the present methods described herein are primarily referenced to forming a single electrode device , and in particular a neural electrode device . however , it should be understood that the present methods can be configured to form a plurality of electrode devices that are suitable for medical sensing or stimulation applications . in a preferred embodiment , the present methods can be adapted to manufacture an electrode that is suitable for any electrical stimulation technology and any recording or sensing technology having conductive electrodes , such as electrodes that are useful in physiological solutions . in that light , the methods described herein are readily adaptable to scaling to batch processes for forming a plurality of electrode devices with reduced impedance at relatively low cost and high uniformity from one electrode to the next . turning now to the drawings , fig1 illustrates a neural interface system 10 according to the present invention . the neural interface system 10 comprises an electrode array 12 having a plurality of electrode sites 14 a and 14 b . the electrodes may be adapted to optimally sample ( record ) 14 a or selectively activate ( stimulate ) 14 b neural populations and may be individually or simultaneously activatable to create an activation pattern . the neural interface system 10 may further include a pre - molded component 15 onto which the neural interface array is attached or assembled that supports the electrode array 12 . the electrode array 12 is coupled to the pre - molded component 15 such that the electrodes 14 a , 14 b are arranged both circumferentially around and axially there along . alternatively the electrode array 12 may be kept in its original planar form and attached to another planar component for mechanical support . the neural interface system 10 of the present invention is preferably designed for deep brain stimulation and , more specifically , for deep brain stimulation with fine electrode site positioning , selectivity , tunability , and precise activation patterning . the neural interface system 10 , however , may be alternatively used in any suitable environment ( such as the spinal cord , peripheral nerve , muscle , or any other suitable anatomical location ) and for any suitable reason . methods for building the electrode array 12 comprising the electrodes 14 a , 14 b formed from shaped metallizations with reduced impedance will now be described . fig2 shows the dielectric substrate 16 contacting a release layer 18 that is directly supported on a carrier 20 . the dielectric layer 16 can be of a flexible thin material , preferably parylene , polyimide , silicone , or even a thin - film of silicon , or some combination of organic and inorganic dielectrics , but may alternatively be of any suitable material . the carrier 20 is preferably made of glass or silicon , but may alternatively be made from any other suitable material . the carrier 20 is may be flexible , rigid , or semi rigid depending on the microfabrication tooling ( organic electronics equipment can increasingly use flexible substrates without a carrier layer such as in roll - to - roll manufacturing , whereas ic and mems microfabrication equipment use a rigid silicon carrier ). a rigid carrier layer 20 has a thickness ranging from about 200 microns to about 925 microns , preferably greater than 500 microns . a metallization layer 22 in fig2 is deposited on the upper or outer surface 16 a of the dielectric substrate 16 . the metallization 22 is shown as a continuous layer and can be patterned using any suitable wet etch or dry etch wherein the mask is a photodefined resist or any other masking material patterned directly or indirectly using standard photolithography techniques having a perimeter extending from a lower metallization surface supported on the upper substrate surface 16 a to an upper metallization surface spaced from the lower metallization surface by a thickness of the perimeter . the metallizations 22 can be deposited using any suitable thin film , semiconductor , microelectromechanical systems ( mems ) manufacturing technique or other microfabrication process , such as physical vapor deposition . exemplary techniques and processes include evaporation and sputtering deposition . the metallizations layer 22 preferably includes a conductive material such as of gold ( au ), platinum ( pt ) or platinum - iridium , iridium oxide , titanium nitride , or any other metal , metal oxide , or conductive polymer having suitable electrically conductive properties . fig3 shows where the continuous metallization 22 has been patterned into a plurality of discrete metallization structures 22 a , 22 