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

• 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
• 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

 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，而侵袭性癌细胞可能有多种。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方法，类似于尺寸排除。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存在重叠，为了实现分离的纯度可能需要能够对细胞进行分级，以便可以收集生物物理值不重叠的亚群。发明了一种微流体分选技术，利用流体动力和压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方法，该方法对细胞的生物物理特性敏感。刚度和粘度是细胞的两种正交生物物理表型，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。 例如，较硬的细胞移向通道的上部，较软的细胞移向通道的底部，以便出口可以通过设计通道几何形状连续收集分选的细胞。脊间间距，可以强调细胞的粘弹性松弛，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细胞。对细胞进行排序，从而通过硬度分级细胞。此外，通过设计具有不同脊间间距的通道，可以利用细胞松弛率的差异。 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

Cellular enrichment through microfluidic fractionation based on cell biomechanical properties.

基于细胞生物力学特性通过微流体分级富集细胞。

• 发表时间: 2015-10
• 作者: Wang, Gonghao;Turbyfield, Cory;Crawford, Kaci;Alexeev, Alexander;Sulchek, Todd
• 通讯作者: Sulchek, Todd

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。

• 发表时间: 2017-11-07
• 影响因子: 7.4
• 作者: Tasadduq, Bushra;McFarland, Brynn;Islam, Muhymin;Alexeev, Alexander;Sarioglu, A Fatih;Sulchek, Todd
• 通讯作者: Sulchek, Todd

Microfluidic synthesis of colloidal nanomaterials

胶体纳米材料的微流控合成

• DOI: 10.1016/j.ijhydene.2010.09.043
• 发表时间: 2024-09-13
• 期刊: Fuel and Energy Abstracts
• 作者: Saif A. Khan

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

基于细胞硬度差异的活力对细胞进行微流体分选。

• 发表时间: 2017-05-17
• 影响因子: 4.6
• 作者: Islam, Muhymin;Brink, Hannah;Blanche, Syndey;DiPrete, Caleb;Bongiorno, Tom;Stone, Nicholas;Liu, Anna;Philip, Anisha;Wang, Gonghao;Lam, Wilbur;Alexeev, Alexander;Waller, Edmund K;Sulchek, Todd
• 通讯作者: Sulchek, Todd

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

通过硬度对微流体细胞进行分选，以检查癌细胞对化疗的异质反应。

• 发表时间: 2018-02-14
• 影响因子: 9
• 作者: Islam, Muhymin;Mezencev, Roman;McFarland, Brynn;Brink, Hannah;Campbell, Betsy;Tasadduq, Bushra;Waller, Edmund K;Lam, Wilbur;Alexeev, Alexander;Sulchek, Todd
• 通讯作者: Sulchek, Todd