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

改性碳納米管可能用于追蹤單獨細胞的蛋白質制造

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的工程師們首次設計了可以在蛋白質分子被某些甚至單個細胞分沁時發現它們的傳感器。
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."
研究人員們介紹說，這些傳感器由化學改性的碳納米管組成，可能會在跟蹤病毒感染，監控細胞制造有用蛋白質，或發現食物污染等任何需要檢定非常小量的蛋白質的領域有所應用。Michael Strano，MIT化學工程系Carbon P. Dubbs Professor，說，“我們希望用這些傳感器陣列來“大海撈針”，這些陣列代表了現有科技條件下我們能制造的最敏感的分子檢測平臺。你可以功能化他們，這樣你就可以觀測到單個分子與它們結合的隨機漲落。”
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上描述新傳感器的論文的通訊作者。論文的主要作者是Markita Landry，前MIT博士后，現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作者有研究科學家Hiroki Ando，前研究生Allen Chen，博士后Jicong Cao和Juyao Dong，電子工程和計算機科學助理教授Timothy Lu。哈佛大學的Vishal Kottadiel，UCB的Linda Chio和Darwin Yang也都是作者。

No detection limit
檢測不受限
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的實驗室先前已開發了多種類型的分子探測器，它們都基于改性碳納米管，碳納米管是中空，納米尺度的碳圓柱體，當暴露于激光時會產生熒光。為了把這些納米管改造為傳感器，Strano的實驗室用可以與特定目標分子結合的DNA，蛋白質或其他分子來覆蓋納米管。當與目標分子結合，納米管的熒光以一種可以測量的方式改變。
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.
在這個案例里，研究人員應用被叫做適配子的DNA鏈來覆蓋碳納米管。因為難于使適配子在保持與目標分子結合的位形的同時仍粘到納米管上，先前的應用DNA適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通過加入了一段“隔離”序列在結合到納米管上的適配子區段和結合到目標分子的區段之間，使每個區段可以獨立實現功能。研究人員們成功示范了信號蛋白質RAP1傳感器和病毒蛋白質HIV1整合酶傳感器，他們任務這一方法應可以用于許多其他蛋白質的檢測。
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.
為了監測單個細胞的蛋白質制造，研究人員在載玻片上建立起一個傳感器陣列。當放置一個細菌，人，或酵母細胞到陣列上，傳感器可以檢測到何時細胞分泌了一個目標蛋白質分子。
"Nanosensor arrays like this have no detection limit," Strano says. "They can see down to single molecules."
Strano說，“像這樣的納米傳感器陣列沒有檢測限制，他們可以看到小至單分子”
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，這里需要做出權衡--分子越少，檢測時間越長。當分子太少時，檢測會花費無限長的時間，Strano說。
"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."
沒有參與研究的布朗大學的工程教授Robert Hurt評論道，“Strano和合作者的最新研究建議了一條令人興奮的新途徑去小至單分子水平檢測蛋白質。”“這一工作推進了單分子檢測，也許可以使研究人員看到單細胞水平的重要的，實時的分子事件，例如細胞分裂過程中的蛋白質釋放。”

Useful tools
有用的工具
The sensor arrays could be useful for many different applications, the researchers say.
研究人員們說，這些傳感器陣列可以有許多不同的應用。
"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說，“這一平臺將開辟一條檢測微生物分泌的痕量蛋白質的途徑，這將推進單個分子的生成的生物研究，同時也將推進生物制藥行業的監測微生物健康和產品質量的努力。”
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.
在制藥領域，這些傳感器可以測試用來治病的工程細胞。很多研究人員在開發一種方法，可以使醫生取出病人自體細胞，基因工程化他們來表達治療蛋白，再把他們放回病人體內。
"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說，“我們認為這些納米傳感器陣列將是檢測這些珍貴的細胞，確認他們以人們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.
他說研究人員也可以應用這些陣列來研究病毒感染，神經傳遞素功能，和群體效應現象--其允許細菌彼此通信來協調他們的基因表達。（2017-01-24）