Patents by Inventor Joshua Coon
Joshua Coon 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).
-
Publication number: 20240060863Abstract: The present invention provides an improved technique for cryogenically fixing biological samples in amorphous ice for analysis by cryo-electron microscopy (cryo-EM). Analyte particles are cooled to very low temperatures prior to depositing the particles onto a cooled substrate surface, such as a transmission electron microscope (TEM) grid. This approach “locks” in the particle structure prior to deposition. Either concurrently with or after deposition, the analyte particles are further contacted with a vapor stream of atoms or molecules at cryogenic or near cryogenic temperatures. As a result, a thin layer of an amorphous solid is formed around each particle without significant conformational changes in the particle structure, thereby forming an improved sample for EM analysis.Type: ApplicationFiled: January 13, 2022Publication date: February 22, 2024Applicant: Wisconsin Alumni Research FoundationInventors: Michael WESTPHALL, Joshua COON
-
Publication number: 20230393041Abstract: Multi-omic analysis (analysis of proteins, lipids, and metabolites) is a powerful and increasingly utilized approach to gain insight into complex biological systems. One major hindrance with multi-omics, however, is the lengthy sample preparation process. Preparing samples for mass spectrometry (MS)-based multi-omics broadly involves extraction of metabolites and lipids with organic solvents, precipitation of proteins, and overnight digestion of proteins. The existing workflows are disparate and laborious, requiring multiple complex operation steps typically taking 1-2 days to perform. The present invention provides methods for preparing multi-omic samples that are faster and simpler than conventional methods, making it easier for a single lab or researcher to collect quality multi-omic data.Type: ApplicationFiled: June 1, 2023Publication date: December 7, 2023Applicant: Wisconsin Alumni Research FoundationInventors: Joshua COON, Laura MUEHLBAUER, Yunyun ZHU, Katherine OVERMYER, Annie JEN
-
Publication number: 20230266214Abstract: The present invention provides methods for controllably forming a layer of amorphous ice and other amorphous solids on a substrate, and also provides cryo-electron microscopy (cryo-EM) sample preparation methods and systems that utilize in vacuo formation of amorphous ice and other solids. Formation of the amorphous solid layer can be independent of the deposition of sample molecules to be analyzed using electron microscopy, and allows for the generation of a uniformly thick layer. Optionally, mass spectrometry instruments are used to generate and purify molecules deposited on the generated amorphous solid layer. The techniques and systems described herein can deliver near ideal cryo-EM sample preparation to greatly increase resolution, sensitivity, scope, and throughput of cryo-EM protein imaging, and therefore greatly impact the field of structural biology.Type: ApplicationFiled: November 10, 2022Publication date: August 24, 2023Applicant: Wisconsin Alumni Research FoundationInventors: Joshua COON, Michael WESTPHALL
-
Publication number: 20230096779Abstract: Systems for monitoring metabolites may include a sample collection system and a urinalysis system of or for a toilet. The sample collection system may be automated to collect sample urine from a toilet or toilet area, transport the sample to the urinalysis system, and/or the sample urine for analysis at a later time or after analysis by the urinalysis system. The urinalysis system may be automated by proactively providing test material on which a subject may provide a urine sample. Once the urine sample has been provided the urinalysis system may provide the test material to an analyzer for analysis. Results of the analysis of the test material and sample urine may be provided to a mobile device of the subject and/or a remote server. The urinalysis system may provide a urine sample to a mass spectrometry unit for analysis.Type: ApplicationFiled: December 2, 2022Publication date: March 30, 2023Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventors: JOSHUA COON, MICHAEL WESTPHALL, IAN MILLER, LLOYD SMITH, KEATON MERTZ
-
Patent number: 11525760Abstract: The present invention provides methods for controllably forming a layer of amorphous ice and other amorphous solids on a substrate, and also provides cryo-electron microscopy (cryo-EM) sample preparation methods and systems that utilize in vacuo formation of amorphous ice and other solids. Formation of the amorphous solid layer can be independent of the deposition of sample molecules to be analyzed using electron microscopy, and allows for the generation of a uniformly thick layer. Optionally, mass spectrometry instruments are used to generate and purify molecules deposited on the generated amorphous solid layer. The techniques and systems described herein can deliver near ideal cryo-EM sample preparation to greatly increase resolution, sensitivity, scope, and throughput of cryo-EM protein imaging, and therefore greatly impact the field of structural biology.Type: GrantFiled: July 1, 2021Date of Patent: December 13, 2022Assignee: Wisconsin Alumni Research FoundationInventors: Joshua Coon, Michael Westphall
-
Publication number: 20220365028Abstract: The present invention provides methods and systems using gas-phase separation with mass spectrometry analysis instead of liquid chromatography, thereby enabling faster peptide, proteome, and multi-omic analysis. Also provided are improved methods and software for data independent acquisition. One embodiment referred to as Direct Infusion—Shotgun Proteome Analysis (DI-SPA) used with data-independent acquisition mass spectrometry (DIA-MS), resulted in targeted quantification of over 500 proteins within minutes of MS data collection (˜3.5 proteins/second). Enabling fast, unbiased protein and proteome quantification without liquid chromatography, DI-SPA offers a new approach to boosting throughput critical to drug and biomarker discovery studies that require analysis of thousands of proteomes. This invention is also able to perform complex multi-omic analysis of proteomes, lipidomes, and metabolomes on a single platform.Type: ApplicationFiled: May 10, 2022Publication date: November 17, 2022Inventors: Jesse MEYER, Joshua COON, Alexander HEBERT, Caleb CRANNEY
-
Publication number: 20220065761Abstract: The present invention provides methods for controllably forming a layer of amorphous ice and other amorphous solids on a substrate, and also provides cryo-electron microscopy (cryo-EM) sample preparation methods and systems that utilize in vacuo formation of amorphous ice and other solids. Formation of the amorphous solid layer can be independent of the deposition of sample molecules to be analyzed using electron microscopy, and allows for the generation of a uniformly thick layer. Optionally, mass spectrometry instruments are used to generate and purify molecules deposited on the generated amorphous solid layer. The techniques and systems described herein can deliver near ideal cryo-EM sample preparation to greatly increase resolution, sensitivity, scope, and throughput of cryo-EM protein imaging, and therefore greatly impact the field of structural biology.Type: ApplicationFiled: July 1, 2021Publication date: March 3, 2022Applicant: Wisconsin Alumni Research FoundationInventors: Joshua COON, Michael WESTPHALL
-
Patent number: 11092523Abstract: The present invention provides methods for controllably forming a layer of amorphous ice and other amorphous solids on a substrate, and also provides cryoelectron microscopy (cryo-EM) sample preparation methods and systems that utilize in vacuo formation of amorphous ice and other solids. Formation of the amorphous solid layer can be independent of the deposition of sample molecules to be analyzed using electron microscopy, and allows for the generation of a uniformly thick layer. Optionally, mass spectrometry instruments are used to generate and purify molecules deposited on the generated amorphous solid layer. The techniques and systems described herein can deliver near ideal cryo-EM sample preparation to greatly increase resolution, sensitivity, scope, and throughput of cryo-EM protein imaging, and therefore greatly impact the field of structural biology.Type: GrantFiled: July 6, 2018Date of Patent: August 17, 2021Assignee: Wisconsin Alumni Research FoundationInventors: Joshua Coon, Michael Westphall
-
Publication number: 20210239708Abstract: In shotgun proteomics, generally only a fraction of peptides from a parent protein are actually detected. Because a large portion of the protein sequence is not detected, it is often impossible to determine whether the expressed protein is present in a modified, spliced, or truncated form. Provided herein are methods and systems for analyzing polypeptides which allow for the increase of the mean sequence coverage of a protein concomitant with bioinformatics analysis in order to distinguish putative proteoforms with improved amino acid resolution. Aspects of the invention include (1) a deep sequencing strategy to provide more protein sequence coverage than is typically achieved, and (2) a computational approach to view protein expression across its full length and identify regions of the protein that are potentially subject to such regulation. This technology has global utility in proteomics and will be of particular use for the analysis of biosimilar protein drug therapeutics.Type: ApplicationFiled: April 15, 2021Publication date: August 5, 2021Applicant: Wisconsin Alumni Research FoundationInventors: Joshua COON, Harald MARX
-
Publication number: 20200158607Abstract: The present invention provides methods for controllably forming a layer of amorphous ice and other amorphous solids on a substrate, and also provides cryoelectron microscopy (cryo-EM) sample preparation methods and systems that utilize in vacuo formation of amorphous ice and other solids. Formation of the amorphous solid layer can be independent of the deposition of sample molecules to be analyzed using electron microscopy, and allows for the generation of a uniformly thick layer. Optionally, mass spectrometry instruments are used to generate and purify molecules deposited on the generated amorphous solid layer. The techniques and systems described herein can deliver near ideal cryo-EM sample preparation to greatly increase resolution, sensitivity, scope, and throughput of cryo-EM protein imaging, and therefore greatly impact the field of structural biology.Type: ApplicationFiled: July 6, 2018Publication date: May 21, 2020Applicant: Wisconsin Alumni Research FoundationInventors: Joshua COON, Michael WESTPHALL
-
Publication number: 20180340941Abstract: In shotgun proteomics, generally only a fraction of peptides from a parent protein are actually detected. Because a large portion of the protein sequence is not detected, it is often impossible to determine whether the expressed protein is present in a modified, spliced, or truncated form. Provided herein are methods and systems for analyzing polypeptides which allow for the increase of the mean sequence coverage of a protein concomitant with bioinformatics analysis in order to distinguish putative proteoforms with improved amino acid resolution. Aspects of the invention include (1) a deep sequencing strategy to provide more protein sequence coverage than is typically achieved, and (2) a computational approach to view protein expression across its full length and identify regions of the protein that are potentially subject to such regulation. This technology has global utility in proteomics and will be of particular use for the analysis of biosimilar protein drug therapeutics.Type: ApplicationFiled: May 24, 2018Publication date: November 29, 2018Inventors: Joshua COON, Harald MARX
-
Publication number: 20180286649Abstract: A new approach is described herein for outfitting a mass spectrometer with an infrared laser that provides an improved method of ion dissociation. One embodiment, generally referred to as Activated Ion Electron Transfer Dissociation (AI-ETD) utilizes additional energy from photons during fragmentation to generate extensive fragmentation by interacting with peptides or proteins that are not fully fragmented or separated in the high pressure linear ion trap, thus allowing for increased information during MS/MS. Additionally, a new activation scheme generally referred to as AI-ETD+ is also described that combines AI-ETD in the high pressure cell of the linear ion trap with additional infrared multi-photon dissociation (IRMPD) activation in the low pressure cell. These methods provide improved fragmentation and sequence coverage without introducing additional time to the scan duty cycle.Type: ApplicationFiled: March 26, 2018Publication date: October 4, 2018Applicant: Wisconsin Alumni Research FoundationInventors: Joshua COON, Nicholas RILEY, Michael WESTPHALL
-
Patent number: 9359391Abstract: A method to cleave C—C and C—O bonds in ?-O-4 linkages in lignin or lignin sub-units is described. The method includes oxidizing at least a portion of secondary benzylic alcohol groups in ?-O-4 linkages in the lignin or lignin sub-unit to corresponding ketones and then leaving C—O or C—C bonds in the oxidized lignin or lignin sub-unit by reacting it with an organic carboxylic acid, a salt of an organic carboxylic acids, and/or an ester of an organic carboxylic acids. The method may utilize a metal or metal-containing reagent or proceed without the metal or metal-containing reagent.Type: GrantFiled: March 14, 2014Date of Patent: June 7, 2016Assignee: Wisconsin Alumni Research FoundationInventors: Shannon S. Stahl, Joshua Coon, Alireza Rahimi, Arne Ulbrich
-
Publication number: 20150259368Abstract: A method to cleave C—C and C—O bonds in ?-O-4 linkages in lignin or lignin sub-units is described. The method includes oxidizing at least a portion of secondary benzylic alcohol groups in ?-O-4 linkages in the lignin or lignin sub-unit to corresponding ketones and then leaving C—O or C—C bonds in the oxidized lignin or lignin sub-unit by reacting it with an organic carboxylic acid, a salt of an organic carboxylic acids, and/or an ester of an organic carboxylic acids. The method may utilize a metal or metal-containing reagent or proceed without the metal or metal-containing reagent.Type: ApplicationFiled: March 14, 2014Publication date: September 17, 2015Applicant: Wisconsin Alumni Research FoundationInventors: Shannon S. Stahl, Joshua Coon, Alireza Rahimi, Arne Ulbrich
-
Publication number: 20130240722Abstract: An algorithm-based system and method for tandem mass spectrometry data acquisition in which multiple precursor ion attributes, such as mass, intensity, mass-to-charge ratio and charge state, as well as results from previously performed mass spectrometry scans, are used to determine the likelihood of identification for each precursor ion. This information is then used to prioritize subsequent tandem mass spectrometry events, such as which precursor ions are to be fragmented and undergo further mass spectrometry analysis.Type: ApplicationFiled: March 13, 2012Publication date: September 19, 2013Applicant: Wisconsin Alumni Research FoundationInventors: Joshua Coon, Douglas Phanstiel, Graeme McAlister
-
Patent number: 8530831Abstract: An algorithm-based system and method for tandem mass spectrometry data acquisition in which multiple precursor ion attributes, such as mass, intensity, mass-to-charge ratio and charge state, as well as results from previously performed mass spectrometry scans, are used to determine the likelihood of identification for each precursor ion. This information is then used to prioritize subsequent tandem mass spectrometry events, such as which precursor ions are to be fragmented and undergo further mass spectrometry analysis. By interrogating precursor ions in order of probability of successful identification, an increase in identified proteins and peptides is achieved.Type: GrantFiled: March 13, 2012Date of Patent: September 10, 2013Assignee: Wisconsin Alumni Research FoundationInventors: Joshua Coon, Douglas Phanstiel, Graeme McAlister
-
Publication number: 20080050833Abstract: Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic kit facilitating relative quantification and providing tangible evidence for the existence of specific functional groups. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules, such as biological samples. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. Advantageously, the labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC/MS) applications.Type: ApplicationFiled: March 21, 2007Publication date: February 28, 2008Inventors: Lloyd Smith, Michael Shortreed, Brian Frey, Margaret Phillips, Joshua Coon, Shane Lamos, Casey Krusemark, Peter Belshaw, Madhusudan Patel, Neil Kelleher
-
Publication number: 20080048109Abstract: Methods and apparatus for data-dependent mass spectrometric MS/MS or MSn analysis are disclosed. The methods may include determination of the charge state of an ion species of interest, followed by automated selection of a dissociation type (e.g., CAD, ETD, or ETD followed by a non-dissociative charge reduction or collisional activation) based at least partially on the determined charge state. The ion species of interest is then dissociated in accordance with the selected dissociation type, and an MS/MS or MSn spectrum of the resultant product ions may be acquired.Type: ApplicationFiled: August 27, 2007Publication date: February 28, 2008Inventors: Jae Schwartz, John Syka, Andreas Huhmer, Joshua Coon
-
Publication number: 20080044915Abstract: The present invention relates to a new method for identifying polypeptides by deducing the amino acid sequence of the carboxy and amino termini by a mass spectrometer analysis. The method comprises the steps of dissociating highly charged peptide precursor ions (e.g., z>4) using electron transfer dissociation inducing anions followed by removal of those reagents and introduction of a second, proton transfer inducing anion type. The second PTR reaction duration is adjusted to convert the ETD products to primarily the +1 charge-state to reduce the highly charged c and z-type fragments, producing an m/z spectrum containing a series of c and z-type fragment ions that are easily interpreted to reveal the sequence of the amino and carboxy terminus, respectively.Type: ApplicationFiled: October 7, 2005Publication date: February 21, 2008Inventors: Donald Hunt, Joshua Coon, John Syka
-
Publication number: 20050199804Abstract: The present invention relates to a new method for fragmenting ions in a mass spectrometer through the use of electron transfer dissociation, and for performing sequence analysis of peptides and proteins by mass spectrometry. In the case of peptides, the invention promotes fragmentation along the peptide backbone and makes it possible to deduce the amino acid sequence of the sample, including modified amino acid residues, through the use of an RF field device.Type: ApplicationFiled: March 14, 2005Publication date: September 15, 2005Inventors: Donald Hunt, Joshua Coon, John Syka, Jarrod Marto