Magnetic Platform for Sample Orientation
20210255091 · 2021-08-19
Inventors
Cpc classification
G01N21/25
PHYSICS
G01N15/1456
PHYSICS
G01N21/01
PHYSICS
G01N23/2204
PHYSICS
International classification
G01N21/01
PHYSICS
G01N21/25
PHYSICS
Abstract
A method is provided for positioning and orienting a platform such as a sample or workpiece relative to a frame of reference where the platform is a complex magnetic object that contains at least two magnetic domains with non-collinear magnetic moments and the method includes generating a spatially and temporally varying magnetic field so that each magnetic moment of the complex magnetic object interacts with the applied magnetic field. This can be used to performs an operation on a workpiece such as addition or removal of material. This can be used where the object includes a sample and, in each measurement configuration of the sample, radiation transmitted, reflected or scattered is measured from said sample material and analyzed to obtain information about the sample material;
Claims
1. A method for positioning and orienting a platform relative to a frame of reference; wherein the platform is a complex magnetic object that contains at least two magnetic domains with non-collinear magnetic moments; and generating a spatially and temporally varying magnetic field so that each magnetic moment of the complex magnetic object interacts with the applied magnetic field.
2. The method according to claim 1 wherein the complex magnetic object has at least three whole body translational degrees of freedom and at least three whole body rotational degrees of freedom.
3. The method according to claim 1 wherein the complex magnetic object includes an integral tool that performs an operation on a workpiece.
4. The method according to claim 1 wherein the complex magnetic object is positioned and oriented relative to a location on a workpiece and an operation performed by the complex magnetic object causes material to be added to the workpiece.
5. The method according to claim 4 wherein the material is added by providing the complex magnetic object with a source of directional radiation and emitting the directional radiation to the additive location causing photo-polymerization of the additive material to the substrate at said additive location.
6. The method according to claim 5 wherein the directional radiation means is either integral to the complex magnetic object or an optical element that directs radiation from an external radiation source.
7. The method according to 5 wherein the directional radiation means directs a plurality of different wavelengths to different substrate locations and wherein each different wavelength causes a different additive material to be added.
8. The method according to claim 4 wherein the material is added by providing the complex magnetic object with a catalyst storage device and releasing catalyst from the catalyst storage device to the additive location causing polymerization of the additive material to the substrate at said additive location.
9. The method according to claim 4 wherein a plurality of complex magnetic objects add material to a plurality of different substrate locations.
10. The method according to claim 4 wherein the complex magnetic object causes radiation incident at the location causing the addition of material via photo-polymerization.
11. The method according to claim 1 wherein the complex magnetic object is positioned and oriented relative to a location on a workpiece and an operation performed by the complex magnetic object causes material at the location to be modified.
12. The method according to claim 1 wherein the position and orientation of the complex magnetic object is measured by a sensor and the information from the sensor is used at least in part to calculate a magnetic field pattern required to cause a change in the position or orientation of the complex magnetic object.
13. The method according to claim 1 wherein the complex magnetic object includes an energy transformation device that transforms energy from a first form to a second form.
14. The method according to claim 1 wherein the complex magnetic object includes an integral light source and the complex magnetic object is positioned and oriented relative to a workpiece by the sequence of applied magnetic fields; and upon receiving a signal, said light source emits light toward a location on the workpiece to perform an operation.
15. The method according to claim 1 wherein a machining operation performed by the complex magnetic object causes material to be removed from the workpiece.
16. The method of claim 1 wherein the complex magnetic object includes an integral energy storage device.
17. The method of claim 1 wherein the complex magnetic object includes an integral energy conversion device and at least one integral electronic device.
18. The method according to claim 1 wherein an electric field is generated between two points on the complex magnetic object.
19. The method according to claim 1 wherein the complex magnetic object includes an integral radiation source and radiation from said radiation source is emitted at least in part into a material.
20. The method according to claim 1 wherein the complex magnetic object is surrounded by a viscous material that produces a viscous drag force in opposition to magnetic forces on the complex magnetic object.
