Patents Assigned to Laboratory of Molecular Biophotonics
  • Patent number: 6333199
    Abstract: The method of analyzing polyphenols and bisphenols in accordance with the present invention comprises a step of reacting a bisphenol and/or a polyphenol with a labeling reagent having a pyrene group, so as to generate a fluorescent derivative; a step of irradiating the fluorescent derivative with excitation light and detecting fluorescence emitted from the fluorescent derivative; and a step of calculating an amount of the bisphenol and/or polyphenol in a test sample according to an intensity of thus detected fluorescence and a relationship between a known concentration of a bisphenol and/or a polyphenol contained in a standard sample and fluorescence intensity.
    Type: Grant
    Filed: December 10, 1999
    Date of Patent: December 25, 2001
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Hitoshi Nohta, Hideyuki Yoshida, Masatoshi Yamaguchi
  • Patent number: 6329546
    Abstract: The caged amino acid in accordance with the present invention has the structure represented by the following formula 1: where X and Y each represent a halogen atom, an alkyl group, an alkyloxy group, an alkylamino group, or a benzo group; R1 represents a hydrogen atom or an alkyl group; R2 and R3 each represent a hydrogen atom or an alkyl group; A represents an amino acid residue; and M represents a hydrogen atom, an alkali metal, or an alkaline-earth metal.
    Type: Grant
    Filed: January 11, 2000
    Date of Patent: December 11, 2001
    Assignee: Laboratory of Molecular Biophotonics
    Inventor: Hirofumi Shiono
  • Patent number: 6284462
    Abstract: Detection probes and a method of detection for the detection of a specimen having a specified sequence in a sample are disclosed that utilize two fluorophore-labeled (donor and acceptor) probes which are designed to display changes in a fluorescence decay curve by their hybridization to the specific sequence of a specimen, thus allowing for the detection with great accuracy and high sensitivity, particularly under the conditions where the probes may be abundant relative to the specimen in the sample.
    Type: Grant
    Filed: June 16, 1998
    Date of Patent: September 4, 2001
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Yoshihiro Sato, Akihiko Tsuji, Takayuki Suga
  • Patent number: 6255048
    Abstract: This invention provides fluoroassay which comprises labeling analyte molecules with a fluorescent material having a nucleic acid portion stained with a sufficient number of fluorochrome molecules so as to be measurable as fluorescent spots, and a reactive group binding to the analyte molecule specifically, immobilizing the labeled analyte on a solid phase, and counting the number of fluorescent spots. The nucleic acid portion of the fluorescent labeling material is a double-stranded or single-stranded nucleic acid, and the staining with the fluorochrome molecules is performed with intercalating type, minor groove binding type, or covalently binding to the nucleic acid type.
    Type: Grant
    Filed: February 9, 1998
    Date of Patent: July 3, 2001
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Shigeru Hosoi, Makiko Kojima, Sachiko Kadouchi
  • Patent number: 6242430
    Abstract: This invention provides rotaxane type dyes. Specifically, the rotaxane type dye according to the invention has a rotaxane structure which binds dye molecules to both of the termini of a chain group penetrating a cyclodextrin ring, which possesses excellent water-solubility, and which is capable of having a plurality of different dyes.
    Type: Grant
    Filed: April 29, 1999
    Date of Patent: June 5, 2001
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Tomomi Suzuki, Hitoshi Nohta, Shigetoshi Okazaki
  • Patent number: 6229020
    Abstract: A new reagent for preparation of a caged compound in accordance with the present invention is a compound having, as a basic structure, an N-succinimidyl cinnamate structure expressed by the following formula 1: Another reagent for preparation of a caged compound in accordance with the present invention is a compound having, as a basic structure, a p-nitrophenyl cinnamate structure expressed by the following formula 3:
    Type: Grant
    Filed: January 11, 2000
    Date of Patent: May 8, 2001
    Assignee: Laboratory of Molecular Biophotonics
    Inventor: Hirofumi Shiono
  • Patent number: 6228592
    Abstract: Detection probes labeled with fluorescent dyes, to which are bound nuclear membrane unpermeable molecules via linkers, having base sequences that can hybridize to a target nucleic acid. The probes are introduced into the cytoplasm of a living cell in which the target nucleic acid is present, and the target nucleic acid is detected by measurement of the change in fluorescence of the fluorescent dyes due to the formation of a hybrid of the target nucleic acid and the probes.
    Type: Grant
    Filed: December 30, 1999
    Date of Patent: May 8, 2001
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Akihiko Tsuji, Masahiko Hirano, Hiroyuki Koshimoto, Kaname Ishibashi
  • Patent number: 6225056
    Abstract: A solid phase comprising at least one pair of probes which are capable of sequentially hybridizing with a particular target nucleic acid sequence is provided. The probe pair(s) are immobilized on the solid phase through a linker portion wherein they occupy a restricted spatial arrangement such that they can be ligated by an enzyme when the they sequentially hybridize to a selected target sequence. In addition a method wherein the solid phase is utilized to detection a target nucleic acid is disclosed.
