Fourier ptychographic microscopy for filtration-based circulating tumor cell enumeration and analysis

Circulating tumor cells (CTCs) are recognized as a candidate biomarker with strong prognostic and predictive potential in metastatic disease. Filtration-based enrichment technologies have been used for CTC characterization, and our group has previously developed a membrane microfilter device that de...

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Bibliographic Details
Published in:Journal of biomedical optics 2014-06, Vol.19 (6), p.066007-066007
Main Authors: Williams, Anthony, Chung, Jaebum, Ou, Xiaoze, Zheng, Guoan, Rawal, Siddarth, Ao, Zheng, Datar, Ram, Yang, Changhuei, Cote, Richard
Format: Article
Language:English
Subjects:
Automation
Biomarkers
Breast Neoplasms - blood
Breast Neoplasms - pathology
Cell Line, Tumor
Cell Separation - methods
Circulating
Female
Filtration
Focal plane
Fourier Analysis
Humans
Image Processing, Computer-Assisted - methods
Imaging
Immunohistochemistry
Mathematical models
Microscopy
Microscopy - methods
Neoplastic Cells, Circulating
Optics and Photonics
Research Papers: Imaging
Tumors
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Summary:Circulating tumor cells (CTCs) are recognized as a candidate biomarker with strong prognostic and predictive potential in metastatic disease. Filtration-based enrichment technologies have been used for CTC characterization, and our group has previously developed a membrane microfilter device that demonstrates efficacy in model systems and clinical blood samples. However, uneven filtration surfaces make the use of standard microscopic techniques a difficult task, limiting the performance of automated imaging using commercially available technologies. Here, we report the use of Fourier ptychographic microscopy (FPM) to tackle this challenge. Employing this method, we were able to obtain high-resolution color images, including amplitude and phase, of the microfilter samples over large areas. FPM's ability to perform digital refocusing on complex images is particularly useful in this setting as, in contrast to other imaging platforms, we can focus samples on multiple focal planes within the same frame despite surface unevenness. In model systems, FPM demonstrates high image quality, efficiency, and consistency in detection of tumor cells when comparing corresponding microfilter samples to standard microscopy with high correlation (R2=0.99932). Based on these results, we believe that FPM will have important implications for improved, high throughput, filtration-based CTC analysis, and, more generally, image analysis of uneven surfaces.
ISSN:1083-3668
1560-2281
DOI:10.1117/1.JBO.19.6.066007