21. The method according to claim 1 comprising the steps of attaching a sample material to a sample location on a surface of a complex magnetic object (CMO); directing a beam of radiation toward the sample location; for a plurality of measurement configurations, rotating and translating the complex magnetic object to bring the sample location position and orientation into correspondence with each measurement configuration and measuring radiation transmitted, reflected or scattered from said sample material; analyzing said plurality of measurements with a computation device to obtain information about the sample material; and wherein the complex magnetic object is rotated and translated to each measurement configuration by generating a sequence of magnetic fields that interact with a plurality of magnetic moments integral to the complex magnetic object to produce forces and torques.
22. The method according to claim 21 wherein the sample material is placed on the complex magnetic object with at least one sample material axis statistically related to the direction of a complex magnetic object axis.
23. The method according to claim 22 wherein the substrate property axis is a crystallographic axis of the substrate material.
24. The method according to claim 21 23 wherein the sample material orientation is related to the radiation beam direction and polarization by a set of Euler angles.
25. The method according to claim 21 wherein the complex magnetic object further includes surface features that enhance the electromagnetic field in an enhancement region proximate to the surface features and at least a portion of the sample material is placed in the enhancement region.
26. The method according to claim 21 wherein the sample material is positioned and oriented relative to a plurality of enhancement regions on separate substrate(s) wherein each enhancement region changes a different spectral property of the sample material.
27. The method according to claim 21 wherein the same type of sample material is attached to substrates with different properties wherein each substrate with a different property is located on a different face of the complex magnetic object.
28. The method according to claim 21 wherein the sample material is attached to the complex magnetic object by an antibody.
29. The method according to claim 21 wherein the complex magnetic object includes a label material that is added to the sample material.
30. The method according to claim 21 wherein the sample material is a cell, tissue, antigen, biological macromolecule or a biological reagent.
31. The method according to claim 1 comprising the steps of attaching an optical element at a location on a surface of the complex magnetic object; directing a beam of radiation toward the optical element location; rotating and translating the complex magnetic object to bring the optical element location position and orientation into correspondence with a required optical configuration; wherein the complex magnetic object is rotated and translated to each optical configuration by generating a sequence of magnetic fields that interact with a plurality of magnetic moments integral to the complex magnetic object to produce forces and torques.
32. The method according to claim 31 wherein the optical element is selected from the list of an absorbing element, a filter, an aperture, a mirror, a lens, a prism, and a grating.
33. The method according to claim 28 wherein the optical element is positioned relative to a sample material to make a measurement.
34. The method according to claim 1 wherein a three-dimensional object is fabricated on the complex magnetic object by the steps of providing an additive material proximate to the complex magnetic object, rotating and translating the complex magnetic object to bring the additive location position and orientation into correspondence with a required additive configuration and causing the additive material to be added.
35. The method according to claim 34 wherein a first set of material is added to the complex magnetic object in a first orientation and a second set of material is added to the complex magnetic object in a second orientation.
36. The method according to claim 34 wherein the material is added by directing a beam of radiation toward an additive location on the complex magnetic object to cause photo-polymerization of the additive material to the complex magnetic object.
37. The method according to any claim 34 wherein the three-dimensional object is formed on a plurality of complex magnetic objects.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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DETAILED DESCRIPTION
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[0093] CMO 20 as shown is has three magnetic domains indicated at 21, 22 and 23 with magnetic moments in non-collinear directions. The spatially varying magnetic field generated by magnetic array 11 interacts with the magnetic moments of CMO to produce forces and torques that operate to translate and rotate CMO 20 toward a desired position and orientation. CMO 20 may have three translational and three rotational degrees of freedom as indicated at 40. In some embodiments, one or more degrees of freedom are limited by a physical constraint such as for example the channel wall. CMO 20 must include at least two non-collinear magnetic moments to be oriented by a spatially varying magnetic field. CMO has a plurality of facets and each facet may have different surface properties. For illustrative purposes, five different facet surfaces are shown. Different facet surfaces are possible and within the scope and spirit of the invention.
