Centimeter-scale subwavelength photolithography using metal-coated elastomeric photomasks with modulated light intensity at the oblique sidewalls.

By coating polydimethylsiloxane (PDMS) relief structures with a layer of opaque metal such as gold, the incident light is strictly allowed to pass through the nanoscopic apertures at the sidewalls of PDMS reliefs to expose underlying photoresist at nanoscale regions, thus producing subwavelength nanopatterns covering centimeter-scale areas. It was found that the sidewalls were a little oblique, which was the key to form the nanoscale apertures. Two-sided and one-sided subwavelength apertures can be constructed by employing vertical and oblique metal evaporation directions, respectively. Consequently, two-line and one-line subwavelength nanopatterns with programmable feature shapes, sizes, and periodicities could be produced using the obtained photomasks. The smallest aperture size and line width of 80 nm were achieved. In contrast to the generation of raised positive photoresist nanopatterns in phase shifting photolithography, the recessed positive photoresist nanopatterns produced in this study provide a convenient route to transfer the resist nanopatterns to metal nanopatterns. This nanolithography methodology possesses the distinctive advantages of simplicity, low cost, high throughput, and nanoscale feature size and shape controllability, making it a potent nanofabrication technique to enable functional nanostructures for various potential applications.

Parallel near-field photolithography with metal-coated elastomeric masks.

Developing a cost-effective nanolithography strategy that enables the production of subwavelength features with various shapes over large areas is a long-standing goal in the nanotechnology community. Herein, an inexpensive nanolithographic technique that combines the wafer-scale production capability of photolithography with the subwavelength feature size controllability of near-field photolithography was developed to fabricate centimeter-scale up to wafer-scale sub-100-nm variously shaped nanopatterns on surfaces. The wafer-scale elastomeric trench-based photomasks with subwavelength apertures created at the apexes were compatible with mask aligners, allowing for the production of wafer-scale subwavelength nanopatterns with adjustable feature sizes, shapes, and periodicities. The smallest feature sizes of 50 and 80 nm were achieved on positive tone and negative tone photoresist surfaces, respectively, which could be ascribed to a near-field optical effect. The fabricated centimeter-scale nanopatterns were functionalized to study cell-matrix adhesion and migration. Compared to currently developed nanolithographic methods that approach similar functionalities, this facile nanolithographic strategy combines the merits of low cost, subwavelength feature size, high throughput, and varied feature shapes, making it an affordable approach to be used in academic research for researchers at most institutions.

Microstructured graphene arrays for highly sensitive flexible tactile sensors.

A highly sensitive tactile sensor is devised by applying microstructured graphene arrays as sensitive layers. The combination of graphene and anisotropic microstructures endows this sensor with an ultra-high sensitivity of -5.53 kPa(-1) , an ultra-fast response time of only 0.2 ms, as well as good reliability, rendering it promising for the application of tactile sensing in artificial skin and human-machine interface.

Polysarcosine as PEG Alternative for Enhanced Camptothecin-Induced Cancer Immunogenic Cell Death.

Nanomedicine-enhanced immunogenic cell death (ICD) has attracted considerable attention for its great potential in cancer treatment. Even though polyethylene glycol (PEG) is widely recognized as the gold standard for surface modification of nanomedicines, some shortcomings associated with this PEGylation, such as hindered cell endocytosis and accelerated blood clearance phenomenon, have been revealed in recent years. Notably, polysarcosine (PSar) as a highly biocompatible polymer can be finely synthesized by mild ring-opening polymerization (ROP) of sarcosine N-carboxyanhydrides (Sar-NCAs) and exhibit great potential as an alternative to PEG. In this article, PSar-b-polycamptothecin block copolymers are synthesized by sequential ROP of camptothecin-based NCAs (CPT-NCAs) and Sar-NCAs. Then, the detailed and systematic comparison between PEGylation and PSarylation against the 4T1 tumor model indicates that PSar decoration can facilitate the cell endocytosis, greatly enhancing the ICD effects and antitumor efficacy. Therefore, it is believed that this well-developed PSarylation technique will achieve effective and precise cancer treatment in the near future.

Polymeric Nanoreactors as Emerging Nanoplatforms for Cancer Precise Nanomedicine.

How to precisely detect and effectively cure cancer which is defined as precise nanomedicine has drawn great attention worldwide. Polymeric nanoreactors which can in situ catalyze inert species into activated ones, can greatly increase imaging quality and enhance therapeutic effects along with decreased background interference and reduced serious side effects. After a brief introduction, the design and preparation of polymeric nanoreactors are discussed from the following aspects, that is, solvent-switch, pH-tuning, film rehydration, hard template, electrostatic interaction, and polymerization-induced self-assembly (PISA). Subsequently, the biomedical applications of these nanoreactors in the fields of cancer imaging, cancer therapy, and cancer theranostics are highlighted. The last but not least, conclusions and future perspectives about polymeric nanoreactors are given. It is believed that polymeric nanoreactors can bring a great opportunity for future fabrication and clinical translation of precise nanomedicine.

Colorimetric assay for heterogeneous-catalyzed lipase activity: enzyme-regulated gold nanoparticle aggregation.

