Fall 2014, Prof. JB Lee Ion Sensitive FET (ISFET) - What and Why?

Fall 2014, Prof. JB Lee Indicator electrode: ISEs  Ion selective electrodes (ISEs)  Fritz Haber discovered (1901) that there is a change in potential across a glass membrane when its two sides are in solutions of different acidity.  This led to the development of a new class of indicator electrodes called ISEs.  In addition to the glass pH electrode, ISEs are available for a wide range of ions. The development of new ISEs continues to be an active area of research.  The ISE’s membrane separates the sample, which contains the analyte at an activity of (a A ) sample, from an internal solution containing the analyte with an activity of (a A ) int.  Because the junction potential and the potential of the two reference electrodes are constant, any change in E cell is a result of a change in the membrane’s potential. E cell = E ref(int) − E ref(sample) + E mem + E j

Fall 2014, Prof. JB Lee By the way, what is pH again?  pH is the measurement of acidity (hydrogen ion concentration)  pH = -log 10 [H + ], for [H + ] = 1.8 x M, pH =  An important example of pH is that of the blood. Its nominal value of pH = 7.4 is regulated very accurately by the body. If the pH of the blood gets outside the range 7.35 to 7.45 the results can be fatal.

Fall 2014, Prof. JB Lee ISE: glass pH electrode  Glass pH electrode  pH sensitive glasses are manufactured typically with a composition ~22% Na 2 O, ~6% CaO and ~72% SiO 2.  Oxygen atoms within the lattice that are not bound to two Si atoms possess a negative charge. Cations (primarily Na + ) pair with these oxygen atoms and are able to diffuse slowly in the lattice, moving from one charge pair site to another. This movement of cations within the glass allows a potential to be measured across it.  Advantages  Its potential is essentially not affected by the presence of oxidizing or reducing agents.  Operates over a wide pH range  Fast  Functions well in physiological systems.

Fall 2014, Prof. JB Lee Gas-sensing electrodes  Gas-sensing electrodes  A thin membrane that separates the sample from an inner solution containing an ISE.  The membrane is permeable to the gaseous analyte, but impermeable to other components. The gaseous analyte passes through the membrane where it reacts with the inner solution, producing a species whose concentration is monitored by the ISE.  For example, CO 2 diffuses across the membrane where it reacts in the inner solution to produce H 3 O +. The change in the activity of H 3 O + in the inner solution is monitored with a pH electrode  CO 2 (aq) + 2H 2 O(l) ⇋ HCO 3 − (aq) + H 3 O + (aq)  CO 2, HCN, HF, H 2 S, NH 3, NO 2, SO 2 are commonly measured in this manner.

Fall 2014, Prof. JB Lee Potentiometric biosensors  Potentiometric biosensors  Gas-sensing electrodes are modified to create potentiometric electrodes that respond to a biochemically important species.  Potentiometric biosensors have been designed around other biologically active species, including enzymes, antibodies, bacterial particles, tissues, and hormone receptors.  Ex: enzyme (urease) electrode  Urease catalyzes the hydrolysis of urea (CO(NH 2 ) 2 ) to produce NH 3 (ammonia) and CO 2  CO(NH 2 ) 2 (aq) + 2H 2 O(l) ⇋ 2NH 4 + (aq) + CO 3 2− (aq)

Fall 2014, Prof. JB Lee Demand for in vivo biosensing

Fall 2014, Prof. JB Lee Why ISFET?  Why do we need ISFET? Strong demand in biomedical sensing (H, K, Na ions) Miniaturized versions of the glass-membrane ion-selective electrode (ISE) appear to be less stable For in vivo monitoring, glass-membrane ISE is fragile and cannot be used  Goals Reduced dimensions to probe biology Fast response Simple integration with measurement electronics  Solution Modify a common electrical engineering device (MOSFET) and use as a sensor (ISFET)

Fall 2014, Prof. JB Lee ISFET – small and reliable Conventional ISE too big, fragile & unstable for in-vivo biosensing applications ISFET small & reliable for in-vivo biosensing applications

Fall 2014, Prof. JB Lee ISFET  ISFET is essentially a type of MOSFET  The metal gate is replaced with electrolytes of interest MOSFET ISFET