Classifications

• • G—PHYSICS
  • G06—COMPUTING; CALCULATING OR COUNTING
  • G06K—GRAPHICAL DATA READING; PRESENTATION OF DATA; RECORD CARRIERS; HANDLING RECORD CARRIERS
  • G06K19/00—Record carriers for use with machines and with at least a part designed to carry digital markings
  • G06K19/06—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code
  • G06K19/06009—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code with optically detectable marking
  • G06K19/06046—Constructional details
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B82—NANOTECHNOLOGY
  • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
  • B82Y15/00—Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
  • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
  • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
  • C12Q1/6804—Nucleic acid analysis using immunogens
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
  • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
  • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
  • C12Q1/6813—Hybridisation assays
  • C12Q1/6841—In situ hybridisation
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
  • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
  • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
  • C12Q1/6844—Nucleic acid amplification reactions
  • C12Q1/686—Polymerase chain reaction [PCR]
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
  • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
  • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
  • C12Q1/6869—Methods for sequencing
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
  • G01N33/531—Production of immunochemical test materials
  • G01N33/532—Production of labelled immunochemicals
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
  • G01N33/531—Production of immunochemical test materials
  • G01N33/532—Production of labelled immunochemicals
  • G01N33/533—Production of labelled immunochemicals with fluorescent label
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
  • G01N33/588—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with semiconductor nanocrystal label, e.g. quantum dots

Definitions

• a traditionally used method for tracking the location or identity of a component or item of interest is Universal Product Code technology, or barcode technology, which uses a linear array of elements that are either printed directly on an object or on labels that are affixed to the object. These bar code elements typically comprise bars and spaces, with bars of varying widths representing strings of binary ones and spaces of varying widths representing strings of binary zeros. Bar codes can be detectable optically using devices such as scanning laser beams or handheld wands, or they can be implemented in magnetic media. The readers and scanning systems electro-optically decode the symbol to multiple alpha-numerical characters that are intended to be descriptive of the article or some characteristic thereof. Such characters are typically represented in digital form as an input to a data processing system for applications in point-of-sale processing and inventory control to name a few.
• Another technology that has been developed for labeling objects includes a composition comprising silicon or silicon dioxide microparticles and a powder, fluid or gas to be applied to objects such as vehicles, credit cards and jewelry (WO 95/29437).
• This system typically allows the formation of 200 million particles on a single wafer, each of the particles on one wafer being designed to be of identical shape and size so that when the particles are freed from the wafer substrate one is left with a suspension containing a single particle type which can thus be identified and associated with a particular item of interest.
• This system although information dense, is also not practical for a wide range of application.
• One of the advantages explicitly stated in the application includes the unlikely event of unauthorized replication of the particles because of the non-trivial process of micromachining used that requires specialized equipment and skills. Thus, this process would not be widely amenable to a range of uses for inventory control.
• the beads in order to keep track of each of the compounds produced from a reaction series, the beads must be "tagged” or encoded with information at each stage to enable identification of the compound of interest or the reaction pathway producing the compound.
• the tags used to encode the information must be robust to the conditions being employed in the chemical synthesis and must be easily identifiable to obtain the information.
• Exemplary encoding techniques include the use of chemically robust small organic molecules (“tags”) that are cleaved from the bead after the synthesis is completed and analyzed using mass spectroscopy. (US 5, 565, 324; US 5, 721, 099).
• tags chemically robust small organic molecules
• Radiofrequency Encoded Combinatorial (RECTM) chemistry combines recent advances in microelectronics, sensors, and chemistry and uses a Single or Multiple Addressable Radiofrequency Tag (SMARTTM) semiconductor unit to record encoding and other relevant information along the synthetic pathway (Nicolaou et al., Angew. Chem. Int. Ed. Engl. 1995, 34, 2289).
• SMARTTM Single or Multiple Addressable Radiofrequency Tag
• on-bead decoding includes the use of colored and fluorescent beads ( Egner et al., Chem. Commun. 1997, 735), in which a confocal microscope laser system was used to obtain the fluorescence spectra of fluorescent dyes.
• the drawback of this method is the tendency of the dyes to undergo internal quenching by either energy transfer or reabsorption of the emitted light. Additionally, this system is not able to identify a range of dyes uniquely and distinctly.
• the present invention provides a novel encoding system and methods for determining the location and/or identity of a particular item or component of interest.
• the present invention utilizes a "barcode" comprising one or more particle size distributions of semiconductor nanocrystals (also known as Quantum DotTM particles) having characteristic spectral emissions to either "track" the location or source of a particular item of interest or to identify a particular item of interest.
• the semiconductor nanocrystals used in the inventive "barcoding" scheme can be tuned to a desired wavelength to produce a characteristic spectral emission by changing the composition and size, or size distribution, of the semiconductor nanocrystal. Additionally, the intensity of the emission at a particular characteristic wavelength can also be varied, thus enabling the use of binary or higher order encoding schemes.
• the information encoded by the semiconductor nanocrystal can be spectroscopically decoded, thus providing the location, source and/or identity of the particular item or component of interest.
• the method involves providing a composition comprising an item of interest, and one or more compositions (e.g., composition of core and or shell), sizes or size distributions of semiconductor nanocrystals having characteristic spectral emissions, or providing a composition comprising a support, an item of interest, and one or more sizes of semiconductor nanocrystals; subjecting said composition to a primary light source to obtain the spectral emissions for said one or more sizes of semiconductor nanocrystals on said composition; and correlating said spectral emission with said item of interest.
