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[EN] We report herein the design of a strip-based rapid test utilizing bio-inspired hybrid nanomaterials for the in situ and at site detection of the drug scopolamine (SCP) using a smartphone for readout, allowing SCP identification in diluted saliva down to 40 nM in less than 15 min. For this purpose, we prepared a nanosensor based on mesoporous silica nanoparticles loaded with a fluorescent reporter (rhodamine B) and functionalized with bethanechol, a potent agonist of recombinant human muscarinic acetylcholine receptor M-2 (M-2-AChR). M-2-AChR interaction with the anchored bethanechol derivative leads to capping of the pores. The sensing mechanism relies on binding of SCP to M-2-AChR resulting in pore opening and delivery of the entrapped rhodamine B reporter. Moreover, the material was incorporated into strips for lateral-flow assays coupled to smartphone readout, giving fast response time, good selectivity, and exceptional sensitivity. In an attempt to a mobile analytical test system for law enforcement services, we have also developed a dualplex lateral flow assay for SCP and 3,4-methylenedioxypyrovalerone (MDPV) also known as the so-called "cannibal drug"., This research was funded by the Ministerio de Ciencia, Innovacion y Universidades (Spanish Government), the Agencia Estatal de Investigacion (AEI), the European Union (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22-AR (MCIU/AEI/FEDER, EU), the Conselleria de Innovacion, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana (Project PROMETEO 2018/024) and the German Research Foundation (DFG; CL 761/1-19). E. G. is grateful to the Spanish MEC for her FPU grant (FPU16/02464).

Functional core/shell particles are highly sought after in analytical chemistry, especially in methods suitable for single-particle analysis such as flow cytometry because they allow for facile multiplexed detection of several analytes in a single run. Aiming to develop a powerful bead platform of which the core particle can be doped in a straightforward manner while the shell offers the highest possible sensitivity when functionalized with (bio)chemical binders, polystyrene particles were coated with different kinds of mesoporous silica shells in a convergent growth approach. Mesoporous shells allow us to obtain distinctly higher surface areas in comparison with conventional nonporous shells. While assessing the potential of narrow- as well as wide-pore silicas such as Mobil composition of matter no. 41 (MCM-41) and Santa Barbara amorphous material no. 15 (SBA-15), especially the synthesis of the latter shells that are much more suitable for biomolecule anchoring was optimized by altering the pH and both, the amount and type of the mediator salt. Our studies showed that the best performing material resulted from a synthesis using neutral conditions and MgSO4 as an ionic mediator. The analytical potential of the particles was investigated in flow cytometric DNA assays after their respective functionalization for individual and multiplexed detection of short oligonucleotide strands. These experiments revealed that a two-step modification of the silica surface with amino silane and succinic anhydride prior to coupling of an amino-terminated capture DNA (c-DNA) strand is superior to coupling carboxylic acid-terminated c-DNA to aminated core/shell particles, yielding limits of detection (LOD) down to 5 pM for a hybridization assay, using labeled complementary single-stranded target DNA (t-DNA) 15mers. The potential of the use of the particles in multiplexed analysis was shown with the aid of dye-doped core particles carrying a respective SBA-15 shell. Characteristic genomic sequences of human papillomaviruses (HPV) were chosen as the t-DNA analytes here, since their high relevance as carcinogens and the high number of different pathogens is a relevant model case. The title particles showed a promising performance and allowed us to unequivocally detect the different high- and low-risk HPV types in a single experimental run.

Antibody-gated indicator delivery (gAID) systems based on mesoporous silica nano- and microparticle scaffolds are a promising class of materials for the sensitive chemical detection of small-molecule analytes in simple test formats such as lateral flow assays (LFAs) or microfluidic chips. Their architecture is reminiscent of drug delivery systems, only that reporter molecules instead of drugs are stored in the voids of a porous host particle. In addition, the pores are closed with macromolecular “caps” through a tailored “gatekeeping” recognition chemistry so that the caps are opened when an analyte has reacted with a “gatekeeper”. The subsequent uncapping leads to a release of a large number of indicator molecules, endowing the system with signal amplification features. Particular benefits of such systems are their modularity and adaptability. With the example of the immunochemical detection of type-I pyrethroids by fluorescent dye-releasing gAID systems, the influence of several tuning modes on the optimisation of such hybrid sensory materials is introduced here. In particular, different mesoporous silica supports (from nano- and microparticles to platelets and short fibres), different functionalisation routes and different loading sequences were assessed. The materials’ performances were evaluated by studying their temporal response behaviour and detection sensitivity, including the tightness of pore closure (through the amount of blank release in the absence of analyte) and the release kinetics. Our results indicate that the better the paratope-accommodating Fab region of the antibody “cap” fits into the host material's pore opening, the better the closing/opening mechanism can be controlled. Because such materials are well-suited for LFAs, performance assessment included a test-strip format besides conventional assays in suspension. In combination with dyes as indicators and smartphones for read-out, simple analytical tests for use by untrained personnel directly at a point-of-need such as an aeroplane cabin can be devised, allowing for sensitivities down to the μg kg−1 range in

