A New Liquid Biopsy Chip Developed at WPI Detects Circulating Tumor Cells in 100 Percent of Blood Samples from Stage 1-4 Breast Cancer Patients

A carbon nanotube liquid biopsy chip captured tumor cells in all seven tested breast cancer blood samples.

Image: Illustrative figure from a related study: Mitrogiannopoulou AM et al., Micromachines (2023), CC BY 4.0

Source: WPI (July 23, 2019). AI-generated summary by biochip.com, published . Not independently reviewed.

Key takeaways

  • WPI's carbon nanotube liquid biopsy chip captured circulating tumor cells in all seven tested breast cancer samples, spanning stages 1 through 4.
  • In spiked blood tests, the chip captured 89% to 100% of fluorescently tagged cancer cells and captured no tumor cells from two healthy samples.
  • The patient study included only seven breast cancer samples, so larger clinical validation is still needed.

Worcester Polytechnic Institute researchers developed a liquid biopsy chip that captured circulating tumor cells from all seven blood samples collected from patients with stage 1 through stage 4 breast cancer. The device uses a carbon nanotube coating to help separate these rare cancer cells from the vast number of normal cells in blood. Circulating tumor cells, often called CTCs, are cells shed by a tumor that travel through the bloodstream and can seed tumors elsewhere in the body. In tests with blood samples spiked with fluorescently labeled cancer cells, the chip captured between 89% and 100% of the target cells. It also captured CTCs in every patient sample while detecting no tumor cells in samples from two healthy participants. The team designed the device to retain living individual cells and cell clusters, allowing them to be counted, identified, and potentially grown for later analysis. Reported in Lab on a Chip, the work points toward a less invasive way to study cancer cells that may be difficult to find before a tumor has spread. The early results are promising, but they come from a small breast cancer cohort and do not yet establish the chip as a clinical diagnostic test.

Finding rare cells in a crowded sample

Detecting CTCs is difficult because they are extraordinarily scarce. Balaji Panchapakesan, a mechanical engineering professor at WPI and the project lead, compared the challenge to finding a needle in a haystack: a blood sample may contain only one to 10 tumor cells among a billion blood cells.

That scarcity matters because cancer mortality often rises when tumors remain undetected until they are advanced or inoperable. CTCs may also offer clues about metastasis, the process in which cancer cells leave an original tumor, travel through blood, and establish tumors in other organs.

A carbon nanotube surface built for attachment

The device centers on a small well in a silicon and glass wafer whose bottom is lined with carbon nanotubes. These microscopic tubes are made of carbon and create a firm textured surface that cancer cells can preferentially attach to. A useful analogy is a selective patch of Velcro: the chip is not simply filtering cells by size, but creating a surface to which CTCs tend to stick.

Panchapakesan's team based the design on the idea that traveling tumor cells need to attach in conditions that are not naturally favorable for attachment. The team had previously shown that CTCs preferentially adhere to carbon nanotubes, whereas white blood cells generally do not. That difference helps leave tumor cells on the chip while unwanted white blood cells can be removed.

Protecting fragile circulating tumor cells

The physical design also reflects a biological constraint. Recent studies cited by the team indicated that CTCs are more fragile than researchers had once believed and face mechanical and environmental stress while moving through blood. Panchapakesan said the cells need a rocklike matrix for attachment because a softer surface would demand too much energy from the cell.

This approach joins mechanical engineering with cancer biology. Rather than relying only on a molecular marker that may appear on some tumor cells but not others, the nanotube surface aims to exploit a behavior shared by invasive circulating cancer cells: their ability to attach.

Preparing blood before it reaches the chip

Red blood cells present another practical obstacle. They greatly outnumber CTCs and tend to settle at the bottom of the chip, where they could block tumor cells from reaching the carbon nanotube layer. The researchers addressed that problem by lysing the red blood cells, meaning they broke them apart before placing a blood sample on the device.

The team reported that this red-cell lysis step did not affect the CTCs. Once the sample reached the nanotube-lined well, captured tumor cells could be counted and identified, and the design was intended to make them accessible for culture and further laboratory analysis.

What the breast cancer tests found

In controlled tests, the researchers added known numbers of fluorescently tagged cancer cells to blood. The chip captured between 89% and 100% of those cells, with sensitivity increasing as blood stayed in contact with the nanotubes for longer periods. Sensitivity describes how effectively a test finds the target it is designed to detect.

The more clinically relevant test used blood from seven breast cancer patients spanning stages 1 through 4. The chip captured CTCs from all seven samples, producing 100% sensitivity within this small group, while no tumor cells were captured from samples from two healthy participants. It also captured individual CTCs with multiple phenotypes, meaning cells with different observable biological characteristics, from both early-stage and late-stage patients.

Why cell diversity matters

A tumor is not always a uniform mass of identical cells. Cancer cells can differ in their features and behavior, especially as disease progresses. A capture method that favors only a narrow subset could miss cells that matter for understanding a patient's disease.

The WPI device was designed to capture CTCs of different sizes and types, including clusters as well as individual cells. Cell clusters are particularly important to study because they represent groups of tumor cells traveling together, though the reported findings do not establish how the chip's performance would compare with other systems across a large and diverse patient population.

Why This Matters

Liquid biopsy technologies seek cancer information from blood rather than from a surgically removed tissue sample. For patients, a blood-based approach could eventually make repeated testing more practical, which may help clinicians monitor how a cancer changes during treatment. For researchers, retrieving living CTCs could provide material for studying the genetic changes associated with metastasis.

The work involved researchers from WPI, the Department of Neurological Surgery at the University of Massachusetts Medical School, and the James Graham Brown Cancer Center at the University of Louisville School of Medicine. Its immediate contribution is a chip platform that demonstrated strong capture performance in laboratory-spiked blood and in a limited set of breast cancer samples. Next steps would need to test the technology in larger patient groups and determine whether its CTC measurements can reliably support early detection, prognosis, or treatment monitoring in real clinical settings.

Topics: Cancer

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