WO2013138208A1

WO2013138208A1 - Research on, identification of and screening for biological materials using low energy electron microscopy

Info

Publication number: WO2013138208A1
Application number: PCT/US2013/030093
Authority: WO
Inventors: Robert T. Dennis; Joseph W. Beyers
Original assignee: Dennis Robert T; Beyers Joseph W
Priority date: 2012-03-16
Filing date: 2013-03-10
Publication date: 2013-09-19

Abstract

Described herein is a system and method for conducting research on and/or screening for viruses, capsids, antibodies, prions, proteins and DNA using a low energy electron microscope (LEEM). In some implementations, the system takes images of a biological sample, extracts information (e.g., size or shape of contents) from the taken images, and determines the presence or absence of biological agents, such as viruses, capsids, antibodies, prions, proteins and DNA, based on the extracted information. In some implementations, the system observes, identifies, and/or detects interactions between antibodies and viruses or other microbes, capsids, antibodies, prions, proteins and DNA, such as the binding of the antibodies to its cognate ligand. In some implementations, the system screens biological samples, based on detected interactions with known antibodies, to determine whether a person should be granted access to a controlled, restricted or protected location.

Description

RESEARCH ON, IDENTIFICATION OF AND SCREENING FOR

BIOLOGICAL MATERIALS USING LOW ENERGY ELECTRON

MICROSCOPY

CROSS-REFERENCE TO RELATED APPLICATIONS

[1] The present application claims priority to U.S. Provisional Patent

Application Serial No. 61/61 1 ,726, entitled "Identification of Viruses Using Low Energy Electron Microscopy", filed 16 March 2012, U.S. Provisional Patent Application Serial No. 61/638,657, entitled "Identification of Antibodies Using Low Energy Electron Microscopy", filed 26 April 2012, U.S. Provisional Patent Application Serial No. 61/681 ,347, entitled "Research On and Screening For Viruses, Capsids, Antibodies, Prions, Proteins and DNA Using Low Energy Electron Microscopy", filed 9 August 2012.

TECHNICAL FIELD

[2] This invention relates to systems and methods for observing, detecting and/or identifying biological components within a sample using a low energy electron microscope (LEEM).

BACKGROUND

[3] One of the greatest risks to the future of mankind is that of a worldwide deadly pandemic. The source of such a devastating impact on the human population may likely be a virus or other microbe that has three key

characteristics-that it be deadly, easily transmittable {e.g., airborne), and slow acting. For example, the HIV virus is deadly and slow acting but not easily transmittable (nor airborne). A virus or other microbe with all three

characteristics has the potential to spread worldwide before its widespread deadly implications are fully understood. In addition, even viruses or other microbes having one or two of the key characteristics cause great harm to humans and animals, such as illness and death. Therefore, early detection of such viruses or other microbes is extremely important to prevent such a cataclysmic event.

[4] The main function of the humoral immune system within humans and other animals is the generation and use of antibodies that neutralize foreign objects, such as bacteria and viruses, within a body. An antibody, or immunoglobulin, is generally a Y-shaped protein produced by B cells within the body and used by the immune system to identify, neutralize, and rid the body of objects that are harmful to the body. The antibody neutralizes a target foreign object by attaching or binding one of the tips, or paratopes, of its Y- shaped body to a specific location on the target for an object. Once attached, the antibody may neutralize the object itself (e.g., by blocking certain functions of the object), or may tag the object for the immune system to attack and neutralize the object.

[5] Known attempts to utilize microscopy to detect viruses, antibodies and other biological structures suffers from a wide variety of drawbacks.

Conventionally, researchers have utilized transmission electron microscopy (TEM) or atomic force microscopy (AFM) to attempt to image, detect, or identify viruses, antibodies and biological structures. However such

techniques are either very complicated or labor-intensive, cause radiation damage (e.g., TEM), or have inferior resolution, so that obtained images are not very useful for the detection and identification of antibodies (e.g., AFM).

[6] The need exists for system that overcomes the above problems, as well as one that provides additional benefits. Overall, the examples herein of some prior or related systems and their associated limitations are intended to be illustrative and not exclusive. Other limitations of existing or prior systems will become apparent to those of skill in the art upon reading the following Detailed Description.

BRIEF SUMMARY OF THE INVENTION

[7] Real time visualization of microbes, cells and subcellular components {e.g., proteins, organelles, etc.) at a resolution allowing identification, detection, research on, screening and so on currently suffers from limitations, such as those described above.

[8] The system and methods provided for herein detect and identify various biological materials, e.g., viruses, capsids, prions, antibodies, antibody-object interactions, proteins, or DNA, in a relatively short time period, including real-time, allowing for rapid medical diagnostics, treatments, experimentation and/or population screening, among other applications. [9] In an aspect, a system for taking one or more images of a biological material is provided. The biological material may be located within a biological sample.

[10] In certain embodiments the system comprises a low energy electron microscope (LEEM) and conductive substrate containing a biological sample that is adapted to be placed in a vacuum environment of the LEEM. The system may further comprise and imaging device that includes components configured to take an image of the biological material using LEEM. The system may also comprise a recording device configured to generate a video from taken images of the biological material.

[11] In certain embodiments, the biological material is selected from a virus, capsid, prion, antibody, protein, DNA and/or other biological structure. In some embodiments, and antibody-object (i.e., antibody-ligand) within a biological material or sample is imaged.

[12] In another aspect, a system for modifying a database of low energy electron microscope (LEEM) images is provided.

[13] In certain embodiments, the system comprises an image component, an information extraction component, a comparison component, and a database component. The image component is configured to receive an image of the biological material taken by a LEEM. The information extraction component is configured to extract information from the received LEEM image of the biological material. The comparison component is configured to compare the extracted information to an index of information associated with known biological material. The database component is configured to update a database of entries associating antibodies with LEEM images of the biological material based on results of the comparison performed by the comparison component.

[14] In some embodiments, the extracted information is selected from size information, shape information, size and shape information, and an image. In other embodiments, the extracted information is size information, shape information, size and shape information, or an image.

[15] In some embodiments, the biological material is selected from a virus, capsid, prion, antibody, protein, DNA, and or other biological structure. [16] In an aspect, a system for identifying a biological material is provided. The biological material may be located within a biological sample.

[17] In certain embodiments, the system comprises a low energy electron microscope (LEEM) and an identification device. The identification device is configured to identify the biological material within one or more images taken by the LEEM. In some embodiments, the imaging component is configured to determine the size and/or shape of an object within the LEEM image(s). In some embodiments, the identification device is configured to identify an interaction between a biological agent and the biological material within an image taken by the LEEM thereby identifying the interaction of a biological agent (e.g., agonist, antagonist or the like) with a biological material

[18] The system may further comprise a query component and an identification component. The query component is configured to query an index of information that associates known biological material with

morphological information associated with said known biological material using a query term associated with the determine size and shape of the object found within the LEEM images. The identification component is configured to identify the object as a biological material based on a positive result of the query.

[19] In certain embodiments, the biological material is selected from a virus, capsid, prion, antibody, protein, DNA, and or other biological structure. In certain embodiments, an interaction is identified within the biological material, e.g., an antibody-object (also referred to herein as an antibody-ligand) interaction. In some embodiments, the interaction is between a biological agent, e.g., a pharmaceutical agent (drug), and the biological material.

[20] In another aspect, there is provided a system for identifying an antibody that recognizes a ligand comprising (a) a low energy microscope having a sample chamber, wherein the sample chamber contains a substrate that includes a ligand sample, (b) a first gas container coupled to the sample chamber, wherein the first gas chamber contains a first gas that includes a first antibody, (c) a second gas container coupled to the sample chamber, wherein the second gas chamber contains a second gas that includes a second antibody, and (d) a computing device that performs actions associated with images taken by the low energy electron microscope.

[21] In some embodiments, the first and/or second antibody may be labeled or tagged to ease detection.

[22] In some embodiments, the ligand is contained within a protein array.

[23] In certain embodiments, the biological material is selected from a virus, capsid, prion, antibody, protein, DNA, and or other biological structure.

[24] In an aspect, a system for confirming the interaction of a biological agent with a biological material is provided. The system comprises an imaging device and an identification device. The imaging device is configured to take multiple low-energy electron microscopy (LEEM) images of a biological material or biological sample. The identification device is configured to identify within one or more of the multiple LEEM images an object having size or shape similar to a size or shape of known interactions. The system may further comprise a query component. The query component is configured to query an index more database of information that associates known biological material(s) with morphological information associated with the known biological material(s).

[25] In some embodiments, the biological agent is selected from and antagonist, agonist, drug, modulator, antibody and the like.

[26] In some embodiments the biological material is selected from a microbe, virus, capsid, prion, antibody, proteins, DNA, and/or other biological structures. The microbe may be a bacteria, fungus, protozoan or virus.

[27] In one embodiment, the interaction is an antibody attached to a microbe. The microbe is selected from a bacteria, fungus, protozoan or virus.

[28] In an embodiment, the interaction is an antibody interacting with its cognate ligand.

[29] In an aspect, a system for observing and antibody-like in interaction within a biological sample or material is provided. The system comprises a low energy electron microscope that includes a sample chamber configured to contain a substrate having a biological sample that includes ligands and antibodies, and a computing device configured to identify and antibody-ligand interaction within images observed or taken by the low energy electron microscope. The ligand is selected from a microbe, capsid, prion, antibody, DNA and/or other biological structure.

[30] In another aspect, a system for observing a real-time antibody-ligand interaction within a biological sample is provided. The system comprises a low-energy electron microscope that includes a sample chamber, a gas container coupled to the sample chamber, and a computing device that performs actions associated with images taken by the low energy electron microscope.

[31] In an embodiment, the sample chamber is configured to house a substrate that contains a ligand and wherein the gas container is configured to contain a gas that includes and antibody. In another embodiment, the sample chamber is configured to house a substrate that contains a ligand and wherein the gas container is configured to contain a gas that includes an antibody or antibodies, and wherein the gas container is coupled to the sample chamber such that the substrate is exposed to the gas that includes an antibody or antibodies during operation of the low energy electron microscope. In some embodiments, the ligand is selected from a microbe, capsid, prion, protein, DNA and/or other biological structure.

[32] In an aspect, there is described a method for determining a type of antibody that attaches to a ligand. In an embodiment, the method comprises preparing multiple substrates, each containing a sample having a similar virus to one another, preparing multiple containers, each containing a different antibody, exposing each of the multiple substrates to a single container of an antibody, taking one or more low energy election microscope images of the exposed substrates and determining, based on the contents of the images, which antibody contained by the multiple containers is attached to the virus contained by the multiple substrates. In another embodiment, the method comprises preparing two or more substrates, each Including a same known virus, exposing each of the two or more substrates to a different known antibody, and identifying, using a low electron energy microscope, the exposed substrate that includes an antibody-virus interaction. In some embodiments, the virus is within a biological sample. In some embodiments, the virus is a biological material. [33] In an aspect, a method for identifying a virus is provided. In an embodiment, the method comprises preparing multiple substrates, each containing a sample having a similar virus to one another, preparing multiple containers each containing a different antibody, exposing each of the multiple substrates to a single container of an antibody, taking one or more low energy election microscope images of the exposed substrates, determining, based on the contents of the images, which antibody contained in one of the multiple (antibody) containers is attached to the virus contained by the multiple (virus) containers, and identifying the similar virus based on the determined antibody is attached to the virus.

[34] In an embodiment, the method comprises preparing two or more substrates, each including a same unknown virus, exposing each of the two or more substrates to a different known antibody, determining, using a low energy electron microscope, the exposed substrate that includes an antibody- virus interaction, and identifying the unknown virus based on determining the exposed substrate that includes the antibody-virus interaction. In some embodiments, the method comprises taking one or more images of the exposed substrates, and matching at least a portion of the contents of the images to an image of an antibody-virus interaction.

[35] In some embodiments, the virus is within a biological sample. In some embodiments, the virus is a biological material.

[36] In an aspect there is provided a method of experimentation, the method comprising collecting information associated with a biological material and/or an interaction with a biological material using a low energy electron microscope. In an embodiment, the method further comprises causing the biological material to interact with an experimental agent, and collecting information associated with the biological material after interactions between the biological material and the experimental agents using the low energy electron microscope.

[37] In some embodiments, the information that is collected is an image of the biological material. In some embodiments, the information that is collected is an image of an interaction within the biological sample or with the biological material. In certain embodiments, the interaction is with a

pharmaceutical agent.

[38] In some embodiments, the information that is collected is associated with protein arrays. In certain embodiments, the protein array is a forward- phase format. In certain embodiments, the protein array is a reverse-phase format.

[39] In some embodiments, the sample chamber is configured to house a substrate that contains a sample biological material, and wherein the gas container is configured to contain a gas that includes one or more antibodies. In certain embodiments, the gas chamber is coupled to the sample chamber such that the substrate is exposed to the gas that includes antibodies during operation of the low energy electron microscope.

[40] In certain embodiments, the biological material is selected from a virus, capsid, prion, antibody, protein, DNA and/or other biological structure located within a biological sample. In certain embodiments, the interaction is an antibody interacting with its cognate ligand. In certain embodiments, an antibody is interacting with a biological material is selected from a virus, capsid, prion, a second antibody, protein, DNA and/or other biological structure located within a biological sample.

[41] In some embodiments, a method of experimentation is observed in real time or ex post facto an interaction using a low energy electron microscope. In certain embodiments, the interaction may be a biological material- experimental agent interaction. In certain embodiments, the interaction may be an interaction selected from virus-antibody, capsid-antibody, preantibody, protein-antibody, DNA-antibody, a virus with an antibody array, a capsid with an antibody array, a protein with an antibody array, DNA with an antibody array, a virus with a protein array, a capsid with a protein array, a antibody with a protein array, a protein with a protein array, and DNA with a protein array. In certain embodiments, the protein array is a forward-phase format. In certain embodiments, the protein array is a reverse-phase format. In some embodiments, the observing in real-time or ex post facto further comprises taking one or more images of the interaction. [42] In an aspect, a method of experimentation is provided. The method comprises collecting information associated with a biological material using a low energy electron microscope, causing the biological material to interact with a pharmaceutical drug, and collecting information associated with the biological material after interactions between the biological material and the pharmaceutical drug using the low energy electron microscope. In some embodiments, the pharmaceutical drug causes the biological material to interact with a biological agent. In some embodiments, the pharmaceutical drug causes the biological material to interact with a chemical agent. In some embodiments, the collected information associated with the biological agent after interactions between the biological material and the pharmaceutical and drug includes one or more low energy electron microscope images of the biological material after interactions between the biological material and the pharmaceutical drug.

[43] In certain embodiments, the biological material is selected from a virus, capsid, prion, antibody, protein, DNA and/or other biological structure located within a biological sample.

[44] In an aspect, a method of experimentation on a modified virus or capsid is provided. The method comprises modifying a virus or a capsid for a viral therapy or gene therapy experiments, or virus-based medical diagnostics and collecting information associated with the modified virus or capsid using a low energy electron microscope. In some embodiments, the method further comprises capturing one or more images of the virus or capsid using a low- energy electron microscope. In some embodiments, more than one virus or capsid is modified. In some embodiments, the information collected includes collecting information associated with the modified viruses or capsid.

[45] In some embodiments, the method comprises causing the modified virus or capsid to interact with an antibody or target cell or biological agent, and collecting information associated with interactions between the modified virus or modified capsid and the antibody or target cell or biological agent using low energy electron microscopy. In some embodiments, the information collected is one or more images of and antibody or target cell or biological agent, or interactions between the modified virus or modified capsid and the antibody or target cell or biological agent. In some embodiments, the images are collected in real time.

[46] In an aspect, a method of screening subjects is provided. In some embodiments, the method comprises receiving a biological sample from a subject and capturing one or more images of the biological sample using a low energy electron microscope. In some embodiments, the subject are screened for infectious particles, e.g., virus, prion, bacteria, fungus, etc.

[47] In some embodiments, subject is a human. In some embodiments, the subject is an animal, e.g., household pets, farm animals, livestock, fish, other sea animals, wildlife, etc. In some embodiments, the biological sample is selected from breath condensate, saliva, blood, plasma, skin cells, etc.

[48] In some embodiments, method further comprises determining that an infectious particle is depicted in one or more of the captured images and identifying infectious particle in the image.

[49] In some embodiments method may further comprise vaccinating subject, receiving a second biological sample from the subject after the vaccination, and capturing one or more images of the second biological sample using the low energy electron microscope.

[50] In an aspect, a method for deciding whether a person should be granted access to controlled, restricted or protected location is provided. In some embodiments, the subject are screened for infectious particles, e.g., virus, prion, bacteria, fungus, etc. The method comprises receiving a biological sample from a person requesting access to the location, screening the received biological sample for and infectious particle using a low energy electron microscopy technique, and authorizing access to the location based on a negative screening result (e.g., no viruses, no prions, etc.). In some embodiments, screening comprises capturing one or more images of the received biological sample using a low energy electron microscope, and identifying one or more infectious particle depicted in at least one of the captured images. In some embodiments, access to the location may be denied if the presence of an infectious particle is detected in one or more of the captured images. [51] In an aspect, a testing package for testing subjects is provided. The package comprises a substrate configured to contain a biological sample taken from a subject, a low energy electron microscope configured to capture images of biological samples contained by the substrate, and the computing device configured to analyze images of the biological sample captured by the low energy electron microscope. In some embodiments, the subject are screened for infectious particles, e.g., virus, prion, bacteria, fungus, etc. in some embodiments, the computing device is configured to identify infectious particles depicted in the images captured by the low energy electron microscope. In some embodiments, subject is a human. In some

embodiments, the subject is an animal, e.g., household pets, farm animals, livestock, fish, other sea animals, wildlife, etc. In some embodiments, the subject is a plant (e.g., wheat, corn, rice, cereals, fruit, vegetables, plants used for bio-fuel production, decorative plants, trees, grass, ground cover, etc.). In some embodiments, the subject is a food product. In some embodiments, the biological sample is selected from breath condensate, saliva, blood, plasma, skin cells, mucosa cells, etc. In some embodiments, the biological sample is selected from root, stem, seed, leaves, flowers, fruit, etc. In some embodiments, the biological sample is selected from fresh food, preserved food, frozen food, dairy, bread, meat, fruit, vegetable, grain, etc. In some embodiments, the biological sample is selected from an air sample, water sample, gas sample, a swabbed sample, etc.

[52] In an aspect, method of screening plant subjects (such as wheat, corn, rice, cereals, fruit, vegetables, plants used for bio-fuel production, decorative plants, trees, grass, ground cover, etc.) for virus or viroid infections is provided. The method comprises receiving a biological sample from a plant subject, and capturing one or more images of the biological sample using a low-energy electron microscope. The method may further comprise

determining that a virus or viroid is depicted in one or more of the captured images and identifying the virus or viroid type of the depicted virus or viroid.

