{"id":"https://openalex.org/W7221119965","doi":"https://doi.org/10.26434/chemrxiv.15010147/v1","title":"Multinotch Isolation Enables Efficient Native Top-down Mass Spectrometry of Proteins in Complex Mixtures.","display_name":"Multinotch Isolation Enables Efficient Native Top-down Mass Spectrometry of Proteins in Complex Mixtures.","publication_year":2026,"publication_date":"2026-10-09","ids":{"openalex":"https://openalex.org/W7221119965","doi":"https://doi.org/10.26434/chemrxiv.15010147/v1"},"language":"en","primary_location":{"id":"doi:10.26434/chemrxiv.15010147/v1","doi":"https://doi.org/10.26434/chemrxiv.15010147/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15010147/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010147/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010147/v1","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5073424141","display_name":"Oliver J. Hale","orcid":"https://orcid.org/0000-0002-2286-5780","observed_orcids":["https://orcid.org/0000-0002-2286-5780"]},"institutions":[{"id":"https://openalex.org/I79619799","display_name":"University of Birmingham","ror":"https://ror.org/03angcq70","country_code":"GB","type":"education","lineage":["https://openalex.org/I79619799"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Oliver J. Hale","raw_affiliation_strings":["School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom, B15 2TT"],"raw_orcid":"https://orcid.org/0000-0002-2286-5780","affiliations":[{"raw_affiliation_string":"School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom, B15 2TT","institution_ids":["https://openalex.org/I79619799"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5014883632","display_name":"Helen J. Cooper","orcid":"https://orcid.org/0000-0003-4590-9384","observed_orcids":["https://orcid.org/0000-0003-4590-9384"]},"institutions":[{"id":"https://openalex.org/I79619799","display_name":"University of Birmingham","ror":"https://ror.org/03angcq70","country_code":"GB","type":"education","lineage":["https://openalex.org/I79619799"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Helen J. Cooper","raw_affiliation_strings":["School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom, B15 2TT"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom, B15 2TT","institution_ids":["https://openalex.org/I79619799"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I79619799"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10519","display_name":"Advanced Proteomics Techniques and Applications","score":0.5175999999046326,"subfield":{"id":"https://openalex.org/subfields/1607","display_name":"Spectroscopy"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T10519","display_name":"Advanced Proteomics Techniques and Applications","score":0.5175999999046326,"subfield":{"id":"https://openalex.org/subfields/1607","display_name":"Spectroscopy"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10683","display_name":"Mass Spectrometry Techniques and Applications","score":0.4812000095844269,"subfield":{"id":"https://openalex.org/subfields/1607","display_name":"Spectroscopy"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10836","display_name":"Metabolomics and Mass Spectrometry Studies","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/native-top-down-mass-spectrometry","display_name":"native top-down mass spectrometry","score":0.9729999899864197},{"id":"https://openalex.org/keywords/charge-reduction","display_name":"charge reduction","score":0.8029999732971191},{"id":"https://openalex.org/keywords/protein-complexes","display_name":"protein complexes","score":0.4410000145435333},{"id":"https://openalex.org/keywords/proteoform-identification","display_name":"proteoform identification","score":0.8840000033378601},{"id":"https://openalex.org/keywords/collisional-activation","display_name":"collisional activation","score":0.7429999709129333},{"id":"https://openalex.org/keywords/sequencing-depth","display_name":"sequencing depth","score":0.5680000185966492},{"id":"https://openalex.org/keywords/tissue-sections","display_name":"tissue sections","score":0.4749999940395355},{"id":"https://openalex.org/keywords/linear-ion-trap","display_name":"linear ion