{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T14:10:09Z","timestamp":1721916609712},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T00:00:00Z","timestamp":1643760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"Fluorescent biomarkers are used to detect target molecules within inhomogeneous populations of cells. When these biomarkers are found in trace amounts it becomes extremely challenging to detect their presence in a flow cytometer. Here, we present a framework to draw a detection baseline for single emitters and enable absolute calibration of a flow cytometer based on quantum measurements. We used single-photon detection and found the second-order autocorrelation function of fluorescent light. We computed the success of rare-event detection for different signal-to-noise ratios (SNR). We showed high-accuracy identification of the events with occurrence rates below 10\u22125 even at modest SNR levels, enabling early disease diagnostics and post-disease monitoring.<\/jats:p>","DOI":"10.3390\/s22031136","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T01:40:18Z","timestamp":1644198018000},"page":"1136","source":"Crossref","is-referenced-by-count":3,"title":["In Situ Flow Cytometer Calibration and Single-Molecule Resolution via Quantum Measurement"],"prefix":"10.3390","volume":"22","author":[{"given":"Javier","family":"Sabines-Chesterking","sequence":"first","affiliation":[{"name":"Joint Quantum Institute, University of Maryland, College Park, MD 20742, USA"},{"name":"National Institute of Standards and Technology, Gaithersburg, MD 20899, USA"}]},{"given":"Ivan A.","family":"Burenkov","sequence":"additional","affiliation":[{"name":"Joint Quantum Institute, University of Maryland, College Park, MD 20742, USA"},{"name":"National Institute of Standards and Technology, Gaithersburg, MD 20899, USA"}]},{"given":"Sergey V.","family":"Polyakov","sequence":"additional","affiliation":[{"name":"National Institute of Standards and Technology, Gaithersburg, MD 20899, USA"},{"name":"Physics Department, University of Maryland, College Park, MD 20742, USA"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3109\/07388551.2015.1128876","article-title":"Flow cytometry: Basic principles and applications","volume":"37","author":"Adan","year":"2017","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Macey, M.G. (2007). Flow Cytometry, Springer.","DOI":"10.1007\/978-1-59745-451-3"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1063\/1.1685647","article-title":"Fluorescence activated cell sorting","volume":"43","author":"Bonner","year":"1972","journal-title":"Rev. Sci. Instrum."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/nri1416","article-title":"Seventeen-colour flow cytometry: Unravelling the immune system","volume":"4","author":"Perfetto","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","first-page":"1","article-title":"Characterization of flow cytometer instrument sensitivity","volume":"40","author":"Hoffman","year":"2007","journal-title":"Curr. Protoc. Cytom."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4087","DOI":"10.1073\/pnas.86.11.4087","article-title":"Single-molecule fluorescence detection: Autocorrelation criterion and experimental realization with phycoerythrin","volume":"86","author":"Peck","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/0009-2614(90)85485-U","article-title":"Detection of single fluorescent molecules","volume":"174","author":"Shera","year":"1990","journal-title":"Chem. Phys. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3208","DOI":"10.1364\/AO.34.003208","article-title":"Rapid and efficient detection of single chromophore molecules in aqueous solution","volume":"34","author":"Li","year":"1995","journal-title":"Appl. Opt."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1021\/ar950250y","article-title":"Single-molecule detection in liquids by laser-induced fluorescence","volume":"29","author":"Goodwin","year":"1996","journal-title":"Acc. Chem. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12A","DOI":"10.1366\/0003702963905600","article-title":"Single-molecule fluorescence analysis in solution","volume":"50","author":"Keller","year":"1996","journal-title":"Appl. Spectrosc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1103\/PhysRevLett.39.691","article-title":"Photon antibunching in resonance fluorescence","volume":"39","author":"Kimble","year":"1977","journal-title":"Phys. Rev. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/177027a0","article-title":"Correlation between photons in two coherent beams of light","volume":"177","author":"Brown","year":"1956","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"143601","DOI":"10.1103\/PhysRevLett.93.143601","article-title":"Determination of the number of atoms trapped in an optical cavity","volume":"93","author":"McKeever","year":"2004","journal-title":"Phys. Rev. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4040","DOI":"10.1021\/ac062024f","article-title":"Exploring fluorescence antibunching in solution to determine the stoichiometry of molecular complexes","volume":"79","author":"Kaiser","year":"2007","journal-title":"Anal. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"073013","DOI":"10.1088\/1367-2630\/aacf21","article-title":"Multiphoton nonclassical light from clusters of single-photon emitters","volume":"20","author":"Qi","year":"2018","journal-title":"New J. Phys."},{"key":"ref_16","first-page":"1","article-title":"Standardization, calibration, and control in flow cytometry","volume":"79","author":"Wang","year":"2017","journal-title":"Curr. Protoc. Cytom."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"093003","DOI":"10.1088\/1367-2630\/ab3ae0","article-title":"Effective second-order correlation function and single-photon detection","volume":"21","year":"2019","journal-title":"New J. Phys."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5342","DOI":"10.1021\/ac025730z","article-title":"Measuring the number of independent emitters in single-molecule fluorescence images and trajectories using coincident photons","volume":"74","author":"Weston","year":"2002","journal-title":"Anal. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1109\/JSTQE.2007.903193","article-title":"Counting constituents in molecular complexes by fluorescence photon antibunching","volume":"13","author":"Fore","year":"2007","journal-title":"IEEE J. Sel. Top. Quantum Electron."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1134\/S1054660X09170204","article-title":"An extended scheme for counting fluorescent molecules by photon-antibunching","volume":"20","author":"Ta","year":"2010","journal-title":"Laser Phys."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10295","DOI":"10.1039\/c0cp00363h","article-title":"Experimental approach to extend the range for counting fluorescent molecules based on photon-antibunching","volume":"12","author":"Ta","year":"2010","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"035009","DOI":"10.1088\/1367-2630\/ab0a99","article-title":"Photon-antibunching in the fluorescence of statistical ensembles of emitters at an optical nanofiber-tip","volume":"21","author":"Suarez","year":"2019","journal-title":"New J. Phys."},{"key":"ref_23","unstructured":"Migdall, A., Polyakov, S.V., Fan, J., and Bienfang, J.C. (2013). Single-Photon Generation and Detection: Physics and Applications, Academic Press."},{"key":"ref_24","unstructured":"Polyakov, S.V., Burenkov, I.A., and Cheng, Y.H. (2021). Quantum Flow Cytometer. (11,022,538), U.S. Patent."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1088\/0034-4885\/65\/2\/203","article-title":"Fluorescence correlation spectroscopy: The technique and its applications","volume":"65","author":"Krichevsky","year":"2002","journal-title":"Rep. Prog. Phys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"12142","DOI":"10.1021\/ja002535y","article-title":"Self-assembly of CdSe- ZnS quantum dot bioconjugates using an engineered recombinant protein","volume":"122","author":"Mattoussi","year":"2000","journal-title":"J. Am. Chem. Soc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.cll.2007.05.013","article-title":"Rare-event analysis in flow cytometry","volume":"27","author":"Donnenberg","year":"2007","journal-title":"Clin. Lab. Med."},{"key":"ref_28","unstructured":"Shapiro, H.M. (2005). Practical Flow Cytometry, John Wiley & Sons."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/labinvest.2016.121","article-title":"Microfluidics-assisted fluorescence in situ hybridization for advantageous human epidermal growth factor receptor 2 assessment in breast cancer","volume":"97","author":"Nguyen","year":"2017","journal-title":"Lab. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nature19328","article-title":"HER2 expression identifies dynamic functional states within circulating breast cancer cells","volume":"537","author":"Jordan","year":"2016","journal-title":"Nature"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/22\/3\/1136\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T13:53:43Z","timestamp":1721915623000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/22\/3\/1136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,2]]},"references-count":30,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["s22031136"],"URL":"https:\/\/doi.org\/10.3390\/s22031136","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,2]]}}}