Abstract

3D paper-based cultures (PBCs) are easy-to-use and provide a biologically representative microenvironment. By stacking a sheet of cell-laden paper below sheets containing cell-free hydrogel, we form an assay capable of segmenting cells by the distance they invaded from the original cell-seeded layer. These invasion assays are limited to end-point analyses with fluorescence-based readouts due to the highly scattering nature of the paper scaffolds. Here we demonstrate that optical coherence tomography (OCT) can distinguish living cells from the surrounding extracellular matrix (ECM) or paper fibers based upon their intracellular motility amplitude (M). M is computed from fluctuation statistics of the sample, rejects shot noise, and is invariant to OCT signal attenuation. Using OCT motility analysis, we tracked the invasion of breast cancer cells over a 3-day period in 4-layer PBCs (160–300 µm thick) in situ. The cell population distributions determined with OCT are highly correlated with those obtained by fluorescence imaging, with an intraclass correlation coefficient (ICC) of 0.903. The ability of OCT motility analysis to visualize live cells and quantify cell distributions in PBC assays in situ and longitudinally provides a novel means for understanding how chemical gradients within the tumor microenvironment affect cellular invasion.

© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. C. L. Chaffer and W. A. Robert, “A perspective on cancer cell metastasis,” Science 331(6024), 1559–1564 (2011).
    [Crossref]
  2. S. Breslin and L. O’Driscoll, “Three-dimensional cell culture the missing link in drug discovery,” Drug Discovery Today 18(5-6), 240–249 (2013).
    [Crossref]
  3. B. Weigelt, C. M. Ghajar, and M. J. Bissell, “The need for complex 3D culture models to unravel novel pathways and identify accurate biomarkers in breast cancer,” Adv. Drug Delivery Rev. 69-70, 42–51 (2014).
    [Crossref]
  4. K. M. Yamada and E. Cukierman, “Modeling tissue morphogenesis and cancer in 3D,” Cell 130(4), 601–610 (2007).
    [Crossref]
  5. P. Friedl and S. Alexander, “Cancer invasion and the microenvironment: plasticity and reciprocity,” Cell 147(5), 992–1009 (2011).
    [Crossref]
  6. V. Brekhman and G. Neufeld, “An asymmetric 3D In vitro assay for the study of tumor cell invasion,” Methods Cell Biol. 112, 311–328 (2012).
    [Crossref]
  7. A. Albini, Y. Iwamoto, and H. K. Kleinman, “A rapid in vitro assay for quantitating the invasive potential of tumor cells,” Cancer Res. 47, 3239–3245 (1987).
  8. M. H. Zaman, L. M. Trapani, A. L. Sieminski, D. Mackellar, H. Gong, R. D. Kamm, A. Wells, D. A. Lauffenburger, and P. Matsudaira, “Migration of tumor cell in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis,” Proc. Natl. Acad. Sci. 103(29), 10889–10894 (2006).
    [Crossref]
  9. E. Wiercinska, H. P. H. Naber, E. Pardali, G. Van Der Pluijm, H. Van Dam, and P. Ten Dijke, “The TGF-β/Smad pathway induces breast cancer cell invasion through the up-regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model system,” Breast Cancer Res. Treat. 128(3), 657–666 (2011).
    [Crossref]
  10. R. M. Kenney, M. W. Boyce, A. S. Truong, C. R. Bagnell, and M. R. Lockett, “Real-time imaging of cancer cell chemotaxis in paper-based scaffolds,” Analyst 141(2), 661–668 (2016).
    [Crossref]
  11. R. M. Kenney, A. Loeser, N. A. Whitman, and M. R. Lockett, “Paper-based transwell assays: an inexpensive alternative to study cellular invasion,” Analyst 144(1), 206–211 (2019).
    [Crossref]
  12. A. S. Truong, C. A. Lochbaum, M. W. Boyce, and M. R. Lockett, “Tracking the invasion of small numbers of cells in paper-based assays with quantitative PCR,” Anal. Chem. 87(22), 11263–11270 (2015).
    [Crossref]
  13. C. C. Lloyd, M. W. Boyce, and M. R. Lockett, “Paper-based invasion assays for quantifying cellular movement in three-dimensional tissue-like structures,” Curr. Protoc. Chem. Biol. 9(2), 75–95 (2017).
    [Crossref]
  14. B. Mosadegh, B. E. Dabiri, M. R. Lockett, R. Derda, P. Campbell, K. K. Parker, and G. M. Whitesides, “Three-dimensional paper-based model for cardiac ischemia,” Adv. Healthcare Mater. 3(7), 1036–1043 (2014).
    [Crossref]
  15. G. Camci-Unal, D. Newsome, B. K. Eustace, and G. M. Whitesides, “Fibroblasts enhance migration of human lung cancer cells in a paper-based coculture system,” Adv. Healthcare Mater. 5(6), 641–647 (2016).
    [Crossref]
  16. B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
    [Crossref]
  17. M. W. Boyce, G. J. Labonia, A. B. Hummon, and M. R. Lockett, “Assessing chemotherapeutic effectiveness using a paper-based tumor model,” Analyst 142(15), 2819–2827 (2017).
    [Crossref]
  18. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
    [Crossref]
  19. A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
    [Crossref]
  20. P. Yu, M. Mustata, J. J. Turek, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83(3), 575–577 (2003).
    [Crossref]
  21. R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, “Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy,” PLoS One 7(11), e49148 (2012).
    [Crossref]
  22. S. A. Boppart, W. Tan, H. J. Ko, and C. Vinegoni, “Optical coherence tomography of cell dynamics in three-dimensional engineered tissues,” Optical Coherence Tomography and Coherence Techniques II (Optical Society of America, 2005).
  23. S. M. Rey, B. Považay, B. Hofer, A. Unterhuber, B. Hermann, A. Harwood, and W. Drexler, “Three- and four-dimensional visualization of cell migration using optical coherence tomography,” J. Biophotonics 2(6-7), 370–379 (2009).
    [Crossref]
  24. K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
    [Crossref]
  25. P. Yu, L. Peng, M. Mustata, J. J. Turek, M. R. Melloch, and D. D. Nolte, “Time-dependent speckle in holographic optical coherence imaging and the health of tumor tissue,” Opt. Lett. 29(1), 68–70 (2004).
    [Crossref]
  26. Z. Li, H. Sun, J. Turek, S. Jalal, M. Childress, and D. D. Nolte, “Doppler fluctuation spectroscopy of intracellular dynamics in living tissue,” J. Opt. Soc. Am. A 36(4), 665 (2019).
    [Crossref]
  27. K. Jeong, J. J. Turek, and D. D. Nolte, “Speckle fluctuation spectroscopy of intracellular motion in living tissue using coherence-domain digital holography,” J. Biomed. Opt. 15(3), 030514 (2010).
    [Crossref]
  28. X. Yu, A. M. Fuller, R. Blackmon, M. A. Troester, and A. L. Oldenburg, “Quantification of the effect of toxicants on the intracellular kinetic energy and cross-sectional area of mammary epithelial organoids by OCT fluctuation spectroscopy,” Toxicol. Sci. 162(1), 234–240 (2018).
    [Crossref]
  29. A. L. Oldenburg, R. K. Chhetri, J. M. Cooper, W.-C. Wu, M. A. Troester, and J. B. Tracy, “Motility-, autocorrelation-, and polarization-sensitive optical coherence tomography discriminates cells and gold nanorods within 3D tissue cultures,” Opt. Lett. 38(15), 2923 (2013).
    [Crossref]
  30. C. Apelian, F. Harms, O. Thouvenin, and A. C. Boccara, “Dynamic full field optical coherence tomography: subcellular metabolic contrast revealed in tissues by interferometric signals temporal analysis,” Biomed. Opt. Express 7(4), 1511 (2016).
    [Crossref]
  31. A. L. Oldenburg, X. Yu, T. Gilliss, O. Alabi, R. M. Taylor, and M. A. Troester, “Inverse-power-law behavior of cellular motility reveals stromal–epithelial cell interactions in 3D co-culture by OCT fluctuation spectroscopy,” Optica 2(10), 877 (2015).
    [Crossref]
  32. L. Yang, X. Yu, A. M. Fuller, M. A. Troester, and A. L. Oldenburg, “Characterizing optical coherence tomography speckle fluctuation spectra of mammary organoids during suppression of intracellular motility,” Quant. Imaging Med. Surg. 10(1), 76–85 (2020).
    [Crossref]
  33. K. B. Yin, “The Mesenchymal-like Phenotype of the MDA-MB-231 Cell Line,” Breast Cancer (IntechOpen, 2012), Chapter 18.
  34. J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
    [Crossref]
  35. G. L. Long and J. D. Winefordner, “Limit of detection: a closer look at the IUPAC definition,” Anal. Chem. 55(7), 712A–724A (1983).
    [Crossref]
  36. R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83(4), 040903 (2011).
    [Crossref]
  37. D. L. Marks, A. L. Oldenburg, J. J. Reynolds, and S. a Boppart, “Digital algorithm for dispersion correction in optical coherence tomography for homogeneous and stratified media,” Appl. Opt. 42(2), 204–217 (2003).
    [Crossref]
  38. J. L. Fleiss, The Design and Analysis of Clinical Experiments (John Wiley & Sons, Inc., 1999).
  39. G. G. Koch, “Intraclass correlation coefficient,” Encycl. Stat. Sci.212–217 (1982).
  40. S. Holm, “A simple sequential rejective method procedure,” Scand. J. Stat. 6, 65–70 (1979).
  41. J. Sapudom, S. Rubner, S. Martin, T. Kurth, S. Riedel, C. T. Mierke, and T. Pompe, “The phenotype of cancer cell invasion controlled by fibril diameter and pore size of 3D collagen networks,” Biomaterials 52, 367–375 (2015).
    [Crossref]
  42. P. J. Magee, H. McGlynn, and I. R. Rowland, “Differential effects of isoflavones and lignans on invasiveness of MDA-MB-231 breast cancer cells in vitro,” Cancer Lett. 208(1), 35–41 (2004).
    [Crossref]
  43. R. Poincloux, O. Collin, F. Lizárraga, M. Romao, M. Debray, M. Piel, and P. Chavrier, “Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel,” Proc. Natl. Acad. Sci. 108(5), 1943–1948 (2011).
    [Crossref]

