Photoacoustic and photothermal detection of circulating tumor cells, bacteria and nanoparticles in cerebrospinal fluid in vivo and ex vivo

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...

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Bibliographic Details
Published in:Journal of biophotonics 2013-06, Vol.6 (6-7), p.523-533
Main Authors: Nedosekin, Dmitry A., Juratli, Mazen A., Sarimollaoglu, Mustafa, Moore, Christopher L., Rusch, Nancy J., Smeltzer, Mark S., Zharov, Vladimir P., Galanzha, Ekaterina I.
Format: Article
Language:English
Subjects:
Animals
bacteria
Bacteria - isolation & purification
Biomarkers - cerebrospinal fluid
Cell Line, Tumor
cerebrospinal fluid
Cerebrospinal Fluid - chemistry
Cerebrospinal Fluid - cytology
Cerebrospinal Fluid - microbiology
cerebrospinal fluid, in vivo flow cytometry
circulating tumor cells
erythrocytes
Flow Cytometry - methods
Gold - chemistry
Humans
in vivo flow cytometry
leukocytes
Mammary Neoplasms, Animal - pathology
Mice
Molecular Imaging
nanoparticles
Nanoparticles - analysis
Neoplastic Cells, Circulating - pathology
photoacoustic and photothermal methods
Photoacoustic Techniques - methods
Spectrum Analysis
Staining and Labeling
Temperature
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Summary: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. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
ISSN:1864-063X
1864-0648
DOI:10.1002/jbio.201200242