Eco-Friendly and Large-Scale Fabrication of Microelectronic Silk-Based Enzymatic Biosensors
Rodríguez Nuñez, Pablo (Institut de Microelectrònica de Barcelona)
Blanes, Carla (Institut de Microelectrònica de Barcelona)
Mena Fernández, Silvia (Institut de Microelectrònica de Barcelona)
Gavira, Sebastián (Institut de Microelectrònica de Barcelona)
Aznar-Cervantes, Salvador D. (Instituto Murciano de Investigación y Desarrollo Agrario y Medioambiental)
Dominguez, Carlos (Institut de Microelectrònica de Barcelona)
Guirado, Gonzalo (Universitat Autònoma de Barcelona)
Santiago, Sara (Universidad Complutense de Madrid)
Muñoz Berbel, Xavier (Institut de Microelectrònica de Barcelona)

Imprint:	IEEE, 2025
Abstract:	Silk fibroin (SF) from Bombyx mori is emerging as a sustainable biomaterial for enzyme-based biosensors due to its ability to stabilize enzyme activity and provide a robust matrix for biomolecule immobilization. Despite its integration into micro- and nanofabrication workflows remains underexplored. This study presents a novel, eco-friendly approach for integrating SF into cleanroom microelectronic workflows by depositing and processing SF at wafer level. Uniform SF films with tunable thicknesses ranging from 59pm 5 to 131 pm 2 nm were spin-coated onto silicon wafers and precisely patterned via electron beam lithography (EBL) using an optimized exposure dose of 1200μ C/cm2. Water was employed as the sole developer, avoiding the use of toxic organic solvents conventionally used in lithographic processes. SEM imaging confirmed high-resolution nano-patterning, with accurate and uniform hole sizes of 200 pm 2 nm. Enzymatic activity assays demonstrated that glucose oxidase (GOx) encapsulated in SF films retained over 90% activity after vacuum water annealing and 75% after chemically-mediated curing using green chemical compounds (GCC), representing a 260-200% improvement over conventional methanol-based curing methods, which has previously limited the application of SF as a bio-modified photoresist in microelectronic biosensor fabrication. Notably, enzymatic activity measured after EBL exposure indicated that the lithographic process did not compromise the enzyme integrity. This protocol enables the scalable fabrication of a novel bio-functional photoresist based on SF combining precise patterning while ensuring enzyme stability, positioning SF as a sustainable material for next-generation biosensor and bioelectronic devices, and eliminating the need for hazardous chemicals in cleanroom fabrication.
Grants:	European Commission 101112669 European Commission 101115182 Agencia Estatal de Investigación PID2021-127653NB-C21
Note:	Altres ajuts: European Commission ERDF/FEDER Operational Programme of Murcia (2021-2027), Project No. 50463 "Development of sustainable models of agricultural, livestock and aquaculture production"
Rights:	Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.
Language:	Anglès
Document:	Capítol de llibre ; recerca ; Versió acceptada per publicar
Subject:	Silk technologies ; Wafer-level processing ; Biosensors production ; Microelectronics ; Spin-coating ; Photoresist ; Electron beam lithography (EBL) ; Eco-friendly microfabrication
Published in:	2025 23rd International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers), August 2025, p. 1358-1361, ISBN 979-8-3315-1381-8

DOI: 10.1109/Transducers61432.2025.11110256

Available from: 2027-08-31 Postprint 4 p, 313.6 KB

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