[53] In an aspect, a method for certifying food products is provided. The method comprises receiving a sample of a food product, screening the received sample for infectious particles using a low energy electron microscopy technique, and certifying or not certifying the food product based on the result of the screening test. In an embodiment the screening comprises capturing one or more images of the received sample using a low-energy electron microscope, and identifying one or more infectious particles depicted in one or more of the captured images. In some embodiments, certification of the food product is based on the negative result of the screening, e.g., no infectious particles identified in the sample. In some embodiments,

certification is denied based on identification of one or more infectious particles in one or more of the captured images. In some embodiments, the food product is selected from fresh food, preserved food, processed food, frozen food, animal-based (e.g., dairy, meat, etc.), bread, plant-based (e.g., fruit, vegetable, grain, etc.), etc.

[54] In an aspect, a LEEM-based apparatus, comprisng the electronics hardware and software (data base, image recognition software, etc.,) for screening of import of plants across the country borders, and into ecologically sensitive areas such as islands, for possible viral and viroid infections is provided.

[55] Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the scope and spirit of the invention will become apparent to one skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

[56] Figure 1 is a block diagram illustrating components of a suitable imaging and identification system.

[57] Figure 2 is a block diagram illustrating components of a low energy electron microscope (LEEM).

[58] Figure 3 is a block diagram illustrating components of a computing device used to identify a biological material from contents within LEEM images. [59] Figure 4 is a flow diagram illustrating a routine for identifying a virus from the characteristics of the contents of LEEM images.

[60] Figure 5 is a flow diagram illustrating a routine for identifying a virus from the comparison of a LEEM image to LEEM images associated with known viruses.

[61] Figure 6 is a flow diagram illustrating a routine for identifying biological material from the characteristics of the contents of LEEM images.

[62] Figure 7 is a flow diagram illustrating a routine for identifying an antibody from the comparison of a LEEM image to LEEM images associated with known antibodies.

[63] Figure 8 is a flow diagram illustrating a method for experimentation utilizing LEEM techniques.

[64] Figure 9 is a flow diagram illustrating a method for authorizing access to a location utilizing LEEM techniques.

[65] Figure 10 is a flow diagram illustrating a method for certifying food products utilizing LEEM techniques.

DETAILED DESCRIPTION

[66] The invention will now be described in detail by way of reference only using the following definitions and examples. All patents and publications, including all sequences disclosed within such patents and publications, referred to herein are expressly incorporated by reference.

[67] A system and method for using low energy electron microscopy (LEEM) techniques in various applications, such as applications of research, screening, identifying and so on, are described. In some implementations, the system takes images of a biological material (e.g., viruses, capsids, prions, antibodies, antibody-object interactions, proteins, DNA), extracts information {e.g., size or shape of contents) from the taken images, and identifies the biological material based on the extracted information. In some examples, an experiment may utilize LEEM techniques when collecting information from an experimental subject. In some examples, a screening procedure may utilize LEEM techniques when screening subjects for viruses and other biological structures, such as human, animal, plant or food product subjects. [68] A system that detects and identifies viruses, prions, antibodies and/or other biological structures in a relatively short period of time may be extremely valuable for medical diagnostics/treatment/experimentation and/or population screening, among other applications. Such a system may enable medical professionals to provide focused and timely treatments to people inflicted with a microbe, e.g., bacteria or virus, or a prion, which can not only enable a more rapid recovery, but also in many cases lead to a greatly reduced chance of death and/or transmission to other people. As a population screening mechanism, the system may provide the ability to track the local, regional or worldwide movement of viruses and prions, better enable the timely quarantine of highly contagious individuals, detect the presence of deadly, latent virus strains or prions in individuals or groups of people, among other benefits.

[69] In performing experiments and/or screening subjects, LEEM techniques may be utilized, adapted and/or configured. LEEM techniques may be used to detect and identify viruses, prions, antibodies, proteins, DNA and/or other biological structures during testing of human, animal, and/or plant subjects, in order to identify whether a subject, or group of subjects, within a human and/or animal population is carrying pathogenic microbes, e.g., bacteria or viruses, or prions. Such testing may be performed to detect and identify microbes transmitted over the air, transmitted via bodily fluids, transmitted via human or animal waste, transmitted via physical contact, deadly microbes, non-deadly microbes, and so on. Thus, a LEEM-based system, in some examples, may be configured to identify virtually any type of virus, prion, or other biological structure, that has infected an animal subject, human or otherwise.

[70] As one example, after passing through security at an airport, a person enters a virus and/or prion screening area and (for example) breathes into a test package that screens for viruses and/or prions. The test package collects breath condensate (or saliva, etc.) as a sample, and screens the sample using a LEEM-based component. If the screening turns a 'positive' finding, /^'.e.,if viruses and/or prions are detected and identified within the collected breath condensate, the passenger can be detained, and not authorized to proceed to the flight.

[71] As another example, a researcher is performing an experiment to identify whether a certain virus or prion affects target cancer cells. The researcher causes the virus or prion to interact with the target cells, and uses a LEEM to take images of the interactions, which are later used to inform further experiments. For example, this information can be used in developing virotherapy or gene therapy for particular forms of cancer, or for treatment of infections by bacteria that are resistant to antibiotics and other treatments, etc.

[72] The system will now be described with respect to various embodiments, examples, and/or implementations. The following description provides specific details for a thorough understanding of, and enabling description for, these embodiments of the system. However, one skilled in the art will understand that the system may be practiced without these details. In other instances, well-known structures and functions have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments of the system.

[73] It is intended that the terminology used in the description presented below be interpreted in its broadest reasonable manner, even though it is being used in conjunction with a detailed description of certain specific embodiments of the system. Certain terms may even be emphasized below; however, any terminology intended to be interpreted in any restricted manner will be overtly and specifically defined as such in this Detailed Description section.

[74] Unless defined otherwise herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described. Numeric ranges are inclusive of the numbers defining the range. It is to be understood that this invention is not limited to the particular methodology, protocols, and reagents described, as these may vary.

[75] Unless the context clearly requires otherwise, throughout the description and the claims, the words "comprise," "comprising," and the like are to be construed in an inclusive sense, as opposed to an exclusive or exhaustive sense; that is to say, in the sense of "including, but not limited to." As used herein, the terms "connected," "coupled," or any variant thereof, means any connection or coupling, either direct or indirect, between two or more elements; the coupling of connection between the elements can be physical, logical, or a combination thereof. Additionally, the words "herein," "above," "below," and words of similar import, when used in this application, shall refer to this application as a whole and not to any particular portions of this application. Where the context permits, words in the above Detailed Description using the singular or plural number may also include the plural or singular number respectively. The word "or," in reference to a list of two or more items, covers all of the following interpretations of the word: any of the items in the list, all of the items in the list, and any combination of the items in the list.

[76] The headings provided herein are not limitations of the various aspects or embodiments of the invention which can be had by reference to the specification as a whole. Accordingly, the terms defined immediately below are more fully defined by reference to the specification as a whole.

Definitions

[77] "Substrate" refers to the surface on which a sample, e.g., a biological sample, is placed for imaging in a LEEM apparatus. Preferred substrates are atomically smooth, metallic, and chemically inert. In particular, single crystal transition-metal oxides coated onto a support surface {e.g., a silicon wafer) find particular use in the present methods and systems.

[78] The term "biological sample" refers not only to the biological material itself (proteins, nucleic acids, tissues, etc.) but also to other materials associated therewith, e.g., tissue or fluid isolated from a subject, including but not limited to, for example, blood, plasma, serum, fecal matter, urine, bone marrow, bile, spinal fluid, lymph tissue and lymph fluid, samples of the skin, external secretions of the skin, respiratory, intestinal, and genitourinary tracts, tears, saliva, milk, blood cells, organs, biopsies and also samples of in vitro cell culture constituents including but not limited to conditioned media resulting from the growth of cells and tissues in culture medium, e.g., recombinant cells, and cell components. A biological sample may also be a plant or a food product. A biological sample can include a "biological material," for instance, a polypeptide or a polynucleotide, or could also include intact or fragmented portions of organisms or cells obtained from sampling the environment, such as airborne pathogens. A biological material may be viruses, capsids, prions, antibodies, antibody-object interactions, proteins, DNA or other biological structures. Biological samples may be fresh, frozen and/or preserved using known methods in the art.

[79] The biological sample may comprise blood, serum, proteins,

lipoproteins, cells, cell constituents, microorganisms, DNA, or combinations thereof. Separation of the biological sample into constituents, e.g., a biological material, if desired, may be effected by density gradient ultracentrifugation, gradient gel electrophoresis, capillary electrophoresis, ultracentrifugation- vertical auto profile, nuclear magnetic resonance, tube gel electrophoresis, chromatography, or combinations thereof. The constituents may be separated according to size (rate zonal), density (isopycnic), or combinations thereof.

[80] "Polypeptide" as used herein refers to a polymer of amino acids and does not refer to a specific length of a polymer of amino acids. Thus, for example, the terms peptide, oligopeptide, protein, and enzyme are included within the definition of polypeptide. This term also includes post-expression modifications of the polypeptide, for example, glycosylations, acetylations, phosphorylations and the like.

[81] Also, as used herein, the term "polynucleotide" refers to a polymeric form of nucleotides of any length, either ribonucleotides or deoxynucleotides, and includes both double- and single-stranded DNA and RNA. A

polynucleotide may include nucleotide sequences having different functions, including for instance coding sequences, and non-coding sequences such as regulatory sequences. A polynucleotide can be obtained directly from a natural source, or can be prepared with the aid of recombinant, enzymatic, or chemical techniques. A polynucleotide can be linear or circular in topology. A polynucleotide can be, for example, a portion of a vector, such as an expression or cloning vector, or a fragment.

[82] "Food Product" refers to a product suitable for human consumption or a pet food. The food product may be raw, processed or prepared. A food product comprises a series of elements having a network of proteins, carbohydrates and/or fats. The term "food products" described herein may be referred to alternatively herein as "food items".

[83] The term "antibody" herein is used in the broadest sense and specifically covers monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g. bispecific antibodies) formed from at least two intact antibodies, and antibody fragments so long as they exhibit the desired biological activity. The antibodies useful in the present invention can encompass monoclonal antibodies, polyclonal antibodies, antibody fragments (e.g., Fab, Fab'-SH, Fv, scFv, and F(ab')2), chimeric antibodies, bispecific antibodies, multivalent antibodies, heteroconjugate antibodies, fusion proteins comprising an antibody portion, humanized antibodies, and any other modified configuration of the immunoglobulin molecule that comprises an antigen recognition site of the required specificity, including glycosylation variants of antibodies, amino acid sequence variants of antibodies, and covalently modified antibodies. The antibodies may be murine, rat, human, or of any other origin (including chimeric or humanized antibodies). "Antibody" as used herein may be used interchangeably with immunoglobulin (Ig).

[84] The basic 4-chain antibody unit is a heterotetrameric glycoprotein composed of two identical light (L) chains and two identical heavy (H) chains. The pairing of a VH and VL together forms a single antigen-binding site. For the structure and properties of the different classes of antibodies, see, e.g., Basic and Clinical Immunology, 8th Ed., Daniel P. Stites, Abba I. Terr and Tristram G. Parslow (eds.), Appleton & Lange, Norwalk, CT, 1994, page 71 and Chapter 6.

[85] The L chain from any vertebrate species can be assigned to one of two clearly distinct types, called kappa ("κ") and lambda ("λ"), based on the amino acid sequences of their constant domains. Depending on the amino acid sequence of the constant domain of their heavy chains (CH),

immunoglobulins can be assigned to different classes or isotypes. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG and IgM, having heavy chains designated alpha ("a"), delta ("δ"), epsilon ("ε"), gamma ("γ") and mu ("μ"), respectively. The γ and a classes are further divided into subclasses (isotypes) on the basis of relatively minor differences in the CH sequence and function, e.g., humans express the following subclasses: IgGI, lgG2, lgG3, lgG4, IgAI and lgA2. The subunit structures and three dimensional configurations of different classes of immunoglobulins are well known and described generally in, for example, Abbas et al., Cellular and Molecular Immunology, 4^th ed. (W.B. Saunders Co., 2000).

[86] "Antibodies" are usually heterotetrameric glycoproteins of about 150,000 daltons, composed of two identical light (L) chains and two identical heavy (H) chains. Each light chain is linked to a heavy chain by one covalent disulfide bond, while the number of disulfide linkages varies among the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain has at one end a variable domain (VH) followed by a number of constant domains. Each light chain has a variable domain at one end (VL) and a constant domain at its other end; the constant domain of the light chain is aligned with the first constant domain of the heavy chain, and the light chain variable domain is aligned with the variable domain of the heavy chain. Particular amino acid residues are believed to form an interface between the light chain and heavy chain variable domains.

[87] An "isolated" antibody is one that has been identified, separated and/or recovered from a component of its production environment {e.g., naturally or recombinantly).

[88] Preferably, the isolated polypeptide is free of association with all other contaminant components from its production environment. Contaminant components from its production environment, such as those resulting from recombinant transfected cells, are materials that would typically interfere with research, diagnostic or therapeutic uses for the antibody, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In preferred embodiments, the polypeptide will be purified: (1 ) to greater than 95% by weight of antibody as determined by, for example, the Lowry method, and in some embodiments, to greater than 99% by weight; (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver stain. Isolated antibody includes the antibody in situ within recombinant T-cells since at least one component of the antibody's natural environment will not be present. Ordinarily, however, an isolated polypeptide or antibody will be prepared by at least one purification step.

[89] As used herein, the term "ligand" refers to a substance that is able to bind to and form a complex with a biomolecule to serve a biological purpose. The binding occurs by intermolecular forces, such as ionic bonds, hydrogen bonds and van der Waals forces. The docking (association) is usually, and preferably, reversible (dissociation). The ligand can be of any chemical class of molecules, such as, without limitation, a naturally occurring or non-natural occurring protein, nucleic acid, hapten, lipid, carbohydrate, as well as chimeras and/or derivatives thereof, in monomeric, polymeric or conjugated forms.

Suitable system

[90] As described herein, in some implementations, the system images viruses, capsids, prions, antibodies, antibody-object interactions, proteins, DNA or other biological structures using a low energy electron microscope, and uses the images to identify the imaged viruses, capsids, prions, antibodies, antibody-object interactions, proteins, DNA or other biological structures. Figure 1 is a block diagram illustrating components of a suitable virus imaging and identification system 100.

[91] The system 100 includes a LEEM 1 10 that takes images of viruses and other biological structures and/or interactions located on a target substrate 1 15, a computing device 120 configured and/or programmed to identify viruses, capsids, prions, antibodies, antibody-object interactions, proteins, DNA or other biological structures within the LEEM images, and a database 130 that stores the taken images and information used to identify the contents of the taken images, among other information.

[92] Figure 1 , device 120, and the discussion herein provide a brief, general description of a suitable computing environment and devices in which the system can be implemented. Although not required, aspects of the system are described in the general context of computer-executable instructions, such as routines executed by a general-purpose computer, e.g., a laptop computer, a mobile device, a smart phone, a tablet computer, a server computer, and/or a personal computer. Those skilled in the relevant art will appreciate that the system can be practiced with other communications, data processing, or computer system configurations, including: Internet appliances, hand-held devices (including personal digital assistants (PDAs)), all manner of cellular or mobile phones, multi-processor systems, microprocessor-based or programmable consumer electronics, network PCs, mini-computers, mainframe computers, and the like. Indeed, the terms "computer," "host," and "host computer," and "mobile device" and "handset" are generally used interchangeably herein, and refer to any of the above devices and systems, as well as any data processor.

[93] Aspects of the system can be embodied in a special purpose computing device or data processor that is specifically programmed, configured, or constructed to perform one or more of the computer-executable instructions explained in detail herein. Aspects of the system may also be practiced in distributed computing environments where tasks or modules are performed by remote processing devices, which are linked through a communications network, such as a Local Area Network (LAN), Wide Area Network (WAN), or the Internet. In a distributed computing environment, program modules may be located in both local and remote memory storage devices.

[94] Aspects of the system may be stored or distributed on computer- readable media, such as tangible computer-readable storage media, including magnetically or optically readable computer discs, hard-wired or preprogrammed chips (e.g., EEPROM semiconductor chips), nanotechnology memory, biological memory, or other data storage media. Indeed, computer implemented instructions, data structures, screen displays, and other data under aspects of the system may be distributed over the Internet or over other networks (including wireless networks), on a propagated signal on a propagation medium (e.g., an electromagnetic wave(s), a sound wave, etc.) over a period of time, or they may be provided on any analog or digital network (packet switched, circuit switched, or other scheme). Those skilled in the relevant art will recognize that portions of the system reside on a server computer, while corresponding portions reside on a client computer such as a mobile or portable device, and thus, while certain hardware platforms are described herein, aspects of the system are equally applicable to nodes on a network. In an alternative embodiment, the mobile device or portable device may represent the server portion, while the server may represent the client portion.

[95] Referring back to Figure 1 , the system 100, which may be considered a testing package, utilizes a LEEM 1 10 to take, create, capture, and/or generate images of samples, such as samples that include viruses, known or unknown, capsids, prions, antibodies, antibody-object interactions, proteins, DNA or other biological structures. Figure 2 provides more details about the components and functionality of the low energy electron microscope (LEEM) 1 10.

[96] A LEEM 1 10 includes an electron source 210, an illumination column 215, a sample chamber 220, which includes a substrate 222 containing a sample 225 and an objective lens 227, a beam separator 230, an imaging column 235, an analyzer 240, a projector column 245, and a detector 250. A LEEM 1 10 operates using reflection geometry as follows.

[97] Electrons are emitted from the electron gun 210 and focused at the sample 225 located on the substrate 222 within the sample chamber 220. The electrons are then reflected back and collected by the objective lens 227, which produces an image in the center of the separator 230.

[98] In order to produce an image, the objective lens 227 acts as a cathode, while the sample 225 itself is used as an anode. The sample may be biased, for example, at 20 kV, and the arising counter-field decelerates the electrons such that they impinge the sample surface with low kinetic energy, typically no more than a few eV. In some cases the kinetic energy can even be zero or negative when operating in "mirror mode," where the electrons are reflected before they touch the sample.

[99] The LEEM 1 10 may include additional electron optics elements - such as quadrupole lenses or mirrors that correct for astigmatism, aberration, and so on. The incident and imaging beams are separated using a beam-splitter. The best current lateral spatial resolution for an aberration-corrected LEEM is 1 .4 nm, with vertical resolutions at about 0.1 nm.

[100] During operation, the LEEM 1 10, in some cases, obtains multiple images often at a video recording rate, producing real-time LEEM video clips and movies of targeted and imaged samples. Thus, the LEEM 1 10 may be used to study the dynamics of objects that move or change shape under the influence of some agent (a reactive gas, heat, or light, the electron beam itself, and so on).

[101] The LEEM 1 10 may provide several modes of operation. In some cases, by changing the aperture, the LEEM 1 10 can operate using low energy electron diffraction (LEED), which provides information about the surface crystallographic structure of a sample. In some cases, when the sample surface is illuminated by an ultraviolet light or X-ray source, the LEEM 1 10 can operate using photo-emission electron microscopy (PEEM).

[102] In addition to producing images that include surface topography maps, a LEEM 1 10 equipped with an energy analyzer may provide spatially resolved spectroscopic information associated with a sample. Using this information, the system may create and/or obtain element-specific maps, which provide information about the spatial distribution of various atoms and molecules of a sample, among other things.