[0094] As indicated at 24 and 26, each facet may lie on a different crystallographic plane and interact differently with a sample molecule 25. The crystal planes for facets 24 and 26 could for example be <1,0,0>and <1,1,1>, respectively. A sample molecule in solution 25 (in this example acetic acid, but may in general be any molecule) may be adsorbed to the crystallographic plane of each facet. In general, the quantum states of an adsorbed molecule interact with quantum states of the substrate crystal causing the adsorbed molecule to have a preferred orientation with respect to the surface normal and a spectrum unique to the surface for each angle of incidence. That is the same type of sample molecule 25 will have different spectra for each angle of incidence and for each facet 24 and 26.
[0095] Facet 27 includes surface texture features 28 that function to locally amplify and concentrate the electric field of an incident electromagnetic wave. The surface features are those known in the art to produce surface enhanced Raman spectra and surface enhanced infrared spectra. A review of the literature is beyond the scope of this document, but it is worth noting that the surface enhancement features can be engineered and fabricated in a manner that provides selective enhancement of spectral features. In the context of the present invention, different types surface enhancement features may be placed on different facets of a CMO so that each facet selectively amplifies a different spectral feature.
[0096] Facet 29 includes tethered template structure 30 that binds specifically to template receptor 31. Facet 32 likewise includes a different tethered template structure 33 that binds specifically to template receptor 34. The template structure 30 may for example be an antibody that is specific to a particular cell type 35 with (template) receptor 31. The template structure 33 may for example bind with a macromolecule in solution 34. The template structure may for example be a functional group that preferentially retains polar molecules. Any type of template structure can be used. All that is required is that the template structure has a higher affinity for a first type of molecule than a second type of molecule. The CMO may include a plurality of different template structures on different facets.
[0097] The magnetic goniometer of the present invention provides a means to measure the spectra of a sample molecule 25 for a plurality of angles of incidence for a plurality of different facets. The plurality of different spectra from a plurality of different facets and angles of incidence may be compared with a spectral database to uniquely identify the sample molecule 25. This feature is particularly useful for distinguishing between different types of biological macromolecules that in solution have similar and perhaps indistinguishable spectra. The spectra of a sample molecule are measured by the steps of: [0098] 1. Place a CMO in a reference solution. [0099] 2. With control means 14 generate a sequence of spatially varying magnetic fields with magnetic array 11 causing CMO 20 to position and orient a first facet at a first angle of incidence and measure a reference spectrum. [0100] 3. Repeat step 2 for sequence of second facets and a sequence of second angles of incidence for each facet. [0101] 4. Add the unknown sample molecule to the solution and adjust the solution parameters (temperature, pH, ionic strength, etc.) to produce conditions conducive to the adsorption of a suspected type of sample molecule onto a plurality of facets on the CMO. [0102] 5. With control means 14 generate a sequence of spatially varying magnetic fields with magnetic array 11 causing first facet of CMO 20 to position and orient relative to radiation source 18 and sensor 17 such that radiation is incident on the first facet at a first angle of incidence and sensor 17 receives reflected, transmitted or scattered radiation from the sample molecule to produce a first spectrum. [0103] 6. Repeat step 5 for a sequence of second facets and a sequence of second angles of incidence. [0104] 7. In the control means 14, remove the spectral contribution of the solution and facet substrate to leave the molecular spectrum for each facet and angle of incidence. In some cases the molecular spectrum may be absent or very weak because the molecule adsorbed weakly or not at all. [0105] 8. Compare the plurality of spectra from a plurality of facets and plurality of angles of incidence with a spectral database to provide information about the type and quantity of sample molecule. The absence of adsorption may be used as an indicator to limit the number of possible matches in the spectral database.
[0106] In another embodiment, each orientation region 24, 25 or facet 27, 29, or 32 of CMO 20 may be selective for a different type of sample material. Each facet or orientation region in this embodiment carries a different test and the CMO is oriented in a sequence to read each test result.
