Developing Nanosensor Chemical Cytometry (NCC) to Support the Development of Cellular Therapeutics

开发纳米传感器化学细胞术 (NCC) 以支持细胞治疗的发展

基本信息

批准号：
2124194
负责人：
Michael Strano
金额：
$ 42.01万
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：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2124194&HistoricalAwards=false
关键词：
Developing Nanosensor Chemical Cytometry NCC

项目摘要

How biology responds to the environment at the cellular level play an important role in human health and diseases. For example, it is common for cells of the same type and origin to be functionally significantly different from one cell to another. While previous methods have studied cell populations as a group, it is becoming increasingly clear that measuring cells individually provides important information that helps to predict their behavior as part of organisms. Thus, the goal of this project is to develop a new platform for probing the functional properties of cells (i. e., cell cytometry) in a nondestructive way at the single cell level in a rapid manner. This platform will make use of novel nanosensors that can determine the properties of single cells flowing in a microchannel by detecting their reflections when illuminated with near infrared light. Potential benefits of this platform include earlier detection of chronic conditions such as diabetes and cancer, as many of the initial changes responsible start as functional shifts within a cell population, and enhancement of new research into the use of cells as therapeutics. Because these cells are extracted from patients, it is important to develop techniques to examine their quality at the single-cell level to ensure that they function as intended. The project will also further educational opportunities for undergraduates, high school students, and underrepresented minorities in the greater Boston area specifically through guided internship programs for teachers and high school and undergraduate underrepresented minority students. The new platform will enhance an ongoing Nanopore Sequencing Laboratory Module by connecting the new cell sensing platform to the existing platform, allowing students to study both the genetic and physical properties of a single cell.The goal of this project is to utilize the interface of fluorescent nanosensor arrays within high throughput microfluidic channels such that scientifically relevant label free cellular populations can be studied nondestructively at the single cell level. The work builds on studies that will advance a new class of biophotonic monitoring platform pioneered by the investigator’s Lab at MIT. The sensor consists of near-infrared (nIR) fluorescent single-walled carbon nanotube (SWNT) nanosensors along a microfluidic channel through which flowing cells are guided. These nanosensors can be engineered to be optically responsive to local concentrations of biologically relevant chemical signals. Preliminary results showed that one can utilize the flowing cell itself as a Gaussian lens to amplify the nanosensor emission signal and extract rich information on a per cell basis in real-time. Due to the investigator’s method of imaging data collection, the biomolecular information extracted can be cross-correlated with individual cellular physical properties. As part of this project, first, the capabilities of such a system to accommodate multiple targeted nanosensors for multiplexed single cell detection will be studied. Next, the physical phenomenon of cellular lensing, including the effects of different cell types and experimental conditions will be studied. Finally, the newly developed sensor platform will be utilized to study commonly used cell types used in cell therapy, including: monocytes, macrophages, T-cells or neural stem cells.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.

生物学如何应对细胞水平的环境在人类健康和疾病中起重要作用。例如，相同类型和原点的细胞在功能上与另一个细胞之间有显着差异是很常见的。尽管以前的方法已经研究了细胞群体，但越来越清楚地测量细胞单独提供重要信息，有助于预测其作为生物的一部分。这是该项目的目的是开发一个新的平台，以快速的方式在单个细胞水平上以非破坏性方式探测细胞的功能特性（即细胞细胞仪）。该平台将利用新型的纳米传感器，这些纳米传感器可以通过检测其反射在用近红外光照射时来确定微通道中流动的单个单元的性质。该平台的潜在优势包括早期检测诸如糖尿病和癌症之类的慢性疾病，因为许多初始变化负责作为细胞种群内的功能转移以及对细胞用作治疗的使用的新研究增强。由于这些细胞是从患者中提取的，因此重要的是要开发技术以在单细胞水平上检查其质量以确保它们按预期发挥作用。该项目还将为大波士顿地区的大学生，高中生和代表性不足的少数群体提供更多教育机会，特别是通过针对教师，高中和本科生代表性不足的少数学生的指导实习计划。 The new platform will enhance an ongoing Nanopore Sequencing Laboratory Module by connecting the new cell sensing platform to the existing platform, allowing students to study both the genetic and physical properties of a single cell.The goal of this project is to utilize the interface of fluorescent nanosensor arrays within high throughput microfluidic channels Such that scientifically relevant label free cellular populations can be studied nondestructively at the single cell level.这项工作以研究为基础，该研究将推进由麻省理工学院研究者实验室开创的新型生物监测平台。该传感器由近红外（NIR）荧光单壁碳纳米管（SWNT）纳米传感器沿微流体通道组成，并通过该通道引导流动的细胞。可以设计这些纳米传感器对生物学相关的化学信号的局部浓度有光学响应。初步结果表明，人们可以利用流动的细胞本身作为高斯镜头来扩增纳米传感器发射信号，并实时以每个细胞为基础提取丰富的信息。由于研究者的成像数据收集方法，提取的生物分子信息可以与单个细胞物理特性交叉相关。作为该项目的一部分，首先，将研究该系统可容纳多个靶向纳米传感器进行多重单细胞检测的功能。接下来，将研究细胞镜头的物理现象，包括不同细胞类型和实验条件的影响。最后，新开发的传感器平台将用于研究细胞疗法中使用的常用细胞类型，包括：单核细胞，巨噬细胞，T细胞或神经元干细胞。该奖项反映了NSF的法定任务，并被认为是通过使用该基金会的智力和更广泛影响的评估来审查CRITERIA的评估来通过评估来获得的支持。