{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:48:52Z","timestamp":1790362132364,"version":"4.1.0"},"reference-count":36,"publisher":"American Chemical Society (ACS)","issue":"14","license":[{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61505027"],"award-info":[{"award-number":["61505027"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61535003"],"award-info":[{"award-number":["61535003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61675042"],"award-info":[{"award-number":["61675042"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61822503"],"award-info":[{"award-number":["61822503"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Quaternary ammonium (QA) plays multiple roles in biological functions, whose dysregulation may result in multiple diseases. However, how to efficiently detect QA-based materials such as acetylcholine (ACh) still remains a great challenge, especially in complex biological environments. Here, a new effect [called quaternary-ammonium-modulated surface-enhanced Raman spectroscopy (QAM-SERS) effect] is discovered, showing that the existence of QA will modulate the intensity of SERS signals in a concentration-dependent manner. When the QAM-SERS effect is used, a new method is easily developed for in vitro detection of ACh with an extremely high sensitivity and an ultrawide dynamic range. Particularly, the linear dynamic range can be freely tuned to adapt for various physiological samples. As a proof-of-concept experiment, the time-dependent secretion of ACh from PC12 cells was successfully monitored using the QAM-SERS method, which were under either the stimulation of potassium ions or the incubation of drugs. The discovery of the QAM-SERS effect provides an easy and universal strategy for detecting ACh as well as other QA-contained molecules, which can also inspire new insights into the roles that QA could play in biology and chemistry.<\/jats:p>","DOI":"10.1021\/acs.analchem.0c01061","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:24:02Z","timestamp":1593044642000},"page":"9706-9713","source":"Crossref","is-referenced-by-count":7,"title":["Quaternary-Ammonium-Modulated Surface-Enhanced Raman\nSpectroscopy Effect: Discovery, Mechanism, and Application for Highly\nSensitive\n                    <i>In Vitro<\/i>\n                    Sensing of Acetylcholine"],"prefix":"10.1021","volume":"92","author":[{"given":"Lang","family":"Li","sequence":"first","affiliation":[{"name":"Southeast University , , , ,","place":["Nanjing, Jiangsu, China, 210096"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenfei","family":"Zong","sequence":"additional","affiliation":[{"name":"Southeast University , , , ,","place":["Nanjing, Jiangsu, China, 210096"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lu","sequence":"additional","affiliation":[{"name":"Southeast University , , , ,","place":["Nanjing, Jiangsu, China, 210096"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Southeast University , , , ,","place":["Nanjing, Jiangsu, China, 210096"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziting","family":"Qian","sequence":"additional","affiliation":[{"name":"Southeast University , , , ,","place":["Nanjing, Jiangsu, China, 210096"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Zhu","sequence":"additional","affiliation":[{"name":"Southeast University , , , ,","place":["Nanjing, Jiangsu, China, 210096"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhile","family":"Wang","sequence":"additional","affiliation":[{"name":"Southeast University , , , ,","place":["Nanjing, Jiangsu, China, 210096"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo","family":"Yang","sequence":"additional","affiliation":[{"name":"Southeast University , , , ,","place":["Nanjing, Jiangsu, China, 210096"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1262-5342","authenticated-orcid":true,"given":"Zhuyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Southeast University , , , ,","place":["Nanjing, Jiangsu, China, 210096"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4648-2506","authenticated-orcid":true,"given":"Yiping","family":"Cui","sequence":"additional","affiliation":[{"name":"Southeast University , , , ,","place":["Nanjing, Jiangsu, China, 210096"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"issue":"11","key":"2026081803304864800_cit1","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1111\/j.1753-4887.2009.00246.x","article-title":"Choline: an essential\nnutrient for public health","volume":"67","author":"Zeisel","year":"2009","journal-title":"Nutr. Rev."