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Novel force sensors for in vivo live animal applications

用于活体动物体内应用的新型力传感器

基本信息

批准号：
2029559
负责人：
Wounjhang Park
金额：
$ 45万
依托单位：
University of Colorado at Boulder
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2029559&HistoricalAwards=false
关键词：
Novel force sensors vivo live

项目摘要

Physical forces impact a wide variety of cell functions ranging from stem cell differentiations to cell migration, malignancy and wound healing. Monitoring internal stresses is of critical importance in medical applications such as tissue implants, prosthetics and minimally invasive surgery. Despite the clear needs, the currently available force-sensing techniques are inadequate for force-sensing in intact tissues in their natural states. This project presents a novel nanosensor capable of highly sensitive force measurements in live animals. The nanosensor makes use of specialized nanoparticles (upconversion nanoparticles (UCNPs)), that, when excited by infrared light, will emit light bands that can be manipulated to measure forces and tissue displacements at the nanoscale in deep tissues. The proposed force sensor represents a transformative new technique that will allow remote sensing of forces inside biological tissues and generate 3D force maps, which will have far-reaching impacts on biology and medicine as well as on a wide range of engineering applications.The ultimate goal of this project is to develop a novel force sensing technique that allows minimally invasive in vivo sensing of local force within a 3D volume of biological tissues. It promises force measurements in the range of 1 nN and local deformation down to ~1 nm using a conventional scanning optical microscope. The nanosensor is composed of upconversion nanoparticles (UCNPs), a flexible polymer and a metal nanostructure. The proposed ratiometric sensing UCNP signal is excited by an infrared light and thus does not excite background autofluorescence. By exploiting the short-range UCNP-metal interaction, the sensor achieves high sensitivity. Upconversion luminescence is a nonlinear process and naturally allows imaging with excellent spatial resolution. The Research Plan is organized under three phases: (1) design and fabrication of the nanosensor, (2) sensor calibration and (3) demonstration of in vivo force sensing in live animal skin, i.e., fully characterized and calibrated sensors will be injected subcutaneously into live mice to measure mechanical forces in the epidermis during epithelial cell migrations. It is expected that this novel technique will be capable of producing 3D force maps of biological tissues in their natural states with extremely high force sensitivity and spatial resolution. The research goals of the project are integrated well with the education and outreach plans. Research opportunities for graduate students will allow research to be integrated into education. Research results will be integrated into courses and outreach activities. The PIs have track records of mentoring graduate students, undergraduate students and encouraging the participation of women and minority students. The PIs are actively engaged in outreach programs to general public and local industry.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.

物理力影响各种各样的细胞功能，从干细胞分化到细胞迁移、恶性肿瘤和伤口愈合。监测内部应力在诸如组织植入物、假体和微创手术等医疗应用中至关重要。尽管有明确的需求，目前可用的力感测技术是不足以在其自然状态下的完整组织的力感测。该项目提出了一种新型的纳米传感器，能够在活体动物中进行高灵敏度的力测量。纳米传感器利用专门的纳米颗粒（上转换纳米颗粒（UCNPs）），当被红外光激发时，将发出可以被操纵的光带，以测量深层组织中纳米级的力和组织位移。所提出的力传感器代表了一种变革性的新技术，该技术将允许远程感测生物组织内部的力并生成3D力图，这将有很大的-该项目的最终目标是开发一种新型的力传感技术，该技术允许在3D体积内对局部力进行微创体内传感。生物组织它承诺在1 nN范围内的力测量和局部变形低至~1 nm，使用传统的扫描光学显微镜。该传感器由上转换纳米粒子（UCNPs）、柔性聚合物和金属纳米结构组成。所提出的比率传感UCNP信号由红外光激发，因此不会激发背景自发荧光。通过利用短程UCNP-金属相互作用，传感器实现了高灵敏度。上转换发光是一个非线性过程，自然允许成像具有优异的空间分辨率。研究计划分为三个阶段：（1）纳米传感器的设计和制造，（2）传感器校准和（3）在活体动物皮肤中演示体内力传感，即，将完全表征和校准的传感器皮下注射到活小鼠中，以测量上皮细胞迁移期间表皮中的机械力。预计这种新技术将能够以极高的力灵敏度和空间分辨率产生自然状态下生物组织的3D力图。该项目的研究目标与教育和推广计划很好地结合在一起。研究生的研究机会将使研究融入教育。研究成果将纳入课程和外联活动。PI有指导研究生、本科生和鼓励妇女和少数民族学生参与的记录。该奖项反映了NSF的法定使命，并被认为是值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估的支持。