[103] In some cases, the LEEM 1 10 requires a high vacuum to operate, and thus may only be used with samples that are vacuum-compatible. Samples also should be conductive, or capable of being conductive, in order to achieve a high bias between the sample and the objective lens 227.

[104] In some implementations, the sample chamber may include components configured to support and/or provide a high vacuum within the chamber, to maintain a substrate that contains a biological sample with a high vacuum, to support a conductive substrate, and so on. For example, the sample chamber 220 may include a load-lock, an ultrahigh vacuum pumping capability, such as provided by a turbo-molecular pump, a cryo-pump, an a ion pump and/or a titanium sublimation pump, a sample holder, a sample heater, inlets for reactive gasses, a device to enable supply of biological agents, such as antibodies, a mechanical sample manipulator with several degrees of freedom, including sample translation, rotation, and tilting, and allowing for accurate samples positioning, and so on.

[105] Therefore, within the system 100, utilization of a LEEM 1 10 may provide many advantages with respect to the identification of viruses, capsids, prions, antibodies, antibody-object interactions, proteins, DNA and/or other biological structures over the techniques known in the art, such as simplified sample preparation due to the reflection geometry, low energy operation, which allows imaging soft samples without radiation damage, high resolution, very fast (tens of frames per second) image acquisition, real-time video-rate monitoring of surface dynamics, and/or compatibility with a number of agents, such as high temperature, reactive gasses, sample illumination and irradiation, and so on.

[106] As mentioned herein, the resolution of LEEM instruments has been greatly improved in recent years. In state-of-the-art aberration-corrected LEEM instruments and with adequate vibration insulation it can be better than 1 .4 nm - which enables the observation of proteins in biological membranes (typical dimensions being 5 - 10 nm) and even individual DNA molecules (about 2 nm diameter). Also, in some implementations, a LEEM equipped with an electron energy analyzer provides spatially resolved spectroscopic information, which can be used to study a variety of processes, such as the metal uptake by different type of cells, which is of great interest in toxicology, among other benefits.

[107] Thus, as described herein, a LEEM device, such as LEEM 1 10, may be configured and/or adapted to take images and videos of biological samples, such as viruses, capsids, prions, antibodies, antibody-object interactions, proteins, DNA and/or other biological structures. Because a LEEM can take images with very high resolutions, among other things, the LEEM images may include various types of infornnation associated with the samples included in the images, such as size information, shape information, spatial and/or dimensional information, and so on. Therefore, the system may utilize LEEM images of samples, as well as information gleaned and/or extracted from the images, to identify viruses, capsids, prions, antibodies, antibody-object interactions, proteins, DNA and/or other biological structures within the samples, among other things. Figure 3 is a block diagram illustrating components of a computing device 120 used to identify viruses, capsids, prions, antibodies, antibody-object interactions, proteins, DNA and/or other biological structures from contents within LEEM images.

[108] The computing device 120, which may be considered an identification device, includes various hardware and/or software components programmed and/or configured to identify viruses, capsids, prions, antibodies, antibody- object interactions, proteins, DNA and/or other biological structures based on information within the contents of LEEM images. The identification device 120 includes an imaging component 310 configured and/or programmed to receive images from a LEEM 1 10 and extract, retrieve, identify, and/or determine information from the images, such as information associated with the contents of the images.

[109] The identification device 120 also includes an identification component 320 configured and/or programmed to identify a biological structure represented by the images and/or the contents of the images. That is, the identification component 320 may receive various information from the imaging component 310, such as the image and/or information associated with shape, size, spatial relationship, and so on, of the contents of the image, and perform various image recognition and/or matching routines in order to identify a virus, capsids, prions, antibodies, antibody-object interactions, proteins, DNA and/or other biological structure represented by the images.

[110] The system, via the identification component 320, may utilize a variety of different image search or identification systems and associated techniques, such as content-based image retrieval (CBIR) systems. For example, in some cases, the identification component 320 may employ a "query by example" technique that extracts a shape or object from a captured image and uses the extracted shape or object to search for matching images. Other techniques utilized by the system may include image distance measurement and/or filtering techniques (e.g., using color, texture, shape, and so on) to match images, semantic retrieval techniques, and other known query methods. For example, in some cases, the identification component 320, upon receiving a set of captured images, may follow pre-specified instructions, such as an instruction to "look for a certain type of virus," among other things.

[111] In some implementations, the identification device 120 may utilize a communication component 330 configured and/or programmed to transmit and/or receive information. For example, the identification device 120 may transmit instructions to an operator of the LEEM 1 10 requesting additional images, may receive information associated with the images and/or the images themselves, may receive information associated with certain types of biological structures to be identified, and so on. The communication component 330 may receive and/or transmit information over a variety of different networks and/or protocols, including wireless networks, wired networks, virtual networks, private networks, cellular communications networks, Bluetooth, near-field networks, the Internet, and so on.

[112] Of course, one of ordinary skill in the art will realize that the identification device 120 may include other components 340, such as components configured and/or programmed to store information, to provide metadata and/or context information to the identification component 320 and/or the imaging component 310, and so on.

[113] Thus, the system, in some implementations, utilizes images taken by a LEEM 1 10 of a biological sample, and the information contained therein, to identify a type of virus, capsids, prions, antibodies, antibody-object interactions, proteins, DNA and/or other biological structures located within the sample. The utilization of LEEM images and the information that can be extracted from the images enables the system to identify with certainty the type of virus, capsids, prions, antibodies, antibody-object interactions, proteins, DNA and/or other biological structures within a sample, among other benefits. Such a system may be adapted in various environments (e.g., schools, airports, hospitals) where the early and accurate detection of viruses, capsids, prions, antibodies, antibody-object interactions, proteins, DNA and/or other biological structures may prevent widespread illnesses and epidemics, greatly benefiting mankind.

[114] In some examples, the system 100 may be a part of the testing package configured to test biological samples in various environments and for a variety of purposes. For example, the system 100 may include substrates, testing kits, testing packages, testing or screening software or hardware components, e.g., components configured to authorize access to restricted and controlled locations (airports, train and bus stations, government buildings, schools, etc.), to certify samples, and so on. The system 100 may be utilized in a variety of ways, such as:

[115] in LEEM-based research, clinical practice, and screening;

[116] in LEEM-based biomedical, veterinary, pharmaceutical, virotherapy, gene therapy, virus-based medical diagnostics, and plant research;

[117] in LEEM-based activities in medical and veterinary clinical practice, as well as for farms and plantations;

[118] in LEEM-based activities in screening of people at airports, other transportation hubs (ports, train stations, bus stations), banks, government buildings, hospitals, schools and colleges, theaters, concert halls, stadiums, large hotels, conventions centers, and so on;

[119] in LEEM-based activities in screening of food, food-related products and facilities for food production, processing, and distribution; and so on.

[120] Thus, the LEEM components described herein, and LEEM-based techniques performed by such components, may be utilized for research purposes {e.g., in the collection of information during an experiment), screening purposes {e.g., in the screening of humans, animals, plants, and other subjects), diagnostic purposes, and so on.

[121] The above detailed description of embodiments of the system is not intended to be exhaustive or to limit the system to the precise form disclosed above. While specific embodiments of, and examples for, the system are described above for illustrative purposes, various equivalent modifications are possible within the scope of the system, as those skilled in the relevant art will recognize. For example, while processes or blocks are presented in a given order, alternative embodiments may perform routines having steps, or employ systems having blocks, in a different order, and some processes or blocks may be deleted, moved, added, subdivided, combined, and/or modified. Each of these processes or blocks may be implemented in a variety of different ways. Also, while processes or blocks are at times shown as being performed in series, these processes or blocks may instead be performed in parallel, or may be performed at different times.

[122] The teachings of the system provided herein can be applied to other systems, not necessarily the system described above. The elements and acts of the various embodiments described above can be combined to provide further embodiments.

[123] All of the above patents and applications and other references, including any that may be listed in accompanying filing papers, are incorporated by reference. Aspects of the system can be modified, if necessary, to employ the systems, functions, and concepts of the various references described above to provide yet further embodiments of the system.

[124] These and other changes can be made to the system in light of the above Detailed Description. While the above description details certain embodiments of the system and describes the best mode contemplated, no matter how detailed the above appears in text, the system can be practiced in many ways. Details of the local-based support system may vary considerably in its implementation details, while still being encompassed by the system disclosed herein. As noted above, particular terminology used when describing certain features or aspects of the system should not be taken to imply that the terminology is being redefined herein to be restricted to any specific characteristics, features, or aspects of the system with which that terminology is associated. In general, the terms used in the following claims should not be construed to limit the system to the specific embodiments disclosed in the specification, unless the above Detailed Description section explicitly defines such terms. Accordingly, the actual scope of the system encompasses not only the disclosed embodiments, but also all equivalent ways of practicing or implementing the system under the claims. [125] While certain aspects of the system are presented below in certain claim forms, the inventors contemplate the various aspects of the system in any number of claim forms. Accordingly, the inventors reserve the right to add additional claims after filing the application to pursue such additional claim forms for other aspects of the system.

Identifying Viruses and Capsids Using Low Energy Electron Microscopy

[126] As described herein, in some implementations, the system and its components perform various routines, techniques, processes, and/or methods in order to identify a type of virus or capsid within a sample imaged by a low energy electron microscope.

[127] Figure 4 is a flow diagram illustrating a routine 400 for identifying a virus or capsid from the characteristics of the contents of LEEM images. In step 410, the system receives an image from a LEEM. For example, the system, via the imaging component 310, receives one or more images taken of a sample 225 within the LEEM 1 10. In some cases, the system may utilize the communication component 330 in order to receive the LEEM images from the LEEM 1 10.

[128] In step 420, the system measures a size and/or shape of the contents of the received image or images. For example, the system, via the identification component 320 (or, in some cases, the imaging component 310), extracts size and/or shape information associated with contents within the received images. The contents may include depictions or representations of viruses or other targeted biological structures, among other representations within an image. The system, therefore, determines the size and/or shape of a targeted subject, namely a virus or capsid located on a substrate within the LEEM 1 10.

[129] As described herein, the system may utilize many different techniques for extracting or gleaning size and/or shape information from the contents of an image. That is, the system may utilize various algorithms or processes to determine a realistic or probable size or shape of a subject within a received image. In some cases, the system may categorize the contents of an image into one or more morphological categories associated with viruses or capsids, in order to assign infornnation suitable to be matched to information associated with viruses or capsids.

[130] In some cases, the LEEM 1 10 may include components configured and/or programmed to determine the size and/or shape/structure of contents within images, and provide such information to the identification component 320 along with taken images.

[131] In step 430, the system searches for viruses or capsids having similar size and/or shape characteristics. For example, the system, via the identification component 320, searches a database that stores information associated with known viruses or capsids for any matches or probable matches to the size and/or shape information extracted from the received LEEM images. Table 1 represents a data structure storing information associated with known viruses that may be queried by the identification component 320 when attempting to match information from a LEEM image to morphological information associated with known viruses.

Table 1 [132] Of course, one of ordinary skill in the art will realize that the system may utilize various different data structures, including data structures that include different types of information, when querying for information associated with known viruses and other biological structures. The system may utilize information associated with certain operation characteristics or metadata of a LEEM device, such as parameters related to or indicative of applied voltage, beam current, field of view, depth of focus from the substrate surface, number of frames per second, integration or averaging time, the conditions under which the images were obtained, (such as temperature, pressure, gas content, or irradiation exposure history), sample preparation details, and so on.

[133] For example, the system, via the identification component 320, searches a data structure, table, or other suitable database or index associated with a database in order to match information associated with a LEEM image or images to information associated with a known virus or capsid.

[134] In some cases, the system may utilize context information, such as information received from a context component configured and/or programmed to provide context information to routine 400, in order to constrain the search information that matches information from a LEEM image or images. For example, the system, when performing a query or search, may utilize context information to eliminate possible matches, or narrow the areas of a database to be searched, among other things.

[135] Once a match, or possible match, has been found, the system, in step 440, identifies a virus or capsid based on the search. For example, the system, via the identification component 320, obtains a positive result of a search for information associated with known viruses or capsids that matches or satisfies a query associated with information gleaned from a LEEM image. Based on the positive result, the system determines that the subject represented by the received LEEM image is to be identified as the virus or capsid associated with information that matches the search.

[136] For example, the system receives multiple images from a LEEM 1 10 that include a distinct subject within the contents of the images. The system, via the imaging component 310, extracts an average size of the contents of the images to be 1 10 nm, with a shape of the contents to be roughly spherical. The system, via the identification component 320, queries an index of information associated with known viruses or capsids, such as Table 1 , and identifies the information associated with the "influenza virus" as satisfying the query. The system, therefore, follows routine 400 and identifies the subject of the LEEM images as the type: influenza virus.

[137] Therefore, the system, in some implementations, may perform morphology comparison in order to identify a biological structure within an image as a known virus or capsid and/or as a virus or capsid within a known category of viruses or capsids, among other benefits.

[138] In some implementations, the system identifies a subject within an imaged sample as a certain virus or capsid based on a successful match of the imaged sample to one or more images associated with known viruses or capsids. Figure 5 is a flow diagram illustrating a routine 500 for identifying a virus or capsid from the comparison of a LEEM image to LEEM images associated with known viruses or capsids.

[139] In step 510, the system receives an image from a LEEM. Similar to step 410 of Figure 4, the system, via the imaging component 310, receives one or more images taken of a sample 225 within the LEEM 1 10. Again, in some cases, the system may utilize the communication component 330 in order to receive the LEEM images from the LEEM 1 10.

[140] In step 520, the system compares the images received from the LEEM, or multiple images (e.g., video) received from the LEEM, to a group of images associated with various known viruses or capsids and/or known types of viruses or capsids. For example, the system, via the identification component 320, compares the received image or images, to images that represent or are indicative of known viruses or capsids.

[141] The identification component 320 may perform the comparison using a variety of image search and/or matching techniques, such as those described herein. For example, in some implementations, the identification component 320 may perform a variety of different content-based image retrieval (CBIR) techniques using when comparing a query image (i.e., the received image) to a group of known images. That is, the system may utilize a CBIR engine (e.g., Google image search, Visual Recognition Factory, and so on) to perform the comparison. Of course, one of ordinary skill in the art will realize that other image comparison techniques may be utilized.

[142] In step 530, the system identifies a virus or capsid within the received image based on the comparison. For example, the system, via the identification component 320, identifies a virus or capsid within the LEEM image, and hence within the imaged sample, based on a match of the query image to an image associated with a know virus or capsid.

[143] Thus, the system may utilize a variety of different search and/or comparison techniques, such as CBIR search techniques, morphological information comparisons, and so on, with respect to received LEEM images, in order to identify a virus or capsid within a sample imaged by a low energy electron microscope.

[144] In some implementations, the system may utilize these techniques in order to identify and/or examine interactions between viruses or capsids and various agents that act upon the viruses or capsid. For example, the system may perform routines 400 and/or 500 using query images and/or query videos taken by a LEEM of a virus-agent or capsid-agent interaction, and identify the interaction, a certain stage of the interaction, a certain result of the interaction, a certain intermediate result of the interaction, a certain complex of the interaction, and so on.

[145] Therefore, the system may utilize LEEM images to record and/or identify viruses and other biological structures within examined samples as well as record and/or identify dynamic interactions between the viruses or capsids and agents that act upon the viruses or capsids during experiments, among other benefits.

Identifying Antibodies Using Low Energy Electron Microscopy

[146] As described herein, in some implementations, the system and its components perform various routines, techniques, processes, and/or methods in order to identify a type of antibody and/or antibody-virus interaction within a sample imaged by a low energy electron microscope. The same applies, in what follows also to antibody-capsid, antibody-prion, antibody-protein and antibody-DNA interactions, as will be apparent to one of average skills in the art, even when it is not stated explicitly.

[147] Figure 6 is a flow diagram illustrating a routine 600 for identifying an antibody and/or antibody-virus t interaction from the characteristics of the contents of LEEM images. In step 610, the system receives an image from a LEEM. For example, the system, via the imaging component 310, receives one or more images taken of a sample 225 within the LEEM 1 10. In some cases, the system may utilize the communication component 330 in order to receive the LEEM images from the LEEM 1 10.

[148] In step 620, the system measures a size and/or shape of the contents of the received image or images. For example, the system, via the identification component 320 (or, in some cases, the imaging component 310), extracts size and/or shape information associated with contents within the received images. The contents may include depictions or representations of antibodies or portions of antibodies, among other representations within an image. The system, therefore, determines the size and/or shape of a targeted subject, namely an antibody located on a substrate within the LEEM 1 10.

[149] As described herein, the system may utilize many different techniques for extracting or gleaning size and/or shape information from the contents of an image. That is, the system may utilize various algorithms or processes to determine a realistic or probable size or shape of a subject within a received image. In some cases, the system may categorize the contents of an image into one or more morphological categories associated with antibodies, in order to assign information suitable to be matched to information associated with antibodies.

[150] In some cases, the LEEM 1 10 may include components configured and/or programmed to determine the size and/or shape/structure of contents within images, and provide such information to the identification component 320 along with taken images.

[151] In step 630, the system searches for antibodies and/or antibody-virus t interactions having similar size and/or shape characteristics. For example, the system, via the identification component 320, searches a database that stores information associated with known antibodies for any matches or probable matches to the size and/or shape information extracted from the received LEEM images.

[152] The system may utilize certain shape characteristics known to be associated with certain antibody, or antibody types, when searching for and/or matching contents of LEEM images to known antibodies. For example, the system may determine that a LEEM image includes a structure having a dimer shape, and match the dimer shape to IgA type antibodies, or may determine that a LEEM image includes a structure having a pentamer shape, and match the pentamer shape to IgM type antibodies, or may determine that a LEEM image includes a structure having a monomer shape, and match the monomer shape to IgD, IgE, or IgG type antibodies, among other things.

[153] Of course, one of ordinary skill in the art will realize that the system may utilize various different data structures, including data structures that include different types of information, when querying for information associated with known antibodies and other biological structures. The system may utilize information associated with certain operation characteristics or metadata of a LEEM device, such as parameters related to or indicative of applied voltage, beam current, field of view, depth of focus from the substrate surface, number of frames per second, integration or averaging time, the conditions under which the images were obtained, (such as temperature, pressure, gas content or irradiation exposure history), sample preparation details, and so on.

[154] For example, the system, via the identification component 320, searches a data structure, table, or other suitable database or index associated with a database in order to match information associated with a LEEM image or images to information associated with a known antibody and/or antibody-agent interaction.

[155] In some cases, the system may utilize context information, such as information received from a context component configured and/or programmed to provide context information to routine 600, in order to constrain the search information that matches information from a LEEM image or images. For example, the system, when performing a query or search, may utilize context information to eliminate possible false positive matches, or narrow the areas of a database to be searched, among other things.

[156] Once a match, or possible match, has been found, the system, in step 640, identifies an antibody based on the search. For example, the system, via the identification component 320, obtains a positive result of a search for information associated with known antibodies that matches or satisfies a query associated with information gleaned from a LEEM image. Based on the positive result, the system determines that the subject represented by the received LEEM image is to be identified as the antibody associated with information that matches the search.

