Multiplexed Nanoplasmonic Temporal Profiling of T-Cell Response under Immunomodulatory Agent Exposure

Bo Ram Oh, Pengyu Chen, Robert Nidetz, Walker McHugh, Jianping Fu, Thomas P. Shanley, Timothy T. Cornell, Katsuo Kurabayashi*

*Corresponding author for this work

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)941-948
Number of pages8
JournalACS Sensors
Volume1
Issue number7
DOIs
StatePublished - Jul 22 2016

Fingerprint

T-cells
drugs
secretions
Immunosuppressive Agents
Cytokines
Pharmaceutical Preparations
immunosuppression
immune systems
Transplants
Immune system
Crosstalk
crosstalk
antibodies
Nanorods
bioinstrumentation
Microfluidics
Biosensors
Antibodies
Grafts
organs

Keywords

  • T cells
  • cytokines
  • immunomodulatory therapy
  • localized surface plasmon resonance (LSPR)
  • multiplexed immunoassay
  • nanoplasmonic biosensing
  • tacrolimus

ASJC Scopus subject areas

  • Bioengineering
  • Fluid Flow and Transfer Processes
  • Process Chemistry and Technology
  • Instrumentation

Cite this

Oh, Bo Ram ; Chen, Pengyu ; Nidetz, Robert ; McHugh, Walker ; Fu, Jianping ; Shanley, Thomas P. ; Cornell, Timothy T. ; Kurabayashi, Katsuo. / Multiplexed Nanoplasmonic Temporal Profiling of T-Cell Response under Immunomodulatory Agent Exposure. In: ACS Sensors. 2016 ; Vol. 1, No. 7. pp. 941-948.
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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.",
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Oh, BR, Chen, P, Nidetz, R, McHugh, W, Fu, J, Shanley, TP, Cornell, TT & Kurabayashi, K 2016, 'Multiplexed Nanoplasmonic Temporal Profiling of T-Cell Response under Immunomodulatory Agent Exposure', ACS Sensors, vol. 1, no. 7, pp. 941-948. https://doi.org/10.1021/acssensors.6b00240

Multiplexed Nanoplasmonic Temporal Profiling of T-Cell Response under Immunomodulatory Agent Exposure. / Oh, Bo Ram; Chen, Pengyu; Nidetz, Robert; McHugh, Walker; Fu, Jianping; Shanley, Thomas P.; Cornell, Timothy T.; Kurabayashi, Katsuo.

In: ACS Sensors, Vol. 1, No. 7, 22.07.2016, p. 941-948.

Research output: Contribution to journalArticle

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T1 - Multiplexed Nanoplasmonic Temporal Profiling of T-Cell Response under Immunomodulatory Agent Exposure

AU - Oh, Bo Ram

AU - Chen, Pengyu

AU - Nidetz, Robert

AU - McHugh, Walker

AU - Fu, Jianping

AU - Shanley, Thomas P.

AU - Cornell, Timothy T.

AU - Kurabayashi, Katsuo

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KW - nanoplasmonic biosensing

KW - tacrolimus

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