Engineering a deformation-free plastic spiral inertial microfluidic system for CHO cell clarification in biomanufacturing

Jeon, Hyungkook; Kwon, Taehong; Yoon, Junghyo; Han, Jongyoon

doi:10.1039/d1lc00995h

Cited by 31 publications

(21 citation statements)

References 52 publications

(73 reference statements)

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“…Then, the particle trajectory was obtained by minimizing the vertical stacking through the ImageJ software for 600 pictures, as shown in Figure 5. It is worth noting that the experimental results may often have a certain deviation from the original design [36]. Through experiments, it was verified that the optimal input flow rate of the multistage channel was adjusted to 1.3 mL/min.…”

Section: Resultsmentioning

confidence: 97%

3D-Stacked Multistage Inertial Microfluidic Chip for High-Throughput Enrichment of Circulating Tumor Cells

Huang

Sun

et al. 2022

Cyborg Bionic Syst

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Whether for cancer diagnosis or single-cell analysis, it remains a major challenge to isolate the target sample cells from a large background cell for high-efficiency downstream detection and analysis in an integrated chip. Therefore, in this paper, we propose a 3D-stacked multistage inertial microfluidic sorting chip for high-throughput enrichment of circulating tumor cells (CTCs) and convenient downstream analysis. In this chip, the first stage is a spiral channel with a trapezoidal cross-section, which has better separation performance than a spiral channel with a rectangular cross-section. The second and third stages adopt symmetrical square serpentine channels with different rectangular cross-section widths for further separation and enrichment of sample cells reducing the outlet flow rate for easier downstream detection and analysis. The multistage channel can separate 5 μ m and 15 μ m particles with a separation efficiency of 92.37% and purity of 98.10% at a high inlet flow rate of 1.3 mL/min. Meanwhile, it can separate tumor cells (SW480, A549, and Caki-1) from massive red blood cells (RBCs) with a separation efficiency of >80%, separation purity of >90%, and a concentration fold of ~20. The proposed work is aimed at providing a high-throughput sample processing system that can be easily integrated with flowing sample detection methods for rapid CTC analysis.

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Section: Resultsmentioning

confidence: 97%

3D-Stacked Multistage Inertial Microfluidic Chip for High-Throughput Enrichment of Circulating Tumor Cells

Huang

Sun

et al. 2022

Cyborg Bionic Syst

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“…In addition to high separation efficiency, high throughput is another key advantage of the MDDS separation technology for large sample volume processing, which can solve a critical limitation of other microfluidic sperm separation technologies in terms of their commercialization 9 , 13 , 21 , 22 . Here, we showed that 1 mL of semen could be processed within 8.5 min in the high-throughput fluidic platform, and further throughput increase can be easily achieved by multiplexing or stacking the devices 30 , 45 – 48 . The advantage of high throughput could enable its standardized usage in handling semen samples with large variations in their cell number and volume (for normozoospermic men, the sperm count is in the range of 15–250 × 10 6 cells/mL in 1.5–7.6 mL semen) 43 .…”

Section: Discussionmentioning

confidence: 94%

“…Check valves (80183 and 80184, QOSINA, USA) were used to regulate the flow direction in the recirculation operation; we used the check-valves for single use to prevent potential cross-contamination caused by an internal membrane inside the check-valves. Furthermore, to switch to a single-use disposable medical device, the PDMS MDDS device can be translated to its plastic equivalent that is mass-producible 30 .…”

Section: Methodsmentioning

confidence: 99%

“…To overcome this limitation, some inertial spiral microfluidic devices have recently been applied for sperm isolation and successfully demonstrated leukocyte removal with higher throughput and sperm recovery compared to the conventional methodologies 17 , 18 , 26 , 27 . In the inertial microfluidics requiring a high flow rate (order of mL/min) with a finite Reynolds number ( , where , , and represent the density, dynamic viscosity, and maximum velocity of the fluid, respectively, and represents the hydraulic diameter of the channel) 28 – 30 , particle behavior in the microchannel is dominantly affected by inertial lift forces. When the microchannel is not straight but curved (like the spiral device), a recirculating flow called Dean flow arises in the cross-section of the microchannel due to a mismatch of velocity between the fluid in the center and near-wall regions 29 .…”

