Single cell manipulation is important in biosensing, biorobotics, and quantitative cell analysis. Although microbeads, droplets, and microrobots have been developed previously, it is still challenging to simultaneously excise, capture, and manipulate single cells in a biocompatible manner. Here, we describe untethered single cell grippers, that can be remotely guided and actuated on-demand to actively capture or excise individual or few cells. We describe a novel molding method to micropattern a thermally responsive wax layer for biocompatible motion actuation. The multifingered grippers derive their energy from the triggered release of residual differential stress in bilayer hinges composed of silicon oxides. A magnetic layer enables remote guidance through narrow conduits and fixed tissue sections ex vivo. Our results provide an important advance in high-throughput single cell scale biopsy tools important to lab-on-a-chip devices, microrobotics, and minimally invasive surgery.

Brain organoids are important models for mimicking some three-dimensional (3D) cytoarchitectural and functional aspects of the brain. Multielectrode arrays (MEAs) that enable recording and stimulation of activity from electrogenic cells offer notable potential for interrogating brain organoids. However, conventional MEAs, initially designed for monolayer cultures, offer limited recording contact area restricted to the bottom of the 3D organoids. Inspired by the shape of electroencephalography caps, we developed miniaturized wafer-integrated MEA caps for organoids. The optically transparent shells are composed of self-folding polymer leaflets with conductive polymer–coated metal electrodes. Tunable folding of the minicaps’ polymer leaflets guided by mechanics simulations enables versatile recording from organoids of different sizes, and we validate the feasibility of electrophysiology recording from 400- to 600-μm-sized organoids for up to 4 weeks and in response to glutamate stimulation. Our studies suggest that 3D shell MEAs offer great potential for high signal-to-noise ratio and 3D spatiotemporal brain organoid recording.

The ability of cells to sense and respond to mechanical signals from their surrounding microenvironments is one of the key issues in tissue engineering and regeneration, yet a fundamental study of cells with both cell observation and mechanical stimulus is challenging and should be based upon an appropriate microdevice. Herein we designed and fabricated a two-layer microfluidic chip to enable simultaneous observation of live cells and cyclic stretching of an elastic polymer, polydimethylsiloxane (PDMS), with a modified surface for enhanced cell adhesion. Human mesenchymal stem cells (hMSCs) were examined with a series of frequencies from 0.00003 to 2 Hz and varied amplitudes of 2%, 5%, or 10%. The cells with an initial random orientation were confirmed to be reoriented perpendicular to the stretching direction at frequencies greater than a threshold value, which we term critical frequency ( f c ); additionally, the critical frequency f c was amplitude-dependent. We further introduced the concept of critical stretching rate (R c ) and found that this quantity can unify both frequency and amplitude dependences. The reciprocal value of R c in this study reads 8.3 min, which is consistent with the turnover time of actin filaments reported in the literature, suggesting that the supramolecular relaxation in the cytoskeleton within a cell might be responsible for the underlying cell mechanotransduction. The theoretical calculation of cell reorientation based on a two-dimensional tensegrity model under uniaxial cyclic stretching is well consistent with our experiments. The above findings provide new insight into the crucial role of critical frequency and critical stretching rate in regulating cells on biomaterials under biomechanical stimuli.

Stimuli responsive self‐folding structures with 2D layered materials (2DLMs) are important for flexible electronics, wearables, biosensors, bioelectronics, and photonics. Previously, strategies have been developed to self‐fold 2D materials to form various robots, sensors, and actuators. Still, there are limitations with scalability and a lack of design tools to obtain complex structures for reversible actuation, high integration, and reliable function. Herein, a mass‐producible strategy for creating monolayer graphene‐based reversible self‐folding structures using either gradient or differentially cross‐linked films of a negative epoxy photoresist widely used in microfluidics and micromechanical systems, namely, SU8 is demonstrated. Wafer‐scale patterning and integration of complex and functional devices in the form of rings, polyhedra, flowers, and bidirectionally folded origami birds are achieved. Also, gold (Au) electrodes to realize functional graphene–Au Schottky interfaces with enhanced photoresponse and 3D angle sensitive detection are integrated. The experiments are guided and rationalized by theoretical methods including coarse‐grained models, specifically developed for the tunable mechanics of this photoresist that simulate the folding dynamics, and finite element method (FEM) electromagnetic simulations. This work suggests a comprehensive framework for the rational design and scalable fabrication of complex 3D self‐actuating optical and electronic devices through the folding of 2D monolayer graphene.

While the microfluidic chips for cell stretching and real-time cell observations have so far been composed of three layers, the present work reports a two-layer one, which is, on the surface, not available due to the ‘inherent’ difficulty of unstable focusing on cells in the microscopic observation under the stretching operation, etc. Herein, this difficulty was overcome to a large extent, in the case of appropriate device parameters, which were determined based upon finite element analysis and orthogonal experimental design. The novel chip was fabricated and confirmed to work in frequency up to 2 Hz and stretching ratio up to 20%. We further performed uniaxial stretching experiments of human mesenchymal stem cells on an elastic polymer, polydimethylsiloxane, and the cells were found to be highly oriented perpendicular to the stretching direction. The short working distance on this simplified two-layer chip enabled clear observation of microtubules and stress fibers of cells under an optical microscope. We also tested radial stretching and gradient stretching as proofs of concept of the extendibility of this type of chip. Therefore, in spite of being simpler, the two-layer chip suggested in this study exhibited enhanced and versatile functions, and the present work has thus afforded a new methodology of fabrication of microfluidic chips for the study of cells on biomaterials under a mechanical stimulus.