Marco Donolato

On-chip manipulation of protein-coated magnetic beads via domain-wall conduits.

For this reasonmanipulationatthenanoscaleofsurfacefunctionalizedmagneticbeads in suspension is of paramount importance in biotechnol-ogy, nanochemistry, and nanomedicine as it leads to a precisecontrol of the tagged biological entity.In the past few years many approaches have been developedboth for the manipulation and transport of a massive particlepopulation or of a single particle, e.g., microfabricated current-carrying wires,

Domain wall displacement in Py square ring for single nanometric magnetic bead detection

physical properties of a domain wall DW localized at a geometric corner. The concept illustrated in the present paper relies on a previous experimental work made on square rings of Permalloy Py for application in magnetic storage of information. 11 In this design head-to-head and tail-to-tail DWs having a transverse structure Neel type 11 can be positioned at a given corner, and their position can be read electrically thanks to the AMR effect: when a DW is present between two sensing leads a reduction in the resistance is observed since some of the magnetization of the DW points perpendicularly to the current flow. Otherwise, when there is no DW present between the two sensing leads, the magnetization follows the direction of the perimeter of the ring and the resistance is higher. In this work we adapted this device to demonstrate a detection concept suitable for the detection of magnetic nanobeads. Panel a of Fig. 1 shows the scanning electron microscopy image of the structure used in the present experiment. The 30 nm thick Py square ring structures have been lithographically patterned on top of 20 nm thick and 100 nm wide Au contacts, previously fabricated on a SiO2 /Si substrate. The outside size of the rings is 1.0 1.0 m 2 , the width of each segment is about 180 nm, and the slit is about 80 nm wide. For the magnetoresistance measurements presented here, the voltage drop was measured

Nanosized corners for trapping and detecting magnetic nanoparticles

We present a device concept based on controlled micromagnetic configurations in a corner-shaped permalloy nanostructure terminated with two circular disks, specifically designed for the capture and detection of a small number of magnetic beads in suspension. A transverse head-to-head domain wall (TDW) placed at the corner of the structure plays the role of an attracting pole for magnetic beads. The TDW is annihilated in the terminating disks by applying an appropriate magnetic field, whose value is affected by the presence of beads chemically bound to the surface. In the case where the beads are not chemically bound to the surface, the annihilation of the TDW causes their release into the suspension. The variation of the voltage drop across the corner, due to the anisotropic magnetoresistance (AMR) while sweeping the magnetic field, is used to detect the presence of a chemically bound bead. The device response has been characterized by using both synthetic antiferromagnetic nanoparticles (disks of 70 nm diameter and 20 nm height) and magnetic nanobeads, for different thicknesses of the protective capping layer. We demonstrate the detection down to a single nanoparticle, therefore the device holds the potential for the localization and detection of small numbers of molecules immobilized on the particles functionalized surface.

Magnetic domain wall conduits for single cell applications

The ability to trap, manipulate and release single cells on a surface is important both for fundamental studies of cellular processes and for the development of novel lab-on-chip miniaturized tools for biological and medical applications. In this paper we demonstrate how magnetic domain walls generated in micro- and nano-structures fabricated on a chip surface can be used to handle single yeast cells labeled with magnetic beads. In detail, first we show that the proposed approach maintains the microorganism viable, as proven by monitoring the division of labeled yeast cells trapped by domain walls over 16 hours. Moreover, we demonstrate the controlled transport and release of individual yeast cells via displacement and annihilation of individual domain walls in micro- and nano-sized magnetic structures. These results pave the way to the implementation of magnetic devices based on domain walls technology in lab-on-chip systems devoted to accurate individual cell trapping and manipulation.

Quantification of rolling circle amplified DNA using magnetic nanobeads and a Blu-ray optical pick-up unit

We present the first implementation of a Blu-ray optical pickup unit (OPU) for the high-performance low-cost readout of a homogeneous assay in a multichamber microfluidic disc with a chamber thickness of 600 μm. The assay relies on optical measurements of the dynamics of magnetic nanobeads in an oscillating magnetic field applied along the light propagation direction. The laser light provided by the OPU is transmitted through the sample chamber and reflected back onto the photo detector array of the OPU via a mirror. Spectra of the 2nd harmonic photo detector signal vs. the frequency of the applied magnetic field show a characteristic peak due to freely rotating magnetic nanobeads. Beads bound to ~1 μm coils of DNA formed off-chip by padlock probe recognition and rolling circle amplification show a different dynamics and the intensity of the characteristic peak decreases. We have determined the optimum magnetic bead concentration to 0.1mg/mL and have measured the response vs. concentration of DNA coils formed from Escherichia Coli. We have found a limit of detection of 10 pM and a dynamic range of about two orders of magnitude, which is comparable to the performance obtained using costly and bulky laboratory equipment. The presented device leverages on the advanced but low-cost technology of Blu-ray OPUs to provide a low-cost and high-performance magnetic bead-based readout of homogeneous bioassays. The device is highly flexible and we have demonstrated its use on microfluidic chambers in a disc with a thickness compatible with current optical media mass-production facilities.

