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【bio-news】纳米结构促发器质谱技术－－新的鉴定疾病的利器！

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http://www.nature.com/news/2007/071024/full/news.2007.193.html

Small-scale technique hits the big time

Mini-explosions under a cell sample could help to identify disease.

Katharine Sanderson

An explosive chemical technique can now be used to identify individual molecules in biological samples, down to the single-cell level.

Researchers hope the procedure could be used in clinics a few years from now to screen blood or urine for metabolites — the final products of biological processes — that can be used to diagnose disease.

"The vast majority of small molecules in humans are unknown," says Gary Siuzdak at the Scripps Center for Mass Spectrometry, La Jolla, California. "People don't appreciate this." But his technique could change that: "The potential for diagnosing and understanding disease is really wonderful," he says.

The mass-spectrometry technique developed by Siuzdak and colleagues, known as nanostructure-initiator mass spectrometry (NIMS), is reported in Nature 1 this week.

The process relies on a slab of silicon etched with nanometre-sized holes filled with 'initiator' molecules. The sample sits on top of this layer. The uneven surface is then hit with an ionising beam, or a laser, at which point the molecules trapped in the nanoholes heat up until they explode outwards into the sample. This pushes molecules off the sample surface as gaseous ions, which can be detected and identified by the mass spectrometer.

Strong but gentle

The technique offers a number of advantages over others, Siuzdak says. Although the exploding initiator molecules are "pretty forceful", in some ways they are relatively gentle: because the sample is ionised by exploding particles — rather than being directly hit with an ion beam or a laser — surface molecules are released whole rather than being shattered into fragments.

And because the sample doesn't need to be mixed with anything, it is easier to identify the molecules coming from it. Metabolites can be tricky to detect using techniques where the sample is dissolved and mixed with a matrix material before it can be analysed, since the metabolites often look similar to the matrix.

Matrix-based systems also don't let the user work out exactly where in a sample a certain molecule has come from. NIMS does.

This is a real advantage, says Renato Zenobi, a mass spectrometry expert at the Swiss Federal Institute of Technology in Zurich. “In any imaging technique, spatial resolution is important,” he says. For example, with NIMS you could potentially tell whether a drug being tested in an animal made it into the intended cell, or if it got stuck in the cell walls.

Siuzdak has used NIMS to detect the metabolites present in a single cancer cell. The spatial resolution of the technique meant that he was able to distinguish cancerous and normal cells in his sample, he says.

The full applications of the technique have not yet been fleshed out. But Siuzdak’s team is dedicated to seeing what it can do: even to the extent of testing it on themselves. “I walked into the lab one day and literally saw [my postdoc] with a needle in his hand,” says Siuzdak.

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Small-scale technique hits the big time

小规模技术开启了重要的时代

Mini-explosions under a cell sample could help to identify disease.

一份细胞样品底部的微型爆炸可能有助于鉴定疾病。

Katharine Sanderson

An explosive chemical technique can now be used to identify individual molecules in biological samples, down to the single-cell level.

一项爆炸化学技术现在可被用于鉴定生物样品中的个别分子，其分析程度可达单个细胞水平。

Researchers hope the procedure could be used in clinics a few years from now to screen blood or urine for metabolites — the final products of biological processes — that can be used to diagnose disease.

研究人员希望该技术能够在几年后用于临床上筛选血液或尿液中可被用来诊断疾病的代谢产物—生物学进程中的终产物。

"The vast majority of small molecules in humans are unknown," says Gary Siuzdak at the Scripps Center for Mass Spectrometry, La Jolla, California. "People don't appreciate this." But his technique could change that: "The potential for diagnosing and understanding disease is really wonderful," he says.

“人体中很大一部分小分子都是未知的，”加州La Jolla质谱分析中心的Gary Siuzdak说。“而人们未认识到这一点。”“但是他的技术可以改变这一切：“该技术在诊断及阐明疾病方面的潜在作用确实很棒。”他说。

The mass-spectrometry technique developed by Siuzdak and colleagues, known as nanostructure-initiator mass spectrometry (NIMS), is reported in Nature this week.

这项由Siuzdak及其同事发展起来的质谱技术，也称纳米级结构促发器质谱技术，发表在本周的Nature上。

The process relies on a slab of silicon etched with nanometre-sized holes filled with 'initiator' molecules. The sample sits on top of this layer. The uneven surface is then hit with an ionising beam, or a laser, at which point the molecules trapped in the nanoholes heat up until they explode outwards into the sample. This pushes molecules off the sample surface as gaseous ions, which can be detected and identified by the mass spectrometer.

该技术的整个过程依赖于一个硅板，其上布满了填充促发器分子的纳米级大小的孔。待测样品位于这层板的顶部。用离子束或激光照射凹凸不平的样品表面，此时纳米孔中的促发器分子被加热到发生爆炸并冲向样品。这就使得分子以气化离子的形式离开样品表面，从而被质谱仪检测到并完成鉴定。

Strong but gentle

强力却是温和的。

The technique offers a number of advantages over others, Siuzdak says. Although the exploding initiator molecules are "pretty forceful", in some ways they are relatively gentle: because the sample is ionised by exploding particles — rather than being directly hit with an ion beam or a laser — surface molecules are released whole rather than being shattered into fragments.