},{"issue":"12","key":"2026081803304864800_cit2","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1038\/nrc3162","article-title":"Choline metabolism in malignant transformation","volume":"11","author":"Glunde","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"2026081803304864800_cit3","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/1743-7075-7-30","article-title":"Role of carnitine\nin disease","volume":"7","author":"Flanagan","year":"2010","journal-title":"Nutr. Metab."},{"issue":"9","key":"2026081803304864800_cit4","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1007\/BF03261931","article-title":"Carnitine and Acylcarnitines Pharmacokinetic, Pharmacological\nand Clinical Aspects","volume":"51","author":"Reuter","year":"2012","journal-title":"Clin. Pharmacokinet."},{"issue":"1","key":"2026081803304864800_cit5","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.plipres.2009.08.004","article-title":"Acylcarnitines:\nRole in brain","volume":"49","author":"Jones","year":"2010","journal-title":"Prog. Lipid Res."},{"key":"2026081803304864800_cit6","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.ejphar.2014.05.006","article-title":"Quaternary ammonium salt of U50488H, a new kappa-opioid\nreceptor agonist, protects rat heart against ischemiaireperfusion\ninjury","volume":"737","author":"Wang","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"2026081803304864800_cit7","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.jchromb.2015.12.002","article-title":"Simultaneous determination\nof phosphatidylcholine-derived quaternary ammonium compounds by a\nLC-MS\/MS method in human blood plasma, serum and urine samples","volume":"1008","author":"Steuer","year":"2016","journal-title":"J. Chromatogr. B: Anal. Technol. Biomed. Life Sci."},{"issue":"5","key":"2026081803304864800_cit8","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1136\/ard.2008.096545","article-title":"Muscarinic-3\nacetylcholine receptor autoantibody in patients with systemic sclerosis:\ncontribution to severe gastrointestinal tract dysmotility","volume":"68","author":"Kawaguchi","year":"2009","journal-title":"Ann. Rheum. Dis."},{"issue":"2","key":"2026081803304864800_cit9","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1136\/jnnp.66.2.137","article-title":"The cholinergic\nhypothesis of Alzheimer\u2019s disease: a review of progress","volume":"66","author":"Francis","year":"1999","journal-title":"J. Neurol., Neurosurg. Psychiatry"},{"issue":"11","key":"2026081803304864800_cit10","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1016\/S1474-4422(06)70600-7","article-title":"A convergent\nmodel for cognitive dysfunctions in Parkinson\u2019s disease: the\ncritical dopamine-acetylcholine synaptic balance","volume":"5","author":"Calabresi","year":"2006","journal-title":"Lancet Neurol."},{"issue":"3","key":"2026081803304864800_cit11","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/85520","article-title":"Auto-antibodies\nto the receptor tyrosine\nkinase MuSK in patients with myasthenia gravis without acetylcholine\nreceptor antibodies","volume":"7","author":"Hoch","year":"2001","journal-title":"Nat. Med."},{"issue":"1","key":"2026081803304864800_cit12","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/S0165-0270(02)00228-5","article-title":"High-performance\nliquid chromatography\/tandem mass spectrometry assay for the rapid\nhigh sensitivity measurement of basal acetylcholine from microdialysates","volume":"121","author":"Hows","year":"2002","journal-title":"J. Neurosci. Methods"},{"key":"2026081803304864800_cit13","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.bios.2016.06.047","article-title":"An electrochemical\nsensor for detection of neurotransmitter-acetylcholine using metal\nnanoparticles, 2D material and conducting polymer modified electrode","volume":"89","author":"Chauhan","year":"2017","journal-title":"Biosens. Bioelectron."