Plume collimation for laser ablation electrospray ionization mass spectrometry
Abstract
In various embodiments, a device may generally comprise a capillary having a first end and a second end; a laser to emit energy at a sample in the capillary to ablate the sample and generate an ablation plume in the capillary; an electrospray apparatus to generate an electrospray plume to intercept the ablation plume to produce ions; and a mass spectrometer having an ion transfer inlet to capture the ions. The ablation plume may comprise a collimated ablation plume. The device may comprise a flow cytometer. Methods of making and using the same are also described.
- Inventors:
- Issue Date:
- Research Org.:
- George Washington Univ., Washington, DC (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1157080
- Patent Number(s):
- 8829426
- Application Number:
- 13/549,988
- Assignee:
- The George Washington University (Washington, DC)
- Patent Classifications (CPCs):
-
H - ELECTRICITY H01 - BASIC ELECTRIC ELEMENTS H01J - ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- DOE Contract Number:
- FG02-01ER15129
- Resource Type:
- Patent
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 47 OTHER INSTRUMENTATION
Citation Formats
Vertes, Akos, and Stolee, Jessica A. Plume collimation for laser ablation electrospray ionization mass spectrometry. United States: N. p., 2014.
Web.
Vertes, Akos, & Stolee, Jessica A. Plume collimation for laser ablation electrospray ionization mass spectrometry. United States.
Vertes, Akos, and Stolee, Jessica A. Tue .
"Plume collimation for laser ablation electrospray ionization mass spectrometry". United States. https://www.osti.gov/servlets/purl/1157080.
@article{osti_1157080,
title = {Plume collimation for laser ablation electrospray ionization mass spectrometry},
author = {Vertes, Akos and Stolee, Jessica A.},
abstractNote = {In various embodiments, a device may generally comprise a capillary having a first end and a second end; a laser to emit energy at a sample in the capillary to ablate the sample and generate an ablation plume in the capillary; an electrospray apparatus to generate an electrospray plume to intercept the ablation plume to produce ions; and a mass spectrometer having an ion transfer inlet to capture the ions. The ablation plume may comprise a collimated ablation plume. The device may comprise a flow cytometer. Methods of making and using the same are also described.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Sep 09 00:00:00 EDT 2014},
month = {Tue Sep 09 00:00:00 EDT 2014}
}
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Isotope-ratio-monitoring gas chromatography-mass spectrometry apparatus and method
patent, April 1991
- Hayes, John
- US Patent Document 5,012,052
Frequency standard using an atomic fountain of optically trapped atoms
patent, August 1994
- Chu, Steven; Weiman, Carl F. R.; Swann, William C.
- US Patent Document 5,338,930
Method and apparatus for determining the size distribution of different types of particles in a sample
patent, August 1999
- Esser, Anton; Runge, Frank; Kaub, Hans-Peter
- US Patent Document 5,940,177
Atmospheric pressure matrix assisted laser desorption
patent, October 1999
- Laiko, Victor; Burlingame, Alma L.
- US Patent Document 5,965,884
Methods for early detection of heart disease
patent, April 2001
- Sabbadini, Roger A.
- US Patent Document 6,210,976
Ion mobility spectrometer, spectrometer analyte detection and identification verification system, and method
patent, December 2002
- Atkinson, David A.
- US Patent Document 6,495,824
Methods and apparatus for cell analysis
patent, March 2003
- Palmer-Toy, Darryl E.; Sarracino, David A.; Sgroi, Dennis
- US Patent Document 6,531,318
Miniaturized cell array methods and apparatus for cell-based screening
patent, April 2003
- Kapur, Ravi; Adams, Terri
- US Patent Document 6,548,263
Automated sample processing for identification of microorganisms and proteins
patent, May 2003
- Krishnamurthy, Thaiyalnayaki
- US Patent Document 6,558,946
Mass spectrometric methods for biomolecular screening
patent, December 2003
- Crooke, Stanley T.; Griffey, Richard H.; Hofstadler, Steven A.
