Magnetically Actuated Cell-Robot System: Precise Control, Manipulation, and Multimode Conversion.

Border-nearing microrobots with self-propelling and navigating capabilities have promising applications in micromanipulation and bioengineering, because they can stimulate the surrounding fluid flow for object transportation. However, ensuring the biosafety of microrobots is a concurrent challenge in bioengineering applications. Here, macrophage template-based microrobots (cell robots) that can be controlled individually or in chain-like swarms are proposed, which can transport various objects. The cell robots are constructed using the phagocytic ability of macrophages to load nanomagnetic particles while maintaining their viability. The robots exhibit high position control accuracy and generate a flow field that can be used to transport microspheres and sperm when exposed to an external magnetic field near a wall. The cell robots can also form chain-like swarms to transport a large object (more than 100 times the volume). This new insight into the manipulation of macrophage-based cell robots provides a new concept by converting other biological cells into microrobots for micromanipulation in biomedical applications.

Bone formation recovery with gold nanoparticle-induced M2 macrophage polarization in mice.

The prevention of fractures induced by inflammatory bone disease remains a clinical challenge. This is because of a lack of bone formation to fill in the bone defects, which are believed to be due in part to persistent inflammation caused by the imbalance of M1 over M2 macrophages. In this study, gold nanoparticles (AuNPs) were synthesized to shift the balance of macrophages at the site of bone damage to improve osteanagenesis in a mouse model of LPS-induced inflammatory bone erosion. Specifically, the AuNPs treatment improved bone structure and increased bone mineral density (BMD) by ~14% compared with model group. Macrophages recruited by LPS treatment were reduced by ~11% after AuNPs injection. Compared to LPS treatment only, the percentage of M2 macrophages increased threefold by AuNPs, while the proportion of M1 macrophages decreased by 59%. This promoted the regeneration of bone matrix proteins in the bone defect site, which finally leads to increased bone mass and improved bone structure in model mice. These data suggest that AuNPs could be a novel candidate therapeutic for inflammatory bone disease rather than a drug carrier.

Postoperative evaluation of tumours based on label-free acoustic separation of circulating tumour cells by microstreaming.

Metastatic tumour recurrence caused by circulating tumour cells (CTCs) after surgery is responsible for more than 90% of tumour-related deaths. A postoperative evaluation system based on the long-term dynamic detection of CTCs helps in guiding the postoperative treatment of tumours in real time and preventing metastases and recurrence of tumours after treatment. In this study, a simple, rapid, and low-cost postoperative evaluation system was established based on the number of CTCs captured by a label-free acoustic separation device from whole blood samples of mice, of which breast tumours were surgically removed, and tumour metastasis was successfully predicted. First, an acoustofluidic device with a custom-designed bottom microcavity array was fabricated to induce highly localised acoustic microstreaming by applying acoustic vibration. Second, experiments of capturing 'defined' cells (artificially mixed individual 4T1 cancer cells into normal blood) based on optimal acoustic streaming were performed. The separation device exhibited a high capture efficiency (>96%). Further applications of capturing the 'true' CTCs derived from postoperative mice were successfully developed to predict tumour prognosis based on the number of captured CTCs. Finally, the prediction was verified through long-term observation of mice with excised tumours. The acoustofluidic device can efficiently capture CTCs and precisely predict tumour metastasis in a low-cost and non-invasive manner. This will help clinicians monitor patients that underwent surgical resection of tumours over a long period of time and facilitate optimal treatment strategies in a timely manner.

Magnetically Driven Bionic Millirobots with a Low-Delay Automated Actuation System for Bioparticles Manipulation.

This paper presents a semi-automatic actuation system which can achieve bio-particles tracking, transportation, and high-precision motion control of robots in a microfluidic chip. This system is mainly applied in magnetically driven robots. An innovative manta ray-like robot was designed to increase stability of robots in a non-contaminated manipulation environment. A multilayer piezo actuator was applied to generate high-frequency vibration to decrease the friction between robots and the glass substrate. We also set up a user-friendly GUI (Graphical User Interface) and realized robot tracking and predetermined trajectory motion through excellent algorithms using Python and C++. In biotechnology, precise transportation of cells is used for the enucleation, microinjection, and investigation of the characteristics of a single cell. Being optimized, the parameters of the robot can effectively reach 10 µm in actuation precision and a maximum actuation speed of 200 mm/s.

On-chip rotational manipulation of microbeads and oocytes using acoustic microstreaming generated by oscillating asymmetrical microstructures.

The capability to precisely rotate cells and other micrometer-sized biological samples is invaluable in biomedicine, bioengineering, and biophysics. We propose herein a novel on-chip cell rotation method using acoustic microstreaming generated by oscillating asymmetrical microstructures. When the vibration is applied to a microchip with our custom-designed microstructures, two different modes of highly localized microvortices are generated that are utilized to precisely achieve in-plane and out-of-plane rotational manipulation of microbeads and oocytes. The rotation mechanism is studied and verified using numerical simulations. Experiments of the microbeads are conducted to evaluate the claimed functions and investigate the effects of various parameters, such as the frequency and the driving voltage on the acoustically induced flows. Accordingly, it is shown that the rotational speed and direction can be effectively tuned on demand in single-cell studies. Finally, the rotation of swine oocytes is involved as further applications. By observing the maturation stages of M2 after the exclusion of the first polar body of operated oocytes, the proposed method is proved to be noninvasive. Compared with the conventional approaches, our acoustofluidic cell rotation approach can be simple-to-fabricate and easy-to-operate, thereby allowing rotations irrespective of the physical properties of the specimen under investigation.