LiDAR is an enabling sensor technology for autonomous vehicles, industrial automation, and robotics. However, large-scale adoption is hindered by cost and robustness. We have developed systems that address these challenges through a camera-like flash architecture, which eliminates moving parts and allows for simple optical and emitter designs that are robust and manufacturable at low cost. Large curved VCSEL arrays created using microtransfer printing illuminate the field of view, and 2D sensor arrays capture high resolution range data from the entire scene at once. Flash architecture with no moving parts enables robust LiDAR with lower cost to facilitate large-scale automation.
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) have promise for elucidating basic biological processes, drug testing, and regenerative medicine, yet are known to be heterogenous and immature. Methods to analyze cardiomyocytes are typically destructive or require labeling that alters the cells’ performance. Thus, we have developed a non-invasive image-based method for analyzing and classifying cardiomyocytes based on their morphology and contractile properties, and applied this method to analyze the effects of controlling cell shape.
We optimized a diffraction phase microscope (DPM) to yield low noise optical thickness measurements at over 100 frames per second. We extracted contraction and relaxation motion cycles of single hiPSC-CMs and analyzed beat frequency and regularity. DPM also enabled comparisons of morphological characteristics by measuring the optical thickness of the cells.
We compared populations of hiPSC-CMs with controlled (patterned) and uncontrolled (unpatterned) shape and we observed the following: 1) patterning effectively controls the shape of the cells, while cells with the desired mature-like shape rarely appear in the unpatterned population, 2) patterned cells are more likely to beat with consistent and lower beat frequency compared to unpatterned cells, and 3) the patterns tend to select for larger (more mature-like) cells. Finally, we identified a cutoff point under which cells of a certain dry mass do not adhere to the patterns. These results indicate that controlling the shape of hiPSC-CMs improves their characteristics, which can be analyzed using DPM, and has the potential to yield more consistent research results and homogenous populations of cells for clinical applications.
Beating heart cells, cardiomyocytes, are used in drug testing and have the potential for regenerative medicine. Currently their classification into atrial, nodal and ventricular subtypes is performed using destructive and tedious patch clamp measurements. We present a method for analyzing cardiomyocyte contraction cycles using diffraction phase microscopy, a fast quantitative phase imaging method based on off-axis common-path interferometry. The phase variation during the beating cycle can exceed 300 mrad in the most active regions, and is about 40 mrad on average. The phase noise is about 2 mrad per pixel, and it can be reduced by temporal averaging over multiple frames and spatial averaging over the cell. With a maximum acquisition rate exceeding 25,000 fps and with approximately 100 fps required for the characterization of cardiomyocyte motion, 250 frames can be averaged per step, reducing the temporally white noise by a factor of 16. Additional improvements can be obtained by averaging over multiple contraction cycles. Averaging over space does not reduce noise to the same extent due to low-pass spatial filtering during the phase extraction procedure. Low-pass filtering by the pinhole in the reference arm, resulting in high-pass filtering of the image, and low-pass filtering during the phase reconstruction highlight the dynamics of redistribution of dry mass within the cell during a beat cycle. Quantitative phase imaging is a promising approach for rapid, non-invasive, high-throughput characterization of human stem cell-derived cardiomyocytes in culture, with applications to modeling of diseases with patients' specific genes, drug development, and repair of damaged heart tissue.
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