Strategies for patterning biomolecules with dip-pen nanolithography

Dip-pen nanolithography (DPN) is an atomic force microscopy (AFM)-based lithography technique, which has the ability to fabricate patterns with a feature size down to approximately 15 nm using both top-down and bottom-up approaches. DPN utilizes the water meniscus formed between an AFM tip and a substrate to transfer ink molecules onto surfaces. A major application of this technique is the fabrication of micro- and nano-arrays of patterned biomolecules. To achieve this goal, a variety of chemical approaches has been used. This review concisely describes the development of DPN in the past decade and presents the related chemical strategies that have been reported to fabricate biomolecular patterns with DPN at micrometer and nanometer scale, classified into direct- and indirect DPN methodologies, discussing tip-functionalization strategies as well.     

Development of Dip‐Pen Nanolithography (DPN) and Its Derivatives

Dip‐pen nanolithography (DPN) is a unique nanofabrication tool that can directly write a variety of molecular patterns on a surface with high resolution and excellent registration. Over the past 20 years, DPN has experienced a tremendous evolution in terms of applicable inks, a remarkable improvement in fabrication throughput, and the development of various derivative technologies. Among these developments, polymer pen lithography (PPL) is the most prominent one that provides a large‐scale, high‐throughput, low‐cost tool for nanofabrication, which significantly extends DPN and beyond. These developments not only expand the scope of the wide field of scanning probe lithography, but also enable DPN and PPL as general approaches for the fabrication or study of nanostructures and nanomaterials. In this review, a focused summary and historical perspective of the technological development of DPN and its derivatives, with a focus on PPL, in one timeline, are provided and future opportunities for technological exploration in this field are proposed.     

Dip‐Pen‐Nanolithographic Patterning of Metallic,Semiconductor, and Metal Oxide Nanostructures on Surfaces

Dip‐pen nanolithography (DPN) is a powerful method to pattern nanostructures on surfaces by the controlled delivery of an “ink” coating the tip of an atomic force microscope upon scanning and contacting with surfaces. The growing interest in the use of nanoparticles as structural and functional elements for the fabrication of nanodevices suggests that the DPN‐stimulated patterning of nanoparticles on surfaces might be a useful technique to assemble hierarchical architectures of nanoparticles that could pave methodologies for functional nanocircuits or nanodevices. This Review presents different methodologies for the nanolithographic patterning of metallic, semiconductor, and metal oxide nanostructures on surfaces. The mechanisms involved in the formation of the nanostructures are discussed and the effects that control the dimensions of the resulting patterns are reviewed. The possible applications of the nanostructures are also addressed.

     

Biochips for Cell Biology by Combined Dip‐Pen Nanolithography and DNA‐Directed Protein Immobilization

A general methodology for patterning of multiple protein ligands with lateral dimensions below those of single cells is described. It employs dip pen nanolithography (DPN) patterning of DNA oligonucleotides which are then used as capture strands for DNA‐directed immobilization (DDI) of oligonucleotide‐tagged proteins. This study reports the development and optimization of PEG‐based liquid ink, used as carrier for the immobilization of alkylamino‐labeled DNA oligomers on chemically activated glass surfaces. The resulting DNA arrays have typical spot sizes of 4–5 μm with a pitch of 12 μm micrometer. It is demonstrated that the arrays can be further functionalized with covalent DNA‐streptavidin (DNA‐STV) conjugates bearing ligands recognized by cells. To this end, biotinylated epidermal growth factor (EGF) is coupled to the DNA‐STV conjugates, the resulting constructs are hybridized with the DNA arrays and the resulting surfaces used for the culturing of MCF‐7 (human breast adenocarcinoma) cells. Owing to the lateral diffusion of transmembrane proteins in the cell's plasma membrane, specific recruitment and concentration of EGF receptor can be induced specifically at the sites where the ligands are bound on the solid substrate. This is a clear demonstration that this method is suitable for precise functional manipulations of subcellular areas within living cells.     

