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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


Wearable Ultrasound Patch Monitors Blood Pressure

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Placement of the blood pressure patch

Caption: Worn on the neck, the device records central blood pressure in the carotid artery (CA), internal jugular vein (Int JV) and external jugular vein (Ext JV).
Credit: Adapted from Wang et al, Nature Biomedical Engineering

There’s lots of excitement out there about wearable devices quietly keeping tabs on our health—morning, noon, and night. Most wearables monitor biological signals detectable right at the surface of the skin. But, the sensing capabilities of the “skin” patch featured here go far deeper than that.

As described recently in Nature Biomedical Engineering, when this small patch is worn on the neck, it measures blood pressure way down in the central arteries and veins more than an inch beneath the skin [1]. The patch works by emitting continuous ultrasound waves that monitor subtle, real-time changes in the shape and size of pulsing blood vessels, which indicate rises or drops in pressure.


DNA-Encoded Movie Points Way to ‘Molecular Recorder’

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Original vs. CRISPR stored images

Credit: Seth Shipman, Harvard Medical School, Boston

There’s a reason why our cells store all of their genetic information as DNA. This remarkable molecule is unsurpassed for storing lots of data in an exceedingly small space. In fact, some have speculated that, if encoded in DNA, all of the data ever generated by humans could fit in a room about the size of a two-car garage and, if that room happens to be climate controlled, the data would remain intact for hundreds of thousands of years! [1]

Scientists have already explored whether synthetic DNA molecules on a chip might prove useful for archiving vast amounts of digital information. Now, an NIH-funded team of researchers is taking DNA’s information storage capabilities in another intriguing direction. They’ve devised their own code to record information not on a DNA chip, but in the DNA of living cells. Already, the team has used bacterial cells to store the data needed to outline the shape of a human hand, as well the data necessary to reproduce five frames from a famous vintage film of a horse galloping (see above).

But the researchers’ ultimate goal isn’t to make drawings or movies. They envision one day using DNA as a type of “molecular recorder” that will continuously monitor events taking place within a cell, providing potentially unprecedented looks at how cells function in both health and disease.


Creative Minds: Rapid Testing for Antibiotic Resistance

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Ahmad Khalil

Ahmad (Mo) Khalil

The term “freeze-dried” may bring to mind those handy MREs (Meals Ready to Eat) consumed by legions of soldiers, astronauts, and outdoor adventurers. But if one young innovator has his way, a test that features freeze-dried biosensors may soon be a key ally in our nation’s ongoing campaign against the very serious threat of antibiotic-resistant bacterial infections.

Each year, antibiotic-resistant infections account for more than 23,000 deaths in the United States. To help tackle this challenge, Ahmad (Mo) Khalil, a researcher at Boston University, recently received an NIH Director’s New Innovator Award to develop a system that can more quickly determine whether a patient’s bacterial infection will respond best to antibiotic X or antibiotic Y—or, if the infection is actually viral rather than bacterial, no antibiotics are needed at all.