Embodiments of the present invention relate to specimens for use in microanalysis processes, including specimens created via a casting process and/or atom probe specimens.
Nanoparticles of various types and compositions are finding increasing applications in biomedicine for functions as diverse as detectors, optical and electron microscope labels, contrast agents for diagnostic magnetic resonance and optical coherence tomography imaging, bio-separations, catalysis, and drug delivery devices. Nanoparticulate materials are also extremely important in many non-medical applications including catalysis, material coatings, data storage, nano-electronics, cosmetics (e.g., sunscreen), and many other applications in order to impart unique properties to these various materials and devices. For example, nanoparticles can include magnetic and paramagnetic particles, metal colloids, semiconductor quantum dots, carbon nanotubes and nanowires, metal oxides, organic particles, fullerenes, biological particles and macromolecular complexes (proteins, viruses, and ribosomes), various types of colloids, nanoshells, dendrimers, and the like.
The special properties of nanoparticles that have created such excitement in the biomedical, biotechnology, and nanotechnology communities are due to their quantum-level properties. By one commonly used definition, nanoparticles are no larger than 100 nm in size; therefore each individual particle consists of a small, finite number of atoms. For example, a 4 nm diameter nanoparticle contains only about 4000 atoms. Because nanoparticles are often composed of only a few atoms, the position and type of each individual atom can be important. Therefore, in order to develop better nanoparticles and improve or develop nanoparticle-based devices and technologies, it is imperative to understand their structure at the atomic level. Unfortunately, nanoparticles can be difficult to analyze and are often do not have a size, shape, and geometry that is suitable for many microanalysis processes.
The present invention is directed generally toward specimens for use in microanalysis processes. One aspect of the invention is directed toward a method for producing a specimen for a microanalysis processes that includes providing specimen material to be analyzed via a microanalysis process and placing the specimen material into a mold configured to form the specimen material into a shape suitable for the microanalysis process. The method further includes forming a specimen suitable for use in the microanalysis process using the mold. The specimen includes the specimen material. A further aspect of the invention is directed toward analyzing at least a portion of the specimen produced by the method discussed above using the microanalysis process.
Other aspects of the invention are directed toward a method for producing a specimen for a microanalysis processes that includes providing a specimen material to be analyzed via a microanalysis process, providing an embedment material, and binding the specimen material and the embedment material together. The specimen material includes multiple noncontiguous portions spaced apart from one another in the embedment material. The method further includes forming a specimen from the specimen material and the embedment material that are bound together. The specimen includes the multiple noncontiguous portions spaced apart from one another in the embedment material. A further aspect of the invention is directed toward analyzing at least a portion of the specimen produced by the method discussed above using the microanalysis process.
Still other aspects of the invention are directed toward a method for producing a specimen for a microanalysis processes that includes providing a specimen material to be analyzed via a microanalysis process, providing an embedment material, and binding the specimen material and the embedment material together. The embedment material has a selected thermal and/or electrical conductivity characteristic. The method further includes forming a specimen from the specimen material and the embedment material that are bound together. A further aspect of the invention is directed toward analyzing at least a portion of the specimen produced by the method discussed above using the microanalysis process.
Yet other aspects of the invention are directed toward a method for producing a specimen for a microanalysis processes that includes providing a specimen material to be analyzed via a microanalysis process, providing a first embedment material, and binding the specimen material and the first embedment material together. The method further includes providing a second embedment material and binding the second embedment material to a portion of the specimen material and/or a portion of the second embedment material. The method still further includes forming a specimen from the specimen material, the first embedment material, and the second embedment material after the second embedment material is bound to the portion of the specimen material and/or the portion of the second embedment material. A further aspect of the invention is directed toward analyzing at least a portion of the specimen produced by the method discussed above using the microanalysis process.
This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.
In the following description, numerous specific details are provided in order to give a thorough understanding of embodiments of the invention. One skilled in the relevant art will recognize, however, that the invention may be practiced without one or more of the specific details, or with other methods, components, materials, etc. In other instances, well known structures, materials, or operations are not shown or described in order to avoid obscuring aspects of the invention.