- US Patent Document 6,656,690
Method and apparatus for feedback controlled electrospray
patent, June 2004
- Valaskovic, Gary A.; Lee, Mike
- US Patent Document 6,744,046
Method and device for manipulating microscopic quantities of material
patent, September 2005
- Taylor, Rod; Hnatovsky, Cyril
- US Patent Document 6,941,033
Microstructure apparatus and method for separating differently charged molecules using an applied electric field
patent, September 2005
- Jalali, Shila; Harper, Alan Roger; Simpson, Matt
- US Patent Document 6,942,778
Atmospheric pressure ion source
patent, September 2005
- Cody, Robert B.; Laramee, James A.
- US Patent Document 6,949,741
Gold implantation/deposition of biological samples for laser desorption three dimensional depth profiling of tissues
patent, January 2006
- Schultz, J. Albert; Ugarov, Michael V.; Egan, Thomas F.
- US Patent Document 6,989,528
Solid phase sequencing of double-stranded nucleic acids
patent, January 2006
- Fu, Dong-Jing; Cantor, Charles R.; Koster, Hubert
- US Patent Document 6,991,903
Method for predicting cardiovascular events
patent, July 2006
- Yusuf, Salim; Hirsh, Jack; Eikelboom, John
- US Patent Document 7,081,347
Method for increasing ionization efficiency in mass spectroscopy
patent, August 2006
- Schneider, Luke V.
- US Patent Document 7,084,396
Apparatus and method for sensor control and feedback
patent, August 2006
- Fischer, Steven M.; Gourley, Darrell L.; Ingle, Glen F.
- US Patent Document 7,091,483
Method for atmospheric pressure analyte ionization
patent, September 2006
- Laramee, James A.; Cody, Robert B.
- US Patent Document 7,112,785
Laser desorption and ionization mass spectrometer with quantitative reproducibility
patent, October 2006
- Youngquist, Michael; Keller, Craig A.
- US Patent Document 7,129,483
MALDI-IM-ortho-TOF mass spectrometry with simultaneous positive and negative mode detection
patent, January 2007
- Furutani, Hiroshi; Ugarov, Michael V.; Prather, Kimberly A.
- US Patent Document 7,170,052
Diagnosis of Smith-Lemli-Optiz syndrome
patent, March 2007
- Shackleton, Cedric
- US Patent Document 7,192,779
Combined chemical/biological agent detection system and method utilizing mass spectrometry
patent, September 2007
- Bryden, Wayne A.; Cotter, Robert J.; Ecelberger, Scott
- US Patent Document 7,271,397
Method and system for desorption electrospray ionization
patent, February 2008
- Takats, Zoltan; Gologan, Bogdan; Wiseman, Justin
- US Patent Document 7,335,897
Mass spectrometric based method for sample identification
patent, March 2008
- Amirav, Aviv; Alon, Tal
- US Patent Document 7,345,275
Laser desorption—electrospray ion (ESI) source for mass spectrometers
patent, April 2009
- Kovtoun, Viatcheslav V.
- US Patent Document 7,525,105
Computational method and system for mass spectral analysis
patent, August 2009
- Wang, Yongdong
- US Patent Document 7,577,538
Gold implantation/deposition of biological samples for laser desorption two and three dimensional depth profiling of biological tissues
patent, December 2009
- Schultz, J. Albert; Ugarov, Michael V.; Egan, Thomas F.
- US Patent Document 7,629,576
Pattern recognition of whole cell mass spectra
patent, March 2010
- Shvartsburg, Alexandre A.; Wilkes, Jon G.; Chiarelli, Paul
- US Patent Document 7,684,934
Mass spectrometric imaging method under ambient conditions using electrospray-assisted laser desorption ionization mass spectrometry
patent, March 2010
- Shiea, Jentaie
- US Patent Document 7,687,772
Electrospray-assisted laser desorption ionization device, mass spectrometer, and method for mass spectrometry
patent, April 2010
- Shiea, Jentaie; Huang, Min
- US Patent Document 7,696,475
Methods for direct biomolecule identification by matrix-assisted laser desorption ionization (MALDI) mass spectrometry
patent, May 2010
- Pevsner, Paul H.; Naftolin, Frederick; Miller, Douglas C.
