Liquid Biopsy Chip Detects Cancer Cells in Blood

A liquid biopsy chip measures metastatic breast cancer cells in the bloodstream with great precision.

by Mark Crawford
April 10, 2017

Quick and accurate measurement of circulating tumor cells (CTCs) in the bloodstream is a popular way to learn if tumors are metastasizing in the body. Current CTC isolation techniques are mostly based on immunomagnetic and microfluidic enrichment methods, both of which present accuracy issues with low yields of CTCs.

To improve this situation, Balaji Panchapakesan, an associate professor of mechanical engineering and director of the Small Systems Laboratory at Worcester Polytechnic Institute (WPI), has developed a liquid biopsy chip that measures, with high precision, metastatic breast cancer cells in the bloodstream. Antibodies are attached to an array of carbon nanotubes at the bottom of a tiny well. Cancer cells from the blood sample settle to the bottom, where they selectively bind to the antibodies based on their surface markers, with nearly a 100-percent capture rate. That is far more effective than microfluidic approaches being used today.

A close-up of the liquid biopsy chip developed in WPI’s Small Systems Laboratory. Etched into the chip are 76 test units.   

Capturing Cancer Cells

“The research focus on capturing circulating tumor cells is quite new,” says Panchapakesan. “It is a very difficult challenge, not unlike looking for a needle in a haystack. There are billions of red blood cells, hundreds of thousands of white blood cells, and only one to ten circulating tumor cells in 7.2 milliliters of blood. Our device can find these cells with very high precision.”

Blood is fractionated into small droplets for CTC isolation. The instant detection and micro-array isolation of the CTCs are based on the technique of detecting free-energy change for specific versus nonspecific interactions using carbon nanotubes. The nanotube-micro-arrays include both detection/stratification and capture capabilities. Once the CTCs are captured by the antibodies, an electrical response is triggered, which is then detected by the electrodes.

In this study, Panchapakesan attached antibodies specific for two markers of metastatic breast cancer, EpCam and Her2, to the carbon nanotubes in the chip. When a blood sample that had been “spiked” with cells expressing those markers was placed on the chip, the device captured only the marked cells.

In addition to tumor cells, the chip also captures exosomes, which are produced by cancer cells and carry the same markers.

“These highly elusive three-nanometer structures are too small to be captured with other types of liquid biopsy devices, such as microfluidics, due to shear forces that can potentially destroy them,” says Panchapakesan. “Our chip is currently the only device that can potentially capture circulating tumor cells and exosomes directly on the chip, increasing its ability to detect metastasis. This is important, because emerging evidence suggests that tiny proteins excreted with exosomes can drive reactions that may become major barriers to effective cancer drug delivery and treatment.”

Other key functions of the chip include:

  • Multiple antibodies (for different cancers) can be functionalized on the same nanotube micro-array.
  • The design is tunable to capturing 1-80,000 individual cells or 22,500 cell clusters per device or exosomes based on differential centrifugation.
  • The entire assembly can be automated into a compact handheld device or laboratory based instrument.
  • The captured cells are viable, enabling downstream molecular analysis such as quantitative polymerase chain reaction (qPCR).

 

Cancer Screening

Although the initial work was done with breast cancer cells, Panchapakesan is confident an advanced version of his device will detect a wide range of cancer types, including lung and pancreas cancers. Within the next five years, he hopes to have prototype devices that have been tested in clinics and commercialized for breast and other types of cancer, or possibly even routine cancer screening.

“Imagine going to the doctor for your yearly physical,” says Panchapakesan. “A blood sample is drawn that can be tested for a comprehensive array of cancer cell markers. Cancers could be caught at all stages of development, and doctors would have the necessary protein or genetic information from these captured cells to customize a treatment based on the specific markers for your cancer. This would truly put your health in your own hands.”

Mark Crawford is an independent writer.

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