Reducing sensor foreign body response via high surface area metal structures

Abstract

Embodiments of the invention provide optimized sputtered metallic surfaces adapted for use with implantable medical devices as well as methods for making and using such polymeric surfaces. These sputtered metallic surfaces have features that function to inhibit or avoid an inflammatory immune response generated by implantable medical devices. Typical embodiments of the invention include an implantable glucose sensor used in the management of diabetes having a sputtered metallic surface adapted to contact an in vivo environment.

1 . A method of making an electrochemical analyte sensor comprising:
 providing a base layer;   forming a conductive layer over the base layer, wherein the conductive layer includes a working electrode;   forming an analyte sensing layer over the conductive layer, wherein the analyte sensing layer includes a composition that can alter the electrical current at the working electrode in the conductive layer in the presence of an analyte;   forming an analyte modulating layer over the analyte sensing layer; and   
       forming a surface adapted to contact an in vivo environment, the surface comprising a sputtered metallic composition having the following characteristics:
 the sputtered metallic composition is deposited on a surface of the electrochemical analyte sensor adapted to contact an in vivo environment using physical vapor deposition (PVD) process; and 
 the sputtered metallic composition comprises pillars; 
 
       so that the electrochemical analyte sensor is made. 
     
     
         2 . The method of  claim 1 , further comprising:
 placing a substrate for the sensor surface adapted to contact an in vivo environment in a physical vapor deposition (PVD) chamber;   setting a pressure of a gas in the chamber; and   depositing the sputtered metallic composition on the substrate using physical vapor deposition at the pressure.   
     
     
         3 . The method of  claim 2 , wherein the sputtered metallic composition comprises as at least one structured layer selected from a patterned layer, a roughened layer, a non-uniform layer, and a layer including voids. 
     
     
         4 . The method of  claim 2 , wherein the sputtered metallic composition comprises gold. 
     
     
         5 . The method of  claim 2 , wherein:
 the sputtered metallic composition comprises a second layer on a first layer, the first layer between the second layer;   the first layer is deposited at the pressure comprising a first pressure, and   the second layer is deposited at the pressure comprising a second pressure lower than the first pressure.   
     
     
         6 . The method of  claim 2 , wherein the physical vapor deposition at a pressure in a range of 2-250 millitorr. 
     
     
         7 . The method of  claim 1 , wherein the sputtered metallic composition is formed to comprise nanostructures with dimensions in a range from 1 nm-1000 nm and/or max peak/valley heights in a range of 1 nm-1000 nm. 
     
     
         8 . The method of  claim 7 , wherein the physical vapor deposition comprises:
 ionizing the gas so as to form ionized gas particles; and   accelerating the ionized gas particles onto a target comprising the sputtered metallic composition using an electric and/or magnetic field having a power in a range of 10 watts to 100 kilowatts.   
     
     
         9 . The method of  claim 1 , wherein the sputtered metallic composition is formed so that when exposed to the surface comprising the sputtered metallic composition, RAW264.7 macrophages are influenced in a manner that inhibits their differentiation into an inflammatory (M1) phenotype, and/or influenced in a manner that facilitates their differentiation into an anti-inflammatory (M2) phenotype. 
     
     
         10 . The method of  claim 9 , wherein when exposed to the surface comprising the sputtered metallic composition, RAW264.7 macrophages produce less TNF-α than an amount of TNF-α produced in response to a control electrochemical analyte sensor that is identical to said electrochemical analyte sensor except that said control electrochemical analyte sensor comprises a sensor surface adapted to contact an in vivo environment formed from a polyimide composition.