• the present method in preferred embodiments, can be used to encode the identity of biomolecules, particularly DNA sequences, or other items, including, but not limited to, consumer products, identification tags and fluids.
• the present invention provides compositions.
• the composition comprises a support, and one or more particle size distributions of semiconductor nanocrystals having different characteristic spectral emissions.
• the composition comprises a support, one or more items of interest and one or more sizes of semiconductor nanocrystals having different characteristic spectral emissions.
• the composition comprises an item of interest and one or more sizes of semiconductor nanocrystals having different characteristic spectral emissions.
• the semiconductor nanocrystals can be associated with, attached thereto, or embedded within said support structure. Additionally, the semiconductor nanocrystal can optionally have an overcoating comprised of a material having a band gap greater than that of the semiconductor nanocrystal.
• the present invention provides libraries of compounds and/or items of interest.
• each compound in the library is bound to an individual support, and each support has attached thereto or embedded therein one or more identifiers comprising one or more particle size distributions of semiconductor nanocrystals having characteristic spectral emissions.
• each item of interest has attached thereto, or embedded therein one or more identifiers comprising one or more particle size distributions of semiconductor nanocrystals having characteristic spectral emissions.
• kits for identifying an item of interest comprising a collection of items of interest, and wherein each member of said collection of objects has attached thereto or embedded therein one or more particle size distributions of semiconductor nanocrystals having characteristic spectral emissions.
• the kit comprises a collection of items of interest, each bound to a solid support, wherein each support has attached thereto, associated therewith, or embedded therein one or more unique identifiers.
• the present invention provides methods for identifying a compound having a particular characteristic of interest comprising providing a library of compounds, testing said library of compounds for a particular characteristic of interest, observing the photoluminescence spectrum for each identifier attached to each support containing a compound of interest, and identifying the compound of interest by determining the reaction sequence as encoded by said one or more sizes of semiconductor nanocrystals.
• the step of identifying the reaction sequence can be determined before testing the library of compounds because the reaction sequence can be recorded during the synthesis of the compound by "reading" the beads (i.e., observing the photoluminescence spectrum) prior to each reaction step to record the reaction stages.
• the present invention additionally provides methods for recording the reaction stages of a synthesis concurrently with the synthesis.
• the present invention provides methods for identifying a molecule having a characteristic of interest comprising contacting a first library of molecules with a second library of molecules, wherein each of the molecules in the first library is encoded using one or more sizes of semiconductor nanocrystals and the second library has attached thereto or embedded therein one or more sizes of semiconductor nanocrystals acting as "probes".
• This method provides simultaneously a way to identify the binding of one or more molecules from the second library 7 to the first library and determining the structure of said one or more molecules from the first library.
• composition comprising of one or more populations of member semiconductor nanocrystals, wherein each population has a distinct characteristic spectral emission.
• composition comprising the aforementioned populations of nanocrystals associated with a support.
• composition comprising the aforementioned populations of nanocrystals associated with an item of interest, preferably the nanocrystals are associated with a support.
• a library of compounds is provided, wherein each compound in the library is bound to an individual support, each support having associated therewith one or more populations of semiconductor nanocrystals, each population having distinct characteristic spectral emissions.
• a method is provided for identifying a compound having a characteristic of interest.
• the method comprises (a) providing a library of member compounds, wherein each member of said library of compounds is attached to a support, and wherein each support also has attached thereto or embedded therein one or more populations of semiconductor nanocrystals each population having distinct characteristic spectral emissions, (b) testing each member of said library of compounds to identify compounds having a characteristic of interest, (c) subjecting each support to a light source to obtain the characteristic spectral emission, and (d) correlating the spectral emission with the identity of the compound having the characteristic of interest.
• a method is provided for identifying a molecule having a characteristic of interest.
• the method comprises (a) providing a first library of one or more member molecules, wherein each member of said first library is attached to a first support having attached thereto or embedded therein one or more first populations of semiconductor nanocrystals, each first population having a distinct characteristic first spectral emission, (b) providing a second library of one or more member molecules, wherein each member of said second library is attached to a second support having attached thereto or embedded therein one or more second populations of semiconductor nanocrystals, each second population having a distinct characteristic second spectral emission, and wherein the second spectral emission is distinct from the first spectral emission, (c) contacting said first library of molecules with said second library of molecules, and (d) observing the first and second spectral emissions, wherein said first and second spectral emissions provide information about which of the molecules from the second library of molecules are associated with said first library of molecules, and provides information about the identity of the molecule from said first library of molecules.
• Figure 2 depicts a general displacement reaction to modify the surface of the semiconductor nanocrystal.
• Figure 3 depicts the use of the inventive system in fluid dynamics.
• Figure 4 depicts the use of the inventive system in the identification of an object of interest.
• Figure 5 depicts the use of the inventive system in the encoding of combinatorial libraries. Description of Certain Preferred Embodiments
• Quantum DotTM particle As used herein, the term “Quantum DotTM particle” includes a semiconductor nanocrystal with size dependent optical and electrical properties. In particular, the band gap energy of a semiconductor nanocrystal varies with the diameter of the crystal.
• “Semiconductor nanocrystal” includes, for example, inorganic crystallites between about 1 nm and about 1000 nm in diameter, preferably between about 2 nm and about 50 nm, more preferably about 5 nm to about 20 nm (such as about 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nm) that includes a "core” of one or more first semiconductor materials, and which may be surrounded by a “shell” of a second semiconductor material.
• a semiconductor nanocrystal core surrounded by a semiconductor shell is referred to as a "core/shell" semiconductor nanocrystal.
• the surrounding "shell” material will preferably have a bandgap greater than the bandgap of the core material and can be chosen so to have an atomic spacing close to that of the "core" substrate.
