title: Fourier ptychographic microscopy for filtration-based circulating tumor cell enumeration and analysis.
abstract: 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.
authors.affiliation: University of Miami, Miller School of Medicine, Department of Pathology, 1501 NW 10th Avenue BRB 742, Miami, Florida 33136bUniversity of Miami, Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), 1501 NW 10th Avenue BRB 714, Mi.
authors.forename: Anthony
authors.initials: A
authors.lastname: Williams
authors.affiliation: California Institute of Technology, Departments of Electrical Engineering, Bioengineering, and Medical Engineering, 1200 East California Boulevard MC 136-93, Pasadena, California 91125.
authors.forename: Jaebum
authors.initials: J
authors.lastname: Chung
authors.affiliation: California Institute of Technology, Departments of Electrical Engineering, Bioengineering, and Medical Engineering, 1200 East California Boulevard MC 136-93, Pasadena, California 91125.
authors.forename: Xiaoze
authors.initials: X
authors.lastname: Ou
authors.affiliation: California Institute of Technology, Departments of Electrical Engineering, Bioengineering, and Medical Engineering, 1200 East California Boulevard MC 136-93, Pasadena, California 91125.
authors.forename: Guoan
authors.initials: G
authors.lastname: Zheng
authors.affiliation: University of Miami, Miller School of Medicine, Department of Pathology, 1501 NW 10th Avenue BRB 742, Miami, Florida 33136bUniversity of Miami, Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), 1501 NW 10th Avenue BRB 714, Mi.
authors.forename: Siddarth
authors.initials: S
authors.lastname: Rawal
authors.affiliation: University of Miami, Miller School of Medicine, Department of Pathology, 1501 NW 10th Avenue BRB 742, Miami, Florida 33136bUniversity of Miami, Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), 1501 NW 10th Avenue BRB 714, Mi.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ao
authors.affiliation: University of Miami, Miller School of Medicine, Department of Pathology, 1501 NW 10th Avenue BRB 742, Miami, Florida 33136bUniversity of Miami, Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), 1501 NW 10th Avenue BRB 714, Mi.
authors.forename: Ram
authors.initials: R
authors.lastname: Datar
authors.affiliation: California Institute of Technology, Departments of Electrical Engineering, Bioengineering, and Medical Engineering, 1200 East California Boulevard MC 136-93, Pasadena, California 91125.
authors.forename: Changhuei
authors.initials: C
authors.lastname: Yang
authors.affiliation: University of Miami, Miller School of Medicine, Department of Pathology, 1501 NW 10th Avenue BRB 742, Miami, Florida 33136bUniversity of Miami, Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), 1501 NW 10th Avenue BRB 714, Mi.
authors.forename: Richard
authors.initials: R
authors.lastname: Cote
mesh_terms: D001331:Automation; D015415:Biomarkers; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology*; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods; D005260:Female; D005374:Filtration; D005583:Fourier Analysis; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007150:Immunohistochemistry; D008853:Microscopy / Q000379:methods*; D009360:Neoplastic Cells, Circulating; D055095:Optics and Photonics
chemical_list: D015415:Biomarkers