Biomolecular diagnostics by a magnetic lab-on-a-chip H. Brückl*, M. Eggeling*, R. Heer*, C. Nöhammer** and J. Schotter* *ARC Seibersdorf research GmbH, Nano-System-Technologies Donau-City-Strasse 1, 1220 Vienna, Austria, hubert.brueckl@acrs.ac.at ** ARC Seibersdorf research GmbH, Life Sciences, 2444 Seibersdorf, Austria ABSTRACT Compared to the established fluorescent labeling method, the use of magnetic markers in biochip sensors has important advantages with respect to the detection of biomolecules at low concentrations. The direct availability of an electronic signal allows the design of inexpensive integrated detection units. In addition, the magnetic beads can be used as carriers for biomolecules. They can be manipulated on-chip via currents running through specially designed line patterns on a chip platform. An obvious benefit is a much shorter incubation time of the marker binding in biochip applications. Therefore, magnetic markers in combination with magnetoresistive sensors are a promising choice for future integrated “magnetic lab-on-a- chip” systems. Keywords: biochip, magnetoresistance, bead, sensor 1 INTRODUCTION Magnetic micro- and nanoparticles are gaining a growing interest in the field of biology, biotechnology and medicine. While the application of magnetic beads for cell or molecule separation is well established since decades, new ideas came up in the recent years to use magnetic particles in diagnostics and therapy, too. The selective transport and specific enrichment of magnetic nanoparticles in vivo are remarkable benefits for magnetic drug targeting or hyperthermia. The latter applies a local particle heating by an external ac-field for cancer treatment. For diagnosis, nanoparticles are adopted for contrast enhancement in imaging methods, or for molecular recognition in assays or on a chip platform. The idea of integrating standard laboratory diagnostics into easy-to-use portable devices has received growing attention both by researchers and biotechnology companies. A recent development is to combine magnetic markers and magnetoresistive (MR) sensors in a magnetic biochip [1-9]. Such systems promise a number of advantages. First of all, the MR sensors are compatible with the established semiconductor process technology and directly provide an electronic signal suitable for automated analysis. They are scaleable and can be tailored to meet any desired functionality. Furthermore, there is no disturbing background signal like in the case of fluorescent methods. Contrary to fluorescent markers, magnetic markers are stable, so that measurements can be repeated many times. By applying magnetic gradient fields, the magnetic markers can also be manipulated on-chip, which for example can be utilized to pull the analyte molecules to specific binding sites or to test the binding strength and distinguish between specifically and unspecifically bound molecules. These fields can be generated on-chip using either conducting lines [4,10-13] or static traps [14]. Furthermore, a strong magnetic gradient field can also remove the hybridized analyte DNA and ensure reusability of the biosensor. 2 MAGNETIC LAB-ON-A-CHIP Magnetic particles and so-called beads are commercially available in a wide range of sizes, functionalities and magnetic properties. They can be used as markers and carriers for the detection and manipulation of biomolecules, e.g. DNA, on a chip platform. Like in the case of standard fluorescent DNA microarrays, the magnetoresistive biochip is based on the principle of molecular recognition between specific known DNA sequences immobilized locally on the sensor surface (so- called probe DNA) and the DNA sequences which are to be analyzed (so-called analyte DNA). The only difference between the fluorescent and the magnetoresistive biosensor are the markers (magnetic instead of fluorescent) and the method of detection. The principle and the underlying physical mechanisms are briefly illustrated and described in figure 1. The platform components, i.e. the sensors and the manipulators, are prepared by modern thin film and lithography technology on a Si wafer or glass. 2.1 On-chip detection For detection, thin film stacks exhibiting the giant magnetoresistance (GMR) effect [15,16] are developed as sensor elements for magnetic bead detection. They consist of multilayers in the second antiferromagnetic coupling maximum (Si/(Ni 80 Fe 20 ) 1.6nm / [Cu 1.9nm /(Ni 80 Fe 20 ) 1.6nm ] 10 / Ta 3nm ). The patterned sensors consist of lines with a thickness of 1 μm and a total length of about 1,8 mm which are wound into spirals with a total diameter of 70 μm and an electrical in-plane resistance at zero magnetic field of about 10 kΩ. At a saturation magnetic field of about 12 kA/m, the parallel configuration of the magnetization directions is reached, and the resistance drops by about 7,4 % relative to the high resistance state. Thus, the overall sensitivity to in-plane magnetic fields for this type of GMR- NSTI-Nanotech 2006, www.nsti.org, ISBN 0-9767985-7-3 Vol. 2, 2006 267