Laser micro-surgery upgrade to robotic microscope system

在早期胚胎发育期间，称为上皮细胞的细胞片经历了戏剧性的、自我驱动的形状变化，以形成器官和其他关键结构。这些形态发生运动是组织之间复杂但看不见的机械相互作用的结果，当它们出现问题时，可能会导致出生缺陷。要阐明这些运动是如何驱动的，所需的关键实验非常具有挑战性，因为胚胎的直径通常为1至3毫米，而且它们极其脆弱。尽管我的实验室可以测量小到4纳米牛顿的力，但我们在两栖动物胚胎上的实验是有限的，因为我们无法做出长度小于500微米的一致伤口。拟议的激光显微手术系统将使我们能够在整个胚胎上进行短至50微米的精确切割，并切割出准确的测试样本。这些测试对于了解器官形成形态发生运动实际上是如何驱动的，以及验证我们开发的相关计算模型是至关重要的。进行所需切割所需的激光束将由一台Nd：YAG型半导体激光器产生。光学元件将被用来去除原始光束中不需要的波长，对其进行调节和聚焦，并在计算机控制下对其进行控制。由于激光及其相关光学元件将被集成到现有的显微镜系统中，因此可以以较低的成本实现所需的功能。我们预计，通过我们的研究计划获得的见解最终将导致改进预防畸形型出生缺陷的策略，如脊柱裂。

During early embryo development, sheets of cells called epithelia undergo dramatic, self-driven changes of shape in order to form organs and other critical structures. These morphogenetic movements are the consequence of complex, but unseen, mechanical interactions between tissues and, when something goes wrong with them, a birth defect can result. The crucial experiments needed to elucidate how these motions are driven are very challenging to carry out because embryos are typically 1 to 3 mm in diameter and they are extremely fragile. Although my lab can measure forces as small as 4 nano-Newtons, our experiments on amphibian embryos are limited because we cannot make consistent incisions smaller than 500 microns in length. The proposed laser micro-surgery system would allow us to make precise incisions as short as 50 microns in whole embryos and to cut out accurate test specimens. These tests are crucial for learning how organ-forming morphogenetic movements are actually driven and for validating associated computational models we have developed. The laser beam needed to make the required incisions will be generated using a Nd:YAG semiconductor laser. Optical elements will be used to remove unwanted wavelengths from the raw beam, to condition and focus it and to steer it under computer control. Because the laser and its associated optics are being incorporated into an existing microscope system, the required capabilities can be realized at modest cost. We anticipate that insights gained through our research program will ultimately lead to improved strategies for the prevention of malformation-type birth defects, such as spina bifida.