},{"issue":"8","key":"2026081803304864800_cit14","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1038\/nbt.4184","article-title":"A genetically encoded\nfluorescent acetylcholine indicator for in vitro and in vivo studies","volume":"36","author":"Jing","year":"2018","journal-title":"Nat. Biotechnol."},{"issue":"22","key":"2026081803304864800_cit15","doi-asserted-by":"publisher","first-page":"9706","DOI":"10.1021\/ac300867s","article-title":"Enzyme Mimics of Au\/Ag Nanoparticles\nfor Fluorescent Detection of Acetylcholine","volume":"84","author":"Wang","year":"2012","journal-title":"Anal. Chem."},{"issue":"5","key":"2026081803304864800_cit16","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/nrn2635","article-title":"PERSPECTIVES Phasic acetylcholine\nrelease and the volume transmission hypothesis: time to move on","volume":"10","author":"Sarter","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"2026081803304864800_cit17","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.neulet.2015.11.028","article-title":"Extracellular\nlevels of ATP and acetylcholine\nduring lithium-pilocarpine induced status epilepticus in rats","volume":"611","author":"Lietsche","year":"2016","journal-title":"Neurosci. Lett."},{"issue":"10","key":"2026081803304864800_cit18","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.1016\/j.bios.2010.03.031","article-title":"An electrochemical\nacetylcholine\nbiosensor based on nanoshells of hollow nickel microspheres-carbon\nmicroparticles-Nafion nanocomposite","volume":"25","author":"Sattarahmady","year":"2010","journal-title":"Biosens.\nBioelectron."},{"issue":"2","key":"2026081803304864800_cit19","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1021\/jacs.6b10727","article-title":"Label-free Imaging of Neurotransmitter\nAcetylcholine at Neuromuscular Junctions with Stimulated Raman Scattering","volume":"139","author":"Fu","year":"2017","journal-title":"J. Am. Chem. Soc."},{"issue":"33","key":"2026081803304864800_cit20","doi-asserted-by":"publisher","first-page":"15530","DOI":"10.1039\/C9NR04864B","article-title":"Highly sensitive\ndetection of prostate\ncancer specific PCA3 mimic DNA using SERS-based competitive lateral\nflow assay","volume":"11","author":"Fu","year":"2019","journal-title":"Nanoscale"},{"issue":"10","key":"2026081803304864800_cit21","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1002\/jrs.5216","article-title":"Liquid magnetic\ncompetitive immunoassay of clenbuterol based on surface-enhanced Raman\nspectroscopy","volume":"48","author":"Wei","year":"2017","journal-title":"J. Raman Spectrosc."},{"issue":"18","key":"2026081803304864800_cit22","doi-asserted-by":"publisher","first-page":"10407","DOI":"10.1039\/C7NJ01394A","article-title":"Simultaneous\ndetection of clenbuterol and ractopamine\nbased on multiplexed competitive surface enhanced Raman scattering\n(SERS) immunoassay","volume":"41","author":"Yu","year":"2017","journal-title":"New J. Chem."},{"issue":"1\u20132","key":"2026081803304864800_cit23","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.aca.2011.04.031","article-title":"Highly sensitive detection of clenbuterol\nusing competitive surface-enhanced Raman scattering immunoassay","volume":"697","author":"Zhu","year":"2011","journal-title":"Anal. Chim. Acta"},{"issue":"17","key":"2026081803304864800_cit24","doi-asserted-by":"publisher","first-page":"3391","DOI":"10.1021\/j100214a025","article-title":"ADSORPTION AND SURFACE-ENHANCED\nRAMAN OF DYES ON SILVER\nAND GOLD SOLS","volume":"86","author":"Lee","year":"1982","journal-title":"J. Phys. Chem."},{"issue":"27","key":"2026081803304864800_cit25","doi-asserted-by":"publisher","first-page":"7764","DOI":"10.1002\/anie.201702099","article-title":"Lithiophilic Sites in Doped Graphene Guide Uniform\nLithium Nucleation for Dendrite-Free Lithium Metal Anodes","volume":"56","author":"Zhang","year":"2017","journal-title":"Angew. Chem., Int. Ed."},{"issue":"32","key":"2026081803304864800_cit26","doi-asserted-by":"publisher","first-page":"3338","DOI":"10.1016\/j.jchromb.2010.10.016","article-title":"Quantification of acetylcholine,\ncholine, betaine, and dimethylglycine in human plasma and urine using\nstable-isotope dilution ultra performance liquid chromatography-tandem\nmass spectrometry","volume":"878","author":"Kirsch","year":"2010","journal-title":"J. Chromatogr. B: Anal. Technol.