生物谷報(bào)道：來(lái)自于美國(guó)國(guó)家標(biāo)準(zhǔn)局（National Institute of Standards and Technology ,，NIST)、美國(guó)海軍研究實(shí)驗(yàn)室（Naval Research Laboratory ,，NRL)和馬里蘭大學(xué)的研究人員最近研制出一種簡(jiǎn)單易行的操作方法,，能夠?qū)捂淒NA化學(xué)鍵和到金粒子上。研究結(jié)果刊登于《PNAS》（Proceedings of the National Academy of Sciences）,。這種新技術(shù)能夠幫助研究人員輕易地控制片基（substrate）上的DNA鏈濃度,，也許能夠?yàn)樽顑?yōu)化DNA傳感器微列陣提供一臂之力。
排列在玻璃,、硅,、或金質(zhì)的生化傳感器片基上的短DNA序列，可用于檢測(cè)特異DNA“靶標(biāo)”序列或者分析復(fù)雜序列,。這些微列陣中,，DNA序列的一端綁定在片基上，如同牙刷上豎起的刷毛,。比如微列陣“基因芯片”,，能夠鑒別出樣本中的特異“靶標(biāo)”DNA序列，因?yàn)橹挥邪袠?biāo)序列能夠與微列陣中的互補(bǔ)序列鍵合（雜交）,。金是制作傳感器片基最常用物質(zhì),，制做DNA傳感器的一種流行技術(shù)（NIST制造），是將硫原子附著在DNA鏈一端,，硫原子將DNA鏈黏附在金質(zhì)片基上,。
圖：?jiǎn)捂淒NA通過(guò)添加腺嘌呤尾，錨定在金片基表面,，用于生物檢測(cè)器,。腺嘌呤與金的強(qiáng)親合力不僅將DNA鏈錨定到目的位點(diǎn)，而且能夠通過(guò)調(diào)節(jié)腺嘌呤尾的長(zhǎng)度,，控制微列陣上DNA鏈的密度,。
NIST、NRL和UMD小組通過(guò)采用一串腺嘌呤核苷酸作為“錨”將技術(shù)更進(jìn)一步,，成本更低,，操作更為簡(jiǎn)便。在組成DNA分子的四種核苷分子中,，屬腺嘌呤與金的親合力最強(qiáng),。完全由腺嘌呤組成的短鏈，能夠力排眾DNA鏈阻礙,，結(jié)合到金片基上,。結(jié)果,，研究人員發(fā)現(xiàn)DNA鏈一端的腺嘌呤區(qū)域能夠發(fā)揮“錨”的作用，甚至效果更加——這種腺嘌呤區(qū)域可控制DNA與片基結(jié)合的速度,。因?yàn)槊織l腺嘌呤尾都“平躺”在片基上，加快了速度,。在一定范圍內(nèi),，腺嘌呤尾越長(zhǎng)，其在底物面上的“足跡”越長(zhǎng),，DNA鏈的總密度越低,。
控制片基上的DNA“刷子”的密度，對(duì)于設(shè)計(jì)傳感器至關(guān)重要,。因?yàn)槊芏冗^(guò)大會(huì)導(dǎo)致沒(méi)有足夠的空間供樣品中的“靶標(biāo)”DNA鏈結(jié)合,，密度過(guò)小，微列陣又不會(huì)產(chǎn)生足夠強(qiáng)的信號(hào),。
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.
