11b illustrates the
 discontinous transition as measured through the twist angle that was
 observed for all the monolayers that were tested.
 The pH transition from uniform to twisted alignment was shifted by 0.4 pH
 units through control of the cell thickness. Since the distortion energy
 due to the twist distortion varies as the inverse of cell thickness,
 higher anchoring energies (which manifest in higher pH pretreatments) were
 required to induce a twist distortion in thinner cells. FIG. 12
 illustrates this dependence for three nominal cell thicknesses, 2 .mu.m,
 12 .mu.m, and 30 .mu.m over a pH range spanning uniform to twisted
 orientation. In the 2 .mu.m cells, domains of twist as well as a complete
 twist in the bulk were observed over pH 3.8-4.0.
 In cells prepared with HS(CH.sub.2).sub.10 COOH on each surface, the
 orientation of 5CB went through the discontinuous, in-plane transition
 between pH 3.8 and 4.0. Since bulk distortions are not induced by these
 surfaces, we assumed this transition range is representative of the onset
 of ionization of the surface.
 FIG. 13 plots .THETA.aC.sub.8 (H.sub.2 O) as a function of pH for monolayer
 prepared from mixtures HS(CH.sub.2).sub.10 COOH and HS(CH.sub.2).sub.12
 CH.sub.3. The percentage of chains terminated with COOH is labelled for
 each titration curve. The bolded arrows indicate the pH range where 5CB
 orientations in optical cells reoriented from uniform to twisted
 alignment. A number of features are present in these curves. First, as
 observed by Bain, the contact angles at low pH were constant and decreased
 at higher pH. See, Bain, C. D.; Whitesides, G. M., Langmuir, 5:1370-1378
 (1989)). Similarly, the breakpoint in the titration curves occurred at
 higher pH as the proportion of methyl terminated chains in the monolayer
 was increased. However, the pH transition for 5CB orientation increased
 with respect to the breakpoint pH (observed by contact angles) as the
 proportion of HS(CH.sub.2).sub.10 COOH decreased on the surface. In fact,
 on a SAM formed from only HS(CH.sub.2).sub.10 COOH, the pH of the twist
 transition (pH 3.8-4.0) was observed to be less than the pH of the
 breakpoint (pH 5.0-5.5).
 These results indicate a critical density of carboxylic acid terminal
 groups is required for the transition in 5CB from uniform to twisted. A
 linear relation is observed up to surface compositions of monolayers
 terminated with 41% carboxylic acid (2:1 HS(CH.sub.2).sub.10 COOH and
 HS(CH.sub.2).sub.12 CH).
 EXAMPLE 4
 Example 4 illustrates the quantitative detection of metal ions by their
 binding to SAMs with carboxylic acid terminal groups. Similar to the
 examples above, the binding of the metal ion is amplified and transduced
 into an optical signal by a liquid crystal layer. We use the binding of
 copper ions from aqueous solutions as an example.
 First, microscope slides were covered with semi-transparent layer of
 titanium (30 Angstroms in thickness) and then gold (140 Angstroms). These
 metals were deposited with an oblique angle of incidence (50 degrees from
 normal of slide) using an electron beam evaporator. The metal-coated
 microscope slides were then immersed into a 1 mM solution of 1
 1-mercaptoundecanoic acid (HOOC(CH.sub.2).sub.10 SH) in ethanol for 1
 hour. This procedure lead to the formation of SAMs that presented
 HOOC-groups at their outer surfaces.
 Second, aqueous solutions of Cu.sup.2+ were prepared from
 Cu(ClO.sub.4).sub.2 with concentrations ranging between 1 mM-20 mM. The
 gold films supporting SAMs were then immersed for 5 minutes into these
 solutions of Cu.sup.2+ below pH 5.5. After removal from the aqueous
 solution, the surfaces were vigorously dried under nitrogen and then
 absolute ethanol in order to remove any nonspecifically attached
 Cu.sup.2+.