Commercial bead-based assays are commonly built upon polystyrene particles. The polymeric carrier can be encoded with organic dyes and has ideal material properties for cytometric applications such as low density and high refractive index. However, functional groups are conventionally integrated during polymerization and subsequent modification is limited to the reactivity of those groups. Additionally, polystyrene as the core material leads to many hydrophobic areas still being present on the beads' surfaces even after functionalization, rendering the particles prone to nonspecific adsorption during an application. The latter calls for several washing steps and the use of additives in (bio)analytical assays. In this contribution, we show how these limitations can be overcome by using monodisperse polystyrene (PS) core/silica (SiO

[EN] A novel nanodevice consisting of mesoporous nanoparticles loaded with vancomycin and capped with epsilon-poly-L-lysine (epsilon-PL) was prepared and its interaction with different Gram-negative bacteria studied. A remarkable improvement in the efficacy of the antimicrobial drug epsilon-PL and a broadening of the antimicrobial spectrum of vancomycin is demonstrated., The authors thank the Spanish Government (project MAT2012-38429-C04-01) the Generalitat Valenciana (project PROMETEO/2009/016) and the CIBER-BBN for their support. N.M. also thanks the Ministerio de Ciencia e Innovacion for her FPI grant. L.M. also thanks Generalitat Valenciana for her post-doc VALI+D contract.

Chemical warfare (CW) agents are toxic chemicals that have been used in several terrorist attacks in recent years. Among CW species, nerve agents are probably the most dangerous; their high toxicity and facile synthesis underscores the need to detect these lethal compounds with quick, reliable procedures. Analytical methods based on enzymatic assays and physical measurements have generally been used to detect these hazards. However, these protocols usually have limitations such as low selectivity, poor portability, and a certain level of complexity. In recent years, several chromogenic and fluorogenic sensors, and reagents for the detection of nerve agents have been described. For instance, approaches that involve perborate-mediated oxidation of organophosphorus agents, fluorescent probes based on polyethylene terephthalate (PET), assays that use oximate-containing derivatives, molecularly imprinted polymers, nanoparticles, carbon nanotubes, porous silicon, displacement-like procedures, and cyclization reactions in push–pull chromophores have been reported. Most of these protocols rely on changes in fluorescence properties, whereas few examples deal with color modulations. Colorimetric detection is particularly appealing because it uses low-cost, widely available instrumentation and allows assays to be detected with the naked eye. However, the development of selective, sensitive chromogenic probes for the detection of deadly chemical species is still rare. Given our interest in the design of novel hybrid organic– inorganic materials as probes, we focused on the preparation of a new optical test for the detection of nerve agent mimics based on nerve agent control of mass transport to the surface of functionalized silica nanoparticles. The chromogenic approach (Scheme 1) involves the use of silica nanoparticles that are functionalized with two different subunits— thiol groups (SH) and aliphatic alcohols (OH). The role of the

This paper describes the design of new controlled delivery systems consisting of a mesoporous support functionalized on the pore outlets with a certain hapten able to interact with an antibody that acts as a nanoscopic cap. The opening protocol and delivery of the entrapped guest is related by a displacement reaction involving the presence in the solution of the antigen to which the antibody is selective. As a proof-of-the-concept, the solid MCM-41 was selected as support and was loaded with the dye [Ru(bipy)(3)]Cl(2). Then a suitable derivative of the hapten 4-(4-aminobenzenesulfonylamino)benzoic acid was anchored on the outer surface of the mesoporous support (solid S1). Finally the pores were capped with a polyclonal antibody for sulfathiazole (solid S1-AB). Delivery of the dye in the presence of a family of sulfonamides was studied in phosphate-buffered saline (PBS; pH 7.5). A selective uncapping of the pores and dye delivery was observed for sulfathiazole. This delivery behavior was compared with that shown by other solids that were prepared as models to assess the effect of the hapten and its interaction with antibody in the dye delivery control in the presence of the antigen.

