Immunodiagnostics based on optically detected rotational dynamics of anisotropic nanoparticles

The concept of patient-near and personalized therapy desirably requires point-of-need analytical devices as alternatives to time-consuming diagnostics in conventional remote laboratories. Here, we present a “Magnetic Lab-on-a-Bead” (MLoB) approach towards the realization of a portable analytical device for point-of-care diagnostics. The underlying homogeneous biosensing method1 is based on the optical detection of the rotational dynamics of anisotropic hybrid nanoparticles immersed in the analyte such as whole-blood. The surface of the multicomponent nanoparticles with appropriate magnetic and plasmon-optical properties is functional-ized by complementary receptors. Nanoparticles rotating in a time-varying magnetic field act as capture probes and specifically bind target molecules on their surface, which leads to an increase in their hydrodynamic volume. As a consequence, the rotational dynamics of particles changes, which is detected by measuring the phase lag between the actual nanoparticle alignment with respect to the rotating external magnetic field. The phase lag signal originates from scattering measurements of polarized light with nanoparticles supporting plasmon resonances, and directly quantifies the target molecule concentration in the analyte. The main focus of this presentation is put on the fabrication of nanoparticles and their plasmon resonance analysis by numerical simulations as well as a brief introduction to our newly designed MLoB prototype including first measurement results. Suitable hybrid nanoparticles consisting of sputter-deposited noble metal (Au) and ferromagnetic (NiFe) layers are structured by lithographic methods to elliptically shaped nanoparticles, thus combining both magnetically and optically anisotropic properties with longitudinal and transversal plasmon mode excitation possibility. In comparison to chemical synthesis, nanoparticles fabricated by physical methods feature a narrow size distribution and homogeneous layers, which result in an increased sensitivity due to a higher average optical extinction. Particle scattering cross section calculations suggest a significant sensitivity increase in the presence of plasmonic amplification. By changing the particle composition and/or geometry, the spectral position of the localized plasmon resonance in the gold layer is tuned within the visible to near-infrared regime, a spectral range where the optical absorption in whole-blood is minimal (Fig.1 a), b)). Scanning laser spectroscopy with laser spot diameter comparable to the particle size is carried out to study the light scattering properties of single nanoparticles. Moreover, our MLoB-Setup represents an all-angle measuring system enabling optical detection in reflection, transmission and scattering geometry (Fig.1c)). Please click Additional Files below to see the full abstract

Noise Characterization of Vortex-State GMR Sensors with Different Free Layer Thicknesses

The spin valve principle is the most prominent sensor design among giant- (GMR) and tunneling (TMR) magnetoresistive sensors. A new sensor concept with a disk shaped free layer enables the formation of a flux-closed vortex magnetization state if a certain relation of thickness to diameter is given. The low frequency noise of current-in-plane GMR sensing elements with different free layer thicknesses at different external field strengths has been measured. The measurements of the 1/f noise in external fields enabled a separation of magnetic and electric noise contributions. It has been shown that while the sensitivity is increasing with a decreasing element thickness, the pink noise contribution is increasing too. Still the detection limit at low frequencies is better in thinner free layer elements due to the higher sensitivity

Biomolecular Detection Based on the Rotational Dynamics of Magneto-Plasmonic Nanoparticles

We report on a nanoparticle-based biosensor that represents a label-free homogeneous bioassay suitable for in-vitro biomolecular diagnostics. The underlying detection principle is based on the optical observation of the rotational dynamics of multicomponent nanoparticles utilizing magnetic and plasmonic properties. The plasmon-optical properties of the anisotropic nanoparticles depending on their material composition and geometrical design were investigated by numerical simulations. Based on such an analysis, monodisperse magneto-plasmonic nanoparticles were fabricated using physical fabrication methods. Rotational dynamics measurements revealed the lowest detectable particle concentration in the picomolar (ng/mL) regime, which is very promising in reaching the biomolecular limit of detection which is relevant for routine clinical diagnostics

Comparison of Sensitivity and Low-Frequency Noise Contributions in Giant-Magnetoresistive and Tunneling-Magnetoresistive Spin-Valve Sensors with a Vortex-State Free Layer

Magnetoresistive spin valve sensors based on the giant- (GMR) and tunnelling- (TMR) magnetoresisitve effect with a flux-closed vortex state free layer design are compared by means of sensitivity and low frequency noise. The vortex state free layer enables high saturation fields with negligible hysteresis, making it attractive for applications with a high dynamic range. The measured GMR devices comprise lower pink noise and better linearity in resistance but are less sensitive to external magnetic fields than TMR sensors. The results show a comparable detectivity at low frequencies and a better performance of the TMR minimum detectable field at frequencies in the white noise limit.Comment: 6 pages, 6 figure

Modeling and Development of a Biosensor Based on Optical Relaxation Measurements of Hybrid Nanoparticles

Schrittwieser S, Ludwig F, Dieckhoff J, et al. Modeling and Development of a Biosensor Based on Optical Relaxation Measurements of Hybrid Nanoparticles. ACS Nano. 2012;6(1):791-801.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

Magnetoresistive sensors and magnetic nanoparticles for biotechnology

Reiss G, Brückl H, Hütten A, et al. Magnetoresistive sensors and magnetic nanoparticles for biotechnology. In: Journal of Materials Research. Journal of Materials Research. Vol 20. MATERIALS RESEARCH SOCIETY; 2005: 3294-3302.Magnetoresistive biosensors use a new detection method for molecular recognition reactions based on two recently developed techniques and devices: Magnetic markers and XMR sensors, where XMR means either giant magnetoresistance (GMR) or tunneling magnetoresistance (TMR). The markers are specifically attached to the target molecules, and their magnetic stray field is picked up by an embedded magnetoresistive sensor as a change of the electrical resistance. Compared to established, e.g., fluorescent, detection methods, magnetic biosensors have a number of advantages, including low molecular detection limits, flexibility, and the direct availability of an electronic signal suitable for further automated analysis. This makes them a promising choice for the detection units of future widespread and easy-to-use lab-on-a-chip systems or biochips. In this article, we discuss recent advances in this field and compare possible approaches toward single molecule detection