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[0108] CMO 50 includes an energy reservoir 53 linked with electric generation means 54 by conduit 53A. Energy generation means 54 is linked with control circuit 55 by cable 54A and conductive plates 56A and 56B. Energy reservoir may receive energy from photodiode 57A illuminated by light source 18B. Light source 18B may be modulated to provide both logic signals to control 55 and energy to energy reservoir 53. Control circuit 55 may receive logic signals derived from modulation of photodiode 57A or from an integral receiver. Control 55 may include circuit to sense a change in the capacitance of plates 56A and 56B due to the change in dielectric constant with a cell 60 in the gap 58 between the plates. The cell 60 in gap region 58 is irradiated by radiation from radiation source 18A and scattered, transmitted or reflected radiation is received by radiation detector 17. As indicated at 59, the gap region may include a reservoir of a labeling substance that is released into or proximate to cell 60 upon command by control 55, for example by sensing a change in capacitance across gap 58. The labeling substance may for example be an isotopic marker, a fluorescent marker, or a dye. The labeling substance may be in a form that metabolized by the cell and the products of metabolism contain a label. For example, a metabolic pathway may be labeled by introducing a carbohydrate food source in which particular atomic positions are labeled with isotopes of C, H or O. Spectral features of metabolic products labeled with the isotopes are shifted in frequency and detected on the basis of frequency shift.
[0109] CMO 50 may include a tethered template 63 that binds with antigen 62 tethered to surface of cell 61. The antigen 62 may be integral to the cell surface or tethered to an integral cell material. Cell 61 may be illuminated by light sources 64 and 65 which are integral to the CMO. Light source 64 may be a non-linear optical material that mixes photons received from light source 18B to produce photons with shifted frequency. Light source 65 may be a thermal source, LED or laser device that is energized by energy converter 54 under the control of control means 55. Electromagnetic radiation from light sources 64 and 65 is emitted proximate to cell 61, interacts with biological macromolecules of the cell changing the spectral content, and the changed spectral content is measured by detector 17.
[0110] In another arrangement radiation from source 18B is directed through window 57C to illuminate cell 60 in gap region 58 and scattered, transmitted or reflected radiation is received by detector 17.
[0111] CMO 50 may include a non-linear optical material 57B that receives a first photon with a first energy and a second photon with a second energy from light source 18B and emits a third photon with a third energy from port 64 in the direction of cell 61 or in the direction of cell 60 (not shown). In both cases, scattered, transmitted or reflected radiation is received by detector 17.
[0112] The detector 17 is any device that receives radiation and produces a signal related at least in part to at least a part of the received radiation. The detector may for example be a photodiode. Preferably detector 17 is a spectrometer that analyzes the radiation power received as a function of radiation wavelength, frequency or energy. The radiation may be any particle type including photons, electrons, neutrons, protons, ions, atoms, and molecules.
[0113] Control circuit 55 may cause a voltage to be applied across plates 56A and 56B from power generator 54 producing an electric field between the plates. The gap between the plates may approximate the size of the object to be measured. For a bacteria cell the gap may for example be in the range of 5 to 10 microns. For eukaryotic cells the gap may for example be in the range of 10 to 100 microns. Because the gap is relatively small, even a modest voltage difference of a few volts will produce a substantial electric field on the order of 100,000 V/m or more. The applied electric field may be used to lift degeneracy of quantum states in the sample material via the Stark Effect thereby providing a richer spectrum with more information.
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[0115] The depth of penetration of the evanescent wave 74 depends upon the ratio of wavelength to aperture size as well as details of the refractive index, angle of incidence and aperture geometry. The depth of penetration decreases as the wavelength to aperture size ratio increases. The depth of penetration decreases as the angle of incidence increases. These properties may be exploited to obtain a depth profile by using a plurality of apertures of different sizes and/or a plurality of different angles of incidence. A three dimensional super resolution spectral map of the sample material may be built up by combining depth profiling with super resolution spatial mapping. In an embodiment not shown the CMO may include a plurality of apertures of different sizes and the aperture size employed for a spectral measurement is determined by the position and orientation of the CMO. In another embodiment not shown, a plurality of CMOs with a plurality of aperture sizes are each positioned and oriented relative to a sample material position and a spectral measurement is made with each aperture size. In another embodiment not shown, the aperture is elongated along a first polarization direction of an incident wave such that the spatial resolution is different along the first polarization direction than along a second orthogonal polarization direction. In another embodiment not shown, the aperture 71 comprises a plurality of apertures and the plurality of apertures collectively determines the spatial extent of the evanescent wave.
