Scanning magnetoresistance microscopy for magnetically labeled DNA microarrays.

摘要

In this work, imaging of magnetically labeled DNA spots using a single magnetic tunnel junction (MTJ) sensor in a scanning probe microscopy setup is demonstrated. This new approach offers the potential to image centimeter-scale arrays of thousands of DNA spots while still achieving the micron-scale spatial resolution required to resolve individual magnetic markers; at the same time avoiding the need to expose the sensor to fluids or biological materials. By combining the MTJ sensor widely used in magnetic recording technology with magnetic particles as the detection labels for the DNA microarrays, we are developing the fundamental technology for quantitative DNA assays using a low-cost instrument inspired by the hard disk-drive.;Using conventional DNA microarray protocols, single stranded DNA (ss-DNA) probe spots are printed on a silanized glass slide. A test sample containing a known quantity of biotinylated target ss-DNA is introduced and hybridization is allowed to occur. The hybridized DNA is labeled with streptavidin-functionalized 2.8 microm paramagnetic particles (Dynal) with target DNA concentrations in the range of 1 pM to 1 nM producing detectable changes in bead coverage. A MTJ sensor is used as a non-contact scanning probe to measure the induced magnetic stray fields from the particles and to generate the magnetic image of the magnetically labeled DNA spots.;Scanning the MTJ sensor across the array allows both a large scanning area and high spatial resolution (∼1microm). Quantitative imaging requires that the sensor-sample spacing be relatively constant. The intrinsic flatness of microarray substrates is ∼2 microns/cm and scan areas larger than 5 cm2 have been demonstrated. Field variation induced by sample flatness can be corrected by encoding magnetic reference marks on the substrate. Furthermore, increasing the scan speed helps to reduce the l/f noise and performing signal averaging through multiple (N) scanning measurements over the same area for √N improvement in SNR yielding a 100:1 dynamic range and a detection limit of 30 magnetic particles within a single 100microm diameter DNA spot.