• the core and/or the shell can be a semiconductor material including, but not limited to, those of the group II-VI (ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, HgTe, MgTe and the like) and III-V (GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb, AlAs, A1P, AlSb, A1S, and the like) and IV (Ge, Si, Pb and the like) materials, and an alloy thereof, or a mixture thereof.
• a semiconductor nanocrystal is, optionally, surrounded by a "coat" of an organic capping agent.
• the organic capping agent may be any number of materials, but has an affinity for the semiconductor nanocrystal surface.
• the capping agent can be an isolated organic molecule, a polymer (or a monomer for a polymerization reaction), an inorganic complex, and an extended crystalline structure.
• the coat is used to convey solubility, e.g., the ability to disperse a coated semiconductor nanocrystal homogeneously into a chosen solvent, functionality, binding properties, or the like.
• the coat can be used to tailor the optical properties of the semiconductor nanocrystal.
• Identity unit or barcode As used herein, the term “identification unit” is used synonymously with the term “barcode”, and comprises one or more sizes of semiconductor nanocrystals, each size of semiconductor nanocrystal having a characteristic emission spectrum. The “identification unit” or “barcode” enables the determination of the location or identity of a particular item or matter of interest.
• “Item of interest” As used herein, the term “item of interest” is used synonymously with the term “component of interest” and refers to any item, including, but not limited to, consumer item, fluid, gas, solid, chemical compound, and biomolecule.
• Biomolecule As used herein, the term “biomolecule” refers to molecules (e.g., proteins, amino acids, nucleic acids, nucleotides, carbohydrates, sugars, lipids, etc.) that are found in nature.
• polynucleotide oligonucleotide
• nucleic acid nucleic acid molecule
• nucleic acid molecule polymeric form of nucleotides of any length, either ribonucleotides or deoxyribonucleotides. This term refers only to the primary structure of the molecule. Thus, the term includes triple-, double- and single-stranded DNA, as well as triple-, double- and single-stranded RNA. It also includes modifications, such as by methylation and/or by capping, and unmodified forms of the polynucleotide.
• polynucleotide examples include polydeoxyribonucleotides (containing 2-deoxy-D- ribose), polyribonucleotides (containing D-ribose), any other type of polynucleotide which is an N- or C-glycoside of a purine or pyrimidine base, and other polymers containing nonnucleotidic backbones, for example, polyamide (e.g., peptide nucleic acids (PNAs)) and polymorpholino (commercially available from the Anti-Virals, Inc., Corvallis, Oregon, as Neugene) polymers, and other synthetic sequence-specific nucleic acid polymers providing that the polymers contain nucleobases in a configuration which allows for base pairing and base stacking, such as is found in DNA and RNA.
• PNAs peptide nucleic acids
• these terms include, for example, 3'-deoxy-2',5'-DNA, oligodeoxyribonucleotide N3' P5' phosphoramidates, 2'-O-alkyl-substituted RNA, triple-, double- and single-stranded DNA, as well as triple-, double- and single-stranded RNA, DNA:RNA hybrids, and hybrids between PNAs and DNA or RNA, and also include known types of modifications, for example, labels which are known in the art, methylation, "caps," substitution of one or more of the naturally occurring nucleotides with an analog, internucleotide modifications such as, for example, those with uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoramidates, carbamates, etc.), with negatively charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.), and with positively charged linkages (e.g., aminoalk
• Polypeptide and “protein” are used interchangeably herein and include a molecular chain of amino acids linked through peptide bonds. The terms do not refer to a specific length of the product. Thus, “peptides,” “oligopeptides,” and “proteins” are included within the definition of polypeptide. The terms include post-translational modifications of the polypeptide, for example, glycosylations, acetylations, phosphorylations and the like. In addition, protein fragments, analogs, mutated or variant proteins, fusion proteins and the like are included within the meaning of polypeptide. The term “sugar moiety” includes reference to monosaccharides, disaccharides, polysaccharides, and the like.
• sugar includes those moieties which have been modified, e.g., wherein one or more of the hydroxyl groups are replaced with halogen, alkoxy moieties, aliphatic groups, or are functionalized as ethers, amines, or the like.
• modified sugars include: those which contain a lower alkoxy group in place of a hydroxyl moiety, i.e., ⁇ - or ⁇ -glycosides such as methyl ⁇ -D-glucopyranoside, methyl ⁇ -D-glucopyranoside, and the like; those which have been reacted with amines, i.e., N-glycosylamines or N-glycosides such as N-( ⁇ -D-glucopyranosyl)methylamine; those containing acylated hydroxyl groups, typically from 1 to 5 lower acyl groups; those containing one or more carboxylic acid groups, e.g., D-gluconic acid or the like; and those containing free amine groups such as D-glucosamine, D-galactosamine, N-acetyl-D- glucosamine or the like.
• Examples of preferred saccharides are glucose, galactose, fructose, ribose, mannose, arabinose, and xylose.
• Examples of polysaccharides is dextran and cellulose.
• one or more sizes of semiconductor nanocrystals is used synonymously with the phrase “one or more particle size distributions of semiconductor nanocrystals".
• One of ordinary skill in the art will realize that particular sizes of semiconductor nanocrystals are actually obtained as particle size distributions.
• the phrase "associated with” is used herein to indicate items that are physically linked by, for example, covalent chemical bonds, physical forces such van der Waals or hydrophbic interactions, encapsulation, embedding, or the like.
• the phrase “associated with” also intends maintaining a correspondence between items by other than physical linkage, e.g., through the use of a look-up table or other method of recording the association/correspondence.
