Design and validation of a tunable inertial microfluidic system for the efficient enrichment of circulating tumor cells in blood

Peña, Andrés de la; Armendariz, Estibaliz; Oyarbide, Alvaro; Morales, Xabier; Ortiz‐Espinosa, Sergio; Córdoba, Borja Ruiz‐Fernández de; Cochonneau, Denis; Cornago, Iñaki; Heymann, Dominique; Argemí, Josepmaria; D’Avola, Delia; Sangro, Bruno; Lecanda, Fernando; Pı́o, Rubén; Cortés-Domínguez, Iván; Ortiz‐de‐Solórzano, Carlos

doi:10.1002/btm2.10331

Cited by 5 publications

(4 citation statements)

References 41 publications

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“…Inertial microfluidics is one technology that has been successful in the isolation of CTCs and clusters [10,[14][15][16][17]. Cells inside an inertial flow are subjected to inertial forces that lead to the lateral migration of cells [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

“…This technology is very promising for the detection of rare cells as no additional labeling is required and the separation process is continuous with high throughput [14]. We and others have demonstrated the isolation of CTCs and clusters from the samples of non-small cell lung carcinoma (NSCLC) [21,22], head and neck cancer (HNC) [23,24], hepatocellular carcinoma (HCC) [17,25], and breast cancer (BCa) [26][27][28][29] patients using inertial microfluidic devices. Work to date has focused on the separation of single CTCs from blood cells.…”

Section: Introductionmentioning

confidence: 99%

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Single Cell Analysis of Inertial Migration by Circulating Tumor Cells and Clusters

et al. 2023

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Single-cell analysis provides a wealth of information regarding the molecular landscape of the tumor cells responding to extracellular stimulations, which has greatly advanced the research in cancer biology. In this work, we adapt such a concept for the analysis of inertial migration of cells and clusters, which is promising for cancer liquid biopsy, by isolation and detection of circulating tumor cells (CTCs) and CTC clusters. Using high-speed camera tracking live individual tumor cells and cell clusters, the behavior of inertial migration was profiled in unprecedented detail. We found that inertial migration is heterogeneous spatially, depending on the initial cross-sectional location. The lateral migration velocity peaks at about 25% of the channel width away from the sidewalls for both single cells and clusters. More importantly, while the doublets of the cell clusters migrate significantly faster than single cells (~two times faster), cell triplets unexpectedly have similar migration velocities to doublets, which seemingly disagrees with the size-dependent nature of inertial migration. Further analysis indicates that the cluster shape or format (for example, triplets can be in string format or triangle format) plays a significant role in the migration of more complex cell clusters. We found that the migration velocity of a string triplet is statistically comparable to that of a single cell while the triangle triplets can migrate slightly faster than doublets, suggesting that size-based sorting of cells and clusters can be challenging depending on the cluster format. Undoubtedly, these new findings need to be considered in the translation of inertial microfluidic technology for CTC cluster detection.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Single Cell Analysis of Inertial Migration by Circulating Tumor Cells and Clusters

et al. 2023

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“…Microfluidic chip technology has been widely applied in the detection of tumor cells in different body fluids, such as blood [10][11][12], urine [13][14][15], sputum [16], ascites [17,18] and pleural effusion. Che et al described a centrifuge chip with microchambers to employ microscale vortices for the isolation and concentration of cancer cells and mesothelial cells [19].…”

Section: Introductionmentioning

confidence: 99%

A Microfluidic System for Detecting Tumor Cells Based on Biomarker Hexaminolevulinate (HAL): Applications in Pleural Effusion

Luan

Xun

et al. 2023

Micromachines

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Malignant pleural effusion is a common clinical problem, which often occurs in cases of malignant tumors, especially in lung cancer. In this paper, a pleural effusion detection system based on a microfluidic chip, combined with specific tumor biomarker, hexaminolevulinate (HAL), used to concentrate and identify tumor cells in pleural effusion was reported. The lung adenocarcinoma cell line A549 and mesothelial cell line Met-5A were cultured as the tumor cells and non-tumor cells, respectively. The optimum enrichment effect was achieved in the microfluidic chip when the flow rates of cell suspension and phosphate-buffered saline achieved 2 mL/h and 4 mL/h, respectively. At the optimal flow rate, the proportion of A549 increased from 28.04% to 70.01% due to the concentration effect of the chip, indicating that tumor cells could be enriched by a factor of 2.5 times. In addition, HAL staining results revealed that HAL can be used to identify tumor cells and non-tumor cells in chip and clinical samples. Additionally, the tumor cells obtained from the patients diagnosed with lung cancer were confirmed to be captured in the microfluidic chip, proving the validity of the microfluidic detection system. This study preliminarily demonstrates the microfluidic system is a promising method with which to assist clinical detection in pleural effusion.

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“…Extensive research has been performed to develop effective CTCs enrichment and isolation strategies, as they are the fundamental step for the CTCs analysis. These strategies are mainly based on the biophysical properties such as size [8][9][10], mass [11] and deformability [12], and/or biochemical properties of CTCs, namely unique biomarkers expressed by CTCs, like epithelial cell adhesion molecules (EpCAM), HER2, CD26 and CD44 [13], etc. Compared to biochemical-based methods, the biophysical properties-based approaches may introduce false positive results in clinical CTCs capture and isolation [5].…”

Section: Introductionmentioning

confidence: 99%

Conductive Nanofibers-Enhanced Microfluidic Device for the Efficient Capture and Electrical Stimulation-Triggered Rapid Release of Circulating Tumor Cells

Huang

Hou

et al. 2023

Biosensors

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The effective detection and release of circulating tumor cells (CTCs) are of great significance for cancer diagnosis and monitoring. The microfluidic technique has proved to be a promising method for CTCs isolation and subsequent analysis. However, complex micro-geometries or nanostructures were often constructed and functionalized to improve the capture efficiency, which limited the scale-up for high-throughput production and larger-scale clinical applications. Thus, we designed a simple conductive nanofiber chip (CNF-Chip)-embedded microfluidic device with a herringbone microchannel to achieve the efficient and specific capture and electrical stimulation-triggered rapid release of CTCs. Here, the most used epithelial cell adhesion molecule (EpCAM) was selected as the representative biomarker, and the EpCAM-positive cancer cells were mainly studied. Under the effects of the nanointerface formed by the nanofibers with a rough surface and the herringbone-based high-throughput microfluidic mixing, the local topographic interaction between target cells and nanofibrous substrate in the microfluidic was synergistically enhanced, and the capture efficiency for CTCs was further improved (more than 85%). After capture, the sensitive and rapid release of CTCs (release efficiency above 97%) could be conveniently achieved through the cleavage of the gold-sulfur bond by applying a low voltage (−1.2 V). The device was successfully used for the effective isolation of CTCs in clinical blood samples from cancer patients, indicating the great potential of this CNF-Chip-embedded microfluidic device in clinical applications.

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Design and validation of a tunable inertial microfluidic system for the efficient enrichment of circulating tumor cells in blood

Cited by 5 publications

References 41 publications

Single Cell Analysis of Inertial Migration by Circulating Tumor Cells and Clusters

Single Cell Analysis of Inertial Migration by Circulating Tumor Cells and Clusters

A Microfluidic System for Detecting Tumor Cells Based on Biomarker Hexaminolevulinate (HAL): Applications in Pleural Effusion

Conductive Nanofibers-Enhanced Microfluidic Device for the Efficient Capture and Electrical Stimulation-Triggered Rapid Release of Circulating Tumor Cells

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