102 CHAPTER 4 Sensors at the micro-scale materials. Also, the ability to track the light-emitting cells within an organism provides powerful in vivo imaging technology [10]. In current applications, light emitted from such in vivo reporters is detected by an external photosensor through the skin and other tissues; thus, the sensitivity of the method is severely limited by the tissue absorption. Implementations of nanomorphic cells could dramatically expand the capability of the technology for in vivo imaging of light- emitting probes. (iv) Thermal. Living cells are open thermodynamic systems and they continuously exchange matter, energy, and entropy with the surrounding medium [11]. Therefore, bio-calorimetry, which monitors the thermal parameters of biosystems, is an important methodology as it provides direct information about the physiological state of organisms [11, 12]. 4.6 SENSORS OF BIOELECTRICITY The primary technological challenge in the development of electrical biosensors is that the charge carriers in the living cells are ions in electrolytes, but in solid-state devices, the charge carriers are electrons. Therefore, integration between microionics and microelectronics is needed [13]. The electrical elements of living cells are comprised of ion pumps and gated ion channels in the cells' membranes. The electrical activity of a cell is accompanied by the opening of the channels which allows ions to flow from/to the cell's exterior. The time scale of this `ionic' event is on the order of milliseconds [14,15]. The current flowing through the ion channels causes a voltage change in the electrolyte, which can be sensed by a FET-type device. To enable the `electronic­ionic' interface, the FET is fabricated without a traditional metal gate electrode; instead, the ion-conductive electrolyte acts as a controlling gate electrode as shown in Figure 4.5. If an ion-sensitive material such as silicon dioxide is used as a gate insulator, the `gate-less' FET will sense the change of ion concentration. Such a structure is referred to as an electrolyte­oxide­silicon FET or EOS FET [13­19]. It is also called an ion-sensitive field-effect transistor (ISFET). To sense extracellular electrical activity, the cell must be brought in proximity to the FET channel, as the extracellular electrolyte plays the role of an FET gate. The FET/transistor hybrid is sometimes (a) (b) Electrolyte Electrolyte Insulator p drain source channel n n Semiconductor FIGURE 4.5 `Ionic' field-effect transistor: (a) materials system; (b) barrier representation