[157] Therefore, the system, in some implementations, may perform morphology (size, shape, etc.) comparisons in order to identify a subject biological structure within an image as a known antibody (e.g., lgA1 ) and/or as an antibody within a known category of antibodies (e.g., IgA), among other benefits.

[158] In some implementations, the system identifies a subject within an imaged sample as a certain antibody based on a successful match of the imaged sample to one or more images associated with known antibodies. Figure 7 is a flow diagram illustrating a routine 700 for identifying an antibody from the comparison of a LEEM image to LEEM images associated with known antibodies.

[159] In step 510, the system receives an image from a LEEM. Similar to step 610 of Figure 6, the system, via the imaging component 310, receives one or more images taken of a sample 225 within the LEEM 1 10. Again, in some cases, the system may utilize the communication component 330 in order to receive the LEEM images from the LEEM 1 10.

[160] In step 720, the system compares the images received from the LEEM, or multiple images (e.g., video) received from the LEEM, to a group of images associated with various known antibodies and/or known types of antibodies. For example, the system, via the identification component 320, compares the received image or images to images that represent or are indicative of known antibodies. [161] The identification component 320 may perform the comparison using a variety of image searching and/or matching techniques, such as those described herein. For example, in some implementations, the identification component 320 may perform a variety of different content-based image retrieval (CBIR) techniques used when comparing a query image (i.e., the received image) to a group of known images. That is, the system may utilize a CBIR engine (e.g., Google image search, Visual Recognition Factory, and so on) to perform the comparison. Of course, one of ordinary skill in the art will realize that other image comparison techniques may be utilized.

[162] In step 730, the system identifies an antibody within the received image based on the comparison. For example, the system, via the identification component 320 identifies that an antibody is contained within the LEEM image, and hence within the imaged sample, based on a match of the query image to an image associated with a known antibody.

[163] Thus, the system may utilize a variety of different search and/or comparison techniques, such as CBIR search techniques, morphological information comparisons, and so on, with respect to the received LEEM images, in order to identify an antibody or antibodies within a sample imaged by a low energy electron microscope.

[164] In some implementations, the system may utilize these techniques in order to identify and/or examine interactions between antibodies and target objects, such as bacteria, viruses, and/or other microbes. For example, the system may perform routines 600 and/or 700 using query images and/or query videos taken by a LEEM of an antibody-agent interaction, and identify the interaction, a certain stage of the interaction, a certain result of the interaction, a certain intermediate result of the interaction, a certain complex of the interaction, and so on.

[165] That is, in some implementations, the system may utilize LEEM images to monitor and/or view aspects of an antibody-object interaction. For example, the LEEM images may show a binding location on an antibody when the antibody binds to a target object (a virus, a prion, a protein, a DNA molecule, a bacterium, etc.), a binding location on a target object when the antibody binds to a target object, and so on. Utilizing the LEEM techniques described herein, the system may capture images of samples that show how antibodies are positioned and distributed on the surface of a virus or viruses. Such information can be very useful to virologists for understanding the detailed mechanism of antibody-virus interaction, as wells as to pharmacologists working on developing antiviral drugs and therapies, among other benefits.

[166] Thus, the system in some implementations may utilize a LEEM to observe dynamic interactions between antibodies and targeted foreign objects, such as the locations of attachment between antibodies and viruses, among other things.

[167] Therefore, the system may utilize LEEM images to record and/or identify antibodies and other biological structures within examined samples as well as record and/or identify dynamic interactions between the antibodies and other biological objects such as viruses, prions, proteins, DNA molecules, bactera, etc.), among other benefits.

Methods of Experimentation With Viruses Using LEEM Techniques

[168] As described herein, in some examples, the LEEM techniques may be utilized during research, such as in experiments designed to collect information about viruses and other biological structures, among other things. For example, an experiment may include a research step of collecting information from a sample using a LEEM technique, such as by capturing images of a sample using a LEEM.

[169] Figure 8 is a flow diagram illustrating a method 800 for experimentation utilizing LEEM techniques. In step 810, information is collected from a sample using a LEEM. For example, a LEEM is used to capture images of viruses or other biological objects under experimentation. In step 820, the sample is modified. For example, experimental agents, such as biological agents, chemical agents and/or physical agents, may interact with the sample, modifying the sample. In step 830, information is collected from the modified sample using the LEEM.

[170] Thus, in addition to collecting information from an original sample, a LEEM may be used to collect information from a sample before, during, and/or after a sample is or has been exposed to a chemical, physical or biological agent. The following are example experiments that may utilize LEEM techniques when collecting information during the experiments:

[171] Basic and applied biomedical research and development, including: imaging, recognition, and identification of viruses, capsids, antibodies, prions, proteins, DNA, etc.; the study of interaction (including in real time) of viruses, capsids, antibodies, prions, proteins, DNA, etc. with various physical agents, such as temperature, illumination by light (from microwaves to gamma rays), irradiation (by electrons or ions), and so on; the study of virus or antibody interaction (including in real time) with various chemical agents, such as reactive gasses of various atoms, molecules, and ions, pharmaceuticals, and so on; the study of interaction (including in real time) of viruses, capsids, prions, proteins, DNA, etc. with various biological agents such as antibodies; and so on.

[172] Pharmaceutical research and development, including: the study of virus or antibody interaction (including in real time) with various chemical agents such as drugs; the study of virus interaction (including in real time) with various biological agents such as antibodies; the study of modification of viruses (including in real time) for pharmaceutical purposes; the study of modification of antibodies (including in real time) for pharmaceutical purposes; the study of modification of virus capsids in various steps of their preparation for pharmaceutical purposes; the study of interaction of viruses (including in real time) or capsids modified for pharmaceutical purposes with various biological agents such as antibodies; and so on.

[173] Virotherapy and gene therapy research and development, including: the study of virus interaction (including in real time) with various biological agents such as antibodies; the study of modification of viruses (including in real time) for virotherapy and gene therapy purposes; the study of modification of antibodies (including in real time) for virotherapy and gene therapy purposes; the study of modification of virus capsids in various steps of their preparation for virotherapy and gene therapy; the study of interaction of viruses (including in real time) or capsids modified for virotherapy and gene therapy purposes with various biological agents such as antibodies; the study of using controlled and modified viruses for medical diagnostic purposes, and so on.

[174] Thus, an experiment, research task, study, and so on may include one or more steps of collecting and/or analyzing information using LEEM-based techniques in order to collect information generally unavailable or uncollectable using conventional research techniques, among other benefits.

Screening Subjects For Viruses and Prions Using LEEM Techniques

[175] As described herein, in some examples, the LEEM techniques may be utilized during the screening of subjects, such as humans, animals, plants, and so on, in order to determine whether a screened subject is infected with or otherwise carrying a virus, viroid, prion or other biological structure, among other things. For example, a screening procedure may include a step of capturing images of biological samples taken from a subject using a LEEM, and determining whether the captured images depicts viruses, viroids, prions or other biological structures. The following environments may include LEEM- based screening procedures:

[176] Medical clinical practice screening, including screening patients and suspects for virus, viroid, or prion infections, (e.g., presence of viruses, viroids, or prions in breath, body fluids such as saliva or blood, on skin, and so on); screening patients and healthy population for immunological response to controlled doses of weakened virions and vaccines, or viruses modified and engineered for virotherapy, gene therapy, or virus-based medical diagnostics; and so on.

[177] Veterinary clinical and field practice screening, including screening pets and farm animals for virus, viroid, or prion infections, (e.g., presence of viruses, viroids, or prions in breath, body fluids such as saliva or blood, on skin, and so on); and so on.

[178] Plant screening, including screening plants at farms, plantations, nurseries, and so on for virus or viroid infections.

[179] Figure 9 is a flow diagram illustrating a method 900 for screening humans for possible virus or prion infections as a precondition for authorizing access to a sensitive, controlled and protected locations utilizing LEEM techniques. In step 910, a biological sample is taken from a subject, such as a human subject requesting access to enter or proceed to a controlled or protected location.

[180] In step 920, the sample is screened using LEEM techniques. For example, a test package may capture one or more images of the received biological sample using a LEEM, and either determine that the captured one or more images do not depict a virus or prion or determine and/or identify a virus or a prion within one or more of the captured images.

[181] In step 930, the method authorizes access to the location based on the screen. For example, the method may grant, allow or permit access to a location when the screen does not identify a virus depicted within the captured images, when the screen does not identify a virus depicted within the captured images above a certainty threshold, does not identify other indicators (e.g., presence of antibodies) within a captured image. Also, the method may deny access to a location when the screen identifies a virus depicted within the captured images, when the screen identifies structures that indicate a possible virus within the captured images, and so on.

[182] The following are example screening environments that may utilize LEEM techniques when determining whether to permit or deny a person access to a location:

[183] Airports and airport terminals, ports, train and bus stations, underground trains, border crossings and other transportation hubs, and so on;

[184] Entry points to large buildings that house government institutions, courts, banks, office and large corporation buildings, hospitals, schools, universities, theaters, sport stadiums, and so on; and

[185] Food production facilities, water purification facilties, and other public spaces; and so on.

[186] Thus, in some examples, LEEM-based techniques may assist in screening humans, animal or plant subjects before they enter a new location, such as crossing country frontiers or disembarking on a ecologically sensitive locality such as islands, which may possibly prevent the transmission of carried viruses from one location to another, among other benefits. [187] In addition, to screening subjects in order to protect locations from possibly contaminated subjects, the LEEM techniques described herein may be used in screening procedures used to certify whether food and other plant products are safe and do not contain certain contaminants, such as viruses or prions. Figure 10 is a flow diagram illustrating a method 1000 for certifying food products utilizing LEEM techniques.

[188] In step 1010, a biological sample is taken from a subject, such as matter from a food product under certification testing. In step 1020, the sample is screened using LEEM techniques. For example, a test package may capture one or more images of the received biological sample using a LEEM, and either determine that the captured one or more images do not depict a virus or a prion, or determine and/or identify a virus or a prion within one or more of the captured images. In step 1030, the method certifies the sample based on the negative outcome of the screening test. For example, the method may certify a food product when the screening does not identify a virus or a prion depicted within the captured images, when the screening does not identify viruses or prions depicted within the captured images above a certainty threshold, and/or does not identify other indicators (e.g., presence of antibodies) within a captured image. Also, the method may fail or otherwise deny certification for a food product when the screening identifies a virus or a prion depicted within the captured images, when the screen identifies structures that indicate a possible virus or a prion within the captured images, and so on.

[189] In some examples, LEEM-based techniques may be utilized in periodic screening of food and food-related products, as a commercial service to food industry, government oversight and control organizations, and so on. Thus, in some examples, LEEM-based techniques may assist in screening food and other products for contaminants, which may prevent illnesses and deaths due to food borne contaminants, among other benefits.

[190] In the experimental disclosure which follows, the following

abbreviations apply: eq (equivalents); M (Molar); μΜ (micromolar); N

(Normal); mol (moles); mmol (millimoles); μιτιοΙ (micromoles); nmol

(nanomoles); g (grams); mg (milligrams); kg (kilograms); g (micrograms); L (liters); ml (milliliters); μΙ (microliters); cm (centimeters); mm (millimeters); μιτι (micrometers); nm (nanometers); ° C. (degrees Centigrade); h (hours); min (minutes); sec (seconds); msec (milliseconds).

EXAMPLES

[191] The present invention is described in further detain in the following examples which are not in any way intended to limit the scope of the invention as claimed. The attached Figures are meant to be considered as integral parts of the specification and description of the invention. All references cited are herein specifically incorporated by reference for all that is described therein. The following examples are offered to illustrate, but not to limit the claimed invention.

Example 1

Preparation of LEEM Su itable Substrates

[192] This example illustrates the development and production of a substrate suitable for LEEM system and methods described herein.

[193] One of the key technical challenges is finding an appropriate substrate (Birrell et ai, Biophys. J. (1994) 67:2041 ; and Peles & Simon, Photochem. Photobiol. 85 (2009) 8). Prior methods have used gold-coated stainless steel plates or 5-mm chromium-coated circular glass microscope cover slips.

Indeed, initial attempts to image viruses were performed on a 5 nm-thick film of gold deposited by electron-beam evaporation on a single-crystal silicon wafer, with or without a 5-nm-thick titanium buffer layer, but with only moderate success. These substrates were not smooth enough and their topography interfered with virus imaging.

[194] Thus, a new class of LEEM substrates, single-crystal transition-metal oxides have proven to perform the best. In particular, bulk single-crystal Sr₀.995Nbo.oo5TiO3 substrates, and thin SrRuO3 films grown on single-crystal SrTiO3 substrates may be chosen since both of them are metallic, chemically inert and can be made atomically smooth.

[195] SrRuO3 thin films are grown by sputtering on single-crystal SrTiO3 substrates polished perpendicular to the (001 ) crystallographic direction, with a typical miscut of -0.1 °. A home-made reactive magnetron RF-sputtering system with two cathodes may be used. A SrRuO3 target (manufactured by Kurt J. Lesker Co.) is mounted on the cathode. Ar and O2 gases are mixed (80% O2 - 20% Ar) outside the chamber using two mass-flow controllers and then circulated through each cathode into the chamber to stabilize a pressure of 30 mTorr. The RF power applied to the cathode is 100 W, resulting in a growth rate of 1 .1 nm/min. The substrate temperature is kept at 650°C. A single crystal of Sr₀.995N bo.oo5TiO3, i.e., SrTiO3 doped with 0.5% Nb in order to achieve metallic conductivity, may be provided by Crystec GmbH.

[196] All the substrates are sequentially cleaned in acetone and isopropyl alcohol for 15 minutes using ultrasonic agitation. SrTiO3 and

Sr₀.995Nbo.oo5TiO3 crystals are etched for 20 s with buffered hydrofluoric acid (HF) to reduce surface roughness and achieve a clean, single-termination (T1O2) surface. All the substrates are studied by atomic force microscopy (AFM) and X-ray diffraction (XRD) before loading them into the LEEM.

[197] The X-ray diffraction measurements are performed using a high- resolution, four-circle Panalytical Xpert Pro Materials research diffractometer. The finite-thickness (Kiessig) fringes evidence that both the film surface and the substrate-film interface are atomically smooth. These fringes also allow one to measure the film thickness. The position of the Bragg peaks indicates that the SrRuO3 film is pseudomorphic with the SrTiO3 monocrystal.

[198] AFM images of the films prove that they are atomically smooth except for occasional one-unit-cell tall steps that largely originate from the

unintentional miscut of the substrate from the desired crystallographic plane perpendicular to the (001 ) direction. The surface rms roughness, with the steps included, is typically in the range of 0.1 - 0.3 nm.

[199] SrRuO3 and Sr₀.995N bo.oo5TiO3 prove to be excellent substrates for LEEM observation of viruses. To the best of our knowledge, complex oxides have so far neither been used as substrates nor studied by LEEM, with the exception of a few reports on metal oxidation (Altman & Bauer, Surface Sci. (1996) 347:265; and Flege & Sutter, J. Phys.: Condens. Matter (2009) 21 :314018). [200] Both substrates are in fact capable of withstanding temperature in excess of 120°C without any obvious damage or change to the surface. In particular, SrRuO₃ showed no changes in the LEED pattern even after heating to ~800°C.

Example 2

Preparation and LEEM Identification of Virus Samples

[201] This example illustrates the preparation and identification the tobacco mosaic virus.

[202] The tobacco mosaic virus (TMV) may be supplied as a solution in 20 mM NHAc and 10 mM MgCI. Depending on the targeted virus density on the substrate, the concentration of TMV in the solution may be varied from 100 g/ml to 250 g/ml. In all cases a droplet is deposited on the surface of the substrate and kept for 25 min. After this time, the sample is set to fast rotation for 4 min. During the first minute the rotation speed of the spinner is gradually increased from 1 ,000 revolutions per minute (rpm) to 5,000 rpm. After the maximum speed is reached, droplets of water are allowed to fall on the spinning sample for the rest of the process. The preparation is finished by keeping the sample under distilled water for 3 h and then drying it under nitrogen gas flow. After this, each sample is measured by atomic force microscopy (AFM) to verify the virus density, and loaded into the LEEM system.

[203] After TMV deposition, all the samples are loaded without any outgassing into the main chamber, and imaged at room temperature. After applying 20 kV bias to the sample, the pressure in the chamber increased to 5x10^"9 Torr due to outgassing of adsorbates from the sample surface.

Generally, no diffraction is observed in this situation since the adsorbed material forms an amorphous layer on the surface that also affects the image. All the samples are then exposed to NO2 or O2 in order to evaluate the reaction of TMV under an oxidizing environment at different temperatures. The pressure of the chamber during these studies is kept in the range between 1 x10^"7 Torr and 5x10^"7 Torr. LEED images are taken subsequently at several electron energies ranging between 10 eV and 100 eV. The total electron gun current used is -0.5 mA, of which about 10% reaches the sample surface.

[204] Using SrRuO3 and Sr₀.995Nbo.oo5^~nO3 substrates, we are able to reproducibly observe and record LEEM images of TMVs, at room temperature and without any surface treatment. Individual TMVs are clearly visible, as are aggregated pairs, triples, and chains up to about 1 mm in length. For the most part, the TMVs and aggregates are parallel to one another; this (partial) orientation is due to centrifugation at 5,000 rpm and is indeed radial. The micrographs are acquired in 1 .6 s and represents an average of 16 frames. The picture is as-recorded; it is neither filtered nor enhanced in any other way.

[205] One skilled in the art will recognize that other viruses may be identified in a similar manner.

Example 3

LEEM Identification of capsids, prions, antibodies, antibody-object interactions, proteins, DNA and/or other biological structures

[206] This example illustrates identification of capsids, prions, antibodies, antibody-object (ligand) interactions, proteins, DNA and/or other biological structures. LEEM may be used to identify capsids, prions, antibodies, antibody-object interactions, proteins, DNA and/or other biological structures within a biological sample or biological material in a manner similar to that described in Example 2, herein.

Example 4

Protein Arrays and LEEM

[207] This example illustrates the use of a protein array to identify of capsids, prions, antibodies, antibody-object interactions, proteins, DNA and/or other biological structures.

[208] A protein microarray (or protein chip) is a high-throughput method used to track the interactions and activities of proteins, and to determine their function, and determining function on a large scale. Its main advantage lies in the fact that large numbers of proteins can be tracked in parallel. The chip consists of a support surface such as a glass slide, nitrocellulose membrane, bead, or microtitre plate, to which an array of proteins is bound. [209] Proteins are arrayed onto a solid surface such as microscope slides, membranes, beads or microtitre plates. The protein array is produced by placing large numbers of proteins or their ligands onto a coated solid support in a pre-defined pattern, usually by a robot. This is known as robotic contact printing or robotic spotting. Another fabrication method is ink-jetting, a drop- on-demand, non-contact method of dispersing the protein polymers onto the solid surface in the desired pattern. However, any method known in the art may be used.

[210] The polypeptides arrayed on the solid surface may be antibodies, antigens, aptamers (nucleic acid-based ligands), affibodies (small molecules engineered to mimic monoclonal antibodies), or full-length proteins. Sources of such proteins include cell-based expression systems for recombinant proteins, purification from natural sources, production in vitro by cell-free translation systems, and synthetic methods for peptides. Care to avoid conditions of synthesis or extraction must be taken as protein denaturation may render the array useless.

