WO2002031191A2 - Dendritically amplified detection method - Google Patents
Dendritically amplified detection method Download PDFInfo
- Publication number
- WO2002031191A2 WO2002031191A2 PCT/IL2001/000886 IL0100886W WO0231191A2 WO 2002031191 A2 WO2002031191 A2 WO 2002031191A2 IL 0100886 W IL0100886 W IL 0100886W WO 0231191 A2 WO0231191 A2 WO 0231191A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- nucleic acid
- nanoparticle
- probe
- target nucleic
- electrode
- Prior art date
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y10/00—Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
-
- 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
- C12Q1/6816—Hybridisation assays characterised by the detection means
- C12Q1/6825—Nucleic acid detection involving sensors
-
- 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
- C12Q1/6816—Hybridisation assays characterised by the detection means
- C12Q1/682—Signal amplification
-
- H—ELECTRICITY
- H10—SEMICONDUCTOR DEVICES; ELECTRIC SOLID-STATE DEVICES NOT OTHERWISE PROVIDED FOR
- H10K—ORGANIC ELECTRIC SOLID-STATE DEVICES
- H10K85/00—Organic materials used in the body or electrodes of devices covered by this subclass
- H10K85/761—Biomolecules or bio-macromolecules, e.g. proteins, chlorophyl, lipids or enzymes
Definitions
- This invention relates to a method and system for detecting nucleic acids.
- DNA-based electronics has been the subject of extensive recent research activities that address the conductivity features of double-stranded (ds) DNA [1,2].
- ds-DNA double-stranded DNA
- the optical properties of DNA-crosslinked Au-nanoparticles were recently studied and applied for DNA sensing [5], and nano-architectures of DNA/Au-nanoparticles were assembled [6].
- the electronic transduction of DNA sensing, and specifically the amplified DNA analyses, were recently reported by the use of electrochemical [7] or microgravimetric quartz-crystal-microbalance measurements.
- detect or “detection” in this specification refer collectively to both a qualitative determination and identification of the target nucleic acid in the sample as well as, at times, a quantitative determination of the level of the target nucleic acid in the sample.
- the present invention provides a method for constructing a dendritic architecture of double-stranded nucleic acid crosslinked seniconductor-nanoparticle arrays on solid supports and the structurally-controlled generation of photocurrents and/or optical signals upon irradiation of these arrays.
- the present invention provides a method for the detection of a target nucleic acid in a sample solution, said target nucleic acid comprising a first and a second end sequence, one of said end sequences being a 5' end sequence and the other end sequence being a 3' end sequence, said method comprising:
- step (c) contacting the solid surface of step (b) with said sample solution, thereby allowing said first probe to bind said target nucleic acid;
- step (e) contacting the solid surface of step (c) with said second nanoparticle, thereby allowing said second probe to bind said bound target nucleic acid;
- step (f) providing a first semiconductor nanoparticle to which has been attached said first oligonucleotide probe and pre-incubating said first nanoparticle with said target nucleic acid, thereby allowing said first probe to bind said target nucleic acid;
- step (e) contacting the solid surface of step (e) with said pre-incubated first nanoparticle, thereby allowing said target nucleic acid bound to said first probe to bind said second probe on said second nanoparticle;
- the target nucleic acid in the sample solution is first contacted with the immobilized oligonucleotide probe on the solid surface.
- the target nucleic acid is first contacted with the immobilized oligonucleotide probe on the nanoparticle.
- this alternate embodiment is performed as follows: (a) providing a solid surface; (b) attaching to said solid surface a first oligonucleotide probe, at least a portion of which is complementary to the first end sequence of said target nucleic acid;
- step (d) contacting the solid surface of step (b) with said pre-incubated second nanoparticle, thereby allowing said bound target nucleic acid to bind said first probe;
- the nanoparticle used in the method of the invention may comprise any semiconducting compound having photoconductive properties. Examples of such compounds include CdS, CdSe, GaAs, PbS and ZnS. CdS is a preferred nanoparticle compound.
- the nanoparticles in one array may comprise the same or different semiconducting compounds. In a preferred embodiment, the nanoparticles comprise the same semiconducting compound. The presence of the nanoparticles may be detected optically or photoelectrochemically.
- the nanoparticles are detected optically, this may be by any technique known per se, such as fluorescence detection or light absorbance detection.
