Source: uFluidix, by Pouriya Bayat. AI-generated summary by biochip.com, published . Not independently reviewed.
Key takeaways
- A two-stage Dean Flow Fractionation chip processed about 100 microliters of blood in five minutes without centrifugation.
- The PMMA device removed about 96% of red blood cells and recovered 70% to 80% of leukocytes.
- Its diagnostic performance across broad clinical populations has not yet been established.
Researchers have built a two-stage microfluidic chip that separates platelets and white blood cells from about 100 microliters of whole blood in roughly five minutes, without centrifugation or chemical labels. The system is designed to preserve a crucial but fragile part of blood biology: the interactions between platelets and leukocytes, also called white blood cells. Platelets help blood clot, while leukocytes coordinate immune responses, and the way these cells interact can reveal signs of thrombosis, inflammation, and treatment response. Standard laboratory preparation can alter those interactions because spinning blood in a centrifuge and repeatedly transferring samples can activate platelets unintentionally. The new device uses carefully shaped channels and fluid forces to sort cells according to their size. In tests, the polymer chip removed most red blood cells, retained substantial fractions of platelets and leukocytes, and produced lower activation-marker signals than conventional preparation approaches. It also processed blood from fever patients and enabled repeated measurements in diabetic mice using small sample volumes. The work points toward gentler blood preparation for research and potentially for future near-patient testing workflows.
Why blood preparation can change the answer
Blood testing often begins with a seemingly routine task: separating the cells of interest from a crowded mixture. But platelets are highly responsive cells. Like a smoke alarm that is useful because it reacts quickly, a platelet can be triggered by physical stress or changes in its surroundings, creating a signal that may not reflect the patient's biology.
That sensitivity creates a problem for studies of platelet activation and platelet-leukocyte aggregates, meaning platelets physically attached to white blood cells. Conventional centrifugation generally needs larger blood volumes and several handling steps. Those steps can disturb native cell-cell contacts or activate platelets before researchers measure them.
Sorting cells with curved channels
The platform uses Dean Flow Fractionation, or DFF, a label-free cell-separation method. Label-free means it does not depend on antibodies, magnetic beads, or fluorescent tags to identify and pull out cells. Instead, it exploits how cells move through liquid flowing around curves.
A useful analogy is a river bend. Water moving through a bend forms secondary swirling currents, and objects of different sizes do not all follow exactly the same path. Inside the chip's curved microchannels, larger leukocytes experience stronger inertial lift forces and move toward the inner wall, while smaller platelets are carried by Dean-flow currents toward the outer wall.
The first stage is a spiral channel that directs leukocytes, platelets, and red blood cells into different outlets. Red blood cells mainly move to a central waste outlet. The second stage sends the leukocyte-rich fraction through a serpentine channel, where the cells become more tightly focused while side outlets remove roughly 70% to 80% of the surrounding sheath fluid.
From a prototype to a sturdier chip
The team first tested the channel geometry in devices made from polydimethylsiloxane, or PDMS, a silicone-like material widely used for early microfluidic prototypes. After confirming the separation behavior, they transferred the design to polymethyl methacrylate, or PMMA, a transparent rigid plastic that could better support mechanically robust and scalable manufacturing.
The PMMA chip was made by computer numerical control machining and thermal bonding of two plastic layers. Its enlarged outlet reservoirs let users collect sorted cells directly with a pipette. That design choice matters for small samples because it reduces dead volume, the liquid left behind in tubing or channels that cannot be recovered.
What the device recovered
For each run, whole blood was diluted tenfold and fed into the spiral channel at 150 microliters per minute. A sheath buffer entered through a separate inlet at about 900 to 1,000 microliters per minute, helping position the blood stream and guide cells into their size-dependent paths.
The PMMA system removed about 96% of red blood cells. It recovered approximately 70% to 80% of leukocytes and 45% of platelets, showing the practical tradeoff in the design: it does not capture every platelet, but it produces usable platelet- and leukocyte-enriched fractions from a small initial sample.
Just as important, untreated platelets collected by the device showed little expression of P-selectin, a surface protein commonly used as a marker of platelet activation. Compared with conventional platelet-rich plasma preparation and commercial red blood cell depletion, DFF-processed samples also had lower signals from platelet and neutrophil activation markers. Neutrophils are a type of white blood cell that acts as an early responder during infection and inflammation.
Testing patient and animal samples
The researchers applied the workflow to blood samples from 20 patients with fever. The chip-based measurements reproduced expected differences from healthy controls, including lower platelet counts and higher leukocyte counts. The collected fractions also worked with standard hematology analysis and digital holographic microscopy, an imaging technique that reconstructs cells from how they alter light.
In a diabetic mouse model, the small-volume requirement offered another advantage. Researchers could track platelet activation and neutrophil-platelet interactions at multiple time points using about 100 to 200 microliters of blood from the same animals. That can reduce reliance on terminal blood collection, in which animals are euthanized to obtain a final sample.
Why This Matters
Many biological measurements depend as much on sample preparation as on the final instrument used to read the sample. A chip that separates relevant blood cells quickly while limiting artificial activation could make studies of clotting and inflammation more reproducible, especially when samples are scarce or serial sampling is needed.
The work also illustrates a practical route for inertial microfluidics, which uses fluid motion rather than complex chemical labeling to sort cells. Future studies will need to establish how well this approach performs across broader clinical populations and whether its recovered fractions support specific diagnostic decisions. For now, the device offers a compact way to preserve more of the blood's original cellular relationships before analysis begins.