An integrated adipose-tissue-on-chip nanoplasmonic biosensing platform for investigating obesity-associated inflammation

Abstract

Although many advanced biosensing techniques have been purposed for cytokine profiling, there are no clinically available methods that integrate high-resolution immune cell monitoring and in situ multiplexed cytokine detection together in a biomimetic tissue microenvironment. The primary challenge arises due to the lack of suitable label-free sensing techniques and difficulty for sensor integration. In this work, we demonstrated a novel integration of a localized-surface plasmon resonance (LSPR)-based biosensor with a biomimetic microfluidic ‘adipose-tissue-on-chip’ platform for an in-situ label-free, high-throughput and multiplexed cytokine secretion analysis of obese adipose tissue. Using our established adipose-tissue-on-chip platform, we were able to monitor the adipose tissue initiation, differentiation, maturation and simulate the hallmark formation of crown-like structures (CLS) during pro-inflammatory stimulation. With integrated antibody-conjugated LSPR barcode sensor arrays, our platform enables simultaneous multiplexed measurements of pro-inflammatory (IL-6, and TNF-α) and anti-inflammatory (IL-10, and IL-4) cytokines secreted by the adipocytes and macrophages. As a result, our adipose-tissue-on-chip platform is capable of identifying stage-specific cytokine secretion profiles from a complex milieu during obesity progression, highlighting its potential as a high-throughput preclinical readout for personalized obesity treatment strategies.

Review of Integrated Optical Biosensors for Point-of-Care Applications

“…From their results, a rapid, sensitive, multiplex, and real-time assay was achieved. Moreover, the process of adipose tissue turning into the adipocyte was also observed [ 95 ].…”

Metallic Nanoparticle-Based Optical Cell Chip for Nondestructive Monitoring of Intra/Extracellular Signals

“…Moreover, as previously mentioned, LSPR offers unique dark-field imaging of the cells simultaneously [86,95]. Zhu et al developed LSPR-based biosensor-integrated adipose-tissue-on-chip for multiplexed cytokines secretion analysis [87] (Figure 2c). Adipocyte was cultured on the center of the chip with the macrophages, and the four surrounded circle rings functionalized by the Au nanorod and anti-cytokines, which capture each cytokine (IL-4, IL-6, IL-10, and TNF-α, respectively).…”

Optical Interrogation Techniques for Nanophotonic Biochemical Sensors

“…In the second approach, ensemble intensity variations from microarrays of NPs were measured from dark-field images using low-NA objectives with larger FOV. This method was used for multiplexed detection of serum cytokines for diagnostic purposes [85], temporal profiling of T-cell secretion [86], and to monitor the secretion from tissue-on-chip platform [87].…”