A Parallel Approach for Subwavelength Molecular Surgery Using Gene-Specific Positioned Metal Nanoparticles as Laser Light Antennas Andrea Csaki, † Frank Garwe, ‡,| Andrea Steinbr 1 uck, † Gunter Maubach, †,⊥ Grit Festag, † Anja Weise, § Iris Riemann, ‡,X Karsten Ko 1 nig,* ,‡,X and Wolfgang Fritzsche* ,† Institute for Physical High Technology, P.O. Box 100239, 07702 Jena, Germany, JenLab GmbH, Schillerstrasse 1, 07745 Jena, Germany, and Friedrich-Schiller-UniVersity, Institute for Human Genetics and Anthropology, 07745 Jena, Germany Received August 22, 2006; Revised Manuscript Received December 20, 2006 ABSTRACT An optical technique for the parallel manipulation of nanoscale structures with molecular resolution is presented. Bioconjugated metal nanoparticles are thereby positioned at the location of interest, such as, e.g., certain DNA sequences along metaphase chromosomes, prior to pulsed laser light irradiation of the whole sample. The nanoparticles are designed to absorb the introduced energy highly efficiently, in that way acting as nanoantenna. As result of the interaction, structural changes of the sample with subwavelength dimensions and nanoscale precision are observed at the location of the particles. The process leading to the nanolocalized destruction is caused by particle ablation as well as thermal damage of the surrounding material. Nanotechnology implies the control of nanomaterials and nanodevices. Thereby, this field depends on the availability of methods for manipulation at the nanoscale. Chemical approaches based on specific molecular binding and self- organization provide a tremendous potential in the prepara- tion of a variety of possible structures reaching high levels of complexity. Thereby, a controlled manipulation of indi- vidual molecular species, usually in a mixture of quite similar molecules, is an often required but difficult task. Especially, the selection of the molecule of interest and further on the localization of the region to be manipulated (e.g., by cutting or destroying) represent a limiting factor. One approach uses microscopic techniques. A highly focused laser beam is an established tool for manipulation at the microscale, 1 achieving cut widths of subwavelength dimensions. 2 Another truly nanoscopic tool is the AFM, which can be used for manipulations at the molecular scale. 3 Although these microscopic methods provide an impressive control over the location of manipulation, they are limited regarding their degree of parallelization: they manipulate one molecule at a time with a throughput of probably tens per day and require qualified personnel and sophisticated equipment. For applications toward the manipulation of all structures (such as molecules) with a given property in a sample, the above-mentioned microscopic methods are insufficient. This task requires a parallel approach such as nature demonstrates in the case of DNA restriction enzymes that manipulate (cut) all DNA molecules with a specific sequence. Although the creation of similar artificial autonomous and active nanoma- nipulators seems infeasible today, there are approaches that combine the basic feature of manipulation at the nanoscale with an external control: an established example represents the photothermal therapy, where active reagents (photoactive compound) are positioned at a certain localization prior to activation by an external trigger (i.e., light). As result, these cells or tissues are damaged due to produced toxic products. The same basic principle of internal nanoscale converter and external trigger is utilized in several approaches to thermal therapy of cancer, where nanoparticles represent the active elements transforming, e.g., magnetic fields 4 or laser light, 5 * Corresponding authors. E-mail: fritzsche@ipht-jena.de (W.F.), karsten.koenig@ibmt.fraunhofer.de (K.K.). † Institute for Physical High Technology. ‡ JenLab GmbH. § Friedrich-Schiller-University. | Present address: Institute for Applied Physics (IAP), Ultra-optics Group, Albert-Einstein-Strasse 15, 07745 Jena, Germany. ⊥ Present address: IBN Singapore, 31 Biopolis Way, The Nanos #04- 01 Singapore 128669. X Present address: Fraunhofer Institute of Biomedical Technology (IBMT), Ensheimer Strasse 48, 66386 St. Ingbert, Germany. NANO LETTERS 2007 Vol. 7, No. 2 247-253 10.1021/nl061966x CCC: $37.00 © 2007 American Chemical Society Published on Web 01/24/2007