• binding pair refers first and second molecules that specifically bind to each other "Specific binding" of the first member of the binding pair to the second member of the binding pair in a sample is evidenced by the binding of the first member to the second member, or vice versa, with greater affinity and specificity than to other components in the sample
• the binding between the members of the binding pair is typically non-covalent
• affinity molecule and “target analyte” are used herein to refer to first and second members of a binding pair, respectively.
• Exemplary binding pairs include any haptenic or antigenic compound in combination with a corresponding antibody or binding portion or fragment thereof (e.g., digoxigenin and anti-digoxigenin; mouse immunoglobulin and goat anti-mouse immunoglobulin) and nonimmunological binding pairs (e.g., biotin-avidin, biotin- strepavidin, hormone [e.g., thyroxine and cortisol]-hormone binding protein, receptor- receptor agonist or antagonist (e.g., acetylcholine receptor-acetylcholine or an analog thereof) IgG-protein A, lectin-carbohydrate, enzyme-enzyme cofactor, enzyme-enzyme- inhibitor, and complementary polynucleotide pairs capable of forming nucleic acid duplexes) and the like.
• biotin-avidin e.g., digoxigenin and anti-digoxigenin; mouse immunoglobulin and goat anti-mouse immunoglobulin
• the present invention provides a novel encoding system.
• the present invention utilizes a "barcode” comprising one or more particle size distributions of semiconductor nanocrystals, having characteristic spectral emissions, to either "track” the location of a particular item of interest or to identify a particular item of interest.
• the semiconductor nanocrystals used in the inventive "barcoding" scheme can be tuned to a desired wavelength to produce a characteristic spectral emission by changing the composition and size of the semiconductor nanocrystal, and additionally, the intensity of the emission at a particular characteristic wavelength can also be varied, thus enabling the use of binary or higher order encoding schemes.
• the information encoded by the semiconductor nanocrystals can be spectroscopically decoded, thus providing the location and/or identity of the particular item or component of interest.
• semiconductor nanocrystals have radii that are smaller than the bulk exciton Bohr radius and constitute a class of materials intermediate between molecular and bulk forms of matter. Quantum confinement of both the electron and hole in all three dimensions leads to an increase in the effective band gap of the material with decreasing crystallite size. Consequently, both the optical absorption and emission of semiconductor nanocrystals shift to the blue (higher energies).
• each semiconductor nanocrystal distribution Upon exposure to a primary light source, each semiconductor nanocrystal distribution is capable of emitting energy in narrow spectral linewidths, as narrow as 25- 30 nm, and with a symmetric, nearly Gaussian line shape, thus providing an easy way to identify a particular semiconductor nanocrystal.
• the linewidths are dependent on the size heterogeneity, i.e., monodispersity, of the semiconductor nanocrystals in each preparation.
• Single semiconductor nanocrystal complexes have been observed to have full width at half max (FWHM) as narrow as 12- 15 nm.
• semiconductor nanocrystal distributions with larger linewidths in the range of 40-60 nm can be readily made and have the same physical characteristics as semiconductor nanocrystals with narrower linewidths.
• Exemplary materials for use as semiconductor nanocrystals in the present invention include, but are not limited to group II-IV, III-V and group IV semiconductors such as ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, GaN, GaP, GaAs, GaSb, InP, InAs, InSb, A1S, A1P, AlSb, PbS, PbSe, Ge and Si and ternary and quaternary mixtures thereof.
• the semiconductor nanocrystals are characterized by their uniform nanometer size. By “nanometer” size, it is meant less than about 150 Angstroms (A), and preferably in the range of 12-150 A.
• a particular composition of a semiconductor nanocrystal as listed above will be selected based upon the spectral region being monitored
• semiconductor nanocrystals that emit energy in the visible range include, but are not limited to CdS, CdSe, CdTe, ZnSe, ZnTe, GaP, and GaAs.
• Figure 1 depicts a color photograph of several suspensions of different sizes of ZnS overcoated CdSe semiconductor nanocrystals in hexane illustrating the wide range of colors available for use in the present invention
• Semiconductor nanocrystals that emit energy in the near IR range include, but are not limited to, InP, InAs, InSb, PbS, and PbSe
• semiconductor nanocrystals that emit energy in the blue to near-ultraviolet include, but are not limited to ZnS and GaN
• it is possible to tune the emission to a desired wavelength by controlling the size of the particular composition of the semiconductor nanocrystal In preferred embodiments, 5-20 discrete emissions (five to twenty different size populations or distributions distinguishable from one another) are obtained for any particular composition, although one of ordinary skill in the art will realize that fewer than five emissions and more than twenty emissions could be used depending on the monodispersity of the semiconductor nanocrystal particles.
• the nanocrystals are also substantially monodisperse within the broad nanometer range given above (12-150 A).
• monodisperse as that term is used herein, it means a colloidal system in which the suspended particles have substantially identical size and shape.
• monodisperse particles deviate less than 10% rms in diameter, and preferably less than 5%.
• Monodisperse semiconductor nanocrystals have been described in detail in Murray et al. (J. Am. Chem.
• the linewidth of the emission may be in the range of 40-60 nm.
• the intensities of that particular emission observed at a specific wavelength are also capable of being varied, thus increasing the potential information density provided by the semiconductor nanocrystal "barcode" system.
• 2-15 different intensities may be achieved for a particular emission at a desired wavelength, however, one of ordinary skill in the art will realize that more than fifteen different intensities may be achieved, depending upon the particular application of the inventive identification units.
