Journal
NANO LETTERS
Volume 12, Issue 6, Pages 2697-2704Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nl2041707
Keywords
Circulating tumor cells; quartz nanowire array; laser scanning cytometry; cellomic analysis
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Funding
- U.S. National Cancer Institute (NIH) [4R00 CA136759-02]
- Priority Research Centers Program
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2010-0029706, 2010-0019694]
- Alzheimer's Association New Investigator Research Grant
- KRIBB
- LG-Yonam foundation
- Anderson Postdoctoral Fellowship
- National Research Foundation of Korea [과C6B1912] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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We report on the development of a nanowire substrate-enabled laser scanning imaging cytometry for rare cell analysis in order to achieve quantitative, automated, and functional evaluation of circulating tumor cells. Immuno-functionalized nanowire arrays have been demonstrated as a superior material to capture rare cells from heterogeneous cell populations. The laser scanning cytometry method enables large-area, automated quantitation of captured cells and rapid evaluation of functional cellular parameters (e.g., size, shape, and signaling protein) at the single-cell level. This integrated platform was first tested for capture and quantitation of human lung carcinoma cells from a mixture of tumor cells and leukocytes. We further applied it to the analysis of rare tumor cells spiked in fresh human whole blood (several cells per mL) that emulate metastatic cancer patient blood and demonstrated the potential of this technology for analyzing circulating tumor cells in the clinical settings. Using a high-content image analysis algorithm, cellular morphometric parameters and fluorescence intensities can be rapidly quantitated in an automated, unbiased, and standardized manner. Together, this approach enables informative characterization of captured cells in situ and potentially allows for subclassification of circulating tumor cells, a key step toward the identification of true metastasis-initiating cells. Thus, this nanoenabled platform holds great potential for studying the biology of rare tumor cells and for differential diagnosis of cancer progression and metastasis.
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