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一种用于筛选药物组合的灵活微流控分配系统。

A Flexible, Microfluidic, Dispensing System for Screening Drug Combinations.

作者信息

Davies Mark, Abubaker Mannthalah, Bible Lorraine

机构信息

Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland.

Hooke Bio Ltd., Clare V14 XH92, Ireland.

出版信息

Micromachines (Basel). 2020 Oct 18;11(10):943. doi: 10.3390/mi11100943.

DOI:10.3390/mi11100943
PMID:33080987
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7603205/
Abstract

It is known that in many cases a combination of drugs is more effective than single-drug treatments both for reducing toxicity and increasing efficacy. With the advent of organoid screens, personalised medicine has become possible for many diseases. Automated pipetting to well plates is the pharmaceutical industry standard for drug screening, but this is relatively expensive and slow. Here, a rotary microfluidic system is presented that can test all possible drug combinations at speed with the use of droplets. For large numbers of combinations, it is shown how the experimental scale is reduced by considering drug dilutions and machine learning. As an example, two cases are considered; the first is a three-ring and three radii configuration and the second is a four ring and forty-eight radii configuration. Between these two, all other cases are shown to be possible. The proposed commercial instrument is shown to be flexible, the user choosing which wells to fill and which driver-computational sub-routine to select. The major issues addressed here are the programming theory of the instrument and the reduction of droplets to be generated by drug dilutions and machine learning.

摘要

众所周知,在许多情况下,联合用药在降低毒性和提高疗效方面比单一药物治疗更有效。随着类器官筛选技术的出现,针对许多疾病的个性化医疗已成为可能。使用自动移液器将药物加入微孔板是制药行业药物筛选的标准方法,但这种方法相对昂贵且速度较慢。在此,我们展示了一种旋转微流控系统,该系统可以利用液滴快速测试所有可能的药物组合。对于大量的组合,我们展示了如何通过考虑药物稀释和机器学习来缩小实验规模。作为示例,我们考虑了两种情况;第一种是三环和三个半径配置,第二种是四环和四十八个半径配置。在这两种情况之间,所有其他情况也都被证明是可行的。所提出的商业仪器具有灵活性,用户可以选择填充哪些孔以及选择哪个驱动计算子程序。这里解决的主要问题是仪器的编程理论以及通过药物稀释和机器学习减少要生成的液滴数量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/08bd1793362a/micromachines-11-00943-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/61f9bcdc0d0b/micromachines-11-00943-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/b49f747f611a/micromachines-11-00943-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/146e849841f8/micromachines-11-00943-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/d5fbe0aed05e/micromachines-11-00943-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/c3b4c15d90c9/micromachines-11-00943-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/4ee623681939/micromachines-11-00943-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/08bd1793362a/micromachines-11-00943-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/61f9bcdc0d0b/micromachines-11-00943-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/b49f747f611a/micromachines-11-00943-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/146e849841f8/micromachines-11-00943-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/d5fbe0aed05e/micromachines-11-00943-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/c3b4c15d90c9/micromachines-11-00943-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/4ee623681939/micromachines-11-00943-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2c9/7603205/08bd1793362a/micromachines-11-00943-g007.jpg

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