- the solid surface on which the array is fabricated may be any material to which an oligonucleotide may be bound either directly or indirectly. Examples of such materials include a glass or polymer support.
- the solid support must be an electrode which can sense the photocurrent produced by irradiation of the nanoparticles.
- an electrode is an Au-electrode.
- the nanoparticles may be detected by measuring current flow or voltage.
- the detected signal may be amplified by incubating the electrode with an electron mediator capable of binding nucleic acids
- the electrostatic binding of the electron mediator on the nucleic acid units may provide tunneling routes for the conduction-band electrons, resulting in an enhanced photocurrent.
- electron mediators include organic compounds, transition metal complexes or metallic nanorods which can associate by electrostatic binding and/or intercalate with nucleic acids, thus improving the electrical contacting of the semiconductor nanoparticles with the electrode.
- nucleic acid in the present specification includes both DNA and RNA.
- the oligonucleotide probe will typically, but not exclusively, comprise a number of nucleotides completing about one helix of the nucleic acid strand, i.e. about twelve nucleotides.
- a sequence of twelve oligonucleotides ensures, on the one hand, stable hybridization and, on the other hand, a 12-mer oligonucleotide decreases the chance of binding to an incorrect nucleic acid than in the case of a longer sequence.
- the sample is a digested specimen of genomic DNA, or a fractionation product thereof comprising the nucleic acids
- This probability is lower, as aforesaid in the case of a shorter oligonucleotide.
- the specificity of binding increases with the length of the oligonucleotide with respect to longer target molecules.
- a sequence of about 12 nucleotides is preferred as it is optimal as far as ensuring binding stability, on the one hand, and reducing incorrect binding on the other hand.
- the invention is, however, not limited to such a length of the oligonucleotide probe, and the skilled man of the art will know how to adjust the length of the probe to the requirements of the method.
- a method for fabricating a multi-layered array of semiconductor nanoparticles crosslinked by nucleic acid comprising the steps of the method of the first aspect of the invention in both of its embodiments.
- a method for fabricating a semiconductor nanoparticle electronic circuit comprising electron mediator functionalized nucleic acid comprising: (a) providing an electrode; (b) attaching to said electrode a first oligonucleotide probe, at least a portion of which is complementary to a first end sequence of a nucleic acid; (c) contacting the electrode of step (b) with said nucleic acid, thereby allowing said first probe to bind said nucleic acid; (d) providing a second semiconductor nanoparticle to which has been attached a second oligonucleotide probe, at least a portion of which is complementary to a second end sequence of said nucleic acid;
- step (e) contacting the electrode of step (c) with said second nanoparticle, thereby allowing said second probe to bind said bound nucleic acid;
- step (f) providing a first semiconductor nanoparticle to which has been attached said first oligonucleotide probe and pre-incubating said first nanoparticle with said nucleic acid, thereby allowing said first probe to bind said nucleic acid; (g) contacting the electrode of step (e) with said pre-incubated first nanoparticle, thereby allowing said nucleic acid bound to said first probe to bind said second probe on said second nanoparticle; (h) optionally alternately repeating steps (e) and (g) one or more times; and (i) incubating said electrode with an electron mediator capable of binding nucleic acids.
- An alternate embodiment of the third aspect of the invention provides a method for fabricating a semiconductor nanoparticle electronic circuit comprising semiconductor arrays crosslinked by nano metallic rods in which the last step comprises incubating said electrode with a metal capable of binding nucleic acids.
- a semiconductor device comprising a dendritic nanoparticle array comprising semiconductor nanoparticles cross-linked by nucleic acid chains.
- a system for identifying a target nucleic acid sequence in a sample solution comprising: (a) a biochip comprising a plurality of arrays of functionalized solid surfaces each of which may act as a transducer, each of the surfaces having bound thereto an oligonucleotide probe, at least a portion of which is complementary to a different segment of a target nucleic acid sequence, each of the arrays being specific for a different target nucleic acid sequence; and (b) semiconductor nanoparticles functionalized with oligonucleotide probes, at least a portion of which is complementary to one end sequence or the other end sequence of one of the target nucleic acid sequences.
- a DNA chip or bio-chip may be used in which one row of solid surfaces will comprise probes complementary to different segments of the genetic material of one type of virus, a second row will comprise probes complementary to a second type of virus, etc.
- Application of the sample to the biochip, contacting it with the functionalized semiconductor nanoparticles and locating the row which produces a signal will enable identification of the infecting virus.
