Metasurface-enhanced mid-infrared spectrochemical imaging of tissues.

Label-free and nondestructive mid-infrared vibrational hyperspectral imaging is emerging as an important ex-vivo tissue analysis tool, providing spatially resolved biochemical information critical to understanding physiological and pathological processes. However, the chemically complex and spatially heterogeneous composition of tissue specimens and the inherently weak interaction of infrared light with biomolecules limit the analytical performance of infrared absorption spectroscopy. Here, we introduce an advanced mid-infrared spectrochemical tissue imaging modality using metasurfaces that support strong surface-localized electromagnetic fields to capture quantitative molecular maps of large-area murine brain-tissue sections. Our approach leverages polarization-multiplexed multi-resonance plasmonic metasurfaces to simultaneously detect many different functional biomolecules. The resulting surface-enhanced mid-infrared spectral imaging (SE-MIRSI) method eliminates the non-specific effects of bulk tissue morphology on the quantitative analysis of fingerprint spectra and improves the chemical selectivity. We show that the metasurface enhancement increases the retrieval of amide I and II absorption bands associated with secondary structures of proteins. Moreover, we demonstrate that plasmonic metasurfaces enhance the chemical contrast in infrared images and enable the detection of ultrathin tissue regions that are not otherwise visible to conventional mid-infrared spectral imaging. While we tested our approach on murine brain tissue sections, this chemical imaging method is well-suited for any tissue type, which significantly broadens the potential impacts of our method for both translational research and clinical histopathology.

Highly efficient and gentle trapping of single cells in large microfluidic arrays for time-lapse experiments.

The isolation of single biological cells and their further cultivation in dedicated arrayed chambers are key to the collection of statistically reliable temporal data in cell-based biological experiments. In this work, we present a hydrodynamic single cell trapping and culturing platform that facilitates cell observation and experimentation using standard bio-lab equipment. The proposed design leverages the stochastic position of the cells as they flow into the structured microfluidic channels, where hundreds of single cells are then arrayed in nanoliter chambers for simultaneous cell specific data collection. Numerical simulation tools are used to devise and implement a hydrodynamic cell trapping mechanism that is minimally detrimental to the cell cycle and retains high overall trapping efficiency (∼70%) with the capability of reaching high fill factors (>90%) in short loading times (1-4 min) in a 400-trap device. A Monte Carlo model is developed using the design parameters to estimate the system trapping efficiencies, which show strong agreement with the experimentally acquired data. As proof of concept, arrayed mammalian tissue cells (MIA PaCa-2) are cultured in the microfluidic chambers for two days without viability problems.

3D nanostructures fabricated by advanced stencil lithography.

This letter reports on a novel fabrication method for 3D metal nanostructures using high-throughput nanostencil lithography. Aperture clogging, which occurs on the stencil membranes during physical vapor deposition, is leveraged to create complex topographies on the nanoscale. The precision of the 3D nanofabrication method is studied in terms of geometric parameters and material types. The versatility of the technique is demonstrated by various symmetric and chiral patterns made of Al and Au.