title: Photoacoustic and photothermal detection of circulating tumor cells, bacteria and nanoparticles in cerebrospinal fluid in vivo and ex vivo.
abstract: Circulating cells, bacteria, proteins, microparticles, and DNA in cerebrospinal fluid (CSF) are excellent biomarkers of many diseases, including cancer and infections. However, the sensitivity of existing methods is limited in their ability to detect rare CSF biomarkers at the treatable, early-stage of diseases. Here, we introduce novel CSF tests based on in vivo photoacoustic flow cytometry (PAFC) and ex vivo photothermal scanning cytometry. In the CSF of tumor-bearing mice, we molecularly detected in vivo circulating tumor cells (CTCs) before the development of breast cancer brain metastasis with 20-times higher sensitivity than with current assays. For the first time, we demonstrated assessing three pathways (i.e., blood, lymphatic, and CSF) of CTC dissemination, tracking nanoparticles in CSF in vivo and their imaging ex vivo. In label-free CSF samples, we counted leukocytes, erythrocytes, melanoma cells, and bacteria and imaged intracellular cytochromes, hemoglobin, melanin, and carotenoids, respectively. Taking into account the safety of PAFC, its translation for use in humans is expected to improve disease diagnosis beyond conventional detection limits.
authors.affiliation: Winthrop P. Rockefeller Cancer Institute, 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.forename: Mazen A
authors.initials: MA
authors.lastname: Juratli
authors.forename: Mustafa
authors.initials: M
authors.lastname: Sarimollaoglu
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Moore
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Rusch
authors.forename: Mark S
authors.initials: MS
authors.lastname: Smeltzer
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Zharov
authors.forename: Ekaterina I
authors.initials: EI
authors.lastname: Galanzha
mesh_terms: D000818:Animals; D001419:Bacteria / Q000302:isolation & purification*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D045744:Cell Line, Tumor; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000166:cytology / Q000382:microbiology; D005434:Flow Cytometry / Q000379:methods*; D006046:Gold / Q000737:chemistry; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000473:pathology; D051379:Mice; D057054:Molecular Imaging; D053758:Nanoparticles / Q000032:analysis*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D061088:Photoacoustic Techniques / Q000379:methods*; D013057:Spectrum Analysis; D013194:Staining and Labeling; D013696:Temperature
chemical_list: D015415:Biomarkers; D006046:Gold