Development path and current status of the NANIVID: a new device for cancer cell studies

Cancer cells create a unique microenvironment in vivo which enables migration to distant organs. To better understand the tumor microenvironment, special tools and devices are required to monitor the interactions between different cell types and the effects of particular chemical gradients. This study presents the design and optimization of a new, versatile chemotaxis device called the NANIVID (NANo IntraVital Device). The device is fabricated using BioMEMS techniques and consists of etched and bonded Pyrex substrates, a soluble factor reservoir, fluorescent tracking beads and a microelectrode array for cell quantification. The reservoir contains a customized hydrogel blend loaded with EGF which diffuses out of the hydrogel to create a chemotactic gradient. This reservoir sustains a steady release of growth factor into the surrounding environment for many hours and establishes a concentration gradient that attracts specific cells to the device. In addition to a cell collection tool, the NANIVID can be modified to act as a delivery vehicle for the local generation of alternate soluble factor gradients to initiate controlled changes to the microenvironment such as hypoxia, ECM stiffness and etc. The focus of this study is to design and optimize the new device for wide ranging studies of breast cancer cell dynamics in vitro and ultimately, implantation for in vivo work.

[1]  Alar Ainla,et al.  A microfluidic pipette for single-cell pharmacology. , 2010, Analytical chemistry.

[2]  A. Giaccia,et al.  Hypoxia, inflammation, and the tumor microenvironment in metastatic disease , 2010, Cancer and Metastasis Reviews.

[3]  James Castracane,et al.  A new chemotaxis device for cell migration studies. , 2010, Integrative biology : quantitative biosciences from nano to macro.

[4]  M. Nieto,et al.  Cell movements during vertebrate development: integrated tissue behaviour versus individual cell migration. , 2001, Current opinion in genetics & development.

[5]  James Castracane,et al.  Device for in-vivo study of the tumor micro-environment , 2010, MOEMS-MEMS.

[6]  Charles H. Graham,et al.  Hypoxia-driven selection of the metastatic phenotype , 2007, Cancer and Metastasis Reviews.

[7]  S. Boyden THE CHEMOTACTIC EFFECT OF MIXTURES OF ANTIBODY AND ANTIGEN ON POLYMORPHONUCLEAR LEUCOCYTES , 1962, The Journal of experimental medicine.

[8]  Vermont P. Dia,et al.  The role of nutraceutical proteins and peptides in apoptosis, angiogenesis, and metastasis of cancer cells , 2010, Cancer and Metastasis Reviews.

[9]  P. Vaupel,et al.  Hypoxia in cancer: significance and impact on clinical outcome , 2007, Cancer and Metastasis Reviews.

[10]  Erik Sahai,et al.  Macrophages promote the invasion of breast carcinoma cells via a colony-stimulating factor-1/epidermal growth factor paracrine loop. , 2005, Cancer research.

[11]  James Castracane,et al.  A new diagnostic for cancer dynamics: status and initial tests of the NANIVID , 2009, MOEMS-MEMS.

[12]  Rakesh K Jain,et al.  In vivo imaging of extracellular matrix remodeling by tumor-associated fibroblasts , 2009, Nature Methods.

[13]  R. Futrelle,et al.  Cell behavior in Dictyostelium discoideum: preaggregation response to localized cyclic AMP pulses , 1982, The Journal of cell biology.

[14]  James Castracane,et al.  The NANIVID: a new device for cancer cell migration studies , 2008, SPIE BiOS.

[15]  G. Schultz,et al.  EGF and TGF-alpha in wound healing and repair. , 1991, Journal of cellular biochemistry.

[16]  P. A. Dimilla,et al.  Vascular smooth muscle cell durotaxis depends on substrate stiffness gradient strength. , 2009, Biophysical journal.

[17]  F. Sturtz,et al.  Improved agarose gel assay for quantification of growth factor-induced cell motility. , 2007, BioTechniques.

[18]  Rachel W. Kasinskas,et al.  A multipurpose microfluidic device designed to mimic microenvironment gradients and develop targeted cancer therapeutics. , 2009, Lab on a chip.

[19]  Albrecht Schwab,et al.  Directional Cell Migration and Chemotaxis in Wound Healing Response to PDGF-AA are Coordinated by the Primary Cilium in Fibroblasts , 2010, Cellular Physiology and Biochemistry.

[20]  J. Condeelis,et al.  Breast Cancer Cells Isolated by Chemotaxis from Primary Tumors Show Increased Survival and Resistance to Chemotherapy , 2004, Cancer Research.

[21]  Yu Zai,et al.  CoCl2-induced expression of p300 promotes neuronal-like PC12 cell damage , 2008, Neuroscience Letters.

[22]  Jeffrey Wyckoff,et al.  Description and characterization of a chamber for viewing and quantifying cancer cell chemotaxis. , 2005, Cell motility and the cytoskeleton.

[23]  Jerry A Nick,et al.  Recombinant human activated protein C reduces human endotoxin-induced pulmonary inflammation via inhibition of neutrophil chemotaxis. , 2004, Blood.

[24]  David J Beebe,et al.  A platform for assessing chemotactic migration within a spatiotemporally defined 3D microenvironment. , 2008, Lab on a chip.

[25]  D Zicha,et al.  A new direct-viewing chemotaxis chamber. , 1991, Journal of cell science.

[26]  Mehmet Toner,et al.  Microfluidic system for measuring neutrophil migratory responses to fast switches of chemical gradients. , 2006, Lab on a chip.

[27]  Mingming Wu,et al.  A hydrogel-based microfluidic device for the studies of directed cell migration. , 2007, Lab on a chip.

[28]  J. Segall,et al.  The collection of the motile population of cells from a living tumor. , 2000, Cancer research.

[29]  Albert Folch,et al.  Measurement of cell migration in response to an evolving radial chemokine gradient triggered by a microvalve. , 2006, Lab on a chip.

[30]  J. Jansen,et al.  The influence of nanoscale topographical cues on initial osteoblast morphology and migration. , 2010, European cells & materials.

[31]  Shur-Jen Wang,et al.  Effective neutrophil chemotaxis is strongly influenced by mean IL-8 concentration. , 2004, Biochemical and biophysical research communications.

[32]  A. Vengellur,et al.  The role of hypoxia inducible factor 1alpha in cobalt chloride induced cell death in mouse embryonic fibroblasts. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[33]  Donald R Schwartz,et al.  Remodeling of the extracellular matrix through overexpression of collagen VI contributes to cisplatin resistance in ovarian cancer cells. , 2003, Cancer cell.

[34]  J. Segall,et al.  Lamellipodia in invasion. , 2001, Seminars in cancer biology.

[35]  Hans-Joachim Gabius,et al.  Inhibition of human retinal pigment epithelial cell attachment, spreading, and migration by the human lectin galectin-1 , 2009, Molecular vision.