Proposed biosensors based on time-dependent properties of magnetic fluids

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Abstract

A new method of detection of biomolecules in aqueous solution is proposed. The method is based on the detection of shifts in the frequency-dependent magnetic susceptibility of magnetic colloids due to increase in hydrodynamic radius on specific binding with biomolecules.

Introduction

Magnetic fluids comprise suspensions of magnetic particles in either aqueous or organic fluids. In order to obtain a stable dispersion of magnetic particles in an aqueous medium, the characteristics of the particle surface have to be tailored to the medium. Particle–solvent interactions and interparticle repulsions must become strong enough to overcome Van der Waals attraction between the particles [1] and magnetic attraction in the case of particles with a permanent magnetic moment.

One method of stabilization is coating of the magnetic particles with organic polymers [2], [3], [4]. This has been shown to stabilise the magnetic particles against aggregation and can produce a biocompatible fluid. Enzymes and other biomolecular recognition elements and receptors can be covalently bound to the organic polymers [5], [6] thus creating composite structure particles that can act as magnetic labels in aqueous media.

Here we propose a novel methodology for the detection of binding of biomolecules to colloidal magnetic particles in suspension. The methodology exploits the time-dependent magnetic properties of magnetic colloidal suspensions and could form the basis for new types of biosensor. The methodology could be applied to the general class of assays based on the streptavidin – biotin interaction, for example.

The time-dependent magnetic properties of aqueous media containing magnetic particles are altered when biomolecules such as proteins bind to the nanoscale particles in suspension [7], [8]. The cause of the change in magnetic relaxation times is the larger hydrodynamic radius of the biomolecule-magnetic particle composite compared with the magnetic particle alone.

Theory shows that the relaxation time is proportional to the hydrodynamic volume of the particle in suspension. Time-sensitive magnetic measurement devices such as AC magnetic susceptometers are able to measure a spectrum of relaxation times within a suspension of magnetic particles thus enabling particle sizes to be measured.

Section snippets

Theoretical background

There are two different mechanisms by which the magnetic moment of a particle suspended in a fluid may relax after removal of a magnetic field. The first mechanism involves the bulk rotation of the particle within the fluid owing to Brownian motion. This mechanism applies mainly to particles whose magnetic moments are fixed relative to the crystal axes of the particles. They are often referred to as magnetically blocked particles. This Brownian rotational diffusion time is given byτB=4πηr3kT,

Experimental method

Measurement of χ′(ω) and χ″(ω) can be achieved by measuring the changes in the inductance and resistance of an induction coil when a magnetic fluid is inserted into its field [12]. When the magnetic fluid is inserted into the coil, the inductance will change by an amount proportional to χ′ while the resistance increases by an amount proportional to χω.

These measurements can be made using the method described in detail by Fannin et al. (1988) to measure χ′ and χ″ as functions of frequency [13].

Discussion

The frequency at which the maximum quadrature susceptibility is calculated to occur for monodisperse particles in aqueous suspension at a temperature of 20°C is shown in Fig. 1. The viscosity of the solution is taken to be that of pure water at a temperature of 20°C (1.002×10−3 Ns m−2). For radii over 200 nm, a change in the hydrodynamic radius of 1 nm causes the frequency peak to shift by approximately 0.1 Hz. For smaller radii, the same change in hydrodynamic radius causes a larger frequency

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