- US Patent Document 7,714,276
Mass spectroscopic reaction-monitoring method
patent, May 2010
- Shiea, Jentaie; Yuan, Cheng-Hui; Jheng, Jhih-Yuan
- US Patent Document 7,718,958
Protein microscope
patent, June 2010
- Vertes, Akos; Reeves, Mark E.; Kashanchi, Fatah
- US Patent Document 7,735,146
Peptide sequencing from peptide fragmentation mass spectra
patent, August 2010
- Walden, Peter; Demine, Rodion
- US Patent Document 7,783,429
Compositions and methods for the treatment and prevention of cancer, angiogenesis, and inflammation
patent, March 2011
- Sabbadini, Roger A.
- US Patent Document 7,901,682
Three-dimensional molecular imaging by infrared laser ablation electrospray ionization mass spectrometry
patent, June 2011
- Vertes, Akos; Nemes, Peter
- US Patent Document 7,964,843
Natural marine source phospholipids comprising polyunsaturated fatty acids and their applications
patent, October 2011
- Sampalis, Fotini
- US Patent Document 8,030,348
Laser ablation electrospray ionization (LAESI) for atmospheric pressure, In vivo, and imaging mass spectrometry
patent, November 2011
- Vertes, Akos; Nemes, Peter
- US Patent Document 8,067,730
Laser desorption ionization and peptide sequencing on laser induced silicon microcolumn arrays
patent, December 2011
- Vertes, Akos; Chen, Yong
- US Patent Document 8,084,734
Three-dimensional molecular imaging by infrared laser ablation electrospray ionization mass spectrometry
patent, October 2012
- Vertes, Akos; Nemes, Peter
- US Patent Document 8,299,429
Method and apparatus for feedback controlled electrospray
patent-application, December 2002
- Valaskovic, Gary A.; Lee, Mike S.
- US Patent Application 10/154767; 20020190203
Size separation of analytes using monomeric surfactants
patent-application, January 2003
- Young, Edward S.; Wei, Wei
- US Patent Application 10/085656; 20030000838
Method for searching for gene encoding nuclear transport protein
patent-application, September 2003
- Maekawa, Takami; Mori, Maiko; Takahara, Yoshiyuki
- US Patent Application 10/204310; 20030180801
Method and device for manipulating microscopic quantities of material
patent-application, March 2004
- Taylor, Rod; Hnatovsky, Cyril
- US Patent Application 10/602604; 20040051037
Method and compositions for identifying anti-HIV therapeutic compounds
patent-application, June 2004
- Birkus, Gabriel; Chen, James M.; Chen, Xiaowu
- US Patent Application 10/424186; 20040121316
Diagnosis of pathogen infections using mass spectral analysis of immune system modulators in post-exposure biological samples
patent-application, November 2004
- Jackman, Joany
- US Patent Application 10/470890; 20040234971
Methods and apparatuses for analyzing biological samples by mass spectrometry
patent-application, February 2005
- Caprioli, Richard
- US Patent Application 10/880750; 20050029444
Gold implantation/deposition of biological samples for laser desorption three dimensional depth profiling of tissues
patent-application, February 2005
- Schultz, J. Albert; Ugarov, Michael V.; Egan, Thomas F.
- US Patent Application 10/861962; 20050035284
Method and apparatus for mass spectrometry analysis of aerosol particles at atmospheric pressure
patent-application, February 2005
- Tan, Phillip V.; Doroshenko, Vladimir M.
- US Patent Application 10/639508; 20050035285
Laser desorption ion source
patent-application, March 2005
- Willoughby, Ross C.; Sheehan, Edward W.; Whitehouse, Craig M.
- US Patent Application 10/862304; 20050056776
Pattern recognition of whole cell mass spectra
patent-application, March 2005
- Shavartsburg, Alexandre; Wilkes, Jon G.; Chiarelli, Paul
- US Patent Application 10/863745; 20050061967
Method and system for desorption electrospray ionization
patent-application, October 2005
- Takats, Zoltan; Gologan, Bogdan; Wiseman, Justin Michael
- US Patent Application 11/090455; 20050230635
Combined chemical/biological agent detection system and method utilizing mass spectrometry
patent-application, November 2005
- Bryden, Wayne A.; Cotter, Robert J.; Ecelberger, Scott A.
- US Patent Application 10/515300; 20050247871
Methods for isolating molecular mimetics of unique Neisseria meningitidis serogroup B epitopes
patent-application, February 2006
- Granoff, Dan M.; Moe, Gregory R.
