Introduction

The information derived from the number and characteristics of circulating tumor cells (CTCs), is crucial to ensure appropriate cancer treatment monitoring. Currently, diverse microfluidic platforms have been developed for isolating CTCs from blood, but it remains a challenge to develop a low-cost, practical, and efficient strategy.

Objectives

This study aimed to isolate CTCs from the blood of cancer patients via introducing a new and efficient micropillar array-based microfluidic chip (MPA-Chip), as well as providing prognostic information and monitoring the treatment efficacy in cancer patients.

Methods

We fabricated a microfluidic chip (MPA-Chip) containing arrays of micropillars with different geometries (lozenge, rectangle, circle, and triangle). We conducted numerical simulations to compare velocity and pressure profiles inside the micropillar arrays. Also, we experimentally evaluated the capture efficiency and purity of the geometries using breast and prostate cancer cell lines as well as a blood sample. Moreover, the device’s performance was validated on 12 patients with breast cancer (BC) in different states.

Results

The lozenge geometry was selected as the most effective and optimized micropillar design for CTCs isolation, providing high capture efficiency (>85 %), purity (>90 %), and viability (97 %). Furthermore, the lozenge MPA-chip was successfully validated by the detection of CTCs from 12 breast cancer (BC) patients, with non-metastatic (median number of 6 CTCs) and metastatic (median number of 25 CTCs) diseases, showing different prognoses. Also, increasing the chemotherapy period resulted in a decrease in the number of captured CTCs from 23 to 7 for the metastatic patient. The MPA-Chip size was only 0.25 cm² and the throughput of a single chip was 0.5 ml/h, which can be increased by multiple MPA-Chips in parallel.

Conclusion

The lozenge MPA-Chip presented a novel micropillar geometry for on-chip CTC isolation, detection, and staining, and in the future, the possibilities can be extended to the culture of the CTCs.

中文翻译：

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基于微柱阵列的微流控芯片，用于循环肿瘤细胞的无标记分离：最好的微柱几何形状？

介绍

来自循环肿瘤细胞 (CTC) 的数量和特征的信息对于确保适当的癌症治疗监测至关重要。目前，已经开发了多种微流控平台用于从血液中分离 CTC，但开发低成本、实用且高效的策略仍然是一个挑战。

目标

本研究旨在通过引入一种新型高效的基于微柱阵列的微流控芯片 (MPA-Chip) 从癌症患者的血液中分离 CTC，并提供预后信息和监测癌症患者的治疗效果。

方法

我们制造了一个微流控芯片 (MPA-Chip)，其中包含具有不同几何形状（菱形、矩形、圆形和三角形）的微柱阵列。我们进行了数值模拟以比较微柱阵列内的速度和压力分布。此外，我们通过实验评估了使用乳腺癌和前列腺癌细胞系以及血液样本的几何形状的捕获效率和纯度。此外，该设备的性能在不同州的 12 名乳腺癌 (BC) 患者身上得到了验证。

结果

菱形几何形状被选为最有效和优化的 CTC 分离微柱设计，提供高捕获效率 (>85%)、纯度 (>90%) 和活力 (97%)。此外，菱形 MPA 芯片通过检测来自 12 名乳腺癌 (BC) 患者的 CTC 得到成功验证，这些患者具有非转移性（6 个 CTC 的中位数）和转移性（25 个 CTC 的中位数）疾病，显示出不同的预后。此外，增加化疗时间导致转移患者捕获的 CTC 数量从 23 个减少到 7 个。MPA-Chip尺寸仅为0.25 cm ²，单个芯片的吞吐量为0.5 ml/h，可以通过多个MPA-Chip并行提高。

结论

菱形 MPA-Chip 提出了一种用于片上 CTC 分离、检测和染色的新型微柱几何形状，并且在未来，这种可能性可以扩展到 CTC 的培养。