Multiparametric quantitative phase imaging for real-time, single cell, drug screening in breast cancer.
Multiparametric quantitative phase imaging for real-time, single cell, drug screening in breast cancer.
复制标题
DOI：
10.1038/s42003-022-03759-1
复制
发表时间：
2022-08-08
影响因子：
5.9
通讯作者：
Zangle, Thomas A.
中科院分区：
文献类型：
--
作者：
Polanco, Edward R.;Moustafa, Tarek E.;Butterfield, Andrew;Scherer, Sandra D.;Cortes-Sanchez, Emilio;Bodily, Tyler;Spike, Benjamin T.;Welm, Bryan E.;Bernard, Philip S.;Zangle, Thomas A.
定量相成像（QPI）通过量化质量随时间的变化来测量单个细胞的生长速度。在这里，我们使用乳腺癌细胞系MCF-7、BT-474和MDA-MB-231来验证QPI作为一种多参数方法来确定对单药治疗的反应。我们的方法允许在单个实验中快速测定多达100,000个单个细胞或小簇的药物敏感性，细胞毒性，异质性和反应时间。我们发现QPI的EC50值与细胞滴度- glo （CTG）一致，这是一种金标准代谢终点测定法。此外，我们应用多参数QPI来表征细胞静态/细胞毒性和快速/慢速反应，并跟踪抗性亚群的出现。因此，除了平均人群反应外，QPI还揭示了反应异质性的动态变化，这是优于终点生存能力或代谢分析的关键优势。总体而言，多参数QPI通过捕获单细胞对候选疗法的反应动态，揭示了细胞生长的丰富图景。作者开发了一种基于定量相成像的实时无标记方法，以确定药物敏感性，与终点活力或代谢测定相比具有显著优势，并揭示了单细胞反应的异质性。
Quantitative phase imaging (QPI) measures the growth rate of individual cells by quantifying changes in mass versus time. Here, we use the breast cancer cell lines MCF-7, BT-474, and MDA-MB-231 to validate QPI as a multiparametric approach for determining response to single-agent therapies. Our method allows for rapid determination of drug sensitivity, cytotoxicity, heterogeneity, and time of response for up to 100,000 individual cells or small clusters in a single experiment. We find that QPI EC50 values are concordant with CellTiter-Glo (CTG), a gold standard metabolic endpoint assay. In addition, we apply multiparametric QPI to characterize cytostatic/cytotoxic and rapid/slow responses and track the emergence of resistant subpopulations. Thus, QPI reveals dynamic changes in response heterogeneity in addition to average population responses, a key advantage over endpoint viability or metabolic assays. Overall, multiparametric QPI reveals a rich picture of cell growth by capturing the dynamics of single-cell responses to candidate therapies. The authors developed a real-time and label-free approach based on quantitative phase imaging to determine drug sensitivity with significant advantages over endpoint viability or metabolic assays, and which reveals single cell response heterogeneity.
登录
查看更多内容
影响因子：
48
作者：
Godin, Michel;Delgado, Francisco Feijo;Son, Sungmin;Grover, William H.;Bryan, Andrea K.;Tzur, Amit;Jorgensen, Paul;Payer, Kris;Grossman, Alan D.;Kirschner, Marc W.;Manalis, Scott R.
通讯作者：
Manalis, Scott R.
DOI：
10.1073/pnas.2002152117
发表时间：
2020-11-03
影响因子：
11.1
作者：
Liu X;Oh S;Peshkin L;Kirschner MW
通讯作者：
Kirschner MW
DOI：
10.14440/jbm.2020.323
发表时间：
2020-01-01
期刊：
Journal of Biological Methods
影响因子：
--
作者：
Lanigan, Thomas M.;Rasmussen, Stephanie M.;Ruth, Jeffrey H.
通讯作者：
Ruth, Jeffrey H.
影响因子：
4.6
作者：
Aknoun S;Yonnet M;Djabari Z;Graslin F;Taylor M;Pourcher T;Wattellier B;Pognonec P
通讯作者：
Pognonec P
影响因子：
2.2
作者：
CROUCH, SPM;KOZLOWSKI, R;FLETCHER, J
通讯作者：
FLETCHER, J