这项技术较其他技术有许多优势，Siuzdak说。尽管发生爆炸的促发器的冲击力稍大了些，但在某些方面它们还是相对温和的：因为样品是被爆炸粒子离子化的，而不是被离子束或激光直接激发生成。表面分子是以完整的颗粒释放出来，而不是被打碎成各种片段。

And because the sample doesn't need to be mixed with anything, it is easier to identify the molecules coming from it. Metabolites can be tricky to detect using techniques where the sample is dissolved and mixed with a matrix material before it can be analysed, since the metabolites often look similar to the matrix.

而且由于样品无须与其他物质混合，因此更容易鉴定出其中的分子。一些技术需将样品溶解并于基质混合后才能对样品进行分析，这样所得结果可能会与真实情况有出入，因为代谢物常常看上去就像基质。

Matrix-based systems also don't let the user work out exactly where in a sample a certain molecule has come from. NIMS does.

依赖于基质的系统也不能让研究者确定某一分子来源于样品的哪一部分。但NIMS可以做到。

This is a real advantage, says Renato Zenobi, a mass spectrometry expert at the Swiss Federal Institute of Technology in Zurich. “In any imaging technique, spatial resolution is important,” he says. For example, with NIMS you could potentially tell whether a drug being tested in an animal made it into the intended cell, or if it got stuck in the cell walls.

这确实是其优势所在，苏黎世瑞士联邦技术研究所的一位质谱专家Renato Zenobi说。“在任何成像技术中，空间分辨率是很重要的。”他说。例如，利用NIMS你可以告诉人们在动物中试验的药物是否也能进入靶细胞，或者是否能穿透细胞壁。

Siuzdak has used NIMS to detect the metabolites present in a single cancer cell. The spatial resolution of the technique meant that he was able to distinguish cancerous and normal cells in his sample, he says.

Siuzdak已经用NIMS检测了单个癌细胞中的代谢物。该项技术的空间分辨率意味着他可以区分样品中的癌细胞和正常细胞，他说。

The full applications of the technique have not yet been fleshed out. But Siuzdak’s team is dedicated to seeing what it can do: even to the extent of testing it on themselves. “I walked into the lab one day and literally saw [my postdoc] with a needle in his hand,” says Siuzdak.

这项技术的全方位的应用还未得以开发。但是Siuzdak的团队决定研究其究竟能做什么：甚至到了拿自己身体做实验的程度。“一天我走进实验室后发现我的一个博士后手里正拿着一个针头，“Siuzdak说。

编译稿(870字)

技术规模虽小，却开启了重要的时代

一份细胞样品底部的微型爆炸可能有助于鉴定疾病

一项爆炸化学技术现在可被用于鉴定生物样品中的个别分子，其分析程度可达单个细胞水平。研究人员希望该技术能够在几年后用于临床上筛选血液或尿液中可被用来诊断疾病的代谢产物—生物学进程中的最终产物。

“人体中很大一部分小分子都是未知的，”加州La Jolla质谱分析中心的Gary Siuzdak说。“而人们未认识到这一点。”“但是他的技术可以改变这一切：“该技术在诊断及阐明疾病方面的潜在作用确实很棒。”他说。这项由Siuzdak及其同事发展起来的质谱技术，也称纳米级结构促发器质谱技术，发表在本周的Nature上。该技术的整个过程依赖于一个硅板，其上布满了填充了促发器分子的纳米级大小的孔。待测样品位于这层板的顶部。用离子束或激光照射凹凸不平的样品表面，此时纳米孔中的促发器分子被加热到发生爆炸并冲向样品。这就使得分子以气化离子的形式离开样品表面，从而被质谱仪检测到并完成鉴定。

强力的同时也是温和的

这项技术较其他技术有许多优势，Siuzdak说。尽管发生爆炸的促发器冲击力稍大了些，但在某些方面它们还是相对温和的：因为样品是被爆炸粒子离子化的，而不是被离子束或激光直接激发生成。表面分子是以完整的颗粒释放出来，而不是被打碎成各种片段。而且由于样品无须与其他物质混合，因此更容易鉴定出其中的分子。一些技术需将样品溶解并于基质混合后才能对样品进行分析，这样所得结果可能会与真实情况有出入，因为代谢物常常看上去就像基质。依赖于基质的系统也不能让研究者确定某一分子来源于样品的哪一部分。但NIMS可以做到。

这确实是其优势所在，苏黎世瑞士联邦技术研究所的一位质谱专家Renato Zenobi说。“在任何成像技术中，空间分辨率是很重要的。”他说。例如，利用NIMS你可以告诉人们在动物中试验的药物是否也能进入靶细胞，或者是否能穿透细胞壁。Siuzdak已经用NIMS检测了单个癌细胞中的代谢物。该项技术的空间分辨率意味着他可以区分样品中的癌细胞和正常细胞，他说。

这项技术的全方位应用尚未得以开发。但是Siuzdak的团队决定研究其到底能做什么：甚至到了拿自己身体做实验的程度。“一天我走进实验室后发现，我的一个博士后手里正拿着一个针头，“Siuzdak说。

2007-10-26 00:30

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npng 编辑于 2007-10-26 08:02

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