    Type: Grant
    Filed: April 27, 1998
    Date of Patent: May 1, 2001
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Satoshi Abe, Yoshihiro Sato
  • Patent number: 6207365
    Abstract: The enzyme substrate according to this invention has within its molecule both a group to be cleaved by an enzyme reaction and a group that forms a strongly fluorescent coumarin derivative through intramolecular lactonization when cleaved by the enzyme reaction. Furthermore, the method for determining an enzyme activity according to this invention comprises conducting the enzyme reaction by the use of the enzyme substrate of the invention and determining the enzyme activity by means of the measurement of fluorescence of the coumarin derivative formed.
    Type: Grant
    Filed: August 14, 1998
    Date of Patent: March 27, 2001
    Assignee: Laboratory of Molecular BioPhotonics
    Inventors: Hirofumi Shiono, Hitoshi Nohta, Chika Utsuyama
  • Patent number: 6180347
    Abstract: This invention provides a method for monitoring the transcriptional synthesis of RNA, and to an apparatus therefor. Specifically, the invention resides in monitoring the initiation and termination of a transcription reaction for RNA synthesis, as well as the synthesis of full-length RNA by measuring the fluorescence of a pair of oligonucleotide probes of two types having a base sequence that continuously hybridizes to a part of a base sequence of the RNA synthesized by transcription, the pair of oligonucleotide probes comprising a donor probe labeled with an energy donor fluorescent molecule and an acceptor probe labeled with an energy acceptor fluorescent molecule.
    Type: Grant
    Filed: April 2, 1999
    Date of Patent: January 30, 2001
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Yukari Iida, Hiroyuki Koshimoto, Satoshi Kondo, Akihiko Tsuji
  • Patent number: 6025917
    Abstract: Provided is a polarization characteristic measuring method and apparatus for accurately measuring a polarization characteristic of fluorescence or Raman-scattered light emitted when a sample is exposed to light. The sample is exposed to excitation light radiated from a pulsed excitation light source and converted to p-polarized light by polarizer and half-wave plate, and photodetectors measure an intensity I.sub.pp of a p-polarized component and an intensity I.sub.ps of an s-polarized component of fluorescence emitted from the sample under irradiation with the excitation light. In similar fashion, the sample is exposed to the excitation light of s-polarized light and the detectors measure an intensity I.sub.sp of a p-polarized component and an intensity I.sub.ss of an s-polarized component of fluorescence emitted from the sample under irradiation. From these measured values, G factor is calculated according to the following equation:G=[(I.sub.pp .multidot.I.sub.sp)/(I.sub.ps .multidot.I.sub.ss)].sup.
    Type: Grant
    Filed: May 1, 1998
    Date of Patent: February 15, 2000
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Shuji Toyonaga, Masahisa Shiroshita, Takayuki Suga, Yoshitaro Nakano
  • Patent number: 5990484
    Abstract: The present invention relates to a method and apparatus for efficiently measuring the lifetime of the fluorescence emitted from a fluorescent material in response to pulsed light. The measuring apparatus according to the present invention includes, at least, an excitation light source whose excitation power is regulated such that at least one fluorescence photon can be detected per light pulse on average. While repeatedly irradiating a sample containing the fluorescent material with excitation pulses of light from the excitation light source, a fluorescence detection time from irradiation to fluorescence detection and the number of detected fluorescence photons are measured for each excitation pulse of light.
    Type: Grant
    Filed: October 14, 1998
    Date of Patent: November 23, 1999
    Assignee: Laboratory of Molecular Biophotonics
    Inventor: Shinji Ohsuka
  • Patent number: 5919917
    Abstract: The photocleavable cyclic oligonucleotide according to the invention is the one that possesses a base sequence having the hybridization ability toward DNA or RNA to targeted, and is further provided with the structure cyclized by a photocleavable group. Accordingly, the photocleavable cyclic oligonucleotide according to the invention, after having been introduced in vivo, is hardly susceptible to the nuclease decomposition reaction owing to its cyclic structure and thus it is capable of diffusing toward the predetermined sites in vivo with sufficient time. Moreover, by being irradiated with the light at an appropriate wavelength after a predetermined period of time, the photocleavable group as described above is cleaved photochemically, thus cutting the predetermined bond. This permits the oligonucleotide that was cyclic to be a linear oligonucleotide which expresses the function of an antisense oligonucleotide.
    Type: Grant
    Filed: March 2, 1998
    Date of Patent: July 6, 1999
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Hirofumi Shiono, Hirofumi Kodama, Makiko Kojima
  • Patent number: 5905030
    Abstract: A method and apparatus for measuring enzyme activity by supplying a substrate solution and an enzyme solution into a reaction vessel combined with a total reflection absorption prism is disclosed. A measurement solution (40) in which the enzyme solution and the substrate solution are combined together is kept at a constant temperature within the reaction vessel (26) by a temperature control unit (23), and is stirred by a stirrer (21). Infrared light (36) emitted from an infrared light source (3) is made incident on the interface between a total reflection absorption prism (28) disposed in contact with the measurement solution (40) and the measurement solution (40) from the side of the total reflection absorption prism (28) and is totally reflected by the interface. The spectrum of transmitted infrared light (37) thus totally reflected and emitted is detected by an infrared light detector (5).