 Third, surfaces treated as described above were assembled into optical
 cells with a thickness (cavity thickness) of 12 micrometers. The cells
 were filled with 4-cyano-4 pentylbiphenyl (5CB) by capillarity at a
 temperature above the clearing temperature of 5CB. The resultant optical
 texture was analyzed with a polarizing microscope (Olympus) after the
 cells were cooled to room temperature.
 When the concentration of Cu.sup.2+ in solution was 0.01 mM or less, the
 alignment of the LC was uniform and planar (FIG. 14A). When the
 concentration of Cu.sup.2+ in solution was 0.1 mM and 1 mM, the alignment
 of the LC was non-uniform and planar (FIG. 14B and 14C). When the
 concentration of Cu.sup.2+ in solution was 18 mM, the alignment of the LC
 was homeotropic (FIG. 14D).
 Further evidence of the Cu.sup.2+ binding to the carboxylic acid
 functionalized surface was observed in patterned optical cells. In these
 devices, the two opposing surfaces were half-dipped into 1 mM
 Cu(ClO.sub.4).sub.2. The other side of the surface were left unpretreated.
 The resultant patterned cell clearly illustrated the difference between
 regions exposed to Cu.sup.2+ (which are nonuniform.) (FIG. 14E).
 EXAMPLE 5
 Example 5 illustrates the control of the alignment of liquid crystals using
 patterned SAMs.
 The patterning of mesogenic layers on surfaces is illustrated by
 fabrication of three linear diffraction gratings (FIG. 15). These gratings
 differ in the manner of distortion of the mesogenic layers and thus their
 optical properties. Patterned SAMs were prepared by microcontact printing
 with an elastomeric stamp (Kumar et al., Acc. Chem. Res. 28, 219 (1995),
 and references therein). The stamp was inked with an ethanolic solution of
 CH.sub.3 (CH.sub.2).sub.15 SH and put in contact with ultrathin (100 .ANG.
 thick), semi-transparent films of polycrystalline gold. SAMs were then
 formed on the unreacted areas of gold by immersion of the gold films in
 ethanolic solutions containing 1 mM of a second alkanethiol for 2 hours.
 Two surfaces supporting SAMs were subsequently paired and spaced apart
 with Mylar film. The space between the surfaces was filled with the
 nematic mesogen 4-cyano-4'-pentylbiphenyl (5CB) by capillarity. A
 polarizing microscope with white light was used to image the patterned
 liquid crystals. Descriptions of experimental procedures have been
 reported elsewhere (Drawhorn et al., J. Phys. Chem. 99, 16511 (1995);
 Gupta et al., Langmuir 12, 2587 (1996)).
 Fabrication of the periodic liquid crystal structure shown in FIG. 15A
 (grating A) requires uniform planar anchoring of the liquid crystal on the
 top surface of the cell and patterned planar anchoring of the mesogen with
 orthogonal azimuthal orientations in adjacent stripes on the bottom
 surface. Planar anchoring of nematic liquid crystals can be achieved by
 using single-component SAMs formed from CH.sub.3
 (CH.sub.2).sub.n-.sub..sub.1 SH (n=4 to 17) on gold. (The observation of
 planar anchoring of mesogens on surfaces with energies as low as
 alkanethiols on gold (19 mN/m) is unusual. For example, monolayers formed
 from octadecyltrichlorosilane on silica have surface energies as low as
 alkanethiols on gold (19 mN/m) yet cause homeotropic anchoring of
 mesogens. The anisotropic part of the dispersion force acting between 5CB
 and gold influences anchoring of 5CB on SAMs formed from CH.sub.3
 (CH.sub.2).sub.n-.sub..sub.1 SH (Miller et al., Appl. Phys. Lett. 69,
 1852 (1996)).