Test strips that in combination with a portable fluorescence reader or digital camera can rapidly and selectively detect chemical warfare agents (CWAs) such as Tabun (GA), Sarin (GB), and Soman (GD) and their simulants in the gas phase have been developed. The strips contain spots of a hybrid indicator material consisting of a fluorescent BODIPY indicator covalently anchored into the channels of mesoporous SBA silica microparticles. The fluorescence quenching response allows the sensitive detection of CWAs in the mu g m(-3) range in a few seconds., Financial support from the Alexander von Humboldt Foundation, the German Federal Ministry for Economic Affairs and Energy, European FEDER funds (MAT2012-38429-C04), the Generalitat Valenciana (PROMETEOII/2014/047), and the Spanish Government is gratefully acknowledged. We thank S. Selve (Technical University Berlin) for TEM images, A. Zehl (Humboldt University Berlin) for elemental analysis, D. Pfeifer (BAM, Div. 1.3) for NMR, A. Zimathies (BAM 1.3) for N2 adsorption/desorption, S. Ewald and A. Lehmann (BAM 1.5 & 1.8) for MS support, and T. Fischer (BAM 1.9) for support with the fluorescence decay measurements.

The design of comparatively simple and modularly configurable artificial systems able to communicate through the exchange of chemical messengers is, to the best of our knowledge, an unexplored field. As a proof-of-concept, we present here a family of nanoparticles that have been designed to communicate with one another in a hierarchical manner. The concept involves the use of capped mesoporous silica supports in which the messenger delivered by a first type of gated nanoparticle is used to open a second type of nanoparticle, which delivers another messenger that opens a third group of gated nanoobjects.We believe that the conceptual idea that nanodevices can be designed to communicate with one another may result in novel applications and will boost further advances towards cooperative systems with complex behavior as a result of the communication between simple abiotic individual components., Financial support from the Spanish government (project MAT2012-38429-C04-01) and the Generalitat Valencia (project PROMETEO/2009/016) is gratefully acknowledged. E.A. thanks the Universitat Politecnica de Valencia (project SP20120795) for support. C.G. is grateful to the Spanish Ministry of Science and Innovation for a grant. E.C. is grateful to the Adolf-Martens-Fonds for a fellowship. We are indebted to M. Dinter (LTB Lasertechnik Berlin GmbH) for assistance with the graphics.

An aptamer-capped mesoporous material for the selective and sensitive detection of &-thrombin in human plasma and serum has been prepared and characterised., The authors thank the Spanish Government (project MAT2012-38429-C04-01, CTQ2010-20541) the Generalitat Valenciana (project PROMETEO/2009/016) and the CIBER-BBN for their support. C. C. thanks the Universitat Politecnica de Valencia (UPV PAID-06-11) for support. M.O. is grateful to the Universitat Politecnica de Valencia for her grant.

[EN] Antibodygated MSNs that are loaded with a rhodamine dye and that can be used for the determination of the presence of peroxide-based explosive TATP with a lateral-flow fluorescence reader have been designed and prepared, thereby allowing for detection limits in the lower ppb range. The mechanism of the detection relies on a displacement of the antibody from the surface of the hybrid material because of highly affine antibody-TATP interactions, which release a much larger number of entrapped dye molecules from the pores than antibodies are displaced. The high selectivity of the antibody is retained in the gated material, thus allowing for a remarkable discrimination against H2O2. System design and optimization led to straightforward integration into a lateral-flow assay without further treatment or conditioning of the test strips while guaranteeing fast overall assay times of minus or equal 10 min. Moreover, besides showing a remarkable robustness, the inherent architecture of the assay relies on a single-step immunochemical reaction, that is, it can dispense with secondary (labeled) antibodies and enables ratiometric signal assessment in the presence of the analyte by simple comparison of the fluorescence signals in two zones. Because of the modularity of the approach, the concept is easily generalizable and applicable for many small-molecule analytes. For instance, assays can be imagined that contain various hybrids of S1-AB(n) type, for which each material capped with a certain antibody is loaded with a different dye, thus envisioning multiplexed analysis with such simple assays., Financial support from the Spanish Government (MAT2009-14564-C04-01), the Generalitat Valenciana (PROMETEO/2009/016), the Innovationsfonds (BAM/Bundesministerium fur Wirtschaft und Technologie), and BAM's PhD Program (M.A.W.) is gratefully acknowledged. E.C. thanks the Ministerio de Educacion for a fellowship. We are indebted to J. Schenk, BAM-1.0, for help with the piezo dispenser and S. Fischer and W. Weigel, Scienion AG, Berlin, for support with the spotter.

