Three-Dimensional Interfacing of Cells with Hierarchical Silicon Nano/Microstructures for Midinfrared Interrogation of In Situ Captured Proteins

• Published in: ACS applied materials & interfaces Vol. 13; no. 7; pp. 8049 - 8059
• Main Authors: Flesch, Julia, Bettenhausen, Maximilian, Kazmierczak, Marcin, Klesse, Wolfgang M, Skibitzki, Oliver, Psathaki, Olympia E, Kurre, Rainer, Capellini, Giovanni, Guha, Subhajit, Schroeder, Thomas, Witzigmann, Bernd, You, Changjiang, Piehler, Jacob
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 24.02.2021
• Subjects: Biological and Medical Applications of Materials and Interfaces; Biosensing Techniques; Electromagnetic Fields; Green Fluorescent Proteins - chemistry; Green Fluorescent Proteins - isolation & purification; HeLa Cells; Humans; Optical Imaging; Particle Size; Protein Array Analysis; Silicon - chemistry; Surface Properties; Tumor Cells, Cultured; CMOS microfabrication; label-free protein sensing; in situ protein immobilization; IR refractive index sensing; cell-sensor-interfacing
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.0c22421

Label-free optical detection of biomolecules is currently limited by a lack of specificity rather than sensitivity. To exploit the much more characteristic refractive index dispersion in the mid-infrared (IR) regime, we have engineered three-dimensional IR-resonant silicon micropillar arrays (Si-MPAs) for protein sensing. By exploiting the unique hierarchical nano- and microstructured design of these Si-MPAs attained by CMOS-compatible silicon-based microfabrication processes, we achieved an optimized interrogation of surface protein binding. Based on spatially resolved surface functionalization, we demonstrate controlled three-dimensional interfacing of mammalian cells with Si-MPAs. Spatially controlled surface functionalization for site-specific protein immobilization enabled efficient targeting of soluble and membrane proteins into sensing hotspots directly from cells cultured on Si-MPAs. Protein binding to Si-MPA hotspots at submonolayer level was unambiguously detected by conventional Fourier transform IR spectroscopy. The compatibility with cost-effective CMOS-based microfabrication techniques readily allows integration of this novel IR transducer into fully fledged bioanalytical microdevices for selective and sensitive protein sensing.