b , 22 c , 22 d , 22 e , etc . the metallization layer 22 can be patterned through etching , liftoff deposition ( not shown ), or any other suitable thin film , semiconductor manufacturing , mems manufacturing , or other microfabrication process . depending on the particular application for the finished neural interface system 10 , the dielectric substrate 16 , the release layer 18 and the carrier 20 can be flexible , semi - flexible , or rigid . the present method can further include patterning the metallization structures 22 a , 22 b , 22 c , 22 d , 22 e , etc . to include conductive traces , bond pads , and other suitable conductive elements . in fig4 , a layer of nanospheres 26 has been deposited onto the dielectric substrate 16 to cover both the shaped metallizations 22 a , 22 b , 22 c , 22 d , 22 e , etc . and the substrate surface 16 a between adjacent metallizations . the nanospheres 26 form a high - density , high - resolution spatial pattern serving as a substantially uniform mask or template over the surface of the individual metallizations . that is because the nanospheres 26 are substantially identical in size and shape . when they are deposited in a monolayer onto the metallizations 22 a , 22 b , 22 c , 22 d , 22 e , etc ., the nanospheres 26 self - assemble into a tightly packed , uniform pattern . for example , the present method can include depositing a monolayer of nanospheres 26 onto the metallizations 22 a , 22 b , 22 c , 22 d , 22 e , etc . by drop wetting ( direct application of the nanospheres in solution ) and then allowing them to self - assemble into hexagonally packed patterns ( fig8 ) upon de - wetting . this embodiment includes depositing a nanosphere solution including nanospheres and a solvent onto the metallization structures 22 a , 22 b , 22 c , 22 d , 22 e , etc . the solvent is then evaporated . the solvent is preferably selected based on its viscosity , evaporation rate , and wettability on the metallizations patterned on the dielectric substrate 16 . in one illustrative example , the solution includes polystyrene spheres mixed in a solvent of ethanol and de - ionized water . the ratio of ethanol to de - ionized water is approximately 4 : 1 . however , the solution can include nanospheres 26 other than those of polystyrene , such as glass , and a suitable solvent other than a mixture of ethanol and de - ionized water . the solution is preferably dropped onto the dielectric substrate 16 such that a monolayer of nanospheres 26 is distributed substantially uniformly on the metallization structures 22 a , 22 b , 22 c , 22 d , 22 e , etc . depositing the nanosphere solution may be performed by using the langmuir - blodgett technique to transfer a pre - fabricated monolayer of nanospheres 26 onto the metallizations 22 a , 22 b , 22 c , 22 d , 22 e , etc . patterned on the dielectric substrate 16 . in an example , nanospheres 26 having a surface tension of γ - ns are in a solvent having a surface tension of γ - solvent . it is given that γ - ns is less than γ - solvent . then , a monolayer of nanospheres 26 forms at the exposed surface of metallizations 22 a , 22 b , 22 c , 22 d , 22 e , etc . patterned on the dielectric substrate 16 . the substrate 16 supported on the carrier 20 can be moved through the solution to transfer the monolayer of the nanospheres 26 thereto . illustratively , one can use the drop wetting method by mixing a nanosphere solution ( e . g ., 5 % w / v solution ) into a 4 : 1 volume mixture of ethanol to de - ionized water . when applied to a patterned dielectric substrate 16 at room temperature on a horizontal surface , the nanospheres 26 will self - assemble along a contact line during the evaporation or de - wetting process . evaporation of the solvent can occur unassisted or be accelerated with environmental changes , such as in temperature and pressure from that of an ambient atmosphere . a second preferred embodiment is where the nanospheres 26 are deposited onto the metallization structures 22 a , 22 b , 22 c , 22 d , 22 e , etc . via spin - coating the above described nanosphere solution . if desired , the nanosphere solution can have a different viscosity , wettability , or other mixture ratio than that used with the drop - wetting or langmuir - elodgett technique . furthermore , depending on the nature of the nanosphere solution , spin - coating can include a particular rate of spinning and / or acceleration . according to the present invention , a series of recessed undulations 22 a ′, 22 b ′, 22 c ′, 22 d ′, 22 e ′, etc . or upstanding undulations 22 a ″, 22 b ″, 22 c ″, 22 d ″, 22 e ″, etc . are formed on the surface of the metallizations 22 a , 22 b , 