Plasmonic nanohole array biosensor for label-free and real-time analysis of live cell secretion

Abstract

Cell secretion dynamics plays a central role in physiological and disease processes. Due to its various temporal profiles, it is essential to implement a precise detection scheme for continuous monitoring of secretion in real time. The current fluorescent and colorimetric approaches hinder such applications due to their multiple time-consuming steps, molecular labeling, and especially the 'snapshot' endpoint readouts. Here, we develop a nanoplasmonic biosensor for real-time monitoring of live cell cytokine secretion in a label-free configuration. Our nanoplasmonic biosensor is composed of gold nanohole arrays supporting extraordinary optical transmission (EOT), which enables sensitive and high-throughput analysis of biomolecules. The nanobiosensor is integrated with an adjustable microfluidic cell module for the analysis of live cells under well-controlled culture conditions. We achieved an outstanding sensitivity for the detection of vascular endothelial growth factor (VEGF) directly in complex cell media. Significantly, the secretion dynamics from live cancer cells were monitored and quantified for 10 hours while preserving good cell viability. This novel approach of probing cytokine secretion activity is compatible with conventional inverted microscopes found in a common biology laboratory. With its simple optical set-up and label-free detection configuration, we anticipate our nanoplasmonic biosensor to be a powerful tool as a lab-on-chip device to analyze cellular activities for fundamental cell research and biotechnologies.

Leveraging of MEMS Technologies for Optical Metamaterials Applications

“…In addition to metamaterials, nanophotonics is another branch of research direction for mid‐IR chemical sensing and functional applications, which is beyond the scope of this review. Many works related to SEIRA have been done to detect analytes in the gas phase, the solid phase (thin films), and the liquid phase (solutions) …”

“…Micro/nanofluidics is another interesting branch of metamaterial SEIRA bio‐sensing application because most of the biomolecular processes happen in the aqueous environment . Micro/nanofluidic chamber integrated on metamaterial sensors enable the transportation of micro/nanoliter scale biomolecular solutions to the hotspot of the sensing area at metasurface.…”

One-Step Rapid Quantification of SARS-CoV-2 Virus Particles via Low-Cost Nanoplasmonic Sensors in Generic Microplate Reader and Point-of-Care Device

“…Diagnosis of patients in the early stage infection are so far limited to viral nucleic acid or antigen detection in human nasopharyngeal swabs or saliva samples. Although traditional approaches, including point-of-care (POC) diagnostics, bedside testing, and community-based approaches, were applied to address these challenges, innovative techniques combining with mobile technologies, nanotechnology, imaging systems, and microfluidic technologies are expected to promote this transformation [36][37][38] . In this work, we also developed a portable and innovative devices controlled by a smartphone App for real-time measurements of the dynamic binging curves of SARS-CoV-2 virus on the nanoplasmonic sensor (Figure 4a).…”

Large‐Scale Plasmonic Hybrid Framework with Built‐In Nanohole Array as Multifunctional Optical Sensing Platforms

“…Two characteristics, plasmonic material that supports surface plasmon (SP) modes as well as holes at subwavelength scale (or called “nanohole,” “nanocavity,” “nanoapertures”), necessitate the strong excitation of the electromagnetic field that is sensitive to the change of local refractive index, making the structure ideal for alternative SP‐based sensors. Reported studies such as microfluidic device fabricated from Au nanohole film on chip have demonstrated the high sensitivity to the refractive index of chemicals and real‐time protein binding or biomolecule detection 4–8. On the other hand, coupling the nanohole film with functional materials provides a direction toward enhanced optical phenomena and nanophotonic device integration.…”