Professor Chad A. Mirkin is Director of the International Institute of nanotechnology at Northwestern University. He is a chemist and a world renowned nanoscience expert, who is known for his development of nanoparticle-based biodetection schemes, the invention of Dip-Pen Nanolithography, and contributions to supramolecular chemistry, nanoelectronics, and nanooptics. He is the author of over 430 manuscripts and over 370 patents and applications, and the founder of three companies, Nanosphere, NanoInk, and Aurasense which are commercializing nanotechnology applications in the life science and semiconductor industries. Currently, he is listed as the most cited (based on total citations) chemist in the world over the past decade and the top most cited nanomedicine researcher in the world. At present, he is a member of President Obama's Council of Advisors for Science and Technology.
The focus of his research is on developing methods for controlling the architecture of molecules and materials on the 1 – 100 nm length scale, and utilizing such structures in the development of analytical tools that can be used in the areas of chemical and biological sensing, gene regulation, lithography, catalysis, optics, and energy generation, storage, and conversion. Mirkin has pioneered the use of biomolecules as synthons in materials science and the development of nanoparticle-based biodiagnostic and gene regulation tools.
In his talk in Atlanta, Polyvalent DNA Architectures: New Modalities for Intracellular Gene Regulation and Detection, Mirkin described his group’s work developing methods for modifying nanoparticles with oligonucleotides and showed how they explored how they can be used as designer constructs for preparing highly ordered, highly functional materials. Some of these structures are crystalline and have lattice parameters which are tailorable by virtue of nanoparticle and DNA synthon. Over the course of these studies, they have discovered many unusual fundamental properties that make these materials particularly useful in biodiagnostics and intracellular gene regulation. His talk focused on the rules that govern the use of these conjugates and sequence specific crystallization, high selectivity and sensitivity nucleic acid and protein detection, and “antisense” therapy. He described the concept of the “antisense particle”, as well as similarly functionalized siRNA particles, which exhibit a range of unique properties that make them very well-suited for gene regulation. In particular, the particles are highly resistant to nuclease digestion, have high and tailorable binding constants for target mRNA, and exhibit high entry efficiency into multiple cell types. He showed how it is possible to tailor the chemistry on the nanoparticle surface, and thus control the particles’ binding strength to complementary target sequences, ultimately demonstrating that changing the binding strength or surface chemistries offers a means to control the degree of protein expression.
Speaking after his presentation, Mirkin talked of his goals and his positive outlook about the development of his nanoscale lithographic methods. Having discovered the ability of delivering nanoscale quantities of materials to precisely defined locations using an atomic force microscope tip(1), the technique was advanced with the use of multiple tips, the technique being known as Dip-Pen Nanolithography, DPN. Although DPN is now used in 22 countries in hundreds of academic and industrial laboratories, the cost of the tip array (also known as probes) can be limiting. Micro-Contact printing pioneered by Whitesides, is a very low cost technique with higher throughput but does not have the resolution of DPN and cannot deliver the perfect registration afforded by the DPN technique. This problem has recently been overcome with the use of arrays of polymer probes costing a few cents per million. This new technique, which merges the attributes of both DPN and contact printing, eliminates almost all of the deficiencies of the parent techniques and has been given the name polymer pen lithography (PPL). The springs defined by cantilevers in a DPN experiment have been built into the elastomeric tips utilized in a PPL experiment. This has enabled many more experiments per unit area opening up the study of combinatorial libraries of nanomaterials. For example, building new structures from individual proteins and viruses is now possible. This is a real example of the bottom-up technology first described by Feynman decades ago.
Building combinatorial arrays from catalysts to biology show PPL as a powerful tool for researchers. Mirkin has demonstrated the production of libraries of materials such as different sized fibronectin features, which can be used to probe the factors critical in controlling the differentiation of stem cells (by identifying which size features control points of cell adhesion and specific differentiation pathways). Looking further ahead, Mirkin sees many applications in optics, plasmonics, catalysis and cellular biology. The development of diagnostic and therapeutic tools with novel nanostructures is really possible as evidenced by the commercial Verigene system (Nanosphere, Illinois), which is also based upon the DNA-modified nanoparticles invented by Mirkin’s lab and has accelerated the development of gene chips for medical diagnostic purposes. It is research that is bringing together multiple disciplines from chemistry to biology where nanotechnology is the truly enabling component.
Additional Information:
The technology of dip-pen nanolithography, DPN, is commercialized by NanoInk (Skokie, IL) and applied to many applications including drug discovery, pharmaceutical counterfeiting and instrumentation for life science and materials research and development. The operation is based on an atomic force microscope. The AFM tip is coated with a suitable chemical “ink” which is programmed to “draw” (deposit) the ink onto a variety of substrates with nanometre precision. This is illustrated in the schematic below:
Detection of the various deposited species is often by fluorescence imaging where a tag has been linked to the species as, at the nanoscale, it would be too small to be seen by normal light microscopy.
One of the key advantages of DPN is the ability to scale up using arrays of AFM tips. This is illustrated by this image of the multiplexed printing of four proteins using NanoInk’s NLP2000, a system designed to create large area nanoscale arrays of biomolecules, nanoparticles and SAM molecules.
This is further demonstrated by this image of fibronectin/laminin patterns were printed to demonstrate multi-component, flexible geometry patterning using NanoInk’s NLP2000, a system designed to create large area nanoscale arrays of biomolecules, nanoparticles and SAM molecules.
References:
- Piner,R. D.; Zhu, J.; Xu, F.; Hong, S.; Mirkin, C. A. "Dip Pen Nanolithography," Science, 1999, 283, 661-663.
- Wooyoung Shim, Adam B. Braunschweig, Xing Liao, Jinan Chai, Jong Kuk Lim, Gengfeng Zheng & Chad A. Mirkin, “Hard tip, soft-spring lithography,” Nature, Vol 469, 27 January 2011, 516-521.
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