- US Patent Application 11/244209; 20060035284
Differential diagnosis of vitamin B12, vitamin B6, and folic acid disorders
patent-application, May 2006
- Lehmann, Paul; Roddiger, Ralf; Klima, Horst
- US Patent Application 11/225287; 20060105392
Peptide sequencing from peptide fragmentation mass spectra
patent-application, August 2006
- Walden, Peter; Rodion, Peter
- US Patent Application 11/060591; 20060190183
Computational method and system for mass spectral analysis
patent-application, September 2006
- Wang, Yongdong
- US Patent Application 10/554768; 20060217911
Systems and methods for characterization of molecules
patent-application, November 2006
- Chait, Arnon; Zaslavsky, Boris Y.
- US Patent Application 10/560373; 20060269964
Mass spectrometric based method for sample identification
patent-application, December 2006
- Amirav, Aviv; Alon, Tal
- US Patent Application 11/303645; 20060284068
Methods for direct biomolecule identification by matrix-assisted laser desorption ionization (MALDI) mass spectrometry
patent-application, May 2007
- Pevsner, Paul; Naftolin, Frederick; Miller, Douglas C.
- US Patent Application 11/541380; 20070114375
Electrospray-Assisted Laser Desorption Ionization Device, Mass Spectrometer, and Method for Mass Spectrometry
patent-application, August 2007
- Shiea, Jentaie; Huang, Min Zong
- US Patent Application 11/561131; 20070176113
Compositions and methods for the treatment and prevention of cancer, angiogenesis, and inflammation
patent-application, September 2007
- Sabbadini, Roger A.
- US Patent Application 11/638730; 20070212348
Reagents and Methods for Using Human Embryonic Stem Cells to Evaluate Toxicity of Pharmaceutical Compounds and Other Chemicals
patent-application, October 2007
- Cezar, Gabriela G.
- US Patent Application 11/733677; 20070248947
Method of Analyzing Biosample by Laser Ablation and Apparatus Therefor
patent-application, January 2008
- Hayashizaki, Yoshide; Kawai, Jun; Hayashi, Toshizo
- US Patent Application 10/594770; 20080020474
Laser Desorption Device, Mass Spectrometer Assembly, and Method for Ambient Liquid Mass Spectrometry
patent-application, May 2008
- Shiea, Jentaie; Yuan, Cheng Hui
- US Patent Application 11/746282; 20080116366
Hypolipidemic and/or hypocholesteremic compounds obtainable from the goldenseal plant
patent-application, May 2008
- Liu, Jingwen; Abidi, Parveen; Chen, Wei
- US Patent Application 11/820288; 20080124404
Mass Spectrometry With Laser Ablation
patent-application, June 2008
- Nikolaev, Evgenij; Franzen, Jochen
- US Patent Application 11/943904; 20080128614
Protein Microscope
patent-application, June 2008
- Vertes, Akos; Reeves, Mark E.; Kashanchi, Farah
- US Patent Application 11/795687; 20080149822
Rare Cell Analysis Using Sample Splitting and DNA Tags
patent-application, September 2008
- Shoemaker, Daniel; Fuchs, Martin; Krueger, Neil X.
- US Patent Application 11/763421; 20080220422
Laser desorption - electrospray ion (ESI) source for mass spectrometers
patent-application, November 2008
- Kovtoun, Viatcheslav V.
- US Patent Document 11/799910; 20080272294
Electrospray-Assisted Laser-Induced Acoustic Desorption Ionization Mass Spectrometer and a Method for Mass Spectrometry
patent-application, December 2008
- Shiea, Jentaie
- US Patent Application 12/112532; 20080308722
Lamp
patent-application, January 2009
- Bremerich, Matthias; Klose, Leonhard
- US Patent Application 11/974517; 20090027892
Method for Analyzing Foods
patent-application, February 2009
- Anderson, Kim A.; Smith, Brain W.
