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microfluidics

Detecting Cancer with a Herringbone Nanochip

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Herringbone lab on a chip
Caption: Lab on a chip with herringbone pattern. Inset shows exosomes.
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


Taking Microfluidics to New Lengths

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Fiber Microfluidics

Caption: Microfluidic fiber sorting a solution containing either live or dead cells. The type of cell being imaged and the real time voltage (30v) is displayed at bottom. It is easy to imagine how this could be used to sort a mixture of live and dead cells. Credit: Yuan et al., PNAS

Microfluidics—the manipulation of fluids on a microscopic scale— has made it possible to produce “lab-on-a-chip” devices that detect, for instance, the presence of Ebola virus in a single drop of blood. Now, researchers hope to apply the precision of microfluidics to a much broader range of biomedical problems. Their secret? Move the microlab from chips to fibers.

To do this, an NIH-funded team builds microscopic channels into individual synthetic polymer fibers reaching 525 feet, or nearly two football fields long! As shown in this video, the team has already used such fibers to sort live cells from dead ones about 100 times faster than current methods, relying only on natural differences in the cells’ electrical properties. With further design and development, the new, fiber-based systems hold great promise for, among other things, improving kidney dialysis and detecting metastatic cancer cells in a patient’s bloodstream.


Red Blood Cells and Mercury

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Red blood cells after mercury exposure

Credit: Courtney Fleming, Birnur Akkaya, and Umut Gurkan, Case Western Reserve University, Cleveland

Mercury is a naturally occurring heavy metal and a well-recognized environmental toxin. When absorbed into the bloodstream at elevated levels, mercury is also extremely harmful to people, causing a range of problems including cognitive impairments, skin rashes, and kidney problems [1].

In this illustration, it’s possible to see in red blood cells the effects of mercury chloride, a toxic chemical compound now sometimes used as a laboratory reagent. Normally, healthy red blood cells have a distinct, doughnut-like shape that helps them squeeze through the tiniest of blood vessels. But these cells are terribly disfigured, with unusual spiky projections, after 24 hours of exposure to low levels of a mercury chloride in solution.


Snapshots of Life: A Flare for the Dramatic

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lipid-covered water drop

Credit: Valentin Romanov, University of Utah, Salt Lake City

Oil and water may not mix, but under the right conditions—like those in the photo above—it can sure produce some interesting science that resembles art. You’re looking at a water droplet suspended in an emulsion of olive oil (black and purple) and lipids, molecules that serve as the building blocks of cell membranes. Each lipid has been tagged with a red fluorescent marker, and what look like red and yellow flames are the markers reacting to a beam of UV light. Their glow shows the lipids sticking to the surface of the water droplet, which will soon engulf the droplet to form a single lipid bilayer, which can later be transformed into a lipid bilayer that closely resembles a cell membrane. Scientists use these bubbles, called liposomes, as artificial cells for a variety of research purposes.

In this case, the purpose is structural biology studies. Valentin Romanov, the graduate student at the University of Utah, Salt Lake City, who snapped the image, creates liposomes to study proteins that help cells multiply. By encapsulating and letting the proteins interact with lipids in the artificial cell membrane, Romanov and his colleagues in the NIH-supported labs of Bruce Gale at the University of Utah and Adam Frost at the University of California, San Francisco, can freeze and capture their changing 3D structures at various points in the cell division process with high-resolution imaging techniques. These snapshots will help the researchers to understand in finer detail how the proteins work and perhaps to design drugs to manipulate their functions.


Shining Light on Ebola Virus for Faster Diagnosis

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Optofluidic analysis system

Caption: A rapid Ebola detection system consisting of a microfluidic chip (left) and an optofluidic chip (right), connected by a curved tube (center).
Credit: Joshua Parks, University of California, Santa Cruz

Many lessons were learned during last year’s devastating outbreak of Ebola virus disease in West Africa. A big one is that field clinics operating in remote settings desperately need a simple, rapid, and accurate test that can tell doctors on the spot—with just a drop of blood—whether or not a person has an active Ebola infection.

A number of point-of-care tests are under development, and it’s exciting to see them moving in the right direction to fill this critical need [1]. As a recent example, a paper published in Nature Scientific Reports by a team of NIH-supported researchers and colleagues shows early success in rapid Ebola detection with an automated lab on a chip [2]. The hybrid system, which combines microfluidics for sample preparation with optofluidics for viral detection, identifies Ebola at concentrations that are typically seen in the bloodstream of an infected person. It also distinguishes between Ebola and the related Marburg and Sudan viruses, suggesting it could be used to detect other infectious diseases.


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