an excited state. The 2PA process is weak relative to one-photon excitation for intensities below about 10 GW/cm2 and nominal values for the absorption cross Materials for sections. The probability of a molecule absorbing one photon is proportional to the intensity of the excitation beam. In Multiphoton 3D contrast, the probability of a molecule absorbing two photons simultaneously is proportional to the square of the intensity of the excitation beam. Microfabrication The nonlinear intensity dependence of 2PA gives rise to some very interesting and useful effects. First, 2PA enables the excita- Seth R. Marder, Jean-Luc Brédas, tion of molecules with a very high degree of spatial confinement in three dimen- and Joseph W. Perry sions,12 leading to feature widths of ~100 nm and excited volumes as small as ~0.003 µm3 or 3 attoliters. This 3D control Abstract of the excitation arises from focusing an Two-photon/multiphoton lithography (MPL) has emerged as a versatile technique for intense beam into a material and the the fabrication of complex 3D polymeric, hybrid organic/inorganic, and metallic fact that the beam intensity decreases structures. This article reviews some recent advances in the development of molecules roughly quadratically with the distance and materials that enable two-photon and multiphoton 3D micro- and nanofabrication. from the focal plane. Because the probabil- Materials that exhibit high sensitivity for the generation of reactive intermediates are ity of 2PA is proportional to the square of described, as are various materials systems that enable functional devices to be made intensity of the laser beam, the probability and in some cases enable structures to be replicated. The combination of advances of 2PA falls off roughly as the fourth illustrates the opportunities for MPL to have a significant impact in the areas of power of the distance from the focus. , microelectromechanical systems, and biomedical technologies. Consequently, 2PA at appreciable dis- tances from the focal plane (say, at roughly twice the Rayleigh length, or 2.5 times the beam radius at the focus) is negligible (5%), relative to that at the focal plane, Introduction leading to a much greater confinement of There is a growing interest in the fabri- have limitations in terms of being quite excitation along the direction of propaga- cation of truly three-dimensional micro - restricted in the range or the spatial reso- tion and at the focus of the beam for 2PA as structures and devices for potential lution of 3D structures that can be formed, compared with one-photon absorption applications in photonics, microelectro- or are consuming in terms of the number (Figure 1a). Second, with 2PA it is possible mechanical systems, , and of masks and amounts of solvent to excite molecules at increased depth, rel- tissue engineering, among other fields.1–3 required. Many new or emerging tech- ative to one-photon absorption, in a nomi- In 2D lithography, major advances have nologies demand fabrication of 3D struc- nally high-absorbing medium, because the been made in decreasing the feature sizes tures with submicron feature sizes and photon energy lies well below that at in devices. For example, lithographic great flexibility in shape and material which the medium absorbs via one- processes for making complex integrated composition. Two-photon/multiphoton photon absorption (Figure 1b). With these circuits with 65-nm features are now used lithography (MPL) offers the potential for features of higher resolution and the abil- in the commercial production of micro- micro- and nanofabrication of arbitrary ity to “write” at different depths, 2PA has processors,4 but these processes are 3D structures in a single coat/expose/ enabled the realization of 3D optical data restricted to 2D patterning in a given develop process cycle. In this article, we storage,13–16 lithographic microfabrica- exposure step. Progress also has been review the development of two-photon tion,15,17 and imaging12 via pulsed laser made in using molecular, nanotube, and absorbing materials that can be used for excitation. By computer-controlled scan- nanoparticle self-assembly to build struc- of a variety of com- ning of the focus of a laser beam within a tures with unique properties in a bottom- plex structures. photochemically active precursor material, up approach.5–7 Such self-assembly many complex 3D structures can be fabri- processes, however, are limited predomi- Two-Photon/Multiphoton cated with submicron resolution (see nantly to the formation of periodic struc- Lithography Figure 1c for a schematic illustrations of an tures. Fabrication of 3D objects of Two-photon absorption (2PA) provides MPL system). arbitrary shapes with feature sizes a means of activating chemical or physical MPL is helping to revolutionize the fab- approaching those achievable by either processes with high spatial resolution in rication of 3D structures on the submicron photon or electron-beam lithography tra- three dimensions and feature widths as scale, because of the following advan- ditionally has been an extremely difficult small as ~100 nm. With sufficiently tages: task. Some types of 3D structures can be intense light, such as from a pulsed laser 1. The numerous types of 3D structures fabricated using sequential layer-by-layer beam, it is possible for a molecule to that can be fabricated, including ones with lithographic processes,8 direct-writing simultaneously absorb two photons, each interlocking or movable parts; with inks,9 stereolithography,10 and multi- approximately half the energy (twice the 2. The ability to directly pattern various beam interference lithography,11 which wavelength λ) normally required to reach materials ranging from transparent

