Nanoimprinted multifunctional nanoprobes for a homogeneous immunoassay in a top-down fabrication approach.

Multifunctional nanoparticles are discussed as versatile probes for homogeneous immunoassays for in-vitro diagnostics. Top-down fabrication allows to combine and tailor magnetic and plasmonic anisotropic properties. The combination of nanoimprint lithography, thin film deposition, and lift-off processing provides a top-down fabrication platform, which is both flexible and reliable. Here, we discuss the material compositions and geometrical designs of monodisperse multicomponent nanoparticles and their consequences on optical and magnetic properties. The rotational hydrodynamics of nanoparticles is measured and considered under the influence of magnetic shape anisotropy in the framework of the Stoner-Wohlfarth theory. The plasmon-optical properties are explained by discrete-dipole finite-element simulations. Rotational dynamical measurements of imprinted nanoprobes for two test proteins demonstrate the applicability as highly sensitive biomolecular nanoprobes.

Integrated silicon nitride organic hybrid DFB laser with inkjet printed gain medium.

The provision of a coherent light source is a prerequisite for a variety of photonic integrated circuits. The integration of semiconductor laser diodes in disposable photonic devices in fields such as biosensing is, however, impeded by the competitive pricing in this application area. In this work, we demonstrate lasing of an alternative laser light source, namely an integrated hybrid organic solid-state distributed feedback laser for a silicon nitride photonic platform. The laser is optically pumped with a high power 450 nm laser diode and emits in the visible at 630 nm into a waveguide taper to reduce the cross-section to a single mode geometry. Inkjet printing of the organic gain medium enables a local, cost-effective, and flexible processing technology. The fabrication of the presented coherent light source is CMOS compatible and therefore highly interesting for co-integrated sensing platforms.

Multifunctional Nanostructures and Nanopocket Particles Fabricated by Nanoimprint Lithography.

Nanostructured surfaces and nanoparticles are already widely employed in many different fields of research, and there is an ever-growing demand for reliable, reproducible and scalable nanofabrication methods. This is especially valid for multifunctional nanomaterials with physical properties that are tailored for specific applications. Here, we report on the fabrication of two types of nanomaterials. Specifically, we present surfaces comprising a highly uniform array of elliptical pillars as well as nanoparticles with the shape of nanopockets, possessing nano-cavities. The structures are fabricated by nanoimprint lithography, physical and wet-chemical etching and sputter deposition of thin films of various materials to achieve a multifunctional nanomaterial with defined optical and magnetic properties. We show that the nanopockets can be transferred to solution, yielding a nanoparticle dispersion. All fabrication steps are carefully characterized by microscopic and optical methods. Additionally, we show optical simulation results that are in good agreement with the experimentally obtained data. Thus, this versatile method allows to fabricate nanomaterials with specific tailor-made physical properties that can be designed by modelling prior to the actual fabrication process. Finally, we discuss possible application areas of these nanomaterials, which range from biology and medicine to electronics, photovoltaics and photocatalysis.

Next-Generation Magnetic Nanocomposites: Cytotoxic and Genotoxic Effects of Coated and Uncoated Ferric Cobalt Boron (FeCoB) Nanoparticles In Vitro.

Metal nanoparticles (NPs) have unique physicochemical properties and a widespread application scope depending on their composition and surface characteristics. Potential biomedical applications and the growing diversity of novel nanocomposites highlight the need for toxicological hazard assessment of next-generation magnetic nanomaterials. Our study aimed to evaluate the cytotoxic and genotoxic properties of coated and uncoated ferric cobalt boron (FeCoB) NPs (5-15 nm particle size) in cultured normal human dermal fibroblasts. Cell proliferation was assessed via ATP bioluminescence kit, and DNA breakage and chromosomal damage were measured by alkaline comet assay and micronucleus test. Polyacryl acid-coated FeCoB NPs [polyacrylic acid (PAA)-FeCoB NPs) and uncoated FeCoB NPs inhibited cell proliferation at 10 µg/ml. DNA strand breaks were significantly increased by PAA-coated FeCoB NPs, uncoated FeCoB NPs and l-cysteine-coated FeCoB NPs (Cys-FeCoB NPs), although high concentrations (10 µg/ml) of coated NPs (Cys- and PAA-FeCoB NPs) showed significantly more DNA breakage when compared to uncoated ones. Uncoated FeCoB NPs and coated NPs (PAA-FeCoB NPs) also induced the formation of micronuclei. Additionally, PAA-coated NPs and uncoated FeCoB NPs showed a negative correlation between cell proliferation and DNA strand breaks, suggesting a common pathomechanism, possibly by oxidation-induced DNA damage. We conclude that uncoated FeCoB NPs are cytotoxic and genotoxic at in vitro conditions. Surface coating of FeCoB NPs with Cys and PAA does not prevent but rather aggravates DNA damage. Further safety assessment and a well-considered choice of surface coating are needed prior to application of FeCoB nanocomposites in biomedicine.

