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Hillary would surely like Giaever & Keese new biosensor system
Biosensors & Bioelectronics Vol. 9 No. 3 (1994)
Hillary would surely like Giaever 81 Keese new biosensor system Jo Ann McDonald, US Correspondent One of the most poignant messages coming out of America’s new health awareness campaign is that Americans have to start employing new ways of looking at age old health care concerns. If so, we,‘11see a world of impressive opportunities lying deep beneath the surface of our current level of understanding.
Tcolumn
he reference to “Hillary” in the title of this is to Hillary Clinton. For lack of a better title, she is America’s co-president rather than simply just another “first lady,” and it is she who is spearheading America’s new health care initiative. Although Hillary Clinton herself is well aware of the cost-saving role innovative technologies must play, few who are participating in the current debate on the subject really understand the far-reaching ramifications such new ways of thinking could bring. Take Professor’s Ivar Giaever and Charles Keese’s electric cell-substrate impedance sensor (ECIS) system as an extraordinarily good illustration of what’s needed to achieve those complex goals. Researchers Giaever and Keese are professors at Rensselaer Polytechnic Institute (RPI) in Troy, New York. They are currently perfecting their very clever biosensor-based generic laboratory analysis system and have recently formed their own company, Applied BioPhysics, to commercialize it. If the system materialized as predicted, and all continues to go well, the founders just might have something Hi&u-y would surely think was right on the mark. The ECIS system is sheer elegance. What it does is measure cell motion by means of electrical current. The thesis is presented in the context of assessing cancer cells, for it was funding from the 0956-5663/94/$7.00
0 1994 Elsevier Science Ltd.
US National Foundation for Cancer Research that spurred the work. When mammalian cells are grown in culture, it seems they do not just sprawl about in a relaxed manner on the culture dish. Quite the contrary, they are extremely active and exhibit a variety of behaviour patterns. Described as “cell gymnastics,” the cells move all sorts of ways covering a few micrometers an hour. Giaever and Keese’s system actually manipulates the cells and monitors their movements as they happen in real time. Prior to the existence of the ECIS system, the only such observation tools available to biologists were time-lapse photography, or the use of substrates that revealed tracks of how and where the cells moved, after the fact. A powerful new tool The ECIS system is a powerful new tool, still in its design infancy, but destined to become one of the most exciting, cost-effective ways of monitoring cell behaviour to come along in quite some time. The researchers first deposit two thin gold strips on the bottom of a petri dish to act as electrodes. One strip is smaller than the other, with the smaller electrode delivering the current nearby the cells, while the larger acts as the counter xvii
Biosensors & Bioelectronics VoL 9 No. 3 (1994)
electrode to receive the current from its smaller brethren. Copper leads are attached to the electrodes, and the electrical circuit is completed by attaching the leads to an oscillator that supplies 1 microamp of alternating current at a frequency of 4000 Hz. An amplifier boosts the electrical signal, measures it, and feeds it to an ordinary computer for analysis. S i n c e the t e c h n i q u e is l i m i t e d to anchorage-dependent cells, such as fibroblasts, macrophages, and endothelial, only small cultures of one to one hundred cells per electrode can be monitored. When the tiny current is turned on, the cells on the electrode divert the current flow and the cells actually force the current to change its course and detour around the cells to reach the counter electrode. The measurement takes place by reading the voltage and calculating the ratio of voltage to current (i.e. impedance). Changes in i m p e d a n c e indicate changes in the cells' behaviour.