• different intensities may be achieved by varying the concentrations of the particular size semiconductor nanocrystal attached to, embedded within or associated with an item or component of interest.
• the surface of the semiconductor nanocrystal is also modified to enhance the efficiency of the emissions, by adding an overcoating layer to the semiconductor nanocrystal.
• the overcoating layer is particularly preferred because at the surface of the semiconductor nanocrystal, surface defects can result in traps for electron or holes that degrade the electrical and optical properties of the semiconductor nanocrystal.
• An insulating layer at the surface of the semiconductor nanocrystal provides an atomically abrupt jump in the chemical potential at the interface that eliminates energy states that can serve as traps for the electrons and holes. This results in higher efficiency in the luminescent process.
• Suitable materials for the overcoating layer include semiconductors having a higher band gap energy than the semiconductor nanocrystal.
• suitable materials for the overcoating layer should have good conduction and valence band offset with respect to the semiconductor nanocrystal.
• the conduction band is desirably higher and the valence band is desirably lower than those of the semiconductor nanocrystal.
• a material that has a band gap energy in the ultraviolet regions may be used.
• Exemplary materials include ZnS, GaN, and magnesium chalcogenides, e.g., MgS, MgSe, and MgTe.
• materials having a band gap energy in the visible such as CdS or CdSe, may also be used.
• the overcoating layer may include as many as eight monolayers of the semiconductor material.
• the preparation of a coated semiconductor nanocrystal may be found in U.S.S.N. 08/969,302, filed November 13, 1997 and entitled "Highly Luminescent Color-Selective Materials", and Dabbousi et al., (J Phys. Chem. B, 1997, 101, 9463) and Kuno et al., ( J. Phys. Chem., 1997, 106, 9869).
• the semiconductor nanocrystals can be attached to, embedded within or associated with that particular item of interest.
• the item of interest must be sufficiently reactive with the surface of the semiconductor nanocrystal, or must be sufficiently compatible with the semiconductor nanocrystal.
• semiconductor nanocrystals are prepared in coordinating solvent, such as trioctylphosphine oxide (TOPO) and trioctyl phosphine (TOP) resulting in the formation of a passivating organic layer on the dot surface comprised of the organic solvent.
• This layer is present on semiconductor nanocrystals containing an overcoating and those that do not contain an overcoating.
• organic solvents such as toluene, chloroform and hexane.
• these functional moieties may be readily displaced or modified to provide an outer coating that renders the semiconductor nanocrystals suitable for use as the identification units of the present invention.
• a portion of the semiconductor nanocrystal functionality, or the entire surface of the semiconductor nanocrystal functionality may be modified by a displacement reaction, based upon the desired application of the inventive identification units.
• Figure 2 depicts general displacement reactions of certain functional moieties to provide a semiconductor nanocrystals with modified functionalities for use in the inventive method.
• Figure 2 also depicts the ability to displace a specific percentage of moieties on the surface of the semiconductor nanocrystals.
• reaction A depicts the partial displacement of moiety X by moiety Y
• reaction B depicts the complete displacement of moiety X by moiety Y for a semiconductor nanocrystal having no overcoating layer.
• Reactions C and D depict the partial and complete displacement reactions for overcoated semiconductor nanocrystals, respectively.
• moieties such as TOPO and TOP, as well as other moieties may be readily displaced and replaced with other functional moieties, including, but not limited to carboxylic acids, amines, aldehydes, and styrene to name a few.
• factors relevant to the success of a particular displacement reaction include the concentration of the replacement moiety, temperature and reactivity.
• any functional moiety may be utilized that is capable of displacing an existing functional moiety to provide a semiconductor nanocrystal with a modified functionality for a specific use of the identification units of the present invention.
• water soluble semiconductor nanocrystals are provided for use in aqueous environments.
• the outer layer includes a compound having at least one linking moiety that attaches to the surface of the particle and that terminates in at least one hydrophilic moiety.
• the linking and hydrophilic moieties are spanned by a hydrophobic region sufficient to prevent charge transfer across the region.
• the hydrophobic region also provides a "pseudo-hydrophobic" environment for the nanocrystal and thereby shields it from aqueous surroundings.
• the hydrophilic moiety may be a polar or charged (positive or negative) group.
• the polarity or charge of the group provides the necessary hydrophilic interactions with water to provide stable solutions or suspensions of the semiconductor nanocrystal.
• hydrophilic groups include polar groups such as hydroxides (-OH), amines, polyethers, such as polyethylene glycol and the like, as well as charged groups, such as carboxylates (-CO 2 ), sulfonates (SO 3" ), phosphates (-PO 4 2” and -PO 3 2 ⁇ ), nitrates, ammonium salts (-NH 4+ ), and the like.
• polar groups such as hydroxides (-OH), amines, polyethers, such as polyethylene glycol and the like
• charged groups such as carboxylates (-CO 2 ), sulfonates (SO 3" ), phosphates (-PO 4 2" and -PO 3 2 ⁇ ), nitrates, ammonium salts (-NH 4+ ), and the like.
• a displacement reaction may be employed to modify the semiconductor nanocrystal to improve the solubility in a particular organic solvent.
• a particular solvent or liquid such as pyridine
• the surface can be specifically modified with pyridine or pyridine-like moieties to ensure solvation.
• the surface layer is modified by displacement to render the semiconductor nanocrystal reactive for a particular coupling reaction.
• displacement of TOPO moieties with a group containing a carboxylic acid moiety enables the reaction of the modified semiconductor nanocrystals with amine containing moieties (commonly found on solid support units) to provide an amide linkage.
