Low-light-level camera for single-molecule imaging

单分子检测技术的发展导致了我们研究生物分子物理方面的能力发生了一场革命。我们现在可以对分子在溶液中的平均行为时被遮挡的特征进行精细的研究。虽然这一应用是为了一台可以拍摄运动图像的相机，暗淡的物体，如溶液中的DNA单分子。它的主要应用将是通过观察单个细胞中的复制来探测DNA复制--一个细胞中的遗传信息是如何传递给它的后代的。以前的工作依赖于从许多细胞中提取DNA。这些实验的一个主要困难是不同细胞的细胞周期不同。单细胞实验将解决这个问题。第二个应用将是开发一种捕获单个分子的方法，以便可以长时间、非常详细地探测它们的行为。因此，这是一个敏感的、需要快速相机来为分子成像并确定其位置。然后，该位置的波动可以通过将其移回所需位置的“踢脚”来补偿。我们将使用这样的陷阱来探测DNA如何与蛋白质等其他分子相互作用。这些都是许多生物过程中的基本步骤，我们在这里收集的那种信息将是独特的，对于给予新的理解具有独特的价值。

The development of single-molecule detection techniques has led to a revolution in our ability to study the physical aspects of biological molecules.  Features that have been obscured when averaging the behaviour of molecules in solution can now be studied in exquisite detail.  This application is for a camera that can image moving, dim objects such as single molecules of DNA in solution.  The main application will be to an experiment that probes DNA replication - how the genetic information in a cell is passed on to its descendants - by looking at replication in a single cell.  Previous work has depended on extracting DNA from many cells.  A major difficulty of those experiments is that the cell cycles of different cells are not well-synchronized.  Single-cell experiments will resolve that problem.A second application will be to develop a way of trapping single molecules so that their behaviour can be probed over long times, in great detail.  For this, a sensitive, rapid camera is needed to image the molecule and determine its position.  Then fluctuations in that position can be compensated by "kicks" that move it back to the desired location.  We will use such a trap to probe how DNA interacts with other molecules such as proteins.  These are basic steps in many biological processes, and the kind of information we can gather here will be unique and uniquely valuable for giving new understanding.