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Swedish Team to Develop Nanobiosensor Platform for Blood-Based Cancer Diagnostics

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NEW YORK (GenomeWeb) – A team of Swedish researchers has received SEK 30 million ($3.3 million) to develop a new nanotechnology platform for detecting blood-borne markers in lung and breast cancer.

The Royal Institute of Technology (KTH) is leading the new project which is set to commence in January 2017. Researchers from Karolinska Institutet, SciLifeLab, and Acreo Swedish ICT, an electronics research institute based in Stockholm, are also taking part in the effort, which is being primarily funded via the Erling-Persson Family Foundation.

Jan Linnros, a professor of materials physics at KTH and project leader, told GenomeWeb that the roots of the current effort date back a decade to the development of a silicon-based electrical biosensor platform. While others have previously tried to use such platforms to detect circulating tumor cells in blood samples, Linnros said that such approaches have faced "major difficulty," as few circulating tumor cells are typically obtained from blood samples.

The researchers' solution to this problem will be to detect DNA or protein biomarkers in exosomes isolated from fine needle biopsies or blood of cancer patients, using their platform. These exosomes should not only come in "much higher quantities," Linnros said, but also reflect the tumor's RNA, microRNA, and surface proteins.

KTH and its partners are looking to pair two in-house detection technologies to do this. The first, described in a 2008 Nano Letters paper, is the use of silicon chips to detect electrical current changes in streptavidin binding to biotin. In the March 2016 edition of the journal Biosensors and Bioelectronics, the researchers outlined another method for label-free detection that works by monitoring changes in electric currents as biomolecules bind to the surface of a capillary channel. To validate the approach, they measured various protein-ligand and protein-protein systems.

According to the authors, the technology could be used to detect biomolecules at a concentration as low as 100 picomolar.

"We are striving for multiple sensing on the same chip for several proteins and DNA strands simultaneously," said Linnros. "We have demonstrated detection of protein and DNA using our sensors," he added, noting that the group ultimately aims to be able to deliver a functional platform for sensing cancer-specific exosomes by the time the project concludes in 2020.

Using the technology, the group will hone methods for detecting cancer-associated biomarkers in exosomes captured from patient blood samples. According to Linnros, they also hope to be able to detect therapeutic tumor targets, including mutated cell receptors like EGFR in non-small cell lung cancer, as well as similar growth factor receptor targets in breast cancer.

"The team at Karolinska already has a biobank of plasma samples from which exosomes have been extracted for other types of analyses," said Linnros. "In addition, there will be a prospective collection of samples during treatment of NSCLC patients with different growth factor receptor-targeting therapies," he said. Linnros added that the exosomes will be extracted from samples including plasma, serum, fine-needle biopsies, and pleural effusions.

The research team will also undertake massively parallel sequencing to characterize both primary tumors and exosomes, Linnros said. They will also analyze blood samples from patients undergoing lung cancer treatment with drugs targeted toward mutated growth factor receptors or immunological signaling pathways.

"In the in vitro model systems of NSCLC, we will test various growth factor receptors and possibly other therapies of relevance for NSCLC," Linnros said. "It will include therapies against mutated EGFR, since those are of high clinical interest in NSCLC," he added. "Corresponding clinical samples will be used for validation."

Linnros said that his materials and nanophysics group at KTH will develop the sensor technology and carry out the sensing of the blood samples. Acreo will contribute hardware help, including clean-room processing and instrument set up, while other groups at KTH will functionalize the biosensors with DNA or protein capture reagents and carry out sequencing of the samples. Another group at Karolinska led by Rolf Lewensohn that specializes in lung cancer treatment will contribute signaling expertise, relevant in vitro model systems, as well as clinical samples from which the exosomes will be extracted and analyzed, Linnros said. Their research focus will be on markers relevant to growth factor-targeting therapies, he noted.

When asked about a clinical or commercial path for the resulting platform, Linnros said it was "too early to speculate" on the outcome of the project.

"It depends on sensor sensitivity, the multiplexing of biomarkers, and whether the technology can have a documented clinical relevance," Linnros said. "A first goal we have in mind is for monitoring of cancer patients during ongoing treatments," he added, "but developing a test for clinical application with full validation will be outside the scope of this three-year project."

The new project is one of several recently funded through the Erling-Persson Family Foundation. A separate, Karolinska-led effort recently received SEK 28 million to develop a multi-omic prostate cancer test called Stockholm3, as well as a follow-on, sequencing-based test.

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