Biostability of micro-photodiode arrays for subretinal implantation
Introduction
Retinitis pigmentosa (RP) is an inherited condition which involves progressive decay of photoreceptor cells and eventually results in complete loss of vision. Histological studies have shown, however, that the neurons following the signal cascade, i.e. the neuronal network, survive for an extended period of time [1], [2]. We therefore attempt the replacement of the photoreceptor cells by an artificial device. It is designed to convert light into electrical current and electrically stimulate retinal neurons. The basic concept comprises arrays of tiny solar cells, the so-called micro-photodiode arrays (MPDA) (Fig. 1). Prototype devices have already been implanted subretinally in animals between the neuronal layer and the pigment epithelium [3], [4]. These so-called sub-retinal implants were first proposed and an MPDA was designed by Chow et al. [5], [6], [7], [8].
A retina implant chip which is intended to remain permanently implanted has to fulfill quite rigorous requirements with respect to biocompatibility. Firstly, it has to be biocompatible in the sense that no toxic materials may leak into the surrounding tissue and no damage occurs to the tissue due to mechanical stress. On the other hand, the implant must withstand corrosive attack of its physiological environment. This includes saline solution, proteins and possibly corrosive products of cell metabolism.
A key element of the MPDA chips in this respect is their passivation layer which encapsulates the chip. It is intended to prevent any leakage of materials into the surrounding tissue and at the same time to shield the chip from chemical attack of the physiological environment. In addition, since the implant is based on a silicon chip, any passivation layer has to be also compatible with the semiconductor process technology. In particular, availability of a low temperature fabrication process, good adhesion to the silicon chip, methods allowing for integration with micro-electrodes and availability of micro-fabrication technology are indispensable prerequisites. For the chips discussed in this study a low temperature silicon oxide deposition process was employed which will be described in more detail below.
Several predominantely polymeric materials have been used for treatments in the posterior region of the eye and have been investigated with respect to their biocompatibility. Findings thereof were reviewed recently by Colthurst et al. [9]. Two major areas of applications are concerned: biomaterials have been introduced into the eye (1) in order to provide positional support and (2) have been applied in sustained release drug therapy.
Only quite recently implants intended for functional stimulation of neurons in the retina have been developed and implanted into animal models [10], [11], [12], [13], [3], [4]. These implants comprise a completely different class of materials namely silicon, silicon oxide and metals such as titanium nitride and gold. So far little is known about the long-term biocompatibility and biostability of these materials when implanted into the eye. This paper reports the first results obtained from about 60 chips which were tested either in vitro or implanted for different periods of time of up to 18 months.
Section snippets
Preparation of individual MPDA chips
Fig. 1 shows both a crosssection and a micrograph of a micro-photodiode. A detailed fabrication procedure is to be published elsewhere. Briefly, micro-photodiode arrays were manufactured on a silicon wafer using the complementary metal oxide semiconductor (CMOS) process technology. After completion of the electrically active structures, a passivation layer consisting of silicon oxide was applied in two steps. The first layer consisted of about 15 nm of silicon oxide grown within 30 min at 900°C
In vitro measurements
Charge delivery as a function of test duration was measured in vitro (Fig. 3). Both MPDA with planar titanium/gold (Ti/Au) micro-electrodes and MPDA with nano-porous titanium/titanium-nitride (Ti/TiN) micro-electrodes were investigated. Titanium in both cases merely served as adhesion layer (thickness: ≈10 nm) between the electrode and the silicon of the MPD. Data were fitted to an exponential decay. The much higher decay time of the current signal in case of the TiN electrodes is indicative of
Summary and conclusions
This paper reports the first results concerning biostability of silicon chips in neuronal tissue obtained in an on-going research project aimed at the development of artificial retina implants. In contrast to the excellent stability observed in vitro considerable degradation of MPDAs was found to occur in vivo. Obviously, additional factors which are not present in the described in vitro corrosion test contribute to the corrosion of the passivation layer and silicon in vivo. This concept is
Acknowledgements
This research was funded by the German ministry for education, science, research and technology (BMBF) under grant 01 IN 502 A, C and D. Diligent electron microscopy work performed by N. Kern is acknowledged. We thank M. Rosner for preparation of Figs. 2 and 4.
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