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

2. 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

3. 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 10 -5 M, pH = 4.745  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.

4. 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.

5. 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.

6. 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)

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

8. 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)

9. 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

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