Simple Patterning of Cells on a Biocompatible Nonchemically Amplified Resist

Summary: A simple lithographic process in conjunction with a novel biocompatible nonchemically amplified photoresist material was successfully used for cell patterning. UV light irradiation on selected regions of the nonchemically amplified resist film renders the exposed regions hydrophilic by the formation of carboxylic groups. Mouse fibroblast cells were found to be preferentially aligned and proliferated on the UV light exposed regions of the nonchemically amplified resist film where carboxylic groups were present.

Schematic representation of the simplified lithographic process used for cell patterning.     

Surface patterning by microcontact chemistry

In this Feature Article we describe recent progress in covalent surface patterning by microcontact chemistry. Microcontact chemistry is a variation of microcontact printing based on the transfer of reactive "ink" molecules from a microstructured, elastomeric stamp onto surfaces modified with complementary reactive groups, leading to a chemical reaction in the area of contact. In comparison with other lithographic methods, microcontact chemistry has a number of advantageous properties including very short patterning times, low consumption of ink molecules, high resolution and large area patterning. During the past 5 years we and many others have investigated a set of different reactions that allow the modification of flat and also spherical surfaces in an effective way. Especially click-type reactions were found to be versatile for substrate patterning by microcontact chemistry and were applied for chemical modification of reactive self-assembled monolayers and polymer surfaces. Microcontact chemistry has already found broad application for the production of functional surfaces and was also used for the preparation of DNA, RNA, and carbohydrate microarrays, for the immobilization of proteins and cells and for the development of sensors.     

Reactive μCP on ultrathin block copolymer films: Localized chemistry for micro- and nano-scale biomolecular patterning

Three different, complementary soft lithographic approaches for the fabrication of chemical patterns on ultrathin polystyrene-block-poly(tert-butyl acrylate) (PS₆₉₀-b-PtBA₁₂₁₀) films are discussed. Central to the methodology is the previously introduced reactive PS₆₉₀-b-PtBA₁₂₁₀ platform that allows one to covalently graft (bio)molecules via robust amide linkages in high densities on flat, as well as on structured, surfaces. As shown in this paper, the combination of the polymer-based platform and reactive microcontact printing (μCP) patterning approaches allows one to obtain patterns of (bio)molecules with (sub)micrometer feature sizes. The μCP approaches comprise: (A) the direct transfer of functional (bio)molecules from an oxidized elastomeric stamp to hydrolyzed and N-hydroxysuccinimide (NHS) activated PS₆₉₀-b-PtBA₁₂₁₀; (B) the transfer of a passivating poly(ethylene glycol) layer to hydrolyzed and NHS-activated PS₆₉₀-b-PtBA₁₂₁₀ followed by wet chemical grafting of functional moieties; (C) the local hydrolysis of the PtBA skin layer with trifluoroacetic acid (TFA), followed by NHS activation and wet chemical derivatization. The applicability and the versatility of the combination of the polymer thin film-based platform and soft lithographic methodologies for patterning biologically relevant molecules is demonstrated for polyamidoamine (PAMAM) dendrimers, different proteins, as well as probe DNA. The successful hybridization of target DNA and the immobilization of fibronectin in micropatterns show that ultrahigh density patterns for micro- and nano-arrays, as well as for studies of cell-surface interactions, can be conveniently fabricated based on these approaches and platforms.     

Chemically Amplified Resist Based on Dendritic Molecular Glass for Electron Beam Lithography

A novel dendritic molecular glass(MG) containing adamantane core(AD-15) was synthesized and characterized. It exhibits good solubility in common organic solvents and a stable amorphous state at room temperature, which contributes to forming films with different thicknesses by spin-coating. The thermal analysis of AD-15 indicates that no apparent glass transition temperature(T_g) is observed before the thermal decomposition temperature(T_d=160 ℃). The good thermal resistance suggests that it can satisfy the lithographic process and is a candidate for photoresist materials. The patterning properties of AD-15 resist were evaluated by electron beam lithography(EBL). By optimizing the lithographic process parameters, AD-15 resist can achieve 40 nm half-pitch patterns with a line-edge roughness of 4.0 nm. The contrast and sensitivity of AD-15 resist were 1.9 and 67 μC/cm², respectively. Compared with the commercial PMMA(950k) electron beam resist, the sensitivity of AD-15 resist increases by 6 times. This study provides a new example of molecular glass resist with high resolution and sensitivity for EBL.     