Probable applications Ivar Giaever, who is no stranger to electrical phenomena, shared the 1973 Nobel Prize in Physics for his studies of electrode tunnelling in superconductors while at the General Electric Research and Development Center. It was at GE where he began working with Charles Keese, a biologist with a physics background, who has done award-winning work on fluorocarbon fluid microcarriers for cell growth. Giaever and Keese feel their ECSI system might be especially useful for finding out how neighbouring cells influence each other's motions, and for studying how cancer cells invade a layer of epithelial cells. There is also growing interest in their biosensor system as a replacement for some toxicity testing of chemical compounds in animals, for the ECIS can quantitatively monitor changes in cell behaviour too tiny to see through a regular microscope, and the electricity has been proven not to disturb the natural behaviour of the cell. With growing pressure from society and humane considerations imploring the world of science to move away from using living animals (including humans) to test the toxicity of new
XV111
drugs, cosmetics, and possible environmental toxins in food, air, and water, such a simple tissue culture-based system could be just the answer to yet another batch of complex problems.
Wave of the future Take the simple situation of testing ones own child for allergies as an example. Instead of putting the child through the usual series of grid-patterned punctures to see how angry the potential toxin can make the skin, a relatively small number of skin cells could instead be taken from the child and all the "pain" transferred to a petri dish for overnight analysis. We take such cultures on a routine basis for determining strep throat in children or pap smears to look for cervical cancer in their mothers. The time and money involved in waiting for test results, not to mention the saving of pain to whatever animal, human or otherwise, would be enormous. Once can also envision such a system eventually being put in portable form such as the medical and environmental sensors field units we're starting to see on the market. Even more than simply what Giaever and Keese's biosensor can do, the discovery illustrates how to successfully bridge the worlds of physics, electronics, and biology, and it is that kind of collective thinking which is being advocated these days. Giaever and Keese's ECIS systems is a powerful new tool in the genre of the so-called "micromachines" we're just beginning to hear about in the electronic trade press. What is all means is that we're on the brink of discovering the tools necessary to look deeper down into the microscopic w o r d for the real workings of life as we currently know it, and as you might expect, the thesis is based on those "cell gymnastics." It is d e l i g h t f u l l y ironic that the key to such understanding lies in monitoring the behaviour of a single cell, which is virtually a throwback to days before whole organisms persevered.
Contact: Dr. Charles Keese, Applied BioPhysics Inc. 1223 Peoples Avenue, Troy, NY 121180 USA; tel: (at Rensselaer Polytechnic Institute [1] (518) 276-6438 ext. 6438.
Hillary would surely like Giaever 81 Keese new biosensor system Jo Ann McDonald, US Correspondent One of the most poignant messages coming out of America’s new health awareness campaign is that Americans have to start employing new ways of looking at age old health care concerns. If so, we,‘11see a world of impressive opportunities lying deep beneath the surface of our current level of understanding.
Tcolumn
he reference to “Hillary” in the title of this is to Hillary Clinton. For lack of a better title, she is America’s co-president rather than simply just another “first lady,” and it is she who is spearheading America’s new health care initiative. Although Hillary Clinton herself is well aware of the cost-saving role innovative technologies must play, few who are participating in the current debate on the subject really understand the far-reaching ramifications such new ways of thinking could bring. Take Professor’s Ivar Giaever and Charles Keese’s electric cell-substrate impedance sensor (ECIS) system as an extraordinarily good illustration of what’s needed to achieve those complex goals. Researchers Giaever and Keese are professors at Rensselaer Polytechnic Institute (RPI) in Troy, New York. They are currently perfecting their very clever biosensor-based generic laboratory analysis system and have recently formed their own company, Applied BioPhysics, to commercialize it. If the system materialized as predicted, and all continues to go well, the founders just might have something Hi&u-y would surely think was right on the mark. The ECIS system is sheer elegance. What it does is measure cell motion by means of electrical current. The thesis is presented in the context of assessing cancer cells, for it was funding from the 0956-5663/94/$7.00
0 1994 Elsevier Science Ltd.
