NATURE MATERIALS DOL: 10.1038/NMAT3404 ARTICLES 353pm 40μm 170um 20 SU-8 350 nm ejected length (um) / Figure 3 Geometry control by design in nanoES. a, b, Basic design and structural subunit for simulation. a, Top-down view of the entire subunit. Blue ribbons are stressed metal lines with SU-8 passivation. Red lines are single Su-8 ribbons without residual stress. b, Cross-sectional views of those two key structural elements used for simulation. c, Plot of projected (on the x-y plane) length versus height (in the z direction) for the vertical blue ribbon in a as determined from the simulation. Open red squares with error bars are experimental data(means +s.d. recorded in air for point a and B in a. The shows a 3D view of the simulated structure, and the scale bar shows different heights in the z direction. d, Schematic showing the integration of period v imulation of the bending of the subunit model for the reticular structure was carried out using the commercial finite element software l S Th reticular-device domains (light blue) into a flexible mesh (green ). In individual reticular domains the 3d device positions relative to the global flexible mesh can be controlled by their geometry designs (a-c). e, f, Design patterns ()and experimental data( ID) for two reticular units. SU-8, metal and nanowires are shown in blue, pink and yellow in e. Changing the structure of the connecting feature (white arrows) between adjacent device units during pattern design (I) yields controlled variations in the 3D positioning of the nanowire FETs, which can be further tuned by the stress in the metal connections. these experiments, the device positions are 40 um(ell) and 23 um(fiD) above the mesh plane Scale bars in e f, 20 um We have carried out simulations of a subunit of the reticular nano ES/collagen scaffold(Fig 4a)shows clearly that self-organizing reticular structure(Fig. 3a-c). Measurements of the collagen nanofibres(green)are fully entangled with the bending for the corresponding experimental structures(Fig 3c, nanoES, with no evidence of phase separation. SEM images of open red squchanges in structural parameters(for example, the lyophilization(Fig. 4b)show that the flexible nanoES mesh is res)are consistent with the simulation(Fig 3c). the open mesh nanoES/alginate hybrid scaffold produced by Additionally, total length of the subunit and thicknesses of SU-8 or metals) intimately anchored to the alginate framework, which has a yield predictable changes in the bending angle of the subunit similar pore structure as the pure alginate scaffold prepared (Supplementary Fig S4). In this way, ordered 3D nanowire FET under similar conditions. Finally, optical micrographs of a arrays can be designed and fabricated using reticular-or mesh-like multilayered mesh nanoESPLGA scaffold(Fig. 4c), which wa structures that incorporate multi-layer metal interconnects with prepared by electrospinning PLGA fibres on both sides of the built-in stress to self-organize(roll-up)the scaffold( Supplementary nanoES and subsequent folding of the hybrid structure, highlight Fig S4). Finally, we have designed reticular domains in mesh-like the intimate contact between nanoES mesh and PLGA fibres. structures(Fig. 3d). Images of reticular domains(Fig. 3e, f) show The hybrid nano ES/biomaterial 3D scaffolds retain the original that regular nanowire FET devices with distinct device positions nanowire Fet device characteristics. For example, measurements can be realized by varying the structural parameters of individual in 1 x phosphate buffered saline solution showed that AG/G elements. Overall, this approach yields hierarchical 3D nanoES with and AS/s were less than +9% for the mesh nanoES/PLGA ubmicrometre to micrometre scale control in reticular domains composite versus bare nanoES Hybrid nanoES were stable under and millimetre to centimetre scale in the mesh matrix by folding or cell culture conditions. For example, nanowire FET devices in rolling as shown above( Fig. 2). the hybrid reticular nanoES/Matrigel scaffold in neuron culture cular and mesh nanoES were also merged with media(Fig. 4d)had AS/S<+11% over a nine-week period conventional macroporous biomaterials. Specifically, gel casting, suggesting a capability for long-term culture and monitoring with lyophilization and electrospinning were used to deposit and the nanoES. These results show that nanoES can be combined construct macroporous collagen (Fig 4a), alginate ( Fig 4b) with conventional biomaterials to produce hybrid scaffolds that and poly(lactic-co-glycolic acid)(PLGA; Fig. 4c), respectively, now provide nanoscale electrical sensory components distributed around nanoES. A confocal fluorescence micrograph of a hybrid in three dimensions NatureMateriAlsIVol11iNovemBer2012Iwww.nature.com/naturematerial G 2012 Macmillan Publishers Limited. All rights reservedNATURE MATERIALS DOI:10.1038/NMAT3404 ARTICLES A B 60 µm Free 40 µm -standing part 56 µm 170 µm fixed part SU-8 350 nm