Is lung cancer treatment working? This chip can tell from a blood draw

January 29, 2024
Written By:
Derek Smith, College of Engineering
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By trapping and concentrating tiny numbers of cancer cells from blood samples, the device can identify whether a treatment is effective at the four-week mark

Two GO chips are laying on a benchtop lined with a paper towel. The chips resemble rectangular microscope slides encased in glass. The inlet line is red with blood, which has also flown into the chip and completely fills the top portion of the chips' internal compartments. Along the chip, a gradient of red to gold-gray shows that the blood has only progressed halfway through the chip.
As blood flows through the GO chips, cancer cells stick to antibodies embedded in the chip. The antibodies specifically target cancer cells, so the sample is not contaminated with other parts of the blood. Image credit: Brenda Ahearn, Michigan Engineering.

Using a chip to process blood samples, doctors can monitor the amount of cancer cells in a patient’s blood to determine how well a treatment is working by the fourth week, according to a new University of Michigan study.

Such data could allow clinicians to adapt cancer treatments to patients’ needs and improve treatment outcomes.

A pair of yellow gloved hands hold a blue wafer, which looks like a glossy, flat circle. Three gold rectangles are arranged vertically on the wafer. Each rectangle is framed by a thin, gold line.
Part of the GO chip manufacturing process takes place in Nagrath’s lab. They start with silicon wafers, on which a tight array of gold dots have been etched into a rectangle pattern at the Lurie Nanofabrication Facility. The gold attracts the graphene oxide, each sheet only a single layer of atoms thick, and the antibodies are attached to the graphene oxide. These antibodies are what allow the chips to trap cancer cells. Image credit: Brenda Ahearn, Michigan Engineering.

“Currently, there’s typically a wait of weeks to months before we can fully assess the effectiveness of cancer treatment,” said Shruti Jolly, professor of radiation oncology, associate chair of community practices at U-M and co-corresponding author of the study.

“However, with this chip, we may be able to sidestep prolonged, ineffective therapy and quickly pivot to alternatives, thus saving patients from needless side effects. This technique has the potential to shift cancer diagnostics, moving from a delayed single assessment to a more continuous surveillance and facilitating the delivery of personalized cancer treatment.”

Today, clinicians use CT scans to see if a tumor shrank or grew, but only large changes in size are easily noticed. Tumor biopsies provide more exact information, but they can’t be done frequently enough to get regular updates.

Bright purple, lightning-like plasma arcs in thin filaments from the tip of the metal wand onto the blue part of the chip, resembling a waterfall. The plasma stands in stark contrast with the dark background and illuminates the wand, which rises like a stem behind the arcs.
To attach the GO chips’ covers, the engineers use a “corona wand,” which creates a high-voltage electric current that heats air into plasma. The plasma adds an electric charge to the chip that forms a permanent bond with the materials on the chip cover. The result is a tight seal that doesn’t allow any fluid to escape from the microscopic channels in the chip. Image credit: Brenda Ahearn, Michigan Engineering.

That’s why many clinicians are turning to liquid biopsies, or tests that look for signs of cancer in the patient’s blood, such as cancer cells that tumors have shed. Blood samples can be collected frequently, but they are only useful if the cells are present in high enough levels for biomedical instruments to detect.

Lung cancer is a particular problem. Other FDA-approved tools for detecting cancer cells in blood samples have proven ineffective for monitoring lung cancer treatments—likely because they targeted a single protein on the cells’ surfaces that is less common in lung cancers, the researchers say.

“We were looking for more sensitive markers of cancer that we could use to closely monitor treatments,” said Sunitha Nagrath, professor of chemical and biomedical engineering and one of the study’s corresponding authors.

Jolly and Nagrath review their research notes together, manila folders in hand. Nagrath is gesturing to a specific point on Jolly's notes, which Jolly reads with a slightly furrowed brow.
Shruti Jolly, professor of radiation oncology and associate chair of community practices at the University of Michigan, (left) and Sunitha Nagrath, professor of chemical and biomedical engineering, (right) are the corresponding authors of the study published this week in Cell Reports. Nagrath’s lab designed the chip that can capture cancer cells while Jolly enrolled patients into the clinical study. Image credit: Brenda Ahearn, Michigan Engineering.

“In some cases, only about half of cancer patients respond to the treatments, leaving the rest with poor outcomes. Treatments may also be expensive and cause adverse reactions in some patients, so it’s important for clinicians to know early on whether a treatment is going to be effective—or whether they may be better off with a different treatment.”

The “GO chip” developed by Nagrath’s team, first demonstrated in 2013, succeeded where others fell short. It traps cancer cells like a piece of flypaper traps flies. But unlike flypaper, the chip only catches its target. Antibodies mounted on microscopically thin sheets of graphene oxide in the chip—which give the device its name—recognize a wide array of cancer-specific protein markers found on the surfaces of cancer cells.

As the blood is pushed through channels in the chip, the antibodies trap cells, eventually concentrating enough to work with. With the cells locked in place, the researchers can not only count them but confirm that they are indeed cancerous and determine how the cells’ biochemistry varies between patients and treatment stages.

A thin, transparent syringe is filled with crimson blood and connected to GO chips by a thin plastic thread. The syringe is held in a gloved hand over the chips, which rest on a benchtop.
Once the GO chips are completely assembled, it’s time to add the blood samples. The researchers add the blood to a syringe, which is loaded into a programmable syringe pump. Plastic lines connect the syringe to the chips, providing a path for the blood to enter the chips. As the pump squeezes the syringe’s plunger closed, it forces blood to flow through the chip and out the other end into a waste collection tube. Image credit: Brenda Ahearn, Michigan Engineering.

To test that the GO chip could monitor lung cancer treatments, the researchers used it to collect cancer cells from the blood of 26 patients receiving both chemotherapy and immunotherapy for stage 3 lung cancer. The researchers took samples before cancer treatment and after the patients’ first, fourth, 10th, 18th and 30th weeks of treatment.

Their experiment revealed that when the number of cancer cells in a patient’s blood doesn’t decrease by at least 75% by the fourth week of treatment, their cancer is more likely to persist after treatment.

The study also showed that cancer cells collected from patients whose cancer did not respond to treatment had activated genes that may have made the cancer resilient. These genes might be good targets for future cancer therapies, but further study is required to test this idea.

The U-M study is published in the journal Cell Reports. The research was funded by the National Institutes of Health. The GO chips were built in the Lurie Nanofabrication Facility.

Shruti Jolly is also the chief clinical strategy officer for cancer services at Michigan Medicine. Sunitha Nagrath is also a co-director of Liquid Biopsy Shared Resources for U-M’s Rogel Cancer Center.