Neuronal research requires to efficiently perform long-time experiments on large-scale neuronal networks in a minimally invasive way. Such experiments imply stimulation and measurements of electrical activity on a large number of neurons. This could be achieved by on-chip integration of actuators, sensors and readout electronics with dimensions comparable to the sizes of neurons. Integration of biosensors at this scale creates new challenges: the processing of the sensors must be compatible with state-of-the art CMOS technology, the system must be biocompatible, and the down-scaled technology imposes restrictions on the applicable stimulation voltages and increases the electrical noise.
Recently it has been demonstrated that biological phenomena can be exploited in order to achieve the best coupling between cells and sub-micron scale electronics. Engulfment of sub-micron nail structures by the cell membrane minimizes the distance between the sensor and the cell , .
This paper presents two methods to produce nails with sizes from sub-micrometer to micrometer scales, on top of a CMOS chip. Prototype chips have been fabricated, and cells have been cultured to examine the in-vitro bio-compatibility of the chip.