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

Lab Chip. 2018 Dec 7;18(23):3550-3560. doi: 10.1039/c8lc00605a. Epub 2018 Oct 10.

Abstract

Although many advanced biosensing techniques have been proposed 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, and maturation and simulate the hallmark formation of crown-like structures (CLSs) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / pathology
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology*
  • Animals
  • Biosensing Techniques / instrumentation*
  • Cytokines / metabolism
  • Inflammation / complications
  • Lab-On-A-Chip Devices*
  • Mice
  • Nanotechnology / instrumentation*
  • Obesity / complications
  • Obesity / pathology*
  • Tissue Array Analysis / instrumentation*

Substances

  • Cytokines