Human-scale navigation of magnetic microrobots in hepatic arteries.

Using external actuation sources to navigate untethered drug-eluting microrobots in the bloodstream offers great promise in improving the selectivity of drug delivery, especially in oncology, but the current field forces are difficult to maintain with enough strength inside the human body (>70-centimeter-diameter range) to achieve this operation. Here, we present an algorithm to predict the optimal patient position with respect to gravity during endovascular microrobot navigation. Magnetic resonance navigation, using magnetic field gradients in clinical magnetic resonance imaging (MRI), is combined with the algorithm to improve the targeting efficiency of magnetic microrobots (MMRs). Using a dedicated microparticle injector, a high-precision MRI-compatible balloon inflation system, and a clinical MRI, MMRs were successfully steered into targeted lobes via the hepatic arteries of living pigs. The distribution ratio of the microrobots (roughly 2000 MMRs per pig) in the right liver lobe increased from 47.7 to 86.4% and increased in the left lobe from 52.2 to 84.1%. After passing through multiple vascular bifurcations, the number of MMRs reaching four different target liver lobes had a 1.7- to 2.6-fold increase in the navigation groups compared with the control group. Performing simulations on 19 patients with hepatocellular carcinoma (HCC) demonstrated that the proposed technique can meet the need for hepatic embolization in patients with HCC. Our technology offers selectable direction for actuator-based navigation of microrobots at the human scale.

3D cellular morphometrics of ovule primordium development in Zea mays reveal differential division and growth dynamics specifying megaspore mother cell singleness.

Introduction: Differentiation of spore mother cells marks the somatic-to-reproductive transition in higher plants. Spore mother cells are critical for fitness because they differentiate into gametes, leading to fertilization and seed formation. The female spore mother cell is called the megaspore mother cell (MMC) and is specified in the ovule primordium. The number of MMCs varies by species and genetic background, but in most cases, only a single mature MMC enters meiosis to form the embryo sac. Multiple candidate MMC precursor cells have been identified in both rice and Arabidopsis, so variability in MMC number is likely due to conserved early morphogenetic events. In Arabidopsis, the restriction of a single MMC per ovule, or MMC singleness, is determined by ovule geometry. To look for potential conservation of MMC ontogeny and specification mechanisms, we undertook a morphogenetic description of ovule primordium growth at cellular resolution in the model crop maize. Methods: We generated a collection of 48 three-dimensional (3D) ovule primordium images for five developmental stages, annotated for 11 cell types. Quantitative analysis of ovule and cell morphological descriptors allowed the reconstruction of a plausible developmental trajectory of the MMC and its neighbors. Results: The MMC is specified within a niche of enlarged, homogenous L2 cells, forming a pool of candidate archesporial (MMC progenitor) cells. A prevalent periclinal division of the uppermost central archesporial cell formed the apical MMC and the underlying cell, a presumptive stack cell. The MMC stopped dividing and expanded, acquiring an anisotropic, trapezoidal shape. By contrast, periclinal divisions continued in L2 neighbor cells, resulting in a single central MMC. Discussion: We propose a model where anisotropic ovule growth in maize drives L2 divisions and MMC elongation, coupling ovule geometry with MMC fate.