A programmable microfluidic device developed at Institute of Science Tokyo, Japan, combines deterministic lateral displacement, a microfluidic technique that is used to separate particles according to their size, with temperature-responsive polymer micropillars to dynamically change the separation conditions along a single channel. Using this device, the researchers successfully separated multiple particle populations. Additionally, they efficiently isolated viable cancer cells, white blood cells, and red blood cells from diluted whole blood.
Biological samples comprise multiple cells and particles varying in size, shape, properties etc. Separation of such fractions from biological samples is the foundation of various fields such as biomedical research, diagnostics, and cell-based therapeutics. However, samples such as blood contain cells with overlapping sizes, making it difficult to isolate multiple fractions. Conventional microfluidic separation systems often rely on fixed separation thresholds and need multiple devices to isolate all fractions.
To fill this gap, a research team from Institute of Science Tokyo (Science Tokyo), Japan, developed a spatially programmable deterministic lateral displacement (DLD) system using temperature-responsive polymer micropillars within the DLD array. The team was led by Professor Takasi Nisisako from the Cutting-edge Biomedical Engineering Research Center, Institute of Biomedical Engineering, and the Laboratory for Future Interdisciplinary Research of Science and Technology, Institute of Integrated Research, Science Tokyo. He was accompanied by Assistant Professor Yusuke Kanno from the Laboratory for Future Interdisciplinary Research of Science and Technology, Institute of Integrated Research, and graduate student Ze Jiang from the Department of Mechanical Engineering, School of Engineering, Science Tokyo. Their study, published online on July 29, 2026, in Lab on a Chip , demonstrates how a single DLD array can be programmed for different separation conditions at different positions along a single microfluidic channel by controlling the temperature across the array.
DLD is a well-known technique that separates particles according to their size as they flow through a series of microscopic pillars arranged in an offset pattern. Particles larger than the critical diameter (the size threshold for migration) are repeatedly pushed sideways by the pillars in bump mode, while smaller particles follow the inter-pillar gaps in a zigzag fashion. In conventional DLD systems, this threshold is fixed by the pillar geometry. In contrast, the new system contains temperature-responsive poly( N -isopropylacrylamide) or PNIPAM polymer pillars that allow the threshold to be regulated.
“PNIPAM hydrogel changes its volume with temperature. At lower temperatures, the micropillars swell and narrow the gaps between them; at higher temperatures, they shrink and widen the gaps,” explains Nisisako.
These temperature-induced changes in pillar geometry regulate and alter the size threshold for particle migration. The researchers used two Peltier elements to establish a temperature gradient along the DLD array. This created a spatially varying separation threshold, allowing particles to encounter different separation conditions as they traveled through the channel. A particle could therefore switch from bump to zigzag mode at a position determined by its size.
Using this approach, the researchers separated three-component mixtures of polystyrene particles into three outlet fractions. Particles measuring 13.0, 9.94, and 5.65 µm were separated with purities of 92.9%, 90.0%, and 97.8%, respectively. They then tested four particle populations to demonstrate the device’s flexibility. By changing the temperature window, they altered which populations were separated or grouped without changing the physical chip’s design. At 23–25 °C, the 20.2 and 13.0 µm particles were grouped at one outlet, while the 9.94 and 5.65 µm particles were collected separately. At 24–26 °C, the two larger populations were separated, while the two smaller populations were grouped together.
“By independently controlling the temperatures at the two ends of the channel, we can spatially program the separation profile of the developed DLD array. This allows a single device to perform different separation tasks without changing its fabricated geometry,” notes Nisisako.
The researchers next tested diluted whole blood spiked with MCF-7 breast cancer cells. The device directed the three cell populations into separate outlets, with 94.8% of processed MCF-7 cells remaining viable. Because cells can deform and change orientation, the geometry-based critical diameter was treated as a design reference rather than a universal cell-specific threshold.
By adjusting the temperature window, the same chip can be programmed to process different mixtures without redesigning. In future, researchers plan to focus on improving throughput and expanding the number of outlets through additional thermal control zones, parallel channels, and integrated temperature sensors.
Artwork illustrating the study has also been selected to appear on the outside front cover of a forthcoming issue of Lab on a Chip .
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About Institute of Science Tokyo (Science Tokyo)
Institute of Science Tokyo (Science Tokyo) was established on October 1, 2024, following the merger between Tokyo Medical and Dental University (TMDU) and Tokyo Institute of Technology (Tokyo Tech), with the mission of “Advancing science and human wellbeing to create value for and with society.”
Lab on a Chip
Experimental study
Cells
Spatially programmable deterministic lateral displacement for multi-stage microfluidic separation
29-Jul-2026
There are no conflicts to declare.