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Microfluidic Monitoring of Single Cell Elasticity, Viscoelasticity, and Plasticity

单细胞弹性、粘弹性和塑性的微流控监测

基本信息

批准号：
9115597
负责人：
Alexander Alexeev
金额：
$ 17.65万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9115597
关键词：
ATP-Binding Cassette Transporters Adrenal Cortex Hormones Affect Apoptosis Architecture Biological Assay Biomechanics Catecholamines Cell Fractionation Cell Separation Cells Chemicals Computer Simulation Data Dependence Detection Device Designs Devices Dexamethasone Diagnostic Dimensions Elasticity Engineering Epinephrine Erythrocytes Flow Cytometry Fractionation Functional disorder Geometry HL-60 Cells Health Hormones Human Individual Interleukins K-562 Label Lead Leukocytes Mechanics Methods Microfluidic Microchips Microfluidics Microscopy Modeling Molecular Sieve Chromatography Monitor Periodicals Pharmaceutical Preparations Phenotype Population Preparation Production Relaxation Research Proposals Resistance Sampling Sensitivity and Specificity Sorting - Cell Movement Specificity Speed System Technology Testing Time Translating Variant Viscosity aldehyde dehydrogenases base biomedical scientist biophysical properties cancer cell cell type chemotherapeutic agent constriction density design disorder subtype improved leukemia malaria infection research study uptake viscoelasticity

项目摘要

DESCRIPTION (provided by applicant): The mechanical stiffness of individual human cells can be a key parameter that reveals dysfunction of the cell. For example, malaria-infected red blood cells are known to be stiffer than uninfected cells and invasive cancer cells can be several times more deformable than healthy phenotypes. However, for biophysical properties to be more useful in biomedical and diagnostic settings, we will require methods for continuous biomechanical fractionation in high throughput, akin to size exclusion chromatography. Although separation by such parameters as size and density are commonly employed, few methods are available for high throughput separation by stiffness and no method for sorting by viscoelasticity. Moreover, because of the potential overlap of biophysical signatures of different cell types, to achieve purity in the separation may require the ability to fractionate cells such that subpopulations can be collected for which the biophysical values do not overlap. Towards these ends, we have created a microfluidic sorting technology that utilizes a combination of hydrodynamic and compressive forces to sort individual cells by biophysical properties. The objective of this research proposal is to create a high-throughput cell fractionation method based on the microfluidic technology that is sensitive to stiffness and viscosity, two orthogonal biophysical phenotypes of cells. The technology consists of a microchannel with periodical, diagonal constrictions that deform cells as they flow to modify their trajectory in a proportion to cell stiffness and viscosity. For example, cells that are stiffer are translated towards the upper part of the channel and cells that are softer migrate towards the bottom part of the channel such that outlets can continuously collect the sorted cells. By engineering channel geometry such as inter-ridge spacing, viscoelastic relaxation of cells can be emphasized, constituting a completely new sorting mechanism not previously utilized. Through computational understanding of channel hydrodynamics and stiffness-dependent trajectories of cells, outlets can be designed to specifically collect the sorted cells and thereby fractionate cells by stiffness. Also, by designin channels with different inter-ridge spacing, differences in cell relaxation rates can be exploited. In preliminary data, we show over 45-fold enrichment of cell types is possible in a label-free manner.

描述（由申请人提供）：单个人类细胞的机械刚度可以是揭示细胞功能障碍的关键参数。例如，已知感染疟疾的红细胞比未感染的细胞更硬，而侵袭性癌细胞的变形程度可能是健康表型的数倍。然而，为了使生物物理特性在生物医学和诊断环境中更有用，我们需要高通量的连续生物力学分级分离方法，类似于尺寸排阻色谱法。尽管通常采用通过尺寸和密度等参数进行分离，但很少有方法可用于通过刚度进行高通量分离，并且没有通过粘弹性进行分选的方法。此外，由于不同细胞类型的生物物理特征可能重叠，为了实现分离的纯度可能需要能够分级细胞，以便可以收集生物物理值不重叠的亚群。为了实现这些目的，我们创建了一种微流体分选技术，该技术利用流体动力和压缩力的组合，根据生物物理特性对单个细胞进行分选。本研究提案的目的是创建一种基于微流体技术的高通量细胞分级分离方法，该方法对细胞的两种正交生物物理表型——刚度和粘度敏感。该技术由具有周期性对角收缩的微通道组成，该微通道在细胞流动时使细胞变形，以按比例改变其轨迹细胞硬度和粘度。例如，较硬的细胞向通道的上部平移，较软的细胞向通道的底部迁移，使得出口可以连续收集分选的细胞。通过设计通道几何形状（例如脊间间距），可以强调细胞的粘弹性松弛，从而构成以前未使用的全新分选机制。通过对通道流体动力学和细胞刚度相关轨迹的计算理解，可以设计出口来专门收集分选的细胞，从而根据刚度对细胞进行分级。此外，通过设计具有不同脊间间距的通道，可以利用细胞弛豫率的差异。在初步数据中，我们表明以无标记的方式可以将细胞类型富集超过 45 倍。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Microfluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness.

DOI：
10.1038/s41598-017-01807-z
发表时间：
2017-05-17
期刊：
Scientific reports
影响因子：
4.6
作者：
Islam M;Brink H;Blanche S;DiPrete C;Bongiorno T;Stone N;Liu A;Philip A;Wang G;Lam W;Alexeev A;Waller EK;Sulchek T
通讯作者：
Sulchek T

Microfluidic generation of transient cell volume exchange for convectively driven intracellular delivery of large macromolecules.

DOI：
10.1016/j.mattod.2018.03.002
发表时间：
2018-09
期刊：
Materials today (Kidlington, England)
影响因子：
0
作者：
Liu A;Islam M;Stone N;Varadarajan V;Jeong J;Bowie S;Qiu P;Waller EK;Alexeev A;Sulchek T
通讯作者：
Sulchek T

Microfluidic cell sorting by stiffness to examine heterogenic responses of cancer cells to chemotherapy.

DOI：
10.1038/s41419-018-0266-x
发表时间：
2018-02-14
期刊：
Cell death & disease
影响因子：
9
作者：
Islam M;Mezencev R;McFarland B;Brink H;Campbell B;Tasadduq B;Waller EK;Lam W;Alexeev A;Sulchek T
通讯作者：
Sulchek T

Enhancing size based size separation through vertical focus microfluidics using secondary flow in a ridged microchannel.

DOI：
10.1038/s41598-017-17388-w
发表时间：
2017-12-12
期刊：
Scientific reports
影响因子：
4.6
作者：
Tasadduq B;Lam W;Alexeev A;Sarioglu AF;Sulchek T
通讯作者：
Sulchek T

Continuous Sorting of Cells Based on Differential P Selectin Glycoprotein Ligand Expression Using Molecular Adhesion.

基于差异 P 选择蛋白糖蛋白配体表达的细胞连续分选，利用分子粘附。

DOI：
10.1021/acs.analchem.7b02878
发表时间：
2017
期刊：
Analytical chemistry
影响因子：
7.4
作者：
Tasadduq,Bushra;McFarland,Brynn;Islam,Muhymin;Alexeev,Alexander;Sarioglu,AFatih;Sulchek,Todd
通讯作者：
Sulchek,Todd