cancer detection
Detecting Cancer with a Herringbone Nanochip
Posted on by Dr. Francis Collins
Credit: Yong Zeng, University of Kansas, Lawrence and Kansas City
The herringbone motif is familiar as the classic, V-shaped patterned weave long popular in tweed jackets. But the nano-sized herringbone pattern seen here is much more than a fashion statement. It helps to solve a tricky design problem for a cancer-detecting “lab-on-a-chip” device.
A research team, led by Yong Zeng, University of Kansas, Lawrence, and Andrew Godwin at the University of Kansas Medical Center, Kansas City. previously developed a lab-on-a-chip that senses exosomes. They are tiny bubble-shaped structures that most mammalian cells secrete constantly into the bloodstream [1]. Once thought of primarily as trash bags used by cells to rid themselves of waste products, exosomes carry important molecular information (RNA, protein, and metabolites) used by cells to communicate and influence the behavior of other cells.
What’s also interesting, tumor cells produce more exosomes than healthy cells. That makes these 30-to-150-nanometer structures (a nanometer is a billionth of a meter) potentially useful for detecting cancer. In fact, these NIH-funded researchers found that their microfluidic device can detect exosomes from ovarian cancer within a 2-microliter blood sample. That’s just 1/25th of a drop!
But there was a technical challenge. When such tiny samples are placed into microfluidic channels, the fluid and any particles within it tend to flow in parallel layers without any mixing between them. As a result, exosomes can easily pass through undetected, without ever touching the biosensors on the surface of the chip.
That’s where the herringbone comes in. As reported in Nature Biomedical Engineering, when fluid flows over those 3D herringbone structures, it produces a whirlpool-like effect [2]. As a result, exosomes are more reliably swept into contact with the biosensors.
The team’s distinctive herringbone structures also increase the surface area within the chip. Because the surface is also porous, it allows fluid to drain out slowly to further encourage exosomes to reach the biosensors.
Zeng’s team put their “lab-on-a-chip” to the test using blood samples from 20 patients with ovarian cancer and 10 age-matched controls. The chip was able to detect rapidly the presence of exosomal proteins known to be associated with ovarian cancer.
The researchers report that their device is sensitive enough to detect just 10 exosomes in a 1-microliter sample. It also could be easily adapted to detect exosomal proteins associated with other cancers, and perhaps other conditions as well.
Zeng and colleagues haven’t mentioned whether they’re also looking into trying other geometric patterns in their designs. But the next time you see a tweed jacket, just remember that there’s more to its herringbone pattern than meets the eye.
References:
[1] Ultrasensitive microfluidic analysis of circulating exosomes using a nanostructured graphene oxide/polydopamine coating. Zhang P, He M, Zeng Y. Lab Chip. 2016 Aug 2;16(16):3033-3042.
[2] Ultrasensitive detection of circulating exosomes with a 3D-nanopatterned microfluidic chip. Zhang P, Zhou X, He M, Shang Y, Tetlow AL, Godwin AK, Zeng Y. Nature Biomedical Engineering. February 25, 2019.
Links:
Ovarian, Fallopian Tube, and Primary Peritoneal Cancer—Patient Version (National Cancer Institute/NIH)
Cancer Screening Overview—Patient Version (NCI/NIH)
Extracellular RNA Communication (Common Fund/NIH)
Zeng Lab (University of Kansas, Lawrence)
Godwin Laboratory (University of Kansas Medical Center, Kansas City)
NIH Support: National Cancer Institute
New ‘Liquid Biopsy’ Shows Early Promise in Detecting Cancer
Posted on by Dr. Francis Collins
Caption: Liquid biopsy. Tumor cells shed protein and DNA into bloodstream for laboratory analysis and early cancer detection.
Early detection usually offers the best chance to beat cancer. Unfortunately, many tumors aren’t caught until they’ve grown relatively large and spread to other parts of the body. That’s why researchers have worked so tirelessly to develop new and more effective ways of screening for cancer as early as possible. One innovative approach, called “liquid biopsy,” screens for specific molecules that tumors release into the bloodstream.
Recently, an NIH-funded research team reported some encouraging results using a “universal” liquid biopsy called CancerSEEK [1]. By analyzing samples of a person’s blood for eight proteins and segments of 16 genes, CancerSEEK was able to detect most cases of eight different kinds of cancer, including some highly lethal forms—such as pancreatic, ovarian, and liver—that currently lack screening tests.
In a study of 1,005 people known to have one of eight early-stage tumor types, CancerSEEK detected the cancer in blood about 70 percent of the time, which is among the best performances to date for a blood test. Importantly, when CancerSEEK was performed on 812 healthy people without cancer, the test rarely delivered a false-positive result. The test can also be run relatively cheaply, at an estimated cost of less than $500.
Cancer Metastasis: Trying to Catch the Culprits Earlier
Posted on by Dr. Francis Collins
Caption: Scaffold of a cancer cell-attracting implant as seen by scanning electron microscopy.
Credit: Laboratory of Lonnie Shea
For many people diagnosed with cancer localized to the breast, prostate, or another organ, the outlook after treatment is really quite good. Still, most require follow-up testing because there remains a risk of the cancer recurring, particularly in the first five years after a tumor is removed. Catching recurrence at an early, treatable stage can be difficult because even a small number of new or “leftover” tumor cells have the ability to enter the bloodstream or lymphatics and silently spread from the original tumor site and into the lung, brain, liver, and other vital organs—the dangerous process of metastasis. What if there was a way to sound the alarm much earlier—to detect tumor cells just as they are starting to spread?
Reporting in Nature Communications [1], an NIH-funded research team from the University of Michigan, Ann Arbor, and Northwestern University, Evanston, IL, has developed an experimental device that appears to fit the bill. When these tiny, biodegradable scaffolds were implanted in mice with a highly metastatic form of breast cancer, the devices attracted and captured migrating cancer cells, making rapid detection possible via a special imaging system. If the results are reproduced in additional tests in animals and humans, such devices might enable earlier identification—and thereby treatment—of one of the biggest challenges in oncology today: metastatic cancer.