• the surface of the semiconductor nanocrystal can also be modified to create a surface on the semiconductor nanocrystal similar to an object that the semiconductor nanocrystal will be associated with.
• the semiconductor nanocrystal surface can be modified using a displacement reaction to create styrene or acrylate moieties, thus enabling the incorporation of the semiconductor nanocrystals into polystyrene, polyacrylate or other polymers such as polymer, such as polyimide, polyacrylamide, polyethylene, polyvinyl, poly-diacetylene, polyphenylene-vinylene, polypeptide, polysaccharide, polysulfone, polypyrrole, polyimidazole, polythiophene, polyether, epoxies, silica glass, silica gel, siloxane, polyphosphate, hydrogel, agarose, cellulose, and the like.
• polymer such as polyimide, polyacrylamide, polyethylene, polyvinyl, poly-diacetylene, polypheny
• selection of the composition of semiconductor nanocrystal for the desired range of spectral emission and selection of a desired surface functionalization compatible with the system of interest it may also be desirable to select the minimum number of semiconductor nanocrystals needed to observe a distinct and unique spectral emission of sufficient intensity for spectral identification.
• Selection criteria important in determining the minimum number of semiconductor nanocrystals needed to observe a distinct and unique spectral emission of sufficient intensity include providing a sufficient number of semiconductor nanocrystals that are bright (i.e., that emit light versus those that are dark) and providing a sufficient number of semiconductor nanocrystals to average out over the blinking effect observed in single semiconductor nanocrystal emissions (M. Nirmal et al., Nature, 1996, 383, 802).
• At least eight semiconductor nanocrystals of a particular composition and particle size distribution are provided.
• a "barcode" were provided that utilized three different particle size distributions of a particular composition, it would be most desirable to utilize eight of each of the three different particle size distributions of a semiconductor nanocrystal, in order to observe sufficiently intense spectral emissions from each to provide reliable information regarding the location or identity of a particular item or matter of interest.
• One of ordinary skill in the art will realize, however, that fewer than eight semiconductor nanocrystals of a particular composition and particle size distribution could be utilized provided that a unique spectral emission of sufficient intensity is observed, as determined by the selection criteria set forth above.
• the ability of the semiconductor nanocrystals to produce discrete optical transitions, along with the ability to vary the intensity of these optical transitions, enables the development of a versatile and dense encoding scheme.
• the characteristic emissions produced by one or more sizes of semiconductor nanocrystals attached to, associated with, or embedded within a particular support or matter enables the identification of the item or composition of interest and/or its location. For example, by providing N sizes of semiconductor nanocrystals (each having a discrete optical transition), each having M distinguishable states resulting from the absence of the semiconductor nanocrystal, or from different intensities resulting from a particular discrete optical transition, M" different states can be uniquely defined.
• the encoding scheme would thus be defined by a base 2 or binary code.
• base M codes where M > 2 are termed higher order codes. The advantage of higher order codes over a binary order code is that fewer identifiers are required to encode the same quantity of information.
• each discrete emission or color is capable of being detectable at two to twenty different intensities.
• a base 11 code comprising the absence of the semiconductor nanocrystal, or the detection of the semiconductor nanocrystal at 10 different intensities.
• one or more semiconductor nanocrystals may act as a barcode, wherein each of the one or more semiconductor nanocrystals produces a distinct emissions spectrum. These characteristic emissions can be observed as colors, as shown in Figure 1, if in the visible region of the spectrum, or may also be decoded to provide information about the particular wavelength at which the discrete transition is observed.
• the characteristic wavelengths that the discrete optical transitions occur at provide information about the identity of the particular semiconductor nanocrystal, and hence about the identity of or location of the item or matter of interest.
• An example of a specific system for automated detection that could be employed for use in the present invention includes, but is not limited to, an imaging scheme comprising an excitation source, a monochromator (or any device capable of spectrally resolving the image, or a set of narrow band filters) and a detector array.
• the apparatus would consist of a blue or UN source of light, of a wavelength shorter than that of the luminescence detected.
• the luminescence from the dots would be passed through an imaging subtracting double monochromator (or two single monochromators with the second one reversed from the first), for example, consisting of two gratings or prisms and a slit between the two gratings or prisms.
• the monochromators or gratings or prisms can also be replaced with a computer controlled color filter wheel where each filter is a narrow band filter centered at the wavelength of emission of one of the dots.
• the monochromator assembly has more flexibility because any color can be chosen as the center wavelength.
• a CCD camera or some other two dimensional detector records the images, and software color codes that image to the wavelength chosen above. The system then moves the gratings to a new color and repeats the process.
• the apparatus is a scanning system as opposed to the above imaging scheme.
• a scanning scheme the sample to be analyzed is scanned with respect to a microscope objective.
• the luminescence is put through a single monochromator or a grating or prism to spectrally resolve the colors.
• the detector is a diode array that then records the colors that are emitted at a particular spatial position.
• the software then ultimately recreates the scanned image and decodes it.
• the inventive system can be utilized to track or trace the location of a component of interest.
• fluid dynamics involves generally monitoring the interaction between different fluid components, and thus the location of individual molecules of the desired fluid provides valuable information about the effectiveness of and the degree of interaction between separate components, specifically the controlled movement and mixing of components.
• the semiconductor nanocrystals can be appropriately functionalized to facilitate interaction with the desired component of interest (so that the semiconductor nanocrystals are compatible with the fluid they are intended to act as tracers for), as discussed in detail earlier, and subsequent mixing of the individual components can be effected.
