Related Experiment Video
Updated: Jul 2, 2026
Detection and Enrichment of Rare Antigen-specific B Cells for Analysis of Phenotype and Function
Published on: February 16, 2017
Label-free electronic detection of the antigen-specific T-cell immune response
Eric Stern1, Erin R Steenblock, Mark A Reed
1Department of Biomedical Engineering, Yale University, 55 Prospect Street, New Haven, Connecticut 06511, USA.
Insights
New nanoscale technology enables label-free electronic detection of antigen-specific T-cell responses. This rapid and sensitive method offers potential for faster clinical testing and high-throughput screening of epitopes and drugs.
Area of Science:
- Immunology
- Nanotechnology
- Biomedical Engineering
Background:
- Detecting antigen-specific T-cells is crucial for diagnosing diseases and developing therapies.
- Current methods like flow cytometry require fluorescent labels and soluble peptide-MHC complexes.
- Monitoring T-cell numbers and functional responses is essential for effective disease management.
Purpose of the Study:
- To demonstrate the use of nanoscale solid-state complementary metal-oxide-semiconductor (CMOS) technology for direct, label-free electronic detection of T-cell responses.
- To assess the sensitivity and speed of this novel detection method for antigen-specific T-cells.
- To explore the potential of this technology for clinical applications and high-throughput screening.
Main Methods:
- Utilized nanoscale solid-state CMOS technology for label-free electronic detection.
- Measured extracellular acidification as an indicator of T-cell activation.
- Triggered T-cell activation using both nonspecific anti-CD3 stimulus and peptide/MHC agonists.
Main Results:
- Direct electronic detection of antigen-specific T-cell responses was achieved within seconds.
- The technology detected T-cell activation from as few as approximately 200 cells.
- Nonspecific T-cell activation was detected within 10 seconds, while antigen-specific responses took over 40 seconds.
Conclusions:
- Nanoscale CMOS technology provides a rapid, sensitive, and label-free method for detecting T-cell responses.
- This technology has the potential to advance our understanding of T-cell activation kinetics.
- The ease of integration with conventional electronics may enable rapid clinical diagnostics and high-throughput screening.
Abstract:
Detection of antigen-specific T-cells is critical for diagnostic assessment and design of therapeutic strategies for many disease states. Effective monitoring of these cells requires technologies that assess their numbers as well as functional response. Current detection of antigen-specific T-cells involves flow cytometry and functional assays and requires fluorescently labeled, soluble forms of peptide-loaded major histocompatability complexes (MHC). We demonstrate that nanoscale solid-state complementary metal-oxide-semiconductor (CMOS) technology can be employed to allow direct, label-free electronic detection of antigen-specific T-cell responses within seconds after stimulation. Our approach relies on detection of extracellular acidification arising from a small number of T-cells (as few as approximately 200), whose activation is induced by triggering the T-cell antigen receptor. We show that T-cell triggering by a nonspecific anti-CD3 stimulus can be detected within 10 s after exposure to the stimulus. In contrast, antigen-specific T-cell responses are slower with response times greater than 40 s after exposure to peptide/MHC agonists. The speed and sensitivity of this technique has the potential to elucidate new understandings of the kinetics of activation-induced T-cell responses. This combined with its ease of integration into conventional electronics potentially enable rapid clinical testing and high-throughput epitope and drug screening.
Related Concept Videos
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
01:24B Cell Activation and Differentiation
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...