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      Homogeneous Biosensing Based on Magnetic Particle Labels

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          Abstract

          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.

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          Tomographic imaging using the nonlinear response of magnetic particles.

          The use of contrast agents and tracers in medical imaging has a long history. They provide important information for diagnosis and therapy, but for some desired applications, a higher resolution is required than can be obtained using the currently available medical imaging techniques. Consider, for example, the use of magnetic tracers in magnetic resonance imaging: detection thresholds for in vitro and in vivo imaging are such that the background signal from the host tissue is a crucial limiting factor. A sensitive method for detecting the magnetic particles directly is to measure their magnetic fields using relaxometry; but this approach has the drawback that the inverse problem (associated with transforming the data into a spatial image) is ill posed and therefore yields low spatial resolution. Here we present a method for obtaining a high-resolution image of such tracers that takes advantage of the nonlinear magnetization curve of small magnetic particles. Initial 'phantom' experiments are reported that demonstrate the feasibility of the imaging method. The resolution that we achieve is already well below 1 mm. We evaluate the prospects for further improvement, and show that the method has the potential to be developed into an imaging method characterized by both high spatial resolution as well as high sensitivity.
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            Janus particles: synthesis, self-assembly, physical properties, and applications.

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              Multifunctional magnetic nanoparticles: design, synthesis, and biomedical applications.

              The combination of nanotechnology and molecular biology has developed into an emerging research area: nanobiotechnology. Magnetic nanoparticles are well-established nanomaterials that offer controlled size, ability to be manipulated externally, and enhancement of contrast in magnetic resonance imaging (MRI). As a result, these nanoparticles could have many applications in biology and medicine, including protein purification, drug delivery, and medical imaging. Because of the potential benefits of multimodal functionality in biomedical applications, researchers would like to design and fabricate multifunctional magnetic nanoparticles. Currently, there are two strategies to fabricate magnetic nanoparticle-based multifunctional nanostructures. The first, molecular functionalization, involves attaching antibodies, proteins, and dyes to the magnetic nanoparticles. The other method integrates the magnetic nanoparticles with other functional nanocomponents, such as quantum dots (QDs) or metallic nanoparticles. Because they can exhibit several features synergistically and deliver more than one function simultaneously, such multifunctional magnetic nanoparticles could have unique advantages in biomedical applications. In this Account, we review examples of the design and biomedical application of multifunctional magnetic nanoparticles. After their conjugation with proper ligands, antibodies, or proteins, the biofunctional magnetic nanoparticles exhibit highly selective binding. These results indicate that such nanoparticles could be applied to biological medical problems such as protein purification, bacterial detection, and toxin decorporation. The hybrid nanostructures, which combine magnetic nanoparticles with other nanocomponents, exhibit paramagnetism alongside features such as fluorescence or enhanced optical contrast. Such structures could provide a platform for enhanced medical imaging and controlled drug delivery. We expect that the combination of unique structural characteristics and integrated functions of multicomponent magnetic nanoparticles will attract increasing research interest and could lead to new opportunities in nanomedicine.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Sensors (Basel)
                Sensors (Basel)
                sensors
                Sensors (Basel, Switzerland)
                MDPI
                1424-8220
                06 June 2016
                June 2016
                : 16
                : 6
                : 828
                Affiliations
                [1 ]Molecular Diagnostics, AIT Austrian Institute of Technology, Vienna1220, Austria; joerg.schotter@ 123456ait.ac.at
                [2 ]Fachbereich Physik, Philipps-Universität Marburg, Marburg 35037, Germany; beatriz.pelazgarcia@ 123456physik.uni-marburg.de (B.P.); wolfgang.parak@ 123456physik.uni-marburg.de (W.J.P.)
                [3 ]Laboratoire de Physique et Chimie des Nano-objets (LPCNO), Université de Toulouse, INSA, UPS, CNRS, Toulouse 31077, France; sergiolentijo@ 123456gmail.com (S.L.-M.); ksoulant@ 123456insa-toulouse.fr (K.S.)
                [4 ]Institute of Electrical Measurement and Fundamental Electrical Engineering, TU Braunschweig, Braunschweig 38106, Germany; j.dieckhoff@ 123456uke.de (J.D.); f.ludwig@ 123456tu-bs.de (F.L.)
                [5 ]Experimentalphysik, Universität des Saarlandes, Saarbrücken 66123, Germany; annegret.guenther@ 123456web.de (A.G.); a.tschoepe@ 123456nano.uni-saarland.de (A.T.)
                Author notes
                [* ]Correspondence: stefan.schrittwieser@ 123456ait.ac.at ; Tel.: +43-50-550-4309
                [†]

                NABLA Lab, Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University for Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia

                [‡]

                Diagnostic and Interventional Radiology Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany

                Article
                sensors-16-00828
                10.3390/s16060828
                4934254
                27275824
                5a89adb5-81d5-4962-9b9d-b7d5ad027b17
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 April 2016
                : 01 June 2016
                Categories
                Review

                Biomedical engineering
                biosensor,magnetic nanoparticle,homogeneous assay,magnetorelaxation,ac susceptibility,nmr,magnetic relaxation switch,asynchronous magnetorotation,magneto-optics,nanorod

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