We have investigated a new magnetic labelling technology for high-throughput biomolecular identification and DNA sequencing. Planar multi-bit magnetic tags comprising a magnetic barcode formed by an ensemble of micron-sized thin film ferromagnetic Co bars and a 15 x 15 micron Au square for immobilization of probe molecules have been designed and fabricated. We show that by using a globally applied magnetic field and magneto-optical Kerr microscopy the magnetic elements in the multi-bit magnetic tags can be addressed individually and encoded/decoded remotely. The power of the approach is the read/write technique, which allows modest globally applied magnetic fields to write almost unlimited numbers of codes to populations of tags rather than individuals. The magnetic nature of the technology also lends itself naturally to fast, remote decoding and the ability to rewrite tags if needed. We demonstrate the critical steps needed to show the feasibility of this technology, including fabrication, remote writing and reading, and successful functionalization of the tags as verified by fluorescence detection. This approach is ideal for encoding information on tags in microfluidic flow or suspension, in order to label oligonucleotides during split-and-mix synthesis, and for combinatorial library-based high-throughput multiplexed bioassays.
A design of a biological molecule carrier is presented for the application of high throughput multiplexing biological assays. This carrier contains a bit addressable “magnetic barcode” made of either Permalloy or cobalt thin films, sandwiched between two planar SU8 protective layers. We describe how the design of the magnetic carriers is optimized by engineering the coercivity of each barcode element, allowing the number of available signatures to be increased. Fully encapsulated digital magnetic carriers which carry a 5 bit addressable barcode were also fabricated and are presented. Writing and reading of digital carriers were both performed after releasing in dried solution.
We have used the scanning probe technique, magnetic force microscopy ͑MFM͒, to study the magnetization distribution in a system of indented rectangles made from permalloy. An accurate linear approximation to the micromagnetic equations was implemented in commercial finite element software. This model was used to study the important effect of tip-sample interaction on our MFM measurements. Comparison between experiment and our model confirmed that even for large indents the nanomagnets adopted vortex ground states. A qualitative relationship between the sample's magnetization, in the absence of the MFM tip's magnetic field, and the induced contrast was identified. The optimum ratio of charge contrast to induced contrast when observing vortex states was found to be proportional to the tip moment raised to the power of 0.4. This was subject to the limitations imposed by resolution and thermal noise. It occurred for large separation between tip and sample.
We describe proof-of-principle experiments and theory that demonstrate a new method of performing multiplexed biological assays by using microscopic tags which carry multi-bit magnetic codes to label probe biomolecules. It is demonstrated that these "micro-barcode tags" can be encoded, transported using micro-fluidics and are compatible with surface chemistry. We also present simulations and experimental results which suggest the feasibility of decoding the micro-barcode tags using magnetoresistive sensors. Together, these results demonstrate substantial progress towards meeting the critical requirements of a magnetically encoded, high-throughput and portable biological assay platform. We also show that an extension of our technology could be potentially used to label libraries consisting of~10 4 distinct probe molecules, and could therefore have a strong impact on mainstream medical diagnostics.
Microarrays and suspension-based assay technologies have attracted significant interest over the past decade with applications ranging from medical diagnostics to high throughput molecular biology. The throughput and sensitivity of a microarray will always be limited by the array density and slow reaction kinetics. Suspension (or bead) based technologies offer a conceptually different approach, improving detection by substituting a fixed plane of operation with millions of microcarriers. However, these technologies are currently limited by the number of unique labels that can be generated in order to identify the molecular probes on the surface. We have proposed a novel suspension-based technology that utilizes patterned magnetic films for the purpose of generating a writable label. The microcarriers consist of an SU-8 substrate that can be functionalized with various chemical or biological probes and magnetic elements, which are individually addressable by a magnetic sensor. The magnetization of each element is aligned in one of two stable directions, thereby acting as a magnetic bit. In order to detect the stray field and identify the magnetic labels, we have developed a microfluidic device with an integrated tunneling magnetoresistive (TMR) sensor, sourced from Micro Magnetics Inc. We present the TMR embedding architecture as well as detection results demonstrating the feasibility of magnetic labeling for lab-on-a-chip applications.
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