Direct‐Patterning SWCNTs Using Dip Pen Nanolithography for SWCNT/Silicon Solar Cells

Dip pen nanolithography (DPN) is used to pattern single‐walled carbon nanotube (SWCNT) lines between the n‐type Si and SWCNT film in SWCNT/Si solar cells. The SWCNT ink composition, loading, and DPN pretreatment are optimized to improve patterning. This improved DPN technique is then used to successfully pattern >1 mm long SWCNT lines consistently. This is a 20‐fold increase in the previously reported direct‐patterning of SWCNT lines using the DPN technique, and demonstrates the scalability of the technique to pattern larger areas. The degree of the uniformity of SWCNTs in these lines is further characterized by Raman spectroscopy and scanning electron microscopy. The patterned SWCNT lines are used as thin conductive pathways in SWCNT/Si solar cells, similar to front contact electrodes. The critical parameters of these solar cells are measured and compared to control cells without SWCNT lines. The addition of SWCNT lines increases power conversion efficiency by 40% (relative). Importantly, the SWCNT lines reduce average series resistance by 44%, and consequently increase average fill factor by 24%.     

Patterning of Hydrophilic and Hydrophobic Gold and Magnetite Nanoparticles by Dip Pen Nanolithography

Nanoparticles offer unique physical and chemical properties. Dip pen nanolithography of nanoparticles enables versatile patterning and nanofabrication with potential application in electronics and sensing, but is not well studied yet. Herein, the patterned deposition of various nanoparticles onto unmodified silicon substrates is presented. It is shown that aqueous solutions of hydrophilic citrate and cyclodextrin functionalized gold nanoparticles as well as poly(acrylic) acid decorated magnetite nanoparticles are feasible for writing nanostructures. Both smaller and larger nanoparticles can be patterned. Hydrophobic oleylamine or n-dodecylamine capped gold nanoparticles and oleic acid decorated magnetite nanoparticles are deposited from toluene. Tip loading is carried out by dip-coating, and writing succeeds fast within 0.1 s. Also, coating with longer tip dwell times, at different relative humidity and varying frequency are studied for deposition of nanoparticle clusters. The resulting feature size is between 300 and 1780 nm as determined by scanning electron microscopy. Atomic force microscopy confirms that the heights of the deposited structures correspond to a single or double layer of nanoparticles. Higher writing speeds lead to smaller line thicknesses, offering possibilities to more complex structures. Dip pen nanolithography can hence be used to pattern nanoparticles on silicon substrates independent of the surface chemistry.     

The Role of Liquid Ink Transport in the Direct Placement of Quantum Dot Emitters onto Sub‐Micrometer Antennas by Dip‐Pen Nanolithography

Dip‐pen nanolithography (DPN) is used to precisely position core/thick‐shell (“giant”) quantum dots (gQDs; ≥10 nm in diameter) exclusively on top of silicon nanodisk antennas (≈500 nm diameter pillars with a height of ≈200 nm), resulting in periodic arrays of hybrid nanostructures and demonstrating a facile integration strategy toward next‐generation quantum light sources. A three‐step reading‐inking‐writing approach is employed, where atomic force microscopy (AFM) images of the pre‐patterned substrate topography are used as maps to direct accurate placement of nanocrystals. The DPN “ink” comprises gQDs suspended in a non‐aqueous carrier solvent, o‐dichlorobenzene. Systematic analyses of factors influencing deposition rate for this non‐conventional DPN ink are described for flat substrates and used to establish the conditions required to achieve small (sub‐500 nm) feature sizes, namely: dwell time, ink‐substrate contact angle and ink volume. Finally, it is shown that the rate of solvent transport controls the feature size in which gQDs are found on the substrate, but also that the number and consistency of nanocrystals deposited depends on the stability of the gQD suspension. Overall, the results lay the groundwork for expanded use of nanocrystal liquid inks and DPN for fabrication of multi‐component nanostructures that are challenging to create using traditional lithographic techniques.