Electricity: measuring and testing – Particle precession resonance
Reexamination Certificate
2003-01-17
2004-12-07
Shrivastav, Brij B (Department: 2859)
Electricity: measuring and testing
Particle precession resonance
Reexamination Certificate
active
06828786
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to nanomagnets and methods of using nanomagnets for biological problems, such as the detection and manipulation of biological molecules and nanosurgery within cells.
2. Description of the Prior Art
Magnetic nanostructures have in the past been fabricated for dense storage media and compact magnetic sensors. As the focus of biological analysis turns to progressively smaller sample volumes, and eventually to single molecules, efforts in nanomanipulation, characterization, and local sensing of biological materials become increasingly important. The integration of nanomagnetic devices into biological research instrumentation will provide powerful new capabilities for sensitive, compact and efficient bio-sensing.
Consider first recent advances in magnetic manipulation technology. Within the past 20 years, the micromanipulation and characterization of objects ranging in size from atomic to micrometer dimensions has become one of the central goals of modern science. Scanning tunneling microscopy and atomic force microscopy enable surface imaging with atomic resolution, as well as atomic manipulation in many environments. Optical trapping methods have also become routine for the manipulation of micron-sized latex spheres attached to objects of biological interest. Similarly, carbon nanotubes are utilized for physical tweezing of micro-objects. Magnetic tweezers have more recently also been applied to the study of the physical properties of the cytoplasm, mechanical properties of cell surfaces, and elasticity and transport of single DNA molecules For cell studies, most of these techniques rely on the micromanipulation of magnetic particles positioned within a cell wall or bound on the surface of a cell. For single molecule investigations, magnetic particles are attached onto one end of a molecule strand. In all of these studies, micromanipulation is typically performed with a magnetic manipulator consisting of permanent or soft coil-wound magnets with macroscopic dimensions.
Nanofluidic chips have been developed in which subnanoliter fluid volumes can be manipulated and biochemical assays performed. See, Unger M. A. Science V. 288, pp 113 (2000). These fluidic circuits can be monolithically integrated with optoelectronic sensors to enable the rapid analysis of 10 pL fluid volumes. Thousands of valves and pumps, made in silicone elastomer, have been aligned onto micro-optic chips such as light emitters or silicon CMOS detector arrays to form nanofluidic analysis systems. The integration of optoelectronics with microfluidics has thus allowed the construction of very compact nanofluidic test systems, where the fluidic structures are inexpensive and disposable. The resulting multifunctional biosensor chips are very compact and can concentrate and measure pathogens or toxins as well as deliver drugs. In turn, these nanofluidic systems are ideal for extracting, delivering and holding single cells for high resolution cellular magnetic resonance imaging (cMRI) and for the manipulation of magnetic nanoprobes.
BRIEF SUMMARY OF THE INVENTION
The invention is a new synergy between biology and magnetic nanostructure design by combining (A) capabilities in nanofabrication, characterization, and manipulation of single domain magnetic nanostructures, with (B) the use of binding chemistry of biological molecules to modify the magnetic nanostructures into magnetic sensors and magnetically controllable nanoprobes. The biological characterization scheme of the invention combines nanomanipulation with the observation of small magnetic structures in fluids. These capabilities allow the construction of fundamentally new magnetic nanostructure geometries that are not easily fabricated by conventional high resolution lithographic methods. By coating nanomagnets with biologically interesting molecules and using the approaches detailed below, ultra-small, highly sensitive and robust biomagnetic devices are defined, and molecular electronics and spin electronics are combined. When these nano-sensors are integrated into microfluidic channels, highly efficient single-molecule detection chips for rapid diagnosis and analysis of biological agents are constructed.
As described below a tool is provided to remotely control the position of magnetic nanoparticles, to pattern magnets lithographically onto chips for magnetic self-assembly, and to suspend magnetic wires into cantilevers. By combining these capabilities, a new generation of sensors and imaging instruments is made possible. These structures are especially useful for the nano-manipulation of magnetic probes in-situ within living biological systems, namely performing nanosurgery within cells or within nanofluidic channels, since the magnets can be remotely actuated and controlled by nanocoil probes as described below in connection, which nanocoil probes locally concentrate magnetic fields.
Together with surface plasmon scatterers, which can be attached to the magnetic nanoparticles, the control coils can be used to move magnets within fluids and optically monitor their precise location without the scattering, heating and bleaching often encountered when using optical tweezer technology.
Moreover, magnetic attraction can be used to self-assemble tunnel junctions and define sensitive nanomechanical structures where magnetic forces can be externally applied to add mechanical gain to cantilevers and increase the effective Q of nanomechanical resonators.
Together with our microfluidic tools to hold biological specimens, miniaturized coils are ideally suited for improving the imaging resolution of cMRI systems for cell development studies, since nanocoils can operate at high frequencies and can establish large gradient fields.
In the illustrated embodiment nanomagnetic and nano-optic manipulators and sensors are combined with the previously developed with microfluidic design technology discussed above. What results is the highest resolution magnetic resonant imaging systems yet devised to date, with an ability to manipulate magnetic nanoparticles and trigger biological reactions within a cell. Further, the highest resolution nano-mechanical resonator sensor built to date for detecting electron spin is realized.
One illustrated embodiment of the invention is a magnetic nanoprobe for use in magnetic micromanipulation comprising a micron-sized soft-ferromagnetic wire serving as a magnetic core, a micron-sized coil wound around the magnetic core, and a sharp tip defined on a distal end of the magnetic core.
In one embodiment the micron-sized coil is comprised of at least two layers of wire coils. The micron-sized magnetic core has a diameter of 100 &mgr;m or less, the micron-sized coil is comprised of magnet wire having a diameter of 50 &mgr;m or less, and the sharp tip defined on a distal end of the magnetic core is formed by electrochemical etching.
The invention can also be described in another embodiment as a method comprising the steps of providing a biofunctionalized magnetically interactive nanoparticle, disposing the biofunctionalized magnetically interactive nanoparticle into a cell, and manipulating the magnetically interactive nanoparticle in the cell by means of a magnetic nanoprobe to interact with intracellular processes.
The invention is also embodied as a nanoelectromagnetic mechanical apparatus comprising a plurality of nanoprobes combined to form a nanoelectromagnet assembly and at least one magnetic nanowire disposed proximate to the nanoelectromagnet assembly and electromagnetically coupled thereto.
The nanoelectromagnetic mechanical apparatus in one embodiment can be embodied as a nanomotor where the nanoelectromagnet assembly is arranged and configured to serve as a stator, and where the nanowire serves as a rotor. In another embodiment the nanoelectromagnet assembly is arranged and configured to serve as a solenoid coil, and where the nanowire serves as an actuator. In still another embodiment the nanoelectromagnet assembly is arranged and configured to serve as a relay coi
Barbic Mladen
Scherer Axel
California Institute of Technology
Dawes Daniel L.
Myers Dawes Andras & Sherman LLP
Shrivastav Brij B
LandOfFree
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