Research Articles


Battling cancer with the help of a chip

By 2030, about 22 million people could be diagnosed with cancer each year, up from 14 million people in 2012, according to projections by the World Health Organization. A new microfluidic chip could give doctors a valuable tool to isolate and study the so-called Circulating Tumor Cells (CTCs). The CTCs originate from a primary tumor location, spread through the circulatory system, and contribute to the development of cancer metastasis.

This device, designed and implemented by Dr. Sajay Bhuvanendran, who worked in a collaborative project between scientists from Singapore’s Agency for Science, Technology and Research’s Institute of Microelectronics (IME) and NTU’s School of Electrical and Electronic Engineering (EEE) under the supervision of Prof. Poenar Daniel and Dr. Chang Chia-Pin, can better isolate circulating tumour cells in cancer patients’ blood samples. These cells, which can form secondary tumours in patients, can be used to predict how the disease will evolve in them and their survival chances.

The chip uses a method called negative selection that eliminates all unwanted cells and components in blood samples. Firstly, it employs magnetic particles that attach themselves to white blood cells when the blood sample is pumped through the chip. Two rows of magnets in the chip then attract and trap the white blood cells.

Secondly, red blood cells are filtered out using a specially designed membrane that has rectangular slits with rounded ends. The shape of the slits, which resembles an elongated race track, allows red blood cells to easily pass through them and fluid flow can still take place even if a large cell blocks most of a slit’s opening. Therefore, the slits in the specially designed membrane are more effective than the typical circular pores that were used in traditional filters.

The CTCs, meanwhile, are captured on the membrane because they are unable to pass through the slits.

When the scientists tested their chip with two millilitres of blood that were spiked with tumour cells of various types, it removed more than 99.9% of the white blood cells, nearly all of the red blood cells and captured more than 80% of the tumour cells. The chip, which processes the samples in just 50 minutes, can capture up to about 95% of the tumour cells in any sample, and at least 77% of them.

This new biochip improves on other hydrodynamic and biorheological methods that rely on the inherent differences between circulating tumour cells and other cells in blood, such as their size, density, hydrodynamic size, shape and stiffness and deformability. All these methods suffer from a well-known trade-off between recovery efficiency and purity which thus prevents achieving high performance.

While researchers and clinicians have become more interested in methods to isolate circulating tumour cells in recent years, there is still no standardised and optimised platform to do so. In this respect, this newly developed miniaturised system provides a way to remove white blood cells without centrifugation and red blood cells without chemicals, both of which would require multiple sample handling steps that can drastically reduce the yield, lengthen the processing time significantly, and can even damage the captured cells. With this new invention, doctors and researchers can easily capture circulating tumour cells with both high efficiency and high purity, and use them for subsequent analysis, e.g. genomic investigations.


By Professor Poenar Daniel Puiu, School of EEE
Published on 14 Nov 2016