Giant Magenetoresistive Sensors. 2. Detection of Biorecognition Events at Self-Referencing and Magnetically Tagged Arrays

Abstract

Microfabricated devices formed from alternating layers of magnetic and nonmagnetic materials at combined thicknesses of a few hundred nanometers exhibit a phenomenon known as the giant magnetoresistance effect. Devices based on this effect are known as giant magnetoresistive (GMR) sensors. The resistance of a GMR is dependent on the strength of an external magnetic field, which has resulted in the widespread usage of such platforms in high-speed, high-data density storage drives. The same attributes (i.e., sensitivity, small size, and speed) are also important embodiments of many types of bioanalytical sensors, pointing to an intriguing opportunity via an integration of GMR technology, magnetic labeling strategies, and biorecognition elements (e.g., antibodies). This paper describes the utilization of GMRs for the detection of streptavidin-coated magnetic particles that are selectively captured by biotinylated gold addresses on a 2 × 0.3 cm sample stick. A GMR sensor network reads the addresses on a sample stick in a manner that begins to emulate that of a "card-swipe" system. This study also takes advantage of on-sample magnetic addresses that function as references for internal calibration of the GMR response and as a facile means to account for small variations in the gap between the sample stick and sensor. The magnetic particle surface coverage at the limit of detection was determined to be ∼2%, which corresponds to ∼800 binding events over the 200 × 200 µm capture address. These findings, along with the potential use of streptavidin-coated magnetic particles as a universal label for antigen detection in, for example, heterogeneous assays, are discussed.Several laboratories are exploring the utility of giant magnetoresistors (GMRs) as a new chip-scale readout tool in the bioanalytical sciences. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Examples include the application of GMRs and magnetic labeling concepts for the detection of DNA hybridization, biotin-avidin coupling, and antibody-antigen binding. We have also been investigating the integration of immunosorbent assays on a GMR platform, 18 as well as the use of GMRs for the detection of magnetic objects in a microfluidics flow stream as a potential basis for a magnetics flow cytometer. 19 These efforts seek to take advantage of the same set of magnetic detection * To whom correspondence should be addressed.

Giant Magnetoresistance Sensors. 1. Internally Calibrated Readout of Scanned Magnetic Arrays

“…The work detailed in this and the accompanying paper 30 is a continuation of our investigations into the use of GMRs as a readout mode in immunosorbent and other assays; however, it takes a much different tactic. Our earlier study immobilized the capture antibodies directly on the surface of the GMR platform.…”

“…As will be shown, magnetic reference addresses can be used not only as standards to internally calibrate the responses of the sample addresses but also as a means to effectively compensate for small variations in the gap between the sample stick and GMR when scanning an individual sample stick. This paper and the companion 30 that follows describe the results from the first step in our assessment of the ability of GMRs to quantitatively detect the magnetic signature that originates from scanning a sample stick. This strategy parallels the methods employed by the induction coil readers for the magnetic strips on credit cards and the GMRs used in hard drives.…”

“…The last sections examine various analytical figures of merit (e.g., limit of detection (LOD) in terms of the amount of magnetizable material on each address) of this concept as part of a discussion of its potential range and scope. The companion paper 30 builds on this framework by employing the specificity of biotin-streptavadin binding and magnetic particle labels as a mimic for assessing performance in a bioassay.…”

Magnetism and Magnetoresistance: Attractive Prospects for Point-of-Care Testing?

“…Magnetic labels have also been used in immunoassay (magneto-immunoassay) and in polynucleotide assays. These labels include superparamagnetic iron oxide nanoparticles detected using a superconducting quantum interference device (SQUID), 3 and paramagnetic materials and dextrancoated nanoscale superparamagnetic particles detected using a magnetic permeability detector.A recent series of studies has fueled interest in magnetoresistance in bioassays and has demonstrated the feasibility of a disposable assay system based on giant magnetoresistance (GMR) (2, 3 ). GMR is the change in resistance to current flow that occurs in a conductor when exposed to an external magnetic field.…”

“…Magnetic labels have also been used in immunoassay (magneto-immunoassay) and in polynucleotide assays. These labels include superparamagnetic iron oxide nanoparticles detected using a superconducting quantum interference device (SQUID), 3 and paramagnetic materials and dextrancoated nanoscale superparamagnetic particles detected using a magnetic permeability detector.…”