Microfluidic Cell Sorting using a Syringe Pump

Microfluidic cell sorting is bringing a change to cell sorting in research laboratories. Unlike traditional techniques, that are often expensive, microfluidic devices are compact and efficient. Among being more cost-effective, they offer precise control over how the cells are sorted. The effectiveness of a microfluidic cell sorter largely depends on key characteristics, including throughput, ease of use, and whether the chip has sensors and pumps built in. The most common actuation product used for microfluidic cell sorting is the syringe pump.

Microfluidic cell sorting

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The ability to separate and isolate specific cell populations is essential in fields raging from immunology to oncology to regenerative medicine and personalised diagnostics. Sorting cell allows researchers to purify cell populations, enrich samples, and identify rare cells. As the demand grows for higher precision and sensitivity, microfluidic cell sorting is increasingly valuable for overcoming limitations posed by traditional technologies. While conventional methods can provide high efficiency sorting in short timescales, advances in microfluidics have enabled the realization of miniaturized devices offering similar capabilities that exploit a variety of physical principles.

Cell sorting is an integral technique in stem cell research and cell line development used to isolate specific cells or purify heterogeneous samples. In microfluidic cell sorting systems, a fluid containing cells is driven through microchannels toward detectors that guide cells into separate compartments based on specific markers or physical properties. The pumping mechanisms used in microfluidic cell sorting can broadly be categorized into active and passive types. Active pumping, such as with a syringe or peristaltic pumps, provides precise control by relying on external power sources. On the other hand, passive pumping utilizes built-in device properties like capillarity and air permeability, trading off precision for simplicity and cost-effectiveness. Active and passive sorting techniques can also be combined for particle sorting.

Microfluidic cell sorting mechanism

Advantages of using microfluidic cell sorters

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Microfluidic cell sorting offers notable advantages over traditional cell sorting techniques. Cell sorting on microchips reduces the size of necessary equipment, eliminates potentially biohazardous aerosols, and simplifies the complex protocols commonly associated with cell sorting. On top of that, microchip devices are well suited for parallelization because they enable a complete lab-on-a-chip devices for cellular isolation, analysis, and experimental processing. The label-free microfluidic device offers a cost-effective alternative to using costly antibodies or chemicals. These devices give useful information for analysing individual cells across several parameters, as well as for identifying cell kinds and understanding their biological functions. Studies carried out on the microfluidic chips demonstrated a separation efficiency raging from 88% to 100% and a purity ranging from 79% to 100%.

Usually in conventional techniques, one or multiple steps of sample preparation are required for cell sorting or cell separation. This prolongs the process and increases the risk of cross-contamination. The reagents and the biological suspensions need to be manipulated and modified to be prepared for cell sorting. However, microfluidic technology requires minimal sample preparation.

Microfluidics is known to deal with small sample volumes. The channels are in micron-scale and thus can operate with sample volumes of a few micro litres. The small sample volume can be essential when isolating a target sample. 

Syringe pumps in microfluidic cell sorting

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Syringe pumps are the most frequently employed active pumping system in microfluidic devices due to their commercial availability, ease of use, and ability to provide continuous or pulsatile flows over extended duration. These devices operate by using a piston to depress fluid from a syringe barrel creating a pressurized, controlled flow through microchannels. They support a wide range of flow rates (from 0.012 to 300 mL/min) and maintain steady operation independent of the fluidic resistance of the microfluidic device.

Despite the advantages of using syringe pumps in microfluidic cell sorting, there are some limitations that need to be considered. Firstly, their reliance on external hardware and bulky form factor makes them unsuitable for portable applications. Secondly, their finite fluid volume, potential for dead volume in connecting tubes, and susceptibility to pressure fluctuations can introduce inconsistencies in flow - particularly at the microscale. Thirdly, the mechanical oscillations caused by the stepper motors can disrupt fluid stability, through pulseless designs help mitigate this. Lastly, the laminar nature of the flow can impede adequate sample mixing, posing challenges for certain cell sorting applications.

Microfluidic cell sorting techniques

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• Microfluidic filters: Use size or deformability to separate cells, with precisely engineered pore sizes. They are simple but prone to clogging due to cell size heterogeneity.
• Hydrodynamic separation: Exploits predictable flow streamlines at low Reynolds numbers. By partitioning flows, cells can be directed based on size-dependent paths.
• Deterministic lateral displacement (DLD): Uses ordered arrays of obstacles to shift cells into specific streams. The displacement depends on size and array geometry.
• Field-flow fractionation (FFF): Applies perpendicular forces to sort particles based on how deeply they penetrate the channel flow profile.
• Microstructure-based sorting: Implements geometrical features like grooves, chevrons, or herringbones to sort particles based on size or deformability.
• Inertial separation: Relies on inertial forces in curved channels to direct cells away from streamlines, offering a clog-resistant method without external fields.
• Gravity and sedimentation: Uses gravity-induced setting, where particles separate based on density and size in specially angled and shaped channels.

Future of microfluidic cell sorting

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The future of microfluidic cell sorting is promising as it offers a large variety of cell sorting devices. Microfluidic cell sorting technologies increase the speed and accuracy in number of ways and rival current commercial devices. The microfluidic cell sorting platform offers more efficient, less complicated and more straightforward standard operating procedure. On top of that, the platform encompasses an all-in-one approach by being highly modular and having the capacity to perform multiple functions in a single compact device. This ability puts microfluidic technologies on the forefront of the next generation of high-level, post-sorting analyses such as biochemical, secretion, and cell culture assays.

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Further Reading

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• C.W. Shields IV, C.D. Reyes, G.P. Lopez (2015). Microfluidic cell sorting: A review of the advances in the separation of cells from debulking to rare cell isolation. Lab Chip. doi: 10.1039/c4lc01246a