CAREER: Design Principles of Deformable and Adhesive Particles in Multiphase Flow through Microchannels

职业：微通道多相流中可变形和粘附颗粒的设计原理

• 批准号: 2339972
• 负责人: Qin Qi
• 金额: $ 58万
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-03-01 至 2029-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2339972&HistoricalAwards=false
• 关键词: CAREER; Design; Principles; Deformable; Adhesive

Cells exhibit varying mechanical properties at healthy and diseased states, presenting enormous opportunities to harness physical principles in engineering applications such as biomedicine. Nanoparticles are commonly used to modify cell biology, but their influence on cell mechanics and movement in a physiological flow environment is poorly understood. This CAREER award aims to understand how nanoparticles adhered to leukocyte surfaces influence cell deformability and migration from blood microcirculation to inflamed tissues. A combination of biophysical models and microfluidic experiments will be used to generate both fundamental knowledge and design rules for engineering cellular drug carriers. The integrated education plan will disseminate research findings by providing enriching learning experiences at various levels: e.g., a nationwide outreach program for K-12 students, new interdisciplinary teaching examples for undergraduates and graduates, and science communications for the public.There exists a critical knowledge gap between multiscale mechanical and adhesive properties and particle transport in microscale flows, hindering the development of architected materials. This award aims to test the hypothesis that drug nanoparticles influence leukocyte mechanical and adhesive properties across multiple length scales, thus modulating the delivery of drug payload to the site of inflammation and therapeutic efficacy through three major transport steps: crossflow movement in small blood vessels; rolling and adhesion on the vascular surface under physiological shear; transendothelial migration through small pores. In contrast to in vivo techniques commonly used in biomedical research, this award explicitly models the physical interaction between nanoparticles and cell membranes to examine multiscale deformations; a microfluidic cell culture recapitulates the kinetics of vascular adhesion and transport in vitro. This in silico-in vitro approach will elucidate fundamental mechanisms of leukocyte transport and efficiently explore a multi-dimensional parameter space for nanoparticles (e.g., shape, size, rigidity, concentration, and adhesion strength). Phase diagrams and multiscale structure-property relationships generated over a broad parameter range will serve as a robust and high throughput platform technology to design drug carriers tailored for various species, diseases, and drug administration methods.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

细胞在健康和患病状态下表现出不同的机械特性，为在生物医学等工程应用中利用物理原理提供了巨大的机会。纳米颗粒通常用于改变细胞生物学，但人们对它们在生理流动环境中对细胞力学和运动的影响知之甚少。该职业奖旨在了解粘附在白细胞表面的纳米颗粒如何影响细胞变形性以及从血液微循环到发炎组织的迁移。生物物理模型和微流体实验的结合将用于生成工程细胞药物载体的基础知识和设计规则。综合教育计划将通过在各个层面提供丰富的学习体验来传播研究成果：例如，针对 K-12 学生的全国性推广计划、针对本科生和研究生的新跨学科教学实例以及针对公众的科学传播。多尺度机械和粘合性能与微尺度流中颗粒传输之间的差距阻碍了建筑材料的发展。该奖项旨在测试药物纳米粒子在多个长度尺度上影响白细胞机械和粘附特性的假设，从而通过三个主要运输步骤调节药物有效负载到炎症部位的输送和治疗效果：小血管中的横流运动；在生理剪切作用下在血管表面滚动、粘附；通过小孔跨内皮迁移。与生物医学研究中常用的体内技术相比，该奖项明确模拟了纳米粒子和细胞膜之间的物理相互作用，以检查多尺度变形；微流体细胞培养物概括了体外血管粘附和运输的动力学。这种体外计算机模拟方法将阐明白细胞运输的基本机制，并有效地探索纳米颗粒的多维参数空间（例如形状、尺寸、刚性、浓度和粘附强度）。在广泛的参数范围内生成的相图和多尺度结构-性质关系将作为一种强大的高通量平台技术来设计适合各种物种、疾病和药物管理方法的药物载体。该奖项反映了 NSF 的法定使命，并被视为值得通过使用基金会的智力优点和更广泛的影响审查标准进行评估来支持。