Cancer Cell Chip: Life Saving Needle in a Haystack?

1 in 5 to 10 billion.  How rare is that needle in a haystack?

Suppose that you were fated to die, and only one person of all the people on Earth could save you.  You’d look very hard for that person, wouldn’t you?

Based on current world population and historic world population totals and growth, in this year, 2011, world population is forecast to reach 7 billion.  In 2025, 8 billion.  In 2050, 9.4 billion.  Unless an asteroid with our name on us does to humanity what the Chicxulub asteroid did 65,000,000 years ago to the dinosaurs, and 90% of the other species on the planet.

One person on Earth?  It’s not as far fetched as it sounds.  Why?  Because a sought-for test might find a particular one among 5 to 10 billion blood cells, and thus could save your life.


This month, Veridex, a company within the Big Pharma giant Johnson & Johnson, announced that they will partner with Massachusetts General Hospital to develop and market a microfluidics chip-based noninvasive test that can detect tiny traces of cancer cells in a blood sample.  Such a high-tech blood test could find a single cancer cell circulating in a person’s blood.

Researchers intend the test to be used by oncologists as a diagnostic tool for discovering as early as possible if a cancer has spread, and also by researchers in coming up with new drug therapies.  They did not announce an existing device, but it’s not mere “vaporware” because it’s backed by a five-year, roughly $30 million deal to develop, refine, and commercialize such a test.  That number is not exact; it depends on achieving intermediate milestones and successes.

Veridex currently has a commercialized diagnostic test that can count circulating tumor cells (CTCs), but that test does not analyze the cells for specific molecular markers, the way that pathologists perform on tumor tissue collected during surgery or from needle biopsies.  “There has been speculation that these [stray] cells are the ones that are responsible for the spreading of the disease,” noted Dr. Massimo Cristofanilli, professor and chairman of medical oncology at Fox Chase Cancer Center in Philadelphia.  “Simple enumeration tells us that this patient has a worse prognosis… Now the question is,
what other information we can gather, if we are able to capture these cells?  For example, could we do gene analysis profiling and can we get information for the best treatment?”

Experts at Massachusetts General Hospital have already developed and demonstrated, in 2007, a prototype  “CellSearch” microchip that can detect tumor cells at extremely low levels in the bloodstream.  The effort to be announced this month is aimed at drawing on the expertise of scientists familiar with how to bring such technologies to patients and doctors.

Dr. Mehmet Toner in Massachusetts General’s Center for Engineering in Medicine, director of the BioMicroElectroMechanical Systems Resource Center, says that though it may take at least five years before the test is on the market, it’s a step toward personalized medicine.  The implications for patients are significant.  “It is very big.  It has the potential to turn cancer into a chronic disease, because we can monitor patients individually and respond with treatment to the genetic makeup of their cancer.”

Toner calls the test a liquid biopsy that targets almost all solid cancers – cancers found in “solid” organs like the breast or prostate.  The patient surrenders two teaspoons of blood.  The cancer cells it finds would be analyzed and their genetic makeup determined by a battery of techniques, existing and in development, which would be useful in monitoring patients and targeting therapies to the individual.

Part of the announced coalition is Ortho Biotech Oncology Research and Development, another unit of Johnson & Johnson Pharmaceutical Research and Development. Ortho has proven expertise in clearing regulatory hurdles and clinically validating new tests.  Johnson and Johnson is a logical place for this technology.  Their company Veridex launched the first commercial test using circulating tumor cell technology in 2004.  Now, they describe circulating tumor cells as cancer cells that have detached from a tumor and are found at very low levels in the bloodstream.  Capturing, counting, and “interrogating” those cells should provide information to patients and doctors about prognoses with certain types of metastatic cancers.  Veridex already successfully brought to market one technology used to detect circulating tumor cells.


“This new technology has the potential to facilitate an easy-to-administer, noninvasive blood test that would allow us to count tumor cells, and to characterize the biology of the cells,” said Robert McCormack, Veridex’s head of technology innovation and
strategy.  “Harnessing the information contained in these cells in an in-vitro clinical setting could enable tools to help select treatment and monitor how patients are responding.”  In vitro meaning in the glassware of the lab, as opposed to in vivo, within your body, or in silico, by computer simulation.

What use is it to find one cell?  What use to count many cells?  “The value of capturing and counting CTCs is evolving as more research data is gathered about the utility of these markers in monitoring disease progression and potentially guiding personalized cancer
therapy,” said the Veridex press release.  Can this be done, inexpensively, worldwide, by minimally trained local medical workers?

“We’re limited by our ability to make it fast, easy, cheap, and something that could be done on a global scale,” said Dr. Daniel Haber, director of the MGH Cancer Center.  “Our goal is to build together a third-generation technology… that would be so easy to
use and so standard, it wouldn’t have to be a research tool.”  Haber said that the test has been used experimentally in about 200 patients.  Haber co-leads the project with Mehmet Toner.

Toner said you are likely to find just one circulating tumor cell in 5 to 10 billion blood cells.  That’s where I got my “one person in the world” figures.  In fact, a tube of blood taken during an annual exam would only have a few CTCs.  In biotech, is this the end, or a new beginning?

“The challenging goal of sorting extremely rare circulating tumor cells from blood requires continuous technological, biological and clinical innovation to fully explore the utility of these precious cells in clinical oncology,” Toner said.  “We have developed and
continue to develop a broad range of technologies that are evolving what we know about cancer and cancer care.”

