Search Results (211)

Precise regulation of micropipette outlet flow is critical for fluorescence imaging in vivo micromanipulations. In such procedures, a micropipette with a micro-sized opening is driven by gas pressure to deliver internal solution into the in vivo environment. The outlet flow rate needs to be precisely regulated to ensure a uniform and stable fluorescence distribution. However, conventional manual pressure injection methods face inherent limitations, including insufficient precision and poor reproducibility. Existing commercial microinjection systems lack a quantitative relationship between pressure and flow rate. And existing calibration methods in the field of microfluidics suffer from a limited flow-rate measurement resolution, constraining the establishment of a precise pressure–flow quantitative relationship. To address these challenges, we developed a closed-loop pressure regulation system with 1 Pa-level control resolution and established a quantitative calibration of the pressure–flow relationship using a droplet-based method. The calibration revealed a linear relationship with a mean pressure–flow gain of 4.846 $\times {10}^{-17}{\mathrm{m}}^3·{\mathrm{s}}^{-1}·{\mathrm{P}\mathrm{a}}^{-1}$ (R² > 0.99). Validation results demonstrated that the system achieved the target outlet flow rate with a flow control error less than 10 fL/s. Finally, the application results in brain-slice environment confirmed its capability to maintain stable fluorescence imaging, with fluorescence intensity fluctuations around 1.3%. These results demonstrated that the proposed approach provides stable, precise, and reproducible flow regulation under physiologically relevant conditions, thereby offering a valuable tool for in vivo micromanipulation and detection. Full article

Mechanical properties are critical for characterizing and fabricating advanced materials. While current characterization methods are well-established for the nanoscale and larger millimeter-scale, a significant gap exists in automated testing at the microscale. To address this, we propose an automated, rapid characterization method based on a microrobotic system. We first develop a 6-degree-of-freedom (DOF) microrobotic system for sample alignment and testing. An image processing method is then designed for real-time sample recognition, supplying essential feedback for both alignment and testing procedures. Furthermore, a soft force sensor is fabricated and calibrated to ensure precise force measurement. Experiments on copper wires and graphite films demonstrate the method’s high precision and reliability. This work provides a robust solution for microscale mechanical property characterization, offering significant potential for advanced material development. Full article

Caenorhabditis elegans is one of the most extensively studied model organisms in biology. Its advantageous features, including genetic homology with humans, conservation of disease pathways, transparency, short lifespan, small size and ease of maintenance have established it as a powerful system for research in aging, genetics, molecular biology, disease modeling and drug discovery. However, traditional methods for worm handling, culturing, scoring and imaging are labor-intensive, low throughput, time consuming, susceptible to operator variability and environmental influences. Addressing these challenges, recent years have seen rapid innovation spanning microfluidics, robotics, imaging platforms and AI-driven analysis in C. elegans-based research. Advances include micromanipulation devices, robotic microinjection systems, automated worm assays and high-throughput screening platforms. In this review, we first summarize foundational developments prior to 2020 that shaped the field, then highlight breakthroughs from the past five years that address key limitations in throughput, reproducibility and scalability. Finally, we discuss ongoing challenges and future directions for integrating these technologies into next-generation automated C. elegans research. Full article

Mechanical models are capable of simulating the deformation and stress distribution of oocytes under external forces, thereby providing insights into the underlying mechanisms of intracellular mechanical responses. Interactions with micromanipulation tools involve forces like compression and punction, which are effectively analyzed using principles of solid mechanics. Alternatively, fluid–structure interactions, such as shear stress at fluid junctions or pressure gradients within microchannels, are best described by a multiphase flow model. Developing the two models instead of a single comprehensive model is necessary due to the distinct nature of cell–tool interactions and cell–fluid interactions. In this study, we developed a finite element (FE) model of porcine oocytes that accounts for the viscoelastic properties of the zona pellucida (ZP) and cytoplasm for the case when the oocytes interacted with a micromanipulation tool. Atomic force microscopy (AFM) was employed to measure the Young’s modulus and creep behavior of these subcellular components that were incorporated into the FE model. When the oocyte was solely interacting with the fluids, we simulated oocyte deformation in microfluidic channels by modeling the oocyte-culture-medium system as a three-phase flow, considering the non-Newtonian behavior of the oocyte’s components. Our results show that the Young’s modulus of the ZP and cytoplasm were determined to be 7 kPa and 1.55 kPa, respectively, highlighting the differences in the mechanical properties between these subcomponents. Using the developed layered FE model, we accurately simulated oocyte deformation during their passage through a narrow-necked micropipette, with a deformation error of approximately 5.2% compared to experimental results. Using the three-phase flow model, we effectively simulated oocyte deformation in microfluidic channels under various pressures, validating the model’s efficacy through close agreement with experimental observations. This work significantly contributes to assessing oocyte quality and serves as a valuable tool for advancing cell mechanics studies. Full article