[211] Once the proteins are arrayed probe molecules with or without a label, e.g., gold, are added to the array. Any reaction/interaction between the probe and the immobilized protein may be imaged, detected, recognized and/or identified by LEEM. Information may also be collected in real-time, e.g., the arrayed protein-probe interaction may be observed in real-time.

[212] It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims. All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety for all purposes. CITATION LIST

Non-Patent Literature

[213] Pereiro et ai, J. Nanosci. Lett. (2012) 2:29

[214] De Stasio et al., Phys. Scr. (1995) 51 :41 1

[215] Griffith et al., J. Microsc. (1992) 168:249

[216] Birrell et al., Biophys. J. (1994) 67:2041 .

[217] Peles & Simon, Photochem. Photobiol. 85 (2009) 8.

[218] Altman & Bauer, Surface Sci. (1996) 347:265.

[219] Flege & Sutter, J. Phys.: Condens. Matter (2009) 21 :314018.

Claims

CLAIMS We claim:

1 . A system for identifying antibodies within an examined sample, the system comprising:

a low energy electron microscope (LEEM); and

an antibody identification device, wherein the antibody identification device is configured to identify that an image taken by the LEEM includes an image of an antibody

2. The system of claim 1 , wherein the antibody identification device includes:

an image comparison component, wherein the image comparison component is configured to match a size of contents of the image taken by the LEEM with a size of contents of one or more images associated with a known antibody.

3. The system of claim 1 , wherein the antibody identification device includes:

an image comparison component, wherein the image comparison component is configured to match a shape of contents of the image taken by the LEEM with a shape of contents of one or more images associated with a known antibody.

4. The system of claim 1 , wherein the antibody identification device includes:

an image comparison component, wherein the image comparison component is configured to match a size and shape of contents of the image taken by the LEEM with a size and shape of contents of one or more images associated with a known antibody.

5. The system of claim 1 , wherein the antibody identification device includes:

an image comparison component, wherein the image comparison component is configured to match a size and shape of contents of the two or more images taken by the LEEM with a size and shape of contents of two or more images associated with a known antibody.

6. The system of claim 1 , wherein the antibody identification device includes:

an image comparison component, wherein the image comparison component is configured to match an average size and shape of contents of two or more images taken by the LEEM with a size and shape of a known antibody.

7. The system of claim 1 , wherein the antibody identification device includes:

an image comparison component, wherein the image comparison component is configured to match information associated with a size and shape of contents of the image taken by the LEEM with information associated with a size and shape attributed to a known antibody.

8. The system of claim 1 , wherein the antibody identification device includes:

an image comparison component, wherein the image comparison component is configured to extract information associated with morphological information of a subject of the image taken by the LEEM with morphological information associated with an antibody.

9. A method for detecting an antibody within a biological sample, the method comprising:

taking an image of a biological sample using a low energy electron microscope;

identifying within the image an object that has a size or shape

indicative of a known antibody.

10. The method of claim 9, wherein identifying within the image an object that has a size or shape indicative of a known antibody includes matching the image to one or more images associated with known antibodies.

1 1 . The method of claim 9, wherein identifying within the image an object that has a size or shape indicative of a known antibody includes: extracting a size of the object within the image;

querying an index of morphological information associated with known antibodies for the extracted size of the object within the image; and identifying the object within the image is a known antibody based on the query.

12. The method of claim 9, wherein identifying within the image an object that has a size or shape indicative of a known antibody includes:

extracting a shape of the object within the image;

querying an index of morphological information associated with known antibodies for the extracted shape of the object within the image; and

identifying the object within the image is a known antibody based on the query.

13. The method of claim 9, wherein identifying within the image an object that has a size or shape indicative of a known antibody includes:

extracting a size and shape of the object within the image;

querying an index of morphological information associated with known antibodies for the extracted size and shape of the object within the image; and

identifying the object within the image is a known antibody based on the query.

14. A system for identifying an antibody within a biological sample, the device comprising:

an imaging device, wherein the imaging device is configured to take multiple low energy electron microscopy (LEEM) images of a biological sample;

an identification device, wherein the identification device is configured to identify within one or more of the multiple LEEM images an object having a size or shape similar to a size or shape of a known antibody.

15. The system of claim 14, wherein the identification device includes: an imaging component, wherein the imaging component is configured to extract the size of shape of the object within the one or more LEEM images;

a query component, wherein the query component is configured to

query an index of information that associates known antibodies with morphological information associated with the known antibodies; and

an identification component, wherein the identification component is configured to identify that the object represents a known antibody based on a result of the query.

16. A system for taking images of antibodies, the system comprising:

a low energy electron microscope; and

a conductive substrate containing a biological sample that is adapted to be placed in a vacuum environment of the low energy electron microscope.

17. The system of claim 16, wherein the low energy electron microscope includes components configured to operate in reflection geometry in order to take an image of the biological sample.

18. The system of claim 16, wherein the low energy electron microscope includes components configured to operate in reflection geometry with respect to the biological sample in order to take an image of the biological sample.

19. The system of claim 16, wherein the low energy electron microscope includes components configured to perform photoemission electron

microscopy with respect to the biological sample in order to take an image of the biological sample.

20. The system of claim 16, wherein the low energy electron microscope includes components configured to perform low energy electron diffraction from a biological sample.

21 . A method for imaging an antibody, the method comprising:

preparing a conductive substrate with a biological sample that includes an antibody to be imaged; placing the prepared substrate within a sample chamber of a low energy electron microscope (LEEM); and

imaging the biological sample in reflection geometry to generate an image of contents of the biological sample within a lens component of the LEEM.

22. A system for taking images of antibodies, the system comprising:

an imaging device that includes components configured to take an

image of an antibody within a biological sample using low energy electron microscopy; and

a recording device configured to generate a video from taken images of the antibody within the biological sample.

23. The system of claim 22, further comprising:

a sample chamber within the imaging device, wherein the sample

chamber is adapted to maintain a biological sample within a vacuum.

24. The system of claim 22, wherein the imaging device includes components configured to take the image of the antibodies within the biological sample using reflection geometry.

25. The system of claim 22, wherein the imaging device includes components configured to take the image of the antibody within the biological sample using low energy electron diffraction.

26. The system of claim 22, wherein the imaging device includes components configured to take the image of the antibody within the biological sample using photoemission electron microscopy.

27. One or more tangible computer memories collectively containing a data structure, the data structure including multiple entries each associated with a known antibody, wherein each of the entries includes morphological information extracted from a low energy electron microscope (LEEM) image of the known antibody

28. The computer memories of claim 27, wherein the morphological information extracted from the low energy electron microscope (LEEM) image of the known antibody includes information associated with a size of an antibody imaged by a low energy electron microscope.

29. The computer memories of claim 27, wherein the morphological information extracted from the low energy electron microscope (LEEM) image of the known antibody includes information associated with a shape of an antibody imaged by a low energy electron microscope.

30. The computer memories of claim 27, wherein the morphological information extracted from the low energy electron microscope (LEEM) image of the known antibody includes information associated with a size of an antibody imaged by a low energy electron microscope and with a shape of the antibody imaged by the low energy electron microscope.

31 . The computer memories of claim 27, wherein each of the entries associated with the known antibody include information associated with operation characteristics of a low energy electron microscope that generated LEEM images of the known antibody.

32. A system for modifying a database of low energy electron microscope (LEEM) images of an antibody, the system comprising:

an image component, wherein the image component is configured to receive an image of the antibody taken by a LEEM;

an information extraction component, wherein the information

extraction component is configured to extract information from the received LEEM image of the antibody;

a comparison component, wherein the comparison component is

configured to compare the extracted information to an index of information associated with known antibodies; and

a database component, wherein the database component is configured to update a database of entries associating antibodies with LEEM images of the antibodies based on results of the comparison performed by the comparison component.

33. The system of claim 32, wherein the extracted information is size information associated with the images of the antibody; and wherein the comparison component is configured to compare the size information with an index of size information associated with known antibodies.

34. The system of claim 32, wherein the extracted information is shape information associated with the images of the antibody; and

wherein the comparison component is configured to compare the

shape information with an index of shape information associated with known antibodies.

35. The system of claim 32, wherein the extracted information is size and shape information associated with the images of the antibody; and

wherein the comparison component is configured to compare the size and shape information with an index of size and shape information associated with known antibodies.

36. The system of claim 32, wherein the extracted information is an image of the antibody; and

wherein the comparison component is configured to compare the

image with an index of images associated with known antibodies using a content based image retrieval engine.

37. A method of assigning metadata to an image taken by a low energy electron microscope (LEEM), the method comprising:

receiving information indicating a LEEM image includes contents

representing a known antibody; and

assigning metadata to the LEEM image that includes information

associated with the known antibody represented by the contents of the LEEM image.

38. The method of claim 37, wherein assigning metadata to the LEEM image that includes information associated with the known antibody represented by the contents of the LEEM image includes assigning metadata that includes morphological information for the known antibody.

39. The method of claim 37, wherein assigning metadata to the LEEM image that includes information associated with the known antibody represented by the contents of the LEEM image includes assigning metadata that includes size information for the known antibody.

40. The method of claim 37, wherein assigning metadata to the LEEM image that includes information associated with the known antibody represented by the contents of the LEEM image includes assigning metadata that includes shape information for the known antibody.

41 . The method of claim 37, wherein assigning metadata to the LEEM image that includes information associated with the known antibody represented by the contents of the LEEM image includes assigning metadata that includes structure information for the known antibody.

42. A system for observing an antibody-object interaction within an examined sample, the system comprising:

a low energy electron microscope (LEEM); and

an observation device, wherein the observation device is configured to take multiple images of an interaction between an antibody and a foreign object.

43. The system of claim 42, wherein the observation device is configured to take multiple images of an interaction between an antibody and a virus.

44. The system of claim 42, wherein the observation device is configured to take multiple images of an interaction between antibodies and bacteria.

45. The system of claim 42, wherein the observation device is configured to take multiple images of an interaction between an antibody and a microbe.

46. The system of claim 42, further comprising:

an identification device, wherein the identification device is configured to identify a specific antibody within the multiple images.

47. The system of claim 42, further comprising:

an identification device, wherein the identification device is configured to identify a specific type of antibody within the multiple images.

48. The system of claim 42, further comprising: an identification device, wherein the identification device is configured to identify within the multiple images a binding location between the antibody and the foreign object.

49. The system of claim 42, further comprising:

an identification device, wherein the identification device is configured to identify within the multiple images a paratope of the antibody that binds to the foreign object.

50. A method for detecting an interaction between an antibody and a microbe within a biological sample, the method comprising:

taking an image of a biological sample using a low energy electron microscope;

identifying within the image a first object that has a size or shape

indicative of an antibody and a second object that has a size or shape indicative of a microbe.

51 . The method of claim 50, wherein identifying within the image a first object that has a size or shape indicative of the antibody includes matching the image to one or more images associated with antibodies

52. The method of claim 50, wherein identifying within the image a first object that has a size or shape indicative of an antibody includes:

extracting a size of the first object within the image;

querying an index of morphological information associated with known antibodies for the extracted size of the first object within the image; and

identifying the first object within the image as a specific antibody based on the query.

53. The method of claim 50, wherein identifying within the image a first object that has a size or shape indicative of an antibody includes:

extracting a shape of the first object within the image;

querying an index of morphological information associated with known antibodies for the extracted shape of the first object within the image; and identifying the first object within the image as a specific antibody based on the query.

54. The method of claim 50, wherein identifying within the image a first object that has a size or shape indicative of an antibody includes:

extracting a size and shape of the first object within the image;

querying an index of morphological information associated with known antibodies for the extracted size and shape of the first object within the image; and

55. A system for confirming an antibody-object interaction within a biological sample, the device comprising:

an identification device, wherein the identification device is configured to identify within one or more of the multiple LEEM images an object having size or shape similar to a size or shape of an antibody attached to a microbe.

56. The system of claim 55, wherein the identification device includes: an imaging component, wherein the imaging component is configured to extract the size of shape of the object within the one or more LEEM images;

a query component, wherein the query component is configured to

query an index of information that associates known antibody-object interactions with morphological information associated with the known antibody-object interactions; and

an identification component, wherein the identification component is configured to identify that the object represents a specific antibody- object interaction based on a result of the query.

57. The system of claim 55, wherein the identification device includes: an imaging component, wherein the imaging component is configured to extract the size of shape of the object within the one or more LEEM images;

a query component, wherein the query component is configured to

an identification component, wherein the identification component is configured to identify that the object represents an antibody bound to a virus based on a result of the query.

58. The system of claim 55, wherein the identification device includes: an imaging component, wherein the imaging component is configured to extract the size of shape of the object within the one or more LEEM images;

a query component, wherein the query component is configured to

an identification component, wherein the identification component is configured to identify that the object represents an antibody bound to a bacterium based on a result of the query.

59. A computing system for identifying antibodies within images taken by a low energy electron microscope (LEEM), the system comprising:

an antibody identification component, wherein the antibody

identification component is configured to determine that an object within contents of a LEEM image is a depiction of an antibody.

60. The system of claim 59, wherein the antibody identification component includes:

an image comparison component, wherein the image comparison

component is configured to match a size of contents of the LEEM image with a size of contents of one or more images associated with a known antibody.

61 . The system of claim 59, wherein the antibody identification component includes:

an image comparison component, wherein the image comparison

component is configured to match a shape of contents of the LEEM image with a shape of contents of one or more images associated with a known antibody.

62. The system of claim 59, wherein the antibody identification component includes:

an image comparison component, wherein the image comparison

component is configured to match a size and shape of contents of the LEEM image with a size and shape of contents of one or more images associated with a known antibody.

63. The system of claim 59, wherein the antibody identification component includes:

an image comparison component, wherein the image comparison

component is configured to extract morphological information from the contents of the LEEM image and compare the extracted information with morphological information associated with known antibodies.

64. A tangible computer-readable medium whose contents, when executed by a computing device, cause the computing device to perform a method for detecting an antibody within a biological sample, the method comprising: taking an image of a biological sample using a low energy electron microscope;

identifying within the image an object that has a size or shape

indicative of a known antibody.

65. The computer-readable medium of claim 64, wherein identifying within the image an object that has a size or shape indicative of a known antibody includes matching the image to one or more images associated with known antibodies.

66. The computer-readable medium of claim 64, wherein identifying within the image an object that has a size or shape indicative of a known antibody includes:

extracting a size of the object within the image;

67. The computer-readable medium of claim 64, wherein identifying within the image an object that has a size or shape indicative of a known antibody includes:

extracting a shape of the object within the image;

identifying the object within the image is a known antibody based on the query.

68. The computer-readable medium of claim 64, wherein identifying within the image an object that has a size or shape indicative of a known antibody includes:

extracting a size and shape of the object within the image;

identifying the object within the image is a known antibody based on the query.

69. A system for identifying an antibody within a low energy electron microscope (LEEM) image of a biological sample, the device comprising: an imaging component, wherein the imaging component is configured to determine a size or shape of an object within the LEEM images; a query component, wherein the query component is configured to query an index of information that associates known antibodies with morphological information associated with the known antibodies using a query term associated with the determined size and shape of the object with the LEEM images; and

an identification component, wherein the identification component is configured to identify the object as an antibody based on a positive result of the query.

70. The system of claim 69, wherein the identification component is configured to determine that the determined size and shape of the object within the LEEM images is similar to a size and shape of a known antibody.

71 . The system of claim 69, wherein the identification component is configured to determine that the determined size and shape of the object within the LEEM images is similar to a size and shape of a known category of antibodies.

72. The system of claim 69, wherein the identification component is configured to determine that the determined size and shape of the object within the LEEM images is similar to a size and shape of a typical antibody.

73. A method for observing an antibody-virus interaction, the method comprising:

preparing a sample that includes one or more viruses of a certain type; exposing the sample to one or more antibodies; and

imaging the exposed sample using a low energy electron microscope.

74. The method of claim 73, further comprising:

identifying within the imaged sample a certain antibody based on

determining that a shape of a biological structure within the imaged sample matches a shape of a known antibody; and

determining within the imaged sample that the identified antibody is attached to one or more viruses of the sample

75. The method of claim 73, further comprising:

identifying within the imaged sample a certain antibody based on

determining that a shape of a biological structure within the imaged sample matches a shape of a known antibody.

76. The method of claim 73, further comprising:

identifying within the imaged sample a certain antibody based on

determining that a shape of a biological structure within the imaged sample is a monomer shape.

77. The method of claim 73, further comprising:

identifying within the imaged sample a certain antibody based on

determining that a shape of a biological structure within the imaged sample is a dimer shape.

78. The method of claim 73, further comprising:

identifying within the imaged sample a certain antibody based on

determining that a shape of a biological structure within the imaged sample is a pentamer shape.

79. A method of determining whether an antibody is attached to a virus within a biological sample, the method comprising:

taking images of the biological sample using a low energy electron microscope; and

determining, from contents of the images, whether the biological sample includes an attachment point between a virus and an antibody.

80. The method of claim 79, wherein determining whether the biological sample includes an attachment point between a virus and an antibody includes performing an image matching technique to the images of the biological sample.

81 . A system for observing an antibody-virus interaction, the system comprising:

a low energy electron microscope that includes a sample chamber configured to contain a substrate having a sample that includes viruses and antibodies; and

a computing device configured to identify an antibody-virus interaction within images observed by the low energy electron microscope.

82. A method for determining a type of antibody that attaches to a virus, the method comprising: preparing multiple substrates, each containing a sample having a similar virus to one another;

preparing multiple containers, each containing a different antibody; exposing each of the multiple substrates to a single container of an antibody;

taking one or more low energy electron microscope images of the

exposed substrates; and

determining, based on contents of the images, which antibody

contained by the multiple containers is attached to the virus contained by the multiple substrates.

83. The method of claim 82, wherein determining which antibody contained by the multiple containers is attached to the virus contained by the multiple substrates includes identifying an attachment point between the antibody and the virus.

84. A method for determining that a certain antibody is attached to a virus within a biological sample, the method comprising:

preparing two or more substrates, each including a same known virus; exposing each of the two or more substrates to a different known

antibody; and

identifying, using a LEEM, the exposed substrate that includes an

antibody-virus interaction.

85. The method of claim 84, wherein identifying the exposed substrate that includes an antibody-virus interaction includes:

taking one or more images of the exposed substrates; and

matching at least a portion of contents of the images to an image of an antibody-virus interaction.

86. A method for identifying a virus, the method comprising:

preparing multiple substrates, each containing a sample having a

similar virus to one another;

preparing multiple containers, each containing a different antibody; exposing each of the multiple substrates to a single container of an antibody; taking one or more low energy electron microscope images of the exposed substrates;

determining, based on contents of the images, which antibody

contained by the multiple containers is attached to the virus contained by the multiple substrates; and

identifying the similar virus based on the determined antibody is

attached to the virus.

87. The method of claim 86, wherein determining which antibody contained by the multiple containers is attached to the virus contained by the multiple substrates includes identifying an attachment point between the antibody and the virus.