Applications, Surface Modification and Functionalization of Nickel Nanorods.

The growing number of nanoparticle applications in science and industry is leading to increasingly complex nanostructures that fulfill certain tasks in a specific environment. Nickel nanorods already possess promising properties due to their magnetic behavior and their elongated shape. The relevance of this kind of nanorod in a complex measurement setting can be further improved by suitable surface modification and functionalization procedures, so that customized nanostructures for a specific application become available. In this review, we focus on nickel nanorods that are synthesized by electrodeposition into porous templates, as this is the most common type of nickel nanorod fabrication method. Moreover, it is a facile synthesis approach that can be easily established in a laboratory environment. Firstly, we will discuss possible applications of nickel nanorods ranging from data storage to catalysis, biosensing and cancer treatment. Secondly, we will focus on nickel nanorod surface modification strategies, which represent a crucial step for the successful application of nanorods in all medical and biological settings. Here, the immobilization of antibodies or peptides onto the nanorod surface adds another functionality in order to yield highly promising nanostructures.

Direct protein quantification in complex sample solutions by surface-engineered nanorod probes.

Detecting biomarkers from complex sample solutions is the key objective of molecular diagnostics. Being able to do so in a simple approach that does not require laborious sample preparation, sophisticated equipment and trained staff is vital for point-of-care applications. Here, we report on the specific detection of the breast cancer biomarker sHER2 directly from serum and saliva samples by a nanorod-based homogeneous biosensing approach, which is easy to operate as it only requires mixing of the samples with the nanorod probes. By careful nanorod surface engineering and homogeneous assay design, we demonstrate that the formation of a protein corona around the nanoparticles does not limit the applicability of our detection method, but on the contrary enables us to conduct in-situ reference measurements, thus further strengthening the point-of-care applicability of our method. Making use of sandwich assays on top of the nanorods, we obtain a limit of detection of 110 pM and 470 pM in 10-fold diluted spiked saliva and serum samples, respectively. In conclusion, our results open up numerous applications in direct protein biomarker quantification, specifically in point-of-care settings where resources are limited and ease-of-use is of essence.

Homogeneous Biosensing Based on Magnetic Particle Labels.

The growing availability of biomarker panels for molecular diagnostics is leading to an increasing need for fast and sensitive biosensing technologies that are applicable to point-of-care testing. In that regard, homogeneous measurement principles are especially relevant as they usually do not require extensive sample preparation procedures, thus reducing the total analysis time and maximizing ease-of-use. In this review, we focus on homogeneous biosensors for the in vitro detection of biomarkers. Within this broad range of biosensors, we concentrate on methods that apply magnetic particle labels. The advantage of such methods lies in the added possibility to manipulate the particle labels by applied magnetic fields, which can be exploited, for example, to decrease incubation times or to enhance the signal-to-noise-ratio of the measurement signal by applying frequency-selective detection. In our review, we discriminate the corresponding methods based on the nature of the acquired measurement signal, which can either be based on magnetic or optical detection. The underlying measurement principles of the different techniques are discussed, and biosensing examples for all techniques are reported, thereby demonstrating the broad applicability of homogeneous in vitro biosensing based on magnetic particle label actuation.

Homogeneous Protein Analysis by Magnetic Core-Shell Nanorod Probes.

