{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:01:46Z","timestamp":1772607706769,"version":"3.50.1"},"reference-count":73,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T00:00:00Z","timestamp":1622592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001692","name":"Croucher Foundation","doi-asserted-by":"publisher","award":["CM\/CT\/CF\/CIA\/0688\/19ay"],"award-info":[{"award-number":["CM\/CT\/CF\/CIA\/0688\/19ay"]}],"id":[{"id":"10.13039\/501100001692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006355","name":"Shun Hing Institute of Advanced Engineering","doi-asserted-by":"publisher","award":["BME-p3-18"],"award-info":[{"award-number":["BME-p3-18"]}],"id":[{"id":"10.13039\/501100006355","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Intelligent Systems"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec><jats:label\/><jats:p>Leukocyte differential test is a widely carried out clinical procedure for screening infectious diseases. Existing hematology analyzers require labor\u2010intensive work and a panel of expensive reagents. Herein, an artificial\u2010intelligence\u2010enabled reagent\u2010free imaging hematology analyzer (AIRFIHA) modality is reported that can accurately classify subpopulations of leukocytes with minimal sample preparation. AIRFIHA is realized through training a two\u2010step residual neural network using label\u2010free images of isolated leukocytes acquired from a custom\u2010built quantitative phase microscope. By leveraging the rich information contained in quantitative phase images, not only high accuracy is achieved in differentiating B and T lymphocytes, but also CD4 and CD8 T cells are classified, therefore outperforming the classification accuracy of most current hematology analyzers. The performance of AIRFIHA in a randomly selected test set is validated and is cross\u2010validated across all blood donors. Due to its easy operation, low cost, and accurate discerning capability of complex leukocyte subpopulations, AIRFIHA is clinically translatable and can also be deployed in resource\u2010limited settings, e.g., during pandemic situations for the rapid screening of infectious diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/aisy.202000277","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T12:22:06Z","timestamp":1622636526000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Artificial\u2010Intelligence\u2010Enabled Reagent\u2010Free Imaging Hematology Analyzer"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9502-9807","authenticated-orcid":false,"given":"Xin","family":"Shu","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering The Chinese University of Hong Kong  Shatin New Territories Hong Kong China"}]},{"given":"Sameera","family":"Sansare","sequence":"additional","affiliation":[{"name":"Connecticut Children's Innovation Center University of Connecticut School of Medicine  Farmington CT 06032 USA"},{"name":"Department of Pharmaceutical Sciences University of Connecticut  Storrs CT 06269 USA"}]},{"given":"Di","family":"Jin","sequence":"additional","affiliation":[{"name":"Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology  Cambridge MA 02139 USA"}]},{"given":"Xiangxiang","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Information Science and Engineering Hunan University  Changsha 410076 China"}]},{"given":"Kai-Yu","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Chinese University of Hong Kong  Shatin New Territories Hong Kong China"}]},{"given":"Rishikesh","family":"Pandey","sequence":"additional","affiliation":[{"name":"Connecticut Children's Innovation Center University of Connecticut School of Medicine  Farmington CT 06032 USA"},{"name":"Department of Biomedical Engineering University of Connecticut  Storrs CT 06269 USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4761-6641","authenticated-orcid":false,"given":"Renjie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The Chinese University of Hong Kong  Shatin New Territories Hong Kong China"},{"name":"Shun Hing Institute of Advanced Engineering The Chinese University of Hong Kong  Shatin New Territories Hong Kong China"}]}],"member":"311","published-online":{"date-parts":[[2021,6,2]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Morphology of Blood Disorders","author":"DOnofrio G.","year":"2015"},{"key":"e_1_2_9_3_1","volume-title":"Dacie and Lewis Practical Haematology","author":"Bain B. J.","year":"2017"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-7020-6696-2.00023-0"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2020.106017"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-020-02374-0"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCP7D8ECZRXGWCG"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-7020-6696-2.00003-5"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902322116"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10256"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2001404117"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09113-4"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-016-0028-x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac3007363"},{"key":"e_1_2_9_15_1","volume-title":"Progress in Optics","author":"Mir M.","year":"2012"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41566-018-0253-x"},{"key":"e_1_2_9_17_1","volume-title":"Quantitative Phase Imaging of Cells and Tissues","author":"Popescu