Modified carbon nanotubes could be used to track protein production by individual cells

Modified carbon nanotubes could be used to track protein production by individual cells

改性碳纳米管可能用于追踪单独细胞的蛋白质制造

For the first time, MIT engineers have designed sensors that can detect single protein molecules as they are secreted by cells or even a single cell.
MIT的工程师们首次设计了可以在蛋白质分子被某些甚至单个细胞分沁时发现它们的传感器。
These sensors, which consist of chemically modified carbon nanotubes, could help scientists with any application that requires detecting very small amounts of protein, such as tracking viral infection, monitoring cells' manufacturing of useful proteins, or revealing food contamination, the researchers say.
"We hope to use sensor arrays like this to look for the 'needle in a haystack,'" says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT. "These arrays represent the most sensitive molecular sensing platforms that we have available to us technologically. You can functionalize them so you can see the stochastic fluctuations of single molecules binding to them."
研究人员们介绍说，这些传感器由化学改性的碳纳米管组成，可能会在跟踪病毒感染，监控细胞制造有用蛋白质，或发现食物污染等任何需要检定非常小量的蛋白质的领域有所应用。Michael Strano，MIT化学工程系Carbon P. Dubbs Professor，说，“我们希望用这些传感器阵列来“大海捞针”，这些阵列代表了现有科技条件下我们能制造的最敏感的分子检测平台。你可以功能化他们，这样你就可以观测到单个分子与它们结合的随机涨落。”
Strano is the senior author of a Jan. 23 Nature Nanotechnology paper describing the new sensors. The paper's lead author is Markita Landry, a former MIT postdoc who is now an assistant professor at the University of California at Berkeley.
Strano是1月23日Nature Nanotechnology上描述新传感器的论文的通讯作者。论文的主要作者是Markita Landry，前MIT博士后，现UCB助理教授。
Other MIT authors are research scientist Hiroki Ando, former graduate student Allen Chen, postdocs Jicong Cao and Juyao Dong, and associate professor of electrical engineering and computer science Timothy Lu. Vishal Kottadiel of Harvard University and Linda Chio and Darwin Yang of the University of California at Berkeley are also authors.
其他MIT作者有研究科学家Hiroki Ando，前研究生Allen Chen，博士后Jicong Cao和Juyao Dong，电子工程和计算机科学助理教授Timothy Lu。哈佛大学的Vishal Kottadiel，UCB的Linda Chio和Darwin Yang也都是作者。

No detection limit
检测不受限
Strano's lab has previously developed sensors that can detect many types of molecules, all based on modifications of carbon nanotubes—hollow, nanometer-thick cylinders made of carbon that naturally fluoresce when exposed to laser light. To turn the nanotubes into sensors, Strano's lab coats them with DNA, proteins, or other molecules that can bind to a specific target. When the target is bound, the nanotubes' fluorescence changes in a measurable way.
Strano的实验室先前已开发了多种类型的分子探测器，它们都基于改性碳纳米管，碳纳米管是中空，纳米尺度的碳圆柱体，当暴露于激光时会产生荧光。为了把这些纳米管改造为传感器，Strano的实验室用可以与特定目标分子结合的DNA，蛋白质或其他分子来覆盖纳米管。当与目标分子结合，纳米管的荧光以一种可以测量的方式改变。
In this case, the researchers used chains of DNA called aptamers to coat the carbon nanotubes. Previous efforts to use DNA aptamers have been stymied because of the difficulty of getting the aptamer to stick to the nanotube while maintaining the configuration it needs to bind to its target.
在这个案例里，研究人员应用被叫做适配子的DNA链来覆盖碳纳米管。因为难于使适配子在保持与目标分子结合的位形的同时仍粘到纳米管上，先前的应用DNA适配子的努力都未成功。
Landry overcame this challenge by adding a "spacer" sequence between the section of the aptamer that attaches to the nanotube and the section that binds to the target, allowing each region the freedom to perform its own function. The researchers successfully demonstrated sensors for a signaling protein called RAP1 and a viral protein called HIV1 integrase, and they believe the approach should work for many other proteins.
Landry通过加入了一段“隔离”序列在结合到纳米管上的适配子区段和结合到目标分子的区段之间，使每个区段可以独立实现功能。研究人员们成功示范了信号蛋白质RAP1传感器和病毒蛋白质HIV1整合酶传感器，他们任务这一方法应可以用于许多其他蛋白质的检测。
To monitor protein production of single cells, the researchers set up an array of the sensors on a microscope slide. When a single bacterial, human, or yeast cell is placed on the array, the sensors can detect whenever the cell secretes a molecule of the target protein.
为了监测单个细胞的蛋白质制造，研究人员在载玻片上建立起一个传感器阵列。当放置一个细菌，人，或酵母细胞到阵列上，传感器可以检测到何时细胞分泌了一个目标蛋白质分子。
"Nanosensor arrays like this have no detection limit," Strano says. "They can see down to single molecules."
Strano说，“像这样的纳米传感器阵列没有检测限制，他们可以看到小至单分子”
However, there is a tradeoff—the fewer molecules there are, the longer it takes to sense them. As the molecule becomes more scarce, detection can take an infinite amount of time, Strano says.
然而，这里需要做出权衡--分子越少，检测时间越长。当分子太少时，检测会花费无限长的时间，Strano说。
"The new study by Strano and co-workers proposes an exciting new approach to detect proteins down to the single molecule level," says Robert Hurt, a professor of engineering at Brown University who was not involved in the research. "The work pushes the forefront in single-protein detection and may allow researchers to see important, real-time molecular events at the single-cell level, such as protein release during cell division."
没有参与研究的布朗大学的工程教授Robert Hurt评论道，“Strano和合作者的最新研究建议了一条令人兴奋的新途径去小至单分子水平检测蛋白质。”“这一工作推进了单分子检测，也许可以使研究人员看到单细胞水平的重要的，实时的分子事件，例如细胞分裂过程中的蛋白质释放。”

Useful tools
有用的工具
The sensor arrays could be useful for many different applications, the researchers say.
研究人员们说，这些传感器阵列可以有许多不同的应用。
"This platform will open a new path to detect trace amounts of proteins secreted by microorganisms," Dong says. "It will advance biological research [on] the generation of signal molecules, as well as the biopharmaceutical industry's [efforts to monitor] microorganism health and product quality."
Dong说，“这一平台将开辟一条检测微生物分泌的痕量蛋白质的途径，这将推进单个分子的生成的生物研究，同时也将推进生物制药行业的监测微生物健康和产品质量的努力。”
In the pharmaceutical realm, these sensors could be used to test cells engineered to help treat disease. Many researchers are now working on an approach where doctors would remove a patient's own cells, engineer them to express a therapeutic protein, and place them back in the patient.
在制药领域，这些传感器可以测试用来治病的工程细胞。很多研究人员在开发一种方法，可以使医生取出病人自体细胞，基因工程化他们来表达治疗蛋白，再把他们放回病人体内。
"We think these nanosensor arrays are going to be useful tools for measuring these precious cells and making sure that they're performing the way that you want them to," Strano says.
Strano说，“我们认为这些纳米传感器阵列将是检测这些珍贵的细胞，确认他们以人们期待的方式工作的有用工具。”
He says researchers could also use the arrays to study viral infection, neurotransmitter function, and a phenomenon called quorum sensing, which allows bacteria to communicate with each other to coordinate their gene expression.
他说研究人员也可以应用这些阵列来研究病毒感染，神经传递素功能，和群体效应现象--其允许细菌彼此通信来协调他们的基因表达。（2017-01-24）