trap","score":0.6439999938011169}],"concepts":[{"id":"https://openalex.org/C49853544","wikidata":"https://www.wikidata.org/wiki/Q206229","display_name":"Biomolecule","level":2,"score":0.7070000171661377},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.680899977684021},{"id":"https://openalex.org/C162356407","wikidata":"https://www.wikidata.org/wiki/Q180809","display_name":"Mass spectrometry","level":2,"score":0.6335999965667725},{"id":"https://openalex.org/C145148216","wikidata":"https://www.wikidata.org/wiki/Q36496","display_name":"Ion","level":2,"score":0.5508000254631042},{"id":"https://openalex.org/C191015642","wikidata":"https://www.wikidata.org/wiki/Q1132459","display_name":"Fragmentation (computing)","level":2,"score":0.5178999900817871},{"id":"https://openalex.org/C186060115","wikidata":"https://www.wikidata.org/wiki/Q30336093","display_name":"Biological system","level":1,"score":0.4131999909877777},{"id":"https://openalex.org/C113196181","wikidata":"https://www.wikidata.org/wiki/Q485223","display_name":"Analytical Chemistry (journal)","level":2,"score":0.38940000534057617},{"id":"https://openalex.org/C111335779","wikidata":"https://www.wikidata.org/wiki/Q3454686","display_name":"Reduction (mathematics)","level":2,"score":0.37610000371932983},{"id":"https://openalex.org/C32909587","wikidata":"https://www.wikidata.org/wiki/Q11369","display_name":"Molecule","level":2,"score":0.3650999963283539},{"id":"https://openalex.org/C40684141","wikidata":"https://www.wikidata.org/wiki/Q902061","display_name":"Electrospray ionization","level":3,"score":0.35510000586509705},{"id":"https://openalex.org/C90673727","wikidata":"https://www.wikidata.org/wiki/Q901718","display_name":"Product (mathematics)","level":2,"score":0.34290000796318054},{"id":"https://openalex.org/C13762613","wikidata":"https://www.wikidata.org/wiki/Q7824366","display_name":"Top-down proteomics","level":5,"score":0.3197000026702881},{"id":"https://openalex.org/C31827203","wikidata":"https://www.wikidata.org/wiki/Q874296","display_name":"Tandem mass spectrometry","level":3,"score":0.3172000050544739},{"id":"https://openalex.org/C188082385","wikidata":"https://www.wikidata.org/wiki/Q73792","display_name":"Charge (physics)","level":2,"score":0.30630001425743103},{"id":"https://openalex.org/C43617362","wikidata":"https://www.wikidata.org/wiki/Q170050","display_name":"Chromatography","level":1,"score":0.305400013923645},{"id":"https://openalex.org/C194451485","wikidata":"https://www.wikidata.org/wiki/Q1327575","display_name":"Electrospray","level":3,"score":0.3003999888896942},{"id":"https://openalex.org/C2775941552","wikidata":"https://www.wikidata.org/wiki/Q25212305","display_name":"Isolation (microbiology)","level":2,"score":0.2928999960422516},{"id":"https://openalex.org/C116834253","wikidata":"https://www.wikidata.org/wiki/Q2039217","display_name":"Identification (biology)","level":2,"score":0.29010000824928284},{"id":"https://openalex.org/C159467904","wikidata":"https://www.wikidata.org/wiki/Q2001702","display_name":"Chemical physics","level":1,"score":0.287200003862381},{"id":"https://openalex.org/C2778112365","wikidata":"https://www.wikidata.org/wiki/Q3511065","display_name":"Sequence (biology)","level":2,"score":0.2784000039100647},{"id":"https://openalex.org/C2779843651","wikidata":"https://www.wikidata.org/wiki/Q7390335","display_name":"SIGNAL (programming language)","level":2,"score":0.2777999937534332},{"id":"https://openalex.org/C40325409","wikidata":"https://www.wikidata.org/wiki/Q2360668","display_name":"Mass spectrum","level":3,"score":0.2639999985694885},{"id":"https://openalex.org/C202157981","wikidata":"https://www.wikidata.org/wiki/Q7251488","display_name":"Protein mass spectrometry","level":4,"score":0.262800008058548},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.25780001282691956},{"id":"https://openalex.org/C161624437","wikidata":"https://www.wikidata.org/wiki/Q1988322","display_name":"Small