Multicellular systems, such as microbial biofilms and cancerous tumors, feature complex biological activities coordinated by cellular interactions mediated via different signaling and regulatory pathways, which are intrinsically heterogeneous, dynamic, and adaptive. However, due to their invasiveness or their inability to interface with native cellular networks, standard bioanalysis methods do not allow in situ spatiotemporal biochemical monitoring of multicellular systems to capture holistic spatiotemporal pictures of systems‐level biology. Here, a high‐throughput reverse nanoimprint lithography approach is reported to create biomimetic transparent nanoplasmonic microporous mesh (BTNMM) devices with ultrathin flexible microporous structures for spatiotemporal multimodal surface‐enhanced Raman spectroscopy (SERS) measurements at the bio‐interface. It is demonstrated that BTNMMs, supporting uniform and ultrasensitive SERS hotspots, can simultaneously enable spatiotemporal multimodal SERS measurements for targeted pH sensing and non‐targeted molecular detection to resolve the diffusion dynamics for pH, adenine, and Rhodamine 6G molecules in agarose gel. Moreover, it is demonstrated that BTNMMs can act as multifunctional bio‐interfaced SERS sensors to conduct in situ spatiotemporal pH mapping and molecular profiling of Escherichia coli biofilms. It is envisioned that the ultrasensitive multimodal SERS capability, transport permeability, and biomechanical compatibility of the BTNMMs can open exciting avenues for bio‐interfaced multifunctional sensing applications both in vitro and in vivo.

Microporous mesh plasmonic devices have the potential to combine the biocompatibility of microporous polymeric meshes with the capabilities of plasmonic nanostructures to enhance nanoscale light–matter interactions for bio‐interfaced optical sensing and actuation. However, scalable integration of dense and uniformly structured plasmonic hotspot arrays with microporous polymeric meshes remains challenging due to the processing incompatibility of conventional nanofabrication methods with flexible microporous substrates. Here, scalable nanofabrication of microporous multiresonant plasmonic meshes (MMPMs) is achieved via a hierarchical micro‐/nanoimprint lithography approach using dissolvable polymeric templates. It is demonstrated that MMPMs can serve as broadband nonlinear nanoplasmonic devices to generate second‐harmonic generation, third‐harmonic generation, and upconversion photoluminescence signals with multiresonant plasmonic enhancement under fs pulse excitation. Moreover, MMPMs are employed and explored as bio‐interfaced surface‐enhanced Raman spectroscopy mesh sensors to enable in situ spatiotemporal molecular profiling of bacterial biofilm activity. Microporous mesh plasmonic devices open exciting avenues for bio‐interfaced optical sensing and actuation applications, such as inflammation‐free epidermal sensors in conformal contact with skin, combined tissue‐engineering and biosensing scaffolds for in vitro 3D cell culture models, and minimally invasive implantable probes for long‐term disease diagnostics and therapeutics.

In situ spatiotemporal characterization of correlated bioelectrical and biochemical processes in living multicellular systems remains a formidable challenge but can offer crucial opportunities in biology and medicine. A promising approach...

Multiresonant plasmonic nanoantennas can enhance nanolocalized multiphoton processes or enable wavelength-multiplexed nano-optic operations by supporting multiple spatially overlapped plasmonic modes. Nevertheless, current multiresonant plasmonic nanoantenna designs do not consider engineering multiresonant spectral responses with strict size and footprint constraints. Developing a strategy to engineer fixed-size nanoantennas with tunable multiresonant responses is highly desirable for maintaining controlled cellular responses at the nano-bio interface and achieving seamless integration with other nanodevices with predefined footprints. Here, we report that fixed-size tapered nanolaminate nanoantennas (TNLNAs) can achieve a wide double-resonance spectral tunability by only changing the metal-to-insulator thickness ratio (t/h). Three separate TNLNAs' samples (8/38 , 20/20, and 28/8 nm) with a nominal total height of ∼100 nm are created from a high-throughput nanofabrication technique. Specifically, we fabricated TNLNAs' samples by exploiting a nanohole array membrane from soft interference lithography as a deposition mask for electron-beam evaporation of alternating Au and SiO2 layers. Transmission and dark field scattering measurements show that TNLNAs support two distinct resonant features with t/h-dependent tunable resonant wavelengths in the range of 730–850 and 840–1050 nm, respectively. Numerical simulations reveal that (i) a bianisotropy-induced magnetoelectric response in top and bottom nanogaps due to the asymmetric tapered shape can enhance light trapping and achieve optical near-field intensity enhancements up to 1000-fold and (ii) while TNLNAs consisting of thin Au nanodisks at low t/h primarily support spatial overlap between modes with enhanced electric polarizability, TNLNAs consisting of thick Au nanodisks at high t/h support spatial overlap between modes with enhanced magnetic polarizability, evoking higher-order multipolar behaviors.

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