\nBiomed. Life Sci."},{"issue":"2","key":"2026081803304864800_cit27","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.jep.2010.07.006","article-title":"Rosmarinus officinalis polyphenols activate cholinergic activities\nin PC12 cells through phosphorylation of ERK1\/2","volume":"131","author":"El\nOmri","year":"2010","journal-title":"J. Ethnopharmacol."},{"issue":"2","key":"2026081803304864800_cit28","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S0022-3565(24)35340-6","article-title":"Pharmacological characterization\nof endogenous acetylcholine release from primary septal cultures","volume":"292","author":"Auld","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"11","key":"2026081803304864800_cit29","doi-asserted-by":"publisher","first-page":"5184","DOI":"10.1073\/pnas.74.11.5184","article-title":"STORAGE AND RELEASE\nOF ACETYLCHOLINE BY A CLONAL CELL\nLINE","volume":"74","author":"Schubert","year":"1977","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"5789","key":"2026081803304864800_cit30","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/288373a0","article-title":"THE OBLIGATORY ROLE OF ENDOTHELIAL-CELLS IN THE RELAXATION\nOF ARTERIAL SMOOTH-MUSCLE BY ACETYLCHOLINE","volume":"288","author":"Furchgott","year":"1980","journal-title":"Nature"},{"issue":"2","key":"2026081803304864800_cit31","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1111\/j.1476-5381.1993.tb13851.x","article-title":"EFFECTS OF PHOSPHOLIPASE-A(2) INHIBITORS ON COUPLING\nOF ALPHA(2)-ADRENOCEPTORS TO INWARDLY RECTIFYING POTASSIUM CURRENTS\nIN GUINEA-PIG SUBMUCOSAL NEURONS","volume":"110","author":"Evans","year":"1993","journal-title":"Br. J. Pharmacol."},{"issue":"4","key":"2026081803304864800_cit32","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/ja.2015.107","article-title":"Natural product-derived quaternary ammonium compounds\nwith potent antimicrobial activity","volume":"69","author":"Joyce","year":"2016","journal-title":"J. Antibiot."},{"key":"2026081803304864800_cit33","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.copbio.2015.03.018","article-title":"Quaternary ammonium disinfectants: microbial adaptation,\ndegradation and ecology","volume":"33","author":"Tezel","year":"2015","journal-title":"Curr. Opin. Biotechnol."},{"issue":"16","key":"2026081803304864800_cit34","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1177\/0040517510363193","article-title":"Structures of Novel\nAntimicrobial Agents for Textiles\n- A Review","volume":"80","author":"Simoncic","year":"2010","journal-title":"Text. Res. J."},{"issue":"1","key":"2026081803304864800_cit35","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1065\/espr2007.02.387","article-title":"Pesticide adsorption\non a calcareous soil modified with sewage sludge and quaternary alkyl-ammonium\ncationic surfactants","volume":"15","author":"Gonzalez","year":"2008","journal-title":"Environ. Sci. Pollut.\nRes."},{"issue":"12","key":"2026081803304864800_cit36","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.2116\/analsci.17.1379","article-title":"Stepwise determination\nof quaternary ammonium salts and aromatic amines in pharmaceuticals\nby ion association titration","volume":"17","author":"Sakai","year":"2001","journal-title":"Anal. Sci."}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.0c01061","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/92\/14\/9706\/8579383\/ac0c01061.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/92\/14\/9706\/8579383\/ac0c01061.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T08:59:14Z","timestamp":1787043554000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/92\/14\/9706\/827203\/Quaternary-Ammonium-Modulated-Surface-Enhanced"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,25]]},"references-count":36,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2020,6,25]]},"published-print":{"date-parts":[[2020,7,21]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.0c01061","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,25]]}}}