ELSEVIER ADVANCED TECHNOLOGY Biosensors & Bioelectronics Vol. I1. No. 12, pp. 1237-1252, 1996 © 1996 Elsevier Science Limited Printed in Great Britain. All rights reserved 0956-5663/96/$15.00 Control of the neuronal cell attachment by functionality manipulation of diazo-naphtho- quinone/novolak photoresist surface Dan V. Nicolau, Takahisa Taguchi, Hideo Tanigawa & Susumu Yoshikawa Osaka National Research Institute, 1-8-31 Midorigaoka, Ikeda, Osaka 563, Japan Tel: [81] (727) 51 9521 Fax: [81] (727) 51 9628 (Received 2 February 1996; accepted 16 April 1996) Abstract: The surface of the photosensitive Diazo-Naphto-quinone/novolak film was chemically manipulated through UV exposure and subsequent thermal processes to obtain different surface functionalities (DNQ, carboxylic, imidazole, indene, silylated and charged groups) and hydrophobicities. The neuronal cell attachment is sensitive to chemical functionalization, with favourable influence from charged, imidazole and carboxylic groups, while the hydrophobic/hydrophilic balance of the photoresist surface plays at best a secondary role. The microlithographic techniques assessed (standard positive tone, negative and positive tone image reversal, and surface imaging based on silylation) can be used to gain insight into the cell attachment mechanisms. The positive tone DNQ/novolak/imidazole system was found to be a suitable candidate for cell patterning. © 1996 Elsevier Science Limited Keywords: cell adhesion, neuronal cells, surface functionalization, photolitho- graphy INTRODUCTION Techniques for controlling biomolecular architec- tures on surfaces have a wide range of potential applications in biosensing, cell guidance, and molecular eletronics (Nicolini, 1995). As knowl- edge regarding architectures ordered vertically incorporating bioactive molecules and cells advanced steadily in the last decade, we witnessed a growing interest in ordering them laterally (Gopel, 1995). This new development requires techniques for patterning areas with different properties that control the selective attachment of the vertically ordered architectures on the same basal surface. Vertically structured cell engineer- ing found applications in biosensors based on plant and animal tissues (Wijeseriya & Rechnitz, 1993), and in creating electronically modulated biological functions (Aizawa et al., 1994). Lat- erally structured cell engineering aims towards multiplication of these functions on the same substrate. The neuronal cell's electrical activity makes it an ideal candidate for integration in a bioelec- tronic device. Although progress has been made in conceiving and building an integrated neuronal- semiconductor device, the technology employed relies only marginally on the possibilities offered 1237