title: Global optimization of the infrared matrix-assisted laser desorption electrospray ionization (IR MALDESI) source for mass spectrometry using statistical design of experiments.
abstract: Design of experiments (DOE) is a systematic and cost-effective approach to system optimization by which the effects of multiple parameters and parameter interactions on a given response can be measured in few experiments. Herein, we describe the use of statistical DOE to improve a few of the analytical figures of merit of the infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) source for mass spectrometry. In a typical experiment, bovine cytochrome c was ionized via electrospray, and equine cytochrome c was desorbed and ionized by IR-MALDESI such that the ratio of equine:bovine was used as a measure of the ionization efficiency of IR-MALDESI. This response was used to rank the importance of seven source parameters including flow rate, laser fluence, laser repetition rate, ESI emitter to mass spectrometer inlet distance, sample stage height, sample plate voltage, and the sample to mass spectrometer inlet distance. A screening fractional factorial DOE was conducted to designate which of the seven parameters induced the greatest amount of change in the response. These important parameters (flow rate, stage height, sample to mass spectrometer inlet distance, and laser fluence) were then studied at higher resolution using a full factorial DOE to obtain the globally optimized combination of parameter settings. The optimum combination of settings was then compared with our previously determined settings to quantify the degree of improvement in detection limit. The limit of detection for the optimized conditions was approximately 10 attomoles compared with 100 femtomoles for the previous settings, which corresponds to a four orders of magnitude improvement in the detection limit of equine cytochrome c.
authors.affiliation: W.M. Keck FT-ICR Mass Spectrometry Laboratory, Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Barry
authors.forename: David C
authors.initials: DC
authors.lastname: Muddiman
mesh_terms: D000818:Animals; D002417:Cattle; D045304:Cytochromes c / Q000032:analysis / Q000737:chemistry; D006736:Horses; D057230:Limit of Detection; D012107:Research Design; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D045304:Cytochromes c
references.citation: J Mass Spectrom. 2008 Sep;43(9):1161-80
references.pmid: 18671242
references.citation: J Am Soc Mass Spectrom. 2002 Jan;13(1):2-9
references.pmid: 11777196
references.citation: Nature. 2003 Mar 13;422(6928):198-207
references.pmid: 12634793
references.citation: Anal Chem. 1988 Oct 15;60(20):2299-301
references.pmid: 3239801
references.citation: Anal Chem. 2008 Sep 15;80(18):6995-7003
references.pmid: 18683952
references.citation: Rapid Commun Mass Spectrom. 2005;19(24):3701-4
references.pmid: 16299699
references.citation: J Am Soc Mass Spectrom. 2011 Apr;22(4):773-83
references.pmid: 21472614
references.citation: Anal Chem. 2008 Jun 15;80(12):4575-82
references.pmid: 18473485
references.citation: Science. 2004 Oct 15;306(5695):471-3
references.pmid: 15486296
references.citation: Science. 2006 Mar 17;311(5767):1566-70
references.pmid: 16543450
references.citation: J Mass Spectrom. 1999 Oct;34(10):1055-62
references.pmid: 10510428
references.citation: Analyst. 2010 Apr;135(4):751-8
references.pmid: 20349540
references.citation: Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7003-7
references.pmid: 8692933
references.citation: Mass Spectrom Rev. 2009 Nov-Dec;28(6):870-97
references.pmid: 19626583
references.citation: J Am Soc Mass Spectrom. 2006 Dec;17(12):1712-6
references.pmid: 16952462
references.citation: Anal Chem. 1995 Oct 15;67(20):3802-5
references.pmid: 8644926
references.citation: Rapid Commun Mass Spectrom. 2010 May 15;24(9):1365-70
references.pmid: 20391610
references.citation: Anal Chem. 2007 Apr 15;79(8):3105-16
references.pmid: 17378541
references.citation: Analyst. 2010 Apr;135(4):661-8
references.pmid: 20309440
references.citation: Analyst. 2010 Apr;135(4):767-72
references.pmid: 20349541
references.citation: Anal Chem. 2007 Nov 1;79(21):8098-106
references.pmid: 17900146
references.citation: J Biomed Opt. 2002 Apr;7(2):165-78
references.pmid: 11966301
references.citation: Rapid Commun Mass Spectrom. 2009 Oct;23(19):3151-7
references.pmid: 19714710
references.citation: Anal Chem. 2010 Apr 15;82(8):3231-8
references.pmid: 20334359
references.citation: J Am Soc Mass Spectrom. 2009 Apr;20(4):667-73
references.pmid: 19185512
references.citation: J Am Soc Mass Spectrom. 2008 Oct;19(10):1527-34
references.pmid: 18657438
references.citation: J Am Soc Mass Spectrom. 2002 Apr;13(4):354-61
references.pmid: 11951973
references.citation: J Mass Spectrom. 2005 May;40(5):565-79
references.pmid: 15880604
references.citation: Rapid Commun Mass Spectrom. 2006;20(8):1299-304
references.pmid: 16548069
references.citation: Int J Mass Spectrom. 2011 Mar 1;300(2-3):99-107
references.pmid: 21499524
references.citation: Anal Chem. 2010 Aug 1;82(15):6636-42
references.pmid: 20590124
references.citation: Science. 1989 Oct 6;246(4926):64-71
references.pmid: 2675315
references.citation: Analyst. 2010 May;135(5):880-2
references.pmid: 20419234
references.citation: Analyst. 2008 Feb;133(2):226-32
references.pmid: 18227946
references.citation: Rapid Commun Mass Spectrom. 2007;21(7):1150-4
references.pmid: 17318926
references.citation: J Am Soc Mass Spectrom. 2004 Aug;15(8):1201-15
references.pmid: 15276167
references.citation: Anal Chem. 2005 Apr 15;77(8):2297-302
references.pmid: 15828760
references.citation: Anal Chem. 2008 Feb 1;80(3):873-7
references.pmid: 18177019
references.citation: Anal Chem. 2009 Dec 1;81(23):9682-8
references.pmid: 19886638
references.citation: J Am Soc Mass Spectrom. 2009 Nov;20(11):1947-63
references.pmid: 19748284
references.citation: Anal Chem. 2005 Dec 1;77(23):7826-31
references.pmid: 16316194