Laser particles for multi-dimensional single-cell analysis

项目摘要 这项拟议工作的广泛目标是通过引入新的细胞条形码来推进单细胞分析 技术。了解细胞是生命科学的基石。单细胞测序导致了一种范式 我们分析细胞的方法从整体到单个细胞的转变。不幸的是，目前的单细胞 分析技术几乎完全是静态的，在体外执行，因此不容易探测动态 细胞过程。除了静态分析，下一个重要的步骤是添加更多维度：符合以下条件的所有内容 使细胞成为有生命的实体，包括时间变化、空间运动、与体内其他细胞的相互作用。 该项目将开发激光粒子(LP)，它可以实时和重复地光学读取，如 多维单细胞分析所需的。使用光学条形码，可以从 在不同的时间、地点和设备上对单元格进行统计，并汇编数据以生成单元格的完整说明。一个 LP与寡核苷酸条形码的结合使获取大规模数据成为可能 从活体生理学到分子组学，使用多种仪器串联。该项目的组织方式是 三个具体目标。目标1开发与寡头条码相结合的大规模LP条码。AIM 2结构 将LP条形码读取器集成到商业平台的几种仪器。目标3涉及验证 研究以展示新技术的立竿见影的效用。光学条形码有望 改变单细胞分析的范式。这将改变多维单细胞 分析用于医疗保健中的科学发现以及诊断和治疗应用。

Project Summary The broad objective of this proposed work is to advance single-cell analysis by introducing novel cell-barcoding technologies. Understanding cells is a cornerstone of life sciences. Single-cell sequencing led to a paradigm shift in our approach to analyze cells from ensembles to individual cells. Unfortunately, the current single-cell analysis techniques are almost exclusively static, performed ex vivo, and thus cannot easily probe the dynamic cellular processes. Beyond static analysis, the next important step is to add more dimensions: everything that makes a cell a living entity, including temporal changes, spatial movement, interactions with other cells in vivo. This project will develop laser particles (LPs), which can be read optically in real time and repeatedly as needed, for multi-dimensional single-cell analysis. With the optical barcode, it is possible to acquire data from a cell at different times, locations and apparatuses, and compile the data to produce a full account of the cell. A combination of LPs with oligonucleotide barcodes enables a breakthrough approach acquiring large-scale data from in vivo physiology to molecular omics using multiple instruments in series. This project is organized in three specific aims. Aim 1 develops large-scale LP barcodes combined with oligo barcodes. Aim 2 constructs several instruments integrating LP barcode readers into commercial platforms. Aim 3 involves validation studies to demonstrate the immediate utilities of the new technologies. The optical barcoding is expected to make a paradigm change in single-cell analysis. This will transform the way multi-dimensional single-cell analysis is used for scientific discovery and diagnostic and therapeutic applications in healthcare.