G.","year":"2011"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00121.2008"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100506108"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909533107"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1117\/1.2149847"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1364\/AO.58.00G162"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-018-0008-7"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep21471"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0004723"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1700606"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1109\/JSTQE.2018.2859234"},{"key":"e_1_2_9_28_1","doi-asserted-by":"crossref","first-page":"Th3A.39","DOI":"10.1364\/DH.2019.Th3A.39","volume-title":"Proc. Digital Holography and Three-Dimensional Imaging 2019","author":"Strbkova L.","year":"2019"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.23765"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.24227"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0211347"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1364\/BOE.399020"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2018.09.068"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.8b04895"},{"key":"e_1_2_9_35_1","unstructured":"M.Fanous G.Popescu K.Tangella N.Sobh inProc. SPIE 11653 Quantitative Phase Imaging VII SPIE Bellingham WA2021 p.1165311."},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06311-y"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2018.03.008"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201800761"},{"key":"e_1_2_9_39_1","doi-asserted-by":"crossref","first-page":"86.5","DOI":"10.4049\/jimmunol.204.Supp.86.5","volume":"204","author":"Ryu D.","year":"2020","journal-title":"J. Immunol."},{"key":"e_1_2_9_40_1","unstructured":"K.Simonyan A.Zisserman (preprint) arXiv:1409.1556 v6 submitted 2015."},{"key":"e_1_2_9_41_1","first-page":"1","volume-title":"Proc. 2015 IEEE Conference on Computer Vision and Pattern Recognition","author":"Szegedy C.","year":"2015"},{"key":"e_1_2_9_42_1","doi-asserted-by":"crossref","unstructured":"K.He X.Zhang S.Ren J.Sun inProc. 2016 IEEE Conference on Computer Vision and Pattern Recognition(Ed:L.O'Conner) IEEE Computer Society Washington DC2016 p.770.","DOI":"10.1109\/CVPR.2016.90"},{"key":"e_1_2_9_43_1","unstructured":"K.He X.Zhang S.Ren J.Sun inProc. 2016 European Conference on Computer Vision(Eds:B.Leibe J.Matas N.Sebe M.Welling) Springer Cham Switzerland2016 p.630."},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-45528-0"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022602019183"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41377-019-0129-y"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1109\/ACCESS.2019.2924255"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0239-0"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.23794"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201600205"},{"key":"e_1_2_9_51_1","doi-asserted-by":"crossref","first-page":"DT3B.3","DOI":"10.1364\/BODA.2019.DT3B.3","volume-title":"Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA,BRAIN,NTM,OMA,OMP)","author":"Shu X.","year":"2019"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1364\/OL.31.000775"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1364\/AOP.6.000057"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbio.201800291"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.23106"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/169366b0"},{"key":"e_1_2_9_57_1","unstructured":"S.Ioffe C.Szegedy (preprint) arXiv:1502.03167 v3 submitted 2015."},{"key":"e_1_2_9_58_1","unstructured":"V.Nair G. E.Hinton inProc. 2010 Int. Conf. on Machine Learning Omnipress Madison WI2010 p.432."},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-76153-9_28"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13042-011-0012-5"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0118432"},{"key":"e_1_2_9_62_1","first-page":"2579","volume":"9","author":"Maaten L. v. d.","year":"2008","journal-title":"J. Mach. Learn. Res."},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61052-0"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2011.06.015"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0047-6374(00)00210-4"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.2527\/2006.843567x"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep37210"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nphoton.2013.187"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1109\/TIP.2017.2753404"},{"key":"e_1_2_9_70_1","volume-title":"Single-Frame Cell Tomography at Speed in Excess of 10,000 Three-Dimensional Images Per Second","author":"Ge B."},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep24821"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1364\/PRJ.396135"},{"key":"e_1_2_9_73_1","unstructured":"D. P.Kingma J.Ba (preprint) arXiv:1412.6980 v9 submitted 2017."},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1214\/aoms\/1177729586"}],"container-title":["Advanced Intelligent Systems"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/aisy.202000277","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/aisy.202000277","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/aisy.202000277","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T19:02:40Z","timestamp":1759863760000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/aisy.202000277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,2]]},"references-count":73,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1002\/aisy.202000277"],"URL":"https:\/\/doi.org\/10.1002\/aisy.202000277","archive":["Portico"],"relation":{},"ISSN":["2640-4567","2640-4567"],"issn-type":[{"value":"2640-4567","type":"print"},{"value":"2640-4567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,2]]},"assertion":[{"value":"2020-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2000277"}}