Article pubs.acs.org/Langmuir
Rapid Nucleation of Iron Oxide Nanoclusters in Aqueous Solution by Plasma Electrochemistry Mathieu Bouchard,†,‡,§ Mathieu Létourneau,†,‡,§ Christian Sarra-Bournet,†,‡,§ Myriam Laprise-Pelletier,†,‡,§ Stéphane Turgeon,† Pascale Chevallier,†,§ Jean Lagueux,† Gaétan Laroche,†,‡,§ and Marc-A. Fortin*,†,‡,§ †
Axe Médecine Régénératrice, Centre Hospitalier Universitaire (CHU) de Québec, 10 rue de l’Espinay, Québec, G1L 3L5, Canada Département de Génie des Mines, de la Métallurgie et des Matériaux and §Centre de Recherche sur les Matériaux Avancés (CERMA), Université Laval, Québec, G1V 0A6, Canada
‡
S Supporting Information *
ABSTRACT: Progresses in cold atmospheric plasma technologies have made possible the synthesis of nanoparticles in aqueous solutions using plasma electrochemistry principles. In this contribution, a reactor based on microhollow cathodes and operating at atmospheric pressure was developed to synthesize iron-based nanoclusters (nanoparticles). Argon plasma discharges are generated at the tip of the microhollow cathodes, which are placed near the surface of an aqueous solution containing iron salts (FeCl2 and FeCl3) and surfactants (biocompatible dextran). Upon reaction at the plasma−liquid interface, reduction processes occur and lead to the nucleation of ultrasmall iron-based nanoclusters (IONCs). The purified IONCs were investigated by XPS and FTIR, which confirmed that the nucleated clusters contain a highly hydrated form of iron oxide, close to the stoichiometric constituents of α-FeOOH (goethite) or Fe5O3(OH)9 (ferrihydrite). Relaxivity values of r1 = 0.40 mM−1 s−1 and r2/r1 = 1.35 were measured (at 1.41 T); these are intermediate values between the relaxometric properties of superparamagnetic iron oxide nanoparticles used in medicine (USPIO) and those of ferritin, an endogenous contrast agent. Plasma-synthesized IONCs were injected into the mouse model and provided positive vascular signal enhancement in T1-w. MRI for a period of 10−20 min. Indications of rapid and strong elimination through the urinary and gastrointestinal tracts were also found. This study is the first to report on the development of a compact reactor suitable for the synthesis of MRI iron-based contrast media solutions, on site and upon demand.
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INTRODUCTION The advent of a new generation of plasma reactors operating at atmospheric pressure (AP) has led to the development of innovative concepts and processes in the fields of surface treatment,1−3 water purification,4−7 and nanomaterials synthesis,8−10 to name only a few. In particular, the interactions between plasma and water solutions containing metal salts and surfactants can lead to efficient metal nanoparticles synthesis procedures, referred to as plasma electrochemistry.11−13 Conventional nanoparticle synthesis procedures based on colloidal chemistry usually require multiple solvent transfers and cleaning steps as well as the use of potentially toxic chemical reducing agents (e.g., NaBH4). In comparison, plasma electrochemistry is faster and more efficient and is performed entirely in aqueous media, significantly reducing the number of manipulations and purification steps. Because of its simplicity, efficiency, and rapidity, the nucleation and growth of nanoparticles using plasma−liquid interactions at atmospheric pressure has emerged as a promising synthesis route.11−16 Until recently, plasma-based nanoparticle nucleation methods were all based on low-pressure plasma apparatuses.17,18 Although these nanomaterials can be synthesized in high purity © 2015 American Chemical Society
from a broad range of precursor elements, the low-pressure conditions had so far prevented the direct synthesis of nanoparticles in aqueous media. Moreover, low-pressure plasmas are associated with poorly versatile equipment and high maintenance costs compared to those operating near or at atmospheric pressure, which are cheaper and easier to implement in routine production processes.19 An increasingly popular medium for nanomaterials synthesis at atmospheric pressure is the liquid-state plasma, commonly referred to as solution plasma. It has recently been used to induce the nucleation and growth of noble metal nanoparticles (Ag, Au, and Pt).20−22 However, its use requires immersing two metallic electrodes in the solution, often leading to contamination of the nanoparticle suspension. A third innovative synthesis route based on plasma electrochemistry is the AP microplasma technology.23,24 It is characterized by the spatial confinement of gaseous discharges to submillimeter dimensions. Of the few schemes employed to Received: April 3, 2015 Revised: June 5, 2015 Published: June 18, 2015 7633
DOI: 10.1021/acs.langmuir.5b01235 Langmuir 2015, 31, 7633−7643
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Langmuir
Figure 1. (A) Photograph and (B) corresponding diagram of a plasma microdischarge. (C) IONC synthesis process including electrochemical reduction at the plasma−liquid interface and stabilization by dextran.
neous nanoparticles with wide distributions of size and magnetic properties.32,33 In comparison, the thermal decomposition of iron organometallic precursors is a more recent approach. It is completed in a few hours and allows the production of fine monocrystalline magnetite particles with narrow size distributions.34−36 The main disadvantage of this synthesis method is its necessity to disperse particles in water using time- and solvent-consuming surface ligand exchange procedures. It also implies tedious liquid medium changing steps. This often results in a global loss of nanoparticles in the transfer. New chemical routes to nucleate ultrasmall IONs directly in water and to allow their in situ coverage with biocompatible surfactants are therefore highly desirable (e.g., plasma synthesis or microfluidics).37 In this study, we report on the design and use of a multicathode (multiplasma) reactor, which was used to synthesize ultrasmall iron (hydro)oxide nanoparticles, referred to as iron oxide nanoclusters (IONCs). The synthesis process takes advantage of gaseous instead of liquid-phase plasma. It consists of multiple stable plasma microdischarges generated by microhollow cathodes fed with an inert gas. The plasma is projected at the surface of a liquid containing metal ions. A current flow is thus generated, leading to the reduction of these ions at the plasma−liquid interface. This reactor allows the preparation of IONCs in aqueous media in only a few minutes.
attain such confinement, the microhollow cathode setup is particularly attractive for its simplicity and low cost. It is essentially formed from a capillary metallic tube to which is applied a constant voltage of a few kilovolts, producing a glow discharge in the gas flowing through it by virtue of the hollow cathode principle.25 When placing a counter electrode, solid or liquid, a few millimeters from the end of the tube, the discharge extends to it. A significant fraction of energetic electrons (>10 eV) in these plasmas are known to allow efficient, nonthermal dissociation of molecular gases and other vapor precursors.26 Thus, with an inert gas, the electrons can become electrochemical reaction promoters. Moreover, the addition of reactive gases can modify the kinetics of chemical reactions occurring in the fluid by producing high concentrations of reactive radicals such as nitrogen, nitric oxide, hydroxyl, and other reactive oxygen species.27 Sankaran et al. used a microhollow cathode over a solution of gold and silver ionic precursors to demonstrate their rapid reduction into Au and Ag nanoparticles.12 This type of electrochemical cell allowed the nanoparticles to nucleate and stabilize efficiently in less than 10 min. The exact electrochemical mechanisms by which nanoparticle nucleation and growth occur are still unknown; however, this work clearly showed that a fast redox reaction is initiated at the plasma− liquid interface by the electrons contained in the plasma. The efficiency of this process remains strongly related to the relatively limited area of the liquid surface treated by the plasma. Therefore, in order for (micro)plasma electrochemistry processes to become an efficient alternative to the synthesis of nanoparticles by conventional colloidal chemistry, it is necessary to expand the plasma−liquid interface. Until now, the principles of AP electrochemistry using a microhollow cathode had never been extended to the synthesis of iron oxide nanoparticles (IONs). These particles are a class of nanomaterials with direct applications in medicine, as magnetic resonance imaging (MRI) contrast agents. In particular, ultrasmall (
