Skip to main content
Premium Trial:

Request an Annual Quote

IBM Looks to Develop Applications for Nanoscale Sort-by-Size Microfluidics Chip


NEW YORK (GenomeWeb) – IBM has developed a silicon microfluidics chip that can sort biological particles by size. With a proof-of-concept paper now in the literature, the company is looking to develop applications for the technology, which handles entities as small as 20 nanometers.

The chip features a technology called deterministic lateral displacement (DLD) pillar arrays. Like the "Price Is Right" TV show game "Plinko," DLD pillar arrays take advantage of the fact that particles will more or less bounce to the left or right of a narrow impediment. By manipulating the gaps between pillars and the angles in which they're arrayed, the IBM researchers are able to nudge larger particles to one side where they can be binned.

In a recent Nature Nanotechnology paper, a team led by IBM researchers described an incredibly small DLD pillar array, dubbed "nano-DLD," which was able to sort particles between 20 nm and 110 nm.

"This is a stake in the ground showing what we can do with IBM technology," IBM researcher Josh Smith, a lead author on the paper, told GenomeWeb. "It shows the ability to resolve particles at the nanoscale. We can split particle populations with laser focus, taking a population of particles and pull out particles of a specific size."

While it's still early in development — there isn't even a way to count up the sorted particles yet — IBM researchers have already thought up a number of applications they'd like to target with the technology. Exosomes, the vesicles rich in biomarkers (and which can be biomarkers themselves), will be an early focus. To that end, IBM has already entered into a collaboration with Carlos Cordon-Cardo, chair of pathology at Mount Sinai Health System.

But Smith and fellow IBM researcher Gustavo Stolovitzky think that further development could make their chip a broadly applicable platform for lab-on-a-chip technology and diagnostics in general.

Smith predicted that the chips are so versatile that they could become a commodity, like computer chips.

"We are very interested in making a product that has a salient impact and could become a business that self sustains," Stolovitzky said. "But we are not a diagnostics company. We need to find the right partners to do this with in the areas that are beyond the technology."

With a long history of hardware development, Smith said the group working on the nano-DLD pillar array has been together for about two and a half years. "It was put together with the mandate to produce hardware that can separate, detect, and manipulate single molecules on chip," Smith said. "We decided to first focus on that separation component." 

DLD pillar arrays had been pioneered more than a decade ago by Robert Austin at Princeton University. But until now, the technology focused on larger particles, about 1,000 nanometers or more. That scale allows separation of cells from, say, blood, but there wasn't much benefit to getting incrementally smaller, Smith said.

"Biologically speaking, it's very uninteresting until you get down to about 200 microns, where you start to encounter viruses," he said. But getting a DLD array that small is incredibly difficult — and IBM's chip features a much smaller array. One nano-DLD array could fit on the head of a single pillar on the earlier generation of technologies, he said.

The power to separate particles as small as 20 nm opens up many possibilities and IBM is looking at number applications to make use of its technology.

Early on, it'll be focusing a lot on exosomes, which are difficult to isolate. Existing approaches to isolating exosomes include cell culture centrifugation, filtration, and precipitation. Some existing commercial offerings for this job include Qiagen's exoEasy Maxi kits, Thermo Fisher Scientific's Total Exosome Isolation products, and BioVision's ExoPure immunoplates.

Simply collecting exosomes in sample preparation is one possible direction to take the chip, Smith said.

"The lowest-hanging fruit is on the preparative side," Smith said. "There's a lot of expense [and] a lot of lab space that goes into sorting materials. We're looking at a cartridge throw-away system where the research simply dispenses the sample and gets the sorted outcome they want on which to do further analysis."

For a researcher interested in exosomes from a particular cell type, expressing a particular membrane protein, antibodies could be designed against those proteins to increase their "size." The pillar array could be designed to slough off all the smaller exosomes in a sample, enriching for the exosome of interest.

"It's not just a binary system," he said. "You can get a prismatic effect. By choosing the gap size and angle of the pillars, you can splay out exosomes of different size ranges." And, analogous to flow cytometry, it could be possible to direct single exosomes into particular wells, where they could be opened up and their cargo analyzed.

The collaboration with Mount Sinai and Cordon-Cardo will be the first test of the technology outside IBM, using it to advance basic exosome biology in the context of prostate cancer.

"By bringing together Mount Sinai's domain expertise in cancer and pathology with IBM's systems biology experience and its latest nanoscale separation technology, the hope is to look for specific, sensitive biomarkers in exosomes that represent a new frontier to offering clues that might hold the answer to whether a person has cancer or how to treat it," Cordon-Cardo said in a statement.

"We are starting off with cell lines and not necessarily patient samples," said Stolovitzky, who is also an adjunct professor at the Icahn School of Medicine at Mount Sinai.  "Eventually we would like to do this with prostate cancer patients looking at specific markers and the exosomes that could determine how aggressive a prostate cancer is in a patient."

Mount Sinai, with its access to patient samples, is the kind of partners IBM will need to advance development of diagnostic applications for nano-DLD arrays, Stolovitzky said. The IBM team has other pilot projects, but no other institutional partners, though they're very interested in finding more.

"We are interested in partnering with other domains, industries that could complement us. We are experts in tech and they are experts in a potential product," he said.