Acoustic actuation of bioinspired microswimmers is experimentally demonstrated. Microswimmers are in situ fabricated in a microchannel. Upon acoustic excitation, the flagellum of the microswimmer oscillates, which in turn generates linear or rotary movement depending on the swimmer design. The speed of these bioinspired microswimmers is tuned by adjusting the voltage amplitude applied to the acoustic transducer. Simple microfabrication and remote actuation are promising for biomedical applications.
The appearance of DNA in the cytosol is perceived as a danger signal that stimulates potent immune responses through cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS). How cells regulate the activity of cGAS toward self-DNA and guard against potentially damaging autoinflammatory responses is a fundamental biological question. Here, we identify barrier-to-autointegration factor 1 (BAF) as a natural opponent of cGAS activity on genomic self-DNA. We show that BAF dynamically outcompetes cGAS for DNA binding, hence prohibiting the formation of DNA-cGAS complexes that are essential for enzymatic activity. Upon acute loss of nuclear membrane integrity, BAF is necessary to restrict cGAS activity on exposed DNA. Our observations reveal a safeguard mechanism, distinct from physical separation, by which cells protect themselves against aberrant immune responses toward genomic DNA.
Malignancy and tumour progression are associated with cancer-cell softening. Yet how the biomechanics of cancer cells affects T-cell mediated cytotoxicity and thus the outcomes of adoptive T-cell immunotherapies is unknown. Here, we show that T-cell-mediated cancer-cell killing is hampered for cortically soft cancer cells, whose plasma membrane is enriched with cholesterol, and that cancer-cell stiffening via cholesterol depletion augments T-cell cytotoxicity and enhances the efficacy of adoptive T-cell therapy against solid tumours in mice. We also show that the enhanced cytotoxicity against stiffened cancer cells is mediated by augmented T-cell forces arising from an increased accumulation of filamentous actin at the immunological synapse, and that cancer-cell stiffening has a negligible influence on T-cell-receptor signalling, on the production of cytolytic proteins such as granzyme B, on the secretion of interferon gamma and tumour necrosis factor alpha, and on Fas-receptor–Fas-ligand interactions. Our findings reveal a mechanical immune checkpoint that could be targeted therapeutically to improve the effectiveness of cancer immunotherapies. Cancer cells enriched with cholesterol in their plasma membrane impair T-cell mediated cytotoxicity, which can be augmented by stiffening the cancer cells via cholesterol depletion, as shown in mouse models of adoptive T-cell therapy.
We have demonstrated in situ fabricated and acoustically actuated microrotors. A polymeric microrotor with predefined oscillating sharp-edge structures is fabricated in situ by applying a patterned UV light to polymerize a photocrosslinkable polyethylene glycol solution inside a microchannel around a polydimethylsiloxane axle. To actuate the microrotors by oscillating the sharp-edge structures, we employed piezoelectric transducers which generate tunable acoustic waves. The resulting acoustic streaming flows rotate the microrotors. The rotation rate is tuned by controlling the peak-to-peak voltage applied to the transducer. A 6-arm microrotor can exceed 1200 revolutions per minute. Our technique is an integration of single-step microfabrication, instant assembly around the axle, and easy acoustic actuation for various applications in microfluidics and microelectromechanical systems (MEMS).
Controllable rotational manipulation enables multi-dimensional imaging and rapid screening of single cells and model organisms. Current approaches to rotationally maneuver small objects depend on optical, magnetic, or electrical properties of the sample under investigation. This dependence renders the existing methods sample-specific which limits their applicability. Here we present a new rotational manipulation method based on oscillating sidewall sharp-edge microstructures and thin glass slides in a microchannel. This method is independent of the intrinsic properties of sample under investigation and can be effectively applied to particles, cells, and multicellular organisms.
A design, manufacturing, and control methodology is presented for the transduction of ultrasound into frequency-selective actuation of multibody hydrogel mechanical systems. The modular design of compliant mechanisms is compatible with direct laser writing and the multiple degrees of freedom actuation scheme does not require incorporation of any specific material such as air bubbles. These features pave the way for the development of active scaffolds and soft robotic microsystems from biomaterials with tailored performance and functionality. Finite element analysis and computational fluid dynamics are used to quantitatively predict the performance of acoustically powered hydrogels immersed in fluid and guide the design process. The outcome is the remotely controlled operation of a repertoire of untethered biomanipulation tools including monolithic compound micromachinery with multiple pumps connected to various functional devices. The potential of the presented technology for minimally invasive diagnosis and targeted therapy is demonstrated by a soft microrobot that can on-demand collect, encapsulate, and process microscopic samples. Microfabricated devices have led to revolutionary changes in our ability to manipulate small volumes of fluid and microscopic samples contained therein. [1] As a result, majority of state-of-the-art in vitro biomedical platforms contain microfluidic components. Operating these devices requires the use of bulky pumps, compressors, or tethered electrical powering units, which significantly increase the overall size and limit the portability. A key technological challenge has been the development of untethered microfluidic systems that are capable of providing such functionality with wireless control for in vivo applications. Ideally, such systems are expected to determine the timing, duration, and dosage of the intervention and allow remote, noninvasive, repeatable, and reliable control of diagnostic or
We present an acoustofluidic micromixer which can perform rapid and homogeneous mixing of highly viscous fluids in the presence of an acoustic field. In this device, two high-viscosity polyethylene glycol (PEG) solutions were co-injected into a three-inlet PDMS microchannel with the center inlet containing a constant stream of nitrogen flow which forms bubbles in the device. When these bubbles were excited by an acoustic field generated via a piezoelectric transducer, the two solutions mixed homogenously due to the combination of acoustic streaming, droplet ejection, and bubble eruption effects. The mixing efficiency of this acoustofluidic device was evaluated using PEG-700 solutions which are ~106 times more viscous than deionized (DI) water. Our results indicate homogenous mixing of the PEG-700 solutions with a ~0.93 mixing index. The acoustofluidic micromixer is compact, inexpensive, easy to operate, and has the capacity to mix highly viscous fluids within 50 milliseconds.
We present a methodology for building biologically inspired, soft microelectromechanical systems (MEMS) devices.
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