Section: Introductionmentioning

confidence: 99%

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Multi-dimensional-double-spiral (MDDS) inertial microfluidic platform for sperm isolation directly from the raw semen sample

Jeon

Cremers

et al. 2022

Sci Rep

Self Cite

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Here, we propose a fully-automated platform using a spiral inertial microfluidic device for standardized semen preparation that can process patient-derived semen samples with diverse fluidic conditions without any pre-washing steps. We utilized the multi-dimensional double spiral (MDDS) device to effectively isolate sperm cells from other non-sperm seminal cells (e.g., leukocytes) in the semen sample. The recirculation platform was employed to minimize sample dependency and achieve highly purified and concentrated (up to tenfold) sperm cells in a rapid and fully-automated manner (~ 10 min processing time for 50 mL of diluted semen sample). The clinical (raw) semen samples obtained from healthy donors were directly used without any pre-washing step to evaluate the developed separation platform, which showed excellent performance with ~ 80% of sperm cell recovery, and > 99.95% and > 98% removal of 10-μm beads (a surrogate for leukocytes) from low-viscosity and high-viscosity semen samples, respectively. We expect that the novel platform will be an efficient and automated tool to achieve purified sperm cells directly from raw semen samples for assisted reproductive technologies (ARTs) as an alternative to density centrifugation or swim-up methods, which often suffer from the low recovery of sperm cells and labor-intensive steps.

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“…The flow rate could not be increased for the 3000-ppm PEO solution considering the flow resistance in the microchannel due to the deformation of the polydimethylsiloxane (PDMS) channel. Using a rigid, deformation-free plastic-based microfluidic device with leak-tight connections [ 33 ], the device throughput and concentration performance can be further enhanced, finally enabling the commercialization process.…”

Section: Resultsmentioning

confidence: 99%

A Continuous Microfluidic Concentrator for High-Sensitivity Detection of Bacteria in Water Sources

et al. 2022

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Water contamination is a critical issue that threatens global public health. To enable the rapid and precise monitoring of pathogen contamination in drinking water, a concentration technique for bacterial cells is required to address the limitations of current detection methods, including the culture method and polymerase chain reaction. Here we present a viscoelastic microfluidic device for the continuous concentration of bacterial cells. To validate the device performance for cell concentration, the flow characteristics of 2-μm particles were estimated in viscoelastic fluids at different concentrations and flow rates. Based on the particle flow distributions, the flow rate factor, which is defined as the ratio of the inlet flow rate to the outlet flow rate at the center outlet, was optimized to achieve highly concentrated bacterial cells by removal of the additional suspending medium. The flow characteristics of 0.5-, 0.7-, and 1.0-μm-diameter particles were evaluated to consider the effect of a wide spectrum of bacterial size distribution. Finally, the concentration factor of bacterial cells, Staphylococcus aureus, suspended in a 2000-ppm polyethylene oxide solution was found to be 20.6-fold at a flow rate of 20 μL/min and a flow rate factor of 40.

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Engineering a deformation-free plastic spiral inertial microfluidic system for CHO cell clarification in biomanufacturing

Abstract: Inertial microfluidics has enabled many impactful high throughput applications. However, devices fabricated in soft elastomer (i.e., polydimethylsiloxane (PDMS)) suffer reliability issues due to significant deformation generated by the high pressure...

Cited by 31 publications

References 52 publications

3D-Stacked Multistage Inertial Microfluidic Chip for High-Throughput Enrichment of Circulating Tumor Cells

3D-Stacked Multistage Inertial Microfluidic Chip for High-Throughput Enrichment of Circulating Tumor Cells

Multi-dimensional-double-spiral (MDDS) inertial microfluidic platform for sperm isolation directly from the raw semen sample

A Continuous Microfluidic Concentrator for High-Sensitivity Detection of Bacteria in Water Sources

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