88. A method for identifying a virus within a biological sample, the method comprising:

preparing two or more substrates, each including a same unknown virus;

exposing each of the two or more substrates to a different known

antibody;

determining, using a LEEM, the exposed substrate that includes an antibody-virus interaction; and

identifying the unknown virus based on determining the exposed

substrate that includes the antibody-virus interaction.

89. The method of claim 88, wherein determining the exposed substrate that includes an antibody-virus interaction includes:

taking one or more images of the exposed substrates; and

90. A system for observing a real-time interaction of a virus and an antibody, the system comprising:

a low energy electron microscope that includes a sample chamber; a gas container coupled to the sample chamber; and

a computing device that performs actions associated with images taken by the low energy electron microscope.

91 . The system of claim 90, wherein the sample chamber is configured to house a substrate that contains a virus sample, and wherein the gas container is configured to contain a gas that includes antibodies.

92. The system of claim 90, wherein the sample chamber is configured to house a substrate that contains a virus sample, and wherein the gas container is configured to contain a gas that includes antibodies; and

wherein the gas container is coupled to the sample chamber such that the substrate is exposed to the gas that includes antibodies during operation of the low energy electron microscope.

93. A system for identifying an antibody that attaches to a virus, the system comprising:

a low energy electron microscope having a sample chamber, wherein the sample chamber contains a substrate that includes a virus sample;

a first gas container coupled to the sample chamber, wherein the first gas chamber contains a first gas that includes a first antibody;

a second gas container coupled to the sample chamber, wherein the second gas chamber contains a second gas that includes a second antibody; and

94. A method for identifying an antibody that attaches to a virus, the method comprising:

placing a substrate that includes a virus sample into a sample chamber of a low energy electron microscope;

exposing the virus sample to a first antibody from a first gas container coupled to the sample chamber;

exposing the virus sample to a second antibody from a second gas container coupled to the sample chamber; and

determining whether the first antibody or the second antibody attaches to a virus within the exposed virus sample based on observing images taken by the low energy electron microscope.

95. A method of experimentation, the method comprising:

collecting information (such as imaging, recognition, identification, etc.) associated with viruses or capsids using a low energy electron microscopy technique.

96. The method of claim 95, wherein the low energy electron microscopy technique includes capturing one or more images of viruses or capsids using a low energy electron microscope.

97. The method of claim 95, further comprising:

performing an experiment-related action using the collected

information.

98. The method of claim 95, further comprising:

storing the collected information in a database associated with an

experiment.

99. The method of claim 95, further comprising:

performing an experimental task using the collected information.

100. The method of claim 95, further comprising:

performing a diagnosis using the collected information.

101 . The method of claim 95, further comprising:

causing interactions between viruses or capsids and an experimental agent; and

collecting information associated with the interaction using the low

energy electron microscopy technique.

102. The method of claim 95, further comprising:

causing interactions between viruses or capsids and a biological agent; and

collecting information associated with the interaction using the low

energy electron microscopy technique.

103. The method of claim 95, further comprising:

causing interactions between viruses or capsids and a chemical agent (such as reactive gasses of various atoms, molecules, ions, etc.); and collecting infornnation associated with the interaction using the low energy electron microscopy technique.

104. The method of claim 95, further comprising:

causing interactions between viruses or capsids and a physical agent (such as temperature, illumination by light from microwaves to gamma rays, irradiation by electrons, ions, etc.); and

collecting information associated with the interaction using the low

energy electron microscopy technique.

105. The method of claim 95, wherein the information associated with viruses or capsids includes information associated with identification of a virus or a capsid.

106. The method of claim 95, wherein the information associated with viruses includes information associated with captured images of an interaction between a virus and an experimental agent.

107. The method of claim 95, wherein the information associated with capsids includes information associated with captured images of an

interaction between a capsid and an experimental agent.

108. A method of experimentation, the method comprising:

collecting information associated with viruses using a low energy

electron microscope;

causing the viruses to interact with an experimental agent; and collecting information associated with the viruses after interactions

between the viruses and the experimental agents using the low energy electron microscope.

109. The method of claim 108, wherein causing the viruses to interact with an experimental agent includes causing the viruses to interact with a biological agent.

1 10. The method of claim 108, wherein causing the viruses to interact with an experimental agent includes causing the viruses to interact with a chemical agent.

1 1 1 . The method of claim 108, wherein causing the viruses to interact with an experimental agent includes causing the viruses to interact with a physical agent.

1 12. The method of claim 108, wherein the collected information associated with viruses includes one or more low energy electron microscope images of the viruses, and wherein the collected information associated with the viruses after interactions between the viruses and the experimental agents includes one or more low energy electron microscope images of the viruses after interactions between the viruses and the experimental agents.

1 13. A method of experimentation, the method comprising:

collecting information associated with capsids using a low energy

electron microscope;

causing the capsids to interact with an experimental agent; and collecting information associated with the capsids after interactions between the capsids and the experimental agents using the low energy electron microscope.

1 14. The method of claim 113, wherein causing the capsids to interact with an experimental agent includes causing the capsids to interact with a biological agent.

1 15. The method of claim 113, wherein causing the capsids to interact with an experimental agent includes causing the capsids to interact with a chemical agent.

1 16. The method of claim 113, wherein causing the capsids to interact with an experimental agent includes causing the capsids to interact with a physical agent.

1 17. The method of claim 113, wherein the collected information associated with capsids includes one or more low energy electron microscope images of the capsids, and wherein the collected information associated with the capsids after interactions between the capsids and the experimental agents includes one or more low energy electron microscope images of the capsids after collecting information associated with the capsids after interactions between the capsids and the experimental agents using the low energy electron microscope.

1 18. A method of experimentation, the method comprising:

collecting information (such as imaging, recognition, identification, etc.) associated with antibodies using a low energy electron microscopy technique.

1 19. The method of claim 118, wherein the low energy electron microscopy technique includes capturing one or more images of antibodies using a low energy electron microscope.

120. The method of claim 118, further comprising:

performing an experiment-related action using the collected

information.

121 . The method of claim 118, further comprising:

storing the collected information in a database associated with an

experiment.

122. The method of claim 118, further comprising:

performing an experimental task using the collected information.

123. The method of claim 118, further comprising:

performing a diagnosis using the collected information.

124. The method of claim 118, further comprising:

causing interactions between antibodies and an experimental agent; and

collecting information associated with the interaction using the low

energy electron microscopy technique.

125. The method of claim 118, further comprising:

causing interactions between antibodies and a biological agent; and collecting information associated with the interaction using the low

energy electron microscopy technique.

126. The method of claim 118, further comprising:

causing interactions between antibodies and a chemical agent (such as reactive gasses of various atoms, molecules, ions, etc.); and collecting information associated with the interaction using the low energy electron microscopy technique.

127. The method of claim 118, further comprising:

causing interactions between antibodies and a physical agent (such as temperature, illumination by light from microwaves to gamma rays, irradiation by electrons, ions, etc.); and

collecting information associated with the interaction using the low energy electron microscopy technique.

128. The method of claim 118, wherein the information associated with antibodies includes information associated with identification of antibodies.

129. The method of claim 118, wherein the information associated with antibodies includes information associated with captured images of an interaction between an antibody and an experimental agent.

130. The method of claim 118, wherein the information associated with antibodies includes information associated with captured images of an interaction between an antibody and an experimental agent.

131 . A method of experimentation, the method comprising:

collecting information associated with antibodies using a low energy electron microscope;

causing the antibodies to interact with an experimental agent; and collecting information associated with the antibodies after interactions between the antibodies and the experimental agents using the low energy electron microscope.

132. The method of claim 131 , wherein causing the antibodies to interact with an experimental agent includes causing the antibodies to interact with a biological agent.

133. The method of claim 131 , wherein causing the antibodies to interact with an experimental agent includes causing the antibodies to interact with a chemical agent.

134. The method of claim 131 , wherein causing the antibodies to interact with an experimental agent includes causing the antibodies to interact with a physical agent.

135. The method of claim 131 , wherein the collected information associated with antibodies includes one or more low energy electron microscope images of the antibodies, and wherein the collected information associated with the antibodies after interactions between the antibodies and the experimental agents includes one or more low energy electron microscope images of the antibodies after interactions between the antibodies and the experimental agents.

136. A method of experimentation, the method comprising:

collecting information (such as imaging, recognition, identification, etc.) associated with prions using a low energy electron microscopy technique.

137. The method of claim 136, wherein the low energy electron microscopy technique includes capturing one or more images of prions using a low energy electron microscope.

138. The method of claim 136, further comprising:

performing an experiment-related action using the collected

information.

139. The method of claim 136, further comprising:

storing the collected information in a database associated with an

experiment.

140. The method of claim 136, further comprising:

performing an experimental task using the collected information.

141 . The method of claim 136, further comprising:

performing a diagnosis using the collected information.

142. The method of claim 136, further comprising:

causing interactions between prions and an experimental agent; and collecting information associated with the interaction using the low

energy electron microscopy technique.

143. The method of claim 136, further comprising:

causing interactions between prions and a biological agent; and collecting information associated with the interaction using the low energy electron microscopy technique.

144. The method of claim 136, further comprising:

causing interactions between prions and a chemical agent (such as reactive gasses of various atoms, molecules, ions, etc.); and collecting information associated with the interaction using the low energy electron microscopy technique.

145. The method of claim 136, further comprising:

causing interactions between prions and a physical agent (such as temperature, illumination by light from microwaves to gamma rays, irradiation by electrons, ions, etc.); and

146. The method of claim 136, wherein the information associated with prions includes information associated with identification of prions.

147. The method of claim 136, wherein the information associated with prions includes information associated with captured images of an interaction between a prion and an experimental agent.

148. The method of claim 136, wherein the information associated with prions includes information associated with captured images of an interaction between a prion and an experimental agent.

149. A method of experimentation, the method comprising:

collecting information associated with prions using a low energy

electron microscope;

causing the prions to interact with an experimental agent; and collecting information associated with the prions after interactions between the prions and the experimental agents using the low energy electron microscope.

150. The method of claim 149, wherein causing the prions to interact with an experimental agent includes causing the prions to interact with a biological agent.

151 . The method of claim 149, wherein causing the prions to interact with an experimental agent includes causing the prions to interact with a chemical agent.

152. The method of claim 149, wherein causing the prions to interact with an experimental agent includes causing the prions to interact with a physical agent.

153. The method of claim 149, wherein the collected information associated with prions includes one or more low energy electron microscope images of the prions, and wherein the collected information associated with the prions after interactions between the prions and the experimental agents includes one or more low energy electron microscope images of the prions after interactions between the prions and the experimental agents.

154. A method of experimentation, the method comprising:

collecting information (such as imaging, recognition, identification, etc.) associated with proteins or DNA using a low energy electron microscopy technique.

155. The method of claim 154, wherein the low energy electron microscopy technique includes capturing one or more images of proteins or DNA using a low energy electron microscope.

156. The method of claim 154, further comprising:

performing an experiment-related action using the collected

information.

157. The method of claim 154, further comprising:

storing the collected information in a database associated with an experiment.

158. The method of claim 154, further comprising:

performing an experimental task using the collected information.

159. The method of claim 154, further comprising:

performing a diagnosis using the collected information.

160. The method of claim 154, further comprising:

causing interactions between proteins or DNA and an experimental agent; and

161 . The method of claim 154, further comprising:

causing interactions between proteins or DNA and a biological agent; and

162. The method of claim 154, further comprising:

causing interactions between proteins or DNA and a chemical agent (such as reactive gasses of various atoms, molecules, ions, etc.); and

163. The method of claim 154, further comprising:

causing interactions between protein or DNA and a physical agent (such as temperature, illumination by light from microwaves to gamma rays, irradiation by electrons, ions, etc.); and

164. The method of claim 154, wherein the information associated with proteins or DNA includes information associated with identification of proteins or DNA.

165. The method of claim 154, wherein the information associated with proteins includes information associated with captured images of an interaction between a protein and an experimental agent.

166. The method of claim 154, wherein the information associated with DNA includes information associated with captured images of an interaction between a DNA and an experimental agent.

167. A method of experimentation, the method comprising:

collecting information associated with proteins using a low energy

electron microscope;

causing the proteins to interact with an experimental agent; and collecting information associated with the proteins after interactions between the proteins and the experimental agents using the low energy electron microscope.

168. The method of claim 167, wherein causing the proteins to interact with an experimental agent includes causing the proteins to interact with a biological agent.

169. The method of claim 167, wherein causing the proteins to interact with an experimental agent includes causing the proteins to interact with a chemical agent.

170. The method of claim 167, wherein causing the proteins to interact with an experimental agent includes causing the proteins to interact with a physical agent.

171 . The method of claim 167, wherein the collected information associated with proteins includes one or more low energy electron microscope images of the proteins, and wherein the collected information associated with the proteins after interactions between the proteins and the experimental agents includes one or more low energy electron microscope images of the proteins after interactions between the proteins and the experimental agents.

172. A method of experimentation, the method comprising:

collecting information associated with DNA using a low energy electron microscope;

causing the DNA to interact with an experimental agent; and

collecting information associated with the DNA after interactions

between the DNA and the experimental agents using the low energy electron microscope.

173. The method of claim 172, wherein causing the DNA to interact with an experimental agent includes causing the DNA to interact with a biological agent.

174. The method of claim 172, wherein causing the DNA to interact with an experimental agent includes causing the DNA to interact with a chemical agent.

175. The method of claim 172, wherein causing the DNA to interact with an experimental agent includes causing the DNA to interact with a physical agent.

176. The method of claim 172, wherein the collected information associated with DNA includes one or more low energy electron microscope images of the DNA, and wherein the collected information associated with the DNA after interactions between the DNA and the experimental agents includes one or more low energy electron microscope images of the DNA after collecting information associated with the DNA after interactions between the DNA and the experimental agents using the low energy electron microscope.

177. A method of experimentation, the method comprising:

collecting information (such as imaging, recognition, identification, etc.) associated with interaction of antibodies with viruses, capsids, prions, proteins, or DNA using a low energy electron microscopy technique.

178. The method of claim 177, wherein the low energy electron microscopy technique includes capturing one or more images of antibodies interacting with viruses, capsids, prions, proteins, or DNA using a low energy electron microscope.

179. The method of claim 177, further comprising:

performing an experiment-related action using the collected

information.

180. The method of claim 177, further comprising:

storing the collected information in a database associated with an

experiment.

181 . The method of claim 177, further comprising:

performing an experimental task using the collected information.

182. The method of claim 177, further comprising: performing a diagnosis using the collected information.

183. A method of experimentation, the method comprising:

Observing in real time or ex post facto a virus-antibody interaction using a low energy electron microscope.

184. The method of claim 183, wherein observing a virus-antibody interaction using a low energy electron microscope includes taking one or more images of the virus-antibody interaction using the low energy electron microscope.

185. A method of experimentation, the method comprising:

Observing in real time or ex post facto a capsid-antibody interaction using a low energy electron microscope.

186. The method of claim 185, wherein observing a capsid-antibody interaction using a low energy electron microscope includes taking one or more images of the capsid-antibody interaction using the low energy electron microscope.

187. A method of experimentation, the method comprising:

Observing in real time or ex post facto a prion-antibody interaction using a low energy electron microscope.

188. The method of claim 187, wherein observing a prion-antibody interaction using a low energy electron microscope includes taking one or more images of the prion -antibody interaction using the low energy electron microscope.

189. A method of experimentation, the method comprising:

Observing in real time or ex post facto a protein-antibody interaction using a low energy electron microscope.

190. The method of claim 189, wherein observing a protein-antibody interaction using a low energy electron microscope includes taking one or more images of the protein-antibody interaction using the low energy electron microscope.

191 . A method of experimentation, the method comprising: Observing in real time or ex post facto a DNA-antibody interaction using a low energy electron microscope.

192. The method of claim 177 or 191 , wherein observing a DNA-antibody interaction using a low energy electron microscope includes taking one or more images of the DNA-antibody interaction using the low energy electron microscope.

193. The method of claim 177 or 191 , further comprising:

exposing complexes of antibodies interacting with viruses, capsids, prions, proteins or DNA to an experimental agent; and

194. The method of claim 177 or 191 , further comprising:

exposing complexes of antibodies interacting with viruses, capsids, prions, proteins or DNA to a biological agent; and

195. The method of claim 177 or 191 , further comprising:

exposing complexes of antibodies interacting with viruses, capsids, prions, proteins or DNA to a chemical agent (such as reactive gasses of various atoms, molecules, ions, etc.); and

196. The method of claim 177 or 191 , further comprising:

exposing complexes of antibodies interacting with viruses, capsids, prions, proteins or DNA to a physical agent (such as temperature, illumination by light from microwaves to gamma rays, irradiation by electrons, ions, etc.); and

197. The method of claim 177 or 191 , wherein the information associated with viruses, capsids, prions or antibodies includes information associated with identification of a virus-antibody or capsid-antibody or prion-antibody or protein-antibody or DNA-antibody interactions.

198. The method of claim 177 or 191 , wherein the information associated with complexes of antibodies interacting with viruses, capsids, prions, proteins or DNA includes information associated with captured images of an

interaction between a complex of antibodies interacting with viruses, capsids, prions, proteins or DNA and an experimental agent.

199. The method of claim 177 or 191 , wherein the information includes captured images of an interaction between a virus-antibody complex and an experimental agent.

200. The method of claim 177 or 191 , wherein the information includes captured images of an interaction between a capsid-antibody complex and an experimental agent.

201 . The method of claim 177 or 191 , wherein the information includes captured images of an interaction between a prion-antibody complex and an experimental agent.

202. The method of claim 177 or 191 , wherein the information includes captured images of an interaction between a protein-antibody complex and an experimental agent.

203. The method of claim 177 or 191 , wherein the information includes captured images of an interaction between a DNA-antibody complex and an experimental agent.

204. The method of claim 177 or 191 , wherein exposing complexes of antibodies interacting with viruses, capsids, prions, proteins or DNA to an experimental agent includes exposing complexes of antibodies interacting with viruses, capsids, prions, proteins or DNA to a biological agent.

205. The method of claim 177 or 191 , wherein exposing complexes of antibodies interacting with viruses, capsids, prions, proteins or DNA to an experimental agent includes exposing complexes of antibodies interacting with viruses, capsids, prions, proteins or DNA to interact to a chemical agent such as a gas of atoms, ions, or molecules.

206. The method of claim 177 or 191 , wherein exposing complexes of antibodies interacting with viruses, capsids, prions, proteins or DNA to an experimental agent includes exposing complexes of antibodies interacting with viruses, capsids, prions, proteins or DNA to a physical agent such as elevated temperature, illumination by electromagnetic radiation from microwave to visible light to UV to X-rays, irradiations by electrons, etc.

207. A method of experimentation, the method comprising:

collecting information (such as imaging, recognition, identification, etc.) associated with antibody arrays and their interaction with viruses, capsids, prions, proteins, or DNA using a low energy electron microscopy technique.

208. The method of claim 207, wherein the low energy electron microscopy technique includes capturing one or more images of combinatorial chips containing antibody arrays.

209. The method of claim 207, further comprising:

performing an experiment-related action using the collected

information.

210. The method of claim 207, further comprising:

storing the collected information in a database associated with an

experiment.

21 1 . The method of claim 207, further comprising:

performing an experimental task using the collected information.

