Abstract:
An interface for selective excitation of a biological neural network is provided. The interface includes a microelectromechanical (MEMS) device having a deformable membrane, and a tactile-sensitive neural cell disposed on the deformable membrane. The cell on the deformable membrane senses motion or deformation of the membrane and provides a signal, responsive to membrane motion or deformation, to the biological neural network. Preferably, the deformable membrane and cell have about equal areas, to provide selective excitation. An interface array including at least two such interfaces is also provided. A retinal prosthesis interface array having, in each element of the array, a photodiode within the MEMS device for electrostatically actuating the deformable membrane is also provided. For this alternative, the cells and deformable membranes are preferably transparent.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is related to and claims priority from U.S. Provisional Application 60/447,572 filed on Feb. 14, 2003, hereby incorporated by reference. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates to neural prostheses. More particularly, the present invention relates to selective excitation of a biological neural network. 
     BACKGROUND 
     Several degenerative retinal diseases that commonly lead to blindness, such as retinitis pigmentosa and age-related macular degeneration, are primarily caused by degradation of photoreceptors (i.e., rods and cones) within the retina, while other parts of the retina, such as bipolar cells and ganglion cells, remain largely functional. 
     Accordingly, provision of a retinal prosthesis connected to functional parts of the retina and providing photoreceptor functionality is an approach for treating blindness caused by such conditions that has been under investigation for some time. Known retinal prostheses provide either electrical stimulation of neural cells or chemical stimulation of neural cells. 
     However, retinal prostheses making use of electrical or chemical stimulation of neural cells typically require external (i.e., outside the eye) power and/or information supplies, because such prostheses usually require more power than is available at the retina. The requirement for an external supply is disadvantageous, since connecting an external supply to an implant within the eye raises a host of practical issues. Furthermore, both electrical and chemical stimulation, as used in known retinal prostheses, do not stimulate neural cells in a naturally occurring manner, which raises concerns about the long-term viability of such prostheses. 
     Accordingly, it would be an advance in the art to provide a retinal prosthesis which does not require an external supply and which stimulates neural cells in a more natural manner than electrical or chemical stimulation. 
     SUMMARY 
     The present invention provides an interface for selective excitation of a biological neural network. The interface includes a microelectromechanical (MEMS) device having a deformable membrane, and a tactile-sensitive neural cell disposed on the deformable membrane. The cell on the deformable membrane senses motion or deformation of the membrane and provides a signal, responsive to membrane motion or deformation, to the biological neural network. Preferably, the deformable membrane and cell have about equal areas, to provide selective excitation. An interface array including at least two such interfaces is also provided. A preferred embodiment of the invention is a retinal prosthesis interface array having, in each element of the array, a photodiode within the MEMS device for electrostatically actuating the deformable membrane. In this embodiment, the cells and deformable membranes are preferably transparent. 
     An advantage of the present invention is that a low level of light is required for membrane deflection. This allows a retinal neural prosthesis to operate at ambient levels of light with or without an external power supply and with a total number of pixels of up to 100,000 pixels within a 3 mm×3 mm chip. Another advantage is that the retinal prosthesis provides a natural and thus sustainable mechanism of cellular excitation, namely mechanical deformation of tactile sensors. Still another advantage is that the retinal prosthesis allows for good visual acuity (i.e. spatial resolution). More specifically, pixel sizes can be on the order of 10-20 microns, geometrically corresponding to visual acuity of 20/40-20/80, respectively. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows an example of an interface according to the present invention. 
         FIG. 2  shows an example of light penetrating through the cells and membrane to reach a photodiode. Cells sitting on top of an illuminated segment, being deformed, are excited. 
         FIG. 3  shows an interface according to the present invention positioned under a retina with a diseased layer of photoreceptors. 
         FIG. 4  shows an example of an interface according to the present invention with tactile cells creating synaptic connections with bipolar cells in a retina. 
         FIG. 5  shows an example of light illuminating several segments of the interface of  FIG. 4 . 