 The anchoring is azimuthally uniform on SAMs supported on films of gold
 deposited with a 50.degree. angle of incidence (Gupta et al., Langmuir 12,
 2587 (1996)). Oblique deposition of silicon oxide (SIO.sub.x) and metals
 can be used to align mesogens at surfaces (Urbach et al., ibid. 25, 479
 (1974); J. L. Janning, ibid 21, 173 (1972)). This method, however, is not
 economically competitive with methods based on rubbed polymers when
 uniform alignment of a mesogen over a large area is required. In contrast,
 when patterned orientations of mesogens are required, processes based on
 rubbing become complex, and oblique deposition of metals can form the
 basis of simple and economical procedures.
 The anchoring of 5CB is perpendicular to the direction of deposition of the
 gold on SAMs formed from odd alkanethiols (for example, n=11; FIG. 15A)
 and parallel to the direction of deposition of gold on SAMs formed from
 even alkanethiols (for example, n=12; FIG. 15B) (Gupta et al., Phys. Rev.
 E 54, 4540 (1996)); the alignment of 5CB on "bare," obliquely deposited
 gold is planar and perpendicular to the direction of deposition of the
 gold). Differences in the orientation of the methyl groups at the surface
 of SAMs formed from odd and even alkanethiols on gold direct the in-plane
 orientation of the nematic mesogen (Gupta et al., Phys. Rev. E 54, 4540
 (1996)); the orientation of methyl groups exposed at the surface of SAMs
 formed from CH.sub.3 (CH.sub.2).sub.n-.sub..sub.1 SH on gold differ for
 odd and even alkanethiols because the aliphatic chains within these SAMs
 are tilted away from the surface normal by 30.degree. (Nuzzo et al., J.
 Am. Chem. Soc. 112, 558 (1990)). In contrast, chains within SAMs formed
 from alkanethiols on silver and perfluorinated alkanethiols on gold are
 tilted by less than 10.degree. to 15.degree., and there is no odd-even
 variation in the orientation of the methyl groups (CH.sub.3 or CF.sub.3)
 at the surface of these SAMs (Laibinis et al., ibid., 113, 7152 (1991));
 (Lenk et at., Langmuir 10, 4610 (1994)). No odd-even dependence was
 observed for the orientation of 5CB on SAMs formed from alkanethiols on
 silver or perfluorinated alkanethiols on gold: the anchoring of 5CB was
 perpendicular to the direction of deposition of the gold; a 90 azimuthal
 reorientation of a mesogen on a corrugated surface can be caused by a
 coupling of elastic and flexolectric effects.
 Patterned SAMs formed from CH.sub.3 (CH.sub.2).sub.14 SH and CH.sub.3
 (CH.sub.2).sub.15 SH on obliquely deposited gold were used to fabricate
 grating A. The polarization of linearly polarized light is not changed by
 transmission (along the z direction in FIG. 17A) through the regions of
 the mesogenic layer with uniform planar anchoring but is rotated by
 90.degree. upon transmission through regions of the mesogenic layer that
 are twisted by 90.degree. (Yeh, P., OPTICAL WAVES IN LAYERED MEDIA (Wiley,
 N.Y., 1988)). When viewed through crossed polars, therefore, twisted
 regions of grating A appear bright (light is transmitted by the analyzer)
 and uniform regions appear dark (light is extinguished by the analyzer)
 (FIG. 17A). The periodic change in refractive index across the grating
 causes diffraction of laser light (FIG. 17B).
 The grating in FIG. 15B (grating B) is based on homeotropic anchoring of
 the mesogenic layer on the top surface of the cell and patterned planar
 and homeotropic anchoring of the mesogenic on the bottom surface. Light
 incident on grating B with a linear polarization along the x direction
 will experience a periodic change in refractive index and will be
 diffracted. In contrast, light with polarization along they direction will
 experience no spatial variations in refractive index and will not be
 diffracted. Mixed SAMs formed by coadsorption of long and short
 alkanethiols on gold to homeotropically anchor 5CB (FIG. 16C) (Drawhorn et
 al., J. Phys. Chem. 99, 16511 (1995)) Gupta et al., Langmuir 12, 2587
 (1996); Yeh, P., OPTICAL WAVES IN LAYERED MEDIA (Wiley, N.Y., 1988)).