212. The method of claim 207, further comprising:

evaluating the combinatorial chips containing antibody arrays using the collected information.

213. The method of claim 207, further comprising:

characterizing the combinatorial chips containing antibody arrays using the collected information and verifying the proper placement of the desired antibodies, or groups of antibodies, at desired locations (pixels or addresses) on the chip.

214. The method of claim 207, wherein observing the interaction of a virus with an antibody array using a low energy electron microscope includes taking one or more images of the interaction of a virus with an antibody array using the low energy electron microscope.

215. A method of experimentation, the method comprising:

Observing in real time or ex post facto the interaction of a virus with an antibody array using a low energy electron microscope.

216. The method of claim 215, wherein observing the interaction of a capsid with an antibody array using a low energy electron microscope includes taking one or more images of the interaction of a capsid with an antibody array using the low energy electron microscope.

217. A method of experimentation, the method comprising:

Observing in real time or ex post facto the interaction of a capsid with an antibody array using a low energy electron microscope.

218. The method of claim 207, wherein observing the interaction of a protein with an antibody array using a low energy electron microscope includes taking one or more images of the interaction of a protein with an antibody array using the low energy electron microscope.

219. A method of experimentation, the method comprising:

Observing in real time or ex post facto the interaction of a protein with an antibody array using a low energy electron microscope.

220. The method of claim 207, wherein observing the interaction of DNA with an antibody array using a low energy electron microscope includes taking one or more images of the interaction of DNA with an antibody array using the low energy electron microscope.

221 . A method of experimentation, the method comprising:

Observing in real time or ex post facto the interaction of DNA with an antibody array using a low energy electron microscope.

222. The method of claim 207, further comprising:

exposing arrays of antibodies interacting with viruses, capsids, prions, proteins or DNA to an experimental agent; and collecting infornnation associated with the interaction using the low energy electron microscopy technique.

223. The method of claim 222, further comprising:

exposing arrays of antibodies interacting with viruses, capsids, prions, proteins or DNA to a biological agent; and

224. The method of claim 222, further comprising:

exposing arrays of antibodies interacting with viruses, capsids, prions, proteins or DNA to a chemical agent (such as reactive gasses of various atoms, molecules, ions, etc.); and

225. The method of claim 222, further comprising:

exposing arrays of antibodies interacting with viruses, capsids, prions, proteins or DNA to a physical agent (such as temperature, illumination by light from microwaves to gamma rays, irradiation by electrons, ions, etc.); and

226. The method of claim 207, wherein the information associated with viruses, capsids, prions, proteins or DNA includes information associated with identification of a virus-antibody or capsid-antibody or prion-antibody or protein-antibody or DNA-antibody interactions, based on LEEM images, the location of interactions, and known location of specific antibodies.

227. The method of claim 226, wherein the information on virus-antibody interactions, based on LEEM images, the location of interactions, and known location of specific antibodies, is used to determine to which antibody the virus under study is attached.

228. The method of claim 226, wherein the information on capsid-antibody interactions, based on LEEM images, the location of interactions, and known location of specific antibodies, is used to determine to which antibody the capsid under study is attached.

229. The method of claim 226, wherein the information on prion-antibody interactions, based on LEEM images, the location of interactions, and known location of specific antibodies, is used to determine to which antibody the prion under study is attached.

230. The method of claim 226, wherein the information on protein-antibody interactions, based on LEEM images, the location of interactions, and known location of specific antibodies, is used to determine to which antibody the protein under study is attached.

231 . The method of claim 226, wherein the information on DNA-antibody interactions, based on LEEM images, the location of interactions, and known location of specific antibodies, is used to determine to which antibody the DNA under study is attached.

232. The method of claim 226, wherein the information associated with identification of a virus-antibody or capsid-antibody or prion-antibody or protein-antibody or DNA-antibody interactions, based on LEEM images, the location of interactions, and known location of specific antibodies, is used for fast, high-throughput, combinatorial screening and identification of viruses, capsids, prions, proteins, DNA or its fragments.

233. The method of claim 226, wherein the information associated with identification of a virus-antibody or capsid-antibody or prion-antibody or protein-antibody or DNA-antibody interactions, based on LEEM images, the location of interactions, and known location of specific antibodies, is stored in a database to be used in future for fast, high-throughput, combinatorial screening and identification of viruses, capsids, prions, proteins, DNA or its fragments.

234. A method of experimentation, the method comprising:

collecting information (such as imaging, recognition, identification, etc.) associated with protein arrays, in both forward-phase and reverse- phase formats, and their interaction with viruses, capsids, prions, antibodies, or DNA using a low energy electron microscopy technique.

235. The method of claim 234, wherein the low energy electron microscopy technique includes capturing one or more images of combinatorial chips containing protein arrays;

236. The method of claim 234, further comprising:

performing an experiment-related action using the collected

information.

237. The method of claim 234, further comprising:

storing the collected information in a database associated with an

experiment.

238. The method of claim 234, further comprising:

performing an experimental task using the collected information.

239. The method of claim 234, further comprising:

evaluating the combinatorial chips containing protein arrays using the collected information.

240. The method of claim 234, further comprising:

characterizing the combinatorial chips containing protein arrays using the collected information and verifying the proper placement of the desired proteins, or groups of proteins, at desired locations (pixels or addresses) on the chip.

241 . The method of claim 234, wherein observing the interaction of a virus with a protein array using a low energy electron microscope includes taking one or more images of the interaction of a virus with a protein array using the low energy electron microscope.

242. A method of experimentation, the method comprising:

Observing in real time or ex post facto the interaction of a virus with a protein array (in both forward phase and reverse-phase format) using a low energy electron microscope.

243. The method of claim 234, wherein observing the interaction of a capsid with a protein array using a low energy electron microscope includes taking one or more images of the interaction of a capsid with a protein array using the low energy electron microscope.

244. A method of experimentation, the method comprising:

Observing in real time or ex post facto the interaction of a capsid with a protein array using a low energy electron microscope.

245. The method of claim 234, wherein observing the interaction of an antibody with a protein array using a low energy electron microscope includes taking one or more images of the interaction of an antibody with a protein array using the low energy electron microscope.

246. A method of experimentation, the method comprising:

Observing in real time or ex post facto the interaction of an antibody with a protein array using a low energy electron microscope.

247. The method of claim 234, wherein observing the interaction of DNA with a protein array using a low energy electron microscope includes taking one or more images of the interaction of DNA with a protein array using the low energy electron microscope.

248. A method of experimentation, the method comprising:

Observing in real time or ex post facto the interaction of DNA with a protein array using a low energy electron microscope.

249. The method of claim 234, further comprising:

exposing arrays of proteins interacting with viruses, antibodies,

capsids, prions or DNA to an experimental agent; and

collecting information associated with the interaction using the low

energy electron microscopy technique.

250. The method of claim 249, further comprising:

exposing arrays of proteins interacting with viruses, antibodies,

capsids, prions or DNA to a biological agent; and

collecting information associated with the interaction using the low

energy electron microscopy technique.

251 . The method of claim 249, further comprising: exposing arrays of proteins interacting with viruses, antibodies, capsids, prions or DNA to a chemical agent (such as reactive gasses of various atoms, molecules, ions, etc.); and

collecting information associated with the interaction using the low

energy electron microscopy technique.

252. The method of claim 249, further comprising:

exposing arrays of proteins interacting with viruses, antibodies,

capsids, prions or DNA to a physical agent (such as temperature, illumination by light from microwaves to gamma rays, irradiation by electrons, ions, etc.); and

collecting information associated with the interaction using the low

energy electron microscopy technique.

253. The method of claim 234, wherein the information associated with viruses, capsids, antibodies, prions or DNA includes information associated with identification of a virus-protein or capsid- protein or prion- protein or antibody- protein or DNA- protein interactions, based on LEEM images, the location of interactions, and known location of specific proteins.

254. The method of claim 253, wherein the information on virus- protein interactions, based on LEEM images, the location of interactions, and known location of specific proteins, is used to determine to which protein the virus under study is attached.

255. The method of claim 253, wherein the information on capsid- protein interactions, based on LEEM images, the location of interactions, and known location of specific proteins, is used to determine to which protein the capsid under study is attached.

256. The method of claim 253, wherein the information on antibody - protein interactions, based on LEEM images, the location of interactions, and known location of specific proteins, is used to determine to which protein the antibody under study is attached.

257. The method of claim 253, wherein the information on prion- protein interactions, based on LEEM images, the location of interactions, and known location of specific proteins, is used to determine to which protein the prion under study is attached.

258. The method of claim 253, wherein the information on DNA- protein interactions, based on LEEM images, the location of interactions, and known location of specific proteins, is used to determine to which protein the DNA under study is attached.

259. The method of claim 253, wherein the information associated with identification of a virus-protein or capsid- protein or prion- protein or antibody- protein or DNA- protein interactions, based on LEEM images, the location of interactions, and known location of specific proteinss, is used for fast, high- throughput, combinatorial screening and identification of viruses, capsids, prions, antibodies, DNA or its fragments.

260. The method of claim 253, wherein the information associated with identification of a virus- protein or capsid- protein or prion- protein or antibody- protein or DNA- protein interactions, based on LEEM images, the location of interactions, and known location of specific proteins, is stored in a database to be used in future for fast, high-throughput, combinatorial screening and identification of viruses, capsids, prions, antibodies, DNA or its fragments.

261 . A method of experimentation, the method comprising:

collecting information on interaction between viruses, capsids,

antibodies, prions, proteins or DNA with a pharmaceutical agent, using a low energy electron microscopy technique.

262. The method of claim 261 , wherein the low energy electron microscopy technique includes capturing one or more images of viruses, capsids, antibodies, prions, proteins or DNA using a low energy electron microscope.

263. The method of claim 261 , further comprising:

performing an experiment-related action using the collected

information.

264. The method of claim 261 , further comprising:

storing the collected information in a database associated with an

experiment.

265. The method of claim 261 , further comprising:

performing an experimental task using the collected information.

266. The method of claim 261 , further comprising:

performing a diagnosis using the collected information.

267. The method of claim 261 , wherein the pharmaceutical agent is a biological agent.

268. The method of claim 261 , wherein the pharmaceutical agent is a chemical agent.

269. The method of claim 261 , wherein the information associated with an interaction between viruses, capsids, antibodies, prions, proteins or DNA and a pharmaceutical agent includes image information depicting modifications of the viruses, capsids, antibodies, prions, proteins or DNA based on the interaction.

270. A method of experimentation, the method comprising:

collecting information associated with a virus using a low energy

electron microscope;

causing the virus to interact with a pharmaceutical drug; and

collecting information associated with the virus after interactions

between the virus and the pharmaceutical drug using the low energy electron microscope.

271 . The method of claim 270, wherein causing the virus to interact with a pharmaceutical drug includes causing the virus to interact with a biological agent.

272. The method of claim 270, wherein causing the virus to interact with a pharmaceutical drug includes causing the virus to interact with a chemical agent.

273. The method of claim 270, wherein the collected information associated with virus includes one or more low energy electron microscope images of the virus, and wherein the collected information associated with the virus after interactions between the virus and the pharmaceutical drug includes one or more low energy electron microscope images of the virus after interactions between the virus and the pharmaceutical drug.

274. A method of experimentation, the method comprising:

collecting information associated with a capsid using a low energy electron microscope;

causing the capsid to interact with a pharmaceutical drug; and collecting information associated with the capsid after interactions

between the capsid and the pharmaceutical drug using the low energy electron microscope.

275. The method of claim 274, wherein causing the capsid to interact with a pharmaceutical drug includes causing the capsid to interact with a biological agent.

276. The method of claim 274, wherein causing the capsid to interact with a pharmaceutical drug includes causing the capsid to interact with a chemical agent.

277. The method of claim 274, wherein the collected information associated with capsid includes one or more low energy electron microscope images of the capsid, and wherein the collected information associated with the capsid after interactions between the capsid and the pharmaceutical drug includes one or more low energy electron microscope images of the capsid after interactions between the capsid and the pharmaceutical drug.

278. A method of experimentation, the method comprising:

collecting information associated with an antibody using a low energy electron microscope;

causing the antibody to interact with a pharmaceutical drug; and collecting information associated with the antibody after interactions between the antibody and the pharmaceutical drug using the low energy electron microscope.

279. The method of claim 278, wherein causing the antibody to interact with a pharmaceutical drug includes causing the antibody to interact with a biological agent.

280. The method of claim 278, wherein causing the antibody to interact with a pharmaceutical drug includes causing the antibody to interact with a chemical agent.

281 . The method of claim 278, wherein the collected information associated with antibody includes one or more low energy electron microscope images of the antibody and wherein the collected information associated with the antibody after interactions between the antibody and the pharmaceutical drug includes one or more low energy electron microscope images of the antibody after interactions between the antibody and the pharmaceutical drug.

282. A method of experimentation, the method comprising:

collecting information associated with a prion using a low energy

electron microscope;

causing the prion to interact with a pharmaceutical drug; and

collecting information associated with the prion after interactions

between the prion and the pharmaceutical drug using the low energy electron microscope.

283. The method of claim 282, wherein causing the prion to interact with a pharmaceutical drug includes causing the prion to interact with a biological agent.

284. The method of claim 282, wherein causing the prion to interact with a pharmaceutical drug includes causing the prion to interact with a chemical agent.

285. The method of claim 282, wherein the collected information associated with prion includes one or more low energy electron microscope images of the prion, and wherein the collected information associated with the prion after interactions between the prion and the pharmaceutical drug includes one or more low energy electron microscope images of the prion after interactions between the prion and the pharmaceutical drug.

286. A method of experimentation, the method comprising:

collecting information associated with a protein using a low energy electron microscope;

causing the protein to interact with a pharmaceutical drug; and collecting information associated with the protein after interactions between the protein and the pharmaceutical drug using the low energy electron microscope.

287. The method of claim 286, wherein causing the protein to interact with a pharmaceutical drug includes causing the protein to interact with a biological agent.

288. The method of claim 286, wherein causing the protein to interact with a pharmaceutical drug includes causing the protein to interact with a chemical agent.

289. The method of claim 286, wherein the collected information associated with protein includes one or more low energy electron microscope images of the protein, and wherein the collected information associated with the protein after interactions between the protein and the pharmaceutical drug includes one or more low energy electron microscope images of the protein after interactions between the protein and the pharmaceutical drug.

290. A method of experimentation, the method comprising:

collecting information associated with a DNA using a low energy

electron microscope;

causing the DNA to interact with a pharmaceutical drug; and

collecting information associated with the DNA after interactions

between the DNA and the pharmaceutical drug using the low energy electron microscope.

291 . The method of claim 290, wherein causing the DNA to interact with a pharmaceutical drug includes causing the DNA to interact with a biological agent.

292. The method of claim 290, wherein causing the DNA to interact with a pharmaceutical drug includes causing the DNA to interact with a chemical agent.

293. The method of claim 290, wherein the collected information associated with DNA includes one or more low energy electron microscope images of the DNA, and wherein the collected information associated with the DNA after interactions between the DNA and the pharmaceutical drug includes one or more low energy electron microscope images of the DNA after interactions between the DNA and the pharmaceutical drug.

294. A method of experimentation, the method comprising:

modifying a virus or a capsid for a virotherapy or gene therapy

experiments, or for virus-based medical diagnostics; and collecting information associated with the modified virus or capsid using a low energy electron microscopy technique.

295. The method of claim 294, wherein the low energy electron microscopy technique includes capturing one or more images of the virus or capsid using a low energy electron microscope.

296. The method of claim 294, wherein modifying a virus or capsid for a virotherapy or gene therapy experiments includes modifying multiple viruses or capsids; and wherein collecting information associated with the modified virus or capsid includes collecting information associated with the modified viruses or capsids.

297. The method of claim 294, further comprising:

causing the modified virus or capsid to interact with an antibody; and collecting information associated with interactions between the

modified virus or capsid and the antibody using the low energy electron microscopy technique.

298. The method of claim 294, further comprising:

causing the modified virus or capsid to interact with a biological agent; and

collecting information associated with interactions between the

modified virus or capsid and the biological agent using the low energy electron microscopy technique.

299. The method of claim 294, further comprising:

causing the modified virus or capsid to interact with a target cell; and collecting information associated with the modified virus or capsid during an interaction with the target cell using the low energy electron microscopy technique.

300. The method of claim 294, further comprising:

causing the modified virus or capsid to interact with a target cell; and collecting information associated with the target cell during an

interaction with the modified virus or capsid using the low energy electron microscopy technique.

301 . The method of claim 294, further comprising:

causing the modified virus or capsid to interact with a target cell; and collecting information associated with a location of interaction between the modified virus or capsid and the target cell using the low energy electron microscopy technique.

302. A method of experimentation, the method comprising:

collecting information associated with a virus or capsid using a low energy electron microscope;

modifying the virus or capsid for a virotherapy or gene therapy

experiment; and

collecting information associated with the modified virus or capsid

using the low energy electron microscope.

303. The method of claim 302, further comprising:

modified virus or capsid and the antibody using the low energy electron microscope.

304. The method of claim 302, further comprising:

causing the modified virus or capsid to interact with a biological agent; and

collecting information associated with interactions between the

modified virus or capsid and the biological agent using the low energy electron microscope.

305. The method of claim 302, further comprising:

306. A method for collecting information from a virotherapy or gene therapy experiment, the method comprising:

causing an interaction between a modified virus or capsid and a target cell; and

capturing real-time images of the interaction using a low energy

electron microscope.

307. The method of claim 306, wherein capturing real-time images of the interaction includes capturing images of the modified virus or capsid before, during, and after the interaction using the low energy electron microscope.

308. The method of claim 306, wherein capturing real-time images of the interaction includes capturing images of the modified virus or capsid before and after the interaction using the low energy electron microscope.

309. The method of claim 306, wherein capturing real-time images of the interaction includes capturing images of the target cell before, during, and after the interaction using the low energy electron microscope.

310. The method of claim 306, wherein capturing real-time images of the interaction includes capturing images of the target cell before and after the interaction using the low energy electron microscope.

31 1 . The method of claim 294, further comprising:

causing the modified virus or capsid to interact with an antibody array; and

collecting information associated with interactions between the

modified virus or capsid and the antibody array using the low energy electron microscopy technique.

312. The method of claim 294, further comprising:

causing the modified prion to interact with an antibody array; and collecting information associated with interactions between the modified prion and the antibody array using the low energy electron microscopy technique.

313. The method of claim 294, further comprising:

causing the modified virus or capsid to interact with a protein array; and collecting information associated with interactions between the

modified virus or capsid and the protein array using the low energy electron microscopy technique.

314. The method of claim 294, further comprising:

causing the modified prion to interact with a protein array; and collecting information associated with interactions between the

modified prion and the protein array using the low energy electron microscopy technique.

315. The method of claim 294, further comprising:

causing an array of human proteins to interact with autoantibodies of cancers and

collecting information associated with interactions between an array of human proteins with autoantibodies of cancers using the low energy electron microscopy technique.

316. A method of screening human subjects for virus or prion infections, the method comprising:

receiving a biological sample from a human subject; and

capturing one or more images of the biological sample using a low energy electron microscope.

