Microfluidic platform for solid tumor mechanics and invasion

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

↗ Live URL (may be dead)

Document text

Principal Investigator: Mingming  Wu
Organization: CORNELL UNIVERSITY
Fiscal Year: 2024
Award: $351,339
Funding agency: National Cancer Institute

Project Summary
Cancer metastasis accounts for over 90% of all cancer deaths. Important abilities of metastatic tumor cells
include breaking away from the primary tumor and invading into surrounding tissue before disseminating to
secondary tumor sites. Solid tumor stress caused by rapid growth of tumor cells and abnormality of the vascular
tissue has long been associated with poor prognosis of cancer. Despite the clinical importance, the basic
understanding of tumor mechanics and its relation to tumor invasion is lacking. This is in part due to the lack of
in vitro tools that are able to investigate quantitatively tumor mechanics in a physiologically relevant 3D setting.
Current material mechanical testing tools such as the rheometer have played important roles in our current
understanding of biomaterials and tumor mechanics. However, the conventional rheometer is not easily made
compatible with cell culture conditions and results are spatially averaged, masking important single cell and
molecular level information. Atomic force microscopy and pipette aspiration are cell culture compatible, but low
throughput. The goal of the proposed research is to develop a high throughput microfluidic rheometer for
systematic studies of tumor mechanics and invasion in a physiologically realistic 3D setting and compatible
with dynamic optical imaging at single cell and spheroid levels. We will deliver a set of principles that govern
tumor mechanics and its relation with invasion. We postulate that tumor mechanics is a key predictor for
tumor invasiveness. The proposed project is innovative because it represents the first generation of
microfluidic rheometers that are capable of full mechanical testing for tumor mechanics studies, and at the
same time compatible with tumor invasion experiments. Tools developed here can be easily extended to
use for other living materials, and lessons learned here will eventually lead to knowledge important for
developing novel diagnostic or/and treatment strategies for cancer.

Terms: <3-D><3-Dimensional><3D><Adhesion Molecule><Architecture><Assay><Atomic Force Microscopy><Behavior><Bioassay><Biocompatible Materials><Biologic Sciences><Biological Assay><Biological Sciences><Biomaterials><Bioscience><Blood Vessels><Body Tissues><Cadherin-1><Cancer Prognosis><Cancers><Cell Adhesion Molecule Gene><Cell Adhesion Molecules><Cell Body><Cell Culture Techniques><Cell Line><Cell-Cell Adhesion><Cell-Extracellular Matrix><CellLine><Cells><Cessation of life><Clinical><Data Analyses><Data Analysis><Death><Distant><Domestic Horse><Drug Delivery><Drug Delivery Systems><E-Cadherin><ECM><Engineering><Engineering / Architecture><Epithelial Calcium-Dependent Adhesion Protein><Epithelial-Cadherin><Equine><Equine Species><Equus caballus><Equus przewalskii><Extracellular Matrix><Feedback><Force Microscopy><Funding><Generations><Goals><Horses><Image><Impairment><In Vitro><Invaded><Knowledge><Learning><Life Sciences><Malignant><Malignant - descriptor><Malignant Neoplasms><Malignant Tumor><Materials Testing><Measures><Mechanics><Membrane><Metastasis><Metastasize><Metastatic Lesion><Metastatic Mass><Metastatic Neoplasm><Metastatic Tumor><Methods><Microfluidics><Molecular><Molecular Dynamics Simulation><Neoplasm Metastasis><Optics><Organ><Organoids><Pathway interactions><Physiologic><Physiological><Play><Primary Neoplasm><Primary Tumor><Prognosis><Reporter><Research><Role><Running><Scanning Force Microscopy><Secondary Neoplasm><Secondary Tumor><Secondary to><Site><Solid><Solid Neoplasm><Solid Tumor><Strains Cell Lines><Stress><Stretching><Techniques><Testing><Theoretic Models><Theoretical model><Time><Tissue Engineering><Tissues><Tumor Cell><Tumor Cell Invasion><Tumor Cell Migration><Tumor Invasion><Tumor Promotion><Uvomorulin><Work><aspirate><bioengineered tissue><biological material><cancer metastasis><cancer progression><cell adhesion protein><cell culture><cell cultures><cell type><computer program><computer programming><cultured cell line><data interpretation><diagnostic tool><engineered progenitor cells><engineered stem cells><engineered tissue><experiment><experimental research><experimental study><experiments><fabrication><force sensor><imaging><in vivo><innovate><innovation><innovative><interstitial><intra-vital imaging><intravital imaging><malignancy><mechanic><mechanical><membrane structure><microscope imaging><microscopic imaging><microscopy imaging><molecular dynamics><neoplasm progression><neoplasm/cancer><neoplastic cell><neoplastic progression><new diagnostics><next generation diagnostics><novel diagnostics><optic imaging><optical><optical imaging><pathway><pressure><rapid growth><response><social role><spheroids><technological innovation><three dimensional><tool><treatment strategy><tumor><tumor cell metastasis><tumor progression><vascular><vascular abnormality><µfluidic>