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Encoding of microcarriersRelated Patent Categories: Registers, RecordsEncoding of microcarriers description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060097056, Encoding of microcarriers. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] This application claims priority benefit to U.S. provisional application Ser. No. 60/129,551, filed on Apr. 16, 1999. The content of the provisional application is incorporated by reference herein. FIELD OF THE INVENTION [0002] This invention relates to encoded microcarriers, and more specifically to microcarriers having codes written on them. Any reference in this disclosure to codes written "on" the microcarriers includes codes written on the surface of the microcarriers as well as codes written at an internal depth of the microcarriers. This invention also relates to methods for writing codes on microcarriers, methods of reading the codes, and methods of using the encoded microcarriers. A preferred method of encoding the microcarriers involves exposing microcarriers that carry a bleachable substance to a high spatial resolution light source to bleach the codes on the microcarriers. The encoded microcarriers may be used, for example, as support materials in chemical and biological assays and syntheses. DESCRIPTION OF THE RELATED ART [0003] Drug discovery and drug screening in the chemical and biological arts commonly involve performing assays on very large numbers of compounds or molecules. These assays typically include screening chemical libraries for compounds of interest, screening for particular target molecules in test samples, and testing generally for chemical and biological interactions of interest between molecules. The assays described above often require carrying out thousands of individual chemical or biological reactions. For example, a drug discovery assay may involve testing thousands of compounds against a specific target analyte. Any compounds that are observed to react, bind, or otherwise interact with the target analyte may hold promise for any number of utilities where the observed interaction is believed to be of significance. [0004] A number of practical problems exist in the handling of the large number of individual reactions required in the assays described above. Perhaps the most significant problem is the necessity to label and track each reaction. For example, if a reaction of interest is observed in only one in a group of thousands of reactions, the researcher must be able to determine which one of the thousands of initial compounds or molecules produced that reaction. [0005] One conventional method of tracking the identity of the reactions is by physically separating each reaction into an individual reaction vessel within a high-density array and maintaining a record of what individual reactants were used in each vessel. Thus, for example, when a reaction of interest is observed in a vessel labeled as number 5 of 1000, the researcher can refer to the record of reactants used in the vessels and will learn from the record of vessel 5 what specific reactants were present to lead to the reaction of interest. Examples of the high-density arrays referred to above are 384-, 864-, 1,536-, 3,456-, and 9,600-well microtiter plate containers, where each well of a microtiter plate constitutes a miniature reaction vessel. Miniaturized reaction wells are used because they conserve space and reduce the cost of reagents used in the assays. [0006] The use of microtiter plate containers in chemical and biological assays, however, carries a number of disadvantages. For example, the use of the plates requires carefully separating a very large number of discrete reaction vessels, rather than allowing for all reactions to take place freely, and often more conveniently, in one reaction vessel. Furthermore, the requirement that the reaction volumes be spatially separated carries with it a physical limitation to the size of microtiter plate used, and thus to the number of different reactions that may be carried out on the plate. [0007] In light of the limitations described above in the use of microtiter plates, some attempts have been made to develop other means of tracking individual reactions in high-throughput assays. These methods have abandoned the concept of spatially separating the reactions, and instead track the individual reactions by other means. For example, methods have been developed to carry out high-throughput assays and reactions on microcarriers as supports. Each microcarrier may contain one particular ligand bound to its surface to act as a reactant, and the microcarrier can additionally contain a "code" that identifies the microcarrier and therefore identifies the particular ligand bound to its surface. These methods described above allow for "random processing," which means that thousands of uniquely coded microcarriers, each having a ligand bound to their surface, may all be mixed and subjected to an assay simultaneously. Those microcarriers that show a favorable reaction of interest between the attached ligand and target analyte may then have their code read, thereby leading to the identity of the ligand that produced the favorable reaction. [0008] The practice of random processing described above requires accurate encoding of each of the microcarriers separately, and requires accurate and consistent identification of the codes. Because assays using random processing rely heavily on the coding of the microcarriers for their results, the quality of the assays depends largely on the quality and readability of the codes on the microcarriers. Attempts to code microcarriers are still limited to differential coloring (Dye-Trak microspheres), fluorescent labeling (Fluorospheres; Nu-flow), so-called remotely programmable matrices with memories (IRORI; U.S. Pat. No. 5,751,629), detachable tags such as oligonucleotides