Highly sensitive spatial transcriptomics using FISHnCHIPs of multiple co-expressed genes.

High-dimensional, spatially resolved analysis of intact tissue samples promises to transform biomedical research and diagnostics, but existing spatial omics technologies are costly and labor-intensive. We present Fluorescence In Situ Hybridization of Cellular HeterogeneIty and gene expression Programs (FISHnCHIPs) for highly sensitive in situ profiling of cell types and gene expression programs. FISHnCHIPs achieves this by simultaneously imaging ~2-35 co-expressed genes (clustered into modules) that are spatially co-localized in tissues, resulting in similar spatial information as single-gene Fluorescence In Situ Hybridization (FISH), but with ~2-20-fold higher sensitivity. Using FISHnCHIPs, we image up to 53 modules from the mouse kidney and mouse brain, and demonstrate high-speed, large field-of-view profiling of a whole tissue section. FISHnCHIPs also reveals spatially restricted localizations of cancer-associated fibroblasts in a human colorectal cancer biopsy. Overall, FISHnCHIPs enables fast, robust, and scalable cell typing of tissues with normal physiology or undergoing pathogenesis.

Label-free quantitative measurement of cardiovascular dynamics in a zebrafish embryo using frequency-comb-referenced-quantitative phase imaging.

SIGNIFICANCE: Real-time monitoring of the heart rate and blood flow is crucial for studying cardiovascular dysfunction, which leads to cardiovascular diseases. AIM: This study aims at in-depth understanding of high-speed cardiovascular dynamics in a zebrafish embryo model for various biomedical applications via frequency-comb-referenced quantitative phase imaging (FCR-QPI). APPROACH: Quantitative phase imaging (QPI) has emerged as a powerful technique in the field of biomedicine but has not been actively applied to the monitoring of circulatory/cardiovascular parameters, due to dynamic speckles and low frame rates. We demonstrate FCR-QPI to measure heart rate and blood flow in a zebrafish embryo. FCR-QPI utilizes a high-speed photodetector instead of a conventional camera, so it enables real-time monitoring of individual red blood cell (RBC) flow. RESULTS: The average velocity of zebrafish's RBCs was measured from 192.5 to 608.8 µm / s at 24 to 28 hour-post-fertilization (hpf). In addition, the number of RBCs in a pulsatile blood flow was revealed to 16 cells/pulse at 48 hpf. The heart rates corresponded to 94 and 142 beats-per-minute at 24 and 48 hpf. CONCLUSIONS: This approach will newly enable in-depth understanding of the cardiovascular dynamics in the zebrafish model and possible usage for drug discovery applications in biomedicine.

Ultrasensitive Anti-Interference Voice Recognition by Bio-Inspired Skin-Attachable Self-Cleaning Acoustic Sensors.

Human voice recognition systems (VRSs) are a prerequisite for voice-controlled human-machine interfaces (HMIs). In order to avoid interference from unexpected background noises, skin-attachable VRSs are proposed to directly detect physiological mechanoacoustic signals based on the vibrations of vocal cords. However, the sensitivity and response time of existing VRSs are bottlenecks for efficient HMIs. In addition, water-based contaminants in our daily lives, such as skin moisture and raindrops, normally result in performance degradation or even functional failure of VRSs. Herein, we present a skin-attachable self-cleaning ultrasensitive and ultrafast acoustic sensor based on a reduced graphene oxide/polydimethylsiloxane composite film with bioinspired microcracks and hierarchical surface textures. Benefitting from the synergetic effect of the spider-slit-organ-like multiscale jagged microcracks and the lotus-leaf-like hierarchical structures, our superhydrophobic VRS exhibits an ultrahigh sensitivity (gauge factor, GF = 8699), an ultralow detection limit (ε = 0.000 064%), an ultrafast response/recovery behavior, an excellent device durability (>10 000 cycles), and reliable detection of acoustic vibrations over the audible frequency range (20-20 000 Hz) with high signal-to-noise ratios. These superb performances endow our skin-attachable VRS with anti-interference perception of human voices with high precision even in noisy environments, which will expedite the voice-controlled HMIs.

High-brightness laser imaging with tunable speckle reduction enabled by electroactive micro-optic diffusers.

High coherence of lasers is desirable in high-speed, high-resolution, and wide-field imaging. However, it also causes unavoidable background speckle noise thus degrades the image quality in traditional microscopy and more significantly in interferometric quantitative phase imaging (QPI). QPI utilizes optical interference for high-precision measurement of the optical properties where the speckle can severely distort the information. To overcome this, we demonstrated a light source system having a wide tunability in the spatial coherence over 43% by controlling the illumination angle, scatterer's size, and the rotational speed of an electroactive-polymer rotational micro-optic diffuser. Spatially random phase modulation was implemented for the lower speckle imaging with over a 50% speckle reduction without a significant degradation in the temporal coherence. Our coherence control technique will provide a unique solution for a low-speckle, full-field, and coherent imaging in optically scattering media in the fields of healthcare sciences, material sciences and high-precision engineering.

Speckle reduction in quantitative phase imaging by generating spatially incoherent laser field at electroactive optical diffusers.

We studied quantitative phase imaging (QPI) using coherent laser illumination coupled with static and moving optical diffusers. The spatial coherence of a continuous-wave laser was controlled by tuning the particle size and the diffusion angle of optical diffusers for speckle-reduced 3D phase imaging of transparent objects. We used a common-path QPI configuration to investigate the coherent phase mapping of polystyrene micro-beads and breast cancer cells (MCF-7) under different degrees of coherent speckles. The proposed speckle reduction method could provide an avenue for enhancing lateral resolution and suppressing coherent artifacts of the phase images from QPI.