研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

一种用于浓度相关体外抗癌药物测试的磁控微流体装置。

A magnetically controlled microfluidic device for concentration dependent in vitro testing of anticancer drug.

发表日期:2023 Sep 15
作者: Vinit Kumar Yadav, Preetha Ganguly, Prashant Mishra, Samaresh Das, Dhiman Mallick
来源: Cellular & Molecular Immunology

摘要:

磁控药物分子的隔离对于多种生物分析试验和测试至关重要,如药物筛选、数字PCR、磁致热和控制磁导药物靶向(MDT)。然而,几项研究都侧重于使用基于传统微加工和3D打印技术的各种被动装置稀释非磁性药物,分别导致对无菌洁净室设施和昂贵设备的需求。本研究开发了一种经过战略设计和简便的无光刻工艺,使用多层PMMA基板制备磁性微流控装置,用于磁控抗癌药物的浓度相关分隔。该装置包含一系列的出口室孔,连接到五个主要的分隔微流控通道,用于收集不同药物浓度。微流控设计几何形状、磁铁配置和流体流速通过有限元法(Finite Element Method)模拟进行优化,以在微流控通道内获得系统的浓度梯度区域。阶梯状磁铁模式在磁性纳米颗粒上产生介于0.01-0.24 pN之间的衰减磁力,能够生成临床可接受的流量范围Q = 0.6-1.1 µL min-1的浓度梯度。该装置的室孔设计适应不同的细胞培养,并通过从入口引入预定浓度同时暴露五个不同浓度。因此,这种创新设计通过单一注射口提供了对每个室孔的可预测浓度控制,以最小化药物装载误差。药物的浓度梯度生成和对细胞培养室的暴露通过使用磁力和阻力控制运行一种时间可变的剂量筛选实验。利用电感耦合等离子体质谱(ICPMS)测量和荧光强度,确定了器件中被隔离药物样品的浓度范围为10-480 µg mL-1。使用该装置进行MCF7和NIH3T3细胞的细胞毒性测试结果与手动稀释方法得到的结果一致,证明了该装置的可重复使用性。
Compartmentalizing magnetically controlled drug molecules is critical in several bioanalytical trials and tests, such as drug screening, digital PCR, magnetic hyperthermia, and controlled magnetic drug targeting (MDT). However, several studies have focused on diluting the nonmagnetic drug using various passive devices based on traditional microfabrication and 3D printing techniques, leading to the requirement of sterilized cleanroom facilities and expensive equipment, respectively. This work develops a strategically designed and straightforward lithography-free process to fabricate a magnetic microfluidic device using a multilayered PMMA substrate for concentration-dependent compartmentalization of a magnetically controlled anticancer drug. The device contains an array of outlet chamber wells connected to five primary separation microfluidic channels for collecting different drug concentrations. The microfluidic design geometry, magnet configuration, and fluid flow rate are optimized using FEM (Finite Element Method) simulations to attain a systematic concentration gradient region within the microfluidic channel. A stair-step-like patterned magnet creates an attenuating magnetic force between 0.01-0.24 pN on magnetic nanoparticles, capable of generating the concentration gradient for the clinically acceptable flow range of Q = 0.6-1.1 μL min-1. The chamber well of the device is designed to adapt different cell cultures and simultaneously expose five different concentrations by introducing a predefined concentration from the inlet. As a result, this innovative design provides a predictable concentration control in each well through a single injection port to minimize drug loading errors. The concentration gradient generation of the drug and exposure to cell culture chambers are controlled using the magnetic and drag forces capable of running a time-varying dose screening experiment. The concentration range of the compartmentalized drug sample in the device is determined as 10-480 μg mL-1 using inductively coupled plasma mass spectrometry (ICPMS) measurement and fluorescence intensity. The cytotoxicity test of MCF7 and NIH3T3 cells using the device was consistent with the results obtained with the manual dilution method, resulting in the reusability of the device.