Assay Development and Screening
Label-free three-dimensional (3D) chemical imaging of live cells is critical to map molecular distributions and determine their dynamics in various physiological and pathological transformations of single cells. Yet, existing optical tools are limited by their inability to offer the desired combination of 3D structural information and endogenous molecular contrast. To facilitate such non-perturbative monitoring of single live cells (without loss of information due to averaging in population analyses), we report an approach for trapping arrays of single live cells and profiling intrinsic molecular signatures that collectively enable the monitoring of intracellular events without targeting specific epitopes. Our approach, named mechanical trap surface-enhanced Raman spectroscopy (MT-SERS), employs a combination of nanoparticle coated self-folding microgripper shaped devices and surface-enhanced Raman spectroscopy (SERS). These microgrippers, which roll-up due to tailored residual stresses induced during fabrication, offer a facile biocompatible platform to precisely trap single live cells for longitudinal analysis without the need for any batteries or external power sources. By leveraging functionalization of the inner surfaces of these traps with plasmonic nanostars, the MT-SERS method permits excellent SERS enhancement, which facilitates label-free molecular interrogation without any photodamage to the cells. We show that the developed platform reliably detects intrinsic chemical signatures over trapped microbeads as well as over a single trapped cell, and thus providing a multiplex volumetric distribution of analytes, such as lipids and nucleic acids. Taken together with the demonstrated ability to track compositional changes in dry, fluid and untethered environments, our findings underscore the potential of MT-SERS to furnish biologically interpretable and quantitative molecular maps, and therefore also opens the door for the elucidation of intercellular variability in normal and diseased cell populations.