Mechanical properties have emerged as a significant label-free marker for characterizing deformable particles such as cells. Here, we demonstrated the first single-particle-resolved, cytometry-like deformability-activated sorting in the continuous flow on a microfluidic chip. Compared with existing deformability-based sorting techniques, the microfluidic device presented in this work measures the deformability and immediately sorts the particles one-by-one in real time. It integrates the transit-time-based deformability measurement and active hydrodynamic sorting onto a single chip. We identified the critical factors that affect the sorting dynamics by modeling and experimental approaches. We found that the device throughput is determined by the summation ofmore »
High-throughput continuous dielectrophoretic separation of neural stem cells
We created an integrated microfluidic cell separation system that incorporates hydrophoresis and dielectrophoresis modules to facilitate high-throughput continuous cell separation. The hydrophoresis module consists of a serpentine channel with ridges and trenches to generate a diverging fluid flow that focuses cells into two streams along the channel edges. The dielectrophoresis module is composed of a chevron-shaped electrode array. Separation in the dielectrophoresis module is driven by inherent cell electrophysiological properties and does not require cell-type-specific labels. The chevron shape of the electrode array couples with fluid flow in the channel to enable continuous
sorting of cells to increase throughput. We tested the new system with mouse neural stem cells since their electrophysiological properties reflect their differentiation capacity (e.g., whether they will differentiate into astrocytes or neurons). The goal of our experiments was to enrich astrocyte-biased cells. Sorting parameters were optimized for each batch of neural stem cells to ensure effective and consistent separations. The continuous sorting design of the device significantly improved sorting throughput and reproducibility. Sorting yielded two cell fractions, and we found that astrocyte-biased cells were enriched in one fraction and depleted from the other. This is an advantage of the new continuous sorting device over traditional dielectrophoresis-based sorting more »
- Publication Date:
- NSF-PAR ID:
- 10127977
- Journal Name:
- Biomicrofluidics
- Volume:
- 13
- Page Range or eLocation-ID:
- 064111
- ISSN:
- 1932-1058
- Sponsoring Org:
- National Science Foundation
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Abstract -
The dissociation of tissue and cell aggregates into single cells is of high interest for single cell analysis studies, primary cultures, tissue engineering, and regenerative medicine. However, current methods are slow, poorly controlled, variable, and can introduce artifacts. We previously developed a microfluidic device that contains two separate dissociation modules, a branching channel array and nylon mesh filters, which was used as a polishing step after tissue processing with a microfluidic digestion device. Here, we employed the integrated disaggregation and filtration (IDF) device as a standalone method with both cell aggregates and traditionally digested tissue to perform a well-controlled andmore »
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The mechanical properties of the cell nucleus are increasingly recognized as critical in many biological processes. The deformability of the nucleus determines the ability of immune and cancer cells to migrate through tissues and across endothelial cell layers, and changes to the mechanical properties of the nucleus can serve as novel biomarkers in processes such as cancer progression and stem cell differentiation. However, current techniques to measure the viscoelastic nuclear mechanical properties are often time consuming, limited to probing one cell at a time, or require expensive, highly specialized equipment. Furthermore, many current assays do not measure time-dependent properties, whichmore »
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Size-based microfluidic filtration systems can be affected by clogging, which prevents their use in high-throughput and continuous applications. To address these concerns, we have developed two microfluidic lobe filters bioinspired by the filtration mechanism of two species of manta ray. These chips enable filtration of particles around 10–30 μm with precise control and high throughput by using two arrays of equally spaced filter lobes. For each filter design, we investigated multiple inlet flow rates and particle sizes to identify successful operational parameters. Filtration efficiency increases with fluid flow rate, suggesting that particle inertial effects play a key role in lobemore »
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Microfluidic cell sorters have shown great potential to revolutionize the current technique of enriching rare cells. In the past decades, different microfluidic cell sorters have been developed by researchers for separating circulating tumor cells, T-cells, and other biological markers from blood samples. However, it typically takes months or even years to design these microfluidic cell sorters by hand. Thus, researchers tend to use computer simulation (usually finite element analysis) to verify their designs before fabrication and experimental testing. Despite this, conducting precision finite element analysis of microfluidic devices is computationally expensive and labor-intensive. To address this issue, we recently presentedmore »
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Publisher's Version of Record
- https://doi.org/doi: 10.1063/1.5128797
