In-Vitro Magnetoresistive Biosensors for Single Molecular Based Disease Diagnostics: Optimization of Sensor Geometry and Structure

Abstract

Detection of biological information using magnetoresistance (MR) sensors based on multilayered giant MR (GMR), or exchange biased GMR spin valves, operated by the magnetic field produced by magnetic nanoparticle sensor agents has been paid considerable attention in biomedical sensor technologies (Baselt et al., 1998; Tondra et al., 2000; Rife et al., 2003; Graham et al., 2004). The main reason for this interest is that MR based biosensors provide technical advantages such as high sensitivity, relatively fast and low-volume assay, and easy manipulation of the magnetic sensor agents under the externally applied magnetic field gradients (Graham et al., 2002; Lagae et al., 2002). These advantages lead to improved sensing performance, stimulating the development of functional in-vitro GMR based biosensors to obtain biological information and diagnose diseases more accurately in healthcare (Megen & Prins, 2005). However, all the developed GMR biosensors so far were mostly focused on counting or indentifying multiple biomolecules such as a DNA counter and a bead array counter rather than single molecular detection (SMD) (Baselt et al., 1998; Miller et al., 2001; Graham et al., 2003; Li & Wang, 2003; Schepper et al., 2004; Wang et al., 2005; Shen et al., 2005). The main physical reason for this technical limitation is that the magnetic susceptibility of a single superparamagnetic nanoparticle sensor agent (SPNSA), which can be easily manipulated on the sensor surface without any serious agglomeration and easily retrieve magnetic stray field, is too small to generate a large enough field for acheiving a reasonably high SNR (Singal-to-Noise Ratio). Although superparamagentic microbeads have been attempted to obtain a larger stray field for higher SNR for SMD (Graham et al., 2002; Wirix-Speetiens et al., 2006), these agents were also revealed to have a technical drawback that they can not maintain one to one ratio between the microbead and the biomolecules due to a big mismatch in size. Hence, to develop more powerful in-vitro GMR bisoensor system for SMD, ferrimagentic nanoparticle (FN) sensor agents, which have a high remnant magentization expecting to producing a sufficient stray field for a higher SNR, and a high chemical stability as well as a high biocompatibility with living cells or biological entities, are currently considered as a feasible sensor agent to label the biomolecules. However, the applications of FN to a GMR biosensor agent has been limited for the past few years by a