Single-cell RNA sequencing (scRNA-seq) technologies are poised to reshape the current cell-type classification system. However, a transcriptome-based single-cell atlas has not been achieved for complex mammalian systems. Here, we developed Microwell-seq, a high-throughput and low-cost scRNA-seq platform using simple, inexpensive devices. Using Microwell-seq, we analyzed more than 400,000 single cells covering all of the major mouse organs and constructed a basic scheme for a mouse cell atlas (MCA). We reveal a single-cell hierarchy for many tissues that have not been well characterized previously. We built a web-based "single-cell MCA analysis" pipeline that accurately defines cell types based on single-cell digital expression. Our study demonstrates the wide applicability of the Microwell-seq technology and MCA resource.
Flying insects capable of navigating in highly cluttered natural environments can withstand inflight collisions because of the combination of their low inertia 1 and the resilience of their wings 2 , exoskeletons 1 , and muscles. Current insect-scale (<10 cm, <5 g) aerial robots 3-6 use rigid microscale actuators, which are typically fragile under external impact. Biomimetic artificial muscles 7-10 capable of large deformation offer a promising alternative for actuation because they can endure the stresses caused by such impacts. However, existing soft actuators 11-13 have not yet demonstrated sufficient power density for liftoff, and their actuation nonlinearity and limited bandwidth further create challenges for achieving closed-loop flight control. Here we develop the first heavier-than-air aerial robots powered by soft artificial muscles that demonstrate open-loop, passively stable ascending flight as well as closed-loop, hovering flight. The robots are driven by 100 mg, multilayered dielectric elastomer actuators (DEA) that have a resonant frequency and power density of 500 Hz and 600 W/kg, respectively. To increase actuator output mechanical power and to demonstrate flight control, we present strategies to overcome challenges unique to soft actuators, such as nonlinear transduction and dynamic buckling. These robots can sense, and withstand, collisions with surrounding obstacles, and can recover from in-flight collisions by exploiting material robustness and vehicle passive stability. We further perform a simultaneous flight with two micro-aerial-vehicles (MAV) in cluttered environments. These robots rely on offboard amplifiers and an external motion capture system to provide power to the DEAs and control flights. Our work demonstrates how soft actuators can achieve sufficient power density and bandwidth to enable controlled flight, illustrating the vast potential of developing next-generation agile soft robots. Soft robotics 14-16 is an emerging field aiming to develop versatile systems that can safely interact with humans and manipulate delicate objects in unstructured environments. A major challenge in building softactuated mobile robots involves developing muscle-like actuators that have high energy density, bandwidth, robustness, and lifetime. Previous studies have described soft actuators that can be actuated chemically 17 , pneumatically 18,19 , hydraulically 20 , thermally 21,22 , or electrically 7,23. Among these soft transducers, DEAs have shown a combination of muscle-like energy density and bandwidth 8 , enabling the development of biomimetic robots capable of terrestrial 11,24,25 and aquatic locomotion 26,27. However, while there is growing interest in developing heavier-than-air, soft-actuated aerial robots, existing soft robots 11-13 have been unable to achieve liftoff due to limited actuator power density (<200 W/kg), bandwidth (<20 Hz), and difficulties of integration with rigid robotic structures such as transmission and wings. To enable controlled hovering flight of a soft-actuated robot,...
To precisely deliver drug molecules at a targeted site and in a controllable manner, there has been great interest in designing a synergistical drug delivery system that can achieve both surface charge-conversion and controlled release of a drug in response to different stimuli. Here we outline a simple method to construct an intelligent drug carrier, which can respond to two different pH values, therefore achieving charge conversion and chemical-bond-cleavage-induced drug release in a stepwise fashion. This drug carrier comes from the self-assembly of a block copolymer-DOX conjugate synthesized through a Schiff base reaction between poly(2-(diisopropylamino)ethyl methacrylate-b-poly(4-formylphenyl methacrylate-co-polyethylene glycol monomethyl ether methacrylate) (PDPA-b-P(FPMA-co-OEGMA)) and DOX. The surface charge of the BCP-DOX micelles reversed from negative to positive when encountering a weakly acidic environment due to the protonation of PDPA segments. In vitro cellular uptake measurement shows that the cellular uptake and internalization of the BCP-DOX micelles can be significantly enhanced at pH ∼ 6.5. Moreover, this drug carrier exhibits a pH-dependent drug release owing to the cleavage of the imine bond at pH < 5.5. With this dual-pH responsive feature, these micelles may have the ability to precisely deliver DOX to the cancer cells.
Although there have been notable advances in adhesive materials, the ability to program attaching and detaching behavior in these materials remains a challenge. Here, we report a borate ester polymer hydrogel that can rapidly switch between adhesive and nonadhesive states in response to a mild electrical stimulus (voltages between 3.0 and 4.5 V). This behavior is achieved by controlling the exposure and shielding of the catechol group through water electrolysis–induced reversible cleavage and reformation of the borate ester moiety. By switching the electric field direction, the hydrogel can repeatedly attach to and detach from various surfaces with a response time as low as 1 s. This programmable attaching/detaching strategy provides an alternative approach for robot climbing. The hydrogel is simply pasted onto the moving parts of climbing robots without complicated engineering and morphological designs. Using our hydrogel as feet and wheels, the tethered walking robots and wheeled robots can climb on both vertical and inverted conductive substrates (i.e., moving upside down) such as stainless steel and copper. Our study establishes an effective route for the design of smart polymer adhesives that are applicable in intelligent devices and an electrochemical strategy to regulate the adhesion.
Active soft materials that change shape on demand are of interest for a myriad of applications, including soft robotics, biomedical devices, and adaptive systems. Despite recent advances, the ability to rapidly design and fabricate active matter in complex, reconfigurable layouts remains challenging. Here, the 3D printing of core-sheath-shell dielectric elastomer fibers (DEF) and fiber bundles with programmable actuation is reported. Complex shape morphing responses are achieved by printing individually addressable fibers within 3D architectures, including vertical coils and fiber bundles. These DEF devices exhibit resonance frequencies up to 700 Hz and lifetimes exceeding 2.6 million cycles. The multimaterial, multicore-shell 3D printing method opens new avenues for creating active soft matter with fast programable actuation.
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