Hybrid organic–inorganic sol–gel materials for micro and nanofabrication

In this review hybrid organic–inorganic (HOI) resists as emerging materials alternative to organic polymers for micro and nanolithography are presented and discussed. In particular, results on sol–gel materials belonging to 3-glycidoxypropyltrimethoxysilane based HOI are presented and reviewed, highlighting as various lithographic techniques can be used to pattern their surface and showing examples of micro- and nano-patterned structures achieved with radiation assisted lithography (UV, X-rays and electron beam) or imprint techniques. It will be demonstrated the particular versatility shown by some of these materials, that in some case can be processed with all the lithographic methods herein considered, without any significant modification of their main composition and synthesis procedure. Moreover, results about the investigation of interaction between radiation and HOI materials and thermal treatment will be discussed, as well as possible synthesis strategies and composition modification developed in order to improve efficiency of curing, tailor HOI properties to specific needs (optical properties, resist composition, mechanical stability, etc.) and explore innovative and non conventional patterning techniques. The reported results highlight as these novel materials, thanks to their solution processability and higher performances respect to commercial polymeric resists, allow to use the above mentioned lithographic techniques in a direct patterning process, strongly simplifying conventional technique and reducing their processing time and costs.     

Surface functional group effect on atomic force microscope anodization lithography

The lithographic effect of surface chemical functional groups of organic resists on atomic force microscope (AFM) anodization lithography is investigated using mixed self-assembled monolayers (SAMs). The SAM resist films were prepared with 1,12-diaminododecane dihydrochloride (DAD.2HCl), n-tridecylamine hydrochloride (TDA.HCl), and 1,12-diaminododecane hydrochloride (DAD.HCl), and their film characteristics were evaluated by ellipsometry, zeta-potential measurements, and AFM. The lithographic results indicate that the most dominant factor of the surface functional group effect is the electrochemical property of the surface groups as an anode surface in the anodization reaction, and the dimensions of the protruded patterns are critically determined by the wetting property of the resist surface. By controlling the surface chemical groups with considerations of their effects, high-speed patterning at 2 mm/s was achieved successfully using the mixed SAM resist of DAD.2HCl and TDA.HCl.     

Direct Patterning and Biofunctionalization of a Large‐Area Pristine Graphene Sheet

Direct patterning of streptavidin and NIH 3T3 fibroblast cells was successfully achieved over a large‐area pristine graphene sheet on Si/SiO₂ by aryl azide‐based photografting with the conventional UV lithographic technique and surface‐initiated, atom transfer radical polymerization of oligo(ethylene glycol) methacrylate.     

Fluorous solvent‐soluble imaging materials containing anthracene moieties

Highly fluorinated photoresist polymers that can undergo photodimerization reactions were designed using an anthracene‐based monomer. Through the random radical copolymerizations of 6‐(anthracen‐9‐yl)hexyl methacrylate ( AHMA ) and semiperfluorodecyl methacrylate ( FDMA ) with four different compositions, polymers with M_n = 20,000–27,000 (M_w/M_n = 2.0–2.9) were prepared in benzotrifluoride. The polymers, in particular fluorous solvent‐soluble imaging material‐2 ( FSIM‐2 ), showed sufficient solubility in fluorous solvents, including hydrofluoroethers, but were rendered insoluble by UV exposure (365 nm). This photochemical solubility change was evaluated quantitatively by a quartz crystal microbalance technique, along with tracing the chemical reaction by UV–vis spectroscopy. Finally, FSIM‐2 and fluorous solvents were applied to the photolithographic patterning of organic light‐emitting diode pixels. In the patterning protocol involving the lift‐off of resist films in fluorous solvents, FSIM‐2 was recognized as a promising photoreactive material when compared with a reference polymer P(FDMA‐MAMA) , which necessitates acidolysis reactions for lithographic imaging. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1252–1259     

Chemical amplification resists: Inception,implementation in device manufacture,and new developments

The chemical amplification concept aimed at dramatically boosting the resist sensitivity was invented at IBM Research in San Jose, CA, in 1980. The sensitivity enhancement is achieved by generating acid by irradiation, which induces a cascade of chemical transformations in a resist film. A chemically amplified resist based on acid‐catalyzed deprotection was quickly employed in the mid‐80s in manufacture of 1 megabit (Mbit) dynamic random access memory (DRAM) devices by deep ultraviolet (UV) (～250 nm) lithography in IBM. The unexpectedly high‐resolution capability of chemical amplification resists promoted their acceptance in the resist community and the microelectronics industry. All the advanced lithographic technologies (current workhorse 248 nm, maturing 193 nm, and emerging 157 nm, extreme UV, and projection electron beam) depend on chemical amplification resists. This article describes the invention, implementation in device manufacturing, current status, and future perspective of chemical amplification resists. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3863–3870, 2003     

