Paper has been one of the most popular materials of choice for biomedical applications including for bioanalysis and cell biology studies. Regular cellulose paper-based devices, however, have several key limitations...

Paper‐based surface‐enhanced Raman scattering (SERS) substrates have gained growing interest as an eco‐friendly and low‐cost tool for chemical and biosensing. However, paper‐based SERS substrates often suffer relatively low signal spatial homogeneity because of their nonuniform hot‐spot distribution. In this paper, a nanofibrillated cellulose paper (nanopaper) based SERS multiwell plate is developed for trace chemical detection with high sensitivity and high signal homogeneity. The SERS plate is fabricated from ultrasmooth (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl‐oxidized NFC paper (TO‐nanopaper) through wax‐printing‐based multiwell patterning followed by silver nanoparticle (AgNP) growth based on a successive ionic layer adsorption and reaction (SILAR) process. Taking advantage of the abundance of carboxyl groups on the TO‐nanopaper, uniformly distributed and densely arranged AgNPs are successfully synthesized through the SILAR process on the NFC multiwell surface under ambient conditions. The SERS performance of the device is evaluated for testing two Raman marker chemicals, rhodamine B and 2‐naphthalenethiol, and picomolar detection limit and high Raman enhancement factor (up to 1.46 × 109) are achieved. The Raman signal mapping results show superior signal spatial homogeneity of the device with low variations (≤11%). The nanopaper‐based SERS device represents a promising SERS platform for chemical and biomolecule detections with high sensitivity and high repeatability.

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