DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Chip-Based Magnetic Imager for Molecular Profiling of Ovarian Cancer Cells

Posted September 15, 2017
Hakho Lee, Ph.D., Harvard Medical School and Massachusetts General Hospital

André Lieber, M.D., Ph.D., University of Washington
Hakho Lee, Ph.D.,
Harvard Medical School and Massachusetts General Hospital

Ovarian cancer, the most deadly gynecological cancer, normally does not present symptoms until it has spread to other organs, making treatment more challenging1. This metastasis was previously thought to be solely due to local fluid movement in the abdominal area; however, we now know that ovarian cancer patients have circulating tumor cells in their blood1 which are thought to originate from tumors and are thus likely involved in metastasis and cancer progression2. This indicates a diagnostic opportunity. If it is possible to detect circulating ovarian cancer cells at an early cancer stage, then clinicians may be able to treat the disease earlier and likely improve the survival rate, which is currently at only 30% overall1.

Dr. Hakho Lee, an associate professor at Harvard Medical School and Research Scholar of Massachusetts General Hospital, was awarded an Ovarian Cancer Research Program Fiscal Year 2013 Pilot Award for his proposal to develop a system to detect and profile circulating ovarian cancer cells. Dr. Lee’s system takes advantage of differential protein expression across cell types. Specifically, different proteins on the cell surface can be highly specific to cell type, including cancer cells. By using magnetic nanoparticles (MNPs) attached to antibodies specific to particular cellular surface proteins, cancer cells can be isolated from blood samples by a magnetic field and then analyzed. Dr. Lee’s team has successfully developed a panel of three different-sized MNPs, each with a different magnetic property, which allows simultaneous detection of multiple proteins at varying ratios to determine cell type. Their group has also produced their MNP-labeled cell reader, the imaging Hall Detector (iHD), which is an integrated circuit (IC) chip for magnetic sensing. Because there is very low magnetic background noise in biological samples, the iHD has excellent signal-to-noise ratio and is capable of single-cell resolution, which means this system could detect cancer cells at very low concentrations.

To validate this system, Dr. Lee’s team added ovarian cancer cells to human blood samples and compared the iHD/MNP system to flow cytometry, an established technique for cell isolation and identification. The two systems equally identified ovarian cancer cells using two different cell surface protein markers; however, flow cytometry is more labor intensive because it requires more processing steps3 and is not as small or affordable as the new iHD/MNP system. These advantages make the iHD/MNP system capable of being scaled up for wide application as a screening tool for ovarian cancer and other difficult asymptomatic cancers in the near future. This technology gives hope of catching cancer earlier than the current standard of practice allows and would also enable more effective monitoring of cancer recurrence in patients in remission, thus paving the way for earlier interventions and better patient outcomes.

Publications

1 Yeung T-L, Leung CS, Yip K-P, et al. 2015. Cellular and molecular processes in ovarian cancer metastasis. A review in the theme: Cell and molecular processes in cancer metastasis. Am J Physiol Cell Physiol. 309:C444-456.

2 Ignatiadis M, Lee M, and Jeffrey SS. 2015. Circulating tumor cells and circulating tumor DNA: Challenges and opportunities on the path to clinical utility. Clin Cancer Res. 21(21):4786-800.

3 Lee H, Shin T-H, Cheon J, et al. 2015. Recent developments in magnetic diagnostic systems. Chem Rev. 115:10690-724.

Link:

Public and Technical Abstracts: Chip-Based Magnetic Imager for Molecular Profiling of Ovarian Cancer Cells

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Last updated Friday, September 15, 2017