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a b Accordingly, schemes that seek to exploit the use of 2PA would be aided by the development of molecules with large δ. One key to the design of molecules with high sensitivity in 2PA is a detailed under- standing of how δ depends on molecular structure. Molecules with a large δ would be more efficiently excited than molecules with a small δ at the same laser intensity, enabling the use of lower-power and less costly pulsed lasers19 and increasing the speed with which scanning laser expo- sures could be made, thus making 2PA applications more economically feasible. Recent advances in two-photon materials and processing methods suggest the promise for MPL to become a mainstream, commercially viable fabrication technol- ogy, as we briefly describe here. c Before 1998, the largest value of δ reported was roughly 300 GM for the laser Nd: VO laser Mode-locked dye rhodamine B (where 1 GM ≡ 1 × 10−50 4 Ti:sapphire laser cm4 s).20 We discovered that E-4,4′-bis(di- n-butyl)aminostilbene, 1, had a peak two- δ photon excitation cross section max = 210 GM at 605 nm, which is almost 20 times Sample Varible optical greater than the peak cross section for XYZ translation attenuator trans-stilbene.21 The δ value for 1 was stage among the largest values of δ reported for organic compounds at that time. High-speed shutter Quantum-chemical calculations were per- High-NA formed to insight into the much objective δ larger max value for 1 compared with trans-stilbene. The 2PA spectra were XY raster obtained from the dispersion of the imag- scanner inary part of the second hyperpolarizabil- ity using the sum-over-states expression from perturbation theory that reproduced the experimentally observed order-of- Figure 1. (a) Fluorescence/optical image demonstrating localized excitation in three δ magnitude enhancement in max upon dimensions by two-photon excitation. Top spot, two-photon excitation; bottom streak, one substitution of trans-stilbene with termi- photon excitation. (b) Demonstration of the limited penetration depth of one-photon nal dialkylamino groups. The calculations excitation in a strongly absorbing medium (bottom spot at right edge of cuvette); improved penetration depth via two-photon excitation is clearly seen by the intense spot in the central showed that the lowest singlet excited upper portion of the cuvette. (c) Schematic illustration of a system for two- state (e) is a one-photon-allowed state photon/multiphoton 3D microfabrication. with Bu symmetry, whereas the second singlet excited state (e′) is two-photon- allowed with Ag symmetry and corre- sponds to the observed 2PA peak. The calculations also suggested that the to inorganic–organic hybrids to Two-Photon Absorption Materials ground-state to excited-state (g → e) exci- metals; and Processes tation is accompanied by a substantial 3. The possibility to create “micromolds” To exploit these advantages, it is benefi- charge transfer from the amino groups to that can be used for templated growth of a cial to use specially designed and engi- the central vinylene group, leading to a range of materials, enabling the integra- neered photoactive materials within which large change in quadrupole moment upon tion of disparate materials into devices; it is possible to localize photochemical excitation; a similar sense and magnitude 4. The capability to fabricate features reactions within the excitation volume. of charge transfer is calculated for the g → from the nanoscale (<100 nm) to the Whereas various efforts to exploit 2PA in e′ transition. This pronounced redistribu- microscale, providing a technology for 3D microfabrication and imaging have tion of the π-electronic density was corre- integrating nanostructures with well- been reported, many of these schemes lated with a significant increase in the established microscale components. have employed conventional photoinitia- e→e′ transition dipole moment, which is Thus, two-photon/multiphoton 3D tors or fluorescent chromophores that the major contributor to the enhanced lithography is a disruptive technology were developed for use under one-photon two-photon cross section of 1 with respect that fundamentally changes what 3D excitation conditions. Such chromophores to that of trans-stilbene. Because the sym- microstructures can be fabricated and typically had low efficiency for 2PA (char- metric charge transfer and change in how they can be made. acterized by the 2PA cross section, δ).18 quadrupole moment appeared to be corre-

