title: Photoacoustic Flow Cytometry for Single Sickle Cell DetectionIn VitroandIn Vivo.
abstract: Control of sickle cell disease (SCD) stage and treatment efficiency are still time-consuming which makes well-timed prevention of SCD crisis difficult. We show here thatin vivophotoacoustic (PA) flow cytometry (PAFC) has a potential for real-time monitoring of circulating sickled cells in mouse model.In vivodata were verified byin vitroPAFC and photothermal (PT) and PA spectral imaging of sickle red blood cells (sRBCs) expressing SCD-associated hemoglobin (HbS) compared to normal red blood cells (nRBCs). We discovered that PT and PA signal amplitudes from sRBCs in linear mode were 2-4-fold lower than those from nRBCs. PT and PA imaging revealed more profound spatial hemoglobin heterogeneity in sRBCs than in nRBCs, which can be associated with the presence of HbS clusters with high local absorption. This hypothesis was confirmed in nonlinear mode through nanobubble formation around overheated HbS clusters accompanied by spatially selective signal amplification. More profound differences in absorption of sRBCs than in nRBCs led to notable increase in PA signal fluctuation (fluctuation PAFC mode) as an indicator of SCD. The obtained data suggest that noninvasive label-free fluctuation PAFC has a potential for real-time enumeration of sRBCs bothin vitroandin vivo.
authors.affiliation: Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
authors.forename: Chengzhong
authors.identifier: 0000-0002-0151-5220
authors.initials: C
authors.lastname: Cai
authors.affiliation: Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Nedosekin
authors.affiliation: Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Yulian A
authors.identifier: 0000-0001-5861-3641
authors.initials: YA
authors.lastname: Menyaev
authors.affiliation: Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Sarimollaoglu
authors.affiliation: Chemistry Department, M.V. Lomonosov Moscow State University, Moscow 119991, Russia.
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Proskurnin
authors.affiliation: Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Vladimir P
authors.identifier: 0000-0003-4773-0548
authors.initials: VP
authors.lastname: Zharov
mesh_terms: D000755:Anemia, Sickle Cell / Q000175:diagnosis*; D000818:Animals; D004912:Erythrocytes / Q000473:pathology; D006451:Hemoglobin, Sickle; D006801:Humans; D008810:Mice, Inbred C57BL; D017711:Nonlinear Dynamics; D061088:Photoacoustic Techniques / Q000379:methods*; D059010:Single-Cell Analysis / Q000379:methods*; D013057:Spectrum Analysis
chemical_list: D006451:Hemoglobin, Sickle