Soft lithography for micro- and nanoscale patterning

Nature Protocols, Feb 2010

This protocol provides an introduction to soft lithography—a collection of techniques based on printing, molding and embossing with an elastomeric stamp. Soft lithography provides access to three-dimensional and curved structures, tolerates a wide variety of materials, generates well-defined and controllable surface chemistries, and is generally compatible with biological applications. It is also low in cost, experimentally convenient and has emerged as a technology useful for a number of applications that include cell biology, microfluidics, lab-on-a-chip, microelectromechanical systems and flexible electronics/photonics. As examples, here we focus on three of the commonly used soft lithographic techniques: (i) microcontact printing of alkanethiols and proteins on gold-coated and glass substrates; (ii) replica molding for fabrication of microfluidic devices in poly(dimethyl siloxane), and of nanostructures in polyurethane or epoxy; and (iii) solvent-assisted micromolding of nanostructures in poly(methyl methacrylate).

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Soft lithography for micro- and nanoscale patterning

Abstract This protocol provides an introduction to soft lithography—a collection of techniques based on printing, molding and embossing with an elastomeric stamp. Soft lithography provides access to three-dimensional and curved structures, tolerates a wide variety of materials, generates well-defined and controllable surface chemistries, and is generally compatible with biological applications. It is also low in cost, experimentally convenient and has emerged as a technology useful for a number of applications that include cell biology, microfluidics, lab-on-a-chip, microelectromechanical systems and flexible electronics/photonics. As examples, here we focus on three of the commonly used soft lithographic techniques: (i) microcontact printing of alkanethiols and proteins on gold-coated and glass substrates; (ii) replica molding for fabrication of microfluidic devices in poly(dimethyl siloxane), and of nanostructures in polyurethane or epoxy; and (iii) solvent-assisted micromolding of nanostructures in poly(methyl methacrylate). Introduction The strategy of 'smaller brings new capability' has begun to change the world of biotechnology as it has transformed microelectronics1. Successful applications of small systems include microarrays for high-speed DNA sequencing2, microfluidic devices for performing PCR3, lab-on-a-chip (LOC) systems for synthesis and analysis of peptide and oligonucleotide libraries4, and microchips for drug screening5 and for investigation of cultured cells6. As the workhorse of microfabrication, photolithography7 has contributed an important role in most of these applications, including the fabrication of DNA arrays in the late 1980s (ref. 8). However, this technique has a number of limitations for applications related to biological systems. First, photolithography is an intrinsically expensive process because the equipment used was developed for the highly demanding processes required for fabrication of microelectronic devices. The capital investment required to build a clean room makes photolithography less than accessible to most chemists, biochemists and biologists. Thus, photolithography is most successful when applied to a limited set of materials. Users wishing to study 'dirty' organic systems are usually excluded from an electronics-qualified clean-room facility. Second, photolithography is often carried out by projecting a pattern on a photomask onto a photoresist film. Although photomasks are commercially available, the time and cost involved in the fabrication of such masks present a significant barrier to the use of photolithography in rapid, inexpensive prototyping of test patterns and devices. Third, photolithography provides little or no control over surface chemistry, and it is not applicable to curved or non-planar substrates. Soft lithography9 represents a conceptually different approach to rapid prototyping of various types of both microscale and nanoscale structures, and devices on planar, curved, flexible and soft substrates especially when low cost is required. A large number of patterning techniques—microcontact printing (μCP)10, replica molding (REM)11, microtransfer molding12, micromolding in capillary13, solvent-assisted micromolding (SAMIM)14, phase-shifting edge lithography15, nanotransfer printing16, decal transfer lithography17 and nanoskiving18—form the basis of soft lithography; they are essentially based on printing, molding and embossing with an elastomeric stamp (Protocols for μCP, REM and SAMIM are described in the Procedure and outlined in Fig. 1). New variants such as dip-pen nanolithography have also emerged19,20,21. All these techniques use organic and polymeric materials that are referred to as soft matter by physicists. Figure 1: Schematic illustration of the four major steps involved in soft lithography and three major soft lithographic techniques. Full size image μCP As the forerunner of soft lithography, μCP provides an attractive route to microscale patterns and structures needed for applications in biotechnology. For example, μCP offers an ability to engineer the properties of a surface with molecular-level detail using self-assembled monolayers (SAMs) of alkanethiols on a substrate coated with a metal such as gold (Au), silver (Ag), copper (Cu), palladium (Pd) and platinum (Pt)22. In this study, the substrate refers to a physical object, which is somewhat different from the meaning in enzymology. Typical planar substrates for forming alkanethiolate SAMs include thin films of a metal deposited on silicon, mica, glass or even plastic materials. The substrates can be easily prepared by physical vapor deposition methods, such as thermal or electron beam evaporation23. The patterned SAMs have proved valuable for studying the role of spatial signaling in cell biology by exquisitely controlling the molecular structure of a surface in contact with cells24. One can create well-defined regions with 'cell-friendly' (protein-covered) and (...truncated)


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Dong Qin, Younan Xia, George M Whitesides. Soft lithography for micro- and nanoscale patterning, Nature Protocols, 2010, pp. 491-502, Issue: 5, DOI: 10.1038/nprot.2009.234