Since bloodstream-borne cancer cells are tremendously rare, the microfluids chip technology must be able to detect extremely rare cells.  Once such cancer cells are detected, isolated, and intensely analyzed through a blood test, doctors could better
follow the disease’s course.  The physicians could look to see whether or not the level of
cancer cells circulating declines with treatment.  This would also let doctors test the genetics of the isolated cancer cells.  This is critical because many cancer drugs are targeted treatments that work against a cancer with a particular mutation.

Mutations?  Yes.  Researchers have demonstrated that the device can isolate enough cells to detect a specific mutation in a gene for the EGF (epidermal growth factor) receptor.  The mutation hints that patients will respond to drugs designed to inhibit this pathway.  Other scientists have shown that the FDA-approved device can also detect a molecular
marker linked to drug response.


The chip will not be used alone.  Such blood tests are hoped to be an inexpensive and
noninvasive complement to the CT scans and tissue biopsies that oncologists already use to characterize tumors.  Regular blood tests assessing tumor cell count might be used to
determine if a particular treatment is effective.

What kind of gadget detects the extremely rare cells?  The new technology uses minuscule channels carved into a silicon chip, each coated with a special glue-like
material.  When the blood flows through the channels, Haber said that the technology is able to pick up, on average, about 10 cancer cells per milliliter of blood in patients with metastatic cancer, meaning disease that has spread from a primary tumor to other parts of the body.

How big is the chip?  What does it have besides channels and glue?  It’s a business-card-size silicon chip with an array of tens of thousands of microscopic posts, each coated with a glue-like molecule that binds to a protein unique to cells from a specific type of tumor, such as breast, lung, or prostate cancer.  As blood flows through the chip, tumor cells adhere to the posts. In 2007, the researchers first showed that the chip could capture these rare cells–which make up just one in a billion to ten billion cells in blood – in sufficiently large numbers to allow analysis of the captured cells for molecular markers.  Specific markers might indicate a more aggressive form of cancer or a tumor that will respond to specific cancer drugs.  Genetic changes in the tumor over time might signal the need to change treatments.

How are the channels arranged?  The inner surface of the device has a herringbone design, generating a vortex in the blood flow.  Vortical mixing brings the cells in greater contact with antibodies on the surface of the chip.  According to research published
in 2010 in the Proceedings of the National Academy of Sciences, this chip could detect isolated clusters of tumor cells, which may reveal the cancer’s ability to spread, or metastasize, from its initial birthplace.

How far along are they now?  The Boston researchers have already developed a prototype and, collaborating with four other research institutions, have received a $15 million grant from the organization Stand Up to Cancer to test this prototype.  But that technology is expensive and complicated to use, with each chip costing about $500.  “If the technology gets more and more sensitive, we may be able to use this as an early diagnostic,” Haber said.  “You might be able to pick up any tumor which invades into the blood system, and that could mean there is a chance of catching tumors before they spread.”

What is the managerial goal, and why should this strategy work?  “What we’re trying to do is to develop a more efficient process for translating our early-stage innovations to the point where they can impact patient care,” said Frances Toneguzzo, executive director of
the office of research ventures and licensing at Partners HealthCare.  “We’re doing that by, at least in this case, partnering with a company that can provide the market information and help us with regulatory hurdles.”

“This new technology has the potential to facilitate an easy-to-administer, non-invasive blood test that would allow us to count tumor cells, and to characterize the biology of the cells,” Robert McCormack, head of technology innovation and strategy at Veridex, said in a statement.  If this works, might also detect cancer early in its course, predict the odds for a recurrence, and assess a patient’s general prognosis.


Some caution us not to hype the collaboration and intended future device.  The American Cancer Society agrees the new research is exciting, but insists that it is important to realize that it’s just another step in the scientific process.  “Researchers have been working on this and similar technologies for some time, and others have predicted a day when we will be able to diagnose cancers before they are otherwise visible by current techniques,” explained Dr. Len Lichtenfeld, ACS deputy chief medical officer.  “It is appropriate to view announcements such as the one today with enthusiasm, but recognize that we must temper that excitement with the realization that there is still much research
to be done to determine the true impact of this test on the treatment of patients with cancer.”
“They may be able to detect small amounts of cancer cells but we don’t know the significance of that.  We may be detecting things that don’t have clinical significance,” warned Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge.  As Cristofanilli said, these plans so far are “only for research.  The test is not available for clinical use.”  According to the AP, four major cancer centers – Mass General, Memorial Sloan-Kettering Cancer Center in New York City, the University of
Texas’ M.D. Anderson Cancer Center in Houston, and the Dana-Farber Cancer Institute in Boston – will begin studies using the new test this year.

This matters to me.  Without advances in biomedical science and technology, I expect to die from cancer.  My mother Patricia, who died while in experimental artificial RNA therapy at Memorial Sloan-Kettering, her mother Tillie, my father Sam, his sister Alice, and several cousins died of cancer, though my wife survived.  Maybe it will matter to you.


New test under development could find single cancer cell in blood, CNN Wire Staff, January 3, 2011

MGH test for cancer gets backing: $30m agreement aims to develop, expand use
,  Carolyn Y. Johnson, Boston Globe Staff, January 3, 2011

A Blood Test for Cancer, Technology Review Editors’ blog

Scientists Aim for Test That Could Spot Single Cancer Cell in Blood, Amanda Gardner, Business Week, January 03, 2011

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