Refractive index matched polymeric and preceramic resins for height-scalable two-photon lithography.

Nanofabrication techniques that can generate large and complex 3D structures with nanoscale features are becoming increasingly important in the fields of biomedicine, micro-optics, and microfluidics. Direct laser writing via two-photon polymerization (DLW-TPP) is one such technique that relies on nonlinear absorption of light to form nanoscale 3D features. Although DLW-TPP provides the required nanoscale resolution, its built height is often limited to less than a millimetre. This height limitation is driven by the need to tightly focus the laser beam at arbitrary depths within the photopolymer. This requirement necessitates matching the photopolymer's refractive index to specific values but the required techniques have not been disseminated widely in the open scientific literature. To address this knowledge gap, we test two universal, different approaches to generate refractive index-matched polymeric and preceramic resins and demonstrate their performance by printing of fine submicron features in 3D structures as tall as 2.5 mm. Specifically, we achieve index-matching by mixing commercially-available resins or covalent modification of functional monomers. This work investigates the relationship of voxel shape to RI mismatch, and presents tuning of RI through mixing and covalent modification to a nonconventional material system of preceramic resin which has never been demonstrated before. We demonstrate the material flexibility by generating 3D silicon oxycarbide structures from preceramic resists while simultaneously eliminating the part-height limitation of conventional DLW-TPP.

On the Network Topology of Cross-Linked Acrylate Photopolymers: A Molecular Dynamics Case Study.

A reactive molecular dynamics approach is used to simulate cross-linking of acrylate polymer networks. By employing the same force field and reactive scheme and studying three representative multifunctional acrylate monomers, we isolate the importance of the nonreactive moieties within these model monomers. Analyses of reactive trajectories benchmark the estimated gel points, cyclomatic character, and spatially resolved cross-linking tendencies of the acrylates as a function of conversion. These insights into the similarities and differences of the polymerization and resulting networks suggest molecular mechanics as a useful tool in the rational design of photopolymerization resins.

Fifteen Nanometer Resolved Patterns in Selective Area Atomic Layer Deposition-Defectivity Reduction by Monolayer Design.

Selective area atomic layer deposition (SA-ALD) offers the potential to replace a lithography step and provide a significant advantage to mitigate pattern errors and relax design rules in semiconductor fabrication. One class of materials that shows promise to enable this selective deposition process are self-assembled monolayers (SAMs). In an effort to more completely understand the ability of these materials to function as barriers for ALD processes and their failure mechanism, a series of SAM derivatives were synthesized and their structure-property relationship explored. These materials incorporate different side group functionalities and were evaluated in the deposition of a sacrificial etch mask. Monolayers with weak supramolecular interactions between components (for example, van der Waals) were found to direct a selective deposition, though they exhibit significant defectivity at and below 100 nm feature sizes. The incorporation of stronger noncovalent supramolecular interacting groups in the monolayer design, such as hydrogen bonding units or pi-pi interactions, did not produce an added benefit over the weaker interacting components. Incorporation of reactive moieties in the monolayer component that enabled the polymerization of an SAM surface, however, provided a more effective barrier, greatly reducing the number and types of defects observed in the selectively deposited ALD film. These reactive monolayers enabled the selective deposition of a film with critical dimensions as low as 15 nm. It was also found that the selectively deposited film functioned as an effective barrier for isotropic etch chemistries, allowing the selective removal of a metal without affecting the surrounding surface. This work enables selective area ALD as a technology through (1) the development of a material that dramatically reduces defectivity and (2) the demonstrated use of the selectively deposited film as an etch mask and its subsequent removal under mild conditions.

Boosting the Heavy Atom Effect by Cavitand Encapsulation: Room Temperature Phosphorescence of Pyrene in the Presence of Oxygen.

A deep cavitand is used to encapsulate the aromatic molecule pyrene in its interior while also binding Tl+ ions with its terminal carboxylates. Steady-state and time-resolved spectroscopic experiments, along with quantum yield measurements, quantify the enhancements of intersystem crossing and room temperature phosphorescence due to cavitand encapsulation. These results are compared to those obtained for pyrene contained in sodium dodecyl sulfate micelles, which is the usual system used to generate room temperature phosphorescence. The combination of selective binding and strong Tl+ recognition by the cavitand enhances the intersystem crossing and decreases the phosphorescence radiative lifetime from ∼30 to 0.23 s. The cavitand also decreases the rate of O2 quenching by a factor of 100. Together, these factors can boost the room temperature phosphorescence signal by several orders of magnitude, allowing it to be detected in water without O2 removal. Host:guest recognition provides a route to molecular-scale triplet emitters that can function under ambient conditions.

Lipid bilayer environments control exchange kinetics of deep cavitand hosts and enhance disfavored guest conformations.

The effects on the molecular recognition properties of water-soluble deep cavitand hosts upon embedding them in phosphocholine lipid bilayer environments have been studied by 2D NMR experiments. By employing suitable guests containing 19F or 13C nuclei that can be encapsulated inside the host, 2D EXSY NMR experiments can be used to analyze and compare the in/out guest exchange rates in aqueous solution, isotropically tumbling micelles, or magnetically ordered bicelles. These analyses show that embedding the deep cavitands in lipid bilayers slows the guest exchange rate, due to the lipids acting as a "compression sleeve" around the host, restricting guest egress. This effect also enhances guest conformations in the host that are not observed in free solution, such as axial cyclohexane conformers and ketone hydrates.

Selective Heavy Element Sensing with a Simple Host-Guest Fluorescent Array.

