Publications

Multiparametric magnetic immunoassays utilizing non-linear signatures of magnetic labels
Lenglet L. Journal of Magnetism and Magnetic Materials, 2009, 104.

Résumé.
A powerful route to utilizing magnetic nanoparticles as labels in magnetic immunoassays is to exploit their non-linear response when they are exposed to a multi-frequency alternating magnetic field. We have upgraded this non-linear method allowing for the detection, discrimination and quantification of particles of two kinds when mixed together, with no need for spatial resolution. Each kind of particle is characterized by a specific magnetic signature based on d2B(H)/dH2. Appropriate data processing of the signature measured on a mixture of both particles allows for obtaining the amount of each particle. This will enable utilizing magnetic labels for multiparametric magnetic immunoassays.

Highly sensitive room-temperature method of non-invasive in vivo detection of magnetic nanoparticles
Nikitin M.P. et al. Journal of Magnetism and Magnetic Materials, 2009.

Résumé.
Methods of non-invasive in vivo quantification of magnetic nanoparticles (MP) have been proposed and realized. The methods are based on non-linear MP magnetization at two frequencies and measuring the response at combinatorial frequencies. The first method is developed for real-time study of MP dynamics and their clearance from the blood system of animals. High sensitivity of 3 ng of Fe3O4 in 0.1 ml was achieved for MP detection in mice tail veins. The second technique is proposed for MP detection inside animal tissues by an external probe. The proposed methods could essentially widen capabilities of biomedical research which involves magnetic nanoparticles.

Characterization of magnetic labels for bioassays
Lalatonne Y. et al. Journal of Magnetism and Magnetic Materials, 2009.

Résumé.
Magnetic nanoparticles differing by their size have been synthesized to use them for multiparametric testing, based on their differing magnetic properties. The nanoparticle has two essential roles: to act as a probe owing to its specific magnetic properties and to carry on its surface precursor groups for the covalent coupling of biological recognition molecules, such as antibodies, nucleic acids.

A totally unique, newly patented, method has been used to characterize magnetic signatures using the MIAplex technology. The MIAplex reader, developed by Magnisense, measures the non linear response of the magnetic labels when they are exposed to a multi-frequency alternating magnetic field. This specific signature based on d2B(H)/dH2 was correlated to other more conventional magnetic detection methods (SQUID & Mössbauer).

Magnetic immunoassays: A new paradigm in POC
Lenglet L., Nikitin P.I., Péquignot C. IVD Technology, July/August 2008.

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Magnetic Immunoassays
Nikitin P.I. et al. Sensor Letters, 2007, 5, 1, 296-9.

Résumé.
New low-noise detection method has been developed and used for design of a new type of biosensors based on detection of nano-sized superparamagnetic particles or magnetic beads that serve as labels for biochemical reactions. The method is based on non-linear magnetization of such particles. The particles are exposed to a magnetic field having components at two frequencies f1 and f2. The response is measured at combinatorial frequencies fi = m · f1 + n · f2, where m and n are integers (one of them can be zero). The integers can be varied to get the best signal-to-noise ratio, e.g., fi = f1 ±2 · f2. Several readers have been designed for the particles counting and used for different immunoassay formats, including those compatible with immunoconcentration and magnetic enrichment of antigens. Registration of 0.1 ng/ml of Y. pestis antigen and 103 cell/ml of Salmonella typhimurium has been demonstrated. The developed biosensing platforms can be used for medical diagnostics, points of care, food pathogen detection, water analysis, etc.

New type of biosensor based on magnetic nanoparticle detection
Nikitin P.I. et al. Journal of Magnetism and Magnetic Materials, 2007, 311, 445-9.

Résumé.
A new type of biosensor has been developed based on detection of nanosized superparamagnetic particles that serve as labels in bioreactions. The method is based on non-linear magnetic material detection by a magnetic field having components at two frequencies f1 and f2. The response is measured at the combinatorial frequencies fi = mf1+nf2, where m and n are integers, e.g., fi = f1 ± f2. Several highly sensitive readers of superparamagnetic particles have been designed and used for development of development of various formats of immunoassays, including those compatible with immunoconcentration and magnetic enrichment of antigen.

Quantitative real-time in vivo detection of magnetic nanoparticles by their nonlinear magnetization
M. P. Nikitin, Journal of Applied Physics, 2008, 103, 07A304.

Résumé.
A novel method of highly sensitive quantitative detection of magnetic nanoparticles (MP) in biological tissues and blood system has been realized and tested in real time in vivo experiments.
The detection method is based on nonlinear magnetic properties of MP and the related device can record a very small relative variation of nonlinear magnetic susceptibility up to 10−8 at room temperature, providing sensitivity of several nanograms of MP in 0.1 ml volume. Real-time quantitative in vivo measurements of dynamics of MP concentration in blood flow have been performed. A catheter that carried the blood flow of a rat passed through the measuring device. After an MP injection, the quantity of MP in the circulating blood was continuously recorded. The method has also been used to evaluate the MP distribution between rat’s organs. Its sensitivity was compared with detection of the radioactive MP based on isotope of 59Fe. The comparison of magnetic and radioactive signals in the rat’s blood and organ samples demonstrated similar sensitivity for both methods. However, the proposed magnetic method is much more convenient as it is safe, less expensive, and provides real-time measurements in vivo.Moreover, the sensitivity of the method can be further improved by optimization of the device geometry.