生物谷报道：来自于美国国家标准局（National Institute of Standards and Technology ，NIST)、美国海军研究实验室（Naval Research Laboratory ，NRL)和马里兰大学的研究人员最近研制出一种简单易行的操作方法，能够将单链DNA化学键和到金粒子上。研究结果刊登于《PNAS》（Proceedings of the National Academy of Sciences）。这种新技术能够帮助研究人员轻易地控制片基（substrate）上的DNA链浓度，也许能够为最优化DNA传感器微列阵提供一臂之力。
排列在玻璃、硅、或金质的生化传感器片基上的短DNA序列，可用于检测特异DNA“靶标”序列或者分析复杂序列。这些微列阵中，DNA序列的一端绑定在片基上，如同牙刷上竖起的刷毛。比如微列阵“基因芯片”，能够鉴别出样本中的特异“靶标”DNA序列，因为只有靶标序列能够与微列阵中的互补序列键合（杂交）。金是制作传感器片基最常用物质，制做DNA传感器的一种流行技术（NIST制造），是将硫原子附着在DNA链一端，硫原子将DNA链黏附在金质片基上。
图：单链DNA通过添加腺嘌呤尾，锚定在金片基表面，用于生物检测器。腺嘌呤与金的强亲合力不仅将DNA链锚定到目的位点，而且能够通过调节腺嘌呤尾的长度，控制微列阵上DNA链的密度。
NIST、NRL和UMD小组通过采用一串腺嘌呤核苷酸作为“锚”将技术更进一步，成本更低，操作更为简便。在组成DNA分子的四种核苷分子中，属腺嘌呤与金的亲合力最强。完全由腺嘌呤组成的短链，能够力排众DNA链阻碍，结合到金片基上。结果，研究人员发现DNA链一端的腺嘌呤区域能够发挥“锚”的作用，甚至效果更加——这种腺嘌呤区域可控制DNA与片基结合的速度。因为每条腺嘌呤尾都“平躺”在片基上，加快了速度。在一定范围内，腺嘌呤尾越长，其在底物面上的“足迹”越长，DNA链的总密度越低。
控制片基上的DNA“刷子”的密度，对于设计传感器至关重要。因为密度过大会导致没有足够的空间供样品中的“靶标”DNA链结合，密度过小，微列阵又不会产生足够强的信号。
英文原文：
Researchers from the National Institute of Standards and Technology (NIST), the Naval Research Laboratory (NRL) and the University of Maryland (UMD) have demonstrated a deceptively simple technique for chemically bonding single strands of DNA to gold. Among other features, they report in a forthcoming issue* of the Proceedings of the National Academy of Sciences, the technique offers a convenient way to control the density of the DNA strands on the substrate, which could be important for optimizing DNA sensor arrays.
Short DNA sequences arrayed on substrates like glass, silicon or gold are used in biochemical sensors that can detect specific "target" sequences of DNA or analyze complex sequences. In such arrays, DNA strands are attached to the substrate by one end and stand up like bristles on a brush. Specific "target" DNA sequences from a test sample can be identified because they will bond (hybridize) only to a complementary sequence on the array--microarray "gene chips" are the best-known example of the technology. The properties of gold are well-known, so it is a practicaland convenient substrate for some sensors. One popular technique for making DNA sensors (developed at NIST) is to use DNA with a sulfur atom attached to one end, which acts as "glue" because sulfur readily reacts with gold.
But a potentially less expensive and even simpler approach, according to the NIST, NRL and UMD team, might be to use a string of adenine nucleotides as an anchor. Of the four nucleotides that comprise DNA molecules, adenine, turns out to have a particularly high affinity for gold. Short strands composed entirely of adenine will adhere to a gold surface even if they have to muscle aside other strands in the process. As a result, say the researchers, short blocks of adenine at the end of DNA strands can serve as bonding anchors--but even better, they say, these adenine blocks can be used to control the spacing of the DNA strands on the substrate. This is because each adenine tail lies flat on the substrate, taking up space. Within limits, the longer the adenine tail is, the larger is its footprint on the substrate, and the lower the total density of DNA strands.
Controlling the density of DNA "brushes" on a substrate is important for sensor design because an overly dense thicket does not leave enough room for "target" DNA strands from the test sample to bond, while too sparse an array doesn't produce a strong enough signal.
The authors have applied for a patent on the technique. The research was supported by Office of Naval Research and the Air Force Office of Scientific Research.
