Universal One-Pot and Scalable Synthesis of SERS Encoded Nanoparticles Bernat Mir-Simon, † Irene Reche-Perez, †,‡ Luca Guerrini, †,‡ Nicolas Pazos-Perez,* ,† and Ramon A. Alvarez-Puebla* ,†,‡,§ † Medcom Advance, Viladecans Business Park, Edificio Brasil, Bertran i Musitu 83-85, 08840 Viladecans, Barcelona, Spain ‡ Departamento de Quimica Fisica e Inorganica, Universitat Rovira i Virgili and Centro de Tecnologia Quimica de Cataluñ a, Carrer de Marcel·lí Domingo s/n, 43007 Tarragona, Spain § ICREA, Passeig Lluís Companys 23, 08010 Barcelona, Spain * S Supporting Information ABSTRACT: Encoded particles are one of the most powerful approaches for multiplex high-throughput screening. Surface- enhanced Raman scattering (SERS) based codification can, in principle, avoid many of the intrinsic limitations due to conventional alternatives, as it decreases the reading time and particle size while allowing for almost unlimited codification. Unfortunately, methods for the synthetic preparation of these particles are tedious; often subjected to limited reproducibility (associated with large fluctuations in the size distributions of the polymers employed in the standard protocols); and to date, limited to a small amount of molecules. Herein, we report a universal, one-pot, inexpensive, and scalable synthetic protocol for the fabrication of SERS-encoded nanoparticles. This synthetic strategy is highly reproducible, independent of the chemical nature and size of the Raman code used (31 different codes were tested) and scalable in the liter range without affecting the final properties of the encoded structures. Furthermore, the SERS efficiency of the fabricated encoded nanoparticles is superior to that of the materials produced by conventional methods, while showing a remarkable reproducibility from batch to batch. This encoding strategy can easily be applied to nanoparticles of different materials and shapes. ■ INTRODUCTION Encoded nanoparticles are among the most powerful alternatives for high-throughput multiplex screening 1,2 in microarray technology, 3 diagnosis, 4,5 and bioimaging. 6 These materials are simple and cost-effective platforms that allow for fast, sensitive, and reliable analyses. 2,7-14 During the past decade, several encoded particles have been prepared 15-17 using codification strategies based on changes in particle shape, 18 composition, 19 physical marks, 17 or spectroscopic properties (e.g., luminescence or vibrational fi nger- prints). 6,20-22 Among all of them, those based on surface- enhanced Raman scattering (SERS) are gaining importance 23 because of (i) virtually unlimited multiplexing capability associated with the unique vibrational fingerprints of the different codes; (ii) short detection times (milliseconds) thanks to the intrinsic sensitivity of the SERS phenomenon; 24 (iii) small size, allowing for bioimaging; 25-27 and (iv) photostability and low toxicity (as compared to those of dyes or quantum dots). 28 In essence, a SERS-encoded nanoparticle (also called a SERS tag) comprises a plasmonic nucleus, responsible for the generation of the electric field necessary for the Raman amplification; a Raman probe (i.e., code), responsible for the unique vibrational fingerprint of the encoded particle; and a coating layer. This external coating is of key importance as it (i) prevents the code from leaching out into the medium, thus avoiding toxic effects or vibrational cross-contamination with the codes of other particles; (ii) protects the plasmonic particle from contaminations of the medium that could give rise to vibrational noise that would hinder the particle readout; (iii) increases the colloidal stability of the particle; (iv) provides a convenient surface for further chemical functionalization; and (v) protects the plasmonic core from interacting with other plasmonic particles, avoiding plasmon coupling and thus the uncontrolled generation of hotspots. Although polymers have been reported as particle coatings, 29-31 the unique properties of silica (i.e., known surface chemistry, biocompatibility, optical transparency, and colloidal stability) make this material the most efficient protective layer for nanoparticles by far. 32,33 Silica coating of nanoparticles requires the colloidal stabilization of the particles in ethanolic solution prior to the hydrolysis/condensation of tetraethyl orthosilicate (TEOS). Although a range of polymers has been proposed for this task, 32,34 the most common remains polyvinylpyrrolidone Received: November 19, 2014 Revised: January 7, 2015 Published: January 12, 2015 Article pubs.acs.org/cm © 2015 American Chemical Society 950 DOI: 10.1021/cm504251h Chem. Mater. 2015, 27, 950-958