- US Patent Application 12/255571; 20090042304
Imaging Mass Spectrometry Principle and Its Application in a Device
patent-application, October 2009
- Bamberger, Casimir; Bamberger, Andreas
- US Patent Application 12/424817; 20090261243
Laser Ablation Electrospray Ionization (LAESI) for Atmospheric Pressure, In Vivo, and Imaging Mass Spectrometry
patent-application, November 2009
- Vertes, Akos; Nemes, Peter
- US Patent Application 12/176324; 20090272892
Laser ablation flowing atmospheric-pressure afterglow for ambient mass spectrometry
patent-application, November 2009
- Hieftje, Gary M.; Andrade, Francisco J.; Ray, Steven J.
- US Patent Application 12/387348; 20090272893
Laser Desorption Ionization and Peptide Sequencing on Laser Induced Silicon Microcolumn Arrays
patent-application, December 2009
- Vertes, Akos; Chen, Yong
- US Patent Application 11/674671; 20090321626
Three-Dimensional Molecular Imaging By Infrared Laser Ablation Electrospray Ionization Mass Spectrometry
patent-application, January 2010
- Vertes, Akos; Nemes, Peter
- US Patent Application 12/323276; 20100012831
Microfluidic Devices and Production Methods Therefor
patent-application, April 2010
- Barholm-Hansen, Claus; Jonsman, Jacques; Baekmark, Thomas Rosleff
- US Patent Application 11/813835; 20100089529
Gold Implantation/Deposition of Biological Samples for Laser Desorption Two and Three Dimensional Depth Profiling of Biological Tissues
patent-application, April 2010
- Schultz, J. Albert; Ugarov, Michael V.; Egan, Thomas F.
- US Patent Application 12/630922; 20100090101
Ionization Device
patent-application, April 2010
- Liang, Qiao; Yang, Pengyuan; Liu, Baohong
- US Patent Application 12/522572; 20100090105
Method and device for separation and depletion of certain proteins and particles using electrophoresis
patent-application, October 2010
- Weber, Gerhard
- US Patent Application 12/308648; 20100252435
Methods for Detecting Metabolic States by Laser Ablation Electrospray Ionization Mass Spectrometry
patent-application, November 2010
- Vertes, Akos; Kashanchi, Fatah; Sripadi, Prabhakar
- US Patent Application 12/774533; 20100285446
Method and apparatus for identification of biological material
patent-application, August 2011
- van Wuijckhuijse, Arjan Laurens; Parchen, Rene
- US Patent Application 13/059947; 20110204220
Subcellular Analysis by Laser Ablation Electrospray Ionization Mass Spectrometry
patent-application, September 2011
- Vertes, Akos; Stolee, Jessica A.; Shrestha, Bindesh
- US Patent Application 13/045277; 20110215233
Three-Dimensional Molecular Imaging By Infrared Laser Ablation Electrospray Ionization Mass Spectrometry
patent-application, November 2011
- Vertes, Akos; Nemes, Peter
- US Patent Application 13/101518; 20110272572
Laser Ablation Electrospray Ionization (LAESI) for Atmospheric Pressure, In Vivo, and Imaging Mass Spectrometry
patent-application, February 2012
- Vertes, Akos; Nemes, Peter
- US Patent Application 13/271435; 20120025069
Vaporization Device and Method for Imaging Mass Spectrometry
patent-application, June 2012
- Levis, Robert J.; Brady, John J.; Judge, Elizabeth J.
- US Patent Application 13/390722; 20120149009
Three-Dimensional Molecular Imaging By Infrared Laser Ablation Electrospray Ionization Mass Spectrometry
patent-application, November 2012
- Vertes, Akos; Nemes, Peter
- US Patent Application 13/559943; 20120298857
Laser spray: electric field-assisted matrix-assisted laser desorption/ionization
journal, April 2004
- Hiraoka, Kenzo
- Journal of Mass Spectrometry, Vol. 39, Issue 4
In Situ Metabolic Profiling of Single Cells by Laser Ablation Electrospray Ionization Mass Spectrometry
journal, October 2009
- Shrestha, Bindesh; Vertes, Akos
- Analytical Chemistry, Vol. 81, Issue 20
Intact and top-down characterization of biomolecules and direct analysis using infrared matrix-assisted laser desorption electrospray ionization coupled to FT-ICR mass spectrometry
journal, April 2009
- Sampson, Jason S.; Murray, Kermit K.; Muddiman, David C.
