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Quantification of live cell mass dynamics for drug efficacy assessment and growth studies

  • Author(s): Chun, Jennifer
  • Advisor(s): Teitell, Michael A
  • et al.
Abstract

Direct measurement of cell mass and growth can be difficult with traditional techniques, leaving unanswered questions about how exactly cells grow and divide and how cell mass responds to changes in state or therapeutic treatment. A challenge encountered by other developing mass measurement techniques is accommodating the breadth in the modes of growth of various cell types. This dissertation introduces and develops live cell interferometry (LCI) for the optical tracking and rapid mass profiling of live cells with varying growth types. Mass quantification is demonstrated with picogram resolution on both adherent and non adherent cells as well as single cells and colony-forming cells. The flexibility and speed of the LCI is applied to assess the sensitivity of four human breast cancer lines (BT-474, MDA-MB-231, SK-BR-3, MCF-7) to the HER2-directed monoclonal antibody trastuzumab (Herceptin) and to the growth dynamics of human pluripotent stem cells (HSF1) differentiating under retinoic acid treatment. With the LCI, detecting the sensitivity of the breast cancer lines to trastuzumab is 20 times faster than traditional proliferation assays, an important advancement towards individualized cancer treatment where patient samples are fragile. Dense clusters of stem cells also pose no barrier and intracolony motion is quantified in addition to overall colony growth.

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