Benchtop, turnkey super-resolution microscopy for biology, biophysics and biotechnology

现代生物学的大部分目标是从组成我们身体和生物体的分子尺度构建模块的角度来理解生命、健康和疾病的过程。这类研究的一个主要障碍是很难“看到”这些分子构建块，原因很简单，它们太小了。这方面的重大突破是使用X射线和电子来探测生命系统，但这些方法需要将所研究的样品固定和/或冷冻并置于真空室中。为了看到这些分子构建块在工作，我们需要在盐水中对它们进行成像，最理想的是在活细胞中或活细胞上。在某种程度上，这可以通过将荧光标记附着到感兴趣的分子上，精确定位它们和/或跟踪它们的行为来实现。由于一套统称为“超分辨率显微镜”的方法，在准确性方面取得了重大进展（2014年获得诺贝尔奖）。然而，这种方法并不是简单的用途：这种显微镜的操作仍然很复杂，这种复杂性是其在各个研究领域更广泛使用的障碍。我们的目标是购买一种超分辨率显微镜，该显微镜已开发用于解决这一障碍。它不需要任何特别稳定的环境，也不涉及用户暴露于高功率激光的任何风险（它与低功率激光指示器处于相同的风险等级），并且可以在正常的工作台（或厨房桌子，就此而言）上操作。此外，它还包括一种以更方便的方式处理小体积生物样品的方法（“微流体”），进一步促进实验。我们将使这种显微镜广泛用于学术界，并在适当的情况下，也用于商业用户。首先，我们已经确定了将从这种显微镜中受益的各种研究项目，以解决包括病毒如何感染细胞，我们的DNA如何包装以及在需要时在细胞核中解包，以及如何制造更好的试剂来杀死细菌和/或癌细胞等问题。

Much of modern biology aims to understand processes of life, health and disease in terms of the molecular-scale building blocks that make up our body and living organisms in general. A major obstacle to such research is that it is hard to "see" these molecular building blocks, for the simple reason that they are so small. Major breakthroughs in this direction have been the use of X-rays and of electrons to probe living systems, but these methods require the samples under investigation to be fixed and/or frozen and put in a vacuum chamber. To see these molecular building blocks at work, we need to image them in salty water, and - ideally - in or on living cells. In part, this can be achieved by attaching fluorescent labels to the molecules of interest, precisely locating them and/or tracking their behaviour. Thanks to a set of methods collectively named "super-resolution microscopy", there has been major progress (awarded a Nobel Prize in 2014) in the accuracy by which this can be done. Yet such methods are not trivial to use: the operation of such microscopes remains complex and this complexity is a barrier to its wider use in various fields of research.We aim to purchase a super-resolution microscope that has been developed to address this barrier. It does not require any particularly stable environment nor involves any risk of user exposure to high-power laser (it is in the same risk class as low-power laser pointers), and can operate on a normal bench (or kitchen table, for that matter). Moreover, it includes a way ('microfluidics') to handle small volumes of biological samples in a more convenient matter, further facilitating experiments.We will make this microscope widely accessible to academic and - where appropriate - also commercial users. To start with, we have identified various research projects that will benefit from this microscope, to address questions including how viruses can infect cells, how our DNA is packed and when needed unpacked in the nucleus, and how to make better reagents to kill bacteria and/or cancer cells.