• the surface of the semiconductor nanocrystals can be modified with pyridine or dimethylsulfoxide moieties to ensure association of or compatibility of a particular size distribution of semiconductor nanocrystals with the appropriate fluid. Because each the semiconductor nanocrystals are specifically associated with a particular component, it is then possible to take a photograph of the reaction mixture with a ultraviolet lamp and, based upon the discrete optical emissions produced from the semiconductor nanocrystals, gain information about the degree of interaction of the individual components.
• Figure 3 depicts a general method for fluid dynamics, wherein two streams of fluid (10) and (20), represented by X and Y in Figure 3, are introduced into a reaction chamber (30) and the mixing of the fluids is monitored by taking a "picture" at a given time with an excitation source to observe the position of the semiconductor nanocrystals associated with the particular fluid.
• Figure 3B depicts an enlargement of the reaction chamber (30) and shows the association of the semiconductor nanocrystals (40) with a particular fluid of interest (10).
• N represents the number of discrete transitions.
• microfluidic molecular systems MicroFlumes. These microfluidic systems perform multiple reaction and analysis techniques in one microinstrument for specificity and validation, they are completely automated, they contain multiple parallel reaction paths (as opposed to the sequential analysis required today) and provide the capability for hundreds of operations to be performed without manual intervention. (See http://web-ext2.darpa.mil/eto/mFlumes/index.html)
• the semiconductor nanocrystal semiconductor nanocrystals can be used as in the general method described above, where each semiconductor nanocrystal or combination thereof can be associated with or attached to a specific component of interest and upon mixing of the various components, and providing a primary light source, can provide information about the degree and type of interaction between the different components.
• inventive encoding system is not limited to the fluid dynamics applications described above; rather the inventive system is capable of being utilized in any system where the tracking of the location of a component or item, such as a gas, liquid, solid, or consumer item (such as dry-cleaned clothing) is desired.
• Identification of an object The system of the present invention can also be utilized to identify specific objects including, but not limited to, jewelry, paper, biomolecules such as DNA, vehicles and identification cards.
• the semiconductor nanocrystals can be appropriately functionalized for incorporation into or attachment to the surface of the object of interest, as discussed above, and as shown in Figure 4.
• Figure 4A depicts the incorporation of the semiconductor nanocrystals into an item of interest (50), wherein the surface of semiconductor nanocrystal has been modified to enable incorporation into the item of interest.
• Figure 4B depicts the coating of a semiconductor nanocrystal composition (80) into an item of interest (90), wherein the surface of the semiconductor nanocrystal (70) is modified to interact with the composition medium X (60).
• the semiconductor nanocrystal surface may be functionalized with a specific percentage of amine moieties, thus enabling incorporation into paper, which is comprised of carbohydrate moieties.
• the semiconductor nanocrystals may be appropriately functionalized with moieties such as styrene or acrylate to enable incorporation into polymers.
• the polymers containing the identification units can then be coated onto, or incorporated within specific items such as identification cards. The ease with which the semiconductor nanocrystals can be incorporated into the item and the fact that the semiconductor nanocrystal based "barcode" is invisible, provides a useful system for labeling objects.
• the ability of the semiconductor nanocrystal "barcode" system to encode large amounts of information, and thus large numbers of items, provides an advantage over existing barcode or microparticle systems discussed previously.
• the identification of the item of interest from a collection of items can be effected by providing a primary light source and correlating the spectral emissions to a collection of semiconductor nanocrystals that encode a particular item of interest.
• the present system may be utilized to keep track of the identity of biomolecules, such as DNA sequences, while they are subjected to reaction processes and chemical manipulations.
• biomolecules, or DNA sequences could be "tagged” themselves, or, alternatively, the biomolecules could be attached to a support, wherein the support is "tagged” with one or more sizes of semiconductor nanocrystals encoding the identity of the DNA sequence.
• the inventive semiconductor nanocrystals may also be used to identify a particular compound in a library of compounds by encoding a particular reaction sequence employed for each of the compounds in the synthesis of complex combinatorial libraries, and thus acting as an identifier. Because of the desirability for the production of large numbers of complex compounds, particularly using a split and pool method, the development of encoding techniques to identify each compound of interest has become important. Because of the small quantity of final product or compound produced from such methods, identifying these products would generally not be feasible.
• each stage or combination of stages of the serial synthesis with an identifier which defines the choice of variables such as reactant, reagent, reaction conditions, or a combination of these, one can use the identifiers to define the reaction history of each definable and separable substrate.
• the spectral analysis of the semiconductor nanocrystals allows for ready identification of the reaction history. For example, one can determine a characteristic of a product of a synthesis, usually a chemical or biological characteristic by various screening techniques, and then identify the reaction history and thereby the structure of that product, which has the desired characteristic, by virtue of the semiconductor nanocrystal "barcode" associated with the product.
• the advantage of providing a distinct and non-overlapping resonance, capable of detection at different intensities enables the use of a binary encoding system or higher.
• the absence or presence of a particular size semiconductor nanocrystal could be used in a binary system.
• the use of different intensities, of the same color enables the use of a higher order encoding system, each color intensity encoding a particular characteristic.
• the products to be encoded include, but are not limited to biomolecules (such as peptides and oligonucleotides, organic compounds, and inorganic compounds and catalysts resulting from combinatorial synthesis.
• Exemplary combinatorial libraries that can be synthesized using the present encoding method include, but are not limited to peptide libraries, peptidomimetics, carbohydrates, organometallic catalysts and small molecule libraries (For examples see, Kahne, D. Curr. Opin. Chem. Biol, 1997, 7, 130; Hruby et al., Curr. Opin. Chem. Biol, 1997, 1 , 1 14; Gravert et al., Curr. Opin. Chem. Biol, 1997, /, 107).