Studying protein interactions is of vital importance both to fundamental biology research and to medical applications. Here, we report on the experimental proof of a universally applicable label-free homogeneous platform for rapid protein analysis. It is based on optically detecting changes in the rotational dynamics of magnetically agitated core-shell nanorods upon their specific interaction with proteins. By adjusting the excitation frequency, we are able to optimize the measurement signal for each analyte protein size. In addition, due to the locking of the optical signal to the magnetic excitation frequency, background signals are suppressed, thus allowing exclusive studies of processes at the nanoprobe surface only. We study target proteins (soluble domain of the human epidermal growth factor receptor 2 - sHER2) specifically binding to antibodies (trastuzumab) immobilized on the surface of our nanoprobes and demonstrate direct deduction of their respective sizes. Additionally, we examine the dependence of our measurement signal on the concentration of the analyte protein, and deduce a minimally detectable sHER2 concentration of 440 pM. For our homogeneous measurement platform, good dispersion stability of the applied nanoprobes under physiological conditions is of vital importance. To that end, we support our measurement data by theoretical modeling of the total particle-particle interaction energies. The successful implementation of our platform offers scope for applications in biomarker-based diagnostics as well as for answering basic biology questions.

Air- and water-resistant noble metal coated ferromagnetic cobalt nanorods.

Cobalt nanorods possess ideal magnetic properties for applications requiring magnetically hard nanoparticles. However, their exploitation is undermined by their sensitivity toward oxygen and water, which deteriorates their magnetic properties. The development of a continuous metal shell inert to oxidation could render them stable, opening perspectives not only for already identified applications but also for uses in which contact with air and/or aqueous media is inevitable. However, the direct growth of a conformal noble metal shell on magnetic metals is a challenge. Here, we show that prior treatment of Co nanorods with a tin coordination compound is the crucial step that enables the subsequent growth of a continuous noble metal shell on their surface, rendering them air- and water-resistant, while conserving the monocrystallity, metallicity and the magnetic properties of the Co core. Thus, the as-synthesized core-shell ferromagnetic nanorods combine high magnetization and strong uniaxial magnetic anisotropy, even after exposure to air and water, and hold promise for successful implementation in in vitro biodiagnostics requiring probes of high magnetization and anisotropic shape.

Direct protein detection in the sample solution by monitoring rotational dynamics of nickel nanorods.

The feasibility of a recently introduced homogeneous immunodiagnostic approach to directly detect analyte binding by optical observation of the hydrodynamic properties of magnetically rotated nanorods ("PlasMag") is demonstrated experimentally. Specifically, it is shown that the phase lag of the long axis of nickel nanorods (magnetic core parameters: length 182 nm, diameter 26 nm) with respect to externally applied rotating magnetic fields significantly increases on the adhesion of bovine serum albumin (BSA) protein to their surfaces. To validate these results, the amount of bound protein molecules is independently determined by analysis of the electrophoretic mobility of the nanorods. Furthermore, the data also demonstrate the applicability of recently developed empirical models based on numerical solutions of the Fokker-Planck equation for describing the dynamics of magnetic nanoparticles in rotating magnetic fields.

Modeling and development of a biosensor based on optical relaxation measurements of hybrid nanoparticles.

We present a new approach for homogeneous real-time immunodiagnostics (denoted as "PlasMag") that can be directly carried out in sample solutions such as serum, thus promising to circumvent the need of sample preparation. It relies on highly sensitive plasmon-optical detection of the relaxation dynamics of magnetic nanoparticles immersed in the sample solution, which changes when target molecules bind to the surfaces of the nanoparticles due to the increase in their hydrodynamic radii. This method requires hybrid nanoparticles that combine both magnetic and optical anisotropic properties. Our model calculations show that core-shell nanorods with a cobalt core diameter of 6 nm, a cobalt core length of 80 nm, and a gold shell thickness of 5 nm are ideally suited as nanoprobes. On the one hand, the spectral position of the longitudinal plasmon resonance of such nanoprobes lies in the near-infrared, where the optical absorption in serum is minimal. On the other hand, the expected change in their relaxation properties on analyte binding is maximal for rotating magnetic fields as excitation in the lower kHz regime. In order to achieve high alignment ratios of the nanoprobes, the strength of the magnetic field should be around 5 mT. While realistic distributions of the nanoprobe properties result in a decrease of their mean optical extinction, the actual relaxation signal change on analyte binding is largely unaffected. These model calculations are supported by measurements on plain cobalt nanorod dispersions, which are the base component of the aspired core-shell nanoprobes currently under development.