22 c , 22 d , 22 e , etc . the recessed or upstanding undulations can be approximately pyramidal wave undulations , square wave undulations , approximately triangular wave undulations , or an undulation of any other suitable shape . fig5 , 5 a and 5 a ′ show recessed undulations 22 a ′, 22 b ′, 22 c ′, 22 d ′, 22 e ′, etc . that have been formed by etching 28 recesses 30 into the thickness of the respective metallizations 22 a , 22 b , 22 c , 22 d , 22 e , etc . etching 28 the recesses 30 into the metallizations takes place beneath the interstitial spaces of the layer of assembled nanospheres 26 . the result is undulations 22 a ″, 22 b ″, 22 c ″, 22 d ″, 22 e ″, etc . comprising recesses extending into the original thickness or height ( h ) of the metallization layers supported on the substrate 16 . for etching , it is preferred that the nanospheres 26 a diameter ranging from about 20 nanometer ( nm ) to about 1 , 000 nm . etching can be performed with any suitable etching process . one advantage of etching is that it does not require any adhesion between the existing metallization layer and newly deposited conductive material . platinum , for example , is a commonly used biocompatible metal that can be dry etched using techniques described in u . s . pat . no . 6 , 323 , 132 with a reactive ion etcher . the contents of this patent are incorporated herein by reference . in that manner , etching forms the recesses 30 having a depth extending part - way through the thickness of the metallization 22 b from that portion of its upper surface of the metallization not contacted or otherwise covered by a nanosphere 26 . the recesses 30 can extend from about 1 % to about 99 % into the thickness of the metallizations 22 a , 22 b , 22 c , 22 d , 22 e , etc . more preferably , the recesses are from about 50 % to about 90 % into the original metallization thickness . the metallizations shown in fig5 a have a thickness measured from the upper surface 16 a of the dielectric 18 to the upper surface of the as - deposited metallization of from about 0 . 25 micron to about 20 microns , more preferably from about 10 microns to about 20 microns . fig6 , 6 a and 6 a ′ relate to an alternative method where the upstanding undulations 22 a ″, 22 b ″, 22 c ″, 22 d ″, 22 e ″, etc . are formed by depositing 30 additional metallization material ( e . g ., in a lift - off deposition ) onto the metallizations 22 a , 225 , 22 c , 22 d , 22 e , etc . through the interstitial spaces between the nanospheres 26 . deposition 30 continues until the desired height of the added metallization material 32 measured from its base 32 a supported on the upper surface of the original metallization 22 b is achieved . for this technique , it is preferred that that the nanospheres have a diameter ranging from about 500 nm to about 5 , 000 nm . one advantage of this variation is that depositing material preferably results in metal - metal bonds and predictable surface properties . fig7 a illustrates a representative one of the undulations where the additional metallization material 32 forms a base on the upper surface of the metallization 22 b and build - up in a pyramidal manner . that is without contacting the adjacent nanospheres 26 , but while following their generally circular contour . in that respect , the height of the upstanding undulations is preferably about 90 % of the radius of the nanosphere . it has been discovered that this ratio provides maximum . added surface area for the added metallization . that means the upstanding additional or secondary metallization material has a height ranging from about 225 nm to about 2 , 250 nm above the upper surface of the primary metallization 22 . moreover , the added metallization does not grow so high as to prevent the subsequent removal of the nanospheres . in order for nanosphere removal , it is important that the added metallization not extend past the imaginary equator and over the upper half of the hemisphere . with this rule , it has been determined that approximately a . four - fold increase in the geometric surface area ( gsa ) is achievable . fig7 b is a photograph showing how the deposited metallization material builds up from the upper surface of a metallization without contacting the nanospheres 26 . the nanospheres 26 have been removed in the photograph , but the generally circular shape of one of them is delineated by the circle bordered by the deposited metallization material , which is seen as the off - white pyramidal bodies having somewhat triangular bases . in both embodiments , the recessed undulations 22 a ′, 22 b ′, 22 c ′, 22 d ′, 22 e ′, etc and extending 22 a ″, 22 b ″, 22 c ″, 22 d ″, 22 