    Type: Grant
    Filed: June 5, 1998
    Date of Patent: May 18, 1999
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Shigetoshi Okazaki, Hiroyuki Matsumoto
  • Patent number: 5866683
    Abstract: Provided are isoelectric point(pI) markers for isoelectric focusing with fluorescence detection. The markers are fluorescence-labeled oligopeptides which comprise a fluorescence dye bonded chemically to the amino group of N-terminal amino acid of oligopeptide. The marker shows its unique and narrow pI band(peak) in electrophoresis or isoelectric focusing. The markers can be designed to have appropriate pI value, and cover wide range of pI (3<pI<11). Further, the markers have good storage stability. The markers can be preferably applied to the capillary isoelectric focusing with fluorescence detection due to their sharp and narrow band with strong emitted fluorescence.
    Type: Grant
    Filed: March 29, 1996
    Date of Patent: February 2, 1999
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Kiyohito Shimura, Kenichi Kasai, Hiroyuki Matsumoto, Hisayoshi Takamoto
  • Patent number: 5824559
    Abstract: A method and a device for the analysis of 5-hydroxyindoles or catecholamines with high sensitivity. New chemiluminescence labeling agents, 6-aminomethylphthalhydrazide or 1,2-bis(phthalhydrazino)ethylenediamine, are reacted with 5-hydroxyindoles or catecholamines to form their stable derivatives. The derivatives emit strong luminescence in the presence of an oxidizing agent. In the chemiluminescence detection method, there is extremely low background noise and thus the method enables analysis with high sensitivity.
    Type: Grant
    Filed: June 17, 1996
    Date of Patent: October 20, 1998
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Hitoshi Nohta, Masatoshi Yamaguchi, Junichi Ishida, Kivoshi Zaitsu, Hiroko Iida
  • Patent number: 5789569
    Abstract: The present invention relates to an isothiocyanated cyclodextrin derivative which can label various kinds of organic compounds containing an amino group as their functional group. In some embodiments, the derivative can be a cyclodextrin derivative in which at least one primary hydroxyl group is substituted by an isothiocyanato group and expressed by the compound expressed by formula (I), ##STR1## wherein n is an integer from 5 to 7.
    Type: Grant
    Filed: July 5, 1996
    Date of Patent: August 4, 1998
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Mitsuo Hiramatsu, Hiroshi Satozono, Tomomi Suzuki, Yasuhiro Mizusawa
  • Patent number: 5770408
    Abstract: The present invention relates to a method for the amplification of a base sequence A1A2 consisting of two successive base sequences, A1 and A2, in a single strand polynucleotide as an object to be amplified characterized in that said method comprising at least (1) hybridizing a probe B consisting of a polynucleotide comprising the base sequence B1 complementary to said base sequence A1, a polynucleotide comprising the base sequence B2 complementary to said base sequence A2 and a linkage portion linking the two polynucleotide via itself, with the base sequence A1A2 of said polynucleotide, as the object to be amplified, to form a hybrid, (2) ligating the 5'-end of the base sequence B1 in said probe B to the 3'-end of the base sequence B2 in the same with the aid of ligase, (3) heat denaturating the double strand formed said hybridization, (4) hybridizing said heat denaturated polynucleotide complex with another probe B or a probe A consisting of a polynucleotide comprising said base sequence A1, a polynucleotid
    Type: Grant
    Filed: July 10, 1996
    Date of Patent: June 23, 1998
    Assignee: Laboratory of Molecular Biophotonics
    Inventor: Yoshihiro Sato
  • Patent number: 5715049
    Abstract: When incident light is incident to a photodetector, photoelectrons are emitted therefrom and then multiplied to output an electric current signal. This current signal is integrated over a predetermined period of time in an integrator to be converted to a voltage signal. This voltage signal is converted to a digital signal by an AD converter. This digital signal is supplied to a histogramming memory, which generates a pulse height distribution of voltage signal. Based on a pulse height distribution N(h) generated with incidence of measurement-object light to the photodetector, a pulse height distribution of single photoelectron events p.sub.1 (h) generated by a generator of pulse height distribution of single photoelectron events, and pulse height distributions of k-photoelectron events p.sub.k (h) (k=2, 3, . . .
    Type: Grant
    Filed: November 14, 1996
    Date of Patent: February 3, 1998
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Shinji Ohsuka, Hisayoshi Takamoto
  • Patent number: 5694211
    Abstract: When incident light is incident to a photodetector, photoelectrons are emitted and multiplied in each of incident zones whereby a plurality of current signals are output. These current signals each are processed to estimate a distribution or a mean value of numbers of photoelectrons generated in each incident zone. Then estimated based on the estimate values of respective incident zones is the number of photoelectrons emitted from the entire photoelectric conversion surface. In this way the intensity of incident light is measured with accuracy.
    Type: Grant
    Filed: December 17, 1996
    Date of Patent: December 2, 1997
    Assignee: Laboratory of Molecular Biophotonics
    Inventors: Shinji Ohsuka, Hisayoshi Takamoto