据sciencedaily网站2006年10月21日报道，美国普渡大学研究人员已经开发出一种新的生物芯片，这种芯片可以测量细胞的带电活性情况，它在一次读取过程中采集的数据比使用现有技术获得的数据要多60倍。短期内，生物芯片可能加快科学研究的进程，从而加速肌肉和神经紊乱（例如癫痫症）类药物的研发，它还将有助于开发出更多高产的农作物品种。
生物芯片开发小组的领导人、农业与生物工程教授马歇尔•波特尔菲德称，“现在，我们通常是一天只能做1次试验，由于这项技术能够自动采集数据，在它帮助下，我们每天将可以做数百次试验。”
该设备可以在带电离子出入细胞时测量出它们的密集程度。生物芯片能够记录下封闭在液体毛孔内的16个活细胞的带电离子密度。利用为每个细胞配备4个电极，生物芯片可以同时、持续地为64个数据源提供数据传送。
波特尔菲德教授表示，与现有的技术相比，这些“额外”的数据可以加深研究人员对细胞活动的了解，现有的技术只能测量1个细胞外的1个数据点，而且不能同时进行记录。他称，生物芯片可以在不破坏细胞的条件下直接记录离子密度，而现有技术不能直接测量特殊的离子，并且用于进行针对性研究的细胞还会在研究过程中受到破坏。他认为保持活细胞的完好有几个好处，例如可以对它们进行额外的测试或监控其成长。
波特尔菲德称：“使用现有技术在实验室中进行科学研究是非常缓慢和困难的。”他认为新的芯片将有助于研发与离子通道不畅相关的人类生理紊乱类疾病的治疗药物，例如癫痫和慢性疼痛。他称，目前研发的药物中大约有15%会对离子通道的活动产生影响，而现有技术缓慢的研发进度限制了这些药物的研发。生物芯片将使科研人员在较短的时间内获得更多的数据，这样一来，在对药物以及药物对离子通道产生的不同程度的影响进行评估时，所需的时间大大缩短了。
离子通道对肌肉和神经细胞有着特殊的重要性，这些通道是细胞间相互通信和传送电信号的便利途径。生物芯片的大小为10×10毫米，大约相当于一枚一角硬币的大小。放在芯片内的细胞被封闭在16个锥形小孔内进行分析，分析完成后还能够完好无损地移走。波特尔菲德称，既然该技术不会杀死细胞，它就有可能被用于筛选和确认不同的农作物品种。“例如，假如你有兴趣开发耐氮肥瘠薄的谷物品种，如果拥有与氮肥高效利用相关的基因文库，就可以研制出少施肥的谷物。你可以用这些基因改变一组玉米细胞，然后使用生物芯片对每个细胞进行筛选并选出最有效的那个细胞。接着你就可以培育出少施肥的细胞。你就不会像现在这样，把许多不同的基因接入数百株植物中，然后耐心地等着它们成长。”
波特尔菲德称，除了可以节省时间和花费，这种芯片还可以让他在一些未知领域进行研究。他最近就正在从事“呕吐慧星”（Vomit Comet）研究，“呕吐慧星”是美国宇航局对零重力飞机的妮称，该研究旨在简单地模拟飞行失重状态。实验主要就重力对植物生长的影响进行研究，以便解开植物以怎样的方式“生长”之谜。他说，“使用该芯片，即使在墨西哥湾上空进行抛物线式飞行时，即一次次从两倍重力到失重状态的过程中，我们也可以进行我们的研究工作。没有这样的芯片，我们是绝不可能进行这种实验的。”
目前，对细胞带电活动进行分析的技术称为“膜片钳技术”，该项技术是使用一个微型电性探测器通过显微镜对细胞进行观察。该项技术的发明者在1991年获得了医学和生理学诺贝尔奖。波特尔菲德对膜片钳技术的评价是“它需要许多技巧与很高的手眼协调能力。”而另一方面，该芯片却是自动化的，并且在将来可以进行批量生产。他表示，生物芯片具有很高的可用价值，它可以比膜片钳技术记录更多的数据。
当离子通过一个细胞的隔膜时，离子通道和泵会产生一个不同的电压，细胞通过这种方式制造能量转移电信号。通过允许离子快速的进出，它们会有助于加速细胞的变化，例如肌肉细胞、神经细胞的变化以及胰腺细胞对胰岛素的分泌等。
该生物芯片目前可以探测到不同的离子的特殊层面。波特尔菲德相信，只要对芯片稍作修正，它就能一次对多个离子进行测量，甚至还能执行更多的功能，例如，使用一个电极模拟一个细胞，并记录下其他三个细胞的反应。
由于离子通道是神经系统和其他部位的重要组成部分，它们通常也是药物目标。例如，利多卡因和奴佛卡因的主要目标就是纳离子通道。实际上，一些最厉害的毒液和毒素也是通过堵塞这些通道来发挥其作用的，这其中就包括某些特定的蛇和马钱子碱的毒液。
波特尔菲德所开发的芯片从技术上可以将其划分为“细胞电生理学芯片实验室”。《传感器和制动器》杂志本月在网上公布的一篇文章对该设备进行了详细地介绍，这篇文章预计于11月刊印。波特尔菲德用了近两年的时间来开发生物芯片，目前，他正在对其进行改进。该项研究得到了美国国家宇航局和利里基金会的资助。
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.
