A feasibility study for enrichment of highly aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow.
A feasibility study for enrichment of highly aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow.
复制标题
一项可行性研究，可通过介电性流体增强其生物物理特性来富集高度侵略性的癌症亚群。
DOI：
10.1002/elps.201600530
复制
发表时间：
2017-06
期刊：
影响因子：
2.9
通讯作者：
Davalos RV
中科院分区：
文献类型：
--
作者：
Douglas TA;Cemazar J;Balani N;Sweeney DC;Schmelz EM;Davalos RV
癌症治疗的一个常见问题是治疗耐药性和肿瘤复发的发展，这是由于治疗杀死了大多数肿瘤细胞，但留下了侵袭性细胞重新繁殖。这里介绍的是一种微流体装置，可用于分离肿瘤亚群，以优化治疗选择。介电电泳（DEP）是粒子被电场极化并沿电场梯度沿着移动的现象。不同的细胞亚群有不同的DEP反应，这取决于他们的生物电表型，我们假设，与侵略性。我们已经设计了一种微流体装置，其中包含柱的区域局部地扭曲由跨微流体通道的AC电压产生的电场的通道，并且通过DEP迫使细胞朝向柱。该力与来自流体运动的同时拖曳力平衡，该拖曳力将细胞拉离柱。我们已经表明，通过调整阻力，具有侵略性表型的细胞更多地受到DEP力的影响，并被捕获在柱子上，而其他细胞则不受影响地流过芯片。利用单细胞捕获细胞大小的职位的阻力DEP力平衡，我们表明，分离非常相似的细胞亚群可以实现，这是以前不可能与DEP单独的结果。分离的亚群在下游保持高活力，并保持天然状态，没有荧光标记。然后可以培养这些细胞，以帮助选择一种治疗方法，这种治疗方法可以杀死攻击性亚群，甚至比大部分肿瘤更好，减轻耐药性和复发。
A common problem with cancer treatment is the development of treatment resistance and tumor recurrence that result from treatments that kill most tumor cells yet leave behind aggressive cells to repopulate. Presented here is a microfluidic device that can be used to isolate tumor subpopulations to optimize treatment selection. Dielectrophoresis (DEP) is a phenomenon where particles are polarized by an electric field and move along the electric field gradient. Different cell subpopulations have different DEP responses depending on their bioelectrical phenotype, which, we hypothesize, correlate with aggressiveness. We have designed a microfluidic device in which a region containing posts locally distorts channel of the electric field created by an AC voltage across a microfluidic channel and which forces cells toward the posts through DEP. This force is balanced with a simultaneous drag force from fluid motion that pulls cells away from the posts. We have shown that by adjusting the drag force, cells with aggressive phenotypes are influenced more by the DEP force and trap on posts while others flow through the chip unaffected. Utilizing single-cell trapping on cell-sized posts by a drag-DEP force balance, we show that separation of very similar cell subpopulations may be achieved, a result that was previously impossible with DEP alone. Separated subpopulations maintain high viability downstream, and remain in a native state, without fluorescent labeling. These cells can then be cultured to help select a therapy that kills aggressive subpopulations equally or better than the bulk of the tumor, mitigating resistance and recurrence.
登录
查看更多内容
影响因子：
1.6
作者：
BONNER, WA;SWEET, RG;HERZENBERG, LA
通讯作者：
HERZENBERG, LA
DOI：
10.1016/s0005-2760(97)00092-1
发表时间：
1997-11-15
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM
影响因子：
--
作者：
Chan, KL;Gascoyne, PRC;Pethig, R
通讯作者：
Pethig, R
影响因子：
3.3
作者：
Cohen, Courtney A.;Shea, Amanda A.;Roberts, Paul C.
通讯作者：
Roberts, Paul C.
DOI：
10.1039/c3ib00008g
发表时间：
2013-06
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Salmanzadeh A;Elvington ES;Roberts PC;Schmelz EM;Davalos RV
通讯作者：
Davalos RV
DOI：
10.1056/nejmoa1113205
发表时间：
2012-03-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Gerlinger M;Rowan AJ;Horswell S;Math M;Larkin J;Endesfelder D;Gronroos E;Martinez P;Matthews N;Stewart A;Tarpey P;Varela I;Phillimore B;Begum S;McDonald NQ;Butler A;Jones D;Raine K;Latimer C;Santos CR;Nohadani M;Eklund AC;Spencer-Dene B;Clark G;Pickering L;Stamp G;Gore M;Szallasi Z;Downward J;Futreal PA;Swanton C
通讯作者：
Swanton C