molecule","level":2,"score":0.2538999915122986}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.26434/chemrxiv.15010147/v1","doi":"https://doi.org/10.26434/chemrxiv.15010147/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15010147/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010147/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.26434/chemrxiv.15010147/v1","doi":"https://doi.org/10.26434/chemrxiv.15010147/v1","is_oa":true,"landing_page_url":"https://doi.org/10.26434/chemrxiv.15010147/v1","pdf_url":"https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010147/v1","source":{"id":"https://openalex.org/S4393918830","display_name":"ChemRxiv","issn_l":"2573-2293","issn":["2573-2293"],"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":null,"raw_type":"posted-content"},"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G262107381","display_name":"A laser mass spectrometry platform for in situ analysis of proteins and their complexes in tissue","funder_award_id":"EP/Z53612X/1","funder_id":"https://openalex.org/F4320334627","funder_display_name":"Engineering and Physical Sciences Research Council"},{"id":"https://openalex.org/G422941047","display_name":"A Mass Spectrometer for Structural Biology and Top-down Protein Identification","funder_award_id":"BB/Z515693/1","funder_id":"https://openalex.org/F4320334629","funder_display_name":"Biotechnology and Biological Sciences Research Council"},{"id":"https://openalex.org/G4445064388","display_name":"Transforming spatial and structural biology: Native ambient mass spectrometry","funder_award_id":"305669/Z/23/Z","funder_id":"https://openalex.org/F4320311904","funder_display_name":"Wellcome Trust"},{"id":"https://openalex.org/G511023329","display_name":null,"funder_award_id":"BB/S019456/1","funder_id":"https://openalex.org/F4320334627","funder_display_name":"Engineering and Physical Sciences Research Council"},{"id":"https://openalex.org/G6003682902","display_name":"Transforming spatial and structural biology: Native ambient mass spectrometry","funder_award_id":"305669","funder_id":"https://openalex.org/F4320311904","funder_display_name":"Wellcome Trust"},{"id":"https://openalex.org/G6357860962","display_name":"A new mass spectrometer for structural proteomics and protein imaging","funder_award_id":"BB/S019456/1","funder_id":"https://openalex.org/F4320334629","funder_display_name":"Biotechnology and Biological Sciences Research Council"},{"id":"https://openalex.org/G8220269927","display_name":"NAMS: Native ambient mass spectrometry","funder_award_id":"EP/S002979/1","funder_id":"https://openalex.org/F4320334627","funder_display_name":"Engineering and Physical Sciences Research Council"}],"funders":[{"id":"https://openalex.org/F4320311904","display_name":"Wellcome Trust","ror":"https://ror.org/029chgv08"},{"id":"https://openalex.org/F4320334627","display_name":"Engineering and Physical Sciences Research Council","ror":"https://ror.org/0439y7842"},{"id":"https://openalex.org/F4320334629","display_name":"Biotechnology and Biological Sciences Research Council","ror":"https://ror.org/00cwqg982"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7221119965.pdf","grobid_xml":"https://content.openalex.org/works/W7221119965.grobid-xml"},"referenced_works_count":50,"referenced_works":["https://openalex.org/W1157001583","https://openalex.org/W1568341953","https://openalex.org/W1982463299","https://openalex.org/W1985625499","https://openalex.org/W1994776398","https://openalex.org/W2002506527","https://openalex.org/W2013608848","https://openalex.org/W2018533830","https://openalex.org/W2034240222","https://openalex.org/W2034530880","https://openalex.org/W2035212554","https://openalex.org/W2038805482","https://openalex.org/W2041399392","https://openalex.org/W2047315389","https://openalex.org/W2060047073","https://openalex.org/W2083516906","https://openalex.org/W2083991421","https://openalex.org/W2111306975","https://openalex.org/W2121612064","https://openalex.org/W2131741443","https://openalex.org/W2334348545","https://openalex.org/W2488798338","https://openalex.org/W2604220201","https://openalex.org/W2763289860","https://openalex.org/W2790214985","https://openalex.org/W2915560282","https://openalex.org/W2966700924","https://openalex.org/W2987849054","https://openalex.org/W3028242720","https://openalex.org/W3046239096","https://openalex.org/W3093581066","https://openalex.org/W3159256190","https://openalex.org/W3160851372","https://openalex.org/W3176070044","https://openalex.org/W3194897413","https://openalex.org/W4211134006","https://openalex.org/W4242256187","https://openalex.org/W4388982459","https