Lipase is a neglected enzyme in the field of gold nanoparticle-based enzyme assays. This paper reports a novel colorimetric probe to rapidly visualize lipase activities by using Tween 20 functioned GNPs (Tween 20-GNPs) as a reporter. The present strategy hence could overcome the limitations caused by the heterogeneous interface in lipase assay. Catalytic hydrolytic cleavage of the ester bond in Tween 20-GNPs by lipase will trigger the rapid aggregation of GNPs at a high salt solution. The color change from red to purple could be used to sense the activity of lipase. The detection limit (3σ) is as low as 2.8 × 10-2 mg/mL. A preliminary enzyme activity screening was carried out for seven commercially purchased lipase samples. It also has been successfully applied to detecting lipase in fermentation broth of Bacillus subtilis without any pretreatment.

A plasmonic nanosensor for lipase activity based on enzyme-controlled gold nanoparticles growth in situ.

A plasmonic nanosensor for lipase activity was developed based on one-pot nanoparticle growth. Tween 80 was selected not only as the substrate for lipase recognition but also as the reducing and stabilizing agent for the sensor fabrication. The different molecular groups in Tween 80 could have different roles in the fabrication procedure; the H2O2 produced by the autoxidation of the ethylene oxide subunits in Tween 80 could reduce the AuCl4(-) ions to Au atoms, meanwhile, the lipase could hydrolyze its carboxyl ester bond, which could, in turn, control the rate of nucleation of the gold nanoparticles (AuNPs) and tailor the localized surface plasmon resonance (LSPR) of the AuNP transducers. The color changes, which depend on the absence or presence of the lipase, could be used to sense the lipase activity. A linear response ranging from 0.025 to 4 mg mL(-1) and a detection limit of the lipase as low as 3.47 µg mL(-1) were achieved. This strategy circumvents the problems encountered by general enzyme assays that require sophisticated instruments and complicated assembling steps. The methodology can benefit the assays of heterogeneous-catalyzed enzymes.

Fabrication of porous matrix membrane (PMM) using metal-organic framework as green template for water treatment.

Pressure-driven membranes with high porosity can potentially be fabricated by removing template, such as low water stability metal-organic frameworks (MOFs) or other nanoparticles, in polymeric matrix. We report on the use of benign MOFs as green template to enhance porosity and interconnectivity of the water treatment membranes. Significantly enhanced separation performance was observed which might be attributed to the mass transfer coefficient of the substrate layer increased in ultrafiltration (UF) application.

Beam pen lithography.

Lithography techniques are currently being developed to fabricate nanoscale components for integrated circuits, medical diagnostics and optoelectronics. In conventional far-field optical lithography, lateral feature resolution is diffraction-limited. Approaches that overcome the diffraction limit have been developed, but these are difficult to implement or they preclude arbitrary pattern formation. Techniques based on near-field scanning optical microscopy can overcome the diffraction limit, but they suffer from inherently low throughput and restricted scan areas. Highly parallel two-dimensional, silicon-based, near-field scanning optical microscopy aperture arrays have been fabricated, but aligning a non-deformable aperture array to a large-area substrate with near-field proximity remains challenging. However, recent advances in lithographies based on scanning probe microscopy have made use of transparent two-dimensional arrays of pyramid-shaped elastomeric tips (or 'pens') for large-area, high-throughput patterning of ink molecules. Here, we report a massively parallel scanning probe microscopy-based approach that can generate arbitrary patterns by passing 400-nm light through nanoscopic apertures at each tip in the array. The technique, termed beam pen lithography, can toggle between near- and far-field distances, allowing both sub-diffraction limit (100 nm) and larger features to be generated.

Molecular printing.

Molecular printing techniques, which involve the direct transfer of molecules to a substrate with submicrometre resolution, have been extensively developed over the past decade and have enabled many applications. Arrays of features on this scale have been used to direct materials assembly, in nanoelectronics, and as tools for genetic analysis and disease detection. The past decade has witnessed the maturation of molecular printing led by two synergistic technologies: dip-pen nanolithography and soft lithography. Both are characterized by material and substrate flexibility, but dip-pen nanolithography has unlimited pattern design whereas soft lithography has limited pattern flexibility but is low in cost and has high throughput. Advances in DPN tip arrays and inking methods have increased the throughput and enabled applications such as multiplexed arrays. A new approach to molecular printing, polymer-pen lithography, achieves low-cost, high-throughput and pattern flexibility. This Perspective discusses the evolution and future directions of molecular printing.

Polymer pen lithography.

We report a low-cost, high-throughput scanning probe lithography method that uses a soft elastomeric tip array, rather than tips mounted on individual cantilevers, to deliver inks to a surface in a "direct write" manner. Polymer pen lithography merges the feature size control of dip-pen nanolithography with the large-area capability of contact printing. Because ink delivery is time and force dependent, features on the nanometer, micrometer, and macroscopic length scales can be formed with the same tip array. Arrays with as many as about 11 million pyramid-shaped pens can be brought into contact with substrates and readily leveled optically to ensure uniform pattern development.