Numerous infants have been conceived by in vitro fertilization (IVF) and other assisted reproductive technologies (ART). Increasing evidence indicates that these approaches induce minor alterations in molecules during the initial phases of embryogenesis. This narrative review examines the molecular pathophysiology of embryonic cardiogenesis in the context of assisted reproductive technology, emphasizing transcriptional and epigenetic regulation. Essential transcription factors for cardiac development, including NKX2-5, GATA4, TBX5, ISL1, MEF2C, and HAND1/2, play a crucial role in mesodermal specification, heart tube formation, and chamber morphogenesis. Animal models and human preimplantation embryos have demonstrated that ART-related procedures, including gamete micromanipulation, supraphysiological hormone exposure, and extended in vitro culture, can alter the expression or epigenetic programming of these genes. Subsequent to ART, researchers have identified anomalous patterns of DNA methylation, alterations in histones, and modifications in chromatin accessibility in cardiogenic loci. These alterations indicate that errors occurred during the initial reprogramming process, potentially resulting in structural congenital heart abnormalities (CHDs) or modifications in cardiac function later in life. Analysis of the placental epigenome in babies conceived using assisted reproductive technology reveals that imprinted and developmental genes critical for cardiac development remain dysfunctional. This review proposes a mechanistic theory about the potential subtle alterations in the cardiogenic gene network induced by ART, synthesizing findings from molecular embryology, transcriptomics, and epigenomics. Understanding these molecular issues is crucial not only for enhancing ART protocols but also for evaluating the cardiovascular risk of children conceived by ART postnatally and for early intervention. Full article

In this study we report on the structural, mechanical, and electrical characterization of different structures of vertically aligned zinc oxide (ZnO) nanowires (NWs) synthesized using hydrothermal methods. By optimizing the growth conditions, scanning electron microscopy (SEM) micrographs show that the ZnO NWs could reach an astounding 51.9 ± 0.82 µm in length, 0.7 ± 0.08 µm in diameter, and 3.3 ± 2.1 µm⁻² density of the number of NWs per area within 24 h of growth time, compared with a reported value of ~26.8 µm in length for the same period. The indentation modulus of the as-grown ZnO NWs was determined using contact resonance (CR) measurements using atomic force microscopy (AFM). An indentation modulus of 122.2 ± 2.3 GPa for the NW array sample with an average diameter of ~690 nm was found to be close to the reference bulk ZnO value of 125 GPa. Furthermore, the measurement of the piezoelectric coefficient (d₃₃) using the traceable ESPY33 tool under cyclic compressive stress gave a value of 1.6 ± 0.4 pC/N at 0.02 N with ZnO NWs of 100 ± 10 nm and 2.69 ± 0.05 µm in diameter and length, respectively, which were embedded in an S1818 polymer. Current–voltage (I-V) measurements of the ZnO NWs fabricated on an n-type silicon (Si) substrate utilizing a micromanipulator integrated with a tungsten (W) probe exhibits Ohmic behavior, revealing an important phenomenon which can be attributed to the generated electric field by the tungsten probe, dielectric residue, or conductive material. Full article

This paper presents a three-degrees-of-freedom origami parallel robot that is free from parasitic motion. This robot is designed to achieve one translational and two rotational motions within its workspace, enabling precise orientation about a fixed point—a capability unattainable for parallel robots with parasitic motion. The elimination of parasitic motion is critical, allowing the use of this device in applications requiring high precision. The robot’s key kinematic features include a parasitic motion-free workspace, large orientational capability, compactness, decoupled motion, simplicity in manufacturing and control, mechanically pivoted rotation of the moving platform, and scalability. These characteristics make the robot particularly well-suited for micromanipulation tasks in both manufacturing and medical applications. In manufacturing, it can enable high-precision operations such as micro-assembly, optical fiber alignment, and semiconductor packaging. In medicine, it can support delicate procedures such as microsurgery and cell injection, where sub-micron accuracy, high stability, and precise motion decoupling are critical requirements. The use of nearly identical limbs simplifies the architecture, facilitating easier design, manufacture, and control. The kinematics of the robot is analyzed using reciprocal screw theory for an analytic constraint-embedded Jacobian. To further enhance operational accuracy and robustness, particularly in the presence of uncertainties or disturbances, a deep neural network (DNN)-based state estimation method is integrated, providing accurate forward kinematic predictions. The construction of the robot utilizes origami-inspired limbs and joints, enhancing miniaturization, manufacturing simplicity, and foldability. Although capable of being scaled up or further miniaturized, its current size is 66 mm × 68 mm × 100 mm. The robot’s moving platform is theoretically and experimentally proven to be free of parasitic motion and possesses a large orientation capability. Its unique features are demonstrated, and its potential for high-precision applications is thoroughly discussed. Full article

