Patents by Inventor Markus Kostrzewa

Markus Kostrzewa has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 11754572
    Abstract: A method of detecting specified target microbes in different types of sample uses only one to two cultivation steps for the enrichment of the target microbes from the sample, preferably in selective culture media, combined with a mass spectrometric detection method that identifies the target microbes in mixtures with other microbes even if the target microbes account for only a small proportion of the mixture. The sample may be a food sample, a sample from bodies of water used for bathing, a soil sample, a swabbed sample, a stool sample, an impactor sample with collected aerosol particles, amongst many others. The detection method is several days faster than standard methods and less expensive.
    Type: Grant
    Filed: May 6, 2011
    Date of Patent: September 12, 2023
    Inventors: Markus Kostrzewa, Jochen Franzen
  • Publication number: 20220412988
    Abstract: Microorganisms are identified as present in a complex sample or mixed culture by acquiring a mass spectrum of the sample and comparing it to combination spectra, each of which is formed by combining at least two reference mass spectra of known microorganisms. Microorganisms corresponding to the reference spectra used to form the combination spectrum are identified as present in the sample if that combination spectrum exhibits a better match with the sample mass spectrum than any one of reference mass spectra used to form that combination spectrum. It is also possible to identify microorganisms by forming a difference spectrum by subtracting a reference mass spectrum from the sample mass spectrum and comparing the difference spectrum to the reference mass spectra.
    Type: Application
    Filed: September 6, 2022
    Publication date: December 29, 2022
    Inventors: Markus KOSTRZEWA, Thomas MAIER, Stefan KLEPEL
  • Patent number: 11142784
    Abstract: The invention relates to a mass spectrometric method to determine microbial resistances to antibiotics. The decrease or modification of specific nutrient components by microbes, and thus the metabolism of the microbes, is determined mass spectrometrically in culture media containing antibiotics. Hence it is not the microbes which are introduced into the mass spectrometric analysis, but the culture medium. The special nutrient components which are subject to the mass spectrometric observation are indicators for the metabolism exhibited by the microbes in the culture in the presence of antibiotics, and are thus indicators for their susceptibility or resistance.
    Type: Grant
    Filed: January 14, 2015
    Date of Patent: October 12, 2021
    Inventors: Markus Kostrzewa, Katrin Sparbier
  • Patent number: 10774361
    Abstract: The invention relates to a method for identifying unknown microbes in a sample, wherein a mass spectrometric determination down to the taxonomic level of the genus or species is supplemented by a detailed determination of a lower taxonomic level or variety by means of infrared spectrometry, using restricted reference libraries of infrared spectra. These libraries can be genus-specific, containing only infrared spectra of microbes of one genus, or species-specific, containing only infrared spectra of microbes of one species. In so doing, a robust mass spectrometric identification of the species of unknown microbes is advantageously supplemented with a detailed analysis of the subspecies and varieties by means of infrared spectrometry, primarily in order to identify medically important varieties such as pathovars like EHEC and EPEC, and antibiotic-resistant microbes like MRSA.
    Type: Grant
    Filed: August 31, 2018
    Date of Patent: September 15, 2020
    Inventor: Markus Kostrzewa
  • Patent number: 10597692
    Abstract: The invention relates to methods and instruments for the rapid detection and rapid mass spectrometric identification of microbial infective agents in blood or other body fluids. The invention recognizes that blood is not a good environment for the cultivation of microbes and provides a method which (a) largely destroys or dissolves the human particles in body fluids, such as erythrocytes and leukocytes in blood, without impairing the ability of the microbes to reproduce, (b) separates the microbial pathogens from the fluid, (c) cultivates them in a nutrient broth which contains none of the antimicrobial components of the body fluids, (d) separates them from the nutrient broth, and (e) identifies the microbes by a mass spectrum of the microbial proteins. The dissolution of the human particles also releases the microbes nesting in macrophages.
