Advances in nanoscale directed assembly strategies have enabled researchers to analogize atomic assembly via chemical reactions and nanoparticle assembly, creating a new nanoscale “periodic table.” We are just beginning to realize the nanoparticle equivalents of molecules and extended materials and are currently developing the ground rules for creating programmable nanometer-scale coordination environments. The ability to create a diverse set of nanoscale architectures from one class of nanoparticle building blocks would allow for the synthesis of designer materials, wherein the physical properties of a material could be predicted and controlled a priori. Our group has taken the first steps toward this goal and developed a means of creating tailorable assembly environments using DNA-nanoparticle conjugates. These nanobioconjugates combine the discrete plasmon resonances of gold nanoparticles with the synthetically controllable and highly selective recognition properties of DNA. Herein, we elucidate the beneficial properties of these materials in diagnostic, therapeutic, and detection capabilities and project their potential use as nanoscale assembly agents to realize complex three-dimensional nanostructures.

Localized surface plasmon resonances (LSPR), collective electron oscillations in nanoparticles, are being heavily scrutinized for applications in chemical and biological sensing, as well as in prototype nanophotonic devices. This phenomenon exhibits an acute dependence on the particle’s size, shape, composition, and environment. The detailed characterization of the structure-function relationship of nanoparticles is obscured by ensemble averaging. Consequently, single-particle data must be obtained to extract useful information from polydisperse reaction mixtures. Recently, a correlated high resolution transmission electron microscopy (HRTEM) LSPR technique has been developed and applied to silver nanocubes. We report here a second generation of experiments using this correlation technique, in which statistical analysis is performed on a large number of single particles. The LSPR dependence on size, shape, material, and environment was probed using silver right bipyramids, silver cubes, and gold cubes. It was found that the slope of the dependence of LSPR peak on size for silver bipyramids increases as the edges become sharper. Also, a plasmon shift of 96 nm was observed between similar silver and gold cubes, while a shift of 26 nm was observed, for gold cubes, between substrates of refractive index (RI) of 1.5 and 2.05.

Nanoscale materials are beginning to have an impact in the field of molecular diagnostics. In particular, gold nanoparticles surface-functionalized with DNA have garnered much recent interest. Due to the unusual optical and catalytic properties of gold nanoparticle labels, several distinct advantages for assay readout have been realized. This review focuses on the progress made in our group over the past seven years in the development of particle surface chemistry and ultrasensitive protein and nucleic acid assays based upon DNA-functionalized gold nanoparticles. For DNA targets, experiments demonstrate that assays based upon gold nanoparticle labels have enhanced target specificity and in certain cases the sensitivity of polymerase chain reaction (PCR), without the need for target amplification. For protein targets, similar experiments demonstrate that assays based upon gold nanoparticles are up to one million times more sensitive than conventional protein detection methods. Recent data using human samples demonstrate the utility of such assays.

Dip Pen Nanolithography (DPN) is a lithographic technique that allows direct deposition of chemicals, metals, biological macromolecules, and other molecular “inks” with nanometer dimensions and precision. This paper addresses recent developments in the design and demonstration of high-density multiprobe DPN arrays. High-density arrays increase the process throughput over individual atomic force microscope (AFM) probes and are easier to use than arrays of undiced commercial probes. We have demonstrated passive arrays made of silicon (8 probes, 310 μm tip-to-tip spacing) and silicon nitride (32 probes, 100 μm tip-to-tip spacing). We have also demonstrated silicon nitride “active” arrays (10 probes, 100 μm tip-to-tip spacing) that have embedded thermal actuators for individual probe control. An optimization model for these devices, based on a generalized multilayer thermal actuator, is also described.

As physical processes for generating miniaturized structures increase in resolution, the types of scientific questions one can ask and answer become increasingly refined. Indeed, if one had the capability to control surface architecture on the 1–100-nm length scale with reasonable speed and accuracy, one could ask and answer some of the most important questions in science and, in the process, develop technologies that could allow for major advances in surface science, chemistry, biology, and human health. This length scale, which is exceedingly difficult to control, comprises the length scale of much of chemistry and most of biology. Indeed, chemical and biochemical recognition events are essentially sophisticated examples of pattern-recognition processes. Therefore, if one could pattern on this length scale with control over feature size, shape, registration, and composition, one could systematically uncover the secrets of recognition processes involving extraordinarily complex molecules. Arecent invention, dip-pen nanolithography (DPN), may provide access to this type of control over surface architecture and entry into a new realm of structure-versus-function studies for chemists, biologists, physicists, and materials scientists.

New methods for micro- and nanofabrication will be essential to scientific progress in many areas of biology, physics, chemistry, and materials science. They will also form enabling technologies for applications ranging from microfluidic devices to micro-optical components to molecular diagnostics to plastic electronics to nanoelectromechanical systems. In many cases, advances will be aided by the highly engineered and spectacularly successful lithographic techniques that are used for microelectronics. These methods have certain drawbacks, however, that will limit their applicability to new devices and fields of study. For example, photolithographies cannot be used with many organic and biological materials due to their chemical incompatibility with typical photoresists and developers; they cannot easily pattern features with dimensions of less than ∼100 nm; they require expensive capital equipment and facilities; they have difficulty forming features on curved, uneven, or rough objects; they can only directly pattern a small set of specialized, photosensitive materials; they cannot reproduce features with complex, three-dimensional (3D) shapes; and they can only pattern small areas in a single step. This situation creates a need for research into alternative patterning methods with capabilities that can complement those of photolithography and other established approaches.

The following article is an edited transcript of the presentation given by Chad A. Mirkin (Northwestern University), recipient of the 1999 Outstanding Young Investigator award, at the 1999 Materials Research Society Spring Meeting on April 6 in San Francisco. Some examples of new work have been added to the transcript.

Our group has been developing a couple of projects over the past few years, both of which deal with the general area of nanotechnology. We are very excited about this work because we think it will lead to a general methodology for preparing nanostructured materials from common inorganic building blocks and readily available DNA-interconnect molecules. The intellectual payoff from this work will be a greater understanding of the collective interactions between nanoscale building blocks in the context of organized materials, while the technological payoffs range from the development of new and useful types of DNA detection strategies, to highperformance catalysts, to the realization of bioelectronic nanocircuitry.

The field of nanotechnology faces three main challenges. The first is to develop a combination of tools and materials that allows us to make small structures and control the architecture of large structures on the nanometer-length scale. Of course, we must be able to do this routinely before we can really explore this field in detail. The second important challenge is to determine the chemical and physical consequences of miniaturization, which is where the real science comes into play in nanotechnology.