One-step tumor detection from dynamic morphology tracking on aptamer-grafted surfaces.

In this paper, we report a one-step tumor cell detection approach based on the dynamic morphological behavior tracking of cancer cells on a ligand modified surface. Every cell on the surface was tracked in real time for several minutes immediately after seeding until these were finally attached. Cancer cells were found to be very active in the aptamer microenvironment, changing their shapes rapidly from spherical to semi-elliptical, with much flatter spread and extending pseudopods at regular intervals. When incubated on a functionalized surface, the balancing forces between cell surface molecules and the surface-bound aptamers, together with the flexibility of the membranes, caused cells to show these distinct dynamic activities and variations in their morphologies. On the other hand, healthy cells remained distinguishingly inactive on the surface over the same period. The quantitative image analysis of cell morphologies provided feature vectors that were statistically distinct between normal and cancer cells.

[1]  H. Sönmez,et al.  Sialic acid levels in various types of cancer. , 1992, Cancer biochemistry biophysics.

[2]  R. Bachoo,et al.  CAN-10-0568 Cancer esearch or and Stem Cell Biology face-Immobilized Aptamers for Cancer Cell Isolation R Microscopic Cytology , 2010 .

[3]  J A Sethian,et al.  A fast marching level set method for monotonically advancing fronts. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Feigon,et al.  Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Weihong Tan,et al.  Cancer cell targeting using multiple aptamers conjugated on nanorods. , 2008, Analytical chemistry.

[6]  J. Downward.  Targeting RAS signalling pathways in cancer therapy , 2003, Nature Reviews Cancer.

[7]  Daniel P. Huttenlocher,et al.  Comparing Images Using the Hausdorff Distance , 1993, IEEE Trans. Pattern Anal. Mach. Intell..

[8]  J. Barciszewski,et al.  DNA and RNA Nanobiotechnologies in Medicine: Diagnosis and Treatment of Diseases , 2013, RNA Technologies.

[9]  Revathi Ananthakrishnan,et al.  The Forces Behind Cell Movement , 2007, International journal of biological sciences.

[10]  M. A. Mahmood,et al.  Nucleic Acid-Based Encapsulations for Cancer Diagnostics and Drug Delivery , 2013 .

[11]  Louai Labanieh,et al.  Nucleic acid aptamers in cancer research, diagnosis and therapy. , 2015, Chemical Society reviews.

[12]  A. Ellington,et al.  Aptamer beacons for the direct detection of proteins. , 2001, Analytical biochemistry.

[13]  B. Piro,et al.  Investigations of the steric effect on electrochemical transduction in a quinone-based DNA sensor. , 2007, Biosensors & bioelectronics.

[14]  E. Engvall,et al.  Basement membrane changes in breast cancer detected by immunohistochemical staining for laminin. , 1981, Cancer research.

[15]  Waseem Asghar,et al.  Capture, isolation and release of cancer cells with aptamer-functionalized glass bead array. , 2012, Lab on a chip.

[16]  Rashid Bashir,et al.  Solid-state nanopore channels with DNA selectivity. , 2007, Nature nanotechnology.

[17]  S. Digumarthy,et al.  Isolation of rare circulating tumour cells in cancer patients by microchip technology , 2007, Nature.

[18]  J. Rao,et al.  Nanomechanical analysis of cells from cancer patients. , 2007, Nature nanotechnology.

[19]  M. Berger,et al.  EGFR overexpression and radiation response in glioblastoma multiforme. , 2001, International journal of radiation oncology, biology, physics.

[20]  P. Gascoyne,et al.  Particle separation by dielectrophoresis , 2002, Electrophoresis.

[21]  Q. Pankhurst,et al.  Applications of magnetic nanoparticles in biomedicine , 2003 .

[22]  H. Amini,et al.  Label-free cell separation and sorting in microfluidic systems , 2010, Analytical and bioanalytical chemistry.

[23]  G. Carpenter,et al.  The biochemistry and physiology of the receptor-kinase for epidermal growth factor , 1983, Molecular and Cellular Endocrinology.

[24]  Genee Y. Lee,et al.  The morphologies of breast cancer cell lines in three‐dimensional assays correlate with their profiles of gene expression , 2007, Molecular oncology.

[25]  A. Ellington,et al.  Inhibition of Cell Proliferation by an Anti-EGFR Aptamer , 2011, PloS one.

[26]  Jennifer L Hunt,et al.  Mutant Epidermal Growth Factor Receptor (EGFRvIII) Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting , 2006, Clinical Cancer Research.

[27]  Ron Kimmel,et al.  Efficient Dilation, Erosion, Opening, and Closing Algorithms , 2002, IEEE Trans. Pattern Anal. Mach. Intell..

[28]  P. Kolm,et al.  Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation. , 1996, International journal of radiation oncology, biology, physics.

[29]  Andrew D Ellington,et al.  Nanotextured substrates with immobilized aptamers for cancer cell isolation and cytology , 2012, Cancer.

[30]  C. James,et al.  Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[31]  B. Barlogie,et al.  Flow cytometry in clinical cancer research. , 1983, Cancer research.

[32]  G. Carpenter,et al.  EPIDERMAL GROWTH FACTOR * , 1982, The Journal of biological chemistry.