New cell-collection device could improve early cancer detection

MIT News ·

New cell-collection device could improve early cancer detection

MIT researchers developed a handheld system that gently collects living cells from patient samples to aid cancer testing and development of personalized medicines.

One of the main reasons that ovarian cancer is among the deadliest forms of cancer is timing: When doctors catch it early, the five-year survival rate can be north of 90 percent. But when doctors catch it late, in stages 3 or 4, five-year survival is less than half that .

About 20 years ago, researchers studying ovarian cancer discovered that many cases of high-grade serous ovarian cancer, the most common type, originate in the fallopian tubes. Detecting the disease there remains challenging, in part because its precursor lesions can be microscopic and difficult to sample.

Now researchers in the group of MIT Professor Kripa Varanasi, working with colleagues at MIT and Johns Hopkins University, have developed a handheld device capable of gently collecting living cells from specific locations to test for ovarian and many other types of cancer. The researchers believe the technique could one day be used to catch cancers earlier and more effectively. It could also be used to create treatments based on individual patient samples.

In a study describing the system in the journal Device , the researchers showed their system enables targeted sampling of newly excised tissue, and they used it to recover living cells for cultivation and testing. The device holds a small microfluidic channel against the tissue and uses a syringe to drive fluid through the channel, applying a force parallel to the tissue surface to gently detach living cells from tiny sections of tissue.

“We wanted to collect living cells from specific regions of the fallopian tube while leaving the surrounding tissue intact,” says Varanasi, senior author of the study and the Maher A. Elmasri Professor of Mechanical Engineering. “Once we have these living cells, there are many things we can do with them. We can use them for diagnostics, grow them into organoids, and build living models of disease. Ultimately, this could allow us to test how an individual patient’s cells respond to different treatments and help us develop more personalized medicines.”

Joining Varanasi on the paper are co-first authors Domitille Avalle SM ’25, MIT postdoc Bert Vandereydt PhD ’26, and Sean Parks ’20, SM ’24. The other authors are MIT PhD candidate Huaiyao Peng; Rebecca Stone, the Johns Hopkins University School of Medicine Stoddard and O’Neil Professor in Gynecologic Oncology; and Angela Belcher, MIT’s James Mason Crafts Professor and a professor of biological engineering and of materials science and engineering.

Living cells for ovarian cancer research The discovery that many high-grade serous ovarian cancers originate in the fallopian tubes has opened up new prevention options for women at increased risk, who can have their fallopian tubes removed after childbearing years, largely preserving normal hormone production.

Stone, a gynecologic oncologist at Johns Hopkins University, has long advocated for this procedure for certain women at increased risk of ovarian cancer. Belcher introduced Stone to Varanasi, and the three, together with other collaborators, received funding from Break Through Cancer, a foundation that brings together interdisciplinary teams to tackle some of the most challenging problems in cancer. Their project focuses on developing new approaches for the early detection of ovarian cancer, with the cell-collection technology forming one part of that broader effort.

The researchers began by asking whether they could collect living cells from specific regions of removed fallopian tubes to study the disease’s earliest stages.

"The idea was to see if we could find early signals from precancerous regions of concern,” Varanasi recalls.

The process traditionally involves placing surgically removed fallopian tubes in a chemical preservative and cutting the tissue into sections. The preservative maintains tissue structure, but the cells are no longer alive and cannot be grown in culture. A pathologist then looks for cancerous or precancerous regions in thin sections of the tissue under a microscope.

“It’s very time-consuming and destructive to the cells,” Varanasi says. “We wanted to bring new capabilities to pathology, so we can not only see what these cells look like, but also collect them alive and study how they behave.”

The MIT researchers saw the process firsthand while visiting surgeons in the operating room at Johns Hopkins.

“It inspired us,” Varanasi says. “We do a lot of work on fluid-surface interfaces in my lab, and we realized we could use a fluid instead of a scalpel or brush, because when you flow a fluid it applies shear stress at the interface. We thought it could work because we heard from surgeons that cells in some locations were loose and would come off during routine washing and other procedures.”

“This is exactly the kind of problem that benefits from bringing clinicians and engineers together,” Stone says. “We understand the clinical need, while the MIT team brings a very different perspective from fluid mechanics and engineering. That combination allowed us to approach the problem in a new way.”

The researchers’ new approach uses a 3D-printed microfluidic device that forms a vacuum seal with the tissue. The device confines liquid flow to a small region, where the flowing liquid creates shear stress that gently detaches living cells.

“We came up with this device where one syringe creates a vacuum that holds it against the tissue, and a second syringe pushes liquid through it,” Vandereydt says. “The vacuum creates a seal, so nothing leaks, and then we locally apply what is basically a microfluidic chip on the tissue that gently shears the cells off.”

The researchers showed they could tune the shear stress applied to the tissue and compared their approach to other cell collection workflows. They found the cells collected using their technique remained viable and grew in culture much more readily than cells detached using conventional approaches.

Finally, the researchers tested their device on fresh human fallopian tube samples, which required them to be on call for sample shipments from their collaborators at Johns Hopkins. After experiments, the samples were shipped back for conventional pathology.

“The samples could come at any time. Sometimes, we’d get an email from our collaborators at 11 p.m. saying ‘There are two fallopian tubes coming tomorrow,’” Vandereydt says. “We were able to collect living cells from those fallopian tubes and turn those into organoids, which is important for testing, disease modeling, and eventually developing personalized treatments.”

“We are developing optical approaches to identify suspicious regions of tissue, and this technology could allow us to collect living cells from exactly those locations,” Belcher says. “Being able to first see where the disease may be emerging and then collect those cells for further study could be very powerful.”

From device to diagnostic

The researchers tested the device on different types of cells and found the approach can be tuned to collect cells of all types by applying different levels of shear stress.

“It’s agnostic to the disease,” Vandereydt says. “There are very loosely adherent prostate cancer cells that detach at 1 pascal [of stress], but if you look at bone cancer cells, only a few cells detach under as high as 5 pascals of stress.”

The researchers plan for the early use of their device to involve tissue that has already been removed from the body, as that offers an easier pathway to regulatory approval. But they would also like to see their device used to swab samples inside of patients for easier testing and earlier cancer detection.

“What is exciting about this technology is the ability to collect living cells from a specific area while preserving the tissue for pathology,” Stone says. “In the future, one could imagine integrating it into routine histopathology workflows, creating a powerful new way to study carcinogenesis and fundamental biology directly from human tissue.”

Varanasi credits Break Through Cancer for enabling the project.

“Break Through Cancer brought together people working on not only ovarian cancer but also on pancreatic cancer, brain cancer, leukemia, and other cancers,” Varanasi says. “What we heard again and again is how valuable it would be to have better ways to obtain living cells from specific regions of tissue.”

The researchers hope that by making it possible to collect living cells from precise locations without removing or destroying the surrounding tissue, their approach could eventually help researchers and clinicians identify disease earlier and better understand how it develops.

“If this work can ultimately help women by enabling earlier detection of ovarian cancer, I would find that incredibly fulfilling,” Varanasi says. “That is really what motivates us — taking the science and engineering we develop in the lab and using it to make a difference in people’s lives.”

The work was supported by the Break Through Cancer Foundation.

Источник: MIT News