NEW YORK – A new European project aims to develop microfluidic technology to isolate and culture circulating tumor cells that could be used to predict cancer metastasis and guide treatment. The effort, called 3DSecret, commenced earlier this year with a total budget of €3.4 million ($3.8 million) and will run through the end of 2026.
Researchers from the International Iberian Nanotechnology Laboratory (INL) in Braga, Portugal, are leading 3DSecret. Cambridge, UK-based microfluidics firm Sphere Fluidics is the sole commercial partner and has the right to commercialize any resulting technology.
Other participants include the University of Vigo in Spain; the Italian research institute Fondazione Bruno Kessler; the Clinical Academic Center of Braga in Portugal; and Tecnalia Research and Innovation, a technology development center based in Derio, Spain.
Because Sphere is based in the UK, 3DSecret is being funded in part through UK Research and Innovation, the country's national funding agency. According to Sara Abalde-Cela, a staff researcher at INL and the lead investigator on the project, the European Innovation Council contributed €2.9 million to the project and UKRI the remaining €500,000.
3DSecret aims to develop technologies to understand the stochastic patterns behind metastasis at the single-cell level and to predict the development of cancer.
To that end, the researchers will devise a microfluidic platform to isolate circulating tumor cells and culture them into three-dimensional spheroids of 100 to 1,000 cells for multiparametric analysis. This will include surface-enhanced Raman spectroscopy (SERS) metabolomics profiling to monitor spheroid growth kinetics as well as sequencing of the spheroids. These will retain the clonal information from the original cell and require no DNA amplification, reducing the cost of sequencing.
"With single-cell sequencing, though very useful and interesting, the bottleneck is the cost and the accumulation of errors due to the need for amplification, so we will be avoiding those with our technology," commented Abalde-Cela.
The metabolomics and genomics data will be used to inform an artificial intelligence algorithm that will eventually be able to identify cells causing metastasis and other underlying patterns.
Such tools could be used in the future to diagnose cancer as well as to guide disease treatment, she said, for example by predicting a patient's malignancy score from a liquid biopsy. The technology could also support the discovery of potential "metastatic-associated -omic panels" and even serve as a drug testing platform, she added.
Abalde-Cela works within INL's medical devices group, where she is focused on developing optofluidic platforms for the diagnosis and monitoring of cancer. In her work, she has integrated Raman spectroscopy with biosensors to detect single cells and mechanisms of metastasis, coauthoring a paper in ACS Applied Nano Materials last year describing the use of SERS for cancer diagnosis.
As a technology partner, Sphere Fluidics will contribute its microfluidic, droplet-based Cyto-Mine single-cell isolation and assay platform. The system integrates the isolation, screening, sorting, imaging, and verification of single cells. Sphere Fluidics will also support the development of an integrated microfluidic device, the 3DSecret-chip, for the formation of 3D spheroids from single cancer cells.
According to Sphere Fluidics Chief Technology Officer Richard Hammond, the firm is designing new chips for 3DSecret. "They are based heavily on our existing know-how in pico-droplet microfluidics, particularly pico-droplet formation, pico-injection, and maintaining long-term cell stability in biochips," he said. The chips will increase the pico-droplet size range in order to accommodate spheroids and utilize hydrogels, and will integrate new measurement modalities such as Raman spectroscopy, he noted.
Abalde-Cela also serves as chief technology officer of RubyNanomed, a five-year-old firm based in Braga that has developed a microfluidic device, called the RubyChip, to isolate cancer cells from the blood of metastatic cancer patients. She said that 3DSecret will also use the RubyChip to isolate cancer cells for further analysis, adding that the company, which is not an official project member, could potentially license and commercialize technologies developed at 3DSecret, too.
However, "Sphere Fluidics is the first candidate to do so and has the right of first refusal," Abalde-Cela said. She added that if the technology is developed by several partners, project participants will file IP together and co-manage potential licenses.
Sphere Fluidics CEO Frank Craig agreed. "We have had some discussions on this, and the other grant partners, all academic, see Sphere, the sole industrial partner, as being ideally positioned to commercialize any emerging technology or products that the project generates," he said.
For Sphere, a 2010 University of Cambridge spinout, 3DSecret is another opportunity to build out the number of applications for its platform, a stated goal. To date, its technology has found use in drug discovery and gene editing, among other applications. The technology developed as part of 3DSecret could find use among Sphere's existing biopharma clients, according to a company spokesperson.
According to Craig, the company has worked to build out its team in the past year, particularly on the commercial side. Hammond joined the firm in December, and Kenneth Hitchner was appointed chairman of its board of directors earlier this week.
The company also raised $40 million in venture capital funding in 2021 to expand the range of applications it supports, as well as to raise its headcount — currently 70 employees — and to invest in technology development. In addition, the firm has signed on a dozen global distributors to cover major markets and hired more direct sales personnel in the UK, Germany, Switzerland, and Scandinavia, Craig said.