據(jù)sciencedaily網(wǎng)站2006年10月21日報道,，美國普渡大學(xué)研究人員已經(jīng)開發(fā)出一種新的生物芯片,，這種芯片可以測量細胞的帶電活性情況,，它在一次讀取過程中采集的數(shù)據(jù)比使用現(xiàn)有技術(shù)獲得的數(shù)據(jù)要多60倍,。短期內(nèi)，生物芯片可能加快科學(xué)研究的進程，從而加速肌肉和神經(jīng)紊亂（例如癲癇癥）類藥物的研發(fā),，它還將有助于開發(fā)出更多高產(chǎn)的農(nóng)作物品種,。
生物芯片開發(fā)小組的領(lǐng)導(dǎo)人、農(nóng)業(yè)與生物工程教授馬歇爾•波特爾菲德稱,，“現(xiàn)在,，我們通常是一天只能做1次試驗，由于這項技術(shù)能夠自動采集數(shù)據(jù),，在它幫助下,，我們每天將可以做數(shù)百次試驗。”
該設(shè)備可以在帶電離子出入細胞時測量出它們的密集程度,。生物芯片能夠記錄下封閉在液體毛孔內(nèi)的16個活細胞的帶電離子密度,。利用為每個細胞配備4個電極，生物芯片可以同時,、持續(xù)地為64個數(shù)據(jù)源提供數(shù)據(jù)傳送,。
波特爾菲德教授表示，與現(xiàn)有的技術(shù)相比,，這些“額外”的數(shù)據(jù)可以加深研究人員對細胞活動的了解,，現(xiàn)有的技術(shù)只能測量1個細胞外的1個數(shù)據(jù)點，而且不能同時進行記錄,。他稱,，生物芯片可以在不破壞細胞的條件下直接記錄離子密度，而現(xiàn)有技術(shù)不能直接測量特殊的離子,，并且用于進行針對性研究的細胞還會在研究過程中受到破壞,。他認(rèn)為保持活細胞的完好有幾個好處，例如可以對它們進行額外的測試或監(jiān)控其成長,。
波特爾菲德稱：“使用現(xiàn)有技術(shù)在實驗室中進行科學(xué)研究是非常緩慢和困難的,。”他認(rèn)為新的芯片將有助于研發(fā)與離子通道不暢相關(guān)的人類生理紊亂類疾病的治療藥物，例如癲癇和慢性疼痛,。他稱,，目前研發(fā)的藥物中大約有15%會對離子通道的活動產(chǎn)生影響，而現(xiàn)有技術(shù)緩慢的研發(fā)進度限制了這些藥物的研發(fā),。生物芯片將使科研人員在較短的時間內(nèi)獲得更多的數(shù)據(jù),，這樣一來，在對藥物以及藥物對離子通道產(chǎn)生的不同程度的影響進行評估時,，所需的時間大大縮短了,。
離子通道對肌肉和神經(jīng)細胞有著特殊的重要性，這些通道是細胞間相互通信和傳送電信號的便利途徑,。生物芯片的大小為10×10毫米,，大約相當(dāng)于一枚一角硬幣的大小,。放在芯片內(nèi)的細胞被封閉在16個錐形小孔內(nèi)進行分析，分析完成后還能夠完好無損地移走,。波特爾菲德稱,，既然該技術(shù)不會殺死細胞，它就有可能被用于篩選和確認(rèn)不同的農(nóng)作物品種,。“例如,，假如你有興趣開發(fā)耐氮肥瘠薄的谷物品種，如果擁有與氮肥高效利用相關(guān)的基因文庫,，就可以研制出少施肥的谷物,。你可以用這些基因改變一組玉米細胞，然后使用生物芯片對每個細胞進行篩選并選出最有效的那個細胞,。接著你就可以培育出少施肥的細胞,。你就不會像現(xiàn)在這樣，把許多不同的基因接入數(shù)百株植物中,，然后耐心地等著它們成長,。”
波特爾菲德稱，除了可以節(jié)省時間和花費,，這種芯片還可以讓他在一些未知領(lǐng)域進行研究,。他最近就正在從事“嘔吐慧星”（Vomit Comet）研究，“嘔吐慧星”是美國宇航局對零重力飛機的妮稱,，該研究旨在簡單地模擬飛行失重狀態(tài),。實驗主要就重力對植物生長的影響進行研究，以便解開植物以怎樣的方式“生長”之謎,。他說,，“使用該芯片，即使在墨西哥灣上空進行拋物線式飛行時,，即一次次從兩倍重力到失重狀態(tài)的過程中,，我們也可以進行我們的研究工作。沒有這樣的芯片,，我們是絕不可能進行這種實驗的,。”
目前，對細胞帶電活動進行分析的技術(shù)稱為“膜片鉗技術(shù)”,，該項技術(shù)是使用一個微型電性探測器通過顯微鏡對細胞進行觀察,。該項技術(shù)的發(fā)明者在1991年獲得了醫(yī)學(xué)和生理學(xué)諾貝爾獎。波特爾菲德對膜片鉗技術(shù)的評價是“它需要許多技巧與很高的手眼協(xié)調(diào)能力,。”而另一方面,，該芯片卻是自動化的，并且在將來可以進行批量生產(chǎn),。他表示,，生物芯片具有很高的可用價值,，它可以比膜片鉗技術(shù)記錄更多的數(shù)據(jù)。
當(dāng)離子通過一個細胞的隔膜時,，離子通道和泵會產(chǎn)生一個不同的電壓，細胞通過這種方式制造能量轉(zhuǎn)移電信號,。通過允許離子快速的進出,，它們會有助于加速細胞的變化，例如肌肉細胞,、神經(jīng)細胞的變化以及胰腺細胞對胰島素的分泌等,。
該生物芯片目前可以探測到不同的離子的特殊層面。波特爾菲德相信,，只要對芯片稍作修正,，它就能一次對多個離子進行測量，甚至還能執(zhí)行更多的功能,，例如,，使用一個電極模擬一個細胞，并記錄下其他三個細胞的反應(yīng),。
由于離子通道是神經(jīng)系統(tǒng)和其他部位的重要組成部分,，它們通常也是藥物目標(biāo)。例如,，利多卡因和奴佛卡因的主要目標(biāo)就是納離子通道,。實際上，一些最厲害的毒液和毒素也是通過堵塞這些通道來發(fā)揮其作用的,，這其中就包括某些特定的蛇和馬錢子堿的毒液,。
波特爾菲德所開發(fā)的芯片從技術(shù)上可以將其劃分為“細胞電生理學(xué)芯片實驗室”?！?a href="http://hnhlg.com/sell/show-9573.html" target="_blank">傳感器和制動器》雜志本月在網(wǎng)上公布的一篇文章對該設(shè)備進行了詳細地介紹,，這篇文章預(yù)計于11月刊印。波特爾菲德用了近兩年的時間來開發(fā)生物芯片,，目前,，他正在對其進行改進。該項研究得到了美國國家宇航局和利里基金會的資助,。
英文原文：
New Biochip Helps Study Living Cells, May Speed Drug Development
Purdue University researchers have developed a biochip that measures the electrical activities of cells and is capable of obtaining 60 times more data in just one reading than is possible with current technology.