US National Foundation for Cancer Research that spurred the work. When mammalian cells are grown in culture, it seems they do not just sprawl about in a relaxed manner on the culture dish. Quite the contrary, they are extremely active and exhibit a variety of behaviour patterns. Described as “cell gymnastics,” the cells move all sorts of ways covering a few micrometers an hour. Giaever and Keese’s system actually manipulates the cells and monitors their movements as they happen in real time. Prior to the existence of the ECIS system, the only such observation tools available to biologists were time-lapse photography, or the use of substrates that revealed tracks of how and where the cells moved, after the fact. A powerful new tool The ECIS system is a powerful new tool, still in its design infancy, but destined to become one of the most exciting, cost-effective ways of monitoring cell behaviour to come along in quite some time. The researchers first deposit two thin gold strips on the bottom of a petri dish to act as electrodes. One strip is smaller than the other, with the smaller electrode delivering the current nearby the cells, while the larger acts as the counter xvii
Biosensors & Bioelectronics VoL 9 No. 3 (1994)
electrode to receive the current from its smaller brethren. Copper leads are attached to the electrodes, and the electrical circuit is completed by attaching the leads to an oscillator that supplies 1 microamp of alternating current at a frequency of 4000 Hz. An amplifier boosts the electrical signal, measures it, and feeds it to an ordinary computer for analysis. S i n c e the t e c h n i q u e is l i m i t e d to anchorage-dependent cells, such as fibroblasts, macrophages, and endothelial, only small cultures of one to one hundred cells per electrode can be monitored. When the tiny current is turned on, the cells on the electrode divert the current flow and the cells actually force the current to change its course and detour around the cells to reach the counter electrode. The measurement takes place by reading the voltage and calculating the ratio of voltage to current (i.e. impedance). Changes in i m p e d a n c e indicate changes in the cells' behaviour.
Probable applications Ivar Giaever, who is no stranger to electrical phenomena, shared the 1973 Nobel Prize in Physics for his studies of electrode tunnelling in superconductors while at the General Electric Research and Development Center. It was at GE where he began working with Charles Keese, a biologist with a physics background, who has done award-winning work on fluorocarbon fluid microcarriers for cell growth. Giaever and Keese feel their ECSI system might be especially useful for finding out how neighbouring cells influence each other's motions, and for studying how cancer cells invade a layer of epithelial cells. There is also growing interest in their biosensor system as a replacement for some toxicity testing of chemical compounds in animals, for the ECIS can quantitatively monitor changes in cell behaviour too tiny to see through a regular microscope, and the electricity has been proven not to disturb the natural behaviour of the cell. With growing pressure from society and humane considerations imploring the world of science to move away from using living animals (including humans) to test the toxicity of new
XV111
drugs, cosmetics, and possible environmental toxins in food, air, and water, such a simple tissue culture-based system could be just the answer to yet another batch of complex problems.
Wave of the future Take the simple situation of testing ones own child for allergies as an example. Instead of putting the child through the usual series of grid-patterned punctures to see how angry the potential toxin can make the skin, a relatively small number of skin cells could instead be taken from the child and all the "pain" transferred to a petri dish for overnight analysis. We take such cultures on a routine basis for determining strep throat in children or pap smears to look for cervical cancer in their mothers. The time and money involved in waiting for test results, not to mention the saving of pain to whatever animal, human or otherwise, would be enormous. Once can also envision such a system eventually being put in portable form such as the medical and environmental sensors field units we're starting to see on the market. Even more than simply what Giaever and Keese's biosensor can do, the discovery illustrates how to successfully bridge the worlds of physics, electronics, and biology, and it is that kind of collective thinking which is being advocated these days. Giaever and Keese's ECIS systems is a powerful new tool in the genre of the so-called "micromachines" we're just beginning to hear about in the electronic trade press. What is all means is that we're on the brink of discovering the tools necessary to look deeper down into the microscopic w o r d for the real workings of life as we currently know it, and as you might expect, the thesis is based on those "cell gymnastics." It is d e l i g h t f u l l y ironic that the key to such understanding lies in monitoring the behaviour of a single cell, which is virtually a throwback to days before whole organisms persevered.
Contact: Dr. Charles Keese, Applied BioPhysics Inc. 1223 Peoples Avenue, Troy, NY 121180 USA; tel: (at Rensselaer Polytechnic Institute [1] (518) 276-6438 ext. 6438.