References throughout the specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearances of the phrase “in one embodiment” or “in an embodiment” in various places throughout the specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. Additionally, as used herein, casting is a process by which a material is introduced into a mold, shaped, and then removed producing a fabricated object or part. For example, in selected embodiments a liquid, mixture, suspension, or the like can be introduced into a mold and solidified. In other embodiments, one or more pieces of solid material can be placed in a mold and pressure applied to form the fabricated object (e.g., by applying pressure, sintering, or the like). Furthermore, herein the finished product of a casting process is called a casting or a cast object (e.g., a cast specimen).
Various embodiments discussed below provide a method for producing a specimen for a microanalysis process and/or a method for analyzing a specimen material. For example, selected embodiments are directed toward methods for forming a specimen suitable for use in a microanalysis process. In some embodiments, specimens that do not have the desired shape, size, and/or geometry can be formed or cast into a form suitable for analysis. In certain embodiments, an embedment material having a selected characteristic can be combined with specimen material (e.g., the material of interest) to form a specimen that will have a certain characteristic during microanalysis.
In selected embodiments, methods described below can be used to perform structural and compositional analysis of nanoparticulate and micro-particulate materials, whether these particulate are of natural, biological or synthetic (man-made) origin. Such particulates may be inorganic, organic or composed of a combination of inorganic and organic materials. For example, specimens that can be examined via these methods can include (without limitation), biological materials such as proteins, nucleic acids, biomacromolecules, biomacromolecular complexes and viruses, organic nano-particles (e.g., dendrimers, polymers, fullerenes, and the like), inorganic nano-particles (e.g., ceramics, dielectrics, colloids, and micro- and nano-particulate materials), and nano-porous and micro-porous catalysts, zeolites, and other materials having nano-scale or micro-scale voids and cavities.
In certain embodiments, the specimen material may not be nanoparticulate in its present, original, or native state. Accordingly, the specimen material can be prepared by breaking down/separating the specimen material into multiple portions (e.g., small particulates). In some embodiments, these materials can be extremely small. For example, in selected embodiments the specimen material can be processed into particles or portions with at least two dimensions less than about 1 micron. For example, in selected embodiments the specimen material can be cut, diced, ground, pulverized, fractured, or the like.
In other embodiments, the specimen material can be processed into particles or portions even smaller. For example, in certain embodiments the specimen material can be processed into portions that are on the molecular or atomic level. For example, in certain embodiments the specimen material can be melted (e.g., and placed in a mold to cast a specimen). In still other embodiments, the specimen material can be dissolved in another medium or material. For example, in selected embodiments the specimen material can be dissolved in a solvent and the solvent can then be evaporated to form a specimen in a mold or a structure of specimen material. In another embodiment, the specimen material can be dissolved into an embedment material and a specimen can be formed that includes both the specimen material and the embedment material. In still other embodiments, the specimen material can be dissolved into another medium by transforming the specimen material into a gaseous state and bubbling the gas through a liquid solvent or embedment material to combine the specimen material with the solvent or embedment material. The combined materials in liquid form can then be placed in a mold to cast a specimen or the liquid can be transformed into another type of solid structure and a specimen can be formed from the structure.
In still other embodiments, methods described below can be used to perform structural and compositional analysis of organic and/or inorganic particulate or nanoparticulate materials such as fullerenes, ceramics, dielectrics, nano- and micro-porous catalysts, zeolites, colloids, and other micro and nano-particulate materials. These materials can include magnetic and paramagnetic particles, metal colloids, semiconductor quantum dots, nanowires, metal oxides, organic particles, fullerenes, biological particles and macromolecular complexes (proteins, viruses, and ribosomes), various types of colloids, nanoshells, dendrimers, and the like. In yet other embodiments, methods described below can be used to perform structural and compositional analysis of biological and organic materials, including (without limitation) proteins, lipids, carbohydrates, and nucleic acids, as well as biomolecular and biomacromolecular assemblies such as receptor complexes, receptors coupled with ligands, enzyme-substrate complexes, drug-target complexes, membranes, membrane-bound proteins, cellular organelles, viruses, and portions of whole cells and other biological components, including tissue specimens, proteins, polynucleic acids, oligonucleotides, macromolecular complexes or other structures that are located within biological tissues, cellular components, cellular organelles, extracellular organelles, viruses, bacteria, other micro-organisms, or other biological systems or components. In still other embodiments, methods described below can be used to perform structural and compositional analysis of man-made or partially man-made biological structures, including tissue engineering scaffolds, cell culture systems, and other biological-synthetic constructs.
