Abstract
Immunomodulatory drugs - agents regulating the immune response - are commonly used for treating immune system disorders and minimizing graft versus host disease in persons receiving organ transplants. At the cellular level, immunosuppressant drugs are used to inhibit pro-inflammatory or tissue-damaging responses of cells. However, few studies have so far precisely characterized the cellular-level effect of immunomodulatory treatment. The primary challenge arises due to the rapid and transient nature of T-cell immune responses to such treatment. T-cell responses involve a highly interactive network of different types of cytokines, which makes precise monitoring of drug-modulated T-cell response difficult. Here, we present a nanoplasmonic biosensing approach to quantitatively characterize cytokine secretion behaviors of T cells with a fine time-resolution (every 10 min) that are altered by an immunosuppressive drug used in the treatment of T-cell-mediated diseases. With a microfluidic platform integrating antibody-conjugated gold nanorod (AuNR) arrays, the technique enables simultaneous multi-time-point measurements of pro-inflammatory (IL-2, IFN-γ, and TNF-α) and anti-inflammatory (IL-10) cytokines secreted by T cells. The integrated nanoplasmonic biosensors achieve precise measurements with low operating sample volume (1 μL), short assay time (∼30 min), heightened sensitivity (∼20-30 pg/mL), and negligible sensor crosstalk. Data obtained from the multicytokine secretion profiles with high practicality resulting from all of these sensing capabilities provide a comprehensive picture of the time-varying cellular functional state during pharmacologic immunosuppression. The capability to monitor cellular functional response demonstrated in this study has great potential to ultimately permit personalized immunomodulatory treatment.
Original language | English (US) |
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Pages (from-to) | 941-948 |
Number of pages | 8 |
Journal | ACS Sensors |
Volume | 1 |
Issue number | 7 |
DOIs | |
State | Published - Jul 22 2016 |
Keywords
- T cells
- cytokines
- immunomodulatory therapy
- localized surface plasmon resonance (LSPR)
- multiplexed immunoassay
- nanoplasmonic biosensing
- tacrolimus
ASJC Scopus subject areas
- Bioengineering
- Instrumentation
- Fluid Flow and Transfer Processes
- Process Chemistry and Technology