    Type: Grant
    Filed: May 18, 2018
    Date of Patent: March 24, 2020
    Assignee: Bruker Daltonik GmbH
    Inventors: Jochen Franzen, Markus Kostrzewa, Thomas Maier, Karsten Michelmann, Wolfgang Pusch
  • Patent number: 10457972
    Abstract: The invention relates to a mass spectrometric method for determining microbial resistances to antibiotics. The invention provides specific methods comprising cultivation in synthetic media, in which several amino acids, preferably only a single amino acid, are isotopically labeled by incorporating 13C, 15N, 18O or 34S. If several amino acids are isotopically labeled, they are labeled in such a way that they are each heavier than the corresponding unlabeled amino acids by the same integer mass difference ?m. This ensures that the mass shifts of the peaks always amount to an integer multiple of the mass difference ?m. The total mass difference can be kept relatively small by selecting suitable amino acids. A mass shift of the protein peaks in media with antibiotics indicates that the microbes are resistant. A second embodiment first produces isotopically labeled microbes, which are then tested for their resistance by cultivating them in normal media.
    Type: Grant
    Filed: May 7, 2014
    Date of Patent: October 29, 2019
    Inventors: Jochen Franzen, Markus Kostrzewa, Christoph Lange, Katrin Sparbier
  • Publication number: 20180371521
    Abstract: The invention relates to a method for identifying unknown microbes in a sample, wherein a mass spectrometric determination down to the taxonomic level of the genus or species is supplemented by a detailed determination of a lower taxonomic level or variety by means of infrared spectrometry, using restricted reference libraries of infrared spectra. These libraries can be genus-specific, containing only infrared spectra of microbes of one genus, or species-specific, containing only infrared spectra of microbes of one species. In so doing, a robust mass spectrometric identification of the species of unknown microbes is advantageously supplemented with a detailed analysis of the subspecies and varieties by means of infrared spectrometry, primarily in order to identify medically important varieties such as pathovars like EHEC and EPEC, and antibiotic-resistant microbes like MRSA.
    Type: Application
    Filed: August 31, 2018
    Publication date: December 27, 2018
    Inventor: Markus KOSTRZEWA
  • Patent number: 10144946
    Abstract: The invention relates to the detection of specified, flagellated bacteria, particularly Salmonella, in food and stool. A single culturing period of about 12 to 24 hours in a liquid nutrient medium without agitation is combined with a position-selective sampling of the flagellated microbes from the liquid of the culture, after which a mass spectrometric detection method is used which recognizes the target bacteria in mixtures. A second culture step is only necessary in exceptional cases. A species-selective or genus-selective culture medium is advantageous. Positional selection becomes possible because these bacteria use their flagella to counteract sedimentation by chemotaxis, and they collect near the surface.
    Type: Grant
    Filed: May 6, 2011
    Date of Patent: December 4, 2018
    Assignee: Bruker Daltonik GmbH
    Inventors: Katrin Sparbier, Markus Kostrzewa
  • Patent number: 10106831
    Abstract: The invention relates to a method for identifying unknown microbes in a sample, wherein a mass spectrometric determination termination down to the taxonomic level of the genus or species is supplemented by a detailed determination of a lower taxonomic level or variety by means of infrared spectrometry, using restricted reference libraries of infrared spectra. These libraries can be genus-specific, containing only infrared spectra of microbes of one genus, or species-specific, containing only infrared spectra of microbes of one species. In so doing, a robust mass spectrometric identification of the species of unknown microbes is advantageously supplemented with a detailed analysis of the subspecies and varieties by means of infrared spectrometry, primarily in order to identify medically important varieties such as pathovars like EHEC and EPEC, and antibiotic-resistant microbes like MRSA.
    Type: Grant
    Filed: November 10, 2014
    Date of Patent: October 23, 2018
    Inventor: Markus Kostrzewa
  • Publication number: 20180265909
    Abstract: The invention relates to methods and instruments for the rapid detection and rapid mass spectrometric identification of microbial infective agents in blood or other body fluids. The invention recognizes that blood is not a good environment for the cultivation of microbes and provides a method which (a) largely destroys or dissolves the human particles in body fluids, such as erythrocytes and leukocytes in blood, without impairing the ability of the microbes to reproduce, (b) separates the microbial pathogens from the fluid, (c) cultivates them in a nutrient broth which contains none of the antimicrobial components of the body fluids, (d) separates them from the nutrient broth, and (e) identifies the microbes by a mass spectrum of the microbial proteins. The dissolution of the human particles also releases the microbes nesting in macrophages.