 The planar to homeotropic transition in anchoring of 5CB observed on mixed
 SAMs formed from long and short alkanethiol on gold differs from past
 reports in which Langmuir-Blodgett films of lecithin were used: the
 anchoring of 5CB is homeotropic for all packing densities of lecithin
 (Hiltrop et al., Ber. Bunsen-Ges. Phys. Chem. 98, 209 (1994)) in a grating
 of type B. A polarized light micrograph of the mesogenic grating viewed
 through crossed polars is shown in FIG. 17C. Dark stripes correspond to
 regions of the grating in which the polarization of linearly polarized
 light was not changed by transmission through the mesogen; these stripes
 remained dark when the sample was rotated between the crossed polars, thus
 confirming homeotropic anchoring in these regions. Bright stripes
 correspond to regions of the mesogenic layer distorted by planar anchoring
 of the layer on the bottom surface and homeotropic anchoring of the layer
 on the top surface of the cell. Patterned homeotropic and planar anchoring
 of mesogens has not been demonstrated in past work that was based on
 photo-alignment or rubbing techniques.
 In contrast to grating B, the diffraction of light by the grating in FIG.
 15C (grating C) was polarization insensitive. When grating C was viewed
 under crossed polars, either uniformly bright stripes (FIG. 17D,
 polarization of incident light between x and y) or uniformly dark stripes
 (polarization of incident light along x or y) was observed. The boundaries
 between stripes, which correspond to regions in which two different
 distortions of the mesogens meet, were visible in the optical micrographs
 (dark lines in FIG. 17D). The lack of measurable contrast between adjacent
 stripes for all polarizations of incident light is consistent with the
 mesogenic layer structure of grating C. A similar type of layer structure
 has been reported by Chen and co-workers who use a two-step rubbing
 process (Chen et al., Appl. Phys. Lett. 67,2588 (1995)).
 The polarization sensitivity of gratings B and C was further tested by
 viewing these gratings with linearly polarized light (not crossed polars).
 When grating B was viewed with light having a linear polarization along
 the x direction, the grating pattern was visible (FIG. 18A) because the
 incident light experienced a spatially periodic refractive index. With
 light polarized along they direction, however, only faint edges of the
 stripes were Seen (FIG. 18B); these edges did not cause measurable
 diffraction of light. In contrast, because grating C is insensitive to the
 polarization of incident light, the grating was visible upon illumination
 by light with polarization along x or y (FIG. 18C and 18D).
 Tuning of these patterned mesogen structures was possible by using electric
 fields. When gold surfaces supporting SAMs were used as electrodes, an
 electric field could be applied perpendicular to the surfaces. Reversible
 application of the electric field reorients the mesogens and thus
 modulated the intensity of light diffracted from the gratings (FIG. 18E).
 In-plane electric fields were also used (in-plane switching refers to the
 use of an electric field that is applied parallel to the surface of the
 cell). Devices based on in-plane switching of a mesogen have been used in
 FPDs with wide viewing angles (Ohe et al., Appl. Phys. Lett. 69, 623
 (1996); Ohta et al., IEICE (Inst. Electron Inf. Commun. Eng.) Trans.
 Electron. E79-C, 1069 (1996)) to reorient these patterned mesogenic
 structures. We observe SAMs to be stable upon application of an electric
 field across a cell filled with mesogen. Past studies have reported
 electrochemical desorption of SAMs in aqueous solutions of electrolytes
 (Widrig et al., J. Electroanal. Chem. 310, 335 (1991); Waliquid crystalzak
 et al., Langmuir 7, 2687 (1991)). In general, the alignment of mesogens on
 SAMs formed from long-chain alkanethiols is stable over months. Stability
 over years can be achieved by using polymerizable SAMs (T. Kim et al.,
 Langmuir 12, 6065 (1996)) or mesogens doped with alkanethiols or reducing
 agents to prevent oxidative degradation of the SAMS.
