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Tiny cones in blood tests can help capture cancer early

A team of engineers at Chiba University in Japan created a simple and highly sensitive tool that captures cancer cells from blood samples using a device made of embossed plastic and coated antibodies.

Their microfluidic system, described in the journal The lab on the chipseven at high flow rates, capture efficiency of circulating tumor cells (CTCs) exceeding 90%. This approach can pave the way for affordable minimally invasive blood tests to detect cancer and monitor recurrences after treatment.

How the equipment works

Circulating tumor cells are rare and are known to be difficult to separate from the blood. These cells fall off from the primary tumor and may seed metastasis elsewhere in the body. While microfluidic technologies have been used to capture them before, they often require expensive, complex manufacturing steps. The new device overcomes these obstacles by embedding cell-sized microketones using polycarbonate (PC) paper.

Each microketone has a width of about 30 microns, high and arranged in a tight hexagonal pattern. The textured surfaces of these cones strongly attract antibodies without any chemical linkers. The researchers coated them with antibodies that recognize EPCAM, a protein found on many cancer cells.

Simple assembly, powerful performance

Rather than establishing complex channels, the team formed a “micro-level” channel by sandwiching PC paper between the slide and the soft polymer plate. Blood is then pumped through this gap. As the cancer cells flow, they brush onto the antibody-coated cone and stick to the protein.

  • Capture over 90% of breast cancer cells (MCF-7) at flow rates up to 100 µL/min
  • Optimal cone angle is 15° or 30°, with a cone tilt towards the flow
  • The device removes more than 99% of non-cancerous white blood cells
  • Cancer cells remain in fixed positions during multi-step fluorescence staining
  • Capture is also used for lung cancer cells (A549), although not suitable for Epcam-negative cervical cancer cells (HELA)

“There are many techniques for detecting cancer, but using minimally invasive methods to detect cancer cells with high sensitivity is a long-term challenge,” said Professor Masumi Yamada, the lead investigator of the study.

Why is the cone direction important

To maximize performance, the researchers adjusted the angle between the micropore array and the direction of flow. At 0°, most cells pass directly. However, when tilted at 15° or 30°, the cells and cones are more frequent, thereby improving capture efficiency. High-speed flow imaging confirmed that the tilted array disrupts smooth flow and increased particle interactions.

The team noted that their confocal particle tracking study notes: “regardless of its initial location, cells have an equal chance of colliding with micropores.”

Designed for real-world diagnosis

Unlike many CTC capture devices that rely on complex chemical modifications or softened polymers such as PDM, the system uses mass achievable polycarbonate plates. The surface does not require careful preparation and can contain antibody coatings in more than a year. After the cells were captured, the researchers successfully performed in situ staining within the channel, highlighting the compatibility of the device with downstream analyses.

In future clinical use, different cancer cell types can be captured by binding antibodies to labeled antibodies such as HER2 or CD44. The team also plans to test patient-derived blood samples, simulate the fluid dynamics in silicon and expand throughput.

Road to early, accessible cancer screening

The simplicity of the device can change the way we monitor cancer, which is all about recurrence in early detection and post-treatment examinations. Testing of small blood samples that only need to be processed through low-cost, high-efficiency plastic chips may one day be part of routine cancer screening.

Magazine: The lab on the chips
doi: 10.1039/D5LC00143A
Article title: Controlled nanomembrane arrays that enhance cancer cell immune control in micro AP channels
Publication date: May 28, 2025

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