317. The method of claim 316, further comprising:

determining that a virus or prion is depicted in one or more of the

captured images; and

identifying a virus or prion type of the depicted virus or prion.

318. The method of claim 316, further comprising:

vaccinating the human subject;

receiving a second biological sample from the human subject after the vaccination; and capturing one or more images of the second biological sample using the low energy electron microscope

319. The method of claim 316, wherein the biological sample is breath condensate from the human subject.

320. The method of claim 316, wherein the biological sample is saliva from the human subject.

321 . The method of claim 316, wherein the biological sample is blood from the human subject.

322. The method of claim 316, wherein the biological sample a sample of skin cells from the human subject.

323. A method for deciding whether a person should be granted access to a controlled, restricted or protected location, the method comprising:

receiving a biological sample from a person requesting access to the location;

screening the received biological sample for virus or prions using a low energy electron microscopy technique; and

authorizing access to the location based on the negative screening result (no viruses, no prions).

324. The method of claim 323, wherein screening the received biological sample for virus or prions using a low energy electron microscopy technique includes:

capturing one or more images of the received biological sample using a low energy electron microscope;

identifying one or more virus or prions depicted in one or more of the captured images; and

denying the access to the location based on the identification of the one or more virus or prions depicted in one or more of the captured images.

325. The method of claim 323, wherein screening the received biological sample for virus or prions using a low energy electron microscopy technique includes: capturing one or more images of the received biological sample using a low energy electron microscope;

determining that the captured one or more images do not depict a virus or prion; and

wherein authorizing access to the location based on the screening includes allowing access to the location based on the

determination.

326. The method of claim 325, wherein the location includes a

transportation facility (such as an airport or aiport terminal, port or marina, train station, bust station, etc.), a transportation apparatus (airplane, ship, train, bus, etc.), a government facility, a medical facility, an educational institution (daycare, kindergarden, school, college, university), or an office building (bank, large corporation building, etc.), a theater, a concert hall, a stadium, etc.

327. A testing package for testing subjects, the package comprising:

a substrate configured to contain a biological sample taken from a

subject;

a low energy electron microscope configured to capture images of biological samples contained by the substrate; and

a computing device configured to analyze images captured by the low energy electron microscope.

328. The testing package of claim 327, wherein the computing device is configured to identify virus or prions depicted in the images captured by the low energy electron microscope.

329. The testing package of claim 327, wherein the substrate is configured to contain a biological sample taken from a human subject.

330. The testing package of claim 327, wherein the substrate is configured to contain breath condensate taken from a human subject.

331 . The testing package of claim 327, wherein the substrate is configured to contain saliva taken from a human subject.

332. The testing package of claim 327, wherein the substrate is configured to contain blood taken from a human subject.

333. The testing package of claim 327, wherein the substrate is configured to contain skin cells taken from a human subject.

334. A method of screening animal subjects (such as pets, farm animals, livestock, fish, other sea animals, wildlife, etc.,) for virus or prion infections, the method comprising:

receiving a biological sample from a animal subject; and

335. The method of claim 334, further comprising:

determining that a virus or prion is depicted in one or more of the captured images; and

identifying a virus or prion type of the depicted virus or prion.

336. The method of claim 334, further comprising:

vaccinating the animal subject;

receiving a second biological sample from the animal subject after the vaccination; and

capturing one or more images of the second biological sample using the low energy electron microscope.

337. The method of claim 334, wherein the biological sample is breath condensate from an animal subject.

338. The method of claim 334, wherein the biological sample is saliva from an animal subject.

339. The method of claim 334, wherein the biological sample is blood from the animal subject.

340. The method of claim 334, wherein the biological sample a sample of skin cells from the animal subject.

341 . A testing package for testing an animal subject for virus or prions, the package comprising: a substrate configured to contain a biological sample taken from an animal subject;

342. The testing package of claim 341 , wherein the computing device is configured to identify virus or prions depicted in the images captured by the low energy electron microscope.

343. The testing package of claim 341 , wherein the substrate is configured to contain a biological sample taken from an animal subject.

344. The testing package of claim 341 , wherein the substrate is configured to contain breath condensate taken from an animal subject.

345. The testing package of claim 341 , wherein the substrate is configured to contain saliva taken from an animal subject.

346. The testing package of claim 341 , wherein the substrate is configured to contain blood taken from an animal subject.

347. The testing package of claim 341 , wherein the substrate is configured to contain skin cells taken from an animal subject.

348. A method of screening plant subjects (such as wheat, corn, rice, cereals, fruit, vegetables, plants used for bio-fuel production, decorative plants, trees, grass, ground cover, etc.) for virus or viroid infections, the method comprising:

receiving a biological sample from a plant subject; and

349. The method of claim 348, further comprising:

determining that a virus is depicted in one or more of the captured images; and

identifying the virus type of the depicted virus.

350. A testing package for testing a plant subject for viruses, the package comprising:

a substrate configured to contain a biological sample taken from a plant subject;

351 . The testing package of claim 350, wherein the computing device is configured to identify viruses depicted in the images captured by the low energy electron microscope.

352. The testing package of claim 350, wherein the substrate is configured to contain biological matter taken from a plant-like subject.

353. A LEEM-based apparatus, including the electronics hardware and software (data base, image recognition software, etc.,) for screening of import of plants across the country borders, and into ecologically sensitive areas such as islands, for possible viral and viroid infections.

354. A method for certifying food products, the method comprising:

receiving a sample of a food product;

screening the received sample for viruses, viroids and prions using a low energy electron microscopy technique; and

certifying the food product based on the negative result of the

screening test (no viruses, viroids or prions detected).

355. The method of claim 354, wherein screening of the received sample for viruses, viroids or prions using a low energy electron microscopy technique includes:

capturing one or more images of the received sample using a low

energy electron microscope;

identifying one or more viruses, viroids or prions depicted in one or more of the captured images; and not certifying the food product based on identification of one or more viruses, viroids, or prions depicted in one or more of the captured images.

356. The method of claim 354, wherein screening of the received sample for viruses, viroids, or prions using a low energy electron microscopy technique includes:

capturing one or more images of the received sample using a low

energy electron microscope;

determining that none of the captured images depict a virus; and wherein certifying the food product based on this screening includes certifying the food product based on the determination.

357. The method of claim 354, wherein the food product includes an animal-based food product or a plant-based food product.

358. A testing package for testing biological matter taken from a food product for viruses, viroids and prions, the package comprising:

a substrate configured to contain a biological sample taken from a food product;

359. A system for identifying viruses within an examined sample, the system comprising:

a low energy electron microscope (LEEM); and

a virus identification device, wherein the virus identification device is configured to identify an image taken by the LEEM includes an image of a virus.

360. The system of claim 359, wherein the virus identification device includes:

an image comparison component, wherein the image comparison component is configured to match a size of contents of the image taken by the LEEM with a size of contents of one or more images associated with a known virus.

361 . The system of claim 359, wherein the virus identification device includes:

an image comparison component, wherein the image comparison component is configured to match a shape of contents of the image taken by the LEEM with a shape of contents of one or more images associated with a known virus.

362. The system of claim 359, wherein the virus identification device includes:

an image comparison component, wherein the image comparison component is configured to match a size and shape of contents of the image taken by the LEEM with a size and shape of contents of one or more images associated with a known virus.

363. The system of claim 359, wherein the virus identification device includes:

an image comparison component, wherein the image comparison component is configured to match a size and shape of contents of the two or more images taken by the LEEM with a size and shape of contents of two or more images associated with a known virus.

364. The system of claim 359, wherein the virus identification device includes:

an image comparison component, wherein the image comparison component is configured to match an average size and shape of contents of two or more images taken by the LEEM with a size and shape of a known virus.

365. The system of claim 359, wherein the virus identification device includes:

an image comparison component, wherein the image comparison component is configured to match information associated with a size and shape of contents of the image taken by the LEEM with information associated with a size and shape attributed to a known virus.

366. The system of claim 359, wherein the virus identification device includes:

an image comparison component, wherein the image comparison

component is configured to extract information associated with morphological information of a subject of the image taken by the LEEM with morphological information associated with known viruses.

367. A method for detecting a virus within a biological sample, the method comprising:

taking an image of a biological sample using a low energy electron microscope;

identifying within the image an object that has a size or shape

indicative of a known virus.

368. The method of claim 367, wherein identifying within the image an object that has a size or shape indicative of a known virus includes matching the image to one or more images associated with known viruses.

369. The method of claim 367, wherein identifying within the image an object that has a size or shape indicative of a known virus includes:

extracting a size of the object within the image;

querying an index of morphological information associated with known viruses for the extracted size of the object within the image; and identifying the object within the image is a known virus based on the query.

370. The method of claim 367, wherein identifying within the image an object that has a size or shape indicative of a known virus includes:

extracting a shape of the object within the image;

querying an index of morphological information associated with known viruses for the extracted shape of the object within the image; and identifying the object within the image is a known virus based on the query.

371 . The method of claim 367, wherein identifying within the image an object that has a size or shape indicative of a known virus includes:

extracting a size and shape of the object within the image;

querying an index of morphological information associated with known viruses for the extracted size and shape of the object within the image; and

identifying the object within the image is a known virus based on the query.

372. A system for identifying a virus within a biological sample, the device comprising:

an identification device, wherein the identification device is configured to identify within one or more of the multiple LEEM images an object having a size or shape similar to a size or shape of a known virus.

373. The system of claim 372, wherein the identification device includes: an imaging component, wherein the imaging component is configured to extract the size of shape of the object within the one or more LEEM images;

a query component, wherein the query component is configured to query an index of information that associates known viruses with morphological information associated with the known viruses; and an identification component, wherein the identification component is configured to identify that the object represents a known virus based on a result of the query.

374. A system for taking images of viruses, the system comprising:

a low energy electron microscope; and

375. The system of claim 374, wherein the low energy electron microscope includes components configured to operate in reflection geometry in order to take an image of the biological sample.

376. The system of claim 374, wherein the low energy electron microscope includes components configured to operate in reflection geometry with respect to the biological sample in order to take an image of the biological sample.

377. The system of claim 374, wherein the low energy electron microscope includes components configured to perform photoemission electron

378. The system of claim 374, wherein the low energy electron microscope includes components configured to perform low energy electron diffraction from a biological sample.

379. A system for taking images of viruses, the system comprising:

an imaging device that includes components configured to take an

image of a virus within a biological sample using low energy electron microscopy; and

a recording device configured to generate a video from taken images of the virus within the biological sample.

380. The system of claim 379, further comprising:

a sample chamber within the imaging device, wherein the sample

chamber is adapted to maintain a biological sample within a vacuum.

381 . The system of claim 379, wherein the imaging device includes components configured to take the image of the virus within the biological sample using reflection geometry.

382. The system of claim 379, wherein the imaging device includes components configured to take the image of the virus within the biological sample using low energy electron diffraction.

383. The system of claim 379, wherein the imaging device includes components configured to take the image of the virus within the biological sample using photoemission electron microscopy.

384. One or more tangible computer memories collectively containing a data structure, the data structure including multiple entries each associated with a known virus, wherein each of the entries includes morphological information extracted from a low energy electron microscope (LEEM) image of the known virus.

385. The computer memories of claim 384, wherein the morphological information extracted from the low energy electron microscope (LEEM) image of the known virus includes information associated with a size of a virus imaged by a low energy electron microscope.

386. The computer memories of claim 384, wherein the morphological information extracted from the low energy electron microscope (LEEM) image of the known virus includes information associated with a shape of a virus imaged by a low energy electron microscope.

387. The computer memories of claim 384, wherein the morphological information extracted from the low energy electron microscope (LEEM) image of the known virus includes information associated with a size of a virus imaged by a low energy electron microscope and with a shape of the virus imaged by the low energy electron microscope.

388. The computer memories of claim 384, wherein each of the entries associated with the known virus include information associated with operation characteristics of a low energy electron microscope that generated LEEM images of the known virus.

389. A system for modifying a database of low energy electron microscope (LEEM) images of a virus, the system comprising:

an image component, wherein the image component is configured to receive an image of the virus taken by a LEEM;

an information extraction component, wherein the information

extraction component is configured to extract information from the received LEEM image of the virus; a comparison component, wherein the comparison component is configured to compare the extracted information to an index of information associated with known viruses; and

a database component, wherein the database component is configured to update a database of entries associating viruses with LEEM images of the viruses based on results of the comparison performed by the comparison component.

390. The system of claim 389, wherein the extracted information is size information associated with the images of the virus; and

wherein the comparison component is configured to compare the size information with an index of size information associated with known viruses.

391 . The system of claim 389, wherein the extracted information is shape information associated with the images of the virus; and

wherein the comparison component is configured to compare the

shape information with an index of shape information associated with known viruses.

392. The system of claim 389, wherein the extracted information is size and shape information associated with the images of the virus; and

wherein the comparison component is configured to compare the size and shape information with an index of size and shape information associated with known viruses.

393. The system of claim 389, wherein the extracted information is an image of the virus; and

wherein the comparison component is configured to compare the

image with an index of images associated with known viruses using a content based image retrieval engine.

394. A method of assigning metadata to an image taken by a low energy electron microscope (LEEM), the method comprising:

receiving information indicating a LEEM image includes contents

representing a known virus; and assigning metadata to the LEEM image that includes information associated with the known virus represented by the contents of the LEEM image.

395. The method of claim 394, wherein assigning metadata to the LEEM image that includes information associated with the known virus represented by the contents of the LEEM image includes assigning metadata that includes morphological information for the known virus.

396. The method of claim 394, wherein assigning metadata to the LEEM image that includes information associated with the known virus represented by the contents of the LEEM image includes assigning metadata that includes size information for the known virus.

397. The method of claim 394, wherein assigning metadata to the LEEM image that includes information associated with the known virus represented by the contents of the LEEM image includes assigning metadata that includes shape information for the known virus.

398. The method of claim 394, wherein assigning metadata to the LEEM image that includes information associated with the known virus represented by the contents of the LEEM image includes assigning metadata that includes structure information for the known virus.

399. A system for identifying a virus-agent interaction within an examined sample, the system comprising:

a low energy electron microscope (LEEM); and

an identification device, wherein the identification device is configured to identify an image taken by the LEEM includes an image of an interaction between a virus and a biological agent.

400. The system of claim 399, wherein the virus identification device includes:

an image comparison component, wherein the image comparison

component is configured to match a size of contents of the image taken by the LEEM with a size of contents of one or more images associated with a a known virus or a known biological agent.

401 . The system of claim 399, wherein the virus identification device includes:

an image comparison component, wherein the image comparison

component is configured to match a shape of contents of the image taken by the LEEM with a shape of contents of one or more images associated with a known virus or a known biological agent.

402. The system of claim 399, wherein the virus identification device includes:

an image comparison component, wherein the image comparison

component is configured to match a size and shape of contents of the image taken by the LEEM with a size and shape of contents of one or more images associated with a known virus or a known biological agent.

403. The system of claim 399, wherein the virus identification device includes:

an image comparison component, wherein the image comparison

component is configured to match a size and shape of contents of the two or more images taken by the LEEM with a size and shape of contents of two or more images associated with a known virus or a known biological agent.

404. The system of claim 399, wherein the virus identification device includes:

an image comparison component, wherein the image comparison

component is configured to match an average size and shape of contents of two or more images taken by the LEEM with a size and shape of a known virus or a known biological agent.

405. The system of claim 399, wherein the virus identification device includes:

an image comparison component, wherein the image comparison

component is configured to match information associated with a size and shape of contents of the image taken by the LEEM with information associated with a size and shape attributed to a known virus or a know biological agent.

406. The system of claim 399, wherein the virus identification device includes:

an image comparison component, wherein the image comparison component is configured to extract information associated with morphological information of a subject of the image taken by the LEEM with morphological information associated with known viruses or known biological agents.

407. A system for confirming a virus-agent interaction within a biological sample, the device comprising:

an identification device, wherein the identification device is configured to identify within one or more of the multiple LEEM images an object having a size or shape similar to a size or shape of a known interacting virus-agent complex.

408. The system of claim 407, wherein the identification device includes: an imaging component, wherein the imaging component is configured to extract the size of shape of the object within the one or more LEEM images;

a query component, wherein the query component is configured to query an index of information that associates known viruses with morphological information associated with the known viruses; and an identification component, wherein the identification component is configured to identify that the object represents a specific interacting virus-agent complex based on a result of the query.

409. A computing system for identifying viruses within images taken by a low energy electron microscope (LEEM), the system comprising: a virus identification component, wherein the virus identification component is configured to determine that an object within contents of a LEEM image is a depiction of a virus.

410. The system of claim 409, wherein the virus identification component includes:

an image comparison component, wherein the image comparison

component is configured to match a size of contents of the LEEM image with a size of contents of one or more images associated with a known virus.

41 1 . The system of claim 409, wherein the virus identification component includes:

an image comparison component, wherein the image comparison

component is configured to match a shape of contents of the LEEM image with a shape of contents of one or more images associated with a known virus.

412. The system of claim 409, wherein the virus identification component includes:

an image comparison component, wherein the image comparison

component is configured to match a size and shape of contents of the LEEM image with a size and shape of contents of one or more images associated with a known virus.

413. The system of claim 409, wherein the virus identification component includes:

an image comparison component, wherein the image comparison

component is configured to extract morphological information from the contents of the LEEM image and compare the extracted information with morphological information associated with known viruses.

414. A tangible computer-readable medium whose contents, when executed by a computing device, cause the computing device to perform a method for detecting a virus within a biological sample, the method comprising: taking an image of a biological sample using a low energy electron microscope;

identifying within the image an object that has a size or shape

indicative of a known virus.

415. The computer-readable medium of claim 414, wherein identifying within the image an object that has a size or shape indicative of a known virus includes matching the image to one or more images associated with known viruses.

416. The computer-readable medium of claim 414, wherein identifying within the image an object that has a size or shape indicative of a known virus includes:

extracting a size of the object within the image;

417. The computer-readable medium of claim 414, wherein identifying within the image an object that has a size or shape indicative of a known virus includes:

extracting a shape of the object within the image;

418. The computer-readable medium of claim 414, wherein identifying within the image an object that has a size or shape indicative of a known virus includes:

extracting a size and shape of the object within the image;

querying an index of morphological information associated with known viruses for the extracted size and shape of the object within the image; and identifying the object within the image is a known virus based on the query.

419. A system for identifying a virus within a low energy electron microscope (LEEM) image of a biological sample, the device comprising:

an imaging component, wherein the imaging component is configured to determine a size of shape of an object within the LEEM images; a query component, wherein the query component is configured to

query an index of information that associates known viruses with morphological information associated with the known viruses using a query term associated with the determined size and shape of the object with the LEEM images; and

an identification component, wherein the identification component is configured to identify the object as a virus based on a positive result of the query.

420. The system of claim 419, wherein the identification component is configured to determine that the determined size and shape of the object within the LEEM images is similar to a size and shape of a known virus.

421 . The system of claim 419, wherein the identification component is configured to determine that the determined size and shape of the object within the LEEM images is similar to a size and shape of a known category of viruses.

422. The system of claim 419, wherein the identification component is configured to determine that the determined size and shape of the object within the LEEM images is similar to a size and shape of a typical virus.