2020 (1)

L. Yang, X. Yu, A. M. Fuller, M. A. Troester, and A. L. Oldenburg, “Characterizing optical coherence tomography speckle fluctuation spectra of mammary organoids during suppression of intracellular motility,” Quant. Imaging Med. Surg. 10(1), 76–85 (2020).
[Crossref]

2019 (2)

Z. Li, H. Sun, J. Turek, S. Jalal, M. Childress, and D. D. Nolte, “Doppler fluctuation spectroscopy of intracellular dynamics in living tissue,” J. Opt. Soc. Am. A 36(4), 665 (2019).
[Crossref]

R. M. Kenney, A. Loeser, N. A. Whitman, and M. R. Lockett, “Paper-based transwell assays: an inexpensive alternative to study cellular invasion,” Analyst 144(1), 206–211 (2019).
[Crossref]

2018 (1)

X. Yu, A. M. Fuller, R. Blackmon, M. A. Troester, and A. L. Oldenburg, “Quantification of the effect of toxicants on the intracellular kinetic energy and cross-sectional area of mammary epithelial organoids by OCT fluctuation spectroscopy,” Toxicol. Sci. 162(1), 234–240 (2018).
[Crossref]

2017 (3)

M. W. Boyce, G. J. Labonia, A. B. Hummon, and M. R. Lockett, “Assessing chemotherapeutic effectiveness using a paper-based tumor model,” Analyst 142(15), 2819–2827 (2017).
[Crossref]

K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
[Crossref]

C. C. Lloyd, M. W. Boyce, and M. R. Lockett, “Paper-based invasion assays for quantifying cellular movement in three-dimensional tissue-like structures,” Curr. Protoc. Chem. Biol. 9(2), 75–95 (2017).
[Crossref]

2016 (3)

G. Camci-Unal, D. Newsome, B. K. Eustace, and G. M. Whitesides, “Fibroblasts enhance migration of human lung cancer cells in a paper-based coculture system,” Adv. Healthcare Mater. 5(6), 641–647 (2016).
[Crossref]

R. M. Kenney, M. W. Boyce, A. S. Truong, C. R. Bagnell, and M. R. Lockett, “Real-time imaging of cancer cell chemotaxis in paper-based scaffolds,” Analyst 141(2), 661–668 (2016).
[Crossref]

C. Apelian, F. Harms, O. Thouvenin, and A. C. Boccara, “Dynamic full field optical coherence tomography: subcellular metabolic contrast revealed in tissues by interferometric signals temporal analysis,” Biomed. Opt. Express 7(4), 1511 (2016).
[Crossref]

2015 (4)

A. L. Oldenburg, X. Yu, T. Gilliss, O. Alabi, R. M. Taylor, and M. A. Troester, “Inverse-power-law behavior of cellular motility reveals stromal–epithelial cell interactions in 3D co-culture by OCT fluctuation spectroscopy,” Optica 2(10), 877 (2015).
[Crossref]

A. S. Truong, C. A. Lochbaum, M. W. Boyce, and M. R. Lockett, “Tracking the invasion of small numbers of cells in paper-based assays with quantitative PCR,” Anal. Chem. 87(22), 11263–11270 (2015).
[Crossref]

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

J. Sapudom, S. Rubner, S. Martin, T. Kurth, S. Riedel, C. T. Mierke, and T. Pompe, “The phenotype of cancer cell invasion controlled by fibril diameter and pore size of 3D collagen networks,” Biomaterials 52, 367–375 (2015).
[Crossref]

2014 (2)

B. Mosadegh, B. E. Dabiri, M. R. Lockett, R. Derda, P. Campbell, K. K. Parker, and G. M. Whitesides, “Three-dimensional paper-based model for cardiac ischemia,” Adv. Healthcare Mater. 3(7), 1036–1043 (2014).
[Crossref]

B. Weigelt, C. M. Ghajar, and M. J. Bissell, “The need for complex 3D culture models to unravel novel pathways and identify accurate biomarkers in breast cancer,” Adv. Drug Delivery Rev. 69-70, 42–51 (2014).
[Crossref]

2013 (2)

2012 (3)

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, “Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy,” PLoS One 7(11), e49148 (2012).
[Crossref]

V. Brekhman and G. Neufeld, “An asymmetric 3D In vitro assay for the study of tumor cell invasion,” Methods Cell Biol. 112, 311–328 (2012).
[Crossref]

2011 (5)

P. Friedl and S. Alexander, “Cancer invasion and the microenvironment: plasticity and reciprocity,” Cell 147(5), 992–1009 (2011).
[Crossref]

C. L. Chaffer and W. A. Robert, “A perspective on cancer cell metastasis,” Science 331(6024), 1559–1564 (2011).
[Crossref]

E. Wiercinska, H. P. H. Naber, E. Pardali, G. Van Der Pluijm, H. Van Dam, and P. Ten Dijke, “The TGF-β/Smad pathway induces breast cancer cell invasion through the up-regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model system,” Breast Cancer Res. Treat. 128(3), 657–666 (2011).
[Crossref]

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83(4), 040903 (2011).
[Crossref]

R. Poincloux, O. Collin, F. Lizárraga, M. Romao, M. Debray, M. Piel, and P. Chavrier, “Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel,” Proc. Natl. Acad. Sci. 108(5), 1943–1948 (2011).
[Crossref]

2010 (1)

K. Jeong, J. J. Turek, and D. D. Nolte, “Speckle fluctuation spectroscopy of intracellular motion in living tissue using coherence-domain digital holography,” J. Biomed. Opt. 15(3), 030514 (2010).
[Crossref]

2009 (1)

S. M. Rey, B. Považay, B. Hofer, A. Unterhuber, B. Hermann, A. Harwood, and W. Drexler, “Three- and four-dimensional visualization of cell migration using optical coherence tomography,” J. Biophotonics 2(6-7), 370–379 (2009).
[Crossref]

2007 (1)

K. M. Yamada and E. Cukierman, “Modeling tissue morphogenesis and cancer in 3D,” Cell 130(4), 601–610 (2007).
[Crossref]

2006 (1)

M. H. Zaman, L. M. Trapani, A. L. Sieminski, D. Mackellar, H. Gong, R. D. Kamm, A. Wells, D. A. Lauffenburger, and P. Matsudaira, “Migration of tumor cell in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis,” Proc. Natl. Acad. Sci. 103(29), 10889–10894 (2006).
[Crossref]

2004 (2)

P. Yu, L. Peng, M. Mustata, J. J. Turek, M. R. Melloch, and D. D. Nolte, “Time-dependent speckle in holographic optical coherence imaging and the health of tumor tissue,” Opt. Lett. 29(1), 68–70 (2004).
[Crossref]

P. J. Magee, H. McGlynn, and I. R. Rowland, “Differential effects of isoflavones and lignans on invasiveness of MDA-MB-231 breast cancer cells in vitro,” Cancer Lett. 208(1), 35–41 (2004).
[Crossref]

2003 (3)

D. L. Marks, A. L. Oldenburg, J. J. Reynolds, and S. a Boppart, “Digital algorithm for dispersion correction in optical coherence tomography for homogeneous and stratified media,” Appl. Opt. 42(2), 204–217 (2003).
[Crossref]

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
[Crossref]

P. Yu, M. Mustata, J. J. Turek, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83(3), 575–577 (2003).
[Crossref]

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

1987 (1)

A. Albini, Y. Iwamoto, and H. K. Kleinman, “A rapid in vitro assay for quantitating the invasive potential of tumor cells,” Cancer Res. 47, 3239–3245 (1987).