- a similar detection system may be used to identify genetic mutants and diseases, in tissue typing, gene analysis and forensic applications.
- a functionalized solid surface which acts as a transducer and having a probe attached thereto; and (b) semiconductor nanoparticles functionalized with oligonucleotide probes, a portion of which is complementary to one end or the other end of the target nucleic acid sequence.
- Fig. 1 is a schematic drawing illustrating the organization of oligonucleotide/DNA crosslinked arrays of CdS-nanoparticles according to one embodiment of the invention and the photoelectrochemical response of the nanoarchitectures;
- Fig. 2 is a schematic drawing illustrating an alternate embodiment of the method of the invention
- Fig. 3 shows the frequency change of an Au/quartz crystal (9 MHz, AT-cut upon the assembly of oligonucleotide/DNA crosslinked CdS-nanoparticle layers: the first layer is assembled by the reaction of the (l)-functionalized electrode with (3), lxl 0 "6 M, and then with the (2)-modified CdS nanoparticles. The other layers were constructed by the alternate treatment of the surface with a solution of (3), 1x10 " M that includes the (l)-modified CdS nanoparticles and a solution of (2)-functionalized CdS-nanoparticles;
- Fig. 5 shows photocurrent action spectra of an Au-electrode that includes programmed layers of oligonucleotide/DNA crosslinked CdS nanoparticles: (a) Prior to the deposition of CdS-nanoparticles. (b) to (e) One to four oligonucleotide DNA crosslinked CdS nanoparticle layers. Inset: Comparison of the photocurrent action spectrum of a four-layer CdS nanoparticle array (e) to the absorption spectrum (f) of the array;
- Fig. 6 shows photocurrent action spectra of: two-layer (a) and four layer (c) oligonucleotide CdS-nanoparticle crosslinked arrays.
- All photocurrent spectra were recorded under argon in 0.1 M KC1 using triethanolamine, 2x10 " M as sacrificial electron donor.
- the area of illuminated electrode corresponds to 1 cm ; and
- Fig. 7 shows sensing of the DNA (3) by the photocurrent response of the arrays.
- a 0.24 ml aliquot of a 1.0 M Cd(C10 4 )2 aqueous solution and 0.16 ml of a 1.0 Na 2 S aqueous solution were respectively added to 60 and 40 ml aliquots of the prepared inverse micelle solution. After the solution was stirred individually for 1 hr, these were mixed together and stirred for another 1 hr, resulting in the formation of Q-CdS in the inverse micelles.
- the surface of the resulting Q-CdS was modified both with 2-aminoethanethiol and with 2-mercapto ethanesulfonate.
- the modification with the latter compound was essential to dissolve the resulting particles in water solutions later.
- Both 0.17 mL of an 0.32 M 2-aminoethanethiol aqueous solution and 0.33 mL 0.32 M 2-mercapto ethanesulfonate solution were added to 100 mL of the inverse micelles solution containing !-CdS and stirred for 1 day, under Ar atmosphere, resulting in thiol-capped Q-CdS nanoparticles. After drying under vacuum, the thiol-capped Q-CdS was washed successively with pyridine, n-heptane, petroleum ether, 1-butanol, acetone, and methanol.
- a buffer solution containing the thiolated DNA (10 ).D/mL) was added, and aged for a period of 12 hrs, at 4°C. After that, the excess thiolated oligonucleotides were removed by centrifugation at 20,000 rpm, 1 hr at least, or by dialysis against PBS buffer, containing 0.02% NaN 3 , for 2 days at 4°C.
- the DNA-modified Q-CdS nanoparticles obtained by the two procedures outlined here were extremely soluble in water solutions, compared with the regular Q-CdS nanoparticles before DNA modification. Examples
- oligonucleotides were used as probes or target in the following examples: (4) 5'TCTATCCTACGCT-(CH 2 ) 6 -SH-3' (SEQ ID NO: 1)
- Fig. 1 illustrates the stepwise assembly of the DNA-crosslinked CdS particles on a solid surface in the form of a Au-electrode 2.
- a first oligonucleotide probe 4 e.g. SEQ ID NO:l
- SEQ ID NO: 3 target DNA 6
- the first probe 4 is attached to an Au-electrode 2 (2.3x10 '11 mole-cm " ), and the electrode is then interacted in reaction A with the sample solution containing the target DNA 6 to yield the ds-system.