For example, a three-dimensional atom probe (“AP”) is an analytical instrument capable of providing atomic-scale three-dimensional compositional data. Various embodiments of an atom probe include an ultra high vacuum (“UHV”) chamber in which a very sharp needle-shaped specimen is placed facing a detector that encodes in two dimensions. A large DC potential (e.g., 5 kV) is placed on the specimen that is almost, but not quite, sufficient to field ionize the specimen atoms on the apex. A very fast excitation pulse (e.g., an energy pulse at a pulse rate of up to several hundred kilohertz) is applied to the specimen or a counter electrode. The magnitude of the pulse is chosen such that the combined magnitude of the DC potential and excitation pulse energy is sufficient to occasionally (e.g., one time in 100 pulses) ionize a single atom near the tip of the specimen. This process is called field evaporation (“FE”).
The evaporated ion is accelerated away from the specimen and strikes a detector that records the location of the impact. The time required for the ion to fly from the specimen to the detector (e.g., the Time of Flight [“TOF”]) is related to the ion's mass-to-charge ratio. Consequently, the elemental identity of each ion can be determined from its TOF. Additionally, the location at which the ion hits the detector and the order in which the ion arrives at the detector can be correlated to its original position on the apex of the specimen. Combining the TOF data with the two-dimensional detector information allows the atomic composition of the specimen to be determined in three dimensions.
The excitation pulse(s) can include various forms of energy and can include varying pulse rates. For example, in certain embodiments the excitation pulse(s) can include one or more of the following: a voltage pulse, an electron beam or packet, an ion beam, a laser pulse (e.g., as used in a Pulsed Laser Atom Probe [“PLAP“]), or some other suitable pulsed source. An example of a suitable AP is a Local Electrode Atom Probe (“LEAP®”) available from Imago Scientific Instruments Corporation of Madison, Wis. Although for the purpose of illustration, many of the following embodiments are discussed with reference to laser and/or voltage pulsed atom probes, one skilled in the art will understand that the underlying principles are equally applicable to a wide variety of pulse excitation source(s).
In many microanalysis processes the size, shape, and geometry of the specimen can greatly affect the quality of the analysis process. For example, in an AP, the specimen is the imaging optic, therefore specimen preparation can be extremely important for obtaining useful data. In selected embodiments, the specimen radius can effectively determine the image magnification and the field of view in the AP.
In selected embodiments at least portions of the process in
In certain embodiments, configuring a mold (process portion 202) can include configuring a mold to form the specimen material into a shape suitable for a microanalysis process. In selected embodiments, the mold can be formed by forming mold material around at least a portion of an exemplar specimen shape and/or removing a portion of mold material from a structure of mold material. For example, in certain embodiments molds can be prepared from or using specimen or a specimen shape suitable for AP analysis (e.g., a conventional needle shape specimen several millimeters long, a microtip specimen that is tens of microns long, or a microtip array that includes multiple microtips). Information regarding desirable AP specimen shapes can be found in Kelly, T. F., P. P. Camus, et al. (1995), High Mass Resolution Local-Electrode Atom probe, USA, Wisconsin Alumni Research Foundation, U.S. Pat. No. 5,440,124; Kelly, T. F., R. L. Martens, et al. (2003), Methods of Sampling Specimens for Microanalysis, U.S. Pat. No. 6,700,121; and Kelly, T. F., J. J. McCarthy, et al. (1991), High Repetition Rate Position Sensitive Atom Probe, USA, Wisconsin Alumni Research Foundation, U.S. Pat. No. 5,061,850; Method to Determine 3-D Elemental Composition and Structure of Biological and Organic Material via Atom Probe Microscopy, WO2005/026684, filed Aug. 6. 2004, each of which is fully incorporated herein by reference.