    Type: Application
    Filed: May 18, 2018
    Publication date: September 20, 2018
    Inventors: Jochen Franzen, Markus Kostrzewa, Thomas Maier, Karsten Michelmann, Wolfgang Pusch
  • Patent number: 10043647
    Abstract: The invention concerns the reduction of the risk of an incorrect assignment of samples to sample sites during the manual deposition of samples for ionization by laser desorption (for example MALDI or LDCI). The invention offers a method wherein a sample support with several sample sites is provided, at least one sample site is selected, and the selected sample site is highlighted, at least in contrast to neighboring not selected sample sites, in a way which the human eye can perceive.
    Type: Grant
    Filed: May 29, 2013
    Date of Patent: August 7, 2018
    Inventors: Markus Kostrzewa, Ulrich Weller
  • Patent number: 10006076
    Abstract: The invention relates to methods and instruments for the rapid detection and rapid mass spectrometric identification of microbial infective agents in blood or other body fluids. The invention recognizes that blood is not a good environment for the cultivation of microbes and provides a method which (a) largely destroys or dissolves the human particles in body fluids, such as erythrocytes and leukocytes in blood, without impairing the ability of the microbes to reproduce, (b) separates the microbial pathogens from the fluid, (c) cultivates them in a nutrient broth which contains none of the antimicrobial components of the body fluids, (d) separates them from the nutrient broth, and (e) identifies the microbes by a mass spectrum of the microbial proteins. The dissolution of the human particles also releases the microbes nesting in macrophages.
    Type: Grant
    Filed: July 29, 2011
    Date of Patent: June 26, 2018
    Assignee: Bruker Daltonik GmbH
    Inventors: Jochen Franzen, Markus Kostrzewa, Thomas Maier, Karsten Michelmann, Wolfgang Pusch
  • Publication number: 20170051330
    Abstract: The invention relates to a method for identifying unknown microbes in a sample, wherein a mass spectrometric determination termination down to the taxonomic level of the genus or species is supplemented by a detailed determination of a lower taxonomic level or variety by means of infrared spectrometry, using restricted reference libraries of infrared spectra. These libraries can be genus-specific, containing only infrared spectra of microbes of one genus, or species-specific, containing only infrared spectra of microbes of one species. In so doing, a robust mass spectrometric identification of the species of unknown microbes is advantageously supplemented with a detailed analysis of the subspecies and varieties by means of infrared spectrometry, primarily in order to identify medically important varieties such as pathovars like EHEC and EPEC, and antibiotic-resistant microbes like MRSA.
    Type: Application
    Filed: November 10, 2014
    Publication date: February 23, 2017
    Inventor: Markus KOSTRZEWA
  • Publication number: 20160333388
    Abstract: The invention relates to a mass spectrometric method to determine microbial resistances to antibiotics. The decrease or modification of specific nutrient components by microbes, and thus the metabolism of the microbes, is determined mass spectrometrically in culture media containing antibiotics. Hence it is not the microbes which are introduced into the mass spectrometric analysis, but the culture medium. The special nutrient components which are subject to the mass spectrometric observation are indicators for the metabolism exhibited by the microbes in the culture in the presence of antibiotics, and are thus indicators for their susceptibility or resistance.
    Type: Application
    Filed: January 14, 2015
    Publication date: November 17, 2016
    Inventors: Markus KOSTRZEWA, Katrin SPARBIER
  • Patent number: 9275188
    Abstract: Microbes in a sample are identified by calculating similarities between a mass spectrum of the sample and reference mass spectra in a spectral library. The spectral library is divided into a hierarchy of sub-libraries where each sub-library contains reference mass spectra of microbes which are statistically the most prevalent in the samples, but are not included in other sub-libraries and all additional reference mass spectra in the library that have substantial similarity to the reference mass spectra of these microbes. Only if the search in a sub-library does not provide a hit with sufficient certainty of identification, is the search carried out in sub-libraries of higher stages.