- CdS-nanoparticles (2.6 ⁇ 0.4 nm) were functionalized with the thiolated first and second oligonucleotide probes 4 or 10. These two oligonucleotides are complementary to the 5' and 3'-ends of the target DNA 6, respectively.
- reaction B the electrode 2 is contacted with the second oligonucleotide probe 10 (SEQ ID NO: 2) functionalized nanoparticles 8 resulting in the binding of the CdS-nanoparticles 8 to the target DNA 6 bound to the electrode 2. This is termed the first generation 11 of the nanoparticle array.
- a further CdS nanoparticle 12 functionalized with the first oligonucleotide probe 4 was pre-incubated (lmg.mfl) with the target DNA 6 (1x10 " M), so that the target DNA bound to some of the probes 4 extending from the nanoparticle 12.
- the electrode 2 carrying the first nanoparticle generation was contacted in reaction C with the first probe-functionalized and target DNA- pre-incubated nanoparticles 12 resulting in the binding of the pre-incubated nanoparticles 12 to the first generation nanoparticles 8 This is termed the second generation 14 of the nanoparticle array.
- FIG. 2 An alternate embodiment of the method of the invention is illustrated in Fig. 2.
- the first probe 4 is attached to the Au-electrode 2.
- the second oligonucleotide probe 10-functionalized nanoparticles 18 are pre-incubated with the target DNA 6 so that the target DNA binds to some of the probes 10 extending from the nanoparticle 8.
- These pre-incubated nanoparticles 18 are contacted in reaction A with the electrode 2 so that the target DNA 6 bound to the nanoparticle binds to the immobilized first probe 4 on the electrode, resulting in the first generation 20.
- the electrode is then contacted in reaction B with a nanoparticle 22 functionalized with the first probe 4 which binds to the target DNA 6 forming the second generation 24.
- Example III The build-up of the DNA-crosslinked CdS-nanoparticle array was followed by microgravimetric quartz-crystal- microbalance experiments, the results of which are shown in Fig. 3. Similarly, the DNA-crosslinked CdS-nanoparticle arrays were assembled on glass supports using an aminopropylsiloxane-functionalized glass that was reacted with ⁇ -maleimidocaproic acid N-hydroxysuccinimide ester [10] as a base interface for the covalent linkage of the oligonucleotide probe and the organization of the nanoparticle systems.
- Figure 4 shows the absorbance spectra and the fluorescence spectra corresponding to the DNA-crosslinked CdS-nanoparticle arrays. The absorbance and fluorescence spectra increase as the generation of aggregated CdS increases.
- Figure 5 shows the photocurrent action spectra upon the excitation of the arrays that consist of different numbers of CdS nanoparticle generations that are associated with the electrode.
- the photocurrent follows the absorbance spectrum of the CdS-nanoparticles (inset, Figure 5), and it increases as the number of generations of crosslinked particles is higher.
- the photocurrent can be switched "ON” and “OFF” by pulsed irradiation of the respective arrays.
- the mechanism of photocurrent generation probably involves the photoejection of conduction-band electrons 28 of CdS-particles in contact or at tunneling distances from the electrode 2, as shown in Fig. 1. This suggests, however, that a part of the crosslinked crosslinked-nanoparticles do not participate in the development of the photocurrent.
- the arrays 14 were reacted with an electron mediator 30 such as Ru(NH 3 )e 3+ , 5x10 "6 M, that electrostatically binds to the DNA 32.
- an electron mediator 30 such as Ru(NH 3 )e 3+ , 5x10 "6 M, that electrostatically binds to the DNA 32.
- Figure 6 shows the photocurrents that are generated by the DNA-crosslinked CdS arrays that include two and four CdS-nanoparticle generations in the absence and presence of Ru(NH3) ⁇ 3+ , respectively.
- the photocurrent is ca. two-fold higher, implying that the DNA units act as a template for the electron acceptor units that mediate electron transfer to the electrode.
- the increase of the Ru(NH3) 6 + concentration to 5x10 " M adversely affects the photocurrent and it decreases to values below those observed in the presence of the CdS-arrays without the electron acceptor. This result is reasonable since at high bulk concentrations of Ru(NH 3 ) 6 diffusional electron transfer quenching of the semiconductor nanoparticles proceeds. This process traps the conduction-band electrons and thus prevents even the direct electron photoejection process.
- the photocurrents generated by the DNA-crosslinked array can be used for the quantitative detection of DNA.
