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Chip Device Performs Detailed Cancer Cell Analysis

HydroSeq chip

HydroSeq chip showing channels and chambers for capture and analysis of circulating tumor cells (Yoon Lab, University of Michigan)

16 May 2019. A lab-on-a-chip device shows in tests with cancer patient blood samples to detect and analyze circulating tumor cells providing precise therapy targets. A description of the device developed at University of Michigan and report of tests with blood samples appears in yesterday’s issue of the journal Nature Communications.

A team from Michigan’s engineering and medical schools is seeking simpler and faster diagnostics for cancer patients, to provide a detailed genetic picture of the cancer, and a roadmap for physicians to find therapies that meet the precise molecular nature of the patient. Up to now, techniques for this level of analysis could provide a detailed review of a few genes, or a limited picture of many genes in a sample.

In addition, advances in liquid biopsies, blood tests that detect and capture tumor cells circulating in the blood stream, make it feasible to closely monitor the progression of a patient’s cancer without tissue biopsies requiring surgery. But circulating tumor cells usually make up only a tiny proportion of blood samples making them difficult to isolate for diagnostics, with about 100 circulating tumor cells found among billions of white and red blood cells. As such, note the researchers led by Michigan engineering professor Euisik Yoon, there’s an unmet need for a high-throughput device that provides a comprehensive analysis of blood samples that capture and identify circulating tumor cells.

The technology proposed by Yoon and colleagues uses a microfluidics, or lab-on-a-chip device they call HydroSeq to separate circulating tumor cells in blood vessels and perform a genetic analysis of the captured cells. “Our chip,” says Yoon in a university statement, “allows us to capture pure circulating tumor cells and then extract genetic information without any contamination from red and white blood cells.”

HydroSeq is a matrix of fine channels and chambers with pneumatic valves to push through individual blood cells for scanning and identification of circulating tumor cells. In addition, the channels and chambers can be scaled-up to the thousands, enabling analysis of isolated circulating tumor cells from a high volume of blood cells.

Once captured and isolated, circulating tumor cells are analyzed by HydroSeq looking for characteristic ribonucleic acid or RNA transcribed from the DNA in the tumor. The analysis uses beads with unique identifiers to react with the circulating tumor cells and identify the RNA pointing to the tumor’s DNA.

The Michigan team tested HydroSeq with blood samples first with mixed human and mouse cells. The results show the device accurately separated and identified human from mouse cells, with no cross-contamination. The researchers then analyzed blood samples from 21 breast cancer patients. Hydro-Seq isolated 666 circulating tumor cells in the blood samples, and found expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal receptor 2 (HER2) genes, characteristic breast cancer biomarkers. The authors note that the analysis shows the molecular nature of the patients’ tumors did not always match the initial diagnosis, indicating a change in the composition of the tumors over time.

Co-author and medical school professor Monika Burness plans to try the chip in an upcoming clinical trial of an experimental cancer drug. “It’s a very powerful tool,” says Burness, “to monitor, at the cellular level, what a treatment does to tumors over time.” The university filed for a patent on HydroSeq, with several authors listed as inventors.

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