The core of microfluidic technology is to achieve precise manipulation of fluids at the micrometer scale. This technology provides efficient and low-cost technical support for related research, and has important application value in fields such as chemical synthesis, biological research, and disease diagnosis. From the perspective of technological development, microfluidic systems can be mainly divided into two categories: one is "Lab on a Chip (LoC)", which achieves fluid manipulation and multi-step experimental integration by etching microchannels on micro chips. However, its closed environment leads to poor sample accessibility, high manufacturing costs, and requires professional operational skills for sample loading and unloading; The other type is open microfluidic devices, which solve the accessibility problem of closed systems but are difficult to achieve stable continuous flow pumping. ThereforeThere are limitations in completing complex and multi-step experimental processes.

For a long time, the scientific research field has faced a core challenge: how to achieve stable and controllable continuous flow pumping and multi-step integrated operation while maintaining open and easy to operate characteristics. This issue has become a constraint on the widespread application of microfluidic technology in mainstream scientific research scenarios, and an innovative design based on biological inspiration provides a breakthrough solution to this problem.

Recently,Professor Liu Xiaoming's team from Beijing Institute of Technology in PNASThe journal published an online article titled“Lab on an end: Micromanipulation using the acoustohydrodynamic pillar array as an end effector”The treatise.This study was inspired by the collaborative movement characteristics of cilia structures and designed an acoustic fluid micro column array device called "Lab on an End (LoE)"It has achieved compatibility between microfluidic open environments and spatiotemporal continuous fluid manipulation, demonstrating cross scale, multifunctional, and flexible manipulation capabilities for microscale particles, biological targets, and liquids.

Firstly, the team utilizesMofang Precision Surface Projection Micro Stereoscopic Lithography (P μ SL) 3D Printing Technology (nanoArch) ® P140， Accuracy: 10 μ m)Created comb shaped end effectors. Under the drive of the ultrasonic transducer, a sound field and local acoustic fluid phenomena will be generated near the end effector. By modulating the frequency and amplitude of the input signal, the acoustic fluid can exhibit three effects: in-plane transport flow, out of plane rotation flow, and capture based on acoustic radiation force. This enables the capture, translation, rotation, and bidirectional transport of micro targets, ranging from HeLa cells at the micrometer scale to zebrafish seedlings at the millimeter scale. In addition, the surface of 3D printed comb shaped ends generates significant capillary forces, which can also pull droplets to move on hydrophobic surfaces.

To verify the ability of LoE to manipulate individual targets, researchers validated the three acoustic effects mentioned above through particle tracing (Figure 2A-2C), and further validated its capture, translation, rotation, and bidirectional transport capabilities on targets using 100 μ m sized polystyrene (PS) particles (Figure 2D-2G). Compared to other end effectors, LoE also has parallel manipulation capabilities. Researchers demonstrated the ability to arrange dispersed particles into a "BIT" pattern by simultaneously manipulating multiple targets (Figure 2H).

On the basis of individual particle manipulation, researchers further explored the application of LoE in different biomedical and chemical research fields.

Researchers have utilized LoE to complete an end-to-end assisted reproductive in vitro cell manipulation process. Firstly, utilize the capture function of LoE to capture scattered oocytes and arrange them in a row (Figure 3B); Secondly, the captured oocytes were transported to the manipulation window through the continuous in-plane transport flow of LoE, and the microscope field of view was focused within the window (Figure 3C); Finally, with the help of LoE's out of plane continuous rotational flow adjustment, the posture of oocytes within the manipulation window was observed and repositioned (Figure 3D). The redirected oocytes can continue to develop into embryos after intracytoplasmic sperm injection (Figure 3E); During the process of embryonic development, the state of different stages can be continuously observed through LoE, and the quality of embryonic development can be evaluated using micro vision 3D reconstruction technology (Figure 3F-3G). The above-mentioned multi-step complex operations can all be completed by the same end effector, reflecting its ability to use "spatiotemporal continuous flow" for complex multi-step processing.

Secondly, researchers utilized LoE to investigate the nematode Caenorhabditis elegans（C. elegans）Morphological characterization research. The end effector array can generate stable and consistent time continuous flow at different end unit positions, ensuring stable rotation and transport of targets with large aspect ratios such as nematodes. The researchers also proposed a local confocal imaging technique for nematodes: by adjusting the position and posture of nematodes through LoE, high-precision imaging of different parts of nematodes from different angles can be achieved, thereby avoiding interference of tomographic fluorescence information from the superposition of different planar fluorescence signals (Figure 4).

Thirdly, researchers have confirmed the advantages of LoE in liquid handling. Similar to other open microfluidic platforms, LoE can achieve stable capture and transport of water droplets on hydrophobic surfaces or in oil phase media (Figure 5A). Unlike other devices, LoE can accelerate the mixing of microscale viscous fluids and the dissolution of solid particles under the action of acoustic fluids, effectively solving the problem of difficult diffusion at high concentration interfaces of low Reynolds number fluids (Figure 5B-5C). The researchers also designed experimental scenarios in which LoE promotes chemical reactions, especially in chemical reactions involving precipitation or gas generation that are difficult to handle with traditional LoC chips, where LoE exhibits significant advantages (Figure 5D). Through pre programmed settings, LoE can also simulate the "serialization processing" capability of microfluidics and perform multi-step complex chemical reactions.

In addition, researchers also validated the ability of LoE in single-cell and multicellular operations. The study selected the classic HeLa cell line in the field of life sciences and first confirmed its ability to manipulate single cells, including capture, transport, and rotation (Figure 6A). In addition, LoE can also serve as a high-throughput manipulation tool to achieve aggregation and clustering of HeLa cells (Figure 6B), and has functions such as cell transfection and drug delivery (Figure 6C-6D).

Summary: LoE achieves a balance between "open and easy operation" and "continuous flow multi-step processing" - it not only has the characteristics of flexible and convenient open devices, low cost, and fast start-up, but also can complete complex experiments like a chip laboratory.This device does not require professional operating skills and is suitable for ordinary laboratories. It is expected to promote the popularization of microfluidic technology in fields such as chemical synthesis, biological research, and assisted reproduction, providing efficient and practical tools for related scientific research and helping to achieve research breakthroughs in related fields.