- Figure 7 shows the photocurrents of a two-layer
- DNA-crosslinked nanoparticle array upon the formation of a third generation of CdS-nanoparticles in the presence of probe-functionalized CdS at different concentrations of target nucleic acid.
- concentration of target nucleic acid is increased, enhanced photocurrents are observed, indicating higher coverage of the electrode by the third generation of semiconductor nanoparticles.
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Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002424435A CA2424435A1 (en) | 2000-10-12 | 2001-09-24 | Dendritically amplified detection method |
US10/381,131 US20040048272A1 (en) | 2000-10-12 | 2001-09-24 | Dendritically amplified detection method |
EP01974639A EP1368490A2 (en) | 2000-10-12 | 2001-09-24 | Dendritically amplified detection method |
AU2001294150A AU2001294150A1 (en) | 2000-10-12 | 2001-09-24 | Dendritically amplified detection method |
JP2002534556A JP2005507488A (en) | 2000-10-12 | 2001-09-24 | Dendritic amplification inspection method |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL13898800A IL138988A (en) | 2000-10-12 | 2000-10-12 | Dendritically amplified detection method |
IL138988 | 2000-10-12 |
Publications (2)
Publication Number | Publication Date |
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WO2002031191A2 true WO2002031191A2 (en) | 2002-04-18 |
WO2002031191A3 WO2002031191A3 (en) | 2003-09-12 |
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PCT/IL2001/000886 WO2002031191A2 (en) | 2000-10-12 | 2001-09-24 | Dendritically amplified detection method |
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US (1) | US20040048272A1 (en) |
EP (1) | EP1368490A2 (en) |
JP (1) | JP2005507488A (en) |
AU (1) | AU2001294150A1 (en) |
CA (1) | CA2424435A1 (en) |
IL (1) | IL138988A (en) |
WO (1) | WO2002031191A2 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1375625A1 (en) * | 2002-06-10 | 2004-01-02 | Hitachi Software Engineering Co., Ltd. | Semiconductor nanoparticles and method for producing them |
WO2004090548A1 (en) * | 2003-03-13 | 2004-10-21 | Chengdu Kuachang Medical Industrial Limited | Device for analysis or separation containing an active nanostructured carrier, its preparation method and applications |
JP2005192439A (en) * | 2003-12-29 | 2005-07-21 | Universal Bio Research Co Ltd | Method for detecting target substance |
EP1867990A1 (en) * | 2006-06-14 | 2007-12-19 | Koninklijke Philips Electronics N.V. | Sensitive assay through amplification of a label signal |
US7452478B2 (en) | 2002-08-30 | 2008-11-18 | Hitachi Software Engineering Co., Ltd. | Method for converting and purifying materials for modifying surfaces of semiconductor nanoparticles |
EP2330208A1 (en) * | 2004-05-24 | 2011-06-08 | Midatech Ltd. | Nanoparticles comprising RNA ligands |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1978110B1 (en) * | 2000-09-06 | 2010-05-26 | Transnetyx, Inc. | Computer-based method and system for screening genomic DNA |
JP5611503B2 (en) * | 2007-03-09 | 2014-10-22 | 国立大学法人 香川大学 | Patterned insulating fine particle film, method for producing the same, electronic component, micromachine, and optical component using the same |
JP2008221369A (en) * | 2007-03-09 | 2008-09-25 | Kagawa Univ | Particulate membrane and method of manufacturing the same |
WO2009116551A1 (en) * | 2008-03-17 | 2009-09-24 | 国立大学法人山梨大学 | Bonded mass of accumulated nanoparticles and method of producing the same |
WO2018119128A1 (en) * | 2016-12-22 | 2018-06-28 | Burris Robert Barton | Methods for non-enzymatic amplification of a signal and uses thereof to detect and quantify a target analyte |
Citations (3)
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WO1998004740A1 (en) * | 1996-07-29 | 1998-02-05 | Nanosphere Llc | Nanoparticles having oligonucleotides attached thereto and uses therefor |
EP0990903A1 (en) * | 1998-09-18 | 2000-04-05 | Massachusetts Institute Of Technology | Biological applications of semiconductor nanocrystals |
