Microfluidic device for high-throughput cancer drug screenings

IF 13.2 1区 工程技术 Q1 ENGINEERING, CHEMICAL
Po-Hsun Chen, Lin-Yu Wang, Chia-Yuan Chang, Yuh-Shiuan Chien, Yu-Chia Su, Chi-Kuang Wang, Kuang-Chong Wu, Hsian-Jean Chin, Chien-Fu Chen
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Abstract

High-throughput drug screening is critical in discovering therapeutic compounds, but traditional manual dilution methods are laborious, error-prone, and inefficient. Here, we report on the development of a microfluidic device designed to generate drug concentration gradients accurately and rapidly. This device utilizes laminar flow at low Reynolds numbers to precisely control the volume ratio of the two mixed fluids by adjusting channel length, helping to create precise dilution ratios from 1/3× to 1/300×. We demonstrated that the resulting concentration gradient deviated less than 6 % from the target value, significantly better than manual dilution methods, using bovine serum albumin (BSA) as a sample to simulate actual drug dilution. Furthermore, the device was validated through cytotoxicity tests of the dilution of chemotherapy drug (oxaliplatin) on colorectal cancer cells (HCT-116). The IC50 deviation obtained from the microfluidic device was within 2.45 % of those obtained by manual dilution, showcasing its reliability and accuracy. Multi-drug screening involving 5-FU, oxaliplatin and SN-38 on HCT-116 cells was also conducted to demonstrate the device's applicability in complex screening. Notably, the device achieves steady-state within 30 s at high flow rates, demonstrating scalability and potential for integration into high-throughput screening platforms. This technology reduces the time and labor required for drug screening and improves dilution accuracy, providing a promising avenue for personalized and precision medicine.
用于高通量抗癌药物筛选的微流控装置
高通量药物筛选对于发现治疗性化合物至关重要,但传统的人工稀释方法费力、容易出错且效率低下。在这里,我们报告了一种微流体装置的发展,旨在准确和快速地产生药物浓度梯度。该装置利用低雷诺数层流,通过调节通道长度来精确控制两种混合流体的体积比,有助于创建1/ 3x到1/ 300x的精确稀释比。我们证明,所得浓度梯度偏离目标值小于6 %,明显优于人工稀释方法,以牛血清白蛋白(BSA)为样本模拟实际药物稀释。此外,该装置通过化疗药物(奥沙利铂)稀释对结直肠癌细胞(HCT-116)的细胞毒性试验进行了验证。微流控装置的IC50偏差与人工稀释的IC50偏差在2.45 %以内,显示了其可靠性和准确性。我们还对HCT-116细胞进行了5-FU、奥沙利铂和SN-38的多药筛选,以证明该装置在复杂筛选中的适用性。值得注意的是,该设备在高流速下可在30 s内达到稳态,展示了可扩展性和集成到高通量筛选平台的潜力。这项技术减少了药物筛选所需的时间和劳动力,提高了稀释精度,为个性化和精准医疗提供了一条有前途的途径。
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来源期刊
Chemical Engineering Journal
Chemical Engineering Journal 工程技术-工程:化工
CiteScore
21.70
自引率
9.30%
发文量
6781
审稿时长
2.4 months
期刊介绍: The Chemical Engineering Journal is an international research journal that invites contributions of original and novel fundamental research. It aims to provide an international platform for presenting original fundamental research, interpretative reviews, and discussions on new developments in chemical engineering. The journal welcomes papers that describe novel theory and its practical application, as well as those that demonstrate the transfer of techniques from other disciplines. It also welcomes reports on carefully conducted experimental work that is soundly interpreted. The main focus of the journal is on original and rigorous research results that have broad significance. The Catalysis section within the Chemical Engineering Journal focuses specifically on Experimental and Theoretical studies in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. These studies have industrial impact on various sectors such as chemicals, energy, materials, foods, healthcare, and environmental protection.
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