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) |
|---|---|
| Pages (from-to) | 941-948 |
| Number of pages | 8 |
| Journal | ACS Sensors |
| Volume | 1 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 22 2016 |
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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
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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 journal › Article
TY - JOUR
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
PY - 2016/7/22
Y1 - 2016/7/22
N2 - 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.
AB - 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.
KW - T cells
KW - cytokines
KW - immunomodulatory therapy
KW - localized surface plasmon resonance (LSPR)
KW - multiplexed immunoassay
KW - nanoplasmonic biosensing
KW - tacrolimus
UR - http://www.scopus.com/inward/record.url?scp=84994813898&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994813898&partnerID=8YFLogxK
U2 - 10.1021/acssensors.6b00240
DO - 10.1021/acssensors.6b00240
M3 - Article
C2 - 27478873
AN - SCOPUS:84994813898
VL - 1
SP - 941
EP - 948
JO - ACS Sensors
JF - ACS Sensors
SN - 2379-3694
IS - 7
ER -