In Situ LSPR Sensing of Secreted Insulin in Organ-on-Chip

Abstract

Organ-on-a-chip (OOC) devices offer new approaches for metabolic disease modeling and drug discovery by providing biologically relevant models of tissues and organs in vitro with a high degree of control over experimental variables for high-content screening applications. Yet, to fully exploit the potential of these platforms, there is a need to interface them with integrated non-labeled sensing modules, capable of monitoring, in situ, their biochemical response to external stimuli, such as stress or drugs. In order to meet this need, we aim here to develop an integrated technology based on coupling a localized surface plasmon resonance (LSPR) sensing module to an OOC device to monitor the insulin in situ secretion in pancreatic islets, a key physiological event that is usually perturbed in metabolic diseases such as type 2 diabetes (T2D). As a proof of concept, we developed a biomimetic islet-on-a-chip (IOC) device composed of mouse pancreatic islets hosted in a cellulose-based scaffold as a novel approach. The IOC was interfaced with a state-of-the-art on-chip LSPR sensing platform to monitor the in situ insulin secretion. The developed platform offers a powerful tool to enable the in situ response study of microtissues to external stimuli for applications such as a drug-screening platform for human models, bypassing animal testing.

Advanced Materials and Sensors for Microphysiological Systems: Focus on Electronic and Electrooptical Interfaces

“…For example, Ortega et al introduced a biomimetic islet-on-a-chip device integrated with an on-chip LSPR sensing module, consisting of functionalized gold nanoantennas, for monitoring and label-free detection of insulin secretion in situ. [132] Lee et al developed a multiple aluminum nanoslit sensing array with a resolution of ≈5 × 10 -5 refractive index unit (RIU) and detectable depth of 600 nm to analyze cell adhesion kinetics under different drug treatments. [133] The SPR sensing platform recorded the transmission intensities of the TM wave incident on the biochip using a photo-scanner.…”

Trends in Nanophotonics‐Enabled Optofluidic Biosensors

“…[63,91,92] In addition, by targeting the characteristic molecular vibrations associated with the chemical bonds of molecules, surface-enhanced Raman spectroscopy (SERS) and surface-enhanced infrared absorption spectroscopy (SEIRAS) enable chemically specific detection, [32,93,94] providing opportunities for realizing real-time studies of molecular binding dynamics and metabolic pathologies. [95,96] Building on these sensing principles, we will highlight how signal readouts can be amplified through specifically designed nanophotonic geometries with a particular focus on recently reported high-end biosensing applications, encompassing the detection of biomolecules (proteins, antigens, biomarkers), exosomes, pathogens (viruses and bacteria), and cell secretion. [97][98][99][100]…”

“…In contrast to SERS geometries operating at visible wavelengths, where the strong field confinement facilitates the detection of very small molecules, SEIRAS with larger decay length can resolve molecules with more than a few nanometers in size, particularly proteins, bacteria, and cells, facilitating detection in complex biological systems like organ-on-chip platforms. [96] Significant efforts have been made to engineer a variety of resonators with enhanced near-fields and controllable resonant frequency, [165] including metallic nanorods/nanoslits, [166] nano-gapped antennas, [33,167] split-ring resonators, [168] fan-shaped nanoantennas, [169] nanoantennas on nanopedestals, [170,171] and metamaterial perfect absorbers (MPAs). [172,173] These SEIRA-based nanophotonic platforms have realized EFs of 10 4 -10 7 [166,174] for biomolecular detection, enabled by the coupling between the enhanced nearfields of the resonators and the vibrational modes of the target molecules.…”

“…Furthermore, an integrated islet‐on‐a‐chip (IOC) module with a LSPR‐based optical sensor has been developed to monitor in‐situ insulin secretion from an integrated device, where the insulin is released by pancreatic islets. [ 96 ] This integrated platform demonstrates the great potential of performing organ‐on‐a‐chip studies with real‐time, in‐situ and label‐free monitoring of different secretion dynamics of cells, tissues and spheroids, providing a robust tool for drug screening, toxicity studies and investigations of metabolic diseases. To close this section and to provide a broader perspective, Table 1 highlights and compares selected recent examples of nanophotonics‐enabled optofluidic biosensors based on different categories including fluidic channel height/function, target analyte, and detection limit.…”

Plasmonic Nanoagents in Biophysics and Biomedicine

“…(Reproduced with permission. [ 70 ] Copyright 2021, MDPI.) b) Top left: Schematic of the measurement setup through the rat's skin in transmission mode.…”