Nanopore Scanning May Detect Biomarkers in Cancer Cells

Nanopore technology may soon be adapted for early disease detection.

Using tiny nanopore scanners that can detect individual DNA molecules may lead scientists to discover biological markers in cancer cells that may help clinicians diagnose colorectal and lung cancers at their earliest stages, according to a new study.

Professor Amit Meller, of the Faculty of Biomedical Engineering at the Technion-Israel Institute of Technology, leads a research group that is a partner in BeyondSeq, an international research consortium looking for new methods of decoding genetic and epigenetic information from medical samples.

“We are the only lab in the consortium working on early diagnosis of cancer biomarkers, which… will allow doctors to combat the cancers much more effectively and save human lives,” Meller explained. “Currently there are no good ways to diagnose colorectal cancer and lung cancer at early stages. Usually these cancer are diagnosed at later stage (stage 2 or above) in which the patients may already have multiple secondary tumors, hence highly complicating treatment.”

The nanopore technology consists of tiny holes, about 100,000 times smaller than the thickness of a piece of paper, drilled in ultra-thin silicon membranes. Scientists then pass a current of electrically charged salt ions through the nanopore, attracting DNA and other similar molecules that have their own natural electrical charge.

The DNA gets passed through the pore and as they slide from one side of the membrane to the other, the pore acts as a scanner. Information about the DNA properties, such as its length and sequence variations, are collected from both optical and electrical signals given off as the molecule passes through the pore.

Meller explained that his team will be using the nanopores to look at slight variations in the DNA nucleotides, which have already been identified as an important biomarker in colorectal and lung cancers.

“We can encode the nucleotides variations in the KRAS gene with sets of color-emitting dyes and read the information with our nanopore sensor,” he said. “We hope that our nanopore technology can be adapted for early detection, where the sensing of these biomarkers is currently extremely challenging and not accessible by conventional methods.”

Nanopores could prove to be especially useful in scanning for cancerous cells as they possess the ability to scan very small amounts of molecules, finding the few cancerous molecules in a pool of healthy blood or tissue.

The team is also developing a nanopore-based method to detect epigenetic modifications at the single-molecule level. Epigenetic modifications are chemical changes made to a DNA molecule. The chemical changes do not affect the sequence of DNA letters, but they do affect how the protein encoded by the gene is expressed inside a cell.

Nanopores allow researchers to see if a piece of DNA has some of these epigenetic instructions attached to it, hopefully allowing scientists to gain a better understanding of how diseases like cancer develop in the future.

Meller and his colleagues have worked to develop nanopore technology for more than 15 years. They demonstrated in a paper published in Scientific Reports that the pores could detect the presence of a single transcription factor, or a protein that activates the production of messenger RNA from the DNA.

The pore’s screening capabilities were even effective enough to detect the different between 2 separate ways that the transcription factor could bind itself to the DNA, each with its own transcriptional effects.

Another paper by the research team showed that nanopore technology could detect different ways that proteins could be altered by another small protein called ubiquitin. This protein is responsible for tagging larger proteins for recycling by the cell. A third paper demonstrated that nanopores can be used as optical scanners to read out a multicolored “barcode” engineered on DNA molecules.

With further research and development, scientists will hopefully be able to ascertain specific details about the inner workings of specialty pharmacy diseases such as cancer.