Dynamic mass spectrometry probe for electrospray ionization mass spectrometry monitoring of bioreactors for therapeutic cell manufacturing.
biomarker monitoring and discovery
cell manufacturing
microfabricated sampling platform
online electrospray ionization mass spectrometry
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
03
07
2018
revised:
29
08
2018
accepted:
05
09
2018
pubmed:
11
9
2018
medline:
18
12
2019
entrez:
11
9
2018
Statut:
ppublish
Résumé
Large-scale manufacturing of therapeutic cells requires bioreactor technologies with online feedback control enabled by monitoring of secreted biomolecular critical quality attributes (CQAs). Electrospray ionization mass spectrometry (ESI-MS) is a highly sensitive label-free method to detect and identify biomolecules, but requires extensive sample preparation before analysis, making online application of ESI-MS challenging. We present a microfabricated, monolithically integrated device capable of continuous sample collection, treatment, and direct infusion for ESI-MS detection of biomolecules in high-salt solutions. The dynamic mass spectrometry probe (DMSP) uses a microfluidic mass exchanger to rapidly condition samples for online MS analysis by removing interfering salts, while concurrently introducing MS signal enhancers to the sample for sensitive biomolecular detection. Exploiting this active conditioning capability increases MS signal intensity and signal-to-noise ratio. As a result, sensitivity for low-concentration biomolecules is significantly improved, and multiple proteins can be detected from chemically complex samples. Thus, the DMSP has significant potential to serve as an enabling portion of a novel analytical tool for discovery and monitoring of CQAs relevant to therapeutic cell manufacturing.
Identifiants
pubmed: 30199089
doi: 10.1002/bit.26832
pmc: PMC6310154
mid: NIHMS1001426
doi:
Substances chimiques
Biological Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
121-131Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM112662
Pays : United States
Informations de copyright
© 2018 Wiley Periodicals, Inc.
Références
Nat Biotechnol. 2016 Apr;34(4):393-400
pubmed: 27054995
Cell Stem Cell. 2008 Oct 9;3(4):369-81
pubmed: 18940729
Anal Chim Acta. 2008 Oct 3;627(1):71-81
pubmed: 18790129
Anal Chem. 2012 Feb 21;84(4):2072-5
pubmed: 22263997
Science. 1989 Oct 6;246(4926):64-71
pubmed: 2675315
Phys Chem Chem Phys. 2010 Nov 7;12(41):13476-83
pubmed: 20877871
Proteomics. 2006 May;6(10):3223-30
pubmed: 16586435
Science. 2007 Jul 13;317(5835):256-60
pubmed: 17569825
Mater Sci Eng C Mater Biol Appl. 2013 Oct;33(7):4453-9
pubmed: 23910365
J Am Soc Mass Spectrom. 2010 Jan;21(1):127-31
pubmed: 19854660
Immunity. 1998 Dec;9(6):765-75
pubmed: 9881967
Anal Chem. 1996 Sep 15;68(18):3295-9
pubmed: 8797389
Anal Chem. 2015 Jan 6;87(1):351-6
pubmed: 25490085
Biotechnol Bioeng. 2014 Jan;111(1):69-83
pubmed: 23893544
Rapid Commun Mass Spectrom. 2017 Feb 15;31(3):264-268
pubmed: 27862466
Anal Chem. 1999 Apr 15;71(8):1485-90
pubmed: 10221069
Biotechnol Bioeng. 2017 Feb;114(2):245-259
pubmed: 27531038
PLoS One. 2010 Apr 16;5(4):e10075
pubmed: 20419124
Blood. 2015 Jun 25;125(26):4017-23
pubmed: 25999455
Stem Cell Res Ther. 2018 Jan 2;9(1):1
pubmed: 29291747
Analyst. 2014 Oct 7;139(19):4810-9
pubmed: 25133273
Biotechnol Bioeng. 2009 Nov 1;104(4):796-808
pubmed: 19591186
J Am Soc Mass Spectrom. 2017 Sep;28(9):1827-1835
pubmed: 28710594
Biotechnol Bioeng. 2011 May;108(5):1215-21
pubmed: 21449033
J Mass Spectrom. 2012 Feb;47(2):201-7
pubmed: 22359330
Cancer Gene Ther. 2015 Mar;22(2):72-8
pubmed: 25613483
Biotechnol Bioeng. 2017 Sep;114(9):2032-2042
pubmed: 28464210
Mass Spectrom Rev. 2001 Nov-Dec;20(6):362-87
pubmed: 11997944
Drug Discov Today. 2011 Apr;16(7-8):293-7
pubmed: 21277382
J Mass Spectrom. 2005 Jul;40(7):924-31
pubmed: 15934039
Circulation. 2006 Jul 25;114(4):353-8
pubmed: 16864740
Nat Biomed Eng. 2018 Jun;2(6):362-376
pubmed: 31011198
Annu Rev Biomed Eng. 2009;11:49-79
pubmed: 19400705
Anal Chem. 2014 May 6;86(9):4455-62
pubmed: 24712886
Br J Haematol. 2001 Sep;114(3):671-80
pubmed: 11552997
Biotechnol Bioeng. 1994 Apr 5;43(8):693-9
pubmed: 18615793
Biotechnol Bioeng. 2018 Jun;115(6):1509-1520
pubmed: 29427454
J Am Soc Mass Spectrom. 2016 Feb;27(2):255-64
pubmed: 26466600
J Am Chem Soc. 2003 Feb 26;125(8):2319-27
pubmed: 12590562
Stem Cell Res. 2016 Sep;17(2):379-390
pubmed: 27639108
J Immunol Methods. 2009 Aug 15;347(1-2):3-11
pubmed: 19538965