A research collaboration between the Wyss Institute for
Biologically Inspired Engineering at Harvard
University and Childrens
Hospital Boston has created a microfluidic device that can harvest rare
circulating tumor cells (CTCs) from blood to enable their expansion in culture
for analysis. These cells, which have detached from a primary cancer site and
often create a secondary — or metastasized — tumor, hold an extraordinary
amount of information regarding patient-specific drug sensitivity, cancer
progression, and patient response to therapy. Such information could help
clinicians treat patients, but it has not been easily accessed due to the
difficulty of isolating CTCs and expanding them in culture for subsequent
analysis. In alleviating this problem, the new technology has the potential to
become a valuable tool for cancer diagnosis and personalized treatment. The
research findings appear online in the journal Lab on a Chip.
Wyss Founding Director, Donald Ingber, M.D., Ph.D., and Wyss
Postdoctoral Fellow Joo Kang, Ph.D., led the research team. Ingber is the Judah
Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and the
Vascular Biology Program at Children’s Hospital Boston, and Professor of
Bioengineering at Harvard’s School
of Engineering and
Applied Sciences. Kang is a Research Fellow at Childrens Hospital. Also on the
team were Wyss Postdoctoral Fellow Mathumai Kanapathipillai; Childrens
Hospital Research Fellow Silva Krause and Research Associate Heather Tobin; and
Akiko Mammoto, an Instructor in Surgery at HMS and Childrens Hospital.
This novel approach for capturing and culturing CTCs
combines micromagnetics and microfluidics within a cell-separation device,
about the size of a credit card, in which microfluidic channels have been molded
into a hard clear polymer. As blood flows through these channels, magnetic
beads that have been coated to selectively stick to the CTCs are used to
separate them from the other cells in the blood. The dimensions of the channels
have been designed to protect CTCs from mechanical stresses that might alter
their structure or biochemistry, as well as to maximize the number of CTCs that
can be captured.
In the lab, the new approach demonstrated extremely high
efficiency by capturing more than 90 percent of CTCs from the blood of mice
with breast cancer. Of particular significance was the fact that the captured
CTCs were able to be grown and expanded in culture. These intact living tumor
cells could be used for additional testing and molecular analysis, for example,
in screening drugs to meet the personal needs of individual patients in the
future. Further testing found that the device is sensitive enough to detect the
sudden increases in the number of CTCs that signal a cancers metastatic
transition and could therefore alert clinicians to possible disease
progression.
The Wyss Institute/Childrens Hospital team carried out
their studies with one common type of breast cancer. But the same device could
be used to address a wide range of tumor types as well as applications beyond
cancer, such as collecting circulating stem cells or endothelial progenitor
cells from the blood and growing them for use in organ repair, in the future.
About the Wyss Institute for Biologically Inspired
Engineering at Harvard University
The Wyss Institute for Biologically Inspired Engineering at Harvard University
(http://wyss.harvard.edu) uses Natures design principles to develop
bioinspired materials and devices that will transform medicine and create a
more sustainable world. Working as an alliance among Harvards Schools of
Medicine, Engineering, and Arts & Sciences, and in partnership with Beth
Israel Deaconess Medical Center, Brigham and Womens Hospital, Childrens
Hospital Boston, Dana Farber Cancer Institute, Massachusetts General Hospital,
the University of Massachusetts Medical School, Spaulding Rehabilitation
Hospital, and Boston University, the Institute crosses disciplinary and
institutional barriers to engage in high-risk research that leads to
transformative technological breakthroughs. By emulating Natures principles
for self-organizing and self-regulating, Wyss researchers are developing
innovative new engineering solutions for healthcare, energy, architecture,
robotics, and manufacturing. These technologies are translated into commercial
products and therapies through collaborations with clinical investigators,
corporate alliances, and new start-ups.