In
In other embodiments, the mold material can include other materials that can be formed around an object to create a mold. For example, in selected embodiments the mold material can include polymers, prepolymers, metals, plastics, composites, ceramics, wax, and the like. In other embodiments, instead of a microtip array another suitable exemplar shape can be used to from a mold configured to form suitable specimens for various microanalysis processes.
In still other embodiments, a mold can be prepared by inserting electro-polished metal needle(s) (or similarly shaped long needles prepared from other materials) into a silicone rubber prepolymer (or other molding material) poured into a suitable vessel (such as a centrifuge tube). Once the silicone rubber is polymerized, the metal needles can be removed from the silicone, thereby leaving behind needle-shaped void(s) that can be used to cast specimen(s). In still other embodiments, a longer (e.g., circa centimeter long atom probe needles) can be used to prepare the molds.
As discussed above, yet other embodiments include forming a mold out of a structure of mold material, for example, using microfabrication to remove mold material from the structure. For example, in selected embodiments voids (e.g., with sub-micron resolution) can be formed in silicon or silicon oxide. The voids can be created by either abrasion (as with a diamond saw or laser ablation), etching, milling or some other method. Chemical etching can be accomplished by a number of methods such as using standard lithographic techniques including wet (as with KOH), dry (as with F) or plasma assisted (as with SFx) etching. Milling can be accomplished with a focused ion beam (FIB) or a broad ion beam with a masking arrangement to mask the areas where material removal is not desired. Other micromanufacturing methods can include, but are not limited to, a polymer based photoresist technique, wherein a solvent can be used to remove the photo-resist while keeping the polymer intact. Additional embodiments include direct photo-ablation processes and where acid-forming dyes are activated with photo-activation processes to locally create voids without the need for additional solvents.
In the illustrated embodiment, an item 794 is positioned in the processing arrangement 790. An energy source 712 (e.g., electrical source) can be provided so that it can create an electrical characteristic (e.g., an electrical field) proximate to the item 794 and/or apply an electrical characteristic (e.g., an electrical current) to the item 794. In some embodiments, the item 794 can include a block of mold material for forming a mold, specimen material (with or without an embedment material) for forming a specimen, a mold containing specimen material, or the like. Additionally, the processing arrangement 790 can include other devices 796 (e.g., mechanical devices, robotic arms, plunger devices, presses, grinders, saws, centrifuges, and the like) used in processing the item 794. For example, as discussed above, in certain embodiments mold material can be removed from a structure of mold material to form a mold. In other embodiments, the processing arrangement 790 can include more, fewer, and/or other arrangements of components.
Once a mold is configured to form material into a shape suitable for a microanalysis process, a specimen material can be provided (process portion 204) for microanalysis and placed in the mold (process portion 210). As discussed above, in selected embodiments the specimen material can be broken down and/or separated into separate portions (process portion 206) before being placed in the mold, Additionally, in selected embodiments an embedment material can be combined with the specimen material (process portion 208) before or after the specimen material is placed in the mold.