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[0117] In
[0118] CMO 80 tows biological cell 78 to position location 78A on the cell surface proximate to needle 91. Electromagnetic radiation is incident as shown at 84 and interacts with needle 91 and proximate region 78A to produce scattered and reflected electromagnetic radiation indicated at 85 which is measured and analyzed by a spectrometer (not shown). The region of maximal interaction is confined to a small volume proximate to the tip of needle 91, which may have dimensions on the order of tens of nanometers. During a spectral measurement of cell region 78A, a biopolymer gel may be formed in solution 12 by adjusting temperature and/or ionic strength to cause junction zones 97 to form in biopolymer strands 96 thereby forming a gel that restrains mobility of the cell-CMO complex. It should be noted that the method described here may be used to probe the gel itself with fine spatial detail. The reader is referred to Prystupa et al, Polymer Gels and Networks 4(2):87-110 (1996) for further details about the spectral features of gels. Subsequent to a spectral measurement at cell location 78A, the temperature and ionic strength of solution 12 may be adjusted to reduce viscosity. Magnetic array 11 produces a spatially and temporally varying magnetic field that brings a second cell surface region 78B proximate to needle 91 where a second spectral measurement is made. By positioning and orienting cell 78 at a plurality of locations and orientations via CMO 80 relative to needle 91, and measuring spectra at each location, a spectral map of cell 78 can be produced. The spatial resolution of the spectral map so produced may be comparable to the scale of the needle tip 91. A spectral map emphasizing different spectral features due to the different composition and geometry of needle 92 may be acquired similarly by bringing positioning and orienting each cell region relative to needle 92 with CMO 80.
[0119] CMO 82 positions and orients biological cell 79 at surface enhancement regions 95, 94, and 93A in sequence where biological cell 79 interacts with probe radiation 86 and spectral measurements of reflected and scattered radiation 87 are made for each region. The spectral measurement at each region emphasizes a different spectral region. This feature can be used for example to distinguish between spectrally similar samples by enhancing the spectral signal at frequencies where differences exist.
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[0121] As indicated at 111 and 112, CMO 110 has two magnetic domains with non-collinear magnetic moments enabling translation in any direction and rotation about any axis as indicated at 114. Radiation source 18 emits electromagnetic radiation in the direction of CMO 110 as indicated at 101 and reflects said radiation from plane reflective surface 113 in the direction 102 toward CMO 120.
[0122] As indicated at 121 and 122, CMO 120 has two magnetic domains with non-collinear magnetic moments enabling translation in any direction and rotation about any axis as indicated at 124. Radiation is reflected from plane reflective surface 123 in the direction 103 of CMO 130. The combination of two goniometer mounted mirrors 113 and 123 allows radiation to be directed toward any point in the container 13.
[0123] As indicated at 131 and 132, CMO 130 has two magnetic domains with non-collinear magnetic moments enabling translation in any direction and rotation about any axis as indicated at 134. CMO 130 includes concave reflective surface 133 that focuses radiation incident along path 103 along paths 104 and 105 which come to a focus at location 67A in biological cell 67. By adjusting each magnetic goniometer platform 110, 120 and 130, the focus can be shifted to another location 67B of cell 67 or to another cell location 68A on cell 68. Each goniometer platform is positioned and oriented independently in this arrangement provided that each platform is separated by more than the spatial resolution of the magnetic array 11. In another arrangement (not shown) magnetic platforms may be operated independently in close proximity if the number of magnetic domains and the directions of corresponding magnetic domains are different so that each behaves differently in the same local magnetic field.
