A common challenge for many proposed drug delivery systems is protection of the drug depot from antibodies and serum proteins. Unlike most current implantable devices, drug delivery devices require an open interface with the body through which to deliver pharmaceutical agents. How does one close off this interface to immunoproteins while permitting free transport of target solutes? In most cases, the large nature of the invading proteins makes size exclusion an attractive barrier option. To this end, we are adapting specialized triblock terpolymers for use as protective membranes in drug delivery/detection devices. We combine the nanoscale pore size of these polymers with thin, rigid silicon supports built using MEMS fabrication technologies.

We begin by coating a 100 µm thick silicon wafer with low-stress silicon nitride (LSN) using low-pressure CVD. Squares with 20 µm sides are then patterned on the bottom side by photolithography, etched into the LSN using reactive ion etching, and etched through the underlying silicon using Bosch-process directed reactive ion etching. The LSN on the top side of the wafer acts as an etch-stop, leaving a silicon membrane with uniform, straight microscale pores capped by a 100 nm layer of LSN.

A poly(styrene)-poly(isoprene)-poly(lactide) (PS-PI-PLA) block copolymer is then spin-coated onto this LSN surface and annealed under vacuum. The PLA block self-assembles into cylinders perpendicular to the coating, nearly spanning it. The PLA block is then etched away, leaving 30 nm pores in the polymer film. The device is then subjected to hydrofluoric acid vapor to remove the LSN capping the microscale pores and a final, brief oxygen plasma etch removes any PS capping the nanoscale pores.

The resulting composite membrane consists of a 100 nm thick PS layer with 30 nm wide pores overlaying a 100 µm thick silicon support with 20 µm wide pores. The nanoscale pores are lined with PI, offering a convenient handle for grafting other materials onto the pore walls, from simple immuno-masking agents like poly(ethylene glycol) to stimuli-responsive polymers for additional functionality. Such membranes should provide immuno-isolation without retarding small molecule transport and should integrate well with the burgeoning number of BioMEMS devices under development