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lated to the increase of the two-photon ab cross section, we examined systems in which the π-conjugation length between h ν the two-donor groups (D-π-D chro- 2 mophores) was increased and in which acceptor groups were attached to the center of the π-conjugated bridge (D-A-D chromophores), and similarly in which the sense of the symmetric charge transfer was reversed (A-π-A and A-D-A chro- mophores).21 In this manner, many com- pounds that exhib itedlarge δ were identified. Some of these compounds were strong excited-state–reducing agents Figure 2. (a) Schematic illustration of scanning laser exposure of a two-photon absorbing and were used for MPL, as described next. photopolymer resin in multiphoton lithography (MPL). (b) Freestanding microchain fabricated by MPL; the entire structure is approximately 150 µm from end to end. Two-Photon Initiated Chemistry for 3D Microfabrication Several groups have used the capabili- ties of 2PA to demonstrate 3D optical data a b storage and MPL using various photoacti- vated reactions (such as photoinitiated and fabrication of hybrid materials,15,17,22–25 photocleavage of func- tional groups,26,27 photoreduction of met- als,28–30 and photochromic reactions31,32). We have developed highly efficient two- photon photopolymer resins based on our high-δ chromophores that exhibit a photo- sensitivity increase of 20- to 50-fold relative to photopolymer resins incorporating pho- toinitiators designed for one-photon lithog- raphy.15 In the MPL scheme employed, 20 µm two-photon excitation of a D-π-D chro- mophore initiates free-radical cross-linking in a multifunctional methacrylate pho- Figure 3. (a) Polymeric “stack-of-logs” structure fabricated using MPL; the topolymer blend that reduces the solubility width of the whole structure is comparable to that of a human hair. (b) Cross-sectional of the exposed material. In this process, an views of a tunnel array structure fabricated by MPL using a chemically amplified positive arbitrary 3D pattern is impressed into the tone resist and a high-sensitivity two-photon photoacid generator. The upper right image is a top view showing the vertical channels that open to the surface. Each tunnel in the photopolymer by scanning the focus of an µ intense laser beam within the material (see structure is 4 m wide. Figure 2a). The exposed 3D pattern can then be developed by dissolving the unex- posed material with a suitable solvent to D-π-D dyes was due almost entirely to tation. Many conventional photoactivator give a freestanding 3D microstructure in a their large δ. We estimated that several of systems, including radical photoinitia- single exposure/development cycle. these two-photon initiators exhibit only tors, photoacid generators, and photo- The MPL approach can be used to pro- modest radical generation efficiencies after deprotection systems, involve excitation of Φ Φ duce a variety of interesting 3D micro- excitation ( R ~ 0.03, where R is the quan- ultraviolet-absorbing chromophores that structures including integrated optical tum yield for radical generation from the directly leads to bond cleavage. Photo- elements1,15,33 as well as micromechanical excited state). Because the overall photo- deprotection is the process of masking a and complex interlocking structures,34,35 sensitivity for a two-photon photoactiva- functional group (for example, an amine or δΦ Φ such as the freestanding microchain tor is dependent on c (with c being the carboxylic acid) with another group; upon shown in Figure 2b.36 Three-dimensional quantum yield for generating a reactive exposure to light the second group cleaves periodic structures are currently of inter- species), these results indicated that signif- from the first group, thus “deprotecting” est as photonic crystals, which have icant further improvements in photosensi- it. In this way, you can use light to unmask unique optical reflection/transmission tivity were possible. Thus, a key challenge the first group. and dispersion properties.15,36–40 Figure 3a in developing efficient two- photon photo - The comparatively high energy of the shows a view of a 3D periodic “stack-of- activators was the requirement that the lowest excited states of photoactivator sys- logs” structure that has an in-plane rod molecule or molecular ensemble simulta- tems provides sufficient energy to cleave spacing of 4 µm and a layer spacing of 1.5 neously have a large two-photon cross sec- bonds. Molecules of this type are generally µm, as appropriate for diffraction of tion and an efficient excited-state pathway small conjugated systems and tend to have infrared radiation. to activate a reaction. small two-photon cross sections. However, The 20- to 50-fold increase in two- These requirements put restrictions on most molecules with large δ typically photon photosensitivity, relative to con- the energy and lifetime of the relaxed absorb at longer wavelengths, and their ventional initiators, discussed earlier for excited state formed after two-photon exci- lowest excited states have insufficient

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energy to directly cleave bonds. Therefore, fore implemented the electron transfer ous schemes, each of these materials we employed an alternative approach approach described earlier by linking a classes by MPL processes.28,40,41 Stellacci based on bond-cleavage reactions activated 2PA chromophore directly to a dialkylsul- et al. have demonstrated the fabrication of by electron transfer.26 In this approach, fonium group and activating it by two- metallic microstructures by exposure of a a molecule absorbs light, creating an photon excitation (Figure 4a).26 The nanocomposite composed of a polyvinyl- excited state that can transfer an electron to two-photon photoacid generator based on carbazole/ethylcarbazole host; a soluble (or accept an electron from) a “cleavable a bis-styrylbenzene conjugated bridge silver salt that can be reduced to form sil- group” (a group containing a cleavable with a moderate δ was estimated to have ver atoms; silver nanoparticles coated with δΦ bond) upon accepting (or giving up) an c ~ 400 GM. a mixture of thiol ligands to promote solu- electron. When the