For example, the mold (e.g., the voids in the mold) can be filled with a specimen material or an embedding material that contains nanoparticles or broken down portions of specimen material. The specimen material or the specimen and embedment material can be positioned in the mold (process portion 212) using centrifugation, plunging, vacuum, and/or by other methods to, for example, force the material(s) to fill the mold appropriately. In selected embodiments, an electrical current characteristic can be used to position at least a portion of the specimen material and/or the embedment material. For example, in some embodiments an electric field can cause a migration of specimen material particles to migrate through an embedment material. In other embodiments, an electrical, magnetic, and/or optical field characteristic can be used to cause particles in the specimen materials and/or the embedment material to assume a selected orientation in the mold (e.g., to assume a selected alignment). Some or all of the processes described with respect to positioning material(s) in the mold can be carried out in a processing arrangement have features similar to those of the processing arrangement discussed above with reference to
Once the material(s) has filled the voids it can then be solidified or hardened to form a specimen (process portion 214) suitable for use in a microanalysis process. For example, in selected embodiments, the specimen material or specimen and embedment materials can be hardened by polymerization (e.g., via annealing or the application of an electrical characteristic), cross-linking, cooling from a melt, heating or baking, a pressure application (e.g., from a plunger, press, or ambient pressure in a processing arrangement), a chemical agent (e.g. a catalyst), via photoactivation, and the like. In selected embodiments where the specimen is formed from a specimen material and an embedment material, the process of forming the specimen can cause the specimen and embedment material to bind together (e.g., stick together, bond together, or the like). Some or all of the processes described with respect to forming a specimen can be carried out in a processing arrangement have features similar to those of the processing arrangement discussed above with reference to
For example,
In the illustrated embodiment, the plunger 386 can be used as a holder to retrieve the specimen and to support the specimen during subsequent handling, processing, and analysis. For example, in selected embodiments the plunger 386 can be electrically conductive and serve as a specimen holder during an AP process (e.g., transmitting an electrical potential to the specimen during AP analysis). In some embodiments, the plunger can also be thermally conductive and facilitate heating or cooling of the specimen, either during processing or analysis. In certain embodiments, the plunger 386 can receive various treatments prior to being used to form and/or remove the specimen. For example, these treatments can include mechanical treatments (e.g., roughening a surface of the plunger) or chemical treatments to improve adhesion, enhance electrical and/or thermal conductivity or provide other properties to improve specimen manipulations and/or analysis.
As shown in
Although in selected embodiments discussed above, the specimens are removed from the mold using a plunger, in other embodiments specimens are removed using other methods. For example, in certain embodiments a specimen can be removed from a mold by melting or other processes that destroy the mold whilst leaving the specimen intact (e.g., as in lost wax casting). This approach may be desirable with certain types of specimen materials and/or embedment materials, such as those that are particularly fragile, and when certain specimen geometries are required that cannot be readily removed from a mold. In some cases, as discussed above, additional processing or preparation of the specimen(s) (process portion 218) maybe accomplished prior to analysis (e.g., to enhance the analysis process).
In other embodiments, portions of an embedment material (e.g. nanoparticles) can be added to a suspension of spheres of indium alloy in a liquid flux poured into a mold with the proper shape for a microanalysis process. Following the addition of nanoparticles, heating can be used to melt the alloy and drives off the flux. The casting or specimen(s) can then removed from the mold. In other embodiments, nanoparticles may also be embedded within a polymer melt or by monomer/prepolymer polymerization using essentially the same protocol.
In still other embodiments, as shown in
As discussed below in further detail, embedment materials can have additional features that can enhance the analysis process (e.g., thermal conductive properties which can be well suited for AP analysis using laser pulsing, evaporation characteristics, and the like). In some embodiments, a specimen material can be combined with an embedment material solely to receive an analysis enhancing feature.
For example, in selected embodiments involving AP analysis, image aberrations can be reduced in some circumstances by making a specimen at least approximately hemispherical in shape with at least approximately a smooth surface (e.g., with few or no voids, albeit with atomic-scale roughness). Additionally, it is sometimes desirable to maintain this configuration during field evaporation throughout the analysis. In selected embodiments where a specimen includes an embedment material, the characteristics of the embedment material can affect the surface condition of a specimen as a specimen is analyzed using a microanalysis process.
In selected embodiments where embedment materials are included in the specimen, the analysis process (process portion 220) includes reconciling the date to account for the embedment material. In some embodiments, this can be accomplished using a computing system, such as the one shown in
Embedment materials can be chosen for any number of their characteristics. For example, these characteristics can include a selected thermal conductivity characteristic, a selected electrical conductivity characteristic, a selected work function characteristic, a selected erosion characteristic (e.g., evaporation characteristic), a selected identification characteristic (as discussed above), a selected compositional characteristic (e.g., elemental, isotopic, molecular, and/or structural) and/or a selected adhesive characteristic. In selected embodiments, the properties of the embedding matrix and how well it interfaces with the embedded nanoparticle can be important to successful imaging. For example, how well an embedment material binds (e.g., adhesive qualities) with a specimen material can be important. Additionally, if the specimen will be evaluated in an AP using pulse laser energy, the heat transfer characteristics (e.g., thermal conductivity characteristics) can be important because the laser energy produces thermal energy that aids in evaporation.