1983 (1)

G. L. Long and J. D. Winefordner, “Limit of detection: a closer look at the IUPAC definition,” Anal. Chem. 55(7), 712A–724A (1983).
[Crossref]

1979 (1)

S. Holm, “A simple sequential rejective method procedure,” Scand. J. Stat. 6, 65–70 (1979).

a Boppart, S.

Alabi, O.

Albini, A.

A. Albini, Y. Iwamoto, and H. K. Kleinman, “A rapid in vitro assay for quantitating the invasive potential of tumor cells,” Cancer Res. 47, 3239–3245 (1987).

Alexander, S.

P. Friedl and S. Alexander, “Cancer invasion and the microenvironment: plasticity and reciprocity,” Cell 147(5), 992–1009 (2011).
[Crossref]

Apelian, C.

Arganda-Carreras, I.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Bagnell, C. R.

R. M. Kenney, M. W. Boyce, A. S. Truong, C. R. Bagnell, and M. R. Lockett, “Real-time imaging of cancer cell chemotaxis in paper-based scaffolds,” Analyst 141(2), 661–668 (2016).
[Crossref]

Bissell, M. J.

B. Weigelt, C. M. Ghajar, and M. J. Bissell, “The need for complex 3D culture models to unravel novel pathways and identify accurate biomarkers in breast cancer,” Adv. Drug Delivery Rev. 69-70, 42–51 (2014).
[Crossref]

Blackmon, R.

X. Yu, A. M. Fuller, R. Blackmon, M. A. Troester, and A. L. Oldenburg, “Quantification of the effect of toxicants on the intracellular kinetic energy and cross-sectional area of mammary epithelial organoids by OCT fluctuation spectroscopy,” Toxicol. Sci. 162(1), 234–240 (2018).
[Crossref]

Boccara, A. C.

Boppart, S. A.

S. A. Boppart, W. Tan, H. J. Ko, and C. Vinegoni, “Optical coherence tomography of cell dynamics in three-dimensional engineered tissues,” Optical Coherence Tomography and Coherence Techniques II (Optical Society of America, 2005).

Boucher, D. M.

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

Boyce, M. W.

C. C. Lloyd, M. W. Boyce, and M. R. Lockett, “Paper-based invasion assays for quantifying cellular movement in three-dimensional tissue-like structures,” Curr. Protoc. Chem. Biol. 9(2), 75–95 (2017).
[Crossref]

M. W. Boyce, G. J. Labonia, A. B. Hummon, and M. R. Lockett, “Assessing chemotherapeutic effectiveness using a paper-based tumor model,” Analyst 142(15), 2819–2827 (2017).
[Crossref]

R. M. Kenney, M. W. Boyce, A. S. Truong, C. R. Bagnell, and M. R. Lockett, “Real-time imaging of cancer cell chemotaxis in paper-based scaffolds,” Analyst 141(2), 661–668 (2016).
[Crossref]

A. S. Truong, C. A. Lochbaum, M. W. Boyce, and M. R. Lockett, “Tracking the invasion of small numbers of cells in paper-based assays with quantitative PCR,” Anal. Chem. 87(22), 11263–11270 (2015).
[Crossref]

Brekhman, V.

V. Brekhman and G. Neufeld, “An asymmetric 3D In vitro assay for the study of tumor cell invasion,” Methods Cell Biol. 112, 311–328 (2012).
[Crossref]

Breslin, S.

S. Breslin and L. O’Driscoll, “Three-dimensional cell culture the missing link in drug discovery,” Drug Discovery Today 18(5-6), 240–249 (2013).
[Crossref]

Camci-Unal, G.

G. Camci-Unal, D. Newsome, B. K. Eustace, and G. M. Whitesides, “Fibroblasts enhance migration of human lung cancer cells in a paper-based coculture system,” Adv. Healthcare Mater. 5(6), 641–647 (2016).
[Crossref]

Campbell, P.

B. Mosadegh, B. E. Dabiri, M. R. Lockett, R. Derda, P. Campbell, K. K. Parker, and G. M. Whitesides, “Three-dimensional paper-based model for cardiac ischemia,” Adv. Healthcare Mater. 3(7), 1036–1043 (2014).
[Crossref]

Cardona, A.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Chaffer, C. L.

C. L. Chaffer and W. A. Robert, “A perspective on cancer cell metastasis,” Science 331(6024), 1559–1564 (2011).
[Crossref]

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

Chavrier, P.

R. Poincloux, O. Collin, F. Lizárraga, M. Romao, M. Debray, M. Piel, and P. Chavrier, “Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel,” Proc. Natl. Acad. Sci. 108(5), 1943–1948 (2011).
[Crossref]

Chhetri, R. K.

A. L. Oldenburg, R. K. Chhetri, J. M. Cooper, W.-C. Wu, M. A. Troester, and J. B. Tracy, “Motility-, autocorrelation-, and polarization-sensitive optical coherence tomography discriminates cells and gold nanorods within 3D tissue cultures,” Opt. Lett. 38(15), 2923 (2013).
[Crossref]

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, “Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy,” PLoS One 7(11), e49148 (2012).
[Crossref]

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83(4), 040903 (2011).
[Crossref]

Childress, M.

Chu, K. K.

K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
[Crossref]

Collin, O.

R. Poincloux, O. Collin, F. Lizárraga, M. Romao, M. Debray, M. Piel, and P. Chavrier, “Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel,” Proc. Natl. Acad. Sci. 108(5), 1943–1948 (2011).
[Crossref]

Cooper, J. M.

Cui, D.

K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
[Crossref]

Cukierman, E.

K. M. Yamada and E. Cukierman, “Modeling tissue morphogenesis and cancer in 3D,” Cell 130(4), 601–610 (2007).
[Crossref]

Dabiri, B. E.

B. Mosadegh, B. E. Dabiri, M. R. Lockett, R. Derda, P. Campbell, K. K. Parker, and G. M. Whitesides, “Three-dimensional paper-based model for cardiac ischemia,” Adv. Healthcare Mater. 3(7), 1036–1043 (2014).
[Crossref]

Debray, M.

R. Poincloux, O. Collin, F. Lizárraga, M. Romao, M. Debray, M. Piel, and P. Chavrier, “Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel,” Proc. Natl. Acad. Sci. 108(5), 1943–1948 (2011).
[Crossref]

Derda, R.

B. Mosadegh, B. E. Dabiri, M. R. Lockett, R. Derda, P. Campbell, K. K. Parker, and G. M. Whitesides, “Three-dimensional paper-based model for cardiac ischemia,” Adv. Healthcare Mater. 3(7), 1036–1043 (2014).
[Crossref]

Drexler, W.

S. M. Rey, B. Považay, B. Hofer, A. Unterhuber, B. Hermann, A. Harwood, and W. Drexler, “Three- and four-dimensional visualization of cell migration using optical coherence tomography,” J. Biophotonics 2(6-7), 370–379 (2009).
[Crossref]

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
[Crossref]

Eaton, A. D.

K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
[Crossref]

Eliceiri, K.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Eustace, B. K.

G. Camci-Unal, D. Newsome, B. K. Eustace, and G. M. Whitesides, “Fibroblasts enhance migration of human lung cancer cells in a paper-based coculture system,” Adv. Healthcare Mater. 5(6), 641–647 (2016).
[Crossref]

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

Fercher, A. F.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
[Crossref]

Fleiss, J. L.

J. L. Fleiss, The Design and Analysis of Clinical Experiments (John Wiley & Sons, Inc., 1999).

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

French, P. M. W.

P. Yu, M. Mustata, J. J. Turek, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83(3), 575–577 (2003).
[Crossref]

Friedl, P.

P. Friedl and S. Alexander, “Cancer invasion and the microenvironment: plasticity and reciprocity,” Cell 147(5), 992–1009 (2011).
[Crossref]

Frise, E.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Fujimoto, J. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

Fuller, A. M.

L. Yang, X. Yu, A. M. Fuller, M. A. Troester, and A. L. Oldenburg, “Characterizing optical coherence tomography speckle fluctuation spectra of mammary organoids during suppression of intracellular motility,” Quant. Imaging Med. Surg. 10(1), 76–85 (2020).
[Crossref]

X. Yu, A. M. Fuller, R. Blackmon, M. A. Troester, and A. L. Oldenburg, “Quantification of the effect of toxicants on the intracellular kinetic energy and cross-sectional area of mammary epithelial organoids by OCT fluctuation spectroscopy,” Toxicol. Sci. 162(1), 234–240 (2018).
[Crossref]

Ghajar, C. M.

