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Biohybrid robots, composed of cellular actuators and synthetic scaffolds, have garnered much attention in recent years owing to the advantages provided by their biological components. In recent years, various forms of biohybrid robots have been developed that are capable of life-like movements, such as walking, swimming, and gripping. Specifically, for walking or crawling biorobots, there is a need for complex functionality and versatile and robust fabrication processes. Here, we designed and fabricated multi-actuator biohybrid walkers with multi-directional walking capabilities in response to noninvasive optical stimulation through a scalable modular biofabrication process. Our new fabrication approach provides a constant mechanical strain throughout the cellular differentiation and maturation process. This maximizes the myotube formation and alignment, limits passive bending, and produces higher active forces. These demonstrations of the new fabrication process and bioactuator designs can pave the way for advanced multi-cellular biohybrid robots and enhance our understanding of the emergent behaviors of these multi-cellular engineered living systems. 

A silicon integrated microfluidics system prints picoliter-segmented analytes for attomole-level chemical analysis with mass spectrometry imaging. 

Biohybrid centimeter-scale robots developed from optoelectronics and optogenetic muscles can be controlled wirelessly. 

Rapid, simple, inexpensive, accurate, and sensitive point-of-care (POC) detection of viral pathogens in bodily fluids is a vital component of controlling the spread of infectious diseases. The predominant laboratory-based methods for sample processing and nucleic acid detection face limitations that prevent them from gaining wide adoption for POC applications in low-resource settings and self-testing scenarios. Here, we report the design and characterization of an integrated system for rapid sample-to-answer detection of a viral pathogen in a droplet of whole blood comprised of a 2-stage microfluidic cartridge for sample processing and nucleic acid amplification, and a clip-on detection instrument that interfaces with the image sensor of a smartphone. The cartridge is designed to release viral RNA from Zika virus in whole blood using chemical lysis, followed by mixing with the assay buffer for performing reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) reactions in six parallel microfluidic compartments. The battery-powered handheld detection instrument uniformly heats the compartments from below, and an array of LEDs illuminates from above, while the generation of fluorescent reporters in the compartments is kinetically monitored by collecting a series of smartphone images. We characterize the assay time and detection limits for detecting Zika RNA and gamma ray-deactivated Zika virus spiked into buffer and whole blood and compare the performance of the same assay when conducted in conventional PCR tubes. Our approach for kinetic monitoring of the fluorescence-generating process in the microfluidic compartments enables spatial analysis of early fluorescent “bloom” events for positive samples, in an approach called “Spatial LAMP” (S-LAMP). We show that S-LAMP image analysis reduces the time required to designate an assay as a positive test, compared to conventional analysis of the average fluorescent intensity of the entire compartment. S-LAMP enables the RT-LAMP process to be as short as 22 minutes, resulting in a total sample-to-answer time in the range of 17–32 minutes to distinguish positive from negative samples, while demonstrating a viral RNA detection as low as 2.70 × 10 2 copies per μl, and a gamma-irradiated virus of 10 3 virus particles in a single 12.5 μl droplet blood sample. 

The ability to engineer complex multicellular systems has enormous potential to inform our understanding of biological processes and disease and alter the drug development process. Engineering living systems to emulate natural processes or to incorporate new functions relies on a detailed understanding of the biochemical, mechanical, and other cues between cells and between cells and their environment that result in the coordinated action of multicellular systems. On April 3–6, 2022, experts in the field met at the Keystone symposium “Engineering Multicellular Living Systems” to discuss recent advances in understanding how cells cooperate within a multicellular system, as well as recent efforts to engineer systems like organ-on-a-chip models, biological robots, and organoids. Given the similarities and common themes, this meeting was held in conjunction with the symposium “Organoids as Tools for Fundamental Discovery and Translation”.