EAGER: Origami inspired 3D Biosensors for Single Cell Analysis

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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.