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The integrated ISFET developed at CNM: from the electronic tongue to DNA sequencing

In 1999, the CSIC’s Centro Nacional de Microelectrónica developed a new procedure that allowed the integration of different chemical sensors ISFET in one chip and to manufacture them with standard technology. Now, this procedure has made possible the creation of a commercial chip that enables mapping the genome of one person for 1000 dollars. Example of a DNA xip based on fluorescence. Every dot is a well. / Wikipedia.Recently, a North American company announced the launch of a device that enables mapping the genome of one person in a day and for less, according to company sources, than 1000 dollars. The tool is based on a chip that contains a high number of pH sensitive transistors (technically called ISFET, from “Ion-sensitive field-effect transistors”). Through them, the chip uses electrical measurements instead of the optical ones used by current DNA chips.  

What not everybody knows is that this type of ISFET was invented in Barcelona, at the CSIC’s Centro Nacional de Microelectrónica, twelve years ago. Then, scientists at the CSIC developed for the first time a procedure that made it possible to manufacture ISFET on a  large scale at a reduced price.  

Joan Bausells, CSIC researcher at the CNM explains: “to make a chemical sensor, the ISFET transistors need to have some area accessible to the liquid which is analyzed, and they have always been manufactured with  custom technology. What we developed for the first time was a way of producing these transistors with the standard technology of an integrated circuit chip factory”.

A procedure developed at CSIC has made possible the creation of a commercial chip that enables mapping the genome of a person

For that it was necessary to change the structure of the transistors which allowed  manufacturing the ISFET sensors and the other circuits in the same chip. This development was published in 1999, in Sensors and Actuators.

Bausells adds: “The new procedure made possible to work as with the normal chips: to put together many small transistors to make simultaneously many measurements and, also, to add in the same chip the electronic circuits needed for every sensor- transistor and to get the results.

As the chip can be manufactured with standard technology, the price is basically the same as for any other chip, therefore very cheap if the chips are produced in large quantities.

Until now, almost all commercial ISFETs are individual, what means only a sensor in a chip. The individual ISFETs manufactured by CNM with its own technology are mainly addressed to chemical analysis applications, such as the electronic tongue.

The electronic tongue is used mainly in environment or food industry, as it can detect any organic and inorganic compound, or a mixture of them.  Therefore, it can be applied to pollutants detection in water, to analyze the taste of food products or as a control system for beverage and food production.

On the contrary, the integrated ISFET created in CNM (different sensors on a chip) had been applied, until now, only in research fields but not in commercial products. This has been done for the first time by the aforementioned company (actually, Life Technologies) in developing a chip for genetic sequencing.

Based on the procedure developed by CNM, their chip for DNA sequencing contains a high number of wells, each one with an ISFET at the bottom. These wells are the equivalent to the wells in the DNA optical test based on fluorescence (see picture). When a DNA molecule, which has been previously treated, falls in the well, the ISFET measures the pH and sends the signal. Although it is now when the development is being launched on the market, the company published the first results last July in Nature, in an article where previous studies by CNM-CSIC are cited.