     
    
    
     DETAILED DESCRIPTION 
       FIG. 1  shows an example of an interface according to the present invention, having a deformable membrane  140 . The interface of the example of  FIG. 1  is a retinal prosthesis. Deformable membrane  140  is part of a MEMS device which, in this example, also includes a photodiode  120  and an electrode  150 . Membrane  140  is separated from electrode  150  by a spacer  180 . Typically, spacer  180  defines independent segments of an interface array. For example,  FIG. 1  shows two such segments. Photodiodes  120  are included in a substrate layer  110 . Substrate layer  110 , membrane  140  and spacer  180  define open chambers  130 . Open chamber  130  can be several microns wide. Deformable membrane  140  is separated from electrodes  150  by a gap on the order of microns. Preferably, this gap is about 1 micron. Deformable membrane  140  is flexible, and is preferably electrically conductive. Standard MEMS technology is suitable for providing the structure and dimensions shown on  FIG. 1  (except cells  160 ), and this fabrication approach is preferred to reduce cost. 
     The interface of  FIG. 1  includes one or more tactile-sensitive neural cells  160  disposed on deformable membrane  140 . Cells  160  may be grown on membrane  140 , attracted to membrane  140 , or may be positioned on membrane  140  after growth or harvesting. Cells  160  are capable of making one or more synaptic connections to neural cells in a retina (e.g., bipolar or ganglion cells). These synaptic connections can be initiated or grown from cells  160  to retinal neural cells, or from retinal neural cells to cells  160  (i.e., these synaptic connections can be made in either direction). Alternatively, cells  160  can be retinal cells attracted to membrane  140  and adhered to its surface. In this case, cells  160  are synaptically connected to the biological neural network prior to being attached to membrane  140 . 
     Cells  160  generate signals upon deformation by deformable membrane  140 . Suitable cells for cells  160  include specialized touch sensor cells or tactile sensors as well as any type of neural cell that has a degree of tactile sensitivity. Furthermore, the signals generated by cells  160  are preferably strong enough to propagate further to the corresponding cells and axons in the retina that are synaptically connected to cells  160 . The propagation eventually goes into the optic nerve and the visual cortex of the brain. 
     Power is preferably provided to photodiodes  120  with a power supply line  170  disposed on a surface of substrate layer  110  facing away from cells  160 . Preferably, power supply line  170  is common to all photodiodes  120 . 
       FIG. 2  shows operation of the example of  FIG. 1 . A localized illumination  220  is received by one of photodiodes  120 , which leads to the presence of a voltage  210  on electrode  150 . As indicated above, voltage  210  is on the order of volts (i.e., about 1-20 volts). Voltage  210  electrostatically deforms membrane  140  to a deformed position  230 , thus stimulating cell  240 . In turn, cell  240  selectively stimulates the biological network it is connected to (i.e., the retina, in this example). Cell  160  in an adjacent segment which is not illuminated is substantially not stimulated. Thus, the stimulation provided by the present invention is selective. 
     In this embodiment, pulsed operation is preferable to reduce power consumption. When a pulse is applied to power supply line  170 , voltage  210  is developed across the gap separating electrode  150  from membrane  140 , and this voltage depends on the local light intensity received by photodiodes  120 , as shown on  FIG. 2 . This locally varying pulsed gap voltage provides a locally varying pulsed deformation of membrane  140 , which in turn provides selective pulsed stimulation of cells  160 . 
     Pulsed excitation of cells  160  will be perceived as a continuous visual input provided the interval between pulses is short enough. This persistence of vision phenomenon is also exploited in standard television and video applications. Suitable pulse durations are between about 0.01 ms and about 10 ms, as known in the art, and suitable repetition rates are between about 25 Hz and about 80 Hz. Since cellular recovery time after stimulation is on the order of 10-20 ms, such a repetition rate is perceived as continuous or nearly continuous illumination. 
     Since the interface of  FIG. 1  is a retinal prosthesis, light must be able to reach photodiodes  120 . Preferably, illumination is from above on  FIG. 1 , and in this case, cells  160 , deformable membrane  140  and electrode  150  are all preferably transparent. Alternatively, illumination can be from below on  FIG. 1 , and in this case power supply line  170  is preferably transparent. Power is preferably supplied to photodiodes  120  with an intra-ocular power supply, e.g., as disclosed in U.S. patent application Ser. No. 10/741,941. Alternatively, an external power supply can be used. 
