Bioaffinity Screening with a Rapid and Sample-Efficient Autosampler for Native Electrospray Ionization Mass Spectrometry
dc.contributor.author
Kaeslin, Jérôme
dc.contributor.author
Brunner, Cyrill
dc.contributor.author
Ghiasikhou, Sahar
dc.contributor.author
Schneider, Gisbert
dc.contributor.author
Zenobi, Renato
dc.date.accessioned
2022-09-21T10:19:36Z
dc.date.available
2021-09-29T07:32:44Z
dc.date.available
2021-10-01T08:58:47Z
dc.date.available
2021-10-07T05:01:46Z
dc.date.available
2021-10-14T12:44:31Z
dc.date.available
2022-09-21T10:19:36Z
dc.date.issued
2021-10-05
dc.identifier.issn
1520-6882
dc.identifier.issn
0003-2700
dc.identifier.other
10.1021/acs.analchem.1c03130
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/507526
dc.identifier.doi
10.3929/ethz-b-000507526
dc.description.abstract
Fast and efficient handling of ligands and biological targets are required in bioaffinity screening based on native electrospray ionization mass spectrometry (ESI-MS). We use a prototype microfluidic autosampler, called the “gap sampler”, to sequentially mix and electrospray individual small molecule ligands together with a target protein and compare the screening results with data from thermal shift assay and surface plasmon resonance. In a first round, all three techniques were used for a screening of 110 ligands against bovine carbonic anhydrase II, which resulted in five mutual hits and some false positives with ESI-MS presumably due to the high ligand concentration or interferences from dimethyl sulfoxide. In a second round, 33 compounds were screened in lower concentrations and in a less complex matrix, resulting in only true positives with ESI-MS. Within a cycle time of 30 s, dissociation constants were determined within an order of magnitude accuracy consuming only 5 pmol of ligand and less than 15 pmol of protein per screened compound. In a third round, dissociation constants of five compounds were accurately determined in a titration experiment. Thus, the gap sampler can rapidly and efficiently be used for high-throughput screening.
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application/pdf
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text/csv
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en
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dc.publisher
American Chemical Society
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http://rightsstatements.org/page/InC-NC/1.0/
dc.title
Bioaffinity Screening with a Rapid and Sample-Efficient Autosampler for Native Electrospray Ionization Mass Spectrometry
en_US
dc.type
Journal Article
dc.rights.license
In Copyright - Non-Commercial Use Permitted
dc.date.published
2021-09-21
ethz.journal.title
Analytical Chemistry
ethz.journal.volume
93
en_US
ethz.journal.issue
39
en_US
ethz.journal.abbreviated
Anal. Chem.
ethz.pages.start
13342
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ethz.pages.end
13350
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ethz.size
8 p. accepted version; 47 p. supplementary information (figure S3-S17); 589.58 kb supplementary information (table S1 and S2)
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ethz.version.deposit
acceptedVersion
en_US
ethz.grant
Soft ionization mass spectrometry for studying noncovalent interactions
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Washington, DC
en_US
ethz.publication.status
published
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ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02514 - Laboratorium für Organische Chemie / Laboratory of Organic Chemistry::03430 - Zenobi, Renato / Zenobi, Renato
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03852 - Schneider, Gisbert / Schneider, Gisbert
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02514 - Laboratorium für Organische Chemie / Laboratory of Organic Chemistry::03430 - Zenobi, Renato / Zenobi, Renato
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03852 - Schneider, Gisbert / Schneider, Gisbert
ethz.grant.agreementno
178765
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Projekte MINT
ethz.relation.isSupplementedBy
10.3929/ethz-b-000494717
ethz.date.deposited
2021-09-29T07:32:59Z
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FORM
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yes
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Open access
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ethz.date.embargoend
2022-09-20
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2021-10-14T12:44:38Z
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