题目：Microfluidic Platforms for In Vitro Molecular Diagnosis in Cancer
时间：2009年1月13日 星期二 下午2:00
地点：33678新甫京国际品牌廖凯原楼2-102会议室
报告人：Prof. Hsian-Rong Tseng（曾宪荣）
    Department of Molecular & Medical Pharmacology
    Crump Institute for Molecular Imaging
    David Geffen School of Medicine at UCLA

Alternations in intracellular signaling networks promote the proliferation and invasion of cancer cells. A
systems-oriented approach to cancer aims to define multiple signaling proteins in the networks that drive
the malignant transformation of cancers, thus necessitating a technology platform capable of detecting
multiple proteins in tumor samples. Since tumor samples are composed of mixtures of cancer, stromal,
vasculature and immune cells, such a technology platform also requires single-cell precision in order to
capture the nature of cellular heterogeneity. As a first step towards creating a technology for the profiling of
cancer signaling networks, our research group has been developing the Microfluidic Image Cytometry (MIC,
Box) technology, based on a microfluidic cell array in conjunction with an automated pipette (for cell
loading, fixation, permeabilization and immunostaining) and a fluorescence microscope (for imagining
acquisition and analysis). With the intrinsic advantages of microfluidics, including sample/reagent economy,
precise flow control, high throughput, scalability and digital controllability, the MIC technology has been
utilized to monitor multiple signaling proteins in a PI3K-Akt-mTOR signaling pathway. A number of cancer
cell lines, as well as genetically modified and primary cancer cells were cultured in the devices, and the
expression levels of receptors (EGFR and EFGRvIII), phosphotase (PTEN) and phosphorylated kinases
(pAkt, pmTOR and pS6) in the chip-cultured cells were first treated by immunocytochemistry, followed by
quantitative imaging cytometry analysis. Remarkably, the dynamic changes of those proteins upon
exogenous stimuli (e.g., growth factors and kinase inhibitors) can be kinetically monitored, providing a
potent tool to understand how certain cells response to a variety of combinations of drug treatment.
We envision that the MIC technology will be able to achieve: i) dramatic improvement in speed, accuracy
and fidelity of cancer diagnosis, ii) reduced cancer sample consumption, thereby tackling the tumor
heterogeneity issue, iii) providing signature identification to guide the implementation of targeted therapies,
iv) a perfect conjunction with the needle biopsy operation, v) greater cost efficiency compared to traditional
methods and other state-of-the-art technologies, and vi) broad application to most types of cancers.
Box. (A) The PI3K-Akt-mTOR signaling network that drives the malignant transformation of cancer. (B) Conceptual
summary of the application of the MIC technology in breast cancer research.
联系人：黄岩谊，62767408， yanyi@pku.edu.cn