and small peptides (U.S. Pat. No. 5,565,324; U.S. Pat. No. 5,721,099; U.S. Pat. No. 5,789,172), and solid phase particles that carry transponders (U.S. Pat. No. 5,736,332). The disclosures of the patents cited above are incorporated by reference herein. [0009] These known methods identified above for coding microcarriers each carry disadvantages. For example, microcarriers that are differentiated solely on the basis of their size, shape, color, fluorescence intensity, or combinations thereof often cannot provide enough unique readable combinations of those variables to create the massive number of unique codes necessary to accompany the testing of a correspondingly large number of different molecules. In addition, any microcarriers carrying foreign bodies on their surface to serve as the codes, such as detachable tags or fluorescent markers, run the risk that the attached moieties may interfere with the binding or reaction of the ligand-bound molecules on the microcarriers that target the analytes in the assays. After the separation of the microcarriers of interest that exhibit a favorable reaction, methods of encoding microcarriers with detachable tags also often involve the additional step of cleaving and analyzing the tags to ultimately learn the identity of the underlying ligands on the microcarriers that produced the favorable reactions. This cleaving step naturally extends the time and effort necessary to determine the results of the tests. [0010] In light of the above, there remains in the art a need for simple ways for identifying single microcarriers in a massive population of otherwise identical microcarriers, especially ways for encoding a larger number of unique codes that need not be attached as foreign bodies to the surfaces of the microcarriers. SUMMARY OF THE INVENTION [0011] An object of the invention is to provide a microcarrier that is encoded without the need for attaching a foreign object to the surface of the microcarrier to serve as the code. Another object of the present invention is to provide a method of encoding microcarriers that may provide essentially unlimited possibilities as to the varieties of unique codes that may be written and read on the microcarriers. [0012] The present invention fulfills these objectives by providing microcarriers having codes written on them. Preferred microcarriers are microcarriers containing bleachable substances, for example, fluorescent molecules. A preferred method of encoding the microcarriers involves exposing microcarriers carrying a bleachable substance to a high spatial resolution light source to bleach the codes on the microcarriers. This method may preferably involve bleaching codes on fluorescent microcarriers, where the bleaching produces either the same or different levels of fluorescent intensity within the bleached portions of the code. A further preferred method of encoding the microcarriers is writing the codes at an internal depth of the microcarriers. [0013] In another preferred embodiment, large numbers of chemical compounds or biological molecules are bound to a correspondingly large number of microcarriers of the invention, the microcarrier-bound ligands are mixed and reacted simultaneously according to a screening or assay protocol, and those ligands that react are identified by reading the code on the microcarriers to which they are bound. [0014] The encoded microspheres of the invention allow for the simultaneous analysis of a large number of analytes in a single reaction vessel using a single sample aliquot. Use of the microcarriers of the invention in high-throughput assays and reactions is therefore far superior compared to the use of conventional microtiter plate technology. [0015] The microcarriers of the invention also provide a virtually unlimited number of codes that may be written and read on the microspheres, and are therefore superior to known microcarriers coded with color or fluorescent tags, which carry a more limited number of coding possibilities. The microcarriers of the invention are also superior to microcarriers coded with moieties attached to the surfaces of microcarriers. This is because the writings on the microcarriers of the invention do not carry the risk associated with those known microcarriers of potentially interfering with the analyte/ligand interactions that take place on the surfaces of the microcarriers. [0016] Additional features and advantages of the invention are set forth in the description that follows, and in part will be apparent from the description or may be learned from practice of the invention. The advantages of the invention will be realized and attained by the encoded microcarriers and methods particularly pointed out in the written description and claims. Both the foregoing general description and the following detailed description of the invention are exemplary and explanatory only and are not restrictive of the claimed invention. BRIEF DESCRIPTION OF THE DRAWINGS [0017] FIG. 1 illustrates a number of principles of conventional microphotolysis and SCAMP. [0018] FIGS. 2a and 2b illustrate a bar code and ring code using different intensities, with each intensity being denoted by the different colors shown in the Figures. [0019] FIGS. 3a and 3b illustrate confocal images of a middle plane of an FD148-dex-ma microsphere before (upper) and after bleaching (under) a stripe of 3 .mu.m at approximately 10 .mu.m under the surface of the microsphere. [0020] FIG. 4 illustrates fluorescence recovery curves of FD148 in 148-dex-ma microspheres (A) and FITC in dex-ma microspheres loaded with FITC by submersion in a FITC solution (B). Continue reading about Encoding of microcarriers... Full patent description for Encoding of microcarriers Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Encoding of microcarriers patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. 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