[0124] As indicated at 141 and 142, CMO 140 has two magnetic domains with non-collinear magnetic moments enabling translation in any direction and rotation about any axis as indicated at 144. CMO 140 includes plano-convex lens 143 and bandpass filter 145 which filter and collimate radiation from paths 104 and 105 to collimated path 106.
[0125] As indicated at 151 and 152, CMO 150 has two magnetic domains with non-collinear magnetic moments enabling translation in any direction and rotation about any axis as indicated at 154. CMO includes reflective surface 153 which reflects incident radiation in the direction 107 toward grating element 163 mounted on CMO 160.
[0126] As indicated at 161 and 162, CMO 160 has two magnetic domains with non-collinear magnetic moments enabling translation in any direction and rotation about any axis as indicated at 164. CMO includes grating 163 which disperses radiation by wavelength along paths 108 and 109. Band pass filter 145 functions to select the grating order and prevent spectral aliasing. CMO 160 may be rotated to direct each wavelength in sequence to detector 19 in communication with control means 14 via cable 19A. In another embodiment, detector 19 is a multiplex spectrometer such as the above cited document High Efficiency Multiplex Spectroscopy.
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[0129] As shown radiation source 245 receives radiation from light source 18 and either reflects and focuses the incident radiation as best shown at133 on
[0130] As material is added the position of CMO 241 is adjusted to a working distance. The working distance may vary depending upon the pattern of deposition desired. For example the radiation source may include a focusing means such as a lens that produces a minimal spot size proximate to the lens focal length and larger spot sizes as distance from the focal length increases. The operator may decide to illuminate a minimal spot to produce a fine feature and a larger spot to produce a smooth feature.
[0131] As shown in
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[0134] Curvilinear path 322 is fabricated by the cutting action of magnetic object 323 that in this example functions as a cutting tool. The cutting tool 323 is first guided to a desired start location 324 on the surface of workpiece 12B and then is oriented and moved by a sequence of magnetic fields to remove material from workpiece creating curvilinear path 322. Because magnetic object 323 is not constrained by a shaft, it can cut in any direction and at any location where a suitable magnetic field can be generated. The path taken by the cutter 323 may for example be a spiral about the direction of the desired path. In this way the cutter 323 may function in a manner similar to a conventional mill or drill except that its range of motion is not constrained by a shaft. Alternately the path taken by the cutter may be reciprocal wherein the cutter is accelerated toward a first cut location where some material is removed, and then the cutter direction is reversed to allow distance for acceleration toward a second cut location. In addition to cutting, magnetic object 323 may be oriented and guided to push cuttings from region 317 along path 322 to path entrance 324.
[0135] As show schematically, radiation source 18 produces x-rays 18F, and the intensities of transmitted x-rays measured by detector 17 are analyzed by control device 14 to provide information about the path cut by magnetic object 323 in workpiece 12B.
[0136] It should be noted that there is no magnetic field that will provide an equilibrium position for the magnetic object as a consequence of the Earnshaw Theorem. It is however possible to oscillate the magnetic object 323 about a fixed point with small amplitude by rapidly adjusting the applied field to counter motion away from the fixed point. This method of dynamic balancing is used, for example in prior art magnetic bearings to balance forces about a single fixed point. In the present invention, the dynamic balancing is about points along an arbitrary curvilinear path specified by the user.
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[0138] In a preferred arrangement, the cutter has point group Cn symmetry in which a plurality (n) of permanent magnetic moments arranged about an axis of rotational symmetry. In this arrangement, the cutter is conceptually similar to the rotor of an electric motor and the array of electromagnets 11 is similar to the stator. However, in this arrangement the axis of rotation for the rotor is not fixed and the stator field is generated by elements that do not necessarily have the same symmetry axis as the rotor.
[0139] In another preferred arrangement, the magnetic cutter object 323 has point group T4 (tetragonal) symmetry and the cutter may rotate about any of the four symmetry axes. In this arrangement, the cutter can change direction of a cut merely by changing the magnetic field applied by the electromagnet array.