://openalex.org/W4390264925","https://openalex.org/W4390781678","https://openalex.org/W4392622747","https://openalex.org/W4394845195","https://openalex.org/W4396692986","https://openalex.org/W4401011139","https://openalex.org/W4401021391","https://openalex.org/W4416193289","https://openalex.org/W4416459470","https://openalex.org/W7128480004","https://openalex.org/W7129223089","https://openalex.org/W7169618951"],"related_works":["https://openalex.org/W3151293110","https://openalex.org/W2087523333","https://openalex.org/W4399939104","https://openalex.org/W4396894833","https://openalex.org/W1261911184","https://openalex.org/W6926865196","https://openalex.org/W4402326155","https://openalex.org/W7171738401","https://openalex.org/W2153180430","https://openalex.org/W4378716275"],"abstract_inverted_index":{"Accurate":[0],"identification":[1,274],"of":[2,36,95,113,141,151,158,167,185,196,230],"intact":[3,114,240],"proteoforms":[4],"and":[5,21,86,191,211,214,221,242,286],"their":[6,17,64],"complexes":[7,243],"directly":[8,117],"from":[9,118],"heterogenous":[10],"biological":[11,37],"samples":[12,38],"is":[13,54,268,280,284,289],"essential":[14],"to":[15,50,63,72,155,226,245],"understand":[16],"role":[18],"in":[19,41,78,84,92,177,188,234,275],"health":[20],"disease.":[22],"While":[23],"native":[24],"top-down":[25],"mass":[26,73,223],"spectrometry":[27,74],"(nTDMS)":[28],"workflows":[29],"enable":[30],"this,":[31],"the":[32,93,122,149,165,194,227,249],"extreme":[33],"molecular":[34],"complexity":[35,53],"inadvertently":[39],"results":[40],"overlapping":[42],"signals":[43],"which":[44,58],"confounds":[45],"protein":[46],"identification.":[47],"One":[48],"approach":[49],"resolving":[51],"this":[52],"gas-phase":[55],"ion-ion":[56],"reactions":[57],"separate":[59],"analytical":[60],"targets":[61,187],"according":[62],"original":[65],"charge":[66,103,129,208],"state.":[67],"Charge":[68],"reduction":[69,209],"techniques":[70,210],"coupled":[71],"resolve":[75],"signal":[76,152],"overlap":[77],"m/z":[79,189],"space,":[80],"when":[81],"ions":[82,197,232],"differ":[83],"charge,":[85],"so":[87],"they":[88],"are":[89],"especially":[90],"useful":[91],"analysis":[94],"large":[96],"biomolecules":[97],"like":[98],"proteins":[99,115,241],"that":[100,260],"form":[101],"multiple":[102,186],"states":[104],"during":[105],"electrospray":[106],"ionisation.":[107],"Previously,":[108],"we":[109,163],"investigated":[110],"multistage":[111],"nTDMS":[112,173,205,267],"sampled":[116],"tissue":[119],"sections":[120],"where":[121,278],"first":[123],"experiment":[124],"stage":[125],"was":[126,145],"separation":[127],"by":[128,132],"reduction,":[130],"followed":[131],"collisional":[133],"activation":[134],"for":[135,172,199,204,238,272],"sequence":[136,236,282],"ion":[137,143,180,287],"production.":[138],"The":[139],"specificity":[140,279],"product":[142,160,231],"spectra":[144],"improved":[146],"but":[147],"at":[148,290],"expense":[150],"intensity":[153],"owing":[154],"inefficient":[156],"use":[157,166],"charge-reduced":[159],"ions.":[161],"Here":[162],"establish":[164],"synchronous":[168],"precursor":[169],"selection":[170],"(SPS)":[171],"via":[174],"multinotch":[175],"isolation":[176,184],"a":[178,254,269,291],"linear":[179],"trap,":[181],"enabling":[182],"simultaneous":[183],"space":[190],"thereby":[192],"increasing":[193],"number":[195],"available":[198],"fragmentation.":[200],"We":[201,252],"implemented":[202],"SPS":[203,250,256,263,266],"across":[206],"three":[207],"collision,":[212],"electron":[213],"photon":[215],"mediated":[216],"fragmentation":[217],"methods":[218],"on":[219],"commercial":[220],"modified":[222],"spectrometers.":[224],"Improvements":[225],"signal-to-noise":[228],"ratio":[229],"resulted":[233],"greater":[235],"coverage":[237,283],"example":[239],"up":[244],"~44":[246],"kDa":[247],"using":[248],"workflow.":[251],"provide":[253],"freely-available":[255],"target":[257],"calculator,":[258],"Novalap,":[259],"enables":[261],"simple":[262],"method":[264],"development.":[265],"methodological":[270],"breakthrough":[271],"proteoform":[273],"complex":[276],"mixtures,":[277],"essential,":[281],"desired":[285],"abundance":[288],"premium.":[292]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2026-10-10T00:00:00"}