Cr 50 nm Pd 75 nm SU-8 350 nm SU-8 350 nm a b 40 30 20 10 0 0 20 40 60 80 A B Projected length (µm) Height (µm) 35.3 µm 0 c d ef I I II II y x Figure 3 | Geometry control by design in nanoES. a,b, Basic design and structural subunit for simulation. a, Top-down view of the entire subunit. Blue ribbons are stressed metal lines with SU-8 passivation. Red lines are single SU-8 ribbons without residual stress. b, Cross-sectional views of those two key structural elements used for simulation. c, Plot of projected (on the x–y plane) length versus height (in the z direction) for the vertical blue ribbon in a as determined from the simulation. Open red squares with error bars are experimental data (means ±s.d.) recorded in air for point A and B in a. The simulation of the bending of the subunit model for the reticular structure was carried out using the commercial finite element software ABAQUS. The inset shows a 3D view of the simulated structure, and the scale bar shows different heights in the z direction. d, Schematic showing the integration of periodic reticular-device domains (light blue) into a flexible mesh (green). In individual reticular domains, the 3D device positions relative to the global flexible mesh can be controlled by their geometry designs (a–c). e,f, Design patterns (I) and experimental data (II) for two reticular units. SU-8, metal and nanowires are shown in blue, pink and yellow in e. Changing the structure of the connecting feature (white arrows) between adjacent device units during pattern design (I) yields controlled variations in the 3D positioning of the nanowire FETs, which can be further tuned by the stress in the metal connections. In these experiments, the device positions are 40 µm (eII) and 23 µm (fII) above the mesh plane. Scale bars in e,f, 20 µm. We have carried out simulations of a subunit of the self-organizing reticular structure (Fig. 3a–c). Measurements of bending for the corresponding experimental structures (Fig. 3c, open red squares) are consistent with the simulation (Fig. 3c). Additionally, changes in structural parameters (for example, the total length of the subunit and thicknesses of SU-8 or metals) yield predictable changes in the bending angle of the subunit (Supplementary Fig. S4). In this way, ordered 3D nanowire FET arrays can be designed and fabricated using reticular- or mesh-like structures that incorporate multi-layer metal interconnects with built-in stress to self-organize (roll-up) the scaffold (Supplementary Fig. S4). Finally, we have designed reticular domains in mesh-like structures (Fig. 3d). Images of reticular domains (Fig. 3e,f) show that regular nanowire FET devices with distinct device positions can be realized by varying the structural parameters of individual elements. Overall, this approach yields hierarchical 3D nanoES with submicrometre to micrometre scale control in reticular domains and millimetre to centimetre scale in the mesh matrix by folding or rolling as shown above (Fig. 2). The reticular and mesh nanoES were also merged with conventional macroporous biomaterials. Specifically, gel casting, lyophilization and electrospinning were used to deposit and construct macroporous collagen (Fig. 4a), alginate (Fig. 4b) and poly(lactic-co-glycolic acid) (PLGA; Fig. 4c), respectively, around nanoES. A confocal fluorescence micrograph of a hybrid reticular nanoES/collagen scaffold (Fig. 4a) shows clearly that the collagen nanofibres (green) are fully entangled with the nanoES, with no evidence of phase separation. SEM images of the open mesh nanoES/alginate hybrid scaffold produced by lyophilization (Fig. 4b) show that the flexible nanoES mesh is intimately anchored to the alginate framework, which has a similar pore structure as the pure alginate scaffold prepared under similar conditions. Finally, optical micrographs of a multilayered mesh nanoES/PLGA scaffold (Fig. 4c), which was prepared by electrospinning PLGA fibres on both sides of the nanoES and subsequent folding of the hybrid structure, highlight the intimate contact between nanoES mesh and PLGA fibres. The hybrid nanoES/biomaterial 3D scaffolds retain the original nanowire FET device characteristics. For example, measurements in 1 × phosphate buffered saline solution showed that 1G/G and 1S/S were less than ±9% for the mesh nanoES/PLGA composite versus bare nanoES. Hybrid nanoES were stable under cell culture conditions. For example, nanowire FET devices in the hybrid reticular nanoES/Matrigel scaffold in neuron culture media (Fig. 4d) had 1S/S < ±11% over a nine-week period, suggesting a capability for long-term culture and monitoring with the nanoES. These results show that nanoES can be combined with conventional biomaterials to produce hybrid scaffolds that now provide nanoscale electrical sensory components distributed in three dimensions. NATURE MATERIALS | VOL 11 | NOVEMBER 2012 | www.nature.com/naturematerials 989 © 2012 Macmillan Publishers Limited. All rights reserved