title: Multiplexed Nanoplasmonic Temporal Profiling of T-Cell Response under Immunomodulatory Agent Exposure.
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.
authors.affiliation: Department of Mechanical Engineering, Department of Pediatrics and Communicable Diseases, Department of Biomedical Engineering, Department of Cell and Developmental Biology, Michigan Center for Integrative Research in Critical Care, and Department of Electrical Engineering and Computer Science, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Bo-Ram
authors.initials: BR
authors.lastname: Oh
authors.affiliation: Department of Mechanical Engineering, Department of Pediatrics and Communicable Diseases, Department of Biomedical Engineering, Department of Cell and Developmental Biology, Michigan Center for Integrative Research in Critical Care, and Department of Electrical Engineering and Computer Science, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Mechanical Engineering, Department of Pediatrics and Communicable Diseases, Department of Biomedical Engineering, Department of Cell and Developmental Biology, Michigan Center for Integrative Research in Critical Care, and Department of Electrical Engineering and Computer Science, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Nidetz
authors.affiliation: Department of Mechanical Engineering, Department of Pediatrics and Communicable Diseases, Department of Biomedical Engineering, Department of Cell and Developmental Biology, Michigan Center for Integrative Research in Critical Care, and Department of Electrical Engineering and Computer Science, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Walker
authors.initials: W
authors.lastname: McHugh
authors.affiliation: Department of Mechanical Engineering, Department of Pediatrics and Communicable Diseases, Department of Biomedical Engineering, Department of Cell and Developmental Biology, Michigan Center for Integrative Research in Critical Care, and Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan 48109, United States; Department of Mechanical Engineering, Department of Pediatrics and Communicable Diseases, Department of Biomedical Engineering, Department of Cell and Developmental Biology, Michigan Center for Integrative Research in Critical Care, and Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan 48109, United States; Department of Mechanical Engineering, Department of Pediatrics and Communicable Diseases, Department of Biomedical Engineering, Department of Cell and Developmental Biology, Michigan Center for Integrative Research in Critical Care, and Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan 48109, United States; Department of Mechanical Engineering, Department of Pediatrics and Communicable Diseases, Department of Biomedical Engineering, Department of Cell and Developmental Biology, Michigan Center for Integrative Research in Critical Care, and Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan 48109, United States.
authors.forename: Jianping
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Mechanical Engineering, Department of Pediatrics and Communicable Diseases, Department of Biomedical Engineering, Department of Cell and Developmental Biology, Michigan Center for Integrative Research in Critical Care, and Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan 48109, United States; Department of Pediatrics, Northwestern University, Evanston, Illinois 60611, United States.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Shanley
authors.affiliation: Department of Mechanical Engineering, Department of Pediatrics and Communicable Diseases, Department of Biomedical Engineering, Department of Cell and Developmental Biology, Michigan Center for Integrative Research in Critical Care, and Department of Electrical Engineering and Computer Science, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Cornell
authors.affiliation: Department of Mechanical Engineering, Department of Pediatrics and Communicable Diseases, Department of Biomedical Engineering, Department of Cell and Developmental Biology, Michigan Center for Integrative Research in Critical Care, and Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan 48109, United States; Department of Mechanical Engineering, Department of Pediatrics and Communicable Diseases, Department of Biomedical Engineering, Department of Cell and Developmental Biology, Michigan Center for Integrative Research in Critical Care, and Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan 48109, United States.
authors.forename: Katsuo
authors.initials: K
authors.lastname: Kurabayashi
keywords: T cells; cytokines; immunomodulatory therapy; localized surface plasmon resonance (LSPR); multiplexed immunoassay; nanoplasmonic biosensing; tacrolimus