Xiaoming Liu

The rotational operation of oocytes plays a critical role in embryo engineering, particularly in assisted reproductive technology, cloning, and gene research. The conventional manual method relies heavily on operator experience and repetitive trial-and-error processes, while existing automated contact-based techniques require complex force control. Although hydrodynamic approaches enable non-contact rotational operations, three-degree-of-freedom (3-DoF) rotation remains unavailable. Here, we propose an acoustically driven 3-DoF rotation method for embryo engineering. By leveraging multiple acoustic microstreaming flows induced by the dynamic responses of microbubbles and microstructures to an acoustic stimulus, we achieve controlled rotation of oocytes about the x, y, and z axes within on-chip chambers. A piezoelectric transducer generates the acoustic field, where the driving frequency determines the rotation direction, and the input amplitude modulates the rotational velocity. Furthermore, stable 3-DoF rotation facilitates high-quality 3-D oocyte reconstruction, outperforming unidirectional rotation methods. Given the diverse oocyte rotation methods developed to date, our approach offers superior degrees of freedom, enhanced controllability, and improved biocompatibility, broadening its potential applications in embryo engineering.

Synthetic nanopores engineered by DNA origami provide a highly biocompatible and structurally programmable platform for elucidating the transmembrane mechanisms of functional macromolecules. However, engineering large DNA nanopores exceeding 30 nm in width remains a significant challenge. Here, we introduce a computer-assisted workflow to significantly reduce the design time and characterization costs of 45 nm-wide triangular DNA nanopores compared to empirical approaches. By leveraging extensive computational simulations, the feasibility of the triangular nanopore design was first validated. Computer-assisted image processing and data analysis confirmed that the majority of nanopore monomers maintained consistent triangular configurations and were capable of single-molecule translocation of trypsin. Long-term fluorescence tracking revealed exponential uptake of dextran into the vesicle interior, suggesting that the triangular DNA nanopore holds promise as a gatekeeper of macromolecular transmembrane transport. We envision that this computer-assisted approach could enhance design efficiency and data-processing accuracy, establishing a robust foundation for the intelligent development of DNA nanopores.

Magnetically actuated liquid robots show promise for microscale liquid manipulation and path navigation because they can be remotely driven, have simple structures and change shape. Here, a silicone-oil-based ferrofluid droplet was used to investigate morphological control and magnetically guided navigation. Contact-angle experiments first examined how substrate wettability affected the droplet contact morphology. The oleophilic surface promoted evident spreading, whereas the oleophobic surface markedly increased the contact angle and reduced adhesion between the droplet and substrate. The deformation response was then evaluated under different magnetic-field strengths and ferrofluid densities. Low-density ferrofluid droplets formed continuous and stable flattened morphologies under the magnetic field, whereas high-density droplets were more likely to develop spike-like instabilities under stronger fields. Finally, circular, square and star-shaped path navigation experiments were performed on the oleophobic surface using low-density ferrofluid droplets. The droplets followed the prescribed trajectories well and showed small motion errors. These results indicate that ferrofluid droplet robots have tunable morphologies governed by wettability and magnetic fields, and can achieve stable magnetically guided path navigation.

Single-cell operations are crucial technologies across fundamental biology, diagnostics, and therapeutics. The precise characterization and measurement of the physical and biological properties of cells provide critical support for disease diagnosis, clinical trial, and pharmaceutical research. Based on different cellular properties and operational objectives, researchers have developed two principal modalities for these operations: contact and non-contact micromanipulation. Contact micromanipulation achieves precise cell operations, such as grasping and injection, through direct mechanical interaction. In contrast, non-contact micromanipulation relies on various physical fields (e.g., electric, optical, acoustic, magnetic, and microfluidics) to apply remote forces, enabling indirect, high-throughput operations. This review systematically covers recent advances in both contact and non-contact single-cell operations. We provide a critical analysis of their core operational principles and a comparative assessment of their advantages and disadvantages across diverse application environments. Furthermore, this review provides an outlook on key future development trends, particularly in advanced materials, multimodal systems, and fluidics, aiming to facilitate the realization of more precise and stable cell operations.

Robotic non-contact three-dimensional (3-D) micromanipulation of micro-objects is critical for micro-assembly applications, but achieving high precision and reliable release in the microscale remains challenging. Traditional contact and non-contact techniques face limitations in automated 3-D operation. We present a fully automated micromanipulation system using an acoustic bubble end-effector for non-contact 3-D handling of microbeads. The system integrates real-time vision feedback with Z-axis autofocus and adaptive proportional-integral-derivative control for precise trapping, transport, and release. Leveraging localized bubble-driven microstreaming and acoustic radiation forces, our end-effector forms a stable trap within 100 ms and transports microbeads at speeds up to 1 mm/s. Experiments demonstrate exceptional 3-D dexterity, with trapping success rates consistently greater than 80% for microbeads of 60-120 μm diameter, and release placement accuracy is confirmed to be within ±2.5 μm when operating below a 150 μm height. The system achieves broad size adaptability and operates in free-space 3-D environments, overcoming workspace constraints of microfluidic setups. By eliminating mechanical contact, this approach reduces contamination and damage while delivering precise 3-D control often lacking in other non-contact methods. Our system bridges acoustofluidics and robotic automation, offering a versatile solution for automated micro-assembly and biomedical applications.

Chemotherapy remains the primary therapeutic option for glioma treatment due to its noninvasive nature and broad applicability. However, most existing chemotherapeutic carriers suffer from poor blood‐brain barrier (BBB) permeability and undefined drug delivery mechanisms, limiting their effectiveness in brain tumor therapy. Here, we present an allosteric DNA nanorobot for targeted glioma therapy, engineered via DNA origami for acid‐triggered doxorubicin (Dox) delivery. This nanorobot features cytosine‐rich pH sensors that facilitate its assembly into a stable tetrahedral configuration, crucial for efficient BBB traversal. Striking in vitro and in vivo studies demonstrate that these Dox‐loaded nanorobots not only effectively cross the BBB but also accumulate in glioma tissues, resulting in significant suppression of tumor growth. We decode the drug delivery mechanism: acid‐induced destabilization of DNA nanorobots triggers Dox release with optimal bioavailability. This pioneering nanorobot, powered by pH‐responsive allosteric dynamics, enables revolutionary precision glioma therapy.

Overview of the classifications and principles of single-cell mechanical characterization methods.