Infrared Spectroscopic Mapping of Single Nanoparticles and Viruses at Nanoscale Resolution Markus Brehm, Thomas Taubner, ² Rainer Hillenbrand, and Fritz Keilmann* Max-Planck-Institut fu ¨r Biochemie & Center for NanoScience (CeNS), 82152 Martinsried, Mu ¨nchen, Germany Received May 12, 2006; Revised Manuscript Received May 22, 2006 ABSTRACT We demonstrate that scattering near-field microscopy (s-SNOM) can determine infrared “fingerprint” spectra of individual poly(methyl methacrylate) nanobeads and viruses as small as 18 nm. Amplitude and phase spectra are found surprisingly strong, even at a probed volume of only 10 -20 l, and robust in regard to particle size and substrate. This makes infrared spectroscopic s-SNOM a versatile tool for chemical andsin the case of proteinssecondary-structure identification. The advancement of nanoscience requires the detection and identification of single small particles. Detection is possible by various microscopies including light microscopy, 1,2 but label-free compositional identification is still a great chal- lenge. Infrared and Raman spectroscopies do provide chemi- cal recognition via molecular-vibrational “fingerprints” and, in principle, offer a nanoscale resolution owing to field confinement 3-7 and enhancement effects 8-11 of a sharp probing tip. Scanning-probe microscopy, especially atomic force microscopy is widely used to map the topography of a sample with resolution of a few nanometers. But the sharp probe tip can also sense other properties such as the local elasticity of the sample. Concerning the important task of recognizing chemical composition, it is fortunate that local optical properties are measurable by light scattering from the tip 3,8 since most materials can be identified from their optical spectra. The highly confined tip near-field permits ultrahigh optical resolution <20 nm with visible and mid- infrared 12 illumination, and furthermore features sensitivity enhancement akin to surface-enhanced Raman scattering 13 and surface-enhanced infrared absorption. 14 The local optical response measured by elastic light scattering from a tip relates to the complex dielectric value of the sample; 15 hence spectroscopic s-SNOM can assess the sample’s optical dispersion, from which one can recognize the infrared fingerprint signature, and finally assign the chemical composition. 5-7 Of utmost practical interest, but still unan- swered, is the question of whether infrared scattering can detect molecular vibrational resonances with sufficient sensitivity to chemically recognize single nanoparticles and even structural subunits of such particles. To prove that fingerprint infrared spectra can be obtained from single nanoparticles, we study spherical beads of poly- (methyl methacrylate) (PMMA) with 30-70 nm diameter * To whom correspondence may be addressed. Phone: +49 89 8578 2617. Fax: +49 89 8578 2641. E-mail: Keilmann@biochem.mpg.de. ² Present address: Department of Material Science and Engineering, Stanford University, Stanford, CA 94305. VOLUME 6, NUMBER 7, JULY 2006 © Copyright 2006 by the American Chemical Society 10.1021/nl0610836 CCC: $33.50 © 2006 American Chemical Society Published on Web 06/10/2006