Nanoparticle Assembly DOI: 10.1002/ange.201006231 Silica-Nanoparticle Coatings by Adsorption from Lysine–Silica- Nanoparticle Sols on Inorganic and Biological Surfaces** Nicole Atchison, Wei Fan, Damien D. Brewer, Manickam A. Arunagirinathan, Bernhard J. Hering, Satish Kumar, Klearchos K. Papas, Efrosini Kokkoli,* and Michael Tsapatsis* Silica nanoparticles have been used in applications including membranes, [1] catalyst supports, [2] optical devices, [3] chemical/ biological sensors, [4] and as building blocks of colloidal and nanoparticle crystals. [5] Furthermore, their relatively low cytotoxicity [6] enables multiple biological applications includ- ing dye-doped nanoparticles for cell imaging, [7] drug and DNA delivery, [8] cell surface modification, [9] cell membrane isolation, [10] and sol–gel cell encapsulation. [11–14] Silica nano- particles are synthesized predominantly using the Stöber method, [15] resulting in narrow distributions of large particles (> 200 nm) but broad distributions of smaller particles. Recently, we [16–18] and others [19, 20] introduced a method for synthesizing small, monodispersed silica nanoparticles in an aqueous environment in the presence of lysine or other basic amino acids. The approach allows for fine-tuning particle size resulting in silica-nanoparticle sols (hereafter referred to as lys–sil sols) that are stable for months, and also resist aggregation after being dispersed in other solvents including certain cell culture media. [14] It has also been demonstrated that lys–sil sols can form colloidal crystal arrays [20] and thin films by convective assembly. [17] In combination with their tuneable particle size, this translates to capability for precise pore size control. However, convective methods, including evaporation- induced self-assembly (EISA), do not allow manipulation of deposit microstructure since they strongly favor close pack- ing. Moreover, they are not compatible with applications where the substrate cannot be dried, such as living cell encapsulation. In this respect, it is desirable to develop functionalization techniques [21] that enable deposition by adsorption. Here, we report new lys–sil sol syntheses that allow for adjustment of particle charge by surface function- alization. We also report on the inclusion of a fluorescent dye in the silica nanoparticles to be rendered observable by optical microscopy. We then demonstrate tuneable and predictable deposition behavior on inorganic surfaces, as well as layer-by-layer (LBL) assembly for living cell encap- sulation. The findings reported here further establish lys–sil sols as a simple and flexible tool for precise colloidal assembly. To create stable, positively charged silica particles, surface modification was performed with N-trimethoxysilylpropyl- N,N,N-trimethylammonium chloride (TMAPS) [22] as well as other functionalizing agents. The modification was assessed with zeta potential measurements as a function of the lys–sil sol pH (Supporting Information, Figure S1). The unmodified silica nanoparticles show slightly negative surface potential at low pH, and the zeta potential decreases to À90 mV when the pH is close to 9.0. The surface potential after surface modification by TMAPS becomes positive when the pH is 7.0 and further increases to around + 40 mV when the pH is below 5. Alternative functionalizations and reaction condi- tions result in distinct behaviors (Figure S1) demonstrating that the surface potential of lys–sil sols can be finely tuned. The modified particles show similar monodispersity, colloidal stability, and evaporative assembly characteristics as those in the original lys–sil sols. By solvent evaporation, three-dimen- sional colloidal crystals with well-defined mesoporosity can be formed from the surface-modified silica nanoparticles (Figure S2). For optical observation, the silica nanoparticles were labeled with a fluorescent dye. Rhodamine 6G was incorporated by physical adsorption and subsequent capping with a silica outer shell. [23] The UV/Vis absorption spectra for the lys–sil sols with surface-modified fluorescent nanoparti- cles show maximum absorption at approximately 526 nm, the same as the free dye, and intensity corresponding to five dye molecules per nanoparticle (Figure S3). Photographs of the sols before and after high-speed centrifugation confirm that the dye is present in the nanoparticles (Figure S3 insets). The ability to precisely control fluorescent and nonfluorescent [*] Dr. W. Fan, [+] D. D. Brewer, Dr. M. A. Arunagirinathan, Prof. S. Kumar, Prof. E. Kokkoli, Prof. M. Tsapatsis Department of Chemical Engineering & Materials Science University of Minnesota, Minneapolis, MN 55455 (USA) Fax: (+ 1) 612-626-7246 E-mail: kokkoli@umn.edu tsapatsis@umn.edu N. Atchison [+] Department of Biomedical Engineering University of Minnesota, Minneapolis, MN 55455 (USA) Prof. B. J. Hering, Prof. K. K. Papas Schulze Diabetes Institute, Department of Surgery University of Minnesota, Minneapolis, MN 55455 (USA) [ + ] These authors contributed equally to this work. [**] Funding was provided by the Center for Nanostructured Applica- tions, the Amundson Chair Fund at University of Minnesota, and the NSF (CBET 0956601). Parts of this work were carried out in the Institute of Technology Characterization Facility, University of Minnesota, which receives support from NSF through the NNIN program. Computational support from the Minnesota Supercom- puting Institute (MSI) is gratefully acknowledged. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201006231. Angewandte Chemie 1655 Angew. Chem. 2011, 123, 1655 –1659  2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim