Lanthanide luminescence to mimic molecular logic and computing through physical inputs

The remarkable advances in molecular logic reported in the last decadedemonstrate the potential of luminescent molecules for logical operations, aparadigm-changing concerning silicon-based electronics. Trivalent lanthanide(Ln3+) ions, with their characteristic narrow line emissions, long-lived excitedstates, and photostability under illumination, may improve the state-ofthe-art molecular logical devices. Here, the use of monolithic silicon-basedstructures incorporating Ln3+ complexes for performing logical functions isreported. Elementary logic gates (AND, INH, and DEMUX), sequential logic(KEYPAD LOCK), and arithmetic operations (HALF ADDER and HALF SUBTRACTOR)exhibiting a switching ratio >60% are demonstrated for the firsttime using nonwet conditions. Additionally, this is the first report showingsequential logic and arithmetic operations combining molecular Ln3+ complexesand physical inputs. Contrary to chemical inputs, physical inputs mayenable the future concatenation of distinct logical functions and reuse of thelogical devices, a clear step forward toward input–output homogeneity that isprecluding the integration of nowadays molecular logic devices.</p

PEG-copolymer-coated iron oxide nanoparticles that avoid the reticuloendothelial system and act as kidney MRI contrast agents

In vitro experiments have shown the great potential of magnetic nanocarriers for multimodal imaging diagnosis and non-invasive therapies. However, their extensive clinical application is still jeopardized by a fast retention in the reticuloendothelial system (RES). The other issue that restrains their potential performance is slow degradation and excretion, which increases their risks of toxicity. We report a promising case in which multicore iron oxide nanoparticles coated with a poly(4-vinylpyridine) polyethylene glycol copolymer show low RES retention and high urinary excretion, as confirmed by single photon emission computerized tomography (SPECT), gamma counting, magnetic resonance imaging (MRI) and electron microscopy (EM) biodistribution studies. These iron oxide-copolymer nanoparticles have a high PEG density in their coating which may be responsible for this effect. Moreover, they show a clear negative contrast in the MR imaging of the kidneys. These nanoparticles with an average hydrodynamic diameter of approximately 20 nm were nevertheless able to cross the glomerulus wall which has an effective pore size of approximately 6 nm. A transmission electron microscopy inspection of kidney tissue revealed the presence of iron containing nanoparticle clusters in proximal tubule cells. This therefore makes them exceptionally useful as magnetic nanocarriers and as new MRI contrast agents for the kidneys.Financial support by the Spanish Ministry of Science and Innovation (MAT2014-52069-R) (SAF2014-53413-R) (PC2015-1-05 (53-80)) is gratefully acknowledged.Peer reviewe

Accreditation of Spanish Engineering Programs, first experiences. The case of the Terrassa School of Engineering

The implementation of the European Space for Higher Education has entailed new requirements for Spanish Higher Education Programs. Regulations (RD 1393, 2007) stablish that university programs, in order to have official validity, must be submitted to an external evaluation process before their official implementation, denominated Validation, and to an ex-post process or Accreditation. Terrassa School of Engineering (EET) was one of the first schools in Spain to adapt to the European Space for Higher Education, in the academic period 2009-10 and then, one of the first university institutions submitted to an accreditation process. In this communication, the important role of the Internal Quality Assurance System in the assessment of the school’s programs is exposed as well as the approach followed in the key steps of the process: AccreditationPostprint (published version

Ultrasmall manganese ferrites for in vivo catalase mimicking activity and multimodal bioimaging

Manganese ferrite nanoparticles display interesting features in bioimaging and catalytic therapies. They have been recently used in theranostics as contrast agents in magnetic resonance imaging (MRI), and as catalase-mimicking nanozymes for hypoxia alleviation. These promising applications encourage the development of novel synthetic procedures to enhance the bioimaging and catalytic properties of these nanomaterials simultaneously. Herein, a cost-efficient synthetic microwave method is developed to manufacture ultrasmall manganese ferrite nanoparticles as advanced multimodal contrast agents in MRI and positron emission tomography (PET), and improved nanozymes. Such a synthetic method allows doping ferrites with Mn in a wide stoichiometric range (MnxFe3-xO4, 0.1 ≤ x ≤ 2.4), affording a library of nanoparticles with different magnetic relaxivities and catalytic properties. These tuned magnetic properties give rise to either positive or dual-mode MRI contrast agents. On the other hand, higher levels of Mn doping enhance the catalytic efficiency of the resulting nanozymes. Finally, through their intracellular catalase-mimicking activity, these ultrasmall manganese ferrite nanoparticles induce an unprecedented tumor growth inhibition in a breast cancer murine model. All of these results show the robust characteristics of these nanoparticles for nanobiotechnological applications.The authors thank M. Jeannin from Lasie Laboratory (La Rochelle University) for the Raman studies. S.C.R. is supported by the grant PID2019-106139RA-100 funded by MCIN. J.R.-C. is supported by grants from the Ministerio de Economía, Industria y Competitividad (MEIC) (SAF2017-84494-C2-R). J.R.C. received funding from the BBVA Foundation (PR [18]_BIO_IMG_0008) and La Caixa (HR18-00052). Y.F.-A. received funding from the Santander-Universidad Zaragoza Fellowship program. L.G. acknowledges financial support from the Ramón y Cajal program (RYC-2014-15512). CIC biomaGUNE is supported by the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (MDM-2017-0720). The authors acknowledge the use of Servicio General de Apoyo a la Investigación-SAI, Universidad de Zaragoza. H.G. is supported by the Ligue contre le Cancer (CD16, CD17) and Région Nouvelle Aquitaine (Projet “Nanovect”). J.A.E. is supported by RTI2018-099357-B-I00, HFSP (RGP0016/2018), CIBERFES16/10/00282 and RED2018-102576-T. The CNIC is supported by the Pro-CNIC Foundation and by the Severo Ochoa of Excellence Program.Peer reviewe

MRI study of the influence of surface coating aging on the in vivo biodistribution of iron oxide nanoparticles

This article belongs to the Special Issue Functional Nanomaterials for Biosensing and Bioimaging.Medical imaging is an active field of research that fosters the necessity for novel multimodal imaging probes. In this line, nanoparticle-based contrast agents are of special interest, since those can host functional entities either within their interior, reducing potential toxic effects of the imaging tracers, or on their surface, providing high payloads of probes, due to their large surface-to-volume ratio. The long-term stability of the particles in solution is an aspect usually under-tackled during probe design in research laboratories, since their performance is generally tested briefly after synthesis. This may jeopardize a later translation into practical medical devices, due to stability reasons. To dig into the effects of nanoparticle aging in solution, with respect to their behavior in vivo, iron oxide stealth nanoparticles were used at two stages (3 weeks vs. 9 months in solution), analyzing their biodistribution in mice. Both sets of nanoprobes showed similar sizes, zeta potentials, and morphology, as observed by dynamic light scattering (DLS) and transmission electronic microscopy (TEM), but fresh nanoparticles accumulated in the kidneys after systemic administration, while aged ones accumulated in liver and spleen, confirming an enormous effect of particle aging on their in vivo behavior, despite barely noticeable changes perceived on a simple inspection of their structural integrity.This research was funded by Ministerio de Ciencia, Innovación y Universidades (MEIC) (grant number SAF2017-87670-R and SAF2017-84494-C2-R), Programa Red Guipuzcoana de Ciencia, Tecnología e Información (Grant number 2018-CIEN-000058-01), and The EU (FET-OPEN NanoTBTech grant Number 801305). J.R.-C. and P.R.-C. are funded by Ikerbasque, The Basque foundation for science.Peer reviewe

PEG-copolymer-coated iron oxide nanoparticles that avoid the reticuloendothelial system and act as kidney MRI contrast agents

In vitro experiments have shown the great potential of magnetic nanocarriers for multimodal imaging diagnosis and non-invasive therapies. However, their extensive clinical application is still jeopardized by a fast retention in the reticuloendothelial system (RES). The other issue that restrains their potential performance is slow degradation and excretion, which increases their risks of toxicity. We report a promising case in which multicore iron oxide nanoparticles coated with a poly(4-vinylpyridine) polyethylene glycol copolymer show low RES retention and high urinary excretion, as confirmed by single photon emission computerized tomography (SPECT), gamma counting, magnetic resonance imaging (MRI) and electron microscopy (EM) biodistribution studies. These iron oxide-copolymer nanoparticles have a high PEG density in their coating which may be responsible for this effect. Moreover, they show a clear negative contrast in the MR imaging of the kidneys. These nanoparticles with an average hydrodynamic diameter of approximately 20 nm were nevertheless able to cross the glomerulus wall which has an effective pore size of approximately 6 nm. A transmission electron microscopy inspection of kidney tissue revealed the presence of iron containing nanoparticle clusters in proximal tubule cells. This therefore makes them exceptionally useful as magnetic nanocarriers and as new MRI contrast agents for the kidneys.Financial support by the Spanish Ministry of Science and Innovation (MAT2014-52069-R) (SAF2014-53413-R) (PC2015-1-05 (53-80)) is gratefully acknowledged.Peer reviewe

Nanoparticles that avoid the ReticuloEndothelialSystem with a dense PEG copolymer coating

Resumen del trabajo presentado a la 1st Spanish Conference on Biomedical Applications of Nanomaterials (SBAN), celebrada en Madrid del 7 al 8 de junio de 2018.A crucial step for in vivo applications of nanoparticles in general and magnetic carriers in particular is to avoid the retention by the Reticuloendothelial System (RES). Without this requisite, the expectable benefits from nanoparticles in in vivo medical applications (controlled targeted delivery, reduced toxicity, early diagnosis, enhanced imaging sensitivity) will be severely limited. In vitro experiments with macrophage cell cultures (Schöttler, et al. Nat. Nanotechnol. 2016, 11, 372) have shown that an adequate polyethylenglycol (PEG) coating can prevent the macrophages uptake. In this manuscript, we show this effect in vivo using multicore iron oxide nanoparticles, opening the way for efficient targeted delivery of these type of magnetic nanocarriers in the future. The dense PEG coating is realized by Michael reaction of PEG acrylate chains on poly(4-vinylpyridine) nanoparticles embedding the iron oxide cores. Two important findings come along with the low RES retention: 1) a clear MRI contrast in kidneys is obtained for the first time with iron oxide nanoparticles; 2) the nanoparticles are excreted by the urinary system. The conclusions are supported by four independent biodistribution techniques: gamma-imaging, gamma-counting, MRI (Fig 1) and TEM histology. Moreover, the manuscript describes a new procedure for a direct radiolabeling of iron oxide nanoparticles through incorporation in the crystal lattice of 111In3+ ions.Peer reviewe

Lanthanide luminescence to mimic molecular logic and computing through physical inputs

The remarkable advances in molecular logic reported in the last decade demonstrate the potential of luminescent molecules for logical operations, a paradigm-changing concerning silicon-based electronics. Trivalent lanthanide (Ln3+) ions, with their characteristic narrow line emissions, long-lived excited states, and photostability under illumination, may improve the state-of-the-art molecular logical devices. Here, the use of monolithic silicon-based structures incorporating Ln3+ complexes for performing logical functions is reported. Elementary logic gates (AND, INH, and DEMUX), sequential logic (KEYPAD LOCK), and arithmetic operations (HALF ADDER and HALF SUBTRACTOR) exhibiting a switching ratio >60% are demonstrated for the first time using nonwet conditions. Additionally, this is the first report showing sequential logic and arithmetic operations combining molecular Ln3+ complexes and physical inputs. Contrary to chemical inputs, physical inputs may enable the future concatenation of distinct logical functions and reuse of the logical devices, a clear step forward toward input–output homogeneity that is precluding the integration of nowadays molecular logic devices.publishe

Acreditación de las titulaciones de grado. Experiencia de la EET-UPC

El proceso de implantación del Espacio Europeo de Educación Superior (EEES) supuso nuevos requerimientos para los estudios universitarios en el Estado Español. La legislación (RD 1393, 2007) establece que los títulos universitarios oficiales, para tener validez oficial, deberán someterse a un proceso de evaluación externa ex ante llamado Verificación y un proceso ex post o Acreditación. La Escuela de Ingeniería de Terrassa (EET) de la Universidad Politécnica de Catalunya (UPC) fue una de las primeras escuelas en adap-tar su oferta de estudios al Espacio Europeo de Educación Superior (EEES) en el curso 2009-10 y por tanto, es de las primeras en someterse al proceso de acreditación. En esta comunicación se expone el importante papel del Sistema de Gestión Interna de la Calidad del centro en el seguimiento de las titulaciones y la forma en que se ha abordado una de las etapas clave im-plicadas en el ciclo de vida de las mismas, la AcreditaciónPostprint (published version

Acreditación de las titulaciones de grado. Experiencia de la EET-UPC

El proceso de implantación del Espacio Europeo de Educación Superior (EEES) supuso nuevos requerimientos para los estudios universitarios en el Estado Español. La legislación (RD 1393, 2007) establece que los títulos universitarios oficiales, para tener validez oficial, deberán someterse a un proceso de evaluación externa ex ante llamado Verificación y un proceso ex post o Acreditación. La Escuela de Ingeniería de Terrassa (EET) de la Universidad Politécnica de Catalunya (UPC) fue una de las primeras escuelas en adap-tar su oferta de estudios al Espacio Europeo de Educación Superior (EEES) en el curso 2009-10 y por tanto, es de las primeras en someterse al proceso de acreditación. En esta comunicación se expone el importante papel del Sistema de Gestión Interna de la Calidad del centro en el seguimiento de las titulaciones y la forma en que se ha abordado una de las etapas clave im-plicadas en el ciclo de vida de las mismas, la Acreditació