B. Weigelt, C. M. Ghajar, and M. J. Bissell, “The need for complex 3D culture models to unravel novel pathways and identify accurate biomarkers in breast cancer,” Adv. Drug Delivery Rev. 69-70, 42–51 (2014).
[Crossref]

Gilbert, K.

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

Gilliss, T.

Gong, H.

M. H. Zaman, L. M. Trapani, A. L. Sieminski, D. Mackellar, H. Gong, R. D. Kamm, A. Wells, D. A. Lauffenburger, and P. Matsudaira, “Migration of tumor cell in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis,” Proc. Natl. Acad. Sci. 103(29), 10889–10894 (2006).
[Crossref]

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

Hall, A. B.

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

Harms, F.

Hartenstein, V.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Harwood, A.

S. M. Rey, B. Považay, B. Hofer, A. Unterhuber, B. Hermann, A. Harwood, and W. Drexler, “Three- and four-dimensional visualization of cell migration using optical coherence tomography,” J. Biophotonics 2(6-7), 370–379 (2009).
[Crossref]

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

Hermann, B.

S. M. Rey, B. Považay, B. Hofer, A. Unterhuber, B. Hermann, A. Harwood, and W. Drexler, “Three- and four-dimensional visualization of cell migration using optical coherence tomography,” J. Biophotonics 2(6-7), 370–379 (2009).
[Crossref]

Hillier, S.

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

Hitzenberger, C. K.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
[Crossref]

Hofer, B.

S. M. Rey, B. Považay, B. Hofer, A. Unterhuber, B. Hermann, A. Harwood, and W. Drexler, “Three- and four-dimensional visualization of cell migration using optical coherence tomography,” J. Biophotonics 2(6-7), 370–379 (2009).
[Crossref]

Holm, S.

S. Holm, “A simple sequential rejective method procedure,” Scand. J. Stat. 6, 65–70 (1979).

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

Hummon, A. B.

M. W. Boyce, G. J. Labonia, A. B. Hummon, and M. R. Lockett, “Assessing chemotherapeutic effectiveness using a paper-based tumor model,” Analyst 142(15), 2819–2827 (2017).
[Crossref]

Hurley, B. P.

K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
[Crossref]

Iwamoto, Y.

A. Albini, Y. Iwamoto, and H. K. Kleinman, “A rapid in vitro assay for quantitating the invasive potential of tumor cells,” Cancer Res. 47, 3239–3245 (1987).

Jalal, S.

Jeong, K.

K. Jeong, J. J. Turek, and D. D. Nolte, “Speckle fluctuation spectroscopy of intracellular motion in living tissue using coherence-domain digital holography,” J. Biomed. Opt. 15(3), 030514 (2010).
[Crossref]

Johnston-Peck, A. C.

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83(4), 040903 (2011).
[Crossref]

Kamm, R. D.

M. H. Zaman, L. M. Trapani, A. L. Sieminski, D. Mackellar, H. Gong, R. D. Kamm, A. Wells, D. A. Lauffenburger, and P. Matsudaira, “Migration of tumor cell in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis,” Proc. Natl. Acad. Sci. 103(29), 10889–10894 (2006).
[Crossref]

Kaynig, V.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Kenney, R. M.

R. M. Kenney, A. Loeser, N. A. Whitman, and M. R. Lockett, “Paper-based transwell assays: an inexpensive alternative to study cellular invasion,” Analyst 144(1), 206–211 (2019).
[Crossref]

R. M. Kenney, M. W. Boyce, A. S. Truong, C. R. Bagnell, and M. R. Lockett, “Real-time imaging of cancer cell chemotaxis in paper-based scaffolds,” Analyst 141(2), 661–668 (2016).
[Crossref]

Kleinman, H. K.

A. Albini, Y. Iwamoto, and H. K. Kleinman, “A rapid in vitro assay for quantitating the invasive potential of tumor cells,” Cancer Res. 47, 3239–3245 (1987).

Ko, H. J.

S. A. Boppart, W. Tan, H. J. Ko, and C. Vinegoni, “Optical coherence tomography of cell dynamics in three-dimensional engineered tissues,” Optical Coherence Tomography and Coherence Techniques II (Optical Society of America, 2005).

Koch, G. G.

G. G. Koch, “Intraclass correlation coefficient,” Encycl. Stat. Sci.212–217 (1982).

Kozek, K. A.

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83(4), 040903 (2011).
[Crossref]

Kurth, T.

J. Sapudom, S. Rubner, S. Martin, T. Kurth, S. Riedel, C. T. Mierke, and T. Pompe, “The phenotype of cancer cell invasion controlled by fibril diameter and pore size of 3D collagen networks,” Biomaterials 52, 367–375 (2015).
[Crossref]

Kusek, M. E.

K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
[Crossref]

Labonia, G. J.

M. W. Boyce, G. J. Labonia, A. B. Hummon, and M. R. Lockett, “Assessing chemotherapeutic effectiveness using a paper-based tumor model,” Analyst 142(15), 2819–2827 (2017).
[Crossref]

Lasser, T.

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
[Crossref]

Lauffenburger, D. A.

M. H. Zaman, L. M. Trapani, A. L. Sieminski, D. Mackellar, H. Gong, R. D. Kamm, A. Wells, D. A. Lauffenburger, and P. Matsudaira, “Migration of tumor cell in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis,” Proc. Natl. Acad. Sci. 103(29), 10889–10894 (2006).
[Crossref]

Leung, H.

K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
[Crossref]

Li, H.

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

Li, Z.

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

Liu, L.

K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
[Crossref]

Lizárraga, F.

R. Poincloux, O. Collin, F. Lizárraga, M. Romao, M. Debray, M. Piel, and P. Chavrier, “Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel,” Proc. Natl. Acad. Sci. 108(5), 1943–1948 (2011).
[Crossref]

Lloyd, C. C.

C. C. Lloyd, M. W. Boyce, and M. R. Lockett, “Paper-based invasion assays for quantifying cellular movement in three-dimensional tissue-like structures,” Curr. Protoc. Chem. Biol. 9(2), 75–95 (2017).
[Crossref]

Lochbaum, C. A.

A. S. Truong, C. A. Lochbaum, M. W. Boyce, and M. R. Lockett, “Tracking the invasion of small numbers of cells in paper-based assays with quantitative PCR,” Anal. Chem. 87(22), 11263–11270 (2015).
[Crossref]

Lockett, M. R.

R. M. Kenney, A. Loeser, N. A. Whitman, and M. R. Lockett, “Paper-based transwell assays: an inexpensive alternative to study cellular invasion,” Analyst 144(1), 206–211 (2019).
[Crossref]

M. W. Boyce, G. J. Labonia, A. B. Hummon, and M. R. Lockett, “Assessing chemotherapeutic effectiveness using a paper-based tumor model,” Analyst 142(15), 2819–2827 (2017).
[Crossref]

C. C. Lloyd, M. W. Boyce, and M. R. Lockett, “Paper-based invasion assays for quantifying cellular movement in three-dimensional tissue-like structures,” Curr. Protoc. Chem. Biol. 9(2), 75–95 (2017).
[Crossref]

R. M. Kenney, M. W. Boyce, A. S. Truong, C. R. Bagnell, and M. R. Lockett, “Real-time imaging of cancer cell chemotaxis in paper-based scaffolds,” Analyst 141(2), 661–668 (2016).
[Crossref]

A. S. Truong, C. A. Lochbaum, M. W. Boyce, and M. R. Lockett, “Tracking the invasion of small numbers of cells in paper-based assays with quantitative PCR,” Anal. Chem. 87(22), 11263–11270 (2015).
[Crossref]

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

B. Mosadegh, B. E. Dabiri, M. R. Lockett, R. Derda, P. Campbell, K. K. Parker, and G. M. Whitesides, “Three-dimensional paper-based model for cardiac ischemia,” Adv. Healthcare Mater. 3(7), 1036–1043 (2014).
[Crossref]

Loeser, A.

R. M. Kenney, A. Loeser, N. A. Whitman, and M. R. Lockett, “Paper-based transwell assays: an inexpensive alternative to study cellular invasion,” Analyst 144(1), 206–211 (2019).
[Crossref]

Long, G. L.

G. L. Long and J. D. Winefordner, “Limit of detection: a closer look at the IUPAC definition,” Anal. Chem. 55(7), 712A–724A (1983).
[Crossref]

Longair, M.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Mackellar, D.

M. H. Zaman, L. M. Trapani, A. L. Sieminski, D. Mackellar, H. Gong, R. D. Kamm, A. Wells, D. A. Lauffenburger, and P. Matsudaira, “Migration of tumor cell in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis,” Proc. Natl. Acad. Sci. 103(29), 10889–10894 (2006).
[Crossref]

Magee, P. J.

