Quantum Dots for Multimodal Bioimaging and Sensing Applications Swadeshmukul Santra, 1 Heesun Yang 2 , Soumitra Kar, 3 Subir K. Sabui 3 , Parvesh Sharma 4 , Paul H. Holloway 5 , Glenn A. Walter 6 , Brij M. Moudgil 4 , and Edward Scott 7 1 NanoScience Technology Center, Department of Chemistry and Biomolecular Science Center, University of Central Florida, Orlando, FL 32826, USA Fax: 1 407 882 2819; Tel: 1 407 882 2848 ssantra@mail.ucf.edu 2 Department of Materials Science and Engineering, Hongik University, Seoul, 121-791, Korea 3 NanoScience Technology Center, University of Central Florida, Orlando, FL 32826, USA 4 Particle Engineering Research Center and Material Science and Engineering, University of Florida, Gainesville, 32611, USA 5 Department of Materials Science and Engineering, University of Florida, Gainesville, 32611, USA 6 Department of Physiology and Functional Genomics, McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA 7 Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, 32611, USA ABSTRACT Fluorescent quantum dots (Qdots) have demonstrated their potential in diagnostic bioimaging applications in vitro. For in vivo bioimaging applications, however, the embodiment of additional properties such as paramagnetism onto the same fluorescent probes is highly desirable. These multimodal probes would benefit in vivo disease diagnosis and surgical guidance based on their ability to be detected in multiple modes (i.e. optically and magnetically). A single-step multimodal Qdot synthesis and surface modification technique that can be used for making various engineered multimodal nanoparticles including Qdots is described here. The development of paramagnetic Gd III - functionalized fluorescent Qdots and their applications in labeling various biological entities such as cells and tissues will be demonstrated. 1. INTRODUCTION More than a decade-long studies on colloidal luminescent quantum dots (Qdots) have revealed that the effective surface passivation is critical in making Qdots extremely bright and photostable[1-7]. A robust surface passivation will thus produce high quality Qdots [7-15]. Over the past several years, fluorescent quantum dots (Qdots) have been well studied and have shown tremendous potential in labeling biological entities such as cells, tissues and biohazard particles (bacteria, viruses, etc.). Qdots stand out from conventional organic based dyes in at least two aspects: photostability and sensitivity. Due to their hydrophobic surface property, an appropriate surface coating is necessary to disperse Qdots in aqueous solution. Coating also protects them from photo-initiated surface degradation, which is directly related to fading of fluorescence intensity and toxicity. Despite recently reported toxic effects of quantum dots, both in vitro and in vivo studies have been reported in favor of using Qdots for biolabeling applications, including in vivo disease diagnosis. 2. EXPERIMENTAL SECTION Qdots were synthesized using AOT/heptane/water microemulsion system. Typically, Cd(CH 3 COO) 2 .2H 2 O, Mn(CH 3 COO) 2 , Na 2 S, and Zn(CH 3 COO) 2 were used for the preparation of (Cd 2+ + Mn 2+ )-, S 2- -, and Zn 2+ -containing the standard aqueous solutions. Each aqueous solution was stirred with an AOT/heptane solution, forming the micellar solution. Mn doped CdS core nanocrystals were formed by mixing (Cd 2+ + Mn 2+ )- and S 2- -containing micellar solutions rapidly for 10-15 min. The W 0 value for the W/O microemulsion was 10 and the total microemulsion volume was 87 ml. For the growth of a shell layer, a Zn 2+ - containing micellar solution was added at a very slow rate (1.5 ml/min) into the CdS:Mn nanocrystal micellar solution. The nucleation and growth of a separate ZnS phase were suppressed by the very slow addition of the Zn 2+ -containing micellar solution. After addition of the Zn 2+ -containing microemulsion, 7.4 mL of tetraethyl orthosilicate (TEOS) was injected into the CdS:Mn/ZnS core/shell Qdot microemulsion and mixed for 15 min at room temperature. The hydrolysis and condensation reactions were initiated by adding NH 4 OH in the form of a microemulsion, which is (a) NSTI-Nanotech 2007, www.nsti.org, ISBN 1420061836 Vol. 2, 2007 263