Laser micro-surgery upgrade to robotic microscope system

在胚胎早期发育过程中，被称为上皮细胞的细胞片经历了剧烈的、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。阐明这些运动是如何驱动的关键实验是非常具有挑战性的，因为胚胎通常直径为1到3毫米，而且它们非常脆弱。虽然我的实验室可以测量小到4纳牛顿的力，但我们在两栖动物胚胎上的实验是有限的，因为我们不能在长度小于500微米的切口上进行一致的切割。提出的激光显微手术系统将使我们能够在整个胚胎上精确切割50微米的切口，并切割出准确的测试样本。这些测试对于了解器官形成的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至关重要。制作所需切口所需的激光束将使用Nd:YAG半导体激光器产生。光学元件将用于从原始光束中去除不需要的波长，对其进行调节和聚焦，并将其置于计算机控制之下。由于激光及其相关的光学元件被整合到现有的显微镜系统中，所需的能力可以以适度的成本实现。我们预计，通过我们的研究项目获得的见解将最终导致改善预防畸形型出生缺陷（如脊柱裂）的策略。

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.