e ″, etc on the respective metallizations are preferably bounded by the interstitial spaces of the nanospheres 26 . since the nanospheres 26 are substantially uniform in shape and arranged in a substantially uniform distribution in the layers of fig5 and 6 supported on the upper surface of the metallization 22 a , 22 b , 22 c , 22 d , 22 e , etc ., there is a substantially uniform distribution of interstitial spaces between the nanospheres 26 . consequently , the undulations 22 a ′, 22 b ′, 22 c ′, 22 d ′, 22 e ′, etc . and 22 a ″, 22 b ″, 22 c ″, 22 d ″, 22 e ”, etc . are substantially uniformly distributed throughout the surface area of the shaped metallization . if desired , the nanospheres 26 are removed from the dielectric substrate 18 after forming recessed or extending the undulations 22 a ′, 22 b ′, 22 c ′, 22 d ′, 22 e ′, etc . and 22 a ″, 22 b ″, 22 c ″, 22 d ″, 22 e ″, etc . on the respective metallizations 22 a , 22 b , 22 c , 22 d , 22 e , etc . or , the nanospheres 26 can be left on the metallizations . the undulations 22 a ′, 22 b ′, 22 c ′, 22 d ′, 22 e ′, etc and 22 a ″, 22 b ″, 22 c ″, 22 d ″, 22 e ″, etc significantly increase the electrochemical surface area ( esa ) of the electrode , particularly relative to the geometric surface area ( gsa ) of an electrode formed from one of the metallization according to the present invention . the interstitial spaces of the nanospheres ( or “ pores ” of the layers of the nanospheres ) are preferably arranged in a . substantially uniform distribution , thereby enabling substantially uniform arrangement of the undulations . the particular form of the undulation , whether they be of the recessed or the extending form ( etching or deposition ) of the metallizations depends on the functional application of the electrode that will be manufactured from the metallization device , desired dimensions of the electrode , extensions , and / or recesses , materials within the metallization , and / or any suitable factor . in any event , the undulating surface provides an increased esa predicated on the diameter and packing arrangement of the nanospheres 26 , and the depth of recess 30 for the recessed undulation 22 a ′, 22 b ′, 22 c ′, 22 d ′, 22 e ′, etc . or the increased thickness of the deposited metallization material 32 for the extending undulations 22 a ″, 22 b ″, 22 c ″, 22 d ″, 22 e ″ etc . as shown in fig8 , the amount that the esa increases as is inversely proportional to the diameter of the sphere : where a inc = additional area additional area created inside the fundamental unit of the equilateral triangle formed by 3 adjacent spheres when hexagonally packed , d s = diameter of a sphere , d m = height of deposition or the depth of etch , and a e = geometric area of electrode ( derived from the metallizations 22 ). estimated area change in various illustrative examples of etched metallization electrode sites ( fig5 , 5 a and 5 a ′) are shown in table 1 of fig9 . in some preferred embodiments , the present invention methods additionally or alternatively include one or more of several variations described below . as shown in fig1 a and 10b , a further surface area increase can be achieved according to the present invention by undercutting one or more alternating layers of patterned metal . in one version of this embodiment , the method includes : depositing a planar metallization layer stack ( e . g ., au / pt , au / ir , or other au stack ) onto the dielectric substrate 16 , and then selectively wet etching the au metal . an example of this is to deposit a layer of platinum 40 onto the dielectric layer ( not shown in fig1 b ) using one of the methods previously described with respect to fig3 and 4 . without removing the nanospheres 26 , a layer of gold 42 is deposited on top of the platinum 40 followed by a second layer of platinum . the nanospheres 26 and the underlying photoresist pattern 24 are then removed and the gold 42 is wet etched . etching serves to expose additional surface area of the platinum 40 that was previously positioned both above and below the gold . this is shown by the exposed surface 42 a of the platinum layers 42 in fig1 b . it is important to not etch too much of the gold 42 so that it can no longer act as a structural support for the platinum . 