Bioengineers develop world's first microfluidic device for rapid separation and detection of non-spherical bioparticles

How the I-shape pillar array works. Non-spherical cells such as rod-shaped ones are rotated by I-shape pillar to increase their effective hydrodynamic size, isolating them from samples. Credit: National University of Singapore

A bioengineering research team from the National University of Singapore (NUS) team led by Associate Professor Zhang Yong has developed a novel microfluidic device for efficient, rapid separation and detection of non-spherical bioparticles. Microfluidic devices deal with the behavior, precise control and manipulation of fluids that are geometrically constrained to sub-millimeter scale. This new device, which separates and detects non-spherical bioparticles such as pathogenic bacteria and malaria infected red blood cells, can potentially be used for rapid medical diagnostics and treatment.

Bioparticles such as bacteria and red blood cells (RBC) are non-spherical. Many are also deformable – for example, our blood cells may change shape when affected by different pathogens in our body. Hence, the team's shape-sensitive technique is a significant discovery. Currently, separation techniques are mostly designed for spherical particles.

Though the team is focusing mainly on the rapid separation and detection of bacteria from pathological samples at the moment, their device has potential as a rapid diagnostic tool as well. Their new technique can potentially replace an age-old method of detection based on bacterial culture.

Explained Assoc Prof Zhang, "The old method was developed about 100 years ago, but it is still being used today as the mainstream technique because no new technique is available for effective separation of bacteria from pathological samples like blood. Many of the pathogenic bacteria are non-spherical but most of microfluidic devices today are for separating spherical cells. Our method uses a special I-shape pillar array which is capable of separating non-spherical or irregularly-shaped bioparticles."

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Microfluidic chip which is only slightly bigger than a Singapore $1 coin. Credit: National University of Singapore

The method developed by the NUS team can complete the diagnosis process in less than an hour compared to 24-48 hours required for bacterial detection by using conventional methods. Their device is also efficient in separating red blood cells (RBCs) from blood samples as RBCs are non-spherical. This enables rapid detection of diagnostic biomarkers which reside in blood sample.

One of the most challenging aspects for the team was designing and fabricating a device that is capable of detecting even the smallest dimension of bioparticles and still provide reasonably good throughput (amount which can be processed through the system in a given time).

How it works and moving forward

Scientists have tried to address the problem of separating non-spherical bioparticles by using techniques such as restricting the flow of particles but these have not shown to be as effective. However, the NUS Bioengineering team's I-shape pillar array device has proven to be successful.

The I-shape pillar array induces rotational movements of the non-spherical particles which in turn increases the effective hydrodynamic size of the bioparticles flowing in the device, allowing for efficient separation. Their design is able to provide 100 percent separation of RBCs from blood samples, outperforming conventional cylindrical pillar array designs.

The device can also potentially separate bioparticles with diverse shapes and sizes. The team has tested their device successfully on rod-shaped bacteria such as Escherichia coli (common bacteria which can cause food poisoning). So far, this has been difficult to achieve using conventional microfluidic chips.

The team's findings were published in the reputed journal Nature Communications on 27 March 2013, in a manuscript titled "Rotational separation of non-spherical bioparticles using I-shaped pillar arrays in a microfluidic device".

Said Assoc Prof Zhang, "With our current findings, we hope to move on to separate other non-spherical bioparticles like fungi, with higher throughput and efficiency, circumventing the spherical size dependency of current techniques."

More information: "Rotational separation of non-spherical bioparticles using I-shaped pillar arrays in a microfluidic device" Nature Communications, 27 March 2013.

Journal reference: Nature Communications

Provided by National University of Singapore

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New device could cut costs on household products, pharmaceuticals

A web-like, gel structure is formed after fluid passes through the flow device. The unit of measurement is 1 micron. Credit: Environmental Molecular Sciences Laboratory and University of Washington

Sometimes cost saving comes in nanoscale packages. A new procedure that thickens and thins fluid at the micron level could save consumers and manufacturers money, particularly for soap products that depend on certain molecules to effectively deal with grease and dirt. Researchers at the University of Washington published their findings online April 9 in the Proceedings of the National Academy of Sciences.

Read the back of most shampoos and dishwashing detergents and you'll find the word "surfactant" in the list of active ingredients. Surfactant molecules are tiny, yet they are the reason dish soap can attack an oily spot and shampoo can rid the scalp of grease.

Surfactant molecules are made up of two main parts, a head and a tail. Heads are attracted to water, while the tails are oil-soluble. This unique structure helps them break down and penetrate grease and oil while immersed in water. It also makes the soaps, shampoos and detergents thicker, or more viscous.

Soap manufacturers add organic and synthetic surfactants – and often a slew of other ingredients – to their products to achieve a desired thickness and to help remove grease and dirt. These extra ingredients add volume to the soap products, which then cost more to manufacture, package and ship, ultimately shifting more costs to consumers, said Amy Shen, a UW associate professor of mechanical engineering and lead author of the paper.

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This is a diagram showing how the microfluidics device works. Water mixed with salt and soap is injected into a spout (left back). The fluid travels through a series of posts (see enlarged segment) that cause the fluid to thicken. Credit: University of Washington

The research team's design could create the same thickening results without having to add extra ingredients.

"Our flow procedure can potentially help companies and consumers save a lot of money," Shen said. "This way, companies don't have to add too many surfactants to their products."

Researchers found that when they manipulated the flow of a liquid through microscopic channels, the resulting substance became thicker. Now, scientists add a lot of salt, or alter the temperature and level of acidity to induce this change, but these methods can be expensive and more toxic, Shen said.

The team built a palm-sized tool called a microfluidics device that lets researchers pump water mixed with a little detergent and salt through a series of vertical posts. The distance between posts is about one-tenth the size of a single human hair. That micron-sized gap squeezes the liquid as it flows, causing it to quickly deform. The end result is a gel-like substance that's more viscous and elastic.

When researchers looked at high-resolution images of the end product, they saw a series of wormlike rods attaching and intermingling with each other, creating an entangled web. This structure stayed intact after the procedure was complete, which suggests this process can create a permanent, scaffold-like network that could prove useful for biological applications, Shen said. She is collaborating with other UW researchers to try to create stable structures that could house enzymes and other biomarkers for detecting certain diseases.

Shen and her team also discovered that when they pumped a thicker, more elastic fluid through the device, the opposite effect happened – the gel became thinner and more porous. This could be useful in biomedical applications, Shen said, though it hasn't yet been tested. In theory, a semi-solid gel could be injected into veins, then transform into a thinner liquid, delivering drugs throughout the body.

Researchers hope one eventual outcome will be a scaled-up industrial design of their microfluidics device that could help manufacturers churn out soap products that aren't filled with an excess of added materials. Shen has presented her initial findings at Procter & Gamble Co.

"What we can provide are all of the important parameters for operating conditions so companies can have an industrial design to achieve their goals," Shen said.

More information: www.pnas.org/content/early/2013/04/03/1215353110.abstract

Journal reference: Proceedings of the National Academy of Sciences

Provided by University of Washington

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