Trying to find rare circulating tumour cells (CTCs) in a patient's blood is akin to finding specific grains of sand mixed into a vast beach. These tiny cells break away from tumours and travel through the bloodstream. Finding them early can be crucial for diagnosing and treating cancer. However, blood is packed with millions of other cells, such as red blood cells, white blood cells, and platelets, making those few CTCs incredibly difficult to spot. Scientists have been working to develop more effective methods for separating these rare cells from the rest of the blood.
Now, researchers from the Indian Institute of Technology (IIT) Guwahati are pushing the boundaries of what's possible using tiny channels and electric forces. They have been using computer simulations to design a microchip that can perform this difficult separation task with incredible precision. Their work focuses on a technology called Dielectrophoresis, or DEP. In simple terms, DEP is a force that acts on tiny particles, like cells, when they are placed in an electric field that isn't uniform, meaning the electric field is stronger in some places than others. It acts as an invisible force that pushes or pulls particles depending on their properties and their position within the uneven electric field.
The scientists designed a virtual microchannel, essentially a tiny tunnel for liquid, with special grooves and metal strips as electrodes along the sides. When a voltage is applied to these electrodes, it creates a non-uniform electric field inside the channel. The key to DEP is that the force it exerts on a particle depends heavily on the particle's size and its electrical properties compared to the liquid it's in. In this study, they used a specific frequency (100 kHz) and voltage range (6-7 volts) that caused what's called negative DEP (nDEP). This means the particles are pushed away from the areas where the electric field is strongest.
The DEP force is proportional to the cube of the particle's radius (R³). This means if one particle is twice as big as another, the DEP force on it is 8 times stronger. Circulating tumour cells are significantly larger than red blood cells, white blood cells, and platelets. So, when the researchers simulated a mixture of these cells flowing through their grooved microchannel with the electric field on, the much larger CTCs felt a much, much stronger nDEP force pushing them away from the electrodes compared to the smaller blood cells.
By carefully designing the channel shape, grooves, and electrode placement, they found that eight flat electrodes were most effective. They could direct the different cells to separate outlets by controlling the flow speed using a faster buffer flow to help push cells along. The simulation showed that the smallest particles (platelets) stayed near the top, followed by RBCs, then WBCs, and finally, the largest particles (CTCs) were pushed most strongly by the DEP force and ended up at the very bottom outlet.
In their simulations, the team achieved a 100% separation efficiency for the circulating tumour cells. This means that every CTC that entered the channel exited through the intended outlet, wholly separated from the other blood cells. They also reported a high transmissivity, meaning that most of the cells that entered made it out, achieving 98% for CTCs. This is important for not losing the rare cells you're trying to find. The grooves in the channel were found to be crucial, as they helped control the electric field and fluid flow. This made a perfect separation possible, which didn't occur in simulations without the grooves. They also tested different electrode shapes and found flat ones worked best for separation quality, although pointed ones were faster.
While other devices have been developed to separate cells using microfluidics and DEP, they often struggle to achieve complete separation efficiency, especially when dealing with multiple types of cells simultaneously, or they require additional steps or techniques to obtain good results. This study is significant because it computationally demonstrates that the complete separation of four different particle types – platelets, RBCs, WBCs, and CTCs – is possible using just the DEP technique in a specifically designed grooved microchannel. This could lead to simpler, more effective devices.
However, it's important to remember that this study is based on computer simulations. The next crucial step is to take these promising results and fabricate a physical microchip based on the design and test it with real blood samples. The simulation also used a simplified model for the fluid (assuming it's like plain water, called a Newtonian fluid), while real blood is more complex, and cells can be squishy and change shape. The researchers noted that future work could utilise more complex fluid models to investigate how these factors might impact the separation.
A device based on this simulation could be a game-changer for early cancer detection. By wholly and efficiently separating CTCs from a small blood sample, doctors could potentially find cancer earlier, monitor how treatments are working, and better understand how cancer spreads. Because microfluidic devices are small, they can be manufactured relatively inexpensively, utilise minimal sample volumes, and potentially lead to faster, less invasive diagnostic tests that could even be used outside traditional labs, bringing advanced medical testing closer to patients. It's a significant step towards powerful lab-on-a-chip technologies that could revolutionise healthcare.
This research article was written with the help of generative AI and edited by an editor at Research Matters.