Lab-on-a-Chip Platform Performs Molecular Dissection of Single Brain Tumor Cells
New technologies for the diagnosis of cancer are rapidly changing the clinical practice of oncology. As scientists learn more about the molecular basis of cancer, the development of new tools capable of multiple, inexpensive biomarker measurements on small samples of clinical tissue will become essential to the success of genetically informed and personalized cancer therapies.
One tool in the eventual armamentarium of clinical oncologists could be the new microfluidic image cytometry (MIC) platform developed by Hsian-Rong Tseng and his colleagues at the University of California, Los Angeles and the Nanosystems Biology Cancer Center, a member of the National Cancer Institute's Alliance for Nanotechnology in Cancer. This new MIC platform can measure cell-signaling pathways in brain tumor samples at the single-cell level. The new technology combines the advantages of microfluidics and microscopy-based cell imaging in one device.
"The MIC is essentially a cancer diagnostic chip that can generate single-cell 'molecular fingerprints' for a small quantity of pathology samples, including brain tumor tissues," said Dr. Tseng. "We are exploring the use of the MIC for generating informative molecular fingerprints from rare populations of oncology samples — for example, tumor stem cells."
The researchers, who published their work in the journal Cancer Research, analyzed a panel of 19 human brain tumor biopsies to show the clinical application of the MIC platform to solid tumors. The investigators also developed a suite of new bioinformatics tools that allowed them to process and analyze the data gleaned from the MIC platform's single-cell measurements.
"Because the measurements are at the single-cell level, computational algorithms are then used to organize and find patterns in the thousands of measurements," explained Thomas Graeber, a senior investigator on the study. "These patterns relate to the growth signaling pathways active in the tumor that should be targeted in genetically informed or personalized anticancer therapies."
Microscale technology platforms are finding wide application in biological assays in which careful manipulation and measurement of limited sample amounts are required, and the new MIC platform is capable of making molecular measurements on small tumor samples provided by tumor resection and biopsy using as few as 1,000 to 3,000 cells, according to the researchers. The investigators will next apply the new platform to larger cohorts of cancer patient samples and integrate the diagnostic approach into clinical trials of molecular therapies.
This work, which is detailed in a paper titled, "A Microfluidic Platform for Systems Pathology: Multiparameter Single-Cell Signaling Measurements of Clinical Brain Tumor Specimens," was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's Web site.