Size-Selective Diffusion in Nanoporous but Flexible Membranes for Glucose Sensors Hiroki Uehara, †, * Masaki Kakiage, †,§ Miho Sekiya, † Daisuke Sakuma, † Takeshi Yamonobe, † Nao Takano ‡, Antoine Barraud, ‡ Eric Meurville ‡, * and Peter Ryser ‡ † Department of Chemistry and Chemical Biology, Gunma University, Kiryu, Gunma 376-8515, Japan, ‡ Laboratoire de Production Microtechnique, Ecole Polytechnique Fe ´de ´rale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland. § Research Fellow of the Japan Society for the Promotion of Science. Present address: Department of Chemistry and Materials Science, Tokyo Institute of Technology.  Present address: Sensile Medical AG, CH-4614 Ha ¨gendorf, Switzerland. N anoporous membranes can be used as molecular or ionic separa- tors for various applications, in- cluding medical devices. For separator ap- plications, molecules or ions must be able to pass through the membrane pores across the entire membrane thickness. There are two approaches for preparing pass-through pores: arrangement of separated pores per- pendicular to the membrane surface, and junctions of pore channels. The typical ex- ample for the former case is an alumina nanoporous membrane. The most remark- able characteristic of this membrane is the straightness of the pores even for thick- nesses beyond the micrometer scale. Since the pore size is easily controlled by the an- odizing voltage as well as the electrolyte employed for the anodization process, the nanoporous alumina membranes have been favorably utilized for biofiltration applications. 1,2 Molecular transport could also be controlled by changing the pore size of the membrane. Likewise, the through hole channels of silica having a few tens of nanometers radii can selectively carry smaller molecules but block the larger ones. Desai et al. 3,4 investigated the difference of molecular transport between glucose and some proteins, such as albumin and immu- noglobulin G, through engineered silica membranes. Teramae et al. 5 also reported that silica nanochannels supported in micropores of an alumina membrane could perfectly shut out the albumin diffusion. Since glucose is one of the most impor- tant molecules in living animals, glucose separation and transport control are neces- sary functions for some medical devices. It is well-known that the glucose concentration in blood fluctuates when the pancreatic function is impaired (Type 1 diabetes) or the response by the body to insulin dimin- ishes (Type 2 and gestational diabetes). Both lead to abnormally high blood sugar levels (hyperglycemia), and monitoring glu- cose is thus a key for effective treatment of diabetes, becoming one of the most popu- lar but serious diseases especially in ad- vanced nations nowadays. An autonomous implantable biosensor equipped with such nanoporous membranes would enable long-term continuous monitoring of the glucose concentration, alleviating diabetic patients’ physical pain caused by daily blood-drawing for screening. However, nanoporous alumina or silica membranes are very brittle, so it is difficult to manufac- ture an actual device, especially a milli- meter-size implantable glucose sensor. In contrast, polymeric materials have superior flexibility and thus are expected to be alternative. *Address correspondence to uehara@chem-bio.gunma-u.ac.jp, eric.meurville@epfl.ch. Received for review December 19, 2008 and accepted March 13, 2009. Published online March 26, 2009. 10.1021/nn8008728 CCC: $40.75 © 2009 American Chemical Society ABSTRACT A series of nanoporous membranes prepared from polyethylene-block-polystyrene were applied for size-selective diffusion of glucose and albumin molecules. Millimeter-sized test cells for characterization of such molecular diffusions were designed assuming an implantable glucose sensor. The prepared nanoporous membrane exhibits excellent flexibility and toughness compared to conventional nanoporous membranes of brittle alumina. Pore size of the membranes could be controlled from 5 to 30 nm by varying preparation conditions. All of these nanoporous membranes prepared in this study let glucose pass through, indicating a continuous pore connection through the entire thickness of the membrane in a few tens of micrometers. In contrast, membranes prepared under optimum conditions could perfectly block albumin permeation. This means that these vital molecules having different sizes can be selectively diffused through the nanoporous membranes. Such a successful combination of size selectivity of molecular diffusion in nanoscale and superior mechanical properties in macroscale is also beneficial for other devices requesting down-sized manufacture. KEYWORDS: nanoporous · membrane · glucose · albumin · biosensor · block copolymer ARTICLE VOL. 3 ▪ NO. 4 ▪ UEHARA ET AL. www.acsnano.org 924