P. J. Magee, H. McGlynn, and I. R. Rowland, “Differential effects of isoflavones and lignans on invasiveness of MDA-MB-231 breast cancer cells in vitro,” Cancer Lett. 208(1), 35–41 (2004).
[Crossref]

Marks, D. L.

Martin, S.

J. Sapudom, S. Rubner, S. Martin, T. Kurth, S. Riedel, C. T. Mierke, and T. Pompe, “The phenotype of cancer cell invasion controlled by fibril diameter and pore size of 3D collagen networks,” Biomaterials 52, 367–375 (2015).
[Crossref]

Matsudaira, P.

M. H. Zaman, L. M. Trapani, A. L. Sieminski, D. Mackellar, H. Gong, R. D. Kamm, A. Wells, D. A. Lauffenburger, and P. Matsudaira, “Migration of tumor cell in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis,” Proc. Natl. Acad. Sci. 103(29), 10889–10894 (2006).
[Crossref]

McGlynn, H.

P. J. Magee, H. McGlynn, and I. R. Rowland, “Differential effects of isoflavones and lignans on invasiveness of MDA-MB-231 breast cancer cells in vitro,” Cancer Lett. 208(1), 35–41 (2004).
[Crossref]

Melloch, M. R.

P. Yu, L. Peng, M. Mustata, J. J. Turek, M. R. Melloch, and D. D. Nolte, “Time-dependent speckle in holographic optical coherence imaging and the health of tumor tissue,” Opt. Lett. 29(1), 68–70 (2004).
[Crossref]

P. Yu, M. Mustata, J. J. Turek, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83(3), 575–577 (2003).
[Crossref]

Mierke, C. T.

J. Sapudom, S. Rubner, S. Martin, T. Kurth, S. Riedel, C. T. Mierke, and T. Pompe, “The phenotype of cancer cell invasion controlled by fibril diameter and pore size of 3D collagen networks,” Biomaterials 52, 367–375 (2015).
[Crossref]

Minn, K. T.

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

Mosadegh, B.

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

B. Mosadegh, B. E. Dabiri, M. R. Lockett, R. Derda, P. Campbell, K. K. Parker, and G. M. Whitesides, “Three-dimensional paper-based model for cardiac ischemia,” Adv. Healthcare Mater. 3(7), 1036–1043 (2014).
[Crossref]

Mustata, M.

P. Yu, L. Peng, M. Mustata, J. J. Turek, M. R. Melloch, and D. D. Nolte, “Time-dependent speckle in holographic optical coherence imaging and the health of tumor tissue,” Opt. Lett. 29(1), 68–70 (2004).
[Crossref]

P. Yu, M. Mustata, J. J. Turek, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83(3), 575–577 (2003).
[Crossref]

Naber, H. P. H.

E. Wiercinska, H. P. H. Naber, E. Pardali, G. Van Der Pluijm, H. Van Dam, and P. Ten Dijke, “The TGF-β/Smad pathway induces breast cancer cell invasion through the up-regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model system,” Breast Cancer Res. Treat. 128(3), 657–666 (2011).
[Crossref]

Neufeld, G.

V. Brekhman and G. Neufeld, “An asymmetric 3D In vitro assay for the study of tumor cell invasion,” Methods Cell Biol. 112, 311–328 (2012).
[Crossref]

Newsome, D.

G. Camci-Unal, D. Newsome, B. K. Eustace, and G. M. Whitesides, “Fibroblasts enhance migration of human lung cancer cells in a paper-based coculture system,” Adv. Healthcare Mater. 5(6), 641–647 (2016).
[Crossref]

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

Nolte, D. D.

Z. Li, H. Sun, J. Turek, S. Jalal, M. Childress, and D. D. Nolte, “Doppler fluctuation spectroscopy of intracellular dynamics in living tissue,” J. Opt. Soc. Am. A 36(4), 665 (2019).
[Crossref]

K. Jeong, J. J. Turek, and D. D. Nolte, “Speckle fluctuation spectroscopy of intracellular motion in living tissue using coherence-domain digital holography,” J. Biomed. Opt. 15(3), 030514 (2010).
[Crossref]

P. Yu, L. Peng, M. Mustata, J. J. Turek, M. R. Melloch, and D. D. Nolte, “Time-dependent speckle in holographic optical coherence imaging and the health of tumor tissue,” Opt. Lett. 29(1), 68–70 (2004).
[Crossref]

P. Yu, M. Mustata, J. J. Turek, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83(3), 575–577 (2003).
[Crossref]

O’Driscoll, L.

S. Breslin and L. O’Driscoll, “Three-dimensional cell culture the missing link in drug discovery,” Drug Discovery Today 18(5-6), 240–249 (2013).
[Crossref]

Oldenburg, A. L.

L. Yang, X. Yu, A. M. Fuller, M. A. Troester, and A. L. Oldenburg, “Characterizing optical coherence tomography speckle fluctuation spectra of mammary organoids during suppression of intracellular motility,” Quant. Imaging Med. Surg. 10(1), 76–85 (2020).
[Crossref]

X. Yu, A. M. Fuller, R. Blackmon, M. A. Troester, and A. L. Oldenburg, “Quantification of the effect of toxicants on the intracellular kinetic energy and cross-sectional area of mammary epithelial organoids by OCT fluctuation spectroscopy,” Toxicol. Sci. 162(1), 234–240 (2018).
[Crossref]

A. L. Oldenburg, X. Yu, T. Gilliss, O. Alabi, R. M. Taylor, and M. A. Troester, “Inverse-power-law behavior of cellular motility reveals stromal–epithelial cell interactions in 3D co-culture by OCT fluctuation spectroscopy,” Optica 2(10), 877 (2015).
[Crossref]

A. L. Oldenburg, R. K. Chhetri, J. M. Cooper, W.-C. Wu, M. A. Troester, and J. B. Tracy, “Motility-, autocorrelation-, and polarization-sensitive optical coherence tomography discriminates cells and gold nanorods within 3D tissue cultures,” Opt. Lett. 38(15), 2923 (2013).
[Crossref]

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, “Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy,” PLoS One 7(11), e49148 (2012).
[Crossref]

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83(4), 040903 (2011).
[Crossref]

D. L. Marks, A. L. Oldenburg, J. J. Reynolds, and S. a Boppart, “Digital algorithm for dispersion correction in optical coherence tomography for homogeneous and stratified media,” Appl. Opt. 42(2), 204–217 (2003).
[Crossref]

Pardali, E.

E. Wiercinska, H. P. H. Naber, E. Pardali, G. Van Der Pluijm, H. Van Dam, and P. Ten Dijke, “The TGF-β/Smad pathway induces breast cancer cell invasion through the up-regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model system,” Breast Cancer Res. Treat. 128(3), 657–666 (2011).
[Crossref]

Parker, K. K.

B. Mosadegh, B. E. Dabiri, M. R. Lockett, R. Derda, P. Campbell, K. K. Parker, and G. M. Whitesides, “Three-dimensional paper-based model for cardiac ischemia,” Adv. Healthcare Mater. 3(7), 1036–1043 (2014).
[Crossref]

Peng, L.

Phillips, Z. F.

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, “Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy,” PLoS One 7(11), e49148 (2012).
[Crossref]

Piel, M.

R. Poincloux, O. Collin, F. Lizárraga, M. Romao, M. Debray, M. Piel, and P. Chavrier, “Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel,” Proc. Natl. Acad. Sci. 108(5), 1943–1948 (2011).
[Crossref]

Pietzsch, T.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Poincloux, R.

R. Poincloux, O. Collin, F. Lizárraga, M. Romao, M. Debray, M. Piel, and P. Chavrier, “Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel,” Proc. Natl. Acad. Sci. 108(5), 1943–1948 (2011).
[Crossref]

Pompe, T.

J. Sapudom, S. Rubner, S. Martin, T. Kurth, S. Riedel, C. T. Mierke, and T. Pompe, “The phenotype of cancer cell invasion controlled by fibril diameter and pore size of 3D collagen networks,” Biomaterials 52, 367–375 (2015).
[Crossref]

Považay, B.

S. M. Rey, B. Považay, B. Hofer, A. Unterhuber, B. Hermann, A. Harwood, and W. Drexler, “Three- and four-dimensional visualization of cell migration using optical coherence tomography,” J. Biophotonics 2(6-7), 370–379 (2009).
[Crossref]

Preibisch, S.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

Rey, S. M.

S. M. Rey, B. Považay, B. Hofer, A. Unterhuber, B. Hermann, A. Harwood, and W. Drexler, “Three- and four-dimensional visualization of cell migration using optical coherence tomography,” J. Biophotonics 2(6-7), 370–379 (2009).
[Crossref]

Reynolds, J. J.

Riedel, S.

J. Sapudom, S. Rubner, S. Martin, T. Kurth, S. Riedel, C. T. Mierke, and T. Pompe, “The phenotype of cancer cell invasion controlled by fibril diameter and pore size of 3D collagen networks,” Biomaterials 52, 367–375 (2015).
[Crossref]

Robert, W. A.