40 . in fig1 b , the depth of etch is depicted as d au , which is less than the original thickness of the gold layer measured parallel to the plane of the dielectric substrate 16 . in addition to platinum , iridium , iridium oxide , and titanium nitride are suitable metallization materials for use with this gold etching process . in that manner , gold etching serves to expose more of the non - au metal surface area . fig1 a and 11b relate to another embodiment of the method according to the present invention . this embodiment additionally or alternatively includes depositing an alternating combination of layers on the dielectric substrate ( not shown in fig1 b ). in one specific embodiment alternating layer of platinum 40 and gold 42 are deposited one on top of the other until a stack of a desired height is achieved . in a similar manner as described above with respect to fig1 a and 10b , the gold layers are wet etched to undercut and expose addition platinum surface area . as described above , it is important not to etch too much of the gold 42 . in fig1 b , the depth of etch is depicted as d au , which is less than the original thickness of the gold layer measured parallel to the plane of the dielectric substrate 16 . enough gold must be left to serve as a structural pillar supporting the above platinum and gold layers . an example of this embodiment is alternating layers of au / pt / au / pt / au / pt stacked one on top of the other . gold . etching preferably forms more esa . although omitted for clarity , the preferred embodiments of the present methods include every combination and permutation of the various processes described above . furthermore , the preferred embodiments of the present method can be executed by a computer program or other system including computer program code for controlling hardware ( e . g ., machines for deposition , sputtering ) in an automated fashion . as previously discussed with respect to fig1 , a neural interface device 10 with reduced impedance according to the present invention includes the dielectric substrate 16 supporting the electrode array 12 comprising the plurality of electrodes 14 a , 14 b . after the metallization material 22 has been provided with an undulating surface characteristic , whether the undulations are recessed or upstanding the neural array is further completed with the addition of top dielectric , bond pads if necessary , vias , and other desired features ( none of these are shown here ). finally the neural array including the dielectric substrate 16 is removed from the carrier 20 . the release layer 18 facilitates this separation in some cases but not always required especially if the dielectric substrate 16 only has weak bonding to the carrier 18 . the dielectric substrates ( top and bottom ) and the electrode array 12 are then formed into a desired shape of the neural interface system 10 , which can be either planar or three - dimensional such as the cylindrical shape shown . the neural interface device 10 can be a planar probe with the electrode array 12 , a cylindrical probe with the electrode array , a substantially planar or curved substrate with the electrode array , or any suitable electrode device . at least a portion of each electrode 14 a , 14 b has a substantially uniform undulating surface described above . at least a portion . of the substantially uniform undulating surfaces of the electrodes 14 a , 14 b includes peaks and / or crevices ( e . g ., recesses ) that are preferably distributed in a regular arrangement and , more preferably , in an approximately hexagonal arrangement as shown in fig5 a , 5 a ′, 6 a and 6 a ′. the undulating surfaces increases the electrochemical surface area of the electrodes 14 a , 14 b , thereby reducing their impedance and improving their functionality for stimulation and sensing purposes . while this invention has been described in conjunction with preferred embodiments thereof , it is evident that many alternatives , modifications , and variations will be apparent to those skilled in the art . accordingly , the present invention is intended to embrace all such alternatives , modifications and variations that fall within the broad scope of the appended claims .
improved low - cost , highly reliable methods for increasing the electrochemical surface area of neural electrodes are described . a mono - layer of polymeric nanospheres is first deposited on a metallization supported on a dielectric substrate . the nanospheres self - assemble into generally repeating lattice forms with interstitial space between them . then , the geometric surface area of the metallization material is increased by either selectively etching part - way into its depth at the interstitial space between adjacent nanospheres . another technique is to deposit addition metallization material into the interstitial space . the result is undulation surface features provided on the exposed surface of the metallization . this helps improve the electrochemical surface area when the treated metallizations are fabricated into electrodes .