A simple three component array of host-fluorophore complexes is capable of sensitive and selective discrimination of heavy metal ions, including lanthanide and actinide salts in aqueous solution. Instead of applying optical sensors that only use "single-mode" detection, i.e., coordination of the metal to a specific ligand and monitoring the change in emission of an appended fluorophore, we exploit a series of host-fluorophore complexes that are affected by the presence of small amounts of metal ions in aqueous solution in different ways. Variable host-metal and host-guest-metal interactions lead to both turn-on and turn-off fluorescence sensing mechanisms, enhancing the discriminatory properties of the array. The limit of detection for certain metals is as low as 70 nM, and highly similar metals such as lanthanides and actinides can be easily distinguished at low micromolar concentrations in complex salt mixtures.

Site-Selective Sensing of Histone Methylation Enzyme Activity via an Arrayed Supramolecular Tandem Assay.

Arrayed deep cavitands can be coupled to a fluorescence-based supramolecular tandem assay that allows site-selective in situ monitoring of post-translational modifications catalyzed by the lysine methyltransferase PRDM9 or the lysine demethylase JMJD2E. An arrayed sensor system containing only three cavitand components can detect the specific substrates of enzyme modification, in the presence of other histone peptides in the enzyme assay, enabling investigation of cross-reactivity over multiple methylation sites and interference from nonsubstrate peptides.

Selective protein recognition in supported lipid bilayer arrays by tailored, dual-mode deep cavitand hosts.

Self-folding deep cavitands with variably functionalized upper rims are able to selectively immobilize proteins at a biomimetic supported lipid bilayer surface. The immobilization process takes advantage of the dual-mode binding capabilities of the hosts, combining a defined binding pocket with upper rim charged/H-bonding groups. A variety of proteins can be selectively immobilized at the bilayer interface, either via complementary charge/H-bonding interactions, cavity-based molecular recognition, or a combination of both. The immobilization process can be used to bind unmodified native proteins, epitopes for bioadhesion, or proteins covalently modified with suitable RNMe3+ binding "handles" and charged groups that can either match or mismatch with the cavitand rim. The immobilization process can be monitored in real time using surface plasmon resonance (SPR) spectroscopy, and applied to the construction of cavitand:lipid arrays using the hosts and trehalose vitrified phospholipid vesicles. The selective, dual-mode protein recognition is maintained in the arrays, and can be visualized using SPR imaging.

Site selective reading of epigenetic markers by a dual-mode synthetic receptor array.

Variably functionalized self-folding deep cavitands form an arrayed, fluorescent indicator displacement assay system for the detection of post-translationally modified (PTM) histone peptides. The hosts bind trimethyllysine (KMe3) groups, and use secondary upper rim interactions to provide more sensitive discrimination between targets with identical KMe3 binding handles. The sensor array uses multiple different recognition modes to distinguish between miniscule differences in target, such as identical lysine modifications at different sites of histone peptides. In addition, the sensor is affected by global changes in structure, so it is capable of discriminating between identical PTMs, at identical positions on amino acid fragments that vary only in peptide backbone length, and can be applied to detect non-methylation modifications such as acetylation and phosphorylations located multiple residues away from the targeted binding site. The synergistic application of multiple variables allows dual-mode deep cavitands to approach levels of recognition selectivity usually only seen with antibodies.

Self-Aggregating Deep Cavitand Acts as a Fluorescence Displacement Sensor for Lysine Methylation.

A dual-mode aggregative host:guest indicator displacement sensing system has been created for the detection of trimethylated peptides and determination of histone demethylase activity. The combination of selective recognition of suitably sized trimethylammonium salts and reversible lipophilic aggregation of the host:guest complex provides a unique quenching mechanism that is not only dependent on affinity for sensitivity but the lipophilicity of the indicator. In addition, aggregation can be controlled by the application of chaotropic anions in the mixture, allowing a second level of discrimination between hard lysine groups and softer trimethyllysines.

Synthesis, guest binding, and metal coordination of functionalized self-folding deep cavitands.

A simple method to introduce donor functions to the upper rim of self-folding benzimidazole-based deep cavitands is described. The upper rim donors allow controlled noncovalent binding of suitably sized guest species via both self-complementary hydrogen bonding and space-filling interactions, and metal-mediated self-folding is possible if bidentate coordinators are incorporated.

Labeled protein recognition at a membrane bilayer interface by embedded synthetic receptors.

Self-folding deep cavitands embedded in a supported lipid bilayer are capable of recognizing suitably labeled proteins at the bilayer interface. The addition of a choline derived binding "handle" to a number of different proteins allows their selective noncovalent recognition, with association constants on the order of 10(5) M(-1). The proteins are displayed at the water:bilayer interface, and a single binding handle allows recognition of the large, charged protein by a small molecule synthetic receptor via complementary shape and charge interactions.

Hydrocarbon oxidation catalyzed by self-folded metal-coordinated cavitands.

Functionalized cavitands have been shown to self-fold via coordination of Fe(II) salts and effect catalytic C-H oxidation reactions of unfunctionalized alkanes under mild aqueous conditions in the presence of tert-butyl hydroperoxide as co-oxidant. Secondary and tertiary C-H bonds can be converted to ketones and alcohols, respectively, and ethers can be converted to esters. The cavitands retain the catalytic metal throughout the reaction, and can be recovered by filtration.

Metal-coordinated water-soluble cavitands act as C-H oxidation catalysts.

Cavitands can be smoothly derivatized by CuAAC chemistry to incorporate ligand species at the upper rim. These species can coordinate metal species in a number of different conformations, leading to self-assembly. The metal-coordination confers water solubility on the cavitands, and the iron-bound species are capable of catalytic C-H oxidations of fluorene under mild conditions.