C. L. Chaffer and W. A. Robert, “A perspective on cancer cell metastasis,” Science 331(6024), 1559–1564 (2011).
[Crossref]

Romao, M.

R. Poincloux, O. Collin, F. Lizárraga, M. Romao, M. Debray, M. Piel, and P. Chavrier, “Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel,” Proc. Natl. Acad. Sci. 108(5), 1943–1948 (2011).
[Crossref]

Rowland, I. R.

P. J. Magee, H. McGlynn, and I. R. Rowland, “Differential effects of isoflavones and lignans on invasiveness of MDA-MB-231 breast cancer cells in vitro,” Cancer Lett. 208(1), 35–41 (2004).
[Crossref]

Rubner, S.

J. Sapudom, S. Rubner, S. Martin, T. Kurth, S. Riedel, C. T. Mierke, and T. Pompe, “The phenotype of cancer cell invasion controlled by fibril diameter and pore size of 3D collagen networks,” Biomaterials 52, 367–375 (2015).
[Crossref]

Rueden, C.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Ryu, J.

K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
[Crossref]

Saalfeld, S.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Sapudom, J.

J. Sapudom, S. Rubner, S. Martin, T. Kurth, S. Riedel, C. T. Mierke, and T. Pompe, “The phenotype of cancer cell invasion controlled by fibril diameter and pore size of 3D collagen networks,” Biomaterials 52, 367–375 (2015).
[Crossref]

Schindelin, J.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Schmid, B.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

Sieminski, A. L.

M. H. Zaman, L. M. Trapani, A. L. Sieminski, D. Mackellar, H. Gong, R. D. Kamm, A. Wells, D. A. Lauffenburger, and P. Matsudaira, “Migration of tumor cell in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis,” Proc. Natl. Acad. Sci. 103(29), 10889–10894 (2006).
[Crossref]

Simon, K. A.

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

Som, A.

K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
[Crossref]

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

Sun, H.

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

Tan, W.

S. A. Boppart, W. Tan, H. J. Ko, and C. Vinegoni, “Optical coherence tomography of cell dynamics in three-dimensional engineered tissues,” Optical Coherence Tomography and Coherence Techniques II (Optical Society of America, 2005).

Taylor, R. M.

Tearney, G. J.

K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
[Crossref]

Ten Dijke, P.

E. Wiercinska, H. P. H. Naber, E. Pardali, G. Van Der Pluijm, H. Van Dam, and P. Ten Dijke, “The TGF-β/Smad pathway induces breast cancer cell invasion through the up-regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model system,” Breast Cancer Res. Treat. 128(3), 657–666 (2011).
[Crossref]

Thouvenin, O.

Tinevez, J.-Y.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Tomancak, P.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Tracy, J. B.

A. L. Oldenburg, R. K. Chhetri, J. M. Cooper, W.-C. Wu, M. A. Troester, and J. B. Tracy, “Motility-, autocorrelation-, and polarization-sensitive optical coherence tomography discriminates cells and gold nanorods within 3D tissue cultures,” Opt. Lett. 38(15), 2923 (2013).
[Crossref]

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83(4), 040903 (2011).
[Crossref]

Trapani, L. M.

M. H. Zaman, L. M. Trapani, A. L. Sieminski, D. Mackellar, H. Gong, R. D. Kamm, A. Wells, D. A. Lauffenburger, and P. Matsudaira, “Migration of tumor cell in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis,” Proc. Natl. Acad. Sci. 103(29), 10889–10894 (2006).
[Crossref]

Troester, M. A.

L. Yang, X. Yu, A. M. Fuller, M. A. Troester, and A. L. Oldenburg, “Characterizing optical coherence tomography speckle fluctuation spectra of mammary organoids during suppression of intracellular motility,” Quant. Imaging Med. Surg. 10(1), 76–85 (2020).
[Crossref]

X. Yu, A. M. Fuller, R. Blackmon, M. A. Troester, and A. L. Oldenburg, “Quantification of the effect of toxicants on the intracellular kinetic energy and cross-sectional area of mammary epithelial organoids by OCT fluctuation spectroscopy,” Toxicol. Sci. 162(1), 234–240 (2018).
[Crossref]

A. L. Oldenburg, X. Yu, T. Gilliss, O. Alabi, R. M. Taylor, and M. A. Troester, “Inverse-power-law behavior of cellular motility reveals stromal–epithelial cell interactions in 3D co-culture by OCT fluctuation spectroscopy,” Optica 2(10), 877 (2015).
[Crossref]

A. L. Oldenburg, R. K. Chhetri, J. M. Cooper, W.-C. Wu, M. A. Troester, and J. B. Tracy, “Motility-, autocorrelation-, and polarization-sensitive optical coherence tomography discriminates cells and gold nanorods within 3D tissue cultures,” Opt. Lett. 38(15), 2923 (2013).
[Crossref]

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, “Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy,” PLoS One 7(11), e49148 (2012).
[Crossref]

Truong, A. S.

R. M. Kenney, M. W. Boyce, A. S. Truong, C. R. Bagnell, and M. R. Lockett, “Real-time imaging of cancer cell chemotaxis in paper-based scaffolds,” Analyst 141(2), 661–668 (2016).
[Crossref]

A. S. Truong, C. A. Lochbaum, M. W. Boyce, and M. R. Lockett, “Tracking the invasion of small numbers of cells in paper-based assays with quantitative PCR,” Anal. Chem. 87(22), 11263–11270 (2015).
[Crossref]

Turek, J.

Turek, J. J.

K. Jeong, J. J. Turek, and D. D. Nolte, “Speckle fluctuation spectroscopy of intracellular motion in living tissue using coherence-domain digital holography,” J. Biomed. Opt. 15(3), 030514 (2010).
[Crossref]

P. Yu, L. Peng, M. Mustata, J. J. Turek, M. R. Melloch, and D. D. Nolte, “Time-dependent speckle in holographic optical coherence imaging and the health of tumor tissue,” Opt. Lett. 29(1), 68–70 (2004).
[Crossref]

P. Yu, M. Mustata, J. J. Turek, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83(3), 575–577 (2003).
[Crossref]

Unterhuber, A.

S. M. Rey, B. Považay, B. Hofer, A. Unterhuber, B. Hermann, A. Harwood, and W. Drexler, “Three- and four-dimensional visualization of cell migration using optical coherence tomography,” J. Biophotonics 2(6-7), 370–379 (2009).
[Crossref]

Van Dam, H.

E. Wiercinska, H. P. H. Naber, E. Pardali, G. Van Der Pluijm, H. Van Dam, and P. Ten Dijke, “The TGF-β/Smad pathway induces breast cancer cell invasion through the up-regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model system,” Breast Cancer Res. Treat. 128(3), 657–666 (2011).
[Crossref]

Van Der Pluijm, G.

E. Wiercinska, H. P. H. Naber, E. Pardali, G. Van Der Pluijm, H. Van Dam, and P. Ten Dijke, “The TGF-β/Smad pathway induces breast cancer cell invasion through the up-regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model system,” Breast Cancer Res. Treat. 128(3), 657–666 (2011).
[Crossref]

Vinegoni, C.

S. A. Boppart, W. Tan, H. J. Ko, and C. Vinegoni, “Optical coherence tomography of cell dynamics in three-dimensional engineered tissues,” Optical Coherence Tomography and Coherence Techniques II (Optical Society of America, 2005).

Weigelt, B.

B. Weigelt, C. M. Ghajar, and M. J. Bissell, “The need for complex 3D culture models to unravel novel pathways and identify accurate biomarkers in breast cancer,” Adv. Drug Delivery Rev. 69-70, 42–51 (2014).
[Crossref]

Wells, A.

M. H. Zaman, L. M. Trapani, A. L. Sieminski, D. Mackellar, H. Gong, R. D. Kamm, A. Wells, D. A. Lauffenburger, and P. Matsudaira, “Migration of tumor cell in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis,” Proc. Natl. Acad. Sci. 103(29), 10889–10894 (2006).
[Crossref]

White, D. J.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Whitesides, G. M.

G. Camci-Unal, D. Newsome, B. K. Eustace, and G. M. Whitesides, “Fibroblasts enhance migration of human lung cancer cells in a paper-based coculture system,” Adv. Healthcare Mater. 5(6), 641–647 (2016).
[Crossref]

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

B. Mosadegh, B. E. Dabiri, M. R. Lockett, R. Derda, P. Campbell, K. K. Parker, and G. M. Whitesides, “Three-dimensional paper-based model for cardiac ischemia,” Adv. Healthcare Mater. 3(7), 1036–1043 (2014).
[Crossref]

Whitman, N. A.