• a solid phase synthesis technique such as split and pool synthesis is utilized, in which the desired scaffold structures are attached to the solid phase directly or though a linking unit, as discussed above.
• Advantages of solid phase techniques include the ability to conduct multi-step reactions more easily and the ability to drive reactions to completion because excess reagents can be utilized and the unreacted reagent washed away.
• One of the most significant advantages of solid phase synthesis is the ability to use a technique called "split and pool", in addition to the parallel synthesis technique, developed by Furka. (Furka et al., Abstr. 14th Int. Congr. Biochem., Prague, Czechoslovakia, 1988, 5, 47; Furka et al., Int. J.
• the solid support scaffolds can be divided into n vessels, where n represents the number species of reagent A to be reacted with the scaffold structures. After reaction, the contents from n vessels are combined and then split into m vessels, where m represents the number of species of reagent B to be reacted with the scaffold structures. This procedure is repeated until the desired number of reagents is reacted with the scaffold structures to yield the inventive library.
• a solid support for the purposes of this invention, is defined as an insoluble material to which compounds are attached during a synthesis sequence.
• the use of a solid support is advantageous for the synthesis of libraries because the isolation of support-bound reaction products can be accomplished simply by washing away reagents from the support-bound material and therefore the reaction can be driven to completion by the use of excess reagents.
• a solid support can be any material that is an insoluble matrix and can have a rigid or semi-rigid surface.
• Exemplary solid supports include but are not limited to pellets, disks, capillaries, hollow fibers, needles, pins, solid fibers, cellulose beads, pore-glass beads, silica gels, polystyrene beads optionally cross-linked with divinylbenzene, grafted co-poly beads, poly-acyrlamide beads, latex beads, dimethylacrylamide beads optionally crosslinked with N-N'-bis-acryloylethylenediamine, and glass particles coated with a hydrophobic polymer.
• a Tentagel amino resin a composite of 1) a polystyrene bead crosslinked with a divinylbenzene and 2) PEG (polyethylene glycol), is employed for use in the present invention.
• the semiconductor nanocrystals of the present invention can readily be functionalized with styrene and thus can be incorporated into Tentagel beads, or the semiconductor nanocrystals may be functionalized with a carboxylate moiety and can be readily attached to the Tentagel support having an amine moiety through an amide linkage.
• Tentagel is a particularly useful solid support because it provides a versatile support for use in on-bead or off-bead assays, and it also undergoes excellent swelling in solvents ranging from toluene to water.
• FIG. 5 depicts the attachment of three different reagents A, B, and C (120) to a solid support, and the attachment of the identification unit (140) to the solid support (100) via a linkage (90).
• the supports are then pooled together (130) and split for reaction with reagents D, E, and F. Attachment of appropriate identification units for each of these reagents enables the encoding of this particular reaction stage as observed previously for reagents A, B, and C.
• the tags may be attached to all (or most) of the solid supports immediately before, during, or immediately after the reaction stage, depending on the particular chemistry used in a given reaction sequence.
• the beads can be labeled with the semiconductor nanocrystals prior to reaction of the beads with any reagents, and as the beads are split in the split and pool process, the beads are read before being added to a new (split stage) container to keep track of the particular reaction at that particular stage in the synthesis.
• the library of compounds can then be screened for biological activity and the supports having a compound of interest can then be analyzed directly (on-bead analysis) to provide information about the reaction stages and history of the synthesis.
• the inventive system can be utilized to gain information about genetic information from oligonucleotide fragments.
• genetic variation and its consequences on biological function, and in order to do this, an enormous comparative sequence analysis must be carried out.
• each DNA strand has the capacity to recognize a uniquely complementary sequence through base pairing, the process of recognition, or hybridization, is highly parallel, as every nucleotide in a large sequence can in principle be queried at the same time.
• DNA chip technology has been an important tool for genomics applications.
• Single nucleotide polymorphisms SNPs are the most frequently observed class of variations in the human genome. Detecting the differences between alleles of genes is a significant goal of medical research into genetic diseases and disorders. (For example, sickle cell anemia, colon cancer, BRCA1).
• Current technology has allowed for large scale screening of DNA sequences for mutations in the sequence. This technology involves the creation of DNA "chips" that contain high-density arrays of DNA sequences (e.g. STSs) covalently bound at specific locations on a surface (glass).
• a set of four oligonucleotides of identical sequence except for a single base alteration (A, G, T, or C) near the center is used to compare two alleles of a gene.
• Single nucleotide differences between alleles at the position complementary to altered sites in the set of four oligos will allow one oligonucleotide to hybridize preferentially over the other three. Detecting which oligonucleotide hybridizes to the sample DNA will then identify the sequence of the polymorphism. By creating sets of these four oligos that are shifted over by one nucleotide each, a researcher can scan a large number of basepairs for single nucleotide polymorphisms.
• the system of the present invention in contrast to fluorescently labeled probes used in the existing methods, is capable of not only acting as a probe for identification of a desired sequence, but is also capable of encoding information about the sequence itself. Because the inventive identification system is capable of providing both a probe and identifier, ordered arrays are not necessary for accessing genetic information, although the inventive system can still be used in traditional arrays. Instead, a collection of beads, for example, can be assembled with the desired labeled DNA fragments, wherein said beads are also encoded with information about the particular sequence.
• the oligonucleotide that hybridizes to the sample DNA can be detected by scanning the sample to identify the semiconductor nanocrystal labeled probe, while at the same time the sequence information can then be decoded by analyzing the semiconductor nanocrystal "barcode".

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