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Title: A SOLUTION TO THE PROBLEM OF ION CONFOUNDING IN EXPERIMENTAL BIOLOGY

Author
item Niedz, Randall
item Evens, Terence

Submitted to: Nature Methods
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/26/2006
Publication Date: 6/1/2006
Citation: Niedz, R.P., Evens, T.J. 2006. A solution to the problem of ion confounding in experimental biology. Nature Methods.Vol 3.No 6.p.417.

Interpretive Summary: Ion confounding is a near universal problem in experimental biology. The problem results from the design of experiments using salts. Each salt is composed of two ions. For example, sodium chloride (NaCl), common table salt, is composed of two ions, a sodium ion, Na+, and a chlorine ion, Cl-. Therefore, changing the concentration of a single ion in solution is difficult since two ions are always changed when adding a salt. The result is that many experiments studying ion-specific effects actually change the concentration of multiple ions and not just the ion(s) of interest. We report an equation that allows for the calculation of what salts, acids, and bases to add to make a solution of any type and concentration of ions. Using this equation scientists will be able to design experiments where the ion levels can be precisely specified.

Technical Abstract: Understanding the ion-specific effects of the mineral elements is a central theme of biology because these ions are fundamental to the composition and maintenance of life. However, experiments concerned with determining ion-specific effects are generally performed with salt, as opposed to ion, manipulations. This means that researchers have had to accept a co-variance in the co-ion of the salt used to manipulate the ion of interest. The result is that the effect of a single ion cannot be determined as it is confounded with the potential combined effects of the other ions that are co-varied. Because of this difficulty, the majority of research studies concerned with determining ion-specific effects exhibit ion confounding. Here we report the following three-component approach that removes ion confounding – 1) a mathematical approach using linear programming optimization of mixtures to determine the combination of salts, acids, and bases that satisfies any given target solution of ions; 2) ion-driven experimentation based on chemical equilibrium modeling rather than solution pH and colligative properties; and 3) experimental designs that use ions, as opposed to salts, as individual factors. Using this three component approach, it is now possible to experimentally determine ion-specific effects on biological responses relating to ion type, concentration, and proportion.