WO2001051665A2 (en) * | 2000-01-13 | 2001-07-19 | Nanosphere Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
Family Cites Families (2)
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US5866434A (en) * | 1994-12-08 | 1999-02-02 | Meso Scale Technology | Graphitic nanotubes in luminescence assays |
US6207392B1 (en) * | 1997-11-25 | 2001-03-27 | The Regents Of The University Of California | Semiconductor nanocrystal probes for biological applications and process for making and using such probes |
-
2000
- 2000-10-12 IL IL13898800A patent/IL138988A/en not_active IP Right Cessation
-
2001
- 2001-09-24 JP JP2002534556A patent/JP2005507488A/en active Pending
- 2001-09-24 EP EP01974639A patent/EP1368490A2/en not_active Withdrawn
- 2001-09-24 CA CA002424435A patent/CA2424435A1/en not_active Abandoned
- 2001-09-24 US US10/381,131 patent/US20040048272A1/en not_active Abandoned
- 2001-09-24 WO PCT/IL2001/000886 patent/WO2002031191A2/en not_active Application Discontinuation
- 2001-09-24 AU AU2001294150A patent/AU2001294150A1/en not_active Abandoned
Patent Citations (3)
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WO1998004740A1 (en) * | 1996-07-29 | 1998-02-05 | Nanosphere Llc | Nanoparticles having oligonucleotides attached thereto and uses therefor |
EP0990903A1 (en) * | 1998-09-18 | 2000-04-05 | Massachusetts Institute Of Technology | Biological applications of semiconductor nanocrystals |
WO2001051665A2 (en) * | 2000-01-13 | 2001-07-19 | Nanosphere Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
Non-Patent Citations (2)
Title |
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PATOLSKY F ET AL: "Dendritic amplification of DNA analysis by oligonucleotide-functionalized Au-nanoparticles" CHEMICAL COMMUNICATIONS, vol. 6, no. 12, 21 June 2000 (2000-06-21), pages 1025-1026, XP002229552 cited in the application * |
SHIPWAY A N ET AL: "Nanoparticles as structural and functional units in surface-confined architectures." CHEMICAL COMMUNICATIONS (CAMBRIDGE, ENGLAND) ENGLAND 21 OCT 2001, no. 20, 21 October 2001 (2001-10-21), pages 2035-2045, XP002229553 ISSN: 1359-7345 * |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1375625A1 (en) * | 2002-06-10 | 2004-01-02 | Hitachi Software Engineering Co., Ltd. | Semiconductor nanoparticles and method for producing them |
US7094623B2 (en) | 2002-06-10 | 2006-08-22 | Hitachi Software Engineering Co., Ltd. | Method for producing semiconductor nanoparticles and semiconductor nanoparticles produced by the same |
US7452478B2 (en) | 2002-08-30 | 2008-11-18 | Hitachi Software Engineering Co., Ltd. | Method for converting and purifying materials for modifying surfaces of semiconductor nanoparticles |
WO2004090548A1 (en) * | 2003-03-13 | 2004-10-21 | Chengdu Kuachang Medical Industrial Limited | Device for analysis or separation containing an active nanostructured carrier, its preparation method and applications |
JP2005192439A (en) * | 2003-12-29 | 2005-07-21 | Universal Bio Research Co Ltd | Method for detecting target substance |
EP1712622A1 (en) * | 2003-12-29 | 2006-10-18 | Universal Bio Research Co., Ltd. | Method of detecting target substance |
EP1712622A4 (en) * | 2003-12-29 | 2007-06-13 | Universal Bio Research Co Ltd | Method of detecting target substance |
EP2330208A1 (en) * | 2004-05-24 | 2011-06-08 | Midatech Ltd. | Nanoparticles comprising RNA ligands |
EP1867990A1 (en) * | 2006-06-14 | 2007-12-19 | Koninklijke Philips Electronics N.V. | Sensitive assay through amplification of a label signal |
WO2007144834A1 (en) * | 2006-06-14 | 2007-12-21 | Koninklijke Philips Electronics N.V. | Sensitive magnetic assay through amplification of a label signal |
Also Published As
Publication number | Publication date |
---|---|
AU2001294150A1 (en) | 2002-04-22 |
US20040048272A1 (en) | 2004-03-11 |
EP1368490A2 (en) | 2003-12-10 |
IL138988A (en) | 2005-09-25 |
IL138988A0 (en) | 2001-11-25 |
CA2424435A1 (en) | 2002-04-18 |
JP2005507488A (en) | 2005-03-17 |
WO2002031191A3 (en) | 2003-09-12 |
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