Micro-electro-mechanical system (MEMS) electromagnetic actuators have rapidly evolved into critical components of various microscale applications, offering significant advantages including precision, controllability, high force density, and rapid responsiveness. Recent advancements in actuator design, fabrication methodologies, smart control integration, and emerging application domains have significantly broadened their capabilities and practical applications. This comprehensive review systematically analyzes the recent developments in MEMS electromagnetic actuators, highlighting core operating principles such as Lorentz force and magnetic attraction/repulsion mechanisms and examining state-of-the-art fabrication technologies, such as advanced microfabrication techniques, additive manufacturing, and innovative material applications. Additionally, we provide an in-depth discussion on recent enhancements in actuator performance through smart and adaptive integration strategies, focusing on improved reliability, accuracy, and dynamic responsiveness. Emerging application fields, particularly micro-optical systems, microrobotics, precision micromanipulation, and microfluidic components, are extensively explored, demonstrating how recent innovations have significantly impacted these sectors. Finally, critical challenges, including miniaturization constraints, integration complexities, power efficiency, and reliability issues, are identified, alongside a prospective outlook outlining promising future research directions. This review aims to serve as an authoritative resource, fostering further innovation and technological advancement in MEMS actuators and related interdisciplinary fields. Full article

This study presents a novel capillary microgripper for manipulating micrometer-sized objects directly within aqueous environments. The system features dynamic, vision-based feedback control of a non-volatile silicone oil droplet volume, enabling precise adjustment of the capillary bridge force for the adaptable capture of varying object sizes. This approach ensures extended working time and stable operation in water, mitigating the issues associated with evaporation common in other systems. COMSOL Multiphysics simulations analyzed capillary bridge formation. Experimental validation demonstrated successful different object shapes and sizes capture in an aqueous environment and further explored active release strategies necessary due to the non-volatile fluid, confirming the system potential for robust underwater micromanipulation. Full article

The optical rotational Doppler effect occurs when vortex beams are scattered by rotating objects and demonstrate the Doppler frequency shifts in scattered beams, which are associated with the optical angular momentum of vortex beams and the relative rotating angular velocity. Here, we investigate the rotational Doppler effect of a rotating vector beam in its tight focusing and find that similar Doppler frequency shifts arise when the polarization order and vortex charge satisfy some specific relations. We note that the vortex charge is the indispensable parameter in the rotational Doppler effect of the vector vortex beam. Nonetheless, the sign and magnitude of the frequency shift are only determined by the angular frequency of the rotating beam and are irrelevant to the vortex charge of the beam. In addition, the on-axis energy flow and spin angular momentum in the focal plane can also be well modulated, accompanying the rotational Doppler effect of the vector vortex beam. Our results may be applied to an optical micro-manipulation, especially for some kinds of microparticles which are sensitive to frequency changes. Full article

Trophectoderm (TE) biopsy is at present the most widely used procedure for preimplantation genetic testing (PGT). At the blastocyst stage, more TE cells (five to seven) can be obtained for genetic analysis. While removing TE cells and not touching the inner cell mass (ICM), the procedure is less invasive. Due to a natural selection happening between day 3 and day 5, 6 or 7 of human embryo development, fewer embryos will have to be biopsied and tested. An additional benefit, especially in view of aneuploidy testing (PGT-A), is the lower level of mosaicism present at the blastocyst stage. The biopsy procedure involves two steps: laser-assisted zona pellucida (ZP) opening and the excision of five to eight TE cells from the blastocyst with or without additional laser energy. Different protocols have emerged over time with variations regarding the technique, the exact moment of ZP opening, and the method of cell removal. The ‘pulling’ method involves laser excision, whereas the ‘flicking’ method represents a mechanical approach with or without laser assistance. Embryo developmental speed reaching the full/expanded or hatching/hatched blastocyst stage dictates the timing of the procedure, mostly on day 5 post-insemination, and to a lesser extent on day 6 or even on day 7. The inclusion of lesser quality or delayed blastocysts may impact the quality of the TE sample as well as the clinical outcome. Intracytoplasmic sperm injection (ICSI) is still the preferred method of fertilization for PGT-M (monogenic disorders) and PGT-SR (structural rearrangements). However, conventional in vitro fertilization (IVF) seems feasible for PGT-A (aneuploidy testing). In the absence of a (conclusive) genetic result, the re-biopsy of cryopreserved blastocysts is possible, however, with reduced clinical outcomes. So far, neonatal outcome post-TE biopsy has so far been reassuringly documented. Full article