cleavable group accepts The photoacid in Figure 4 has been bility in the host and to disfavor aggrega- (or donates) an electron, a bond can be bro- employed in a positive tone resist (i.e., a tion; and a 2PA chromophore that, upon ken and can lead to generation of reactive system that becomes more solu- excitation, is capable of reducing the silver species such as radicals, acids, and bases. ble upon photoexcitation). In positive tone salt.28 Conductive silver features were In order for the electron transfer process resins, the exposed region is removed in fabricated by MPL, and the fabrication of a to be efficient, the excited molecule must the development step. In one implementa- 3D structure was demonstrated. This be sufficiently reducing or oxidizing rela- tion, the photoacid was dissolved in an approach also was applied to nanocom- tive to the cleavable group, and the 2PA acrylate polymer system that contained posites based on gold and copper nanopar- chromophore and the photocleavable acid-cleavable tetrahydropyranyl (THP) ticles. Fourkas and co-workers have group must be in close proximity. To place ester groups (Figure 4b), which give car- reported on an alternative surface modifi- the two groups in close proximity, we boxylic acid groups upon cleavage. cation approach that enables selective dep- directly linked the electron-rich 2PA chro- Exposure of the resin activated the pho- osition of metal on defined regions of a mophore and the “cleavable group” via a toacid, which after a postexposure baking polymeric structure.30,42 Chichkov and co- covalent bond, for example, to make two- process rendered the polymer soluble in workers have used acrylate functionalized photon excitable photoacid generators.26 aqueous base.26,27 For structures where trialkoxysilane-based precursors in MPL to Photoacid generators are chromophores small voids within large volumes of solid form 3D microstructures in hybrid silica that liberate a proton or another acidic materials are required, positive tone sol-gel glass material.22,41 Dong and Perry species upon excitation. Photoacid gener- resists are generally preferable to negative have recently reported on the use of a tita- ators have been used to photoinitiate ring- tone resins because shorter patterning nium alkoxide complex precursor for the opening polymerization of epoxides and times are required. Figure 3b shows a fabrication of titania–organic hybrid struc- to pattern polymeric materials through structure comprising an array of tunnels tures by MPL.43 Another interesting devel- acid-catalyzed cleavage of active ester in the polymer matrix that are connected opment by Fourkas and co-workers, with functional groups; for example, such reac- at the ends by channels that extend to the significance for the potential mass produc- tions are the basis of many commercial upper surface to enable removal of the tion of 3D structures fabricated by MPL, is patterning and lithographic processes. exposed and photocleaved material. We a soft lithography replication method Epoxide systems, in particular, offer some have demonstrated that the channels can based on a removable poly(dimethylsilox- advantages over acrylates for microfabri- be filled with various fluids, including ane) molding process, which enables repli- cation by MPL, since they can be less sus- liquid crystals, and such structures have cation of structures with overhangs and ceptible to shrinkage and deformation. potential for applications in microfluidics even closed-loop structures.44,45 Commercially available photoacid gener- and switchable grating devices. ator systems, such as salts containing tri- In addition to polymeric structures, the arylsulfonium cations, are highly efficient fabrication of structures in a variety of Conclusions under ultraviolet illumination, yet are far other materials, including metals, semicon- We have highlighted the developments from optimized for two-photon excitation ductors, and inorganic–organic hybrids, is in photoinitiators, photoactive materials because their δ is rather small. We there- desirable; it is possible to pattern, by vari- systems, and structure/device fabrication that exemplify the advances made in two- photon/multiphoton lithography. The advent of design principles for two-photon a b absorbing photoinitiators with large cross sections and high chemical efficiency offers CH2 CH2 0.60 0.40 a rational approach to the synthesis of opti- 2PA-absorber O O mized photoactivators with extremely O O high photosensitivity. Various multiphoton Bu O materials platforms have been developed, and new nanocomposites and templating Bu approaches can provide access to a range H+, heat N of compositions for 3D microfabrication. N Three-dimensional structures and devices − CH CH fabricated with unique functionality are 2SbF 2 2 Photocleavable S 6 0.60 0.40 emerging as a result of MPL, and many pos- group O O S sibilities remain unexplored. O HO Although still in its infancy, the field of MPL has advanced to the point where it is Figure 4. (a) A two-photon photoacid generator based on the linking of a two-photon- poised to have a significant impact in pho- absorption chromophore and a photocleavable group. (b) Positive tone resin illustrating tonics, microelectromechanical systems, cleavage of acid-cleavable tetrahydropyranyl groups upon treatment with acid and and biomedical technologies in the com- postexposure bake. ing years. MPL clearly demonstrates that

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