 The methods reported here permit fabrication of complex mesogen structures
 in two simple processing steps. Surfaces can be patterned with regions of
 mesogens that differ in shape and have sizes ranging from micrometers to
 centimeters (FIG. 19A). The mesogens can also be patterned on nonplanar
 surfaces (FIG. 19B).
 EXAMPLE 6
 6.1 Materials and Methods
 Hexadecane was purchased from Aldrich and passed through a column of
 alumina before use. The semifluorinated thiols CF.sub.3 (CF.sub.2).sub.7
 CONH(CH.sub.2).sub.2 SH (1), CF.sub.3 (CF.sub.2).sub.7 (CH.sub.2).sub.2 SH
 (2) and CF.sub.3 (CF.sub.2).sub.7 (CH.sub.2).sub.11 SH (3) were available
 from previous studies. See, Drawhorn, R. A. et al, 1995, J. Phys. Chem.,
 99, 16511; Solution compositions of 1:1 and 3:1 were needed to form
 surface compositions of 1:1 for mixed SAMs formed from 1 and 2 and 1 and
 3, respectively. Decanethiol (4), dodecanethiol (5) and hexadecanethiol
 (6) were purchased from Aldrich, and 4-n-pentyl4'-n-cyanobiphenyl (5CB,
 T.sub.NI =35.degree. C., T.sub.KN= 24.degree. C.) was purchased from EM
 Sciences. Anhydrous ethanol was purchased from Quantum.
 6.1a Sample preparation
 Glass microscope slides were cleaned in "piranha" solution (70:30
 concentrated H.sub.2 SO.sub.4 /30% H.sub.2 O.sub.2, WARNING: piranha
 solution reacts strongly with organic compounds and should be handled with
 extreme caution; do not store the solution in closed containers) for 30
 minutes at 90.degree. C. Substrates of gold were prepared by evaporation
 (100 .ANG. at 0.2 .ANG./s, P&lt;5.times.10.sup.-6 torr, with epicyclic
 rotation of sample relative to the incident flux of Au) onto microscope
 slides. See, Gupta, V. K, et al., 1996, Chemistry of Materials, 8, 1366.
 Approximately 10 .ANG. of titanium was used to promote adhesion between
 the gold and glass microscope slides. Self-assembled monolayers were
 formed for 2 hours in ethanolic solutions that contained a 1 mM total
 concentration of thiol. Binary mixed SAMs were formed by coadsorption of
 the thiols such that the compositions of SAMs were 1:1 for SAMs formed
 from 1 and 2 and from 1 and 3. The compositions of the SAMs were estimated
 by XPS [Solution compositions of 1:1 and 3:1 were needed to form surface
 compositions of 1:1 for mixed SAMs formed from 1 and 2 and 1 and 3,
 respectively.; Laibinis, P. E., et al., 1992, J. Phys. Chem., 96, 5097.
 The compositions of mixed SAMs formed under these conditions were
 determined by the kinetics of chemisorption.
 6.1b Contact Angles
 Advancing and receding contact angles of hexadecane were measured using a
 Rame-Hart goniometer and environmental chamber. A drop of hexadecane was
 placed in contact with the surface using the needle of a syringe. By
 increasing or s decreasing the volume of the drop, the advancing and
 receding contact angles were measured. The environmental chamber was
 purged with nitrogen during measurements of the contact angles to avoid
 contamination of the SAMs. All contact angles reported are the averages of
 at least 12 measurements at four different places on the sample.