The aim of this study was to document the biodiversity of cyanobacteria genera isolated from intertidal and subtidal zones in Cabo Verde. The identification of the strains was conducted using a polyphasic study, comprising 16S rRNA gene maximum likelihood and Bayesian inference phylogeny, 16S rRNA identity (p-distance), 16S–23S ITS secondary structure, morphological, and habitat analyses. A total of 51 strains were isolated by micromanipulation and by streaking biomass onto Petri dishes with a solid medium. Seventeen strains were identified as belonging to the Salileptolyngbya genus and five to Leptothoe; sixteen strains were distributed across twelve genera. Thirteen strains were grouped into eight distinct clades, but could not be assigned to any cyanobacterial genus, indicating that they could be described as new cyanobacterial genera in the future. The phylogenies also exhibited isolates LEGE 181157, LEGE 181224, and LEGE 181227 clustered with Gibliniella, but in a separate clade from the G. alaskensis type. The 16S rRNA gene identity values among these new isolates and G. alaskensis ranged from 94.4% to 95.5%. The 16S–23S ITS dissimilarity between LEGE 181224 and G. alaskensis was 9.4%. Morphologically, these three LEGE strains differ from G. alaskensis in that they have trichomes that are never coiled and have diffluent mucilaginous envelopes, whereas G. alaskensis has coiled trichomes with firm sheaths. Based on these strains, we describe here a new species of Gibliniella. Full article

The ability to control and manipulate biological fluids within microchannels is a fundamental challenge in biological diagnosis and pharmaceutical analyses, particularly when buffers with very high ionic strength are used. In this study, we investigate the numerical and experimental study of fluidic biochips driven by ac electrothermal flow for controlling and manipulating biological samples inside a microchannel, e.g., for fluid-driven and manipulation purposes such as concentrating and mixing. By appropriately switching the voltage on the electrode structures and inducing AC electrothermal forces within the channel, a fluidic network with pumping and manipulation capabilities can be achieved, enabling the control of fluid velocity/direction and also fluid rotation. By using finite element analysis, coupled physics of electrical, thermal, fluidic fields, and molecular diffusion transport were solved. AC electrothermal flow was studied for pumping and mixing applications, and the optimal model was extracted. The microfluidic chip was fabricated using two processes: electrode structure development on the chip and silicon mold fabrication in a cleanroom. PDMS was prepared as the microchannel material and bonded to the electrode structure. After implementing the chip holder and excitation circuit, a biological buffer with varying ionic strengths (0.2, 0.4, and 0.6 [S/m]) was prepared, mixed with fluorescent particles, and loaded into the microfluidic chip. Experimental results demonstrated the efficiency of the proposed chip for biological applications, showing that stronger flows were generated with increasing fluid conductivity and excitation voltage. The system behavior was characterized using an impedance analyzer. Frequency response analysis revealed that for a solution with an electrical conductivity of 0.6 [S/m], the fluid velocity remained almost constant within a frequency range of 100 kHz to 10 MHz. Overall, the experimental results showed good agreement with the simulation outcomes. Full article

An automated micro-tweezers system with a flexible workspace would benefit the intelligent sorting of live cells. Such micro-tweezers could employ a forced vortex strong enough to capture a single cell. Furthermore, addressable control of the position to the vortex would constitute a robotic system. In this study, a spherical micro-object composed of super paramagnetic particles tightly packed in a non-magnetic resin is rotated with a combined magnetic field of permanent magnets. The said magnetic field is articulated by an open-kinematic chain controlled with a simple adaptive PI-control scheme. A vortex is formed as the spherical particle, assumed to be submerged under the surface of fluid, and follows the position and orientation of the external magnetic field. This forced vortex induces a radial pressure gradient that captures the live cell orbiting around the spherical object combined with the inertial effects. Here, a comprehensive mathematical model is presented to reflect on the dynamics of such micro-tweezer systems. Numerical results demonstrate that it is theoretically possible to capture and tow a bacterium cell while meeting extreme tracking references for motion control. Magnetic and fluid forces on the spherical particle traverse the vortex and the bacterium cell, with orbiting and sporadic collusion of the bacterium cell around the spherical particle, and the positions of the end-effector, i.e., the magnets, are analyzed. Full article

This paper presents a model of the bending behavior of a bi-layer cantilever composed of titanium nickelide and a magnetoactive elastomer embedded with magnetically hard particles. The cantilever is initially subjected to an external magnetic field in its high-temperature state, followed by cooling to a low-temperature state before the magnetic field is removed. This sequence results in residual bending deformation. Basic relations describing the material behavior of titanium nickelide and the magnetoactive elastomer are presented. A variational formulation for the problem under consideration is written down. The problem is solved numerically using the finite element method. The influence of the applied magnetic field magnitude and the thickness of the titanium nickelide layer on the cantilever deflection magnitude is studied. The dependence of the residual cantilever deflection on the applied magnetic field is obtained. The possibility of this structure as a controllable gripping element for applications in robotics and micro-manipulation is demonstrated. Full article