Immunochemical Potentiometric Sensors a

It is desirable to design sensors that utilize the high specificity of an immunochemical reaction. There have been two approaches to this goal: optical' and electrochemical.2-10 In this paper, we shall focus on the electrochemical approach. We shall not discuss the cases in which an ion-selective electrode sensitive to a marker ion has been used in an assay type situation. In the above-mentioned references2-" a conventional electrode/pH meter configuration has been used. With the invention of chemically sensitive field-effect transistors (CHEMFET) there have been attempts to incorporate an immunochemical reaction into the CHEMFET structure." This approach is not different, in principle, from the conventional electrode approach. The size of the molecules involved in an immunochemical reaction places special requirements on the electrochemical properties of the sensing membrane. In an ordinary ion-selective electrode (ISE) the selectivity arises from the ability of only one type of ion to permeate from the solution into the membrane. This ion is often called a primary ion as opposed to interfering ions, whose ion fluxes across the solutionmembrane interface are often several orders of magnitude lower than that of the primary ion. Therefore, it is the relative magnitude of the ionic flux of the primary ion with respect to the interfering ions that determines how selective the ISE is. On the other hand, the absolute value of the ion flux affects the drift, sensitivity to motion, and sensitivity to adsorption of both charged and electrically neutral species.'* The ionic flux represents an electrical current. There is an exchange current that flows in both directions through the membrane-solution interface even under the conditions of a zero net current. This exchange current, when greater than lo-' A cm-2, is characteristic of a good ISE. Returning to the original problem of an immunoelectrode, it is difficult to imagine that a membrane could be designed in such a way that it would allow high exchange current density of the immunochemical species of interest and exclude the permeation of small inorganic ions, In other words, it is unlikely that the mechanism that makes ISE selective could be applied in the case of imrnunoelectrodes. Instead, we need to design a sensor in which the immunochemical reagent, antigen or antibody, is confined to the surface. Secondly, we need some mechanism by which the surface concentration can be translated into electrical signal. It was hoped that both these prerequisites could be satisfied using a field-effect transistor.'' Although, in principle, this possibility remains, all attempts to achieve this goal have been unsuccessful so far. However, there have been persistent reports of potentiometric sensors2-'' that produce an electrical signal in response to some immunochemical stimulus. The purpose of this paper is to provide a critical assessment of this situation. Although the discussion will center mainly around a field-effect transistor, it is applicable to conventional electrode arrangement, as will be pointed out later.