       FIG. 3  shows a retinal prosthesis according to the present invention and disposed sub-retinally (i.e., between the retina and the outermost layers of the eye). Cells  160  are in proximity to inner nuclear layer cells  310  (e.g., bipolar cells), which are connected to ganglion cells  320 . Ganglion cells  320  are connected to axons  330  which transmit signals to the visual cortex via the optic nerve. Once cells  160  and cells  310  are positioned in proximity, as shown on  FIG. 2 , natural physiological processes can lead to the formation of synaptic connections between cells  160  and cells  310 . Alternatively or in addition, growth of cellular processes and/or formation of synaptic connections between cells  160  and cells  310  can be stimulated, e.g. by adding a growth factor for a limited period of time. Alternatively, bipolar or ganglion retinal cells can be attracted to membrane  140 , and migrate and adhere to membrane  140  while preserving synaptic connections between migrated cells and the retina. 
       FIG. 4  shows a retinal prosthesis according to the present invention and disposed sub-retinally, after the formation of synaptic connections  410  between cells  160  and cells  310 . 
       FIG. 5  shows operation of the example of  FIG. 4 . Illumination  220  is received by photodiodes  120  in some segments of the interface array. Cells  160  above illuminated photodiodes  120  are stimulated by motion of deformable membrane  140 . The stimulation of cells  160  is transmitted via synaptic connections  410  to inner nuclear layer cells  310 , which transmit the stimulation to ganglion cells  320  and thence to axons  330  and the visual cortex of the brain. 
     Some basic performance parameters of the example of  FIGS. 1-5  can be estimated as follows. Membrane  140  and electrode  150  form a capacitor having a capacitance of about C=1 fF, assuming a 1 μm gap between electrode  150  and membrane  140  having lateral dimensions of 10 μm by 10 μm. For electrostatic deflection of membrane  140  in this example, a voltage on the order of U=10V is required. The energy required to charge this capacitor to U=10 V is E=CU 2 /2=50 fJ. Assuming an image refreshing rate of 100 Hz, the required power per segment is only P=5 pW, and for pixel density of 10,000 pixels/mm 2 , the required power will be 50 nW/mm 2 . 
     A typical power flux on the retina (e.g. outdoors during daytime) is about 900 nW/mm 2 . If about 30% of this light is converted into electricity, the electric power density will be 300 nW/mm 2 . This power flux is more than sufficient to power a pixel density of 10,000 pixel/mm 2 , which geometrically corresponds to a visual acuity of 20/40. To discharge a capacitor after termination of illumination a resistance across each capacitor should be R=t/C, i.e. R=1/(100 Hz·1fF)=10 13  Ohm, corresponding to a time constant t of 10 ms. 
     The above detailed description is by way of example, not limitation. Thus many variations of the above embodiments are within the scope of the present invention. 
     For example, the above embodiments relate to stimulation of a retinal neural network. The invention can also be used to stimulate any kind of biological neural network, including but not limited to: central nervous system (CNS) neural networks (e.g., brain cortex), nuclei within the CNS, and nerve ganglia outside the CNS. A biological neural network is made up of interconnected biological processing elements (i.e., neurons) which respond in parallel to a set of input signals given to each. 
     Another variation is to harvest cells  160  from the same patient (e.g., from the patient&#39;s skin) in which the interface of the present invention is implanted, thereby avoiding rejection of cells  160  by making them autologous. Tactile sensitivity is inherent property of many types of neural cells and not only of specialized tactile sensor cells, thus other neural cells might be used for this purpose as well. 
     Yet another variation is a pulsed contacting mode. In this pulsed contacting mode membrane  140  can touch electrode  150 . This contact will discharge the capacitor formed by membrane  140  and electrode  150 , and then membrane  140  will then return to its original position (as on  FIG. 1 ). If light continues to illuminate photodiode  120 , this process of charging the capacitor, deflection of a membrane, and discharge will continue cyclically. The repetition rate of such a process will depend on the intensity of the light as well as on geometrical and mechanical properties of membrane  140 . 
     Another variation is epi-retinal (i.e., between the retina and the vitreous humor) disposition of a retinal prosthesis, as opposed to the sub-retinal disposition shown in  FIGS. 3-5 . In this variant, cells  160  preferably make synaptic connections to ganglion cells  320 . 
     Still another variation is to perform optical sensing remotely and use electrical signals from the remote optical sensor to drive an interface according to the present invention. In other words, the invention can be practiced, even for a retinal prosthesis, without performing optical to electrical conversion within the prosthetic implant.