EAGER: Origami inspired 3D Biosensors for Single Cell Analysis

人类工程学长期面临的挑战是对单细胞进行高灵敏度和选择性的鉴定、捕获和分析。这一挑战的动机是需要了解组织中的渐进或动态事件，否则这些事件可能在广泛的群体分析中被平均掉。PI建议利用折纸灵感的折叠设计来创建3D图案自主生物传感器，可用于主动捕获和分析相同微观结构中的单个细胞。这种目前尚不存在的设备将显著改善芯片实验室或基于阵列的诊断设备的生物传感协议，使超高分辨率组织采样成为可能，并为科学发现提供新的工具。该方案寻求使用高分辨率光刻方法在2D中绘制透明的生物相容性薄膜，并在这些图案薄膜中进行工程应变，以便它们在单个细胞周围折叠。我们建议开发这种具有生物分子模式的自折叠装置，并表明我们能够同时在单个自折叠结构中以平行和高通量的方式使用光学方法进行单细胞捕获和分析。除了基板上的阵列，我们的方法还可以用于创建自由浮动的自折叠夹具，用于组织样本的单细胞切除和分析。该方法为3D单细胞生物传感器提供了一个新的范例，我们将把我们的研究与针对K-12、本科生和研究生的教育和推广工作结合起来。

A long standing challenge in human engineering has been the identification, capture and analysis of single cells with high sensitivity and selectivity. This challenge is motivated by the need to understand progressive or dynamical events in tissues that might otherwise be averaged away in a population wide analysis. The PI proposes to utilize origami inspired folding designs to create 3D patterned autonomous biosensors that can be used to actively capture and analyze single cells in the same microstructure. Such devices which do not exist at the present time would lead to significantly improved biosensing protocols for lab-on-a-chip or array-based diagnostic devices, enable ultra-high resolution tissue sampling and provide new tools for scientific discovery. The proposal seeks to pattern transparent biocompatible thin films in 2D using high resolution lithographic approaches and engineer strain within these patterned films so that they fold up around single cells. We propose to develop such self-folding devices with biomolecular patterns and show that we are able to simultaneously perform a single cell capture and assay it using optical methods within a single self-folded structure in a parallel and high throughput manner. In addition to arrays on substrates, our methods could also be adapted to create free floating self-folding grippers for single cell excision and analysis from tissue samples. The approach provides a new paradigm for 3D single cell biosensors and we will integrate our research with educational and outreach efforts directed at K-12, undergraduate and graduate students.