A hybrid nanoscopic capped mesoporous material, that is selectively opened in the presence of nerve agent simulants, has been prepared and used as a probe for the chromo-fluorogenic detection of these chemicals. © 2011 The Royal Society of Chemistry., Financial support from the Spanish Government (project MAT2009-14564-C04-01 and -02) and Generalitat Valenciana (project PROMETEO/2009/016) is gratefully acknowledged. I. C. thanks the UPV for her Fellowship. SCSIE (Universidad de Valencia) is gratefully acknowledged for all the equipment employed.

A new chromo-fluorogenic sensing protocol for anionic surfactants in aqueous environments using silica functionalised nanoparticles containing imidazolium and thiol groups has been developed. © 2011 The Royal Society of Chemistry., Financial support from the Spanish Government (project MAT2009-14564-C04-01) and the Generalitat Valencia (project PROMETEO/2009/016) is gratefully acknowledged. E. C. and C. G. thank the MICINN and the UPV for fellowships.

Bis-functionalised silica surfaces have been designed in order to develop selective and sensitive probes for the chromo-fluorogenic detection of certain guests. The designed system consists of a siliceous support bis-functinalised with thiol and polyamine groups. Thiol groups are suitable reactive centres (R) that are know to react with squaraine dyes (D) inducing bleaching, whereas polyamines act as host sites (H) able to coordinate certain target guests (G). In the absence of G, the reactive groups (R) react with the dye resulting in a bleaching of the solution. On the contrary, the presence of certain guest (G) results in a control of the reaction kinetic between R and D and eventually in a complete reaction inhibition. Different functionalised solids were prepared by reaction of the siliceous surface with different concentrations of mercaptopropyltrimethoxysilane (MPTS) and 3-[2-(2-aminoethylamino)ethylamino]propyl-trimethoxysilane (N3TS). The final materials (solids to ) were characterized employing standard procedures. In a first step the reactivity of the signaling dye D (squaraine ) with the reactive centre R (thiol groups) was studied as a function of the pH using solid that showed a most suitable response. At pH 7 and pH 5 there was a quick reaction between the squaraine and the thiol groups on the surface. On the contrary this reaction is significantly slower at pH 3 due to the different degree of protonation of the amines as a function of the pH. Additionally the reaction of with the squaraine has been studied in the presence of a range of inorganic anions with different structural dimensions and charges, including chloride, perchlorate, nitrate, sulfate, phosphate and pyrophosphate. At pH 3 the reaction of the dye with the thiol groups is still effective in the presence of chloride and perchlorate, but the reaction is highly inhibited in the presence of the anions nitrate, sulfate, phosphate and pyrophosphate. At pH 7 the squaraine reacts very fast with the thiol groups in the presence of all the anions studied. In contrast, at pH 5 only pyrophosphate is able to inhibit, to a certain extent, the reaction of the squaraine with the thiols, resulting in a selective chromo-fluorogenic detection of this anion in pure water. Finally, the observed behaviour was discussed in terms of both, the kinetic rates of the reaction between the thiol and the squaraine groups and the thermodynamic interaction reaction between the anions and the polyamine moieties.

Heparin detective: Silica nanoparticles functionalised with ion-channel scaffolds were prepared and used for the chromofluorogenic sensing of heparin in aqueous environments (see figure). The surface of the nanoparticles was functionalised with polyamines (binding sites) and thiols. The reaction of a dye (squaraine) with the surface thiol groups was selectively inhibited by the coordination of heparin with the partly protonated polyamines.

Silica nanoparticles containing polyamines and thiol groups have been used as probes for the selective detection of Tetryl. © 2011 The Royal Society of Chemistry., Financial support from the Spanish Government (project MAT2009-14564-C04-01) and Generalitat Valencia (project PRO-METEO/2009/016) is gratefully acknowledged. Y.S. is grateful to the Spanish Ministry of Science and Innovation for a grant.