- Journal of the American Society for Mass Spectrometry, Vol. 20, Issue 4, p. 667-673
Nanoscale Atmospheric Pressure Laser Ablation-Mass Spectrometry
journal, April 2001
- Stöckle, Raoul; Setz, Patrick; Deckert, Volker
- Analytical Chemistry, Vol. 73, Issue 7
Laser Desorption-Atmospheric Pressure Chemical Ionization Mass Spectrometry for the Analysis of Peptides from Aqueous Solutions
journal, November 2002
- Coon, Joshua J.; Harrison, W. W.
- Analytical Chemistry, Vol. 74, Issue 21
New dimension in nano-imaging: breaking through the diffraction limit with scanning near-field optical microscopy
journal, November 2004
- Rasmussen, Akiko; Deckert, Volker
- Analytical and Bioanalytical Chemistry, Vol. 381, Issue 1
Direct Protein Detection from Biological Media through Electrospray-Assisted Laser Desorption Ionization/Mass Spectrometry
journal, May 2006
- Huang, Min-Zong; Hsu, Hsiu-Jung; Lee, Jen-Yih
- Journal of Proteome Research, Vol. 5, Issue 5
Mass Spectrometry Sampling Under Ambient Conditions with Desorption Electrospray Ionization
journal, October 2004
- Takats, Z.
- Science, Vol. 306, Issue 5695, p. 471-473
Versatile New Ion Source for the Analysis of Materials in Open Air under Ambient Conditions
journal, April 2005
- Cody, Robert B.; Laramée, James A.; Durst, H. Dupont
- Analytical Chemistry, Vol. 77, Issue 8, p. 2297-2302
Laser Ablation Electrospray Ionization for Atmospheric Pressure, in Vivo, and Imaging Mass Spectrometry
journal, November 2007
- Nemes, Peter; Vertes, Akos
- Analytical Chemistry, Vol. 79, Issue 21
Recent Advances in Optical Tweezers
journal, June 2008
- Moffitt, Jeffrey R.; Chemla, Yann R.; Smith, Steven B.
- Annual Review of Biochemistry, Vol. 77, Issue 1
Simultaneous Imaging of Small Metabolites and Lipids in Rat Brain Tissues at Atmospheric Pressure by Laser Ablation Electrospray Ionization Mass Spectrometry
journal, February 2010
- Nemes, Peter; Woods, Amina S.; Vertes, Akos
- Analytical Chemistry, Vol. 82, Issue 3
In Situ Metabolic Profiling of Single Cells by Laser Ablation Electrospray Ionization Mass Spectrometry
journal, October 2009
- Shrestha, Bindesh; Vertes, Akos
- Analytical Chemistry, Vol. 81, Issue 20
Infrared laser-assisted desorption electrospray ionization mass spectrometry
journal, January 2008
- Rezenom, Yohannes H.; Dong, Jianan; Murray, Kermit K.
- The Analyst, Vol. 133, Issue 2
Ablation and analysis of small cell populations and single cells by consecutive laser pulses
journal, June 2010
- Shrestha, Bindesh; Nemes, Peter; Vertes, Akos
- Applied Physics A, Vol. 101, Issue 1
Infrared Laser Ablation Atmospheric Pressure Photoionization Mass Spectrometry
journal, January 2012
- Vaikkinen, Anu; Shrestha, Bindesh; Kauppila, Tiina J.
- Analytical Chemistry, Vol. 84, Issue 3
Elevated subcortical choline metabolites in cognitively and clinically asymptomatic HIV patients
journal, March 1999
- Meyerhoff, D. J.; Bloomer, C.; Cardenas, V.
- Neurology, Vol. 52, Issue 5
High Precision Isotope Ratio Monitoring Techniques in Mass Spectrometry
journal, March 1996
- Brand, Willi A.
- Journal of Mass Spectrometry, Vol. 31, Issue 3, p. 225-235
Works referencing / citing this record:
Plume collimation for laser ablation electrospray ionization mass spectrometry
patent, June 2016
- Vertes, Akos; Stolee, Jessica A.
- US Patent Document 9,362,101
Fluidic channel based on a filtered, free-space electromagnetic wave source
patent, April 2016
- Pascoguin, Bienvenido Melvin L.; Lu, Ryan P.; Ramirez, Ayax D.
- US Patent Document 9,315,846