Microfluidic In Situ Patterning of Silver Nanoparticles for Surface-Enhanced Raman Spectroscopic Sensing of Biomolecules

This work integrates the advantages of microfluidic devices, nanoparticle synthesis, and on-chip sensing of biomolecules. The concept of microreactors brings new opportunities in chemical synthesis, especially for metallic nanoparticles favorable in surface-enhanced Raman spectroscopy (SERS) for high-resolution and low-limit detection of biomolecules. However, still missing is our understanding of reactions at the microscale and how microsystems can be exploited in biosensing applications via precise control of nanomaterial synthesis. We investigate how microfluidic geometry affects nanoparticle patterning for high-resolution SERS-based sensing and propose a spiral-shaped microchannel that can achieve enhanced mixing, rapid reaction at room temperature, and uniform in situ patterning. The roles of channel geometry as the key parameter on patterning have been studied systematically to provide insight into the rational design of continuous microfluidic systems for SERS applications. We also demonstrate potential applications of this integrated system in label-free on-chip detection of 1 pM rhodamine B (enhancement factor, ∼4.3 × 1011) and a 1 nM 41-base single-stranded deoxyribonucleic acid (DNA) sequence (enhancement factor, ∼1.5 × 108). Our ready-to-use multifunctional system provides an alternative strategy for the facile fabrication of SERS-active substrates and promotes system integration, miniaturization, and on-site biological applications.