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HP Labs explores using its microfludics expertise to detect cancers

By Simon Firth, HP Labs Correspondent

October 8, 2019

Members of HP’s microfluidics research group based in Palo Alto

Members of HP’s microfluidics research group based in Palo Alto

A team in HP’s Print Adjacencies and Microfluidics Lab is working to develop a new method for isolating rare cancer cells. Their research project deploys a combination of hydrodynamic and electric fields to separate cells based on their electrical properties and could result in a new tool for liquid biopsies that is cheaper and more accurate than existing methods. 

“HP has decades of experience in manipulating fluids at the microscopic level,” notes Viktor Shkolnikov, microfluidics research lead within HP’s Print Adjacencies and Microfluidics Lab. “We’re now leveraging that knowledge base to improve the technologies available for detecting the evidence of cancer in blood.”

The state of the art

Liquid biopsies take advantage of the fact that cancers metastasize by releasing cells into the bloodstream. Many of these cells are cleared by the immune system, but others can find a new home in the body and begin to grow uncontrollably. A liquid biopsy filters a blood sample in some way to separate out the free-floating cancer cells and enable identification and then treatment of the cancer.

“This has a number of advantages over a traditional cancer biopsy which requires a surgical intervention to remove a sample from the original tumor that is both invasive and can end up spreading the cancer cells,” Shkolnikov explains.

Liquid biopsies typically follow one of two basic methods, either separating complete cells (known as circulating tumor cell biopsies) or finding snippets of cancer DNA in the blood (known as circulating tumor DNA or vesicle biopsies). Both are problematic, however. The former yields whole cells that let you discover whether the mutations it detects are “cooperative” and therefore likely to metastasize, but has trouble distinguishing between cancer cells and other objects, such as white blood cells. That forces diagnosticians to spend money on investigating cells that aren’t actually cancerous.

Circulating tumor DNA or vesicle biopsies, meanwhile, can more easily yield evidence of specific cancers, but the absence of whole cancer cells makes it hard to know which part of a tumor the material came from, which in turn makes it hard to know whether the cancer that you find is likely to metastasize.

“You're basically trying to find about 10 cells in a billion–that’s both very interesting and extremely challenging, and it requires a multidisciplinary effort.”

Viktor Shkolnikov, microfluidics research lead, HP Print Adjacencies and Microfluidics Lab

A better liquid biopsy – based on HP printing technology

The approach taken by the HP Labs team is a variation on the circulating tumor cell biopsy method. Instead of using a characteristic like cell size to filter a blood sample, however, it exploits the fact that cancer cells are known to have specific electrical properties that differ from other kinds of cells and even other cancers.

“By applying a combination of hydrodynamic fields and electric fields to the blood, we can separate out cells based on their electrical properties,” says Shkolnikov. “And based on that we can provide information that can be used to prescribe on a molecular level a customized therapy.”

The new approach has the potential to increase the yield of cancer cells in a specific volume of blood when compared to existing circulating tumor cell biopsy methods and at the same time increase the purity of the cell sample.

The effort builds on HP’s deep experience with high quality liquid ink printing which requires directing milliliters of fluid with picolitre precision. But it adds a new challenge: singling out individual entities within the liquid that are extremely rare.  

“You're basically trying to find about 10 cells in a billion,” observes Shkolnikov. “That’s both very interesting and extremely challenging, and it requires a multidisciplinary effort – it's a biology problem as well a problem in fluid mechanics and in the interaction of fluids with electric fields, and there are plenty of materials science issues in there to solve as well.”

Shkolnikov’s team have already demonstrated that the cell separation is possible in a lab setting and they hope eventually to develop a device fabricated using equipment very similar to the machines that manufacture HP inkjet cartridges. The technique, he believes, has the potential to at least match current solutions in terms of quality – and very possibly outperform them – at a much lower cost.

It also promises to be what’s known as a label-free technique. Current circulating tumor cell isolation methods have to mark target cells with an antibody which impacts the quality of the separation and also alters the composition of the cell.

“Our long term dream would be to create a new HP instrument for doing single cell analysis for rare cells that could join existing, highly precise bio-medical instruments such as the  HP D300e Digital Dispenser,” Shkolnikov says. “And there are other research areas that this technology might one day prove useful for, such as the separation and identification of fetal or immune cells – it’s an exciting space for our lab to be working in.”