Molecular dynamics simulation of DNA‐directed assembly of nanoparticle superlattices using patterned templates

DNA‐directed assembly is a well developed approach in constructing desired nano‐architectures. On the other hand, E‐beam lithography is widely utilized for high resolution nano‐scale patterning. Recently, a new technique combining these two methods was developed to epitaxially grow DNA‐mediated nanoparticle superlattices on patterned substrates. However, defects are observed in epitaxial layers which restricts this technique from building large‐scale superlattices for real applications. Here we use molecular dynamics simulations to study and predict defect formation on adsorbed superlattice monolayers. We demonstrate that this epitaxial growth is energetically driven by maximizing DNA hybridization between the epitaxial layer and the substrate and that the shape anisotropy of the DNA‐mediated template posts leads to structural defects. We also develop design rules to dramatically reduce defects on epitaxial layers. Ultimately, with the assist of the computational study, this technique will open the door to constructing well‐ordered, three‐dimensional novel nanomaterials. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 1687–1692     

Evaporation‐Directed Crack‐Patterning of Metal–Organic Framework Colloidal Films and Their Application as Photonic Sensors

A straightforward crack‐patterning method is reported allowing the direct formation of periodic cracks in metal–organic framework (MOF) nanoparticle films during dip‐coating deposition. The crack propagation and periodicity can be easily tailored by controlling the evaporation front and the withdrawal speed. Several MOF‐patterned films can be fabricated on large surfaces and on several substrates (flat, curved or flexible) including the inner surface of a tube, not achievable by other lithographic techniques. We demonstrate that the periodic cracked arrays diffract light and, due to the MOF sorption properties, photonic vapor sensors are fabricated. A new concept of “in‐tube”, MOF‐based diffraction grating sensors is proposed with outstanding sensitivity that can be easily tuned “on‐demand” as function of the desired detection range.     

Patterning biomolecules with a water-soluble release and protection interlayer

We report on a general lithography method for high-resolution biomolecule patterning with a bilayer resist system. Biomolecules are first immobilized on the surface of a substrate and covered by a release-and-protection interlayer of water-soluble polymer. Patterns can then be obtained by lithography with a spin-coated resist layer in a conventional way and transferred onto the substrate by reactive ion etching. Afterward, the resist layer is removed by dissolution in water. To demonstrate a high-resolution patterning, soft UV nanoimprint lithography has been used to produce high-density dot arrays of poly-(L-lysine) molecules on a glass substrate. Both fluorescence images and cell proliferation behaviors on such a patterned substrate have shown evidence of improved stability of biomolecule immobilization comparing to that obtained by microcontact printing techniques.     

Engineering silicon oxide surfaces using self-assembled monolayers

Although a molecular monolayer is only a few nanometers thick it can completely change the properties of a surface. Molecular monolayers can be readily prepared using the Langmuir-Blodgett methodology or by chemisorption on metal and oxide surfaces. This Review focuses on the use of chemisorbed self-assembled monolayers (SAMs) as a platform for the functionalization of silicon oxide surfaces. The controlled organization of molecules and molecular assemblies on silicon oxide will have a prominent place in "bottom-up" nanofabrication, which could revolutionize fields such as nanoelectronics and biotechnology in the near future. In recent years, self-assembled monolayers on silicon oxide have reached a high level of sophistication and have been combined with various lithographic patterning methods to develop new nanofabrication protocols and biological arrays. Nanoscale control over surface properties is of paramount importance to advance from 2D patterning to 3D fabrication.     

A self-assembling protein template for constrained synthesis and patterning of nanoparticle arrays

Self-assembling biomolecules that form highly ordered structures have attracted interest as potential alternatives to conventional lithographic processes for patterning materials. Here, we introduce a general technique for patterning nanoparticle arrays using two-dimensional crystals of genetically modified hollow protein structures called chaperonins. Constrained chemical synthesis of transition metal nanoparticles is initiated using templates functionalized with polyhistidine sequences. These nanoparticles are ordered into arrays because the template-driven synthesis is constrained by the nanoscale structure of the crystallized protein. We anticipate that this system may be used to pattern different classes of nanoparticles based on the growing library of sequences shown to specifically bind or direct the growth of materials.     

