Liposome-Based Chemical Barcodes for Single Molecule DNA Detection Using Imaging Mass Spectrometry
Liposome-Based Chemical Barcodes for Single Molecule DNA Detection Using Imaging Mass Spectrometry
复制标题
DOI：
10.1021/nl904208y
复制
发表时间：
2010-02-01
期刊：
影响因子：
10.8
通讯作者：
Hook, Fredrik
中科院分区：
文献类型：
--
作者：
Gunnarsson, Anders;Sjovall, Peter;Hook, Fredrik
我们报告了一种基于质谱（飞行时间二次离子质谱，TOF-SIMS）的方法，用于利用随机阵列进行多重DNA检测，其中小单层脂质体的脂质组成作为化学条形码，以识别独特的DNA靶序列，直至单分子水平。在夹心形式中，待检测的悬浮靶DNA介导捕获DNA修饰的脂质体与表面固定的探针DNA的结合。由于每个脂质体的脂质组成编码独特的靶DNA序列，TOF-SIMS分析用于确定结合的脂质体的化学指纹。使用高分辨率TOF-SIMS成像，提供低于200 nm的空间分辨率，可以通过单个脂质体的化学指纹检测和识别单个DNA靶标。结果还证明了TOF-SIMS在微米范围内提供对基底区域上的DNA靶的多重检测的能力。与高复用能力一起，这使得该概念成为基于荧光、拉曼或用于小规模生物分析的图形代码的现有条形码概念的有趣替代方案。
We report on a mass-spectrometry (time-of-flight secondary ion mass spectrometry, TOF-SIMS) based method For multiplexed DNA detection utilizing a random array, where the lipid composition of small unilamellar liposomes act as chemical barcodes to identify unique DNA target sequences down to the single molecule level. In a sandwich format, suspended target-DNA to be detected mediates the binding of capture-DNA modified liposomes to surface-immobilized probe-DNA. With the lipid composition of each liposome encoding a unique target-DNA sequence, TOF-SIMS analysis was used to determine the chemical fingerprint of the bound liposomes. Using high-resolution TOF-SIMS imaging, providing sub-200 nm spatial resolution, single DNA targets could be detected and identified via the chemical fingerprint of individual liposomes. The results also demonstrate the capability of TOF-SIMS to provide multiplexed detection of DNA targets on substrate areas in the micrometer range. Together with a high multiplexing capacity, this makes the concept an interesting alternative to existing barcode concepts based on fluorescence, Raman, or graphical codes for small-scale bioanalysis.