APS March Meeting 2012
Volume 57, Number 1
Monday–Friday, February 27–March 2 2012;
Boston, Massachusetts
Session A1: Focus Session: Novel Instrumentation and measurements for Biomedical Research
8:00 AM–11:00 AM,
Monday, February 27, 2012
Room: 203
Sponsoring
Unit:
GIMS
Chair: Larry Nagahara, National Cancer Institute
Abstract ID: BAPS.2012.MAR.A1.4
Abstract: A1.00004 : Single cell microfluidics for systems oncology*
8:36 AM–9:12 AM
Preview Abstract
Abstract
Author:
Rong Fan
(Department of Biomedical Engineering, Yale University)
The singular term ``cancer'' is never one kind of disease, but deceivingly
encompasses a large number of heterogeneous disease states, which makes it
impossible to completely treat cancer using a generic approach. Rather
systems approaches are urgently required to assess cancer heterogeneity,
stratify patients and enable the most effective, individualized treatment.
The heterogeneity of tumors at the single cell level is reflected by the
hierarchical complexity of the tumor microenvironment. To identify all the
cellular components, including both tumor and infiltrating immune cells, and
to delineate the associated cell-to-cell signaling network that dictates
tumor initiation, progression and metastasis, we developed a single cell
microfluidics chip that can analyze a panel of proteins that are potentially
associated inter-cellular signaling network in tumor microenvironment from
hundreds of single cells in parallel. This platform integrates two advanced
technologies -- microfluidic single cell handling and ultra-high density
protein array. This device was first tested for highly multiplexed profiling
of secreted proteins including tumor-immune signaling molecules from
monocytic leukemia cells. We observed profound cellular heterogeneity with
all functional phenotypes quantitatively identified. Correlation analysis
further indicated the existence of an intercellular cytokine network in
which TNF$\alpha $-induced secondary signaling cascades further increased
functional cellular diversity. It was also exploited to evaluate
polyfunctionality of tumor antigen-specific T cells from melanoma patients
being treated with adoptive T cell transfer immunotherapy. This platform
could be further extended to analyze both solid tumor cells (e.g. human lung
carcinoma cells) and infiltrating immune cells (e.g. macrophages) so as to
enable systems analysis of the complex tumor microenvironment from small
amounts of clinical specimens, e.g. skinny needle biopsies. Thus, it could
potentially become a clinical tool for patient stratification based upon the
inter-cellular signaling network and designing new anti-cancer therapy by
targeting microenvironmental components.
*We acknowledge the support from the NCI K99/R00 award (4R00 CA136759-02), the Bill \& Melinda Gates Foundation GCE Award, the Alzheimer Association NIRG award and the NIH LINCS Program Grant (1 U01 CA16425201).
To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2012.MAR.A1.4