    Type: Grant
    Filed: January 13, 2011
    Date of Patent: March 1, 2016
    Assignee: Bruker Daltonik GmbH
    Inventor: Markus Kostrzewa
  • Publication number: 20150357172
    Abstract: The invention concerns the reduction of the risk of an incorrect assignment of samples to sample sites during the manual deposition of samples for ionization by laser desorption (for example MALDI or LDCI). The invention offers a method wherein a sample support with several sample sites is provided, at least one sample site is selected, and the selected sample site is highlighted, at least in contrast to neighboring not selected sample sites, in a way which the human eye can perceive.
    Type: Application
    Filed: May 29, 2013
    Publication date: December 10, 2015
    Applicants: Bruker Daltonik GmbH
    Inventors: Markus Kostrzewa, Ulrich Weller
  • Publication number: 20150211042
    Abstract: The invention relates to the identification of microbes in a sample by calculating the similarities between a mass spectrum of the sample and all reference spectra in a spectral library; it particularly concerns the detection of microbe mixtures. Microbe mixtures are probably present if several microbe species which are not closely related to each other are among the score list containing the most similar reference spectra. Methods are proposed which (1) operate with a list of the relationships, (2) determine the similarity between the reference spectra of the different microbe species of the score list, or (3) always carry out a mixture analysis in accordance with document DE 10 2009 007 266 A1 from the score list, with the generation of combination spectra, and only afterwards check the similarity of the combined spectra and thus the relationship between the microbe strains concerned.
    Type: Application
    Filed: July 25, 2013
    Publication date: July 30, 2015
    Inventors: Jochen Franzen, Stefan Klepel, Markus Kostrzewa, Thomas Maier
  • Publication number: 20140335556
    Abstract: The invention relates to a mass spectrometric method for determining microbial resistances to antibiotics. The invention provides specific methods comprising cultivation in synthetic media, in which several amino acids, preferably only a single amino acid, are isotopically labeled by incorporating 13C, 15N, 18O or 34S. If several amino acids are isotopically labeled, they are labeled in such a way that they are each heavier than the corresponding unlabeled amino acids by the same integer mass difference ?m. This ensures that the mass shifts of the peaks always amount to an integer multiple of the mass difference ?m. The total mass difference can be kept relatively small by selecting suitable amino acids. A mass shift of the protein peaks in media with antibiotics indicates that the microbes are resistant. A second embodiment first produces isotopically labeled microbes, which are then tested for their resistance by cultivating them in normal media.
    Type: Application
    Filed: May 7, 2014
    Publication date: November 13, 2014
    Inventors: Jochen FRANZEN, Markus KOSTRZEWA, Christoph LANGE, Katrin SPARBIER
  • Publication number: 20130095511
    Abstract: The invention relates to the determination of resistances of microorganisms which produce ?-lactamases, in particular “extended spectrum ?-lactamases” (ESBL). The invention provides a method whereby the microbial resistance can be measured very simply and quickly by means of the catalytic effect of the microbially produced ?-lactamases on ?-lactam antibiotics, which consists in a hydrolytic cleavage of the ?-lactam ring. The method determines the resistance of the bacteria a few hours after a suitable substrate, either a ?-lactam antibiotic or a customized ?-lactam derivative, has been added to a suspension of the microbes, by direct mass spectrometric measurement of the substrate breakdown caused by the ?-lactamases.
    Type: Application
    Filed: June 10, 2011
    Publication date: April 18, 2013
    Inventors: Markus Kostrzewa, Karsten Michelmann, Katrin Sparbier
  • Patent number: 8237107
    Abstract: A dual-stage method is provided for identifying a microbe by, for example, its species or its subspecies. The method includes measuring a mass spectrum of the microbe using a mass spectrometer, calculating indicators for similarities between reference mass spectra in a library and the measured mass spectrum, selecting a group of reference mass spectra similar to the measured mass spectrum, determining a distinguishing weight for each mass signal of the reference mass spectra in the group, where the distinguishing weights emphasize differences between the reference mass spectra in the group, and calculating indicators for similarities between the reference mass spectra in the group and the measured mass spectrum as a function of the distinguishing weights.
    Type: Grant
    Filed: July 12, 2010
    Date of Patent: August 7, 2012
    Assignee: Bruker Daltonik GmbH
    Inventors: Thomas Maier, Markus Kostrzewa