Thursday, November 21, 2024
11/21/2024
PROJECT SUMMARY As the cancer drug industry suffers from the lowest success rate in developing cancer-cure drugs, cell migration assessment assays that evaluate the transition of cells from a benign to a metastatic phenotype have gained more attention. Given the fact that metastatic cancer cells are substantially harder to eradicate than those that are benign, migratory propensity is now understood to be a key metric in both assessing cell migration behavior and screening anti-migratory compounds. However, conventional cell migration assays suffer from high cost of equipment, labor-intensive procedures and non-biomimetic culture environment. In addition, high-throughput, real-time quantification of collective cell migration requires live-cell microscopic monitoring that requires expensive microscope systems and fluorescent cell labeling for automatic tracking. Also, most conventional cell migration assays are performed on flat culture surfaces which lack topographical or mechanical cues necessary to provoke a metastatic phenotype and induce fast, directed collective cell migration observed during in vivo metastasis. The proposed cell migration assay platform incorporating anisotropic nanopatterned polymer substrates provides a more robust alternative to chemotactic systems. Enhanced biomimicry in this culture environment will enhance response sensitivity of the migrating cancer tissues in presence of test compounds, yielding a more predictive assay. In this proposed platform, we propose to integrate unique ion-permeable nanotopographic polymer substrates with a label free, impedance-based interdigitated electrode array (IEA) biosensor for detecting real-time quantification of collective cell migration in a high-throughput manner. We hypothesize that changes in IEA impedance magnitude can be reproducibly correlated to the migration distance, enabling real-time calculation of migratory velocity of the collective cell cultures. We further predict that such a relationship will permit the evaluation of dynamic, nanotopographically- guided tissue responses to anti-migratory agents. Finally, we anticipate that, aided by the proposed platform's biomimetic nanotopography, this system will significantly outperform prior art in its predictive capacity in evaluating cell migration kinetics. To test these hypotheses, single and multi-well unpatterned and nanopatterned IEA sensors will be fabricated and integrated with a simple, custom-made impedance analyzer. Reproducible correlations will be established between collective cellular migration distance and sensor impedance. Once this correlation is established, the IEA sensor will be used to test a series of pharmaceutical compounds through cellular migration assays. Lastly, nanopatterned culture data obtained through this project will be compared to scientific literature data to further evaluate the predictive utility of the proposed nanoIEA platform. Successful validation of this nanoIEA system will clear the way for the commercialization of a product that stands to advance the efficacy of preclinical cancer drug screening, thereby significantly leading to streamlined drug development.
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