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Concentration Gradient Constructions Using Inertial Microfluidics for Studying Tumor Cell-Drug Interactions.

ABSTRACT: With the continuous development of cancer therapy, conventional animal models have exposed a series of shortcomings such as ethical issues, being time consuming and having an expensive cost. As an alternative method, microfluidic devices have shown advantages in drug screening, which can effectively shorten experimental time, reduce costs, improve efficiency, and achieve a large-scale, high-throughput and accurate analysis. However, most of these microfluidic technologies are established for narrow-range drug-concentration screening based on sensitive but limited flow rates. More simple, easy-to operate and wide-ranging concentration-gradient constructions for studying tumor cell-drug interactions in real-time have remained largely out of reach. Here, we proposed a simple and compact device that can quickly construct efficient and reliable drug-concentration gradients with a wide range of flow rates. The dynamic study of concentration-gradient formation based on successive spiral mixer regulations was investigated systematically and quantitatively. Accurate, stable, and controllable dual drug-concentration gradients were produced to evaluate simultaneously the efficacy of the anticancer drug against two tumor cell lines (human breast adenocarcinoma cells and human cervical carcinoma cells). Results showed that paclitaxel had dose-dependent effects on the two tumor cell lines under the same conditions, respectively. We expect this device to contribute to the development of microfluidic chips as a portable and economical product in terms of the potential of concentration gradient-related biochemical research.

SUBMITTER: Shen S

PROVIDER: S-EPMC7281261 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Concentration Gradient Constructions Using Inertial Microfluidics for Studying Tumor Cell-Drug Interactions.

Shen Shaofei S Zhang Fangjuan F Gao Mengqi M Niu Yanbing Y

Micromachines 20200512 5

With the continuous development of cancer therapy, conventional animal models have exposed a series of shortcomings such as ethical issues, being time consuming and having an expensive cost. As an alternative method, microfluidic devices have shown advantages in drug screening, which can effectively shorten experimental time, reduce costs, improve efficiency, and achieve a large-scale, high-throughput and accurate analysis. However, most of these microfluidic technologies are established for nar ...[more]

PMID: 32408585

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Project description:Simple Summary Prostate cancer (PCa) is notoriously difficult to diagnose owing to the lack of reliable biomarkers and the invasiveness of obtaining a tissue biopsy from the prostate. As an alternative, we developed a liquid biopsy technique, based on isolating tumor cells from semen samples via a microfluidic device. To optimize the device, we first attempted to recover PCa cells from semen samples spiked with PCa cell lines, achieving an average efficiency of >87% cell recovery at the chosen flow rate. We then transitioned to a clinical setting using semen samples from PCa patients. The yield of isolated clinical PCa cells varied between 67 and 307 cells per mL of semen (in 15 cancer patients). These cells were stained and compared to the standard prognostic parameters such as Gleason score and PSA serum level. This study presents a potential liquid biopsy technique to augment the existing diagnosis and prognosis of PCa. Abstract Prostate cancer (PCa) diagnosis is primarily based on prostate-specific antigen (PSA) testing and prostate tissue biopsies. However, PSA testing has relatively low specificity, while tissue biopsies are highly invasive and have relatively low sensitivity at early stages of PCa. As an alternative, we developed a technique of liquid biopsy, based on isolation of circulating tumor cells (CTCs) from seminal fluid (SF). The recovery of PCa cells from SF was demonstrated using PCa cell lines, achieving an efficiency and throughput as high as 89% (±3.8%) and 1.7 mL min−1, respectively, while 99% (±0.7%) of sperm cells were disposed of. The introduced approach was further tested in a clinical setting by collecting and processing SF samples of PCa patients. The yield of isolated CTCs measured as high as 613 cells per SF sample in comparison with that of 6 cells from SF of healthy donors, holding significant promise for PCa diagnosis. The correlation analysis of the isolated CTC numbers with the standard prognostic parameters such as Gleason score and PSA serum level showed correlation coefficient values at 0.40 and 0.73, respectively. Taken together, our results show promise in the developed liquid biopsy technique to augment the existing diagnosis and prognosis of PCa.

Dataset Information

Concentration Gradient Constructions Using Inertial Microfluidics for Studying Tumor Cell-Drug Interactions.

Publications

Concentration Gradient Constructions Using Inertial Microfluidics for Studying Tumor Cell-Drug Interactions.

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