In spite of these advantages, there are many challenges in building an EIS-based biosensor. The sensitivity of label-free systems, so far, has been inferior compared with biosensors that use labels. In addition, the required instrumentation for EIS is complex and, today, bulky and expensive bench-top systems are an integral part of EIS platforms. These instruments typically only have a single or a few measurement channels. Hence, it is not practical to develop highly multiplexed assays using EIS, where hundreds to thousands of different analytes need to be detected in parallel. This make EIS, in its current state, not very suitable for developing compact and portable PoC biosensors .

Fully-integrated biosensor systems using semiconductor fabrication processes have been built in the past that promise unprecedented compactness, sensitivity, detection dynamic range (DDR) and cost-efficiency [7].

Reference [10] demonstrates one such work, where a fully integrated EIS IC based system was developed. However, the use of ICs brings a new set of constraints to biosensors in general Brefeldin_A and EIS-based systems in particular, such as the limited availability of surface options, semiconductor-compatible bio-functionalization, hybrid fluidic-electronic packaging and handling. Although such systems are a good candidate for next generation biosensors, they are not easy to build.

The main reason is that the use of ICs brings a new set of constraints to biosensor design, and EIS-based systems are no exception.

For example, limited Batimastat available materials and surface options in fabrication, semiconductor-compatible bio-functionalization, hybrid fluidic-electronic packaging and handling are among some of the limiting challenges.In this paper, we tackle the above challenges by examining various design and optimization aspects of EIS built using complementary metal-oxide-semiconductor (CMOS) processes, particularly its bio-to-semiconductor interface design. We discuss, in detail, considerations such as the choice of the electrode surface, surface linkers, and development of optimal bio-molecular detection protocols, all in view of IC manufacturing.

In Section 1, we will briefly introduce the basic concepts in EIS based biosensing, by examining the equivalent circuit model and explaining how molecular binding changes the electrode-electrolyte interface impedance. In Section 2, we will present an example integrated EIS biosensor platform, and discuss the performance metrics achievable using a CMOS IC. We will be able to see that the performance metrics are superior to that of bench-top instruments.