Chemically amplified photoresists for 193‐nm photolithography: Effect of molecular structure and photonic parameters on photopatterning

Next generations of microelectronic devices request further miniaturized systems. In this context, photolithography is a key step and many efforts have been paid to develop new irradiation setup and materials compatible with sub‐100 nm resolution. Among other resist platforms, chemically amplified photoresists (CAR) are widely used because of their excellent properties in terms of resolution, sensitivity, and etching resistance. However, low information on the impact of the polymer structure on the lithography performance is available. CAR with well‐controlled polymer structures were thus prepared and investigated. In particular, the impact of the polymer structure on the lithographic performance was evaluated. Linear and branched polymers with various molecular weights and polydispersities were compared. We focused on the dependency of the photosensitivity of the resist with the structural parameters. These results allow further understanding the fundamental phenomena involved by 193‐nm irradiation. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1271–1277, 2010     

Spatially controlled DNA nanopatterns by "click" chemistry using oligonucleotides with different anchoring sites

DNA patterning on surfaces has broad applications in biotechnology, nanotechnology, and other fields of life science. The common patterns make use of the highly selective base pairing which might not be stable enough for further manipulations. Furthermore, the fabrication of well-defined DNA nanostructures on solid surfaces usually lacks chemical linkages to the surface. Here we report a template-free strategy based on "click" chemistry to fabricate spatially controlled DNA nanopatterns immobilized on surfaces. The self-assembly process utilizes DNA with different anchoring sites. The position of anchoring is of crucial importance for the self-assembly process of DNA and greatly influences the assembly of particular DNA nanopatterns. It is shown that the anchoring site in a central position generates tunable nanonetworks with high regularity, compared to DNAs containing anchoring sites at terminal and other positions. The prepared patterns may find applications in DNA capturing and formation of pores and channels and can serve as templates for the patterning using other molecules.     

Bridging the Two Worlds: A Universal Interface between Enzymatic and DNA Computing Systems

Molecular computing based on enzymes or nucleic acids has attracted a great deal of attention due to the perspectives of controlling living systems in the way we control electronic computers. Enzyme‐based computational systems can respond to a great variety of small molecule inputs. They have the advantage of signal amplification and highly specific recognition. DNA computing systems are most often controlled by oligonucleotide inputs/outputs and are capable of sophisticated computing as well as controlling gene expressions. Here, we developed an interface that enables communication of otherwise incompatible nucleic‐acid and enzyme‐computational systems. The enzymatic system processes small molecules as inputs and produces NADH as an output. The NADH output triggers electrochemical release of an oligonucleotide, which is accepted by a DNA computational system as an input. This interface is universal because the enzymatic and DNA computing systems are independent of each other in composition and complexity.     

Label‐free Electrochemiluminescent Enantioselective Sensor for Distinguishing between Chiral Metallosupramolecular Complexes

Chiral molecular recognition of DNA is important for rational drug design and for developing structural probes of DNA conformation. Developing a convenient and inexpensive assay for sensitive and selective identification of DNA‐specific binding compounds with rapid, easy manipulation is in ever‐increasing demand. Here, we present a “turn‐on” and label‐free electrochemiluminescent (ECL) biosensor for distinguishing chiral metallosupramolecular complexes based on DNA three‐way junction formation selectively induced by the analyte. The fabricated ECL sensor shows excellent performance in the chiral discrimination of two enantiomers with an enantioselective recognition ratio of up to 4.4. More importantly, as a “turn‐on” detection system, the ECL chiral sensor does not suffer from false positives and limited signal range of “signal‐off” systems. Therefore, this concept may provide a new insight into the design of efficient sensors for distinguishing chiral molecules and for investigating the interactions between DNA and small molecules.     

Simultaneous Detection of Multiple DNA Targets by Integrating Dual‐Color Graphene Quantum Dot Nanoprobes and Carbon Nanotubes

Simultaneous detection of multiple DNA targets was achieved based on a biocompatible graphene quantum dots (GQDs) and carbon nanotubes (CNTs) platform through spontaneous assembly between dual‐color GQD‐based probes and CNTs and subsequently self‐recognition between DNA probes and targets.     

Nano-Patterning via Molecular Self-Assembly

Surface patterning with microscopically defined structures is a rapidly developing topic, although it is still a challenge for generating patterned surface in the size range of nanometer. Molecular assemblies normally in the size range of 1 to 102 nm should overcome easily the conventional lithographic limit. Although many techniques have been developed to generate patterned surface, surface patterning totally directed by molecular self-assembly has been less addressed. For this purpose, ways of molecular self-assembly to generate regular arrays of nanostructures have been demonstrated in our laboratory including chemisorption of dendron-thiols,surface adsorption of bolaform amphiphiles, and nano-phase separation of rod-coil diblock molecules. As to be discussed, molecular self-assembly is an alternative but effective way to produce patterned structures, particularly in the range of a few nanometers.