In the near term, the biochip could speed scientific research, which could accelerate drug development for muscle and nerve disorders like epilepsy and help create more productive crop varieties.
"Instead of doing one experiment per day, as is often the case, this technology is automated and capable of performing hundreds of experiments in one day," said Marshall Porterfield, a professor of agricultural and biological engineering who leads the team developing the chip.
The device works by measuring the concentration of ions — tiny charged particles — as they enter and exit cells. The chip can record these concentrations in up to 16 living cells temporarily sealed within fluid-filled pores in the microchip. With four electrodes per cell, the chip delivers 64 simultaneous, continuous sources of data.
This additional data allows for a deeper understanding of cellular activity compared to current technology, which measures only one point outside one cell and cannot record simultaneously, Porterfield said. The chip also directly records ion concentrations without harming the cells, whereas present methods cannot directly detect specific ions, and cells being studied typically are destroyed in the process, he said. There are several advantages to retaining live cells, he said, such as being able to conduct additional tests or monitor them as they grow.
"The current technology being used in research labs is very slow and difficult," said Porterfield, who believes the new chip could help develop drugs for human disorders involving ion channel malfunction, such as epilepsy and chronic pain. About 15 percent of the drugs currently in development affect the activities of ion channels, he said, and their development is limited by the slower pace of current technology. The biochip would allow researchers to generate more data in a shorter time, thus speeding up the whole process of evaluating potential drugs and their different effects on ion channels.
Ion channels are particularly important in muscle and nerve cells, where they facilitate communication and the transfer of electrical signals from one cell to the next.
Within the 10-by-10 millimeter chip — roughly the size of a dime — cells are sealed inside 16 pyramidal pores, analyzed, and then can be removed intact. Since the technology does not kill the cells, it could be used to screen and identify different crop lines, Porterfield said.
"For example, let's say you were interested in developing corn varieties that need less fertilizer," he said. "If you had a library of genes that were associated with high nitrogen-use efficiency — thus making the plant need less nitrogen fertilizer — you could transform a group of maize cells with these genes and then screen each cell to determine the most efficient. Then you could raise the one that needed the least fertilizer, rather than putting a lot of different genes into hundreds of plants and waiting for them to grow, as is currently done."
In addition to the potential savings in time and money, Porterfield said the chip has allowed him to do research that would otherwise be impossible. He recently conducted a study on the "Vomit Comet," the nickname for a high-flying research plane used by NASA to briefly simulate zero gravity. The experiment analyzed gravity's effect on plant development, trying to solve the riddle of how a plant determines which way is "up."
"We conducted research with the chip while we were flying in parabolas over the Gulf of Mexico, going from two times Earth's gravity to zero gravity again and again," he said. "There is absolutely no way this experiment could have been done without this chip."
The current technology for analyzing cells' electrical activity, called "patch clamping," uses a tiny electrical probe viewed under a microscope. The technology garnered its inventors the Nobel Prize for Medicine and Physiology in 1991.
"It requires a lot of know-how and hand-eye coordination," Porterfield said of patch clamping.
The chip, on the other hand, is automated and could be mass-produced in the future. Such a readily available chip could record reams more data than patch-clamping, he said.
Ion channels and pumps establish a difference in electrical potential across a cell's membrane, which cells use to create energy and transfer electrical signals. By quickly allowing ions in and out, they are useful for rapid cellular changes, the kind which occur in muscles, neurons and the release of insulin from pancreatic cells.
The chip currently can detect individual levels of different ions. Porterfield believes that with some modifications, however, the chip will be able to measure multiple ions at once and perform even more advanced functions such as electrically stimulating a cell with one electrode while recording the reaction with the remaining three.
Because ion channels are a prominent feature of the nervous system and elsewhere, they are a popular target for drugs. For example, lidocaine and Novocain target sodium-channels. In nature, some of the most potent venoms and toxins work by blocking these channels, including the venom of certain snakes and strychnine.
Porterfield's chip is technically classified as a "cell electrophysiology lab-on-a-chip." The device is further described in an article in the journal Sensors and Actuators, published online this month and scheduled to appear in the print edition in November.
Porterfield has been working on the biochip for almost two years and is currently working to expand its capabilities. The just-published study was funded by NASA and the Lilly Foundation.