Novel Readout Method for Molecular Diagnostic Assays Based on Optical Measurements of Magnetic Nanobead Dynamics

We demonstrate detection of DNA coils formed from a Vibrio cholerae DNA target at picomolar concentrations using a novel optomagnetic approach exploiting the dynamic behavior and optical anisotropy of magnetic nanobead (MNB) assemblies. We establish that the complex second harmonic optical transmission spectra of MNB suspensions measured upon application of a weak uniaxial AC magnetic field correlate well with the rotation dynamics of the individual MNBs. Adding a target analyte to the solution leads to the formation of permanent MNB clusters, namely, to the suppression of the dynamic MNB behavior. We prove that the optical transmission spectra are highly sensitive to the formation of permanent MNB clusters and, thereby to the target analyte concentration. As a specific clinically relevant diagnostic case, we detect DNA coils formed via padlock probe recognition and isothermal rolling circle amplification and benchmark against a commercial equipment. The results demonstrate the fast optomagnetic readout of rolling circle products from bacterial DNA utilizing the dynamic properties of MNBs in a miniaturized and low-cost platform requiring only a transparent window in the chip.

Flexible spintronic devices on Kapton

Magnetic tunnel junctions and nano-sized domain-wall conduits have been fabricated on the flexible substrate Kapton. Despite the delicate nature of tunneling barriers and zig-zag shaped nanowires, the devices show an outstanding integrity and robustness upon mechanical bending. High values of bending angle (r = 5 mm) have been achieved without degradation of the device performance, reaching room-temperature tunneling magnetoresistance ratios of 12% in bended Co/Al2O3/NiFe junctions. In addition, a suitable route to pattern high-quality nanostructures directly on the polyimide surface is established. These results demonstrate that Kapton is a promising platform for low-cost, flexible spintronic applications involving tunnel junction elements and nanostructurization.

Flexible and stretchable polymers with embedded magnetic nanostructures.

A novel pathway is presented to transfer and embed functional patterned magnetic nanostructures into flexible and stretchable polymeric membranes. The geometrical and magnetic properties are maintained through the process, realized even directly inside a microfluidic channel. These results pave the way to the realization of smart biomedical systems and devices based on the integration of magnetic nanostructures into new classes of substrates.

Scalable DNA-Based Magnetic Nanoparticle Agglutination Assay for Bacterial Detection in Patient Samples

We demonstrate a nanoparticle-based assay for the detection of bacteria causing urinary tract infections in patient samples with a total assay time of 4 h. This time is significantly shorter than the current gold standard, plate culture, which can take several days depending on the pathogen. The assay is based on padlock probe recognition followed by two cycles of rolling circle amplification (RCA) to form DNA coils corresponding to the target bacterial DNA. The readout of the RCA products is based on optomagnetic measurements of the specific agglutination of DNA-bound magnetic nanoparticles (MNPs) using low-cost optoelectronic components from Blu-ray drives. We implement a detection approach, which relies on the monomerization of the RCA products, the use of the monomers to link and agglutinate two populations of MNPs functionalized with universal nontarget specific detection probes and on the introduction of a magnetic incubation scheme. This enables multiplex detection of Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa at clinically relevant concentrations, demonstrating a factor of 30 improvement in sensitivity compared to previous MNP-based detection schemes. Thanks to the universal probes, the same set of functionalized MNPs can be used to read out products from a multitude of RCA targets, making the approach truly scalable for parallel detection of multiple bacteria in a future integrated point of care molecular diagnostics system.

On‐Chip Detection of Rolling Circle Amplified DNA Molecules from Bacillus Globigii Spores and Vibrio Cholerae

For the first time DNA coils formed by rolling circle amplification are quantified on-chip by Brownian relaxation measurements on magnetic nanobeads using a magnetoresistive sensor. No external magnetic fields are required besides the magnetic field arising from the current through the sensor, which makes the setup very compact. Limits of detection down to 500 Bacillus globigii spores and 2 pM of Vibrio cholerae are demonstrated, which are on the same order of magnitude or lower than those achieved previously using a commercial macro-scale AC susceptometer. The chip-based readout is an important step towards the realization of field tests based on rolling circle amplification molecular analyses.