Medical Device Daily National Editor

About 150 years ago, English physicist Michael Farraday coined the term "electrode," to describe an electrical conduction device. And since then electrodes have been commonly used to send and measure electricity through organisms, those organisms often human.

This year, University of Chicago scientist Rustem Ismagilov, MD – a la Farraday – has coined the term "chemistrode," for a device that has been developed in his lab for measuring the flow of chemicals in living cells.

This isn't such an easy task, according to the researchers working in the Ismagilov Lab at the university.

Measuring the flow of chemicals in cells or live tissues is difficult, they say in explanation. While electricity will flow through living tissue unimpeded, chemical molecules in living tissue interact with their surroundings, mixing and diffusing them.

The chemistrode is able to stimulate, record and analyze molecular signals "at high resolution," the researchers say in a new paper, to determine how the signals occur, "when, where and in what sequence."

The chemistrode will find its first uses in research labs, according to Delai Chen, a graduate student in the Department of Chemistry and Institute for Biophysical Dynamics at the University of Chicago, one of the lead writers of the paper. And it is likely be most beneficial, initially, in drug development, he told Medical Device Daily.

The paper says: "Instead of exchanging electrical signals, molecular signals are delivered by and captured in plugs, aqueous droplets nanoliters in volume surrounded by a fluorocarbon carrier fluid. Compartmentalizing these molecular signals eliminates dispersion and loss of sample due to surface adsorption."

Keeping the chemical-laden droplets intact allows a controlled stream of stimulating chemicals to enter on one end of the device and a steady stream of distinct resultant chemicals to be captured on the other end. The droplets can be analyzed immediately or stored for future analysis. They also can be split up for parallel study by different techniques, using the V shape of the device.

Chen said that establishing the V shape of the device was one of the hurdles first addressed by the research team. "We didn't originally know what the geometry of the device would be," he told MDD.

"We then spent some time to figure out how to detect the molecules in those droplets," a task made easier with mass spectrometry.

"The inspiration for this work," Ismagilov said, "was the microelectrode, but the key to its success was encapsulating the chemicals in aqueus droplets so that the chemicals could be delivered to and picked up from the reactive site in a controllable, measurable fashion." As "an analogue of the electrode," he said, the device will be useful in studying "stimulus-response dynamics in chemistry and biology."

The researchers say the chemistrode can be used to study any surface that responds to chemical stimulation, including cells, tissues, biofilms and catalytic surfaces." Thus far, they have used it to measure how a single murine islet responds to glucose.

Further out, future iterations of the chemistrode could be clinically useful, for instance in diagnostics for neurology, cardiology and endocrinology, they say.

Previous techniques for stimulating and measuring chemical reactions in organisms relied on laminar flow, which allows the chemicals in question to intermingle and disperse, making them hard to control and measure, according to the research paper.

The device, about a year-and-one-half in development, is compatible with traditional methods of culturing cells and tissues because — like the electrode — it can be used on any surface.

Chen told MDD that the chemistrode is relatively easy to use, since it only needs to be brought into contact with the surface of the cell or tissue under investigation. The only expertise needed, he said, is the ability to develop the droplets which contain the chemical stimuli.

These droplets are then delivered to the sample; chemical reactions occur or molecules are released from the sample, as in the case of a hormone; and the resultant chemical-laden droplets are carried away. All the while, the fluorocarbon carrier fluid remains in contact with the droplets and shields them from the wall of the device.

"The chemistrode offers a time-resolved, high-fidelity record of molecular stimulation and response dynamics," Ismagilov said, and that the paper "describes the physical principles that guide the operation of the chemistrode.

"It also implements the chemistrode to test the feasibility of each step and the compatibility of this platform with living cells."

The developers have begun to apply for a patent on the new device, and their research describing was published online Oct. 27, by the Proceedings of the National Academy of Science (the paper will appear in the print version of the journal on Nov. 4).

For now, the device "allows you to look very hard and precisely at living cells in a dish, but it has the potential to be used in whole organisms, as well," said Louis Philipson, a professor in the Department of Medicine and co-author of the paper. "The chemistrode offers real-time input-output analysis captured in excellent resolution. As such, it will facilitate research in a lot of areas and holds the potential for widespread applications in medicine."

Philipson added: "The development of this device is a wonderful example of the lack of walls at the University of Chicago. Here, physicians can interact with other scientists in unconventional ways and bring together different kinds of technology. The result is new ways of looking at things and new answers to old problems."