lab on a chip
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
Taking Microfluidics to New Lengths
Posted on by Dr. Francis Collins
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.
Shining Light on Ebola Virus for Faster Diagnosis
Posted on by Dr. Francis Collins
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.
Snapping Together a New Microlab
Posted on by Dr. Francis Collins
Credit: Viterbi School of Engineering, University of Southern California
Just as the computational power of yesterday’s desktop computer has been miniaturized to fit inside your mobile phone, bioengineers have shrunk traditional laboratory instruments to the size of a dime. To assemble a “snap lab” like the one you see above, all scientists have to do is click together some plastic components in much the same way that kids snap together the plastic bricks in their toy building sets.
The snap lab, developed by an NIH-funded team led by Noah Malmstadt at the University of Southern California (USC) Viterbi School of Engineering, Los Angeles, is an exciting example of a microfluidic circuit—tiny devices designed to test just a single drop of blood, saliva, or other fluids. Such devices have the potential to make DNA analysis, microbe detection, and other biomedical tests easier and cheaper to perform.