R. M. Kenney, A. Loeser, N. A. Whitman, and M. R. Lockett, “Paper-based transwell assays: an inexpensive alternative to study cellular invasion,” Analyst 144(1), 206–211 (2019).
[Crossref]

Wiercinska, E.

E. Wiercinska, H. P. H. Naber, E. Pardali, G. Van Der Pluijm, H. Van Dam, and P. Ten Dijke, “The TGF-β/Smad pathway induces breast cancer cell invasion through the up-regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model system,” Breast Cancer Res. Treat. 128(3), 657–666 (2011).
[Crossref]

Winefordner, J. D.

G. L. Long and J. D. Winefordner, “Limit of detection: a closer look at the IUPAC definition,” Anal. Chem. 55(7), 712A–724A (1983).
[Crossref]

Wu, W.-C.

Yamada, K. M.

K. M. Yamada and E. Cukierman, “Modeling tissue morphogenesis and cancer in 3D,” Cell 130(4), 601–610 (2007).
[Crossref]

Yang, L.

L. Yang, X. Yu, A. M. Fuller, M. A. Troester, and A. L. Oldenburg, “Characterizing optical coherence tomography speckle fluctuation spectra of mammary organoids during suppression of intracellular motility,” Quant. Imaging Med. Surg. 10(1), 76–85 (2020).
[Crossref]

Yin, K. B.

K. B. Yin, “The Mesenchymal-like Phenotype of the MDA-MB-231 Cell Line,” Breast Cancer (IntechOpen, 2012), Chapter 18.

Yonker, L. M.

K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
[Crossref]

Yu, P.

P. Yu, L. Peng, M. Mustata, J. J. Turek, M. R. Melloch, and D. D. Nolte, “Time-dependent speckle in holographic optical coherence imaging and the health of tumor tissue,” Opt. Lett. 29(1), 68–70 (2004).
[Crossref]

P. Yu, M. Mustata, J. J. Turek, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83(3), 575–577 (2003).
[Crossref]

Yu, X.

L. Yang, X. Yu, A. M. Fuller, M. A. Troester, and A. L. Oldenburg, “Characterizing optical coherence tomography speckle fluctuation spectra of mammary organoids during suppression of intracellular motility,” Quant. Imaging Med. Surg. 10(1), 76–85 (2020).
[Crossref]

X. Yu, A. M. Fuller, R. Blackmon, M. A. Troester, and A. L. Oldenburg, “Quantification of the effect of toxicants on the intracellular kinetic energy and cross-sectional area of mammary epithelial organoids by OCT fluctuation spectroscopy,” Toxicol. Sci. 162(1), 234–240 (2018).
[Crossref]

A. L. Oldenburg, X. Yu, T. Gilliss, O. Alabi, R. M. Taylor, and M. A. Troester, “Inverse-power-law behavior of cellular motility reveals stromal–epithelial cell interactions in 3D co-culture by OCT fluctuation spectroscopy,” Optica 2(10), 877 (2015).
[Crossref]

Zaman, M. H.

M. H. Zaman, L. M. Trapani, A. L. Sieminski, D. Mackellar, H. Gong, R. D. Kamm, A. Wells, D. A. Lauffenburger, and P. Matsudaira, “Migration of tumor cell in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis,” Proc. Natl. Acad. Sci. 103(29), 10889–10894 (2006).
[Crossref]

Adv. Drug Delivery Rev. (1)

B. Weigelt, C. M. Ghajar, and M. J. Bissell, “The need for complex 3D culture models to unravel novel pathways and identify accurate biomarkers in breast cancer,” Adv. Drug Delivery Rev. 69-70, 42–51 (2014).
[Crossref]

Adv. Healthcare Mater. (2)

B. Mosadegh, B. E. Dabiri, M. R. Lockett, R. Derda, P. Campbell, K. K. Parker, and G. M. Whitesides, “Three-dimensional paper-based model for cardiac ischemia,” Adv. Healthcare Mater. 3(7), 1036–1043 (2014).
[Crossref]

G. Camci-Unal, D. Newsome, B. K. Eustace, and G. M. Whitesides, “Fibroblasts enhance migration of human lung cancer cells in a paper-based coculture system,” Adv. Healthcare Mater. 5(6), 641–647 (2016).
[Crossref]

Anal. Chem. (2)

A. S. Truong, C. A. Lochbaum, M. W. Boyce, and M. R. Lockett, “Tracking the invasion of small numbers of cells in paper-based assays with quantitative PCR,” Anal. Chem. 87(22), 11263–11270 (2015).
[Crossref]

G. L. Long and J. D. Winefordner, “Limit of detection: a closer look at the IUPAC definition,” Anal. Chem. 55(7), 712A–724A (1983).
[Crossref]

Analyst (3)

R. M. Kenney, M. W. Boyce, A. S. Truong, C. R. Bagnell, and M. R. Lockett, “Real-time imaging of cancer cell chemotaxis in paper-based scaffolds,” Analyst 141(2), 661–668 (2016).
[Crossref]

R. M. Kenney, A. Loeser, N. A. Whitman, and M. R. Lockett, “Paper-based transwell assays: an inexpensive alternative to study cellular invasion,” Analyst 144(1), 206–211 (2019).
[Crossref]

M. W. Boyce, G. J. Labonia, A. B. Hummon, and M. R. Lockett, “Assessing chemotherapeutic effectiveness using a paper-based tumor model,” Analyst 142(15), 2819–2827 (2017).
[Crossref]

Appl. Opt. (1)

Appl. Phys. Lett. (1)

P. Yu, M. Mustata, J. J. Turek, P. M. W. French, M. R. Melloch, and D. D. Nolte, “Holographic optical coherence imaging of tumor spheroids,” Appl. Phys. Lett. 83(3), 575–577 (2003).
[Crossref]

Biomaterials (2)

B. Mosadegh, M. R. Lockett, K. T. Minn, K. A. Simon, K. Gilbert, S. Hillier, D. Newsome, H. Li, A. B. Hall, D. M. Boucher, B. K. Eustace, and G. M. Whitesides, “A paper-based invasion assay: assessing chemotaxis of cancer cells in gradients of oxygen,” Biomaterials 52, 262–271 (2015).
[Crossref]

J. Sapudom, S. Rubner, S. Martin, T. Kurth, S. Riedel, C. T. Mierke, and T. Pompe, “The phenotype of cancer cell invasion controlled by fibril diameter and pore size of 3D collagen networks,” Biomaterials 52, 367–375 (2015).
[Crossref]

Biomed. Opt. Express (1)

Breast Cancer Res. Treat. (1)

E. Wiercinska, H. P. H. Naber, E. Pardali, G. Van Der Pluijm, H. Van Dam, and P. Ten Dijke, “The TGF-β/Smad pathway induces breast cancer cell invasion through the up-regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model system,” Breast Cancer Res. Treat. 128(3), 657–666 (2011).
[Crossref]

Cancer Lett. (1)

P. J. Magee, H. McGlynn, and I. R. Rowland, “Differential effects of isoflavones and lignans on invasiveness of MDA-MB-231 breast cancer cells in vitro,” Cancer Lett. 208(1), 35–41 (2004).
[Crossref]

Cancer Res. (1)

A. Albini, Y. Iwamoto, and H. K. Kleinman, “A rapid in vitro assay for quantitating the invasive potential of tumor cells,” Cancer Res. 47, 3239–3245 (1987).

Cell (2)

K. M. Yamada and E. Cukierman, “Modeling tissue morphogenesis and cancer in 3D,” Cell 130(4), 601–610 (2007).
[Crossref]

P. Friedl and S. Alexander, “Cancer invasion and the microenvironment: plasticity and reciprocity,” Cell 147(5), 992–1009 (2011).
[Crossref]

Curr. Protoc. Chem. Biol. (1)

C. C. Lloyd, M. W. Boyce, and M. R. Lockett, “Paper-based invasion assays for quantifying cellular movement in three-dimensional tissue-like structures,” Curr. Protoc. Chem. Biol. 9(2), 75–95 (2017).
[Crossref]

Drug Discovery Today (1)

S. Breslin and L. O’Driscoll, “Three-dimensional cell culture the missing link in drug discovery,” Drug Discovery Today 18(5-6), 240–249 (2013).
[Crossref]

J. Biomed. Opt. (1)

K. Jeong, J. J. Turek, and D. D. Nolte, “Speckle fluctuation spectroscopy of intracellular motion in living tissue using coherence-domain digital holography,” J. Biomed. Opt. 15(3), 030514 (2010).
[Crossref]

J. Biophotonics (1)

S. M. Rey, B. Považay, B. Hofer, A. Unterhuber, B. Hermann, A. Harwood, and W. Drexler, “Three- and four-dimensional visualization of cell migration using optical coherence tomography,” J. Biophotonics 2(6-7), 370–379 (2009).
[Crossref]

J. Opt. Soc. Am. A (1)

Methods Cell Biol. (1)

