Development of a polymer based neural probe - How to record intracortical neural activity while minimizing the tissue response

Sammanfattning: Intracortical neural probes have in the last couple of years been developed from stiff single probes to stiff multi-electrode neural probes to flexible multi-electrode neural probes. One reason for the change in design is that more than one recording/stimulation electrode, as in the case with a single wire, is needed for more advanced studies. The stiff multi-electrode probes were fabricated using silicon as the base and the stiffness of silicon made the probes unable to follow the micro motions of the brain. This led to the development of polymer based multi-electrode probes that are better to follow the micro motions of the brain. The polymer based neural probes, when comparing to a stiff probe, have less tissue response, reduced encapsulation of the probe by glial cells, increased functional neurons around the probe and a smaller void around the probe in the tissue. It has also been shown that the encapsulation around the neural probe is the largest around the base of the probe, while at the edges the encapsulation is smaller. When designing a neural probe used for neural recordings, it is of interest to keep the electrical impedance of the interface between the electrode and the tissue as small as possible, since it will generate a signal with a better signal to noise ratio than if the electrical impedance is large. The impedance can be decreased by increasing the size of the electrode, but if the size of the electrode gets too large it might act as a direct connection between two neurons, hence the size should be as small as possible. The solution to this is to modify the electrode surface to become porous/rough, which will keep the geometrical size of the electrode small and at the same time keep the active area of the electrode large. With all this in mind, my work has mainly been about designing a flexible polymer based intra cortical neural probe for chronic recordings. The probe, designed by me and my colleges, reassembles a flat and flexible Christmas tree and on the tip of each branch there is an electrode. There are 9-13 platinum black modified recording electrodes on the probe. The platinum black modification decreases the electrical impedance of each electrode by roughly one order of magnitude. In one study the probe recorded neural activity from mossy fibers and climbing fibers in the cerebellar molecular layer in rats. In one study it was used to analyze how hyperalgesia can be seen in the somatosensory cortex of free moving rats. Not only has the overall design of the probe been developed over time, but also the material out of which the probe was constructed. The polymer has been changed first from SU-8 to polyimide, and then to a newly developed polymer called OSTE+. I further developed OSTE+ from it's original use in micro fluidic devices. Polyimide has the benefit over SU-8 that it is not as brittle and OSTE+ has the benefit over polyimide and SU-8 that it can be up to 500 times more flexible. Since OSTE+ is a newly developed polymer two biocompatibility studies were done; the first one used in vitro MTT assays together with mass spectroscopy for analyzing the biocompatibility and in the second one in vitro immunohistochemistry was used for the biocompatibility studies. It was shown that OSTE+ is rendered nontoxic to cells if it is incubated in water for one-week prior to use and that the tissue response of OSTE+ compared to polyimide is similar.