FE characteristics for certain types of materials are shown in
Polymers and/or conductive polymers (e.g., those that are inherently conductive or that have added material to make them conductive) have properties that make them useful for embedding specimen materials in selected embodiments of the invention. Some conductive polymers include, but are not limited to, polyanilines, polythiophenes, polyazines, polypyrroles and the like. In selected embodiments, the polymer may be processed into the molds as a prepolymer suspension, as a solution in a suitable solvent, as a melt, or as monomers that are polymerized in place within the mold. In certain embodiments, thermal annealing can be used to improve the physical properties of the embedment and to improve the binding between the polymer and embedded nanoparticles (e.g., for nanoparticles that will not be damaged by heating, including nanoparticles composed of metals or ceramics that can tolerate the temperatures associated with polymer annealing or melting). In selected embodiments, additional techniques can may be used to modulate either the electrical or thermal conductivity of a polymer. For example, in one embodiment small quantities of carbon nanotubes, carbon black, particulate metals, or other “dopants” can be added to the polymer to enhance the bulk electrical and/or thermal conductivity.
In yet other embodiments, low melting temperature metals and eutectics can be used as an embedment material. For example, in a selected embodiment a mold can be prepared from a silicone (e.g., such as Sylgard 184 available from Dow Corning). Because Sylgard and similar silicone rubbers can have continuous use temperatures of at least approximately 200° C., and short term stability to at least approximately 250° C., silicon molds can be suitable for casting specimens that use some indium alloys. In certain embodiments, some indium alloys can be obtained as particulate suspensions mixed with different fluxes to facilitate adhesion to a variety of materials including metals, oxides, and silicon. In other embodiments, Indiums and other low melting solders can be used as solids or powders. In still other embodiments, where higher melt/eutectic temperature materials are used, the molds can be produced from silicon, ceramics, and/or other materials. In selected embodiments, thermal annealing can be used to improve the physical properties of some metallic embedment materials and their binding properties with a specimen material (e.g., where the specimen material is tolerant of the associated heat).
In still other embodiments, electrical characteristics can be used to aid in binding certain embedment materials with certain specimen materials. For example, nanoparticles can be embedded in an embedment material during a casting process by filling the mold with the particles and the embedment material and applying an electrical characteristic (e.g., electrical current). The electrical characteristic can aid in binding the specimen material to the embedment material in a manner similar to the principles that apply to electroplating. In this way, the nanoparticles can be entrapped within the embedment material as the specimen forms within the mold. In certain embodiments, this process can be performed with Au, In, Ni, Cr and other materials.
Although in many of the embodiments discussed above, the specimen have been formed into shapes, sizes, and/or geometries suitable for use in an atom probe (e.g., a needle shape or a microtip array), as discussed above, in other embodiments the specimen can include a shape, size, geometry, or other characteristic suitable for other types of microanalysis processes. For example,
For example,
Although many of the embodiments discussed above have been discussed with reference to using a mold to form a specimen, in other embodiments many or all of the same features may be used and the specimen can be formed without using a mold. For example, as shown in
In still other embodiments, the process of using an embedment material can have multiple stages. For example, as shown in
In selected embodiments, the process discussed above with reference to
From the foregoing, it will be appreciated that specific embodiments of the invention have been described herein for purposes of illustration, but that various modifications may be made without deviating from the invention. Additionally, aspects of the invention described in the context of particular embodiments may be combined or eliminated in other embodiments. Although advantages associated with certain embodiments of the invention have been described in the context of those embodiments, other embodiments may also exhibit such advantages. Additionally, not all embodiments need necessarily exhibit such advantages to fall within the scope of the invention. Accordingly, the invention is not limited except as by the appended claims.
This application claims the benefit of U.S. Provisional Patent Application No. 60/703,096, filed Jul. 28, 2005, entitled ATOM PROBE SPECIMENS, which is fully incorporated herein by reference.
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/US2006/029323 | 7/28/2006 | WO | 00 | 7/11/2008 |
Number | Date | Country | |
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60703096 | Jul 2005 | US |