 6.1c Polarized Light Microscopy
 Self-assembled monolayers supported on films of gold were paired and spaced
 apart by 2 or 25 .mu.m spacers of mylar to form optical cells. A drop of
 SCB was heated into its isotropic phase, drawn between the surfaces of the
 optical cells by capillary action, and then cooled slowly into its nematic
 phases (.about.1.degree. C./minute). A polarized light microscope
 (Olympus) was used to observe the optical textures of the liquid crystals
 at room temperature. See, Gupta, V. K. et al., 1996, Langmuir, 12, 2587.;
 Gupta, V. K., et al., 1996, Chemistry of Materials, 8, 1366. Conoscopic
 interference figures (Gupta, V. K. et al., 1996, Langmuir, 12, 2587;
 Gupta, V. K., et al., 1996, Chemistry of Materials, 8, 1366) were used to
 confirm the orientation of the direction of liquid crystals relative to
 the substrates in uniformly anchored samples.
 6.2 Results
 6.2a Single component SAMs Formed From Semi Fluorinated Thiols
 The cartoons presented in FIG. 21 summarize the structure of SAMs formed
 from 1-3 and 5. All four compounds form densely packed and highly ordered
 SAMS. The semifluorinated chains are, in general, tilted away from the
 normal less than the chains in SAMs formed from alkanethiols; the
 semifluorinated chains appear to lie normal to the surface when they
 contain short (--CH.sub.2-).sub.n sequences (e.g., 1 and 2) The
 perfluorinated chains (outer region) within SAMs formed from 3 are tilted
 away from the normal more than the perfluorinated chains within SAMs
 formed from 1 and 2. The tilt of the aliphatic chains (inner region) in
 SAMs formed from 3 is less than the tilt of the aliphatic chains of 5
 (Solution compositions of 1:1 and 3:1 were needed to form surface
 compositions of 1:1 for mixed SAMs formed from 1 and 2 and 1 and 3,
 respectively.]. Evidence for hydrogen bonding between C.dbd.O and NH
 within SAMs formed from 1 has been observed in IR spectra: the hydrogen
 bonding does not appear to alter the packing density of the chains on the
 surface.
 Self-assembled monolayers formed from 1-3 were characterized by
 ellipsometry and contact angles of hexadecane, in addition to the IR
 measurements reported above. The ellipsometric thicknesses of SAMs formed
 from 1-3 were measured to be 17 .ANG., 15 .ANG. and 26 .ANG.,
 respectively, consistent with the formation of densely packed. The
 advancing and receding contact angles of hexadecane were 75-76.degree. and
 71-73.degree., respectively, for all samples with the exception of the
 advancing contact angle measured on SAMs formed from 3. All contact angles
 are consistent with presentation of CF.sub.3 and CF.sub.2 groups at the
 outer surface of each SAM. See, Ulman, A., 1991, An Introduction to
 Ultrathin Organic Films: From Langmuir-Blodgett to Self Assembly (San
 Diego, Calif.: Academic Press). The advancing contact angle of hexadecane
 measured on SAMs formed from 3 was 79.degree., suggesting that the outer
 regions of this SAM was structured differently than SAMs formed from 1 or
 2 (see comment above regarding tilt of chains). Optical cells assembled
 with surfaces supporting SAMs formed from 3 did not fill by capillary
 action when 2.mu.m-thick mylar was used to space apart the surfaces of the
 cells. Reported, therefore, are results for 3 with cells with surfaces
 spaced apart by 25 .mu.m-thick mylar.
 Optical textures of 5CB anchored on SAMs formed from 1-3 and 5 are shown in
 FIG. 22. Optical textures of 5CB anchored on SAMs formed from 6 have been
 published elsewhere and are similar to 5. See, Gupta, V. K., et al., 1996,
 Langmuir, 12,2587.; Gupta, V. K.; Miller, W. J.; Pike, C. L. et al., 1996,
 Chemistry of Materials, 8, 1366. The diffuse, meandering branches emerging
 from defects of strength 1/2 (two branches) within 5CB supported on SAMs
 formed from either 1 or 2 (FIG. 22a and 22b) are consistent with planar
 and azimuthally degenerate anchoring of 5CB. In contrast, the optical
 textures of SCB in contact with SAMs formed from 5 (FIG. 22e) have a
 grainy appearance with characteristic dimensions that are much smaller
 than observed with SAMs formed from either 1 and 2. Although meandering
 branches and 1/2 defects are not generally observed when SCB is anchored
 on SAMs formed from alkanethiols, measurements of the polar anchoring of
 SCB on SAMs formed from CH.sub.3 (CH.sub.2).sub.11 SH (an alkanethiol that
 forms a SAM of similar thickness to 1 or 2) confirm planar anchoring. See,
 Gupta, V. K., et al., 1996, Chemistry of Materials, 8, 1366. Thus, the
 anchoring of 5CB on SAMs formed from semifluorinated thiols 1 and 2 and
 alkanethiols is planar. We note also that the spatial correlation of the
 azimuthal alignment of the director is greater on SAMs formed from
 semifluorinated thiols than SAMs formed from alkanethiols.
 The optical textures of 5CB anchored on SAMs formed from 3 were different
 from 1 and 2. The textures observed on SAMs formed from 3 were not
 schlieren, but "marbled" (FIG. 22c). The characteristic dimension of the
 domains was larger than for SAMs formed from CH.sub.3 (CH.sub.2).sub.15 SH
 (a monolayer of similar thickness to 3). In domains that were large enough
 to obtain a conoscopic image (FIG. 22d), the position of the interference
 fringes indicated a tilt of the optical axis (&gt;&gt;15.degree.) away from the
 surface normal.
 6.2b Mixed SAMs formed by Coadsorption of Semifluorinated Thiols.
 Self-assembled monolayers were formed by coadsorption of either 1 and 2 or
 1 and 3. The compositions of the mixed SAMs were confirmed to be 1:1 by
 XPS. FIG. 23 shows schematic illustrations of the mixed SAMs formed from
 the semifluorinated thiols, and a mixed SAM formed from 5 and 6. In the
 discussion that follows we use the variable .DELTA.t to denote the
 difference in the length of the short and long chains within mixed SAMs.
 The contact angles were consistent with the presentation of CF.sub.2 and
 CF.sub.3 groups at the surface of the SAM except perhaps for the receding
 contact angle of SAMs formed from 1 and 3 (68.degree., see below).
 The IR band corresponding to the amide II stretch (NH in-plane bending,
 1545 cm.sup.-1) measured using SAMs formed from 1 and 2 is similar to the
 position of the amide II stretch measured using SAMs formed from 1. This
 observation indicates hydrogen bonding takes place within the mixed SAM
 which, in turn, suggests incomplete mixing--and possibly islanding--of 1
 and 2 within the mixed SAMs; hence, ideal mixing of species within the
 mixed SAM formed from 1 and 2 has not occurred. In contrast, the FTIR
 spectra measured with SAMs formed from 1 and 3 does show a shift of the
 amide II frequency to lower wave numbers, from which it can be inferred
 that there is true mixing of the two species within the SAM. The influence
 of the level of molecular mixing within the mixed SAMs on the anchoring or
 liquid crystals and (and contact angles) is unknown. The degree of
 mixedness could, however, account for the lower receding contact angles of
 hexadecane measured on SAMs formed from 1 and 3 (see above).
 The optical textures of 5CB anchored on mixed SAMs formed from 1 and 2
 (.DELTA..sub.t =2 .ANG.) were schieren (FIG. 24a), although no defects
 with strength 1/2 could be found. Conoscopic images obtained from regions
 removed from defects showed interference fringes consistent with a tilt of
 the director (.apprxeq.15.degree.-20.degree.) away from the surface normal
 (FIG. 24b). In contrast, mixed SAMs formed from 1 and 3 (.DELTA..sub.t =9
 .ANG.) caused homeotropic anchoring of 5CB (FIG. 24c). Mixed SAMs formed
 from 4 and 5 (.DELTA..sub.t =3 .ANG.) cause near-planar anchoring (FIG.
 24d) while past studies have shown that homeotropic anchoring is obtained
 on mixed SAMs formed from 4 and 6 (.DELTA..sub.t =9 .ANG.).