V. Brekhman and G. Neufeld, “An asymmetric 3D In vitro assay for the study of tumor cell invasion,” Methods Cell Biol. 112, 311–328 (2012).
[Crossref]

Nat. Methods (1)

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref]

Opt. Lett. (2)

Optica (1)

Phys. Rev. E (1)

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, “Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography,” Phys. Rev. E 83(4), 040903 (2011).
[Crossref]

PLoS One (1)

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, “Longitudinal study of mammary epithelial and fibroblast co-cultures using optical coherence tomography reveals morphological hallmarks of pre-malignancy,” PLoS One 7(11), e49148 (2012).
[Crossref]

Proc. Natl. Acad. Sci. (2)

M. H. Zaman, L. M. Trapani, A. L. Sieminski, D. Mackellar, H. Gong, R. D. Kamm, A. Wells, D. A. Lauffenburger, and P. Matsudaira, “Migration of tumor cell in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis,” Proc. Natl. Acad. Sci. 103(29), 10889–10894 (2006).
[Crossref]

R. Poincloux, O. Collin, F. Lizárraga, M. Romao, M. Debray, M. Piel, and P. Chavrier, “Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel,” Proc. Natl. Acad. Sci. 108(5), 1943–1948 (2011).
[Crossref]

Quant. Imaging Med. Surg. (1)

L. Yang, X. Yu, A. M. Fuller, M. A. Troester, and A. L. Oldenburg, “Characterizing optical coherence tomography speckle fluctuation spectra of mammary organoids during suppression of intracellular motility,” Quant. Imaging Med. Surg. 10(1), 76–85 (2020).
[Crossref]

Rep. Prog. Phys. (1)

A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Optical coherence tomography - principles and applications,” Rep. Prog. Phys. 66(2), 239–303 (2003).
[Crossref]

Scand. J. Stat. (1)

S. Holm, “A simple sequential rejective method procedure,” Scand. J. Stat. 6, 65–70 (1979).

Sci. Rep. (1)

K. K. Chu, M. E. Kusek, L. Liu, A. Som, L. M. Yonker, H. Leung, D. Cui, J. Ryu, A. D. Eaton, G. J. Tearney, and B. P. Hurley, “Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography,” Sci. Rep. 8, 45789 (2017).
[Crossref]

Science (2)

C. L. Chaffer and W. A. Robert, “A perspective on cancer cell metastasis,” Science 331(6024), 1559–1564 (2011).
[Crossref]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, J. G. Fujimoto, C. P. Lin, J. S. Schuman, and C. A. Puliafito, “Optical Coherence Tomography,” Science 254, 1178–1181 (1991).
[Crossref]

Toxicol. Sci. (1)

X. Yu, A. M. Fuller, R. Blackmon, M. A. Troester, and A. L. Oldenburg, “Quantification of the effect of toxicants on the intracellular kinetic energy and cross-sectional area of mammary epithelial organoids by OCT fluctuation spectroscopy,” Toxicol. Sci. 162(1), 234–240 (2018).
[Crossref]

Other (4)

K. B. Yin, “The Mesenchymal-like Phenotype of the MDA-MB-231 Cell Line,” Breast Cancer (IntechOpen, 2012), Chapter 18.

S. A. Boppart, W. Tan, H. J. Ko, and C. Vinegoni, “Optical coherence tomography of cell dynamics in three-dimensional engineered tissues,” Optical Coherence Tomography and Coherence Techniques II (Optical Society of America, 2005).

J. L. Fleiss, The Design and Analysis of Clinical Experiments (John Wiley & Sons, Inc., 1999).

G. G. Koch, “Intraclass correlation coefficient,” Encycl. Stat. Sci.212–217 (1982).

Supplementary Material (3)

NameDescription
» Visualization 1       Visualization 1: Time-lapse video of cell-free and cell-containing scaffolds
» Visualization 2       Visualization 2: 3D flythrough of motility-contrasted OCT images of a 3D paper-based invasion assay.
» Visualization 3       Visualization 3: 3D visualization of two independent cell-laden invasion assays imaged by OCT-MA on Day 0 (left) and Day 3 (right), respectively.

Cited By

OSA participates in Crossref's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (5)

Fig. 1.
Fig. 1. (a) Schematic of the spectral-domain optical coherence tomography (SD-OCT) system: FC, fiber coupler; BS, beam splitter; PBS, polarized beam splitter; QWP, quarter-wave plate at 22.5°; and SMF, single-mode fiber. (b) Schematic of the PBC invasion culture. (c) Representative time-lapse OCT of a PBC collected as a stack of B-mode (lateral (x) by axial (z)) images in time (t). (d) Spatially-resolved motility amplitude metric, M(x,z), defined by I(x, z, t), the OCT image intensity; $\bar{I}({x,z} )$, the time average of image intensity over the stack, and Γ(x, z, Δt), the autocorrelation of I(x, z, t) computed at the B-mode frame sampling time Δt.
Fig. 2.
Fig. 2. Representative motility-contrasted OCT images of a 4-layer (a) cell-laden and (b) cell-free invasion assay. Both cultures were imaged after 3 days of incubation. Each image is a superposition of a motility map M(x, z) (red) with the time-averaged OCT image $\bar{I}({x,z} )$ (blue). Representative manual segmentation lines depicting the four layers of the (c) cell-laden and (d) cell free invasion assays. The solid yellow lines represent the top and bottom boundaries of the invasion assay; the three yellow dashed lines represent the interfaces between the four scaffolds of the assay. The time-averaged OCT images reveal static components of culture structures, while the motility map is specific to dynamic components, predominantly from live cells. Corresponding time-lapse videos through each OCT stack reveal the speckle fluctuations that cause the motility map of the cell-laden culture (see Visualization 1). To improve the visibility of the cells, these images were mean filtered by the size of a cell (9 µm × 9 µm) and a corresponding threshold, M > 0.124, was applied to M at every pixel to reject background noise.
Fig. 3.
Fig. 3. Four invasion cultures were prepared from a single cell passage, then, one culture was selected on each day for analysis by OCT immediately followed by fluorescence imaging. (a) Scatter plot comparing the OCT and fluorescence imaging PLi values from 22 separate invasion assays (n = 88). A 45-degree dashed line is included to indicate the similarity between the two methods and the calculated ICC value of 0.903 (95% confidence interval, 0.867–0.941) indicates that the two methods are highly correlated. (b – e) End-point PLi distributions determined with OCT and from fluorescence images after approximately (b) zero, (c) one, (d) two, and (e) three days of incubation. Each bar represents the average and SEM of cells in each layer of the invasion assay from a minimum of n = 4 technical replicates. Individual data points are shown as black dots. Each bar also represents the minimum distance the cells must have invaded to reach the next layer, as each scaffold is 40–75 µm thick.
Fig. 4.
Fig. 4. (a) PLI distributions of two separate invasion cultures determined with fluorescence imaging, after a three-day incubation. The post-longitudinal OCT fluorescence values correspond to an end-point measure of an invasion culture whose cell distributions were analyzed with OCT on Days 0–3. The no-OCT fluorescence values correspond to an end-point measure of an invasion culture that was not exposed to OCT. (b) PLI distributions measured with OCT for Days 0–3. (c) Representative OCT motility images for Days 0–3; blue lines show the manually segmented scaffolds (bottom to top: scaffold 0–3). To improve the visibility of cells, these representative images were mean filtered by the size of a cell (9 µm × 9 µm) and a corresponding threshold, M > 0.124, was applied to M at every pixel to reject background noise. All bars are the average and SEM from a minimum of n = 4 replicates. Each bar also represents the minimum distance the cells must have invaded to reach the next layer, as each scaffold is (40 µm) thick.
Fig. 5.
Fig. 5. Representative 3D visualization of invasion cultures on Day 0 and Day 3 by OCT (See Visualization 3). The top row shows OCT signals (blue) overlaid with motility amplitudes, M (red). The bottom row shows M alone. To improve the visibility of cells, these representative images were mean filtered by the size of a cell (9 µm × 9 µm) and a corresponding threshold, M > 0.124, was applied to M at every pixel to reject background noise.

Tables (1)

Tables Icon

Table 1. Holm-Bonferroni statistical test procedure adjusted step-down p-value results

Equations (5)

Equations on this page are rendered with MathJax. Learn more.

L O D = I b g ¯ + 3 S b g
P L i = { B S I L i L i = 0 3 B S I L i , I L i L O D 0 , I L i < L O D }
M ( x , z ) = Γ ( x , z , Δ t ) I ¯ ( x , z ) 2 I ¯ ( x , z )
P L i = N L i ( M > M t h ) 0 3 N L i ( M > M t h ) × 100
( V 1 V 2 V 3 ) = [ 3 1 1 3 1 1 1 1 1 3 3 1 ] ( P L 0 P L 1 P L 2 P L 3 )