Nanobaths for DNA analysis

人类基因组包含31.647亿个核酸碱基(腺嘌呤、鸟嘌呤、胞嘧啶、胸腺嘧啶)，据估计，单个细胞中所有DNA链的长度(如果所有链首尾相连)约为两米。人类基因组序列是在本世纪初完成的；这导致了公众和科学对理解DNA序列“密码”及其如何“翻译”的浓厚兴趣。基因组序列提供了有关我们的祖先、遗传性疾病、我们的特征(如眼睛、皮肤或头发的颜色)和我们的生理“组成”的信息。尽管人类基因组在十年前就被测序了，自那以后已经开发出了更好的DNA测序方法，但更简单、更便宜、更快的DNA序列分析方法是一个重要的目标，这种方法不一定提供完整的基因组序列，但检测序列中的特定差异。因此，要在不评估整个序列的情况下获得所需的信息--本质上就像检查莎士比亚戏剧中的关键语录，而不是阅读整本书。在我们看来，需要一种小规模的技术，它的工作原理就像热敏阅读器，一个微小的读取头扫描通过存储的信息(DNA链)，信息(序列中的差异)直接读取，而不需要对基因组DNA分子进行任何复杂的处理。我们建议让DNA分子通过一个带有光激活加热器的纳米毛细管，该加热器将充当“读取头”，并检测和识别DNA序列中的变异。DNA被限制在通道中，这意味着可能有微米长的长DNA链不会通过所有的“标记”。以这种方式识别DNA碱基序列中的变异将非常简单和快速，我们相信能够检测到特定碱基的修改-特别是从父母那里继承的序列变异，从导致癌症的损伤，从环境或细胞过程中可以控制基因的开启和关闭。这些技术对于更好地了解所有生物体的遗传学至关重要，而不仅仅是人类，一种快速、廉价的DNA分析方法将能够回答更多的问题，并提供一种简单快速的诊断工具。这些研究将提供适当的概念数据，以证明纳米毛细管首次与光学方法集成在有限空间中进行单分子讯问的潜力。我们相信这些毛细血管可以被开发出来，为其他诊断应用提供更简单、更容易的工具。

The human genome contains 3164.7 million nucleic acid bases (adenine, guanine, cytosine, thymine) and it is estimated that the length of all the DNA strands in a single cell (if all the strands were placed end to end) is about two metres. The human genome sequence was completed at the start of the millennium; this resulted in significant public and scientific interest in understanding the DNA sequence 'code' and how it is 'translated'. The sequence of the genome provides information about our ancestry, hereditary diseases, our features (such as eye, skin or hair colour) and our physiological 'make-up'. Despite the fact that the human genome was sequenced a decade ago and better DNA sequencing methods have been since developed, simpler, cheaper, faster DNA sequence analysis methods which do not necessarily provide the full genome sequence but detect specific differences in the sequence is an important goal. Thus to obtain information that is required without evaluating the whole sequence - essentially just like checking the key quotes from a Shakespeare play without reading the whole book 'cover to cover'.In our view, what is needed is a small scale technology, something that works like a thermal reader, where a tiny read head is scanned past the stored information (the DNA strand) and the information (the differences in the sequence) is read directly without need for any complex processing of the genomic DNA molecule. We propose to flow DNA molecules through a nanocapillary with a light activated heater that will act as a 'read head' and detect and identify variations in the DNA sequence. The DNA is confined in channels meaning that the long DNA strand which can be microns long does not travel through all 'noted up'. Identifying variations in the DNA base sequence in this way will be very simple and fast, and we believe capable of detecting modifications to particular bases - notably sequence variations inherited from parents, from damage leading to cancers, from environmental or cellular processes which can control the switching on and off of genes. These sorts of techniques are crucial to obtain a better understand of the genetics of all organisms, not just humans, and a fast, cheap DNA analysis method will be able to answer many more questions as well as also provide a simple fast diagnostic tool. These studies will provide proof of concept data appropriate to demonstrate the potential of nanocapillaries